@article {pmid33466653, year = {2021}, author = {Marcq, E and Van Audenaerde, JRM and De Waele, J and Merlin, C and Pauwels, P and van Meerbeeck, JP and Fisher, SA and Smits, ELJ}, title = {The Search for an Interesting Partner to Combine with PD-L1 Blockade in Mesothelioma: Focus on TIM-3 and LAG-3.}, journal = {Cancers}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/cancers13020282}, pmid = {33466653}, issn = {2072-6694}, support = {141433//Agentschap voor Innovatie door Wetenschap en Technologie/ ; 11455//Kom op tegen Kanker/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer that is causally associated with previous asbestos exposure in most afflicted patients. The prognosis of patients remains dismal, with a median overall survival of only 9-12 months, due to the limited effectiveness of any conventional anti-cancer treatment. New therapeutic strategies are needed to complement the limited armamentarium against MPM. We decided to focus on the combination of different immune checkpoint (IC) blocking antibodies (Abs). Programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), T-cell immunoglobulin mucin-3 (TIM-3), and lymphocyte activation gene-3 (LAG-3) blocking Abs were tested as monotherapies, and as part of a combination strategy with a second IC inhibitor. We investigated their effect in vitro by examining the changes in the immune-related cytokine secretion profile of supernatant collected from treated allogeneic MPM-peripheral blood mononuclear cell (PBMC) co-cultures. Based on our in vitro results of cytokine secretion, and flow cytometry data that showed a significant upregulation of PD-L1 on PBMC after co-culture, we chose to further investigate the combinations of anti PD-L1 + anti TIM-3 versus anti PD-L1 + anti LAG-3 therapies in vivo in the AB1-HA BALB/cJ mesothelioma mouse model. PD-L1 monotherapy, as well as its combination with LAG-3 blockade, resulted in in-vivo delayed tumor growth and significant survival benefit.}, }
@article {pmid33466544, year = {2021}, author = {Mensi, C and Dallari, B and Polonioli, M and Riboldi, L and Consonni, D and Pesatori, AC}, title = {Mesothelioma in Agriculture in Lombardy, Italy: An Unrecognized Risk.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {1}, pages = {}, doi = {10.3390/ijerph18010358}, pmid = {33466544}, issn = {1660-4601}, support = {PRIMATE-code ARL_2/2018//Fondazione Regionale per la Ricerca Biomedica/ ; BRiC P55 and P59//Istituto Nazionale per l'Assicurazione contro gli Infortuni sul Lavoro (INAIL), Rome, Italy/ ; }, abstract = {Cohort studies showed consistently low risks for malignant mesothelioma (MM) among agricultural workers, however the investigated exposures did not include asbestos. Our aim is to describe sources of asbestos exposure of MM in agriculture. Twenty-six MM cases in agricultural or seed trades workers were identified through the MM registry of the Lombardy region, Italy in 2000-2016. Asbestos exposures were investigated through a standardized questionnaire. The most frequent exposure circumstances were recycled jute bags previously containing asbestos (11 cases) and maintenance and repair of asbestos roofs (12 subjects). Three subjects performed maintenance and repair of tractor asbestos brakes and two used asbestos filters for wine production. Our data suggest asbestos exposure opportunities in the agricultural setting, underlining the need to look for this exposure in subjects affected with mesothelioma.}, }
@article {pmid33465294, year = {2021}, author = {Eccher, A and Girolami, I and Lucenteforte, E and Troncone, G and Scarpa, A and Pantanowitz, L}, title = {Diagnostic mesothelioma biomarkers in effusion cytology.}, journal = {Cancer cytopathology}, volume = {}, number = {}, pages = {}, doi = {10.1002/cncy.22398}, pmid = {33465294}, issn = {1934-6638}, abstract = {Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1-associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.}, }
@article {pmid33438079, year = {2021}, author = {Borrelli, EP and McGladrigan, CG}, title = {A Review of Pharmacologic Management in the Treatment of Mesothelioma.}, journal = {Current treatment options in oncology}, volume = {22}, number = {2}, pages = {14}, pmid = {33438079}, issn = {1534-6277}, abstract = {OPINION STATEMENT: Mesothelioma is a rare and severe form of cancer that is associated with asbestos exposure. Approximately 2500 Americans die annually from this condition with a median survival of 1 year. The latency period of this disease ranges anywhere from 20 to 70 years, with shorter latency periods associated with a higher exposure intensity to asbestos. Therefore, cases of mesothelioma are expected in the coming decades. This highlights the need for clinicians to understand the pharmacologic regimens available for treating this rare, yet serious malignancy. With multiple treatment regimens available in the treatment of this condition, clinicians should take an evidence-based approach and consider the totality of evidence and safety information while considering the best patient-centered approach for treatment. This article provides a review of current pharmacologic treatment options available for mesothelioma and goes into detail about the recommended medication regimens and dosages and the available evidence of efficacy, effectiveness, and/or safety and estimates the annual cost of treatment for these medications on the U.S. healthcare system per patient. A brief introduction is provided for several promising agents currently under investigation for mesothelioma as well.}, }
@article {pmid33435788, year = {2021}, author = {Germine, M and Puffer, JH}, title = {Anthophyllite asbestos from Staten Island, New York: Longitudinal fiber splitting.}, journal = {Archives of environmental & occupational health}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/19338244.2021.1873095}, pmid = {33435788}, issn = {2154-4700}, abstract = {Asbestos ore was sampled from a historical anthophyllite mine in Staten Island, New York. High-resolution transmission electron microscopy (HRTEM) was used to image the structure of nineteen fibers of the anthophyllite asbestos. The anthophyllite was characterized by a high level of chain width disorder, involving wide chain multiplicity faults (CMFs) that were frequent in fibers, randomly spaced, and ranged from one to eight chains in width. This chain width disorder was manifest by streaking of electron diffraction rows of chain width. The anthophyllite asbestos fibers were found to be produced by longitudinal splitting rather than crystal growth. Such splitting is a function of cleavage along CMFs rather than crystal boundaries. The morphology of the fibers is consistent with anthophyllite asbestos mined in Finland associated with lung cancer and mesothelioma. These findings may have regulatory implications.}, }
@article {pmid32777272, year = {2020}, author = {Manangama, G and Gramond, C and Audignon-Durand, S and Baldi, I and Fabro-Peray, P and Gilg Soit Ilg, A and Guénel, P and Lebailly, P and Luce, D and Stücker, I and Brochard, P and Lacourt, A}, title = {Occupational exposure to unintentionally emitted nanoscale particles and risk of cancer: From lung to central nervous system - Results from three French case-control studies.}, journal = {Environmental research}, volume = {191}, number = {}, pages = {110024}, doi = {10.1016/j.envres.2020.110024}, pmid = {32777272}, issn = {1096-0953}, mesh = {Adult ; *Asbestos ; Case-Control Studies ; Central Nervous System ; Humans ; Lung ; *Lung Neoplasms/chemically induced/epidemiology ; Male ; *Occupational Diseases ; *Occupational Exposure/adverse effects ; Retrospective Studies ; }, abstract = {OBJECTIVES: Nanoscale particles (1-100 nm) can be of natural origin, and either intentionally or unintentionally produced by human activities. Toxicological data have suggested a possible carcinogenic effect of such particles. The aim of this study was to estimate the association between occupational exposure to nanoscale particles and risk of lung cancer, pleural mesothelioma and brain tumors in adults.<br><br>METHODS: Three French population-based case-control studies were analyzed: 1) the ICARE study including 2029 lung cancer cases and 2591 controls; 2) the PNSM study including 371 pleural mesothelioma cases and 730 controls and 3) the CERENAT study including 257 brain tumor cases and 511 controls. Occupational exposure to unintentionally emitted nanoscale particles (UNPs) was retrospectively assessed by a job exposure matrix providing a probability and a frequency of exposure.<br><br>RESULTS: In adjusted analyses among men, significant associations between occupational exposure to UNPs and lung cancer (OR = 1.51; 95% CI: 1.22-1.86 and brain tumors (OR = 1.69; 95% CI: 1.17-2.44) were observed. No increased OR was observed for pleural mesothelioma (OR = 0.78; 95% CI: 0.46-1.33).<br><br>CONCLUSION: This is the first study showing positive associations between occupational exposure to UNPs and increased risk of lung cancer and brain tumors. These preliminary results should encourage further epidemiological research.}, }
@article {pmid33422732, year = {2020}, author = {Ejegi-Memeh, S and Darlison, L and Moylan, A and Tod, A and Sherborne, V and Warnock, C and Taylor, BH}, title = {Living with mesothelioma: A qualitative study of the experiences of male military veterans in the UK.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {50}, number = {}, pages = {101889}, doi = {10.1016/j.ejon.2020.101889}, pmid = {33422732}, issn = {1532-2122}, abstract = {PURPOSE: The UK has the highest incidence of mesothelioma in the world. Evidence in the United States suggests that mesothelioma may disproportionately affect military veterans. However, there has been no investigation of the experience of UK veterans living with mesothelioma. The Military Mesothelioma Experience Study (MiMES) aimed to understand the experience and health/support needs of British Armed Forces personnel/veterans with mesothelioma.<br><br>METHODS: Semi-structured interviews were conducted with 13 veterans living with mesothelioma, and nine family members of veterans living with mesothelioma. Participants were recruited via charities and asbestos support groups. Data were analysed using thematic analysis.<br><br>RESULTS: Participants' experiences are presented using three themes, i) exposure to asbestos and awareness of asbestos related diseases, ii) using military strategies to cope with mesothelioma and iii) preferences for information and support. MiMES indicates that the nature and range of UK military veterans' asbestos exposure is varied and not limited to high risk occupations. Participants' knowledge of asbestos and experience of mesothelioma influenced their experiences of diagnosis. Participants had coping strategies influenced by their military experiences. Assistance in navigating health and military systems was considered beneficial, especially if support was provided by professionals with knowledge or experience of the military. Attributes which may inhibit veterans from seeking professional support are discussed.<br><br>CONCLUSION: MiMES provides insight into how UK military veterans experience and cope with mesothelioma. Key implications focus on the role that Mesothelioma Nurse Specialists, Asbestos Support Groups and veterans groups play in providing acceptable support for UK veterans.}, }
@article {pmid33419364, year = {2020}, author = {Affatato, R and Mendogni, P and Del Gobbo, A and Ferrero, S and Ricci, F and Broggini, M and Rosso, L}, title = {Establishment and Characterization of Patient-Derived Xenografts (PDXs) of Different Histology from Malignant Pleural Mesothelioma Patients.}, journal = {Cancers}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/cancers12123846}, pmid = {33419364}, issn = {2072-6694}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a very aggressive tumor originating from mesothelial cells. Although several etiological factors were reported to contribute to MPM onset, environmental exposure to asbestos is certainly a major risk factor. The latency between asbestos (or asbestos-like fibers) exposure and MPM onset is very long. MPM continues to be a tumor with poor prognosis despite the introduction of new therapies including immunotherapy. One of the major problems is the low number of preclinical models able to recapitulate the features of human tumors. This impacts the possible discovery of new treatments and combinations.<br><br>METHODS: In this work, we aimed to generate patient-derived xenografts (PDXs) from MPM patients covering the three major histotypes (epithelioid, sarcomatoid, and mixed) occurring in the clinic. To do this, we obtained fresh tumors from biopsies or pleurectomies, and samples were subcutaneously implanted in immunodeficient mice within 24 h.<br><br>RESULTS: We successfully isolated different PDXs and particularly concentrated our efforts on three covering the three histotypes. The tumors that grew in mice compared well histologically with the tumors of origin, and showed stable growth in mice and a low response to cisplatin, as was observed in the clinic.<br><br>CONCLUSIONS: These models are helpful in testing new drugs and combinations that, if successful, could rapidly translate to the clinical setting.}, }
@article {pmid33414743, year = {2020}, author = {Granieri, A and Bonafede, M and Marinaccio, A and Iavarone, I and Marsili, D and Franzoi, IG}, title = {SARS-CoV-2 and Asbestos Exposure: Can Our Experience With Mesothelioma Patients Help Us Understand the Psychological Consequences of COVID-19 and Develop Interventions?.}, journal = {Frontiers in psychology}, volume = {11}, number = {}, pages = {584320}, doi = {10.3389/fpsyg.2020.584320}, pmid = {33414743}, issn = {1664-1078}, abstract = {Since its emergence, the novel coronavirus disease of 2019 (COVID-19) has had enormous physical, social, and psychological impacts worldwide. The aim of this article was to identify elements of our knowledge on asbestos exposure and malignant mesothelioma (MM) that can provide insight into the psychological impact of the COVID-19 pandemic and be used to develop adequate interventions. Although the etiology of Covid-19 and MM differs, their psychological impacts have common characteristics: in both diseases, there is a feeling of being exposed through aerial contagion to an &quot;invisible killer&quot; without boundaries that can strike even the strongest individuals. In both cases, affected persons can experience personality dysfunction, anxiety, depression, and posttraumatic symptoms; helplessness, hopelessness, and projection of destructive thoughts onto external forces often emerge, while defense mechanisms such as denial, splitting, repression, and reduced emotional expression are used by individuals to contain their overwhelming anxieties. We believe that in both diseases, an integrated multidimensional intervention offered by hospitals and other public health services is the most effective approach to alleviating patients' and caregivers' psychological distress. In particular, we emphasize that in the context of both MM and COVID-19, Brief Psychoanalytic Group therapy can help patients and caregivers attribute meaning to the significant changes in their lives related to the experience of the disease and identify adaptive strategies and more realistic relational modalities to deal with what has happened to them. We also highlight the importance of developing a surveillance system that includes individual anamnestic evaluation of occupational risk factors for COVID-19 disease.}, }
@article {pmid33414260, year = {2021}, author = {Gunatilake, S and Lodge, D and Neville, D and Jones, T and Fogg, C and Bassett, P and Begum, S and Kerley, S and Marshall, L and Glaysher, S and Elliott, S and Stores, R and Bishop, L and Chauhan, A}, title = {Predicting survival in malignant pleural mesothelioma using routine clinical and laboratory characteristics.}, journal = {BMJ open respiratory research}, volume = {8}, number = {1}, pages = {}, doi = {10.1136/bmjresp-2019-000506}, pmid = {33414260}, issn = {2052-4439}, abstract = {INTRODUCTION: The prognosis of malignant pleural mesothelioma (MPM) is poor, with a median survival of 8-12 months. The ability to predict prognosis in MPM would help clinicians to make informed decisions regarding treatment and identify appropriate research opportunities for patients. The aims of this study were to examine associations between clinical and pathological information gathered during routine care, and prognosis of patients with MPM, and to develop a 6-month mortality risk prediction model.<br><br>METHODS: A retrospective cohort study of patients diagnosed with MPM at Queen Alexandra Hospital, Portsmouth, UK between December 2009 and September 2013. Multivariate analysis was performed on routinely available histological, clinical and laboratory data to assess the association between different factors and 6-month survival, with significant associations used to create a model to predict the risk of death within 6 months of diagnosis with MPM.<br><br>RESULTS: 100 patients were included in the analysis. Variables significantly associated with patient survival in multivariate analysis were age (HR 1.31, 95% CI 1.09 to 1.56), smoking status (current smoker HR 3.42, 95% CI 1.11 to 4.20), chest pain (HR 2.14, 95% CI 1.23 to 3.72), weight loss (HR 2.13, 95% CI 1.18 to 3.72), platelet count (HR 1.05, 95% CI 1.00 to 1.10), urea (HR 2.73, 95% CI 1.31 to 5.69) and adjusted calcium (HR 1.47, 95% CI 1.10 to 1.94). The resulting risk model had a c-statistic value of 0.76. A Hosmer-Lemeshow test confirmed good calibration of the model against the original dataset.<br><br>CONCLUSION: Risk of death at 6 months in patients with a confirmed diagnosis of MPM can be predicted using variables readily available in clinical practice. The risk prediction model we have developed may be used to influence treatment decisions in patients with MPM. Further validation of the model requires evaluation of its performance on a separate dataset.}, }
@article {pmid33400741, year = {2020}, author = {Reis, K and Arbiser, JL and Hjerpe, A and Dobra, K and Aspenström, P}, title = {Inhibitors of cytoskeletal dynamics in malignant mesothelioma.}, journal = {Oncotarget}, volume = {11}, number = {50}, pages = {4637-4647}, doi = {10.18632/oncotarget.27843}, pmid = {33400741}, issn = {1949-2553}, abstract = {Malignant mesotheliomas (MMs) are highly aggressive mesenchymal tumors that originate from mesothelial cells lining serosal cavities; i.e., the pleura, peritoneum, and pericardium. Classically, there is a well-established link between asbestos exposure, oxidative stress, release of reactive oxygen species, and chronic inflammatory mediators that leads to progression of MMs. MMs have an intermediate phenotype, with co-expression of mesenchymal and epithelial markers and dysregulated communication between the mesothelium and the microenvironment. We have previously shown that the organization and function of key cytoskeletal components can distinguish highly invasive cell lines from those more indolent. Here, we used these tools to study three different types of small-molecule inhibitors, where their common feature is their influence on production of reactive oxygen species. One of these, imipramine blue, was particularly effective in counteracting some key malignant properties of highly invasive MM cells. This opens a new possibility for targeted inhibition of MMs based on well-established molecular mechanisms.}, }
@article {pmid33399341, year = {2021}, author = {Argani, P and Lian, DWQ and Agaimy, A and Metzler, M and Wobker, SE and Matoso, A and Epstein, JI and Sung, YS and Zhang, L and Antonescu, CR}, title = {Pediatric Mesothelioma With ALK Fusions: A Molecular and Pathologic Study of 5 Cases.}, journal = {The American journal of surgical pathology}, volume = {Publish Ahead of Print}, number = {}, pages = {}, doi = {10.1097/PAS.0000000000001656}, pmid = {33399341}, issn = {1532-0979}, abstract = {Pediatric mesotheliomas are rare and their pathogenesis remains undefined. In this study, we report 5 cases of malignant mesothelioma in children, characterized by fusions involving the anaplastic lymphoma kinase (ALK) gene. Four cases occurred in females involving the abdominal cavity and were characterized by a pure epithelioid morphology. The fifth arose in the tunica vaginalis of a 15-year-old male and displayed a biphasic epithelioid-sarcomatoid phenotype. All cases demonstrated the classic morphologic and immunohistochemical features of malignant mesothelioma, including tubulopapillary architecture and cuboidal epithelioid cells with eosinophilic cytoplasm and uniform nuclei with vesicular chromatin. Immunohistochemically, all cases showed labeling for ALK, cytokeratins, WT1, and calretinin, while lacking expression of adenocarcinoma immunomarkers. Four cases demonstrated weak-moderate labeling for PAX8 protein, which resulted in diagnostic challenges with primary peritoneal serous carcinoma. The ALK genetic abnormalities were investigated by a combination of molecular methods. Archer FusionPlex was performed in 2 cases, showing fusions between ALK with either STRN or TPM1 genes, resulting in a transcript that retained the ALK kinase domain. One case was further studied by DNA targeted sequencing, but no additional genetic alterations were observed. In 1 case, cytogenetic analysis showed the presence of a t(2;15)(p23;q22) and fluorescence in situ hybridization confirmed the ALK gene break-apart. In the remaining 2 cases, ALK gene rearrangements were demonstrated by fluorescence in situ hybridization. Unlike adult mesotheliomas, which are tightly linked to asbestos exposure, often show loss of BAP1 expression and have complex karyotypes, ALK-rearranged mesothelioma appears to be similar to other fusion-positive mesotheliomas, such as those harboring EWSR1/FUS-ATF1 fusions, sharing significant morphologic overlap, occurring in young patients and displaying a simple, translocation-driven genetic profile.}, }
@article {pmid33388783, year = {2021}, author = {Marinaccio, A and Consonni, D and Mensi, C and Mirabelli, D and Migliore, E and Magnani, C and Di Marzio, D and Gennaro, V and Mazzoleni, G and Girardi, P and Negro, C and Romanelli, A and Chellini, E and Grappasonni, I and Madeo, G and Romeo, E and Ascoli, V and Carrozza, F and Angelillo, IF and Cavone, D and Tumino, R and Melis, M and Curti, S and Brandi, G and Mattioli, S and Iavicoli, S and , }, title = {Authors' response: Mezei et al's &quot;Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis&quot;.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {47}, number = {1}, pages = {87-89}, doi = {10.5271/sjweh.3910}, pmid = {33388783}, issn = {1795-990X}, abstract = {Mezei et al's letter (1) is an opportunity to provide more details about our study on pericardial and tunica vaginalis testis (TVT) mesothelioma (2), which is based on the Italian national mesothelioma registry (ReNaM): a surveillance system on mesothelioma, with individual asbestos exposure assessment. Incidence of pericardial mesothelioma has been estimated around 0.5 and 0.2 cases per 10 million person-years in men and women, respectively, and around 1 case for TVT mesothelioma. ReNaM collected 138 cases thanks to its long period of observation (1993-2015) and national coverage. Conducting a population-based case-control study with incidence-density sampling of controls across Italy and over a 23 year time-span should have been planned in 1993 and would have been beyond feasibility and ReNaM scope. We rather exploited two existing series of controls (3). The resulting incomplete time- and spatial matching of cases and controls is a limitation of our study and has been acknowledged in our article. The analysis of case-control studies can nevertheless be accomplished in logistic models accounting for the variables of interest, in both individually and frequency matched studies (4). Furthermore, analyses restricted to (i) regions with enrolled controls, (ii) cases with definite diagnosis, (iii) incidence period 2000-2015, and (iv) subjects born before 1950 have been provided in the manuscript, confirming the strength of the association with asbestos exposure (supplemental material tables S4-7). Following Mezei et al's suggestion, we performed further sensitivity analyses by restriction to regions with controls and fitting conditional regression models using risk-sets made of combinations of age and year of birth categories (5-year classes for both). We confirmed positive associations with occupational exposure to asbestos of pericardial mesothelioma, with odds ratios (OR) (adjusted for region) of 9.16 among women [95% confidence interval (CI) 0.56-150] and 5.63 (95% CI 1.02-31.0) among men; for TVT mesothelioma the OR was 7.70 (95% CI 2.89-20.5). Using risk sets of age categories and introducing year of birth (5-year categories) as a covariate (dummy variables) the OR were similar: OR (adjusted for region) of 9.17 among women (95% CI 0.56-150) and 5.76 (95% CI 1.07-31.0) among men; for TVT the OR was 9.86 (95% CI 3.46-28.1). Possible bias from incomplete geographical overlap between cases and controls has been addressed in the paper (table S4) and above. In spatially restricted analyses, OR were larger than in those including cases from the whole country, indicating that bias was towards the null. Mezei et al further noted that &quot;the regional distribution of controls is different from that of person-time observed&quot;. This objection is not relevant because the above analyses were adjusted by region. Our controls were provided by a population-based study on pleural mesothelioma (called MISEM) and a hospital-based study on cholangiocarcinoma (called CARA). In MISEM, the response rate was 48.4%, a low but not unexpected rate as participation among population controls is usually lower and has been declining over time (5). It is important to underline that ReNaM applied the same questionnaire that was used for interviews and carried out the same exposure assessment as both MISEM and CARA. As repeatedly stated in ReNaM papers (6-7), each regional operating center assesses asbestos exposure based on the individual questionnaire, other available information, and knowledge of local industries. Occupational exposure to asbestos is classified as definite, probable or possible. Occupational exposure is (i) definite when the subject`s work was reported or otherwise known to have involved the use of asbestos or asbestos-containing materials (MCA); (ii) probable when subjects worked in factories where asbestos or MCA were used, but their personal exposure could not be documented; and (iii) possible when they were employed in industrial activities known to entail the use of asbestos or MCA. Hence, the definite and probable categories are closer to one another and were combined in our analyses. In any case, restricting analyses to subjects with definite occupational exposure and using each set of controls separately, as suggested by Mezei et al, yielded elevated OR for TVT and pericardial mesothelioma among men using both the above described modelling strategies; the OR could not be calculated for women. There were 70 (25 pericardial and 45 TVT) occupationally exposed mesothelioma cases. In population-based studies, analyses by occupation are limited by the low prevalence of most specific jobs. As briefly reported in our paper, for purely descriptive purposes, the industrial activity of exposure (cases may have multiple exposures), were construction (22 exposures, 7 and 15 for pericardial and TVT mesotheliomas, respectively), steel mills and other metal working industries (4 and 11), textile industries (2 and 3), and agriculture (2 and 5); other sectors had lower exposure frequencies. The absence of industries like asbestos-cement production, shipbuilding and railway carriages production/repair should not be surprising and had already been observed (7). In the Italian multicenter cohort study of asbestos workers (8), given the person-years of observation accrued by workers employed in these industries and gender- and site-specific crude incidence rates, approximately 0.1 case of pericardial and 0.2 of TVT mesothelioma would have been expected from 1970 to 2010. Even increasing ten-fold such figures to account for higher occupational risks among these workers would not change much. Asbestos exposure in agriculture has been repeatedly discussed in ReNaM reports (9: pages 70, 73, 128, 164 and 205). Exposure opportunities included the presence of asbestos in wine production, reuse of hessian bags previously containing asbestos, or construction and maintenance of rural buildings. Similarly, mesothelioma cases and agricultural workers exposed to asbestos have been noted in France (10). In conclusion, the additional analyses we performed according to Mezei et al's suggestions confirm the association between asbestos exposure and pericardial and TVT mesothelioma, supporting the causal role of asbestos for all mesotheliomas. ReNaM`s continuing surveillance system with national coverage is a precious platform for launching analytical studies on pleural and extra pleural mesothelioma. References 1. Mezei G, Chang ET, Mowat FS, Moolgavkar SH. Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis Scand J Work Environ Health. 2021;47(1):85-86. https://doi.org/10.5271/3909 2. Marinaccio A, Consonni D, Mensi C, Mirabelli D, Migliore E, Magnani C et al.; ReNaM Working Group. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks. Scand J Work Environ Health. 2020;46(6):609-617. https://doi.org/10.5271/sjweh.3895. 3. Greenland S. Control-initiated case-control studies. Int J Epidemiol 1985 Mar;14(1):130-4. https://doi.org/10.1093/ije/14.1.130. 4. Pearce N. Analysis of matched case-control studies. BMJ 2016 Feb;352:i969. https://doi.org/10.1136/bmj.i969. 5. Bigert C, Gustavsson P, Straif K, Pesch B, Brüning T, Kendzia B et al. Lung cancer risk among cooks when accounting for tobacco smoking: a pooled analysis of case-control studies from Europe, Canada, New Zealand, and China. J Occup Environ Med 2015 Feb;57(2):202-9. https://doi.org/10.1097/JOM.0000000000000337. 6. Marinaccio A, Binazzi A, Marzio DD, Scarselli A, Verardo M, Mirabelli D et al.; ReNaM Working Group. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer 2012 May;130(9):2146-54. https://doi.org/10.1002/ijc.26229. 7. Marinaccio A, Binazzi A, Di Marzio D, Scarselli A, Verardo M, Mirabelli D et al. Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med 2010 Nov;67(11):760-5. https://doi.org/10.1136/oem.2009.051466. 8. Ferrante D, Chellini E, Merler E, Pavone V, Silvestri S, Miligi L et al.; the working group. Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure. Occup Environ Med 2017 Dec;74(12):887-98. https://doi.org/10.1136/oemed-2016-104100. 9. ReNaM VI Report. Available from: https://www.inail.it/cs/internet/docs/alg-pubbl-registro-nazionale-mesoteliomi-6-rapporto.pdf. Italian 10. Marant Micallef C, Shield KD, Vignat J, Baldi I, Charbotel B, Fervers B et al. Cancers in France in 2015 attributable to occupational exposures. Int J Hyg Environ Health 2019 Jan;222(1):22-9. https://doi.org/10.1016/j.ijheh.2018.07.015.}, }
@article {pmid33381446, year = {2020}, author = {Yoshikawa, Y and Kuribayashi, K and Minami, T and Ohmuraya, M and Kijima, T}, title = {Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors-Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {554570}, pmid = {33381446}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is strongly associated with occupational or environmental asbestos exposure and arises from neoplastic transformation of mesothelial cells in the pleural cavity. The only standard initial treatment for unresectable MPM is combination chemotherapy with cisplatin (CDDP) and pemetrexed (PEM). Further, CDDP/PEM is the only approved regimen with evidence of prolonged overall survival (OS), although the median OS for patients treated with this regimen is only 12 months after diagnosis. Thus, the development of new therapeutic strategies has been investigated for approximately 20 years. In contrast to recent advances in personalized lung cancer therapies, diagnostic and prognostic biomarker research has just started in mesothelioma. Epigenetic alterations include DNA methylation, histone modifications, and other chromatin-remodeling events. These processes are involved in numerous cellular processes including differentiation, development, and tumorigenesis. Epigenetic modifications play an important role in gene expression and regulation related to malignant MPM phenotypes and histological subtypes. An immune checkpoint PD-1 inhibitor, nivolumab, was approved as second-line therapy for patients who had failed initial chemotherapy, based on the results of the MERIT study. Various clinical immunotherapy trials are ongoing in patients with advanced MPM. In this review, we describe recent knowledge on epigenetic alterations, which might identify candidate therapeutic targets and immunotherapeutic regimens under development for MPM.}, }
@article {pmid33380218, year = {2020}, author = {Seastedt, KP and Pruett, N and Hoang, CD}, title = {Mouse models for mesothelioma drug discovery and development.}, journal = {Expert opinion on drug discovery}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/17460441.2021.1867530}, pmid = {33380218}, issn = {1746-045X}, abstract = {INTRODUCTION: Mesothelioma is an aggressive mesothelial lining tumor. Available drug therapies include chemotherapeutic agents, targeted molecular therapies, and immune system modulators. Mouse models were instrumental in the discovery and evaluation of such therapies, but there is need for improved understanding of the role of inflammation, tumor heterogeneity, mechanisms of carcinogenesis, and the tumor microenvironment. Novel mouse models may provide new insights and drive drug therapy discovery that improves efficacy.<br><br>AREAS COVERED: This review concerns available mouse models for mesothelioma drug discovery and development including the advantages and disadvantages of each. Gaps in current knowledge of mesothelioma are highlighted, and future directions for mouse model research are considered.<br><br>EXPERT OPINION: Soon, CRISPR-Cas gene-editing will improve understanding of mesothelioma mechanisms foundational to the discovery and testing of efficacious therapeutic targets. There are at least two likely areas of upcoming methodology development. One is concerned with precise modeling of inflammation - is it a causal process whereby inflammatory signals contribute to tumor initiation, or is it a secondary passenger process driven by asbestos exposure effects? The other area of methods improvement regards the availability of humanized immunocompromised mice harboring patient-derived xenografts. Combining human tumors in an environment with human immune cells will enable rapid innovation in immuno-oncology therapeutics.}, }
@article {pmid33379304, year = {2020}, author = {Oddone, E and Bollon, J and Nava, CR and Minelli, G and Imbriani, M and Consonni, D and Marinaccio, A and Magnani, C and Barone-Adesi, F}, title = {Forecast of Malignant Peritoneal Mesothelioma Mortality in Italy up to 2040.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {1}, pages = {}, doi = {10.3390/ijerph18010160}, pmid = {33379304}, issn = {1660-4601}, support = {BRIC n.59//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; }, abstract = {Despite their differences, pleural and peritoneal mesothelioma are frequently lumped together to describe epidemic curves and to forecast future mesothelioma trends. This study aims to describe the malignant peritoneal mesothelioma (MPeM) epidemic in Italy (1996-2016) and to forecast future trends up to 2040 in order to contribute to the assessment of MPeM future burden. All MPeM deaths in Italy from 1996-2016 were collected (as provided by the Italian National Statistical Institute (ISTAT)) in order to estimate MPeM mortality rates for each 3-year period from 1996 to 2016. Poisson age-period-cohort (APC) models were then used to forecast MPeM future trends. Between 2017 and 2040, 1333 MPeM deaths are expected. The number of MPeM deaths, as well as mortality rates, are expected to constantly decrease throughout the considered period. Based on considering the information from this study, it can be concluded that the MPeM epidemic has probably already reached its peak in Italy.}, }
@article {pmid33363966, year = {2020}, author = {Brahim, D and Mechergui, N and Ben Said, H and Cherif, D and Ladhari, N and Youssef, I}, title = {Peritoneal mesothelioma associated with bladder cancer and occupational exposure to asbestos: A case report.}, journal = {Clinical case reports}, volume = {8}, number = {12}, pages = {3529-3532}, pmid = {33363966}, issn = {2050-0904}, abstract = {Mesothelioma is a rare tumor usually located on the pleura. In this typical location, it is closely linked to asbestos exposure. However, in other locations such as in peritoneal mesothelioma, the association to asbestos remains unusual.}, }
@article {pmid33347735, year = {2020}, author = {Re, A and Shersher, D and Allen, A and Schwarting, R and Ren, S}, title = {Malignant pleural neoplasm with both differentiation of epithelioid mesothelioma and squamous-cell carcinoma, a rare phenomena.}, journal = {Diagnostic cytopathology}, volume = {}, number = {}, pages = {}, doi = {10.1002/dc.24686}, pmid = {33347735}, issn = {1097-0339}, abstract = {Malignant mesothelioma, a neoplasm arising within the serosal surfaces, has been linked closely to asbestos exposure. We present a case of 72-year-old male with a 27 year work-related history of asbestos exposure who presented with dyspnea. Chest computed tomography scan showed a large, right pleural effusion with compressive right lung atelectasis. Biopsies, subsequent pleurectomy and lung wedge resections revealed epithelioid malignant mesothelioma with associated focal non-keratinizing squamous-cell carcinoma, supported by extensive immunohistochemical stains and molecular studies. The patient was treated with 6 cycles of carboplatin/pemetrexed, showing no new metastases. Seven months post-treatment, the patient presented with progressive dyspnea and large pleural effusions. Bilateral pleural fluid was collected and showed malignant epithelioid cells, morphologically similar to the patient's pleural neoplastic cells. However, the tumor was positive for squamous cells markers and showed BAP1 loss, while negative for mesothelial markers. The findings support the diagnosis of squamous-cell carcinoma and were consistent with the patient's previously diagnosed pleural neoplastic origin. A malignant mesothelioma associated with squamous-cell carcinoma is a rare phenonmenon. To our knowledge, only two case reports are available in current literature. This unique case shows a single pleura tumor differentiating as both malignant mesothelioma and squamous-cell carcinoma. Squamous-cell carcinoma is the predominating malignancy seen within the bilateral pleural effusions, a potential pitfall for cytology specimen diagnosis.}, }
@article {pmid33346174, year = {2020}, author = {Fazzo, L and Minelli, G and Bruno, C and Comba, P and Conti, S and De Santis, M and Zona, A and Binazzi, A and Magnani, C and Marinaccio, A and Iavarone, I}, title = {Early mortality from malignant mesothelioma in Italy as a proxy of environmental exposure to asbestos in children.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {56}, number = {4}, pages = {478-486}, doi = {10.4415/ANN_20_04_10}, pmid = {33346174}, issn = {2384-8553}, abstract = {Malignant mesothelioma (MM) is a rare neoplasm caused by asbestos. Mortality from MM in ≤50 years old people, considering the long latency, is likely related to asbestos exposure in childhood. Mortality from MM (C45, ICD10 code) is described among ≤50 years (ys) old people in Italy, in 2003-2016. National and regional Standardized Rates (SRs) were computed by age-class. The North-South trend of regional SRs, increasing in >50ys age-class, showed a flat cline in ≤50ys old people. Municipal Standardized Mortality Ratios (SMRs) were computed, with respect to regional figures, for ≤50 ys old population. In Italy, 487 people ≤50 ys old died from MM, in 2003-2016 (2.5% of all MM deaths), corresponding to 35/year. The highest SMRs were observed in Northern Regions, the most industrialized areas. Exceeding SMRs were found in 10 municipalities where former asbestos-cement plants, shipyards, and a quarry contaminated by fluoro-edenite fibres were present. Early mortality from MM, proxy of childhood environmental asbestos exposure, deserves particular concern.}, }
@article {pmid33344293, year = {2020}, author = {Chand, MT and Edens, J and Lin, T and Anderson, I and Berri, R}, title = {Benign multicystic peritoneal mesothelioma: literature review and update.}, journal = {Autopsy &amp; case reports}, volume = {10}, number = {3}, pages = {e2020159}, pmid = {33344293}, issn = {2236-1960}, abstract = {Benign multicystic peritoneal mesothelioma (BMPM) is a rare peritoneal tumor diagnosed predominantly in pre-menopausal women. Associated risk factors include endometriosis and pelvic inflammatory disease in women, and prior abdominal surgery in both genders. To date, the pathogenesis of this disease remains controversial with possible etiologies, including a neoplastic versus a reactive process. Given the risk factors, some authors believe that this disease is secondary to a reactive process. However, because some studies describe cases where there is no prior surgical history or inflammatory milieu present, and because of this entity's predilection for recurrence, some authors believe the origin to be neoplastic. Some genetic and familial associations have also been reported. Malignant transformation is extremely rare, with only two cases reported in the literature, despite the recurrence potential. Like the etiology, the name of this entity is also controversial. Some authors prefer the term &quot;peritoneal inclusion cyst (PCM)&quot; instead of &quot;benign cystic mesothelioma&quot; and argue that the term mesothelioma should only be used when there is evidence of atypia. Most cases of BMPM are discovered incidentally. Others reflect sequela of tumor mass effect. It appears intra-operatively as large, multi-focal, cystic lesions in the peritoneal and pelvic cavity. Diagnosis is achieved through surgical sampling with histopathological examination. Immunobiologically, BMPM exhibits multiple small cystic spaces with flattened lining containing calretinin positive cells without atypical features, mitotic figures, or tissue invasion. Treatment includes cytoreductive surgery. Here we present a case of BMPM in a 60-year-old male - a rare disease in an uncommon patient population.}, }
@article {pmid33336248, year = {2020}, author = {Bartkowiak, K and Casjens, S and Andreas, A and Ačkar, L and Joosse, SA and Raiko, I and Brüning, T and Geffken, M and Peine, S and Johnen, G and Weber, DG and Pantel, K}, title = {Sensitive Blood-Based Detection of Asbestos-Associated Diseases Using Cysteine-Rich Angiogenic Inducer 61 as Circulating Protein Biomarker.}, journal = {Clinical chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1093/clinchem/hvaa232}, pmid = {33336248}, issn = {1530-8561}, abstract = {BACKGROUND: Detection of asbestos-associated diseases like asbestosis or mesothelioma is still challenging. We sought to improve the diagnosis of benign asbestos-associated disease (BAAD) by detection of the protein cysteine-rich angiogenic inducer 61 (Cyr61) in human plasma.<br><br>METHODS: Plasma Cyr61 was quantified using an enzyme-linked immunosorbent assay. Plasma samples from males diagnosed with BAAD, but without a malignant disease (n = 101), and malignant mesothelioma (n = 21; 15 males, 6 females), as well as nonasbestos-exposed healthy control participants (n = 150; 58 males, 92 females) were analyzed. Clinical sensitivity and specificity of Cyr61 were determined by receiver operating characteristic analysis.<br><br>RESULTS: The median plasma Cyr61 concentration for healthy control participants was 0.27 ng/mL. Cytoplasmic Cyr61 in peripheral blood mononuclear cells from healthy control participants was evenly distributed, as detected by immunofluorescent staining. The increase in plasma Cyr61 concentrations in the BAAD study group was statistically significant compared to the healthy control participants (P < 0.0001). For the detection of BAAD vs male healthy control participants, clinical sensitivity was 88% and clinical specificity 95% with an area under the curve of 0.924 at maximal Youden Index. For a predefined clinical specificity of 100%, the clinical sensitivity was 76%. For male mesothelioma patients vs male healthy control participants, the clinical sensitivity at maximal Youden Index was 95% with a clinical specificity of 100% (area under the curve, 0.997) and for a predefined clinical specificity of 100%, the clinical sensitivity was 93%.<br><br>CONCLUSIONS: In our study, plasma Cyr61 protein concentrations showed to be a new biomarker for asbestos-associated diseases like BAAD and mesothelioma in men, which deserves further investigation in large-scale cohort studies.}, }
@article {pmid33329908, year = {2020}, author = {Park, EK and Johnson, AR and Wilson, D and Thomas, PS and Yates, DH}, title = {Follow-up of Soluble Mesothelin-Related Protein Levels in Participants With Asbestos-Related Disorders.}, journal = {Safety and health at work}, volume = {11}, number = {4}, pages = {425-430}, pmid = {33329908}, issn = {2093-7911}, abstract = {Background: Asbestos exposure is associated with the development of the cancer malignant mesothelioma (MM). Measurement of soluble mesothelin-related protein (SMRP) has been suggested as a method for detection of MM in its early stages. We prospectively examined SMRP levels in participants with asbestos exposure who are a group at a high risk of development of MM.<br><br>Methods: This study was a follow-up of our cohort of 322 asbestos-exposed participants. No further participants developed MM or malignancy over the study period. Mean follow-up time was 22.9 months.<br><br>Results: Mean (standard deviation) SMRP levels at baseline and follow-up were 0.94 (0.79) and 0.91 (0.86) nmol/L (p = 0.1033), respectively. Mean SMRP levels of the healthy individuals exposed to asbestos at baseline was significantly lower than those of participants with asbestosis and pleural plaques alone; similar patterns were found on follow-up measurements. There was a statistically significant effect of age on serial SMRP measurements. Our study confirms higher levels in participants with nonmalignant asbestos-related disorders. Levels decreased in asbestos-related disorders other than asbestosis, where a small increase was observed. We did not detect any further cases of malignancy.<br><br>Conclusion: Monitoring programs for early detection of MM need to take into account increased SMRP levels found in benign asbestos-related diseases.}, }
@article {pmid33319489, year = {2020}, author = {Sakai, K and Inoue, M and Mikami, S and Nishimura, H and Kuwabara, Y and Kojima, A and Toda, M and Ogawa-Kobayashi, Y and Kikuchi, S and Hirata, Y and Mikami-Saito, Y and Kyoyama, H and Moriyama, G and Shiibashi, M and Seike, M and Gemma, A and Uematsu, K}, title = {Functional inhibition of heat shock protein 70 by VER-155008 suppresses pleural mesothelioma cell proliferation via an autophagy mechanism.}, journal = {Thoracic cancer}, volume = {}, number = {}, pages = {}, doi = {10.1111/1759-7714.13784}, pmid = {33319489}, issn = {1759-7714}, support = {16-B-1-22//Saitama Medical University/ ; 18-B-1-19//Saitama Medical University/ ; }, abstract = {BACKGROUND: Pleural mesothelioma, a devastating asbestos-associated malignancy, urgently requires a novel effective therapy. Heat shock protein 70 (HSP70), which is synthesized in the cell response to protein damage, is expected to be a new target for antitumor treatment. In addition to its well-known protein refolding function, HSP70 regulates cell proliferation through different pathways, including PI3K/AKT/mTOR, and autophagy in malignant cells. In this study, we attempted to clarify the effects of VER-155008, an HSP70 inhibitor, on pleural mesothelioma.<br><br>METHODS: Human pleural mesothelioma cell lines 211H, H2452 and H28 were cultured with VER-155008, and protein expression, cell proliferation, colony formation, cell cycle, synergistic effect with cisplatin, and autophagy induction were analyzed.<br><br>RESULTS: In mesothelioma cell lines, VER-155008 (5.0 μM or more) inhibited cell growth and colony formation, accompanied by G1 cell cycle arrest. According to western blot analysis, VER-155008 reduced p-AKT expression. However, VER-155008 failed to show a synergistic effect with cisplatin on cell growth. Mesothelioma cells transfected with the novel plasmid pMRX-IP-GFP-LC3-RFP-LC3ΔG, which was developed for the quantitative and statistical estimation of macroautophagy, showed enhanced macroautophagy upon treatment with VER-155008 and gefitinib which is an EGFR-tyrosine kinase inhibitor. In addition, fetal bovine serum deprivation induced macroautophagy was further enhanced by VER-155008.<br><br>CONCLUSIONS: On the basis of these results, functional HSP70 inhibition by VER-155008 suppressed cell growth in pleural mesothelioma cells, accompanied by enhanced macroautophagy. HSP70 inhibition is thus expected to become a new strategy for treating mesothelioma.<br><br>KEY POINTS: Significant findings of the study In pleural mesothelioma cells, inhibition of HSP70 function by VER-155008 suppressed cell proliferation accompanied by induction of autophagy which was synergistically enhanced under the starvation condition, whereas gefitinib, an EGFR-TKI, did not show the same synergistic effect in autophagy. What this study adds The inhibition of HSP70 induced autophagy and suppressed cell proliferation in mesothelioma cells.}, }
@article {pmid33318203, year = {2020}, author = {Bononi, A and Goto, K and Ak, G and Yoshikawa, Y and Emi, M and Pastorino, S and Carparelli, L and Ferro, A and Nasu, M and Kim, JH and Suarez, JS and Xu, R and Tanji, M and Takinishi, Y and Minaai, M and Novelli, F and Pagano, I and Gaudino, G and Pass, HI and Groden, J and Grzymski, JJ and Metintas, M and Akarsu, M and Morrow, B and Hassan, R and Yang, H and Carbone, M}, title = {Heterozygous germline BLM mutations increase susceptibility to asbestos and mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {52}, pages = {33466-33473}, doi = {10.1073/pnas.2019652117}, pmid = {33318203}, issn = {1091-6490}, abstract = {Rare biallelic BLM gene mutations cause Bloom syndrome. Whether BLM heterozygous germline mutations (BLM+/-) cause human cancer remains unclear. We sequenced the germline DNA of 155 mesothelioma patients (33 familial and 122 sporadic). We found 2 deleterious germline BLM+/- mutations within 2 of 33 families with multiple cases of mesothelioma, one from Turkey (c.569_570del; p.R191Kfs*4) and one from the United States (c.968A>G; p.K323R). Some of the relatives who inherited these mutations developed mesothelioma, while none with nonmutated BLM were affected. Furthermore, among 122 patients with sporadic mesothelioma treated at the US National Cancer Institute, 5 carried pathogenic germline BLM+/- mutations. Therefore, 7 of 155 apparently unrelated mesothelioma patients carried BLM+/- mutations, significantly higher (P = 6.7E-10) than the expected frequency in a general, unrelated population from the gnomAD database, and 2 of 7 carried the same missense pathogenic mutation c.968A>G (P = 0.0017 given a 0.00039 allele frequency). Experiments in primary mesothelial cells from Blm+/- mice and in primary human mesothelial cells in which we silenced BLM revealed that reduced BLM levels promote genomic instability while protecting from cell death and promoted TNF-α release. Blm+/- mice injected intraperitoneally with asbestos had higher levels of proinflammatory M1 macrophages and of TNF-α, IL-1β, IL-3, IL-10, and IL-12 in the peritoneal lavage, findings linked to asbestos carcinogenesis. Blm+/- mice exposed to asbestos had a significantly shorter survival and higher incidence of mesothelioma compared to controls. We propose that germline BLM+/- mutations increase the susceptibility to asbestos carcinogenesis, enhancing the risk of developing mesothelioma.}, }
@article {pmid33314519, year = {2020}, author = {Kishimoto, T and Fujimoto, N and Mizuhashi, K and Kozawa, S and Miura, M}, title = {Retrospective investigation on diagnostic process for benign asbestos pleural effusion (BAPE) using checklist.}, journal = {Journal of occupational health}, volume = {62}, number = {1}, pages = {e12182}, pmid = {33314519}, issn = {1348-9585}, support = {//The research and development, and the dissemination project/ ; //Japan Organization of Occupational Health and Safety/ ; }, abstract = {OBJECTIVES: In Japan, benign asbestos pleural effusion (BAPE) has been eligible for industrial accident compensation since 2003 as an asbestos-related disease despite the lack of good criteria. We compiled a criteria into a checklist of essential items and for excluding other diseases inducing pleural effusion as a diagnosis process.<br><br>METHOD: Thoracentesis was performed in order to confirm the presence of pleural effusion at the initial diagnosis, and 105 suspected BAPE patients were retrospectively examined. We complied a checklist comprising the following diagnostic items: (a) occupational asbestos exposure; (b) confirmation of exudate of pleural effusion; (c) exclusion of pleural effusion with malignant tumors based on negative results of CEA and hyaluronic acid, and cytology of pleural effusion; (d) exclusion of rheumatic, bacterial, and tuberculous pleuritis; (d) radiological findings for exclusion of malignancies; and (e) histopathological findings based on thoracoscopy that exclude malignancies (when thoracoscopy was not performed, there was confirmation that no malignancies were present during 3-month follow-up observation). Cases that satisfied all items were defined as BAPE.<br><br>RESULTS: Among the 105 suspected cases, there were five cases that had no occupational asbestos exposure; six cases in which transudate of on pleural effusion; one case each of rheumatoid pleuritis and tuberculous pleuritis; and five cases of pleural mesothelioma based on chest radiography and histopathological findings within 3 months after initial diagnosis. Therefore, we excluded 18 cases from the 105 candidates and determined 87 cases of BAPE.<br><br>CONCLUSION: We consider that six items described above are suitable for diagnosing BAPE.}, }
@article {pmid33312638, year = {2020}, author = {Moteallemi, A and Minaei, M and Tahmasbizadeh, M and Fadaei, S and Masroor, K and Fanaei, F}, title = {Monitoring of airborne asbestos fibers in an urban ambient air of Mashhad City, Iran: levels, spatial distribution and seasonal variations.}, journal = {Journal of environmental health science &amp; engineering}, volume = {18}, number = {2}, pages = {1239-1246}, pmid = {33312638}, issn = {2052-336X}, abstract = {Asbestos, as with other pollutants in the air, has adverse effects on the health of human beings and animals. Today, the relationship between presence of asbestos fibers in the air breathed by humans and developing serious diseases such as lung cancer (asbestosis) and mesothelioma has been proven. The objectives of this study were to monitor the levels of asbestos fibers in ambient air of Mashhad, Iran during 2018, and to draw its Geographic Information System (GIS) distribution map for the city. In this descriptive study, 13 sampling points in Mashhad city were chosen. Sampling of asbestos was carried out for 3 hour during summer and winter at 2018. Sampling of asbestos was performed using MCE (Mixed Cellulose Ester) membrane filters (pour size 0.45 µm; diameter: 25 mm) and cassette holder and peripheral pump. The samples were the analyzed by the phase contrast microscopy (PCM) method (NIOSH7400). Also, to investigate the type of asbestos and for more accurate counting of fibers, Scanning Electron Microscopy (SEM) analysis was utilized. Meteorological parameter were recorded through portable devices. To draw the graphs, Excel, R and Arc GIS software were used. Results showed that the mean asbestos fiber concentrations were equal to 11.40 ± 2.14 and 14.38 ± 2.52 f/L in summer and winter, respectively. The maximum level of asbestos fiber was detected in the station of Baitolmoghaddas square by 26.64 ± 2.14 and 19.3 SEM f/L in winter and summer, respectively. High concentration of asbestos fiber observed in this study can be attributed to the heavy traffic, the presence of prominent industries in the vicinity of the study area, and topographic features. The results from this research recommends that suitable controlling policies should be regulated to reduce both ambient air asbestos and its adverse health endpoints in Mashhad.}, }
@article {pmid33304846, year = {2020}, author = {Cheng, YY and Yuen, ML and Rath, EM and Johnson, B and Zhuang, L and Yu, TK and Aleksova, V and Linton, A and Kao, S and Clarke, CJ and McCaughan, BC and Takahashi, K and Lee, K}, title = {CDKN2A and MTAP Are Useful Biomarkers Detectable by Droplet Digital PCR in Malignant Pleural Mesothelioma: A Potential Alternative Method in Diagnosis Compared to Fluorescence In Situ Hybridisation.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {579327}, pmid = {33304846}, issn = {2234-943X}, abstract = {Background: The diagnosis of malignant pleural mesothelioma (MPM) can be difficult, in part due to the difficulty in distinguishing between MPM and reactive mesothelial hyperplasia (RMH). The tumor suppressor gene, CDKN2A, is frequently silenced by epigenetic mechanisms in many cancers; in the case of MPM it is mostly silenced via genomic deletion. Co-deletion of the CDKN2A and methylthioadenosine phosphorylase (MTAP) genes has been researched extensively and discovered to be a highly specific characteristic of MPM. Most studies have used FISH to detect the deletion of CDKN2A and IHC for MTAP as a surrogate for this. In this study, we aim to investigate and validate droplet digital PCR (ddPCR) as an emerging alternative and efficient testing method in diagnosing MPM, by particularly emphasizing on the loss of MTAP and CDKN2A.<br><br>Methods: This study included 75 formalin fixed paraffin embedded (FFPE) MPM tissue, and 12 normal pleural tissue and 10 RMH as control. Additionally, primary MPM cell lines and normal pleural samples were used as biomarker detection controls, as established in our previous publication. All FFPE specimens were processed to isolate the DNA, that was subsequently used for ddPCR detection of CDKN2A and MTAP. FFPE samples were also analyzed by fluorescence in situ hybridization (FISH) for CDKN2A and MTAP deletion, and for MTAP IHC expression. Concordance of IHC and ddPCR with FISH were studied in these samples.<br><br>Results: 95% and 82% of cases showed co-deletion of both MTAP and CDKN2A when determined by FISH and ddPCR respectively. ddPCR has a sensitivity of 72% and specificity of 100% in detecting CDKN2A homozygous loss in MPM. ddPCR also has a concordance rate of 92% with FISH in detecting homozygous loss of CDKN2A. MTAP IHC was 68% sensitive and 100% specific for detecting CDKN2A homozygous loss in MPM when these losses were determined by ddPCR.<br><br>Conclusion: Our study confirms that MTAP is often co-deleted with CDKN2A in MPM. Our in-house designed ddPCR assays for MTAP and CDKN2A are useful in differentiating MPM from RMH, and is highly concordant with FISH that is currently used in diagnosing MPM. ddPCR detection of these genetic losses can potentially be utilized as an alternative method in the diagnosis of MPM and for the future development of a less-invasive MPM-specific detection technique on MPM tumor tissue DNA.}, }
@article {pmid33304592, year = {2021}, author = {Cheah, HM and Fitzgerald, D and Louw, A and Creaney, J and Lee, YCG}, title = {Hyaluronic acid in viscous malignant mesothelioma pleural effusion.}, journal = {Respirology case reports}, volume = {9}, number = {1}, pages = {e00694}, pmid = {33304592}, issn = {2051-3380}, abstract = {Malignant pleural effusion (MPE) is common with mesothelioma. We report two cases of extraordinarily viscous MPEs associated with mesothelioma. The viscosity prohibited spontaneous gravity-dependent drainage via indwelling pleural catheters. Our ex vivo experiments found very high hyaluronic acid (HA) content within the fluid. Treatment of the fluid with hyaluronidase, but not with deoxyribonucleases, significantly reduced fluid viscosity. The results provide proof that HA can contribute to high viscosity of pleural fluid in mesothelioma. Research into strategies of counteracting HA properties in the management of MPEs may provide further insight.}, }
@article {pmid33300108, year = {2020}, author = {Dell'Anno, I and Martin, SA and Barbarino, M and Melani, A and Silvestri, R and Bottaro, M and Paolicchi, E and Corrado, A and Cipollini, M and Melaiu, O and Giordano, A and Luzzi, L and Gemignani, F and Landi, S}, title = {Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma.}, journal = {Investigational new drugs}, volume = {}, number = {}, pages = {}, pmid = {33300108}, issn = {1573-0646}, support = {153/16//Fondazione Pisa/ ; }, abstract = {Objectives Malignant pleural mesothelioma (MPM) is an occupational disease mainly due to asbestos exposure. Effective therapies for MPM are lacking, making this tumour type a fatal disease. Materials and Methods In order to meet this need and in view of a future &quot;drug repositioning&quot; approach, here we screened five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) and one SV40-immortalized mesothelial cell line (MeT-5A) as a non-malignant model, with a library of 1170 FDA-approved drugs. Results Among several potential compounds, we found that fludarabine (F-araA) and, to a lesser extent, risedronic acid (RIS) were cytotoxic in MPM cells, in comparison to the non-malignant Met-5A cells. In particular, F-araA reduced the proliferation and the colony formation ability of the MPM malignant cells, in comparison to the non-malignant control cells, as demonstrated by proliferation and colony formation assays, in addition to measurement of the phospho-ERK/total-ERK ratio. We have shown that the response to F-araA was not dependent upon the expression of DCK and NT5E enzymes, nor upon their functional polymorphisms (rs11544786 and rs2295890, respectively). Conclusion This drug repositioning screening approach has identified that F-araA could be therapeutically active against MPM cells, in addition to other tumour types, by inhibiting STAT1 expression and nucleic acids synthesis. Further experiments are required to fully investigate this.}, }
@article {pmid33257382, year = {2020}, author = {Tanaka, T and Miyamoto, Y and Sakai, A and Fujimoto, N}, title = {Nivolumab for malignant peritoneal mesothelioma.}, journal = {BMJ case reports}, volume = {13}, number = {11}, pages = {}, doi = {10.1136/bcr-2020-237721}, pmid = {33257382}, issn = {1757-790X}, abstract = {Malignant peritoneal mesothelioma (MPeM) is a highly malignant neoplasm of the peritoneum, which carries a poor prognosis. A 70-year-old man, who was employed in the shipbuilding industry and exposed to asbestos for 50 years, was found to have a low-density lesion in the peritoneum around the liver and spleen, associated with multiple mediastinal and parasternal lymphadenopathy. Laparoscopic exploration was performed, and biopsy specimen analysis led to a diagnosis of MPeM. Initial systemic chemotherapy comprising cisplatin and pemetrexed yielded a modest cytoreductive effect. However, 4 months later, the patient presented with abdominal distension and anorexia. CT images revealed massive ascites, bowel obstruction and an enlarged intra-abdominal tumour, which was considered progression of the MPeM. The patient was treated with nivolumab. Bowel obstruction was improved after the first administration, and his sense of abdomen distension completely disappeared after the third administration. This case supports the utility of immunotherapy in MPeM.}, }
@article {pmid33238762, year = {2020}, author = {Arulananda, S and Lee, EF and Fairlie, WD and John, T}, title = {The role of BCL-2 family proteins and therapeutic potential of BH3-mimetics in malignant pleural mesothelioma.}, journal = {Expert review of anticancer therapy}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/14737140.2021.1856660}, pmid = {33238762}, issn = {1744-8328}, abstract = {Introduction: With limited recent therapeutic changes, malignant pleural mesothelioma (MPM) is associated with poor survival and death within 12 months, making it one of the most lethal malignancies. Due to unregulated asbestos use in developing countries and home renovation exposures, cases of MPM are likely to present for decades. As MPM is largely driven by dysregulation of tumor suppressor genes, researchers have examined other mechanisms of subverting tumor proliferation and spread. Over-expression of pro-survival BCL-2 family proteins impairs cells from undergoing apoptosis, and BH3-mimetics targeting them are a novel treatment option across various cancers, though have not been widely investigated in MPM. Areas covered: This review provides an overview of MPM and its current treatment landscape. It summarizes the role of BCL-2 family proteins in tumorigenesis and the therapeutic potential of BH3-mimetics . Finally, it discusses the role of BCL-2 proteins in MPM and the pre-clinical rationale for investigating BH3-mimetics as a therapeutic strategy. Expert opinion: As a disease without readily actionable oncogene driver mutations and with modest benefit from immune checkpoint inhibition, novel therapeutic options are urgently needed for MPM. Hence, BH3-mimetics provide a promising treatment option, with evidence supporting dependence on pro-survival BCL-2 proteins for MPM cell survival.}, }
@article {pmid33233407, year = {2020}, author = {Cugliari, G and Catalano, C and Guarrera, S and Allione, A and Casalone, E and Russo, A and Grosso, F and Ferrante, D and Viberti, C and Aspesi, A and Sculco, M and Pirazzini, C and Libener, R and Mirabelli, D and Magnani, C and Dianzani, I and Matullo, G}, title = {DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {12}, number = {11}, pages = {}, pmid = {33233407}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 × 10-9) OS-related differential methylation of a single-CpG (cg03546163), located in the 5'UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm ≥ 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.}, }
@article {pmid33230247, year = {2020}, author = {Jiang, Z and Shen, W and Ying, S and Gao, Z and He, X and Chen, R and Xia, H and Guo, X and Fang, Y and Zhang, Y and Miao, J and Zhou, J and Zhang, X and Chen, J and Lou, J}, title = {Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {20373}, pmid = {33230247}, issn = {2045-2322}, abstract = {Fibulin-3 is an extracellular matrix glycoprotein widely expressed in various tissues. Tissue fibulin-3 expression have never been reported in association with prognosis of mesothelioma. Hence, we sought to determine the association between fibulin-3 expression and mesothelioma survival. We made a tissue microarray, which was comprised of cancer and normal tissue from mesothelioma patients (n = 82) during the period 1998-2017 in China. Fibulin-3 and HGMB1 expression were analyzed by immunohistochemistry method. Kaplan-Meier method and Cox proportional hazard models were used for analyzing survival data. Overall, 61 cases (74.4%) were female; 90.2% were of epithelioid type; the median overall survival time was 12.5 months. Fibulin-3 and HMGB1 were highly expressed in tumor tissue rather than adjacent tissue. The expression of fibulin-3 in tissue was correlated with that of HMGB1 (r = 0.32, P = 0.003). High expression of fibulin-3 in tumor tissue could predict poor survival in patients with mesothelioma (P = 0.02). This remained true in a multivariate model, with a significant hazard ratio of 1.91. We demonstrated that fibulin-3 in tumor tissue was a novel biomarker of poor survival of mesothelioma, suggesting it may be a relevant target for therapeutic intervention.}, }
@article {pmid33197421, year = {2020}, author = {Xia, H and Feng, L and Lin, L and Jiang, Z and Chen, J and Shi, W and Ying, S and Yu, M and Ju, L and Zhu, L and Shi, L and Zhang, X and Lou, J}, title = {Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS.}, journal = {Environmental research}, volume = {193}, number = {}, pages = {110467}, doi = {10.1016/j.envres.2020.110467}, pmid = {33197421}, issn = {1096-0953}, abstract = {Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.}, }
@article {pmid33149905, year = {2020}, author = {Filetti, V and Vitale, E and Broggi, G and Hagnäs, MP and Candido, S and Spina, A and Lombardo, C}, title = {Update of in vitro, in vivo and ex vivo fluoro-edenite effects on malignant mesothelioma: A systematic review (Review).}, journal = {Biomedical reports}, volume = {13}, number = {6}, pages = {60}, pmid = {33149905}, issn = {2049-9434}, abstract = {Fluoro-edenite (FE), asbestiform fiber found in Biancavilla (Sicily, Italy), presents various characteristics similar to the asbestos group, in particular two fibrous phases tremolite and actinolite. Indeed, epidemiological studies have shown that FE fibers have similar effects to those of asbestos fibers. Such studies have reported a high incidence of malignant mesothelioma (MM), an aggressive neoplasm of the serosal membranes lining the pleural cavity, in individuals residing there due to FE exposure in Biancavilla related to environmental contamination. Evidence has led to the classification of FE as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC). The aim of this systematic review is to compare the results achieved in in vitro, in vivo and ex vivo experimental studies involving FE in order to update the current knowledge on the pathogenesis and molecular mechanisms responsible for FE-mediated MM development as well as the availability of effective biomarkers for MM prevention and diagnosis. This review is focused on the pathophysiological mechanisms mediated by inflammation induced by FE fiber exposure and which are responsible for MM development. This review also discusses the discovery of new diagnostic and prognostic biomarkers for the management of this pathology. It is known that the risk of cancer development increases with chronic inflammation, arising from enhanced reactive oxygen species (ROS) and NO• production stimulated by the body to remove exogenous agents, causing DNA damage and enhanced signal transduction that may lead to activation of oncogenes. Studies concerning MM biomarker discovery indicate that several biomarkers have been proposed for MM, but mesothelin is the only Food and Drug Administration (FDA)-approved biomarker for MM, with limitations. In recent studies, in silico analysis to identify selected miRNAs highly deregulated in cancer samples when compared with normal control have been developed. This in silico approach could represent an effort in the field of biomarker discovery for MM.}, }
@article {pmid33149886, year = {2020}, author = {Notue, YA and Mbessoh, UI and Nganwa, G and Pambe, JN and Mefire, AC and Moifo, B and Sando, Z}, title = {Sarcomatoid malignant peritoneal mesothelioma presenting as a localized mesenteric tumor with no previous asbestos exposure.}, journal = {Journal of surgical case reports}, volume = {2020}, number = {10}, pages = {rjaa419}, pmid = {33149886}, issn = {2042-8812}, abstract = {Sarcomatoid malignant peritoneal mesothelioma is the rarest and most lethal form of peritoneal mesothelioma. We present the case of a sarcomatoid malignant peritoneal mesothelioma presenting as a localized mesenteric tumor in a 54-year-old female with no previous asbestos exposure. This clinical presentation is extremely rare and is the first documented in Cameroon.}, }
@article {pmid33148505, year = {2020}, author = {Khaliullin, TO and Kisin, ER and Guppi, S and Yanamala, N and Zhernovkov, V and Shvedova, AA}, title = {Differential responses of murine alveolar macrophages to elongate mineral particles of asbestiform and non-asbestiform varieties: Cytotoxicity, cytokine secretion and transcriptional changes.}, journal = {Toxicology and applied pharmacology}, volume = {409}, number = {}, pages = {115302}, doi = {10.1016/j.taap.2020.115302}, pmid = {33148505}, issn = {1096-0333}, abstract = {Human exposures to asbestiform elongate mineral particles (EMP) may lead to diffuse fibrosis, lung cancer, malignant mesothelioma and autoimmune diseases. Cleavage fragments (CF) are chemically identical to asbestiform varieties (or habits) of the parent mineral, but no consensus exists on whether to treat them as asbestos from toxicological and regulatory standpoints. Alveolar macrophages (AM) are the first responders to inhaled particulates, participating in clearance and activating other resident and recruited immunocompetent cells, impacting the long-term outcomes. In this study we address how EMP of asbestiform versus non-asbestiform habit affect AM responses. Max Planck Institute (MPI) cells, a non-transformed mouse line that has an AM phenotype and genotype, were treated with mass-, surface area- (s.a.), and particle number- (p.n.) equivalent concentrations of respirable asbestiform and non-asbestiform riebeckite/tremolite EMP for 24 h. Cytotoxicity, cytokines secretion and transcriptional changes were evaluated. At the equal mass, asbestiform EMP were more cytotoxic, however EMP of both habits induced similar LDH leakage and decrease in viability at s.a. and p.n. equivalent doses. DNA damage assessment and cell cycle analysis revealed differences in the modes of cell death between asbestos and respective CF. There was an increase in chemokines, but not pro-inflammatory cytokines after all EMP treatments. Principal component analysis of the cytokine secretion showed close clustering for the s.a. and p.n. equivalent treatments. There were mineral- and habit-specific patterns of gene expression dysregulation at s.a. equivalent doses. Our study reveals the critical nature of EMP morphometric parameters for exposure assessment and dosing approaches used in toxicity studies.}, }
@article {pmid33143837, year = {2020}, author = {Liu, Y and Tong, J and Ling, X and Cao, W and Fang, L}, title = {A Case of Systemic Lupus Erythematosus with Malignant Pleural Mesothelioma in a 42-year Woman.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {30}, number = {10}, pages = {1099-1101}, doi = {10.29271/jcpsp.2020.10.1099}, pmid = {33143837}, issn = {1681-7168}, abstract = {Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease characterised by inflammation. Malignant pleural mesothelioma (MPM) is a highly invasive malignant tumor derived from pleural mesothelial cells. Here, we report a case of SLE with MPM. A 42-year woman with no exposure to asbestos presented with severe left chest pain. Initially, we diagnosed her with SLE because of the clinical manifestations and high antinuclear antibody titer. Finally, a diagnosis of MPM was made, based on pleural biopsy. Her condition was under control after one cycle of chemotherapy and oral methotrexate. However, three years later, she was admitted with dyspnea, mild orthopnea, and tachycardia, and died one month later after discontinuing treatment. MPM is rare, and MPM with SLE is even rarer. We should pay attention to pleural effusion when diagnosing SLE. If possible, a pleural biopsy should be performed to reduce misdiagnosis and missed diagnosis. Key Words: Pleural effusion, Systemic lupus erythematosus (SLE), Mesothelioma.}, }
@article {pmid33133607, year = {2020}, author = {MacMillan, M and Roy, B and McLaren, S and Nowak, AK and Thomas, R and Lee, YCG}, title = {Widespread pulmonary invasion by malignant pleural mesothelioma: an important diagnostic consideration.}, journal = {Respirology case reports}, volume = {8}, number = {9}, pages = {e00675}, pmid = {33133607}, issn = {2051-3380}, abstract = {We report a rare case of early and extensive pulmonary invasion of malignant pleural mesothelioma (MPM) in a 70-year-old woman. She first presented with a hydropneumothorax and subsequent workup, including video-assisted thoracoscopy (VAT), confirmed MPM. After VAT, she developed dyspnoea, cough, and widespread pulmonary infiltrates of uncertain aetiology. These infiltrates progressed over the following months, failed to respond to antibiotics, and were strongly fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET). Bronchoalveolar lavage (BAL) yielded extremely viscous fluid containing mesothelioma cells. These cells were also found in the sputum when nebulized deoxyribonuclease (DNase) was trialled to enhance clearance of the pulmonary fluid. The patient deteriorated rapidly with progressive mediastinal and contralateral MPM involvement and died one month later. This case highlights the importance of including tumour invasion as a differential diagnosis of non-resolving pulmonary infiltrates in patients with MPM.}, }
@article {pmid33133014, year = {2020}, author = {Gesmundo, I and Silvagno, F and Banfi, D and Monica, V and Fanciulli, A and Gamba, G and Congiusta, N and Libener, R and Riganti, C and Ghigo, E and Granata, R}, title = {Calcitriol Inhibits Viability and Proliferation in Human Malignant Pleural Mesothelioma Cells.}, journal = {Frontiers in endocrinology}, volume = {11}, number = {}, pages = {559586}, pmid = {33133014}, issn = {1664-2392}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor, often associated with exposure to asbestos and characterized by poor prognosis and limited treatment options. The biologically active form of vitamin D, calcitriol, exerts anticancer effects in many cell types, both alone and in combination with chemotherapy drugs, through binding to vitamin D receptor (VDR); however, the role of calcitriol in MPM is still unknown. This study aimed to determine the potential antitumor role of calcitriol in MPM. The results showed that calcitriol reduces cell viability and proliferation in human MPM cells lines, which express both cytoplasmic and nuclear VDR; furthermore, calcitriol potentiated the inhibitory activity of the chemotherapy drug PEM. These effects were paralleled by cell cycle arrest and inhibition in expression of c-Myc and cyclins involved in cell cycle progression. Exposure of MPM cells to calcitriol also produced an alteration in mitochondrial function and inhibition in the expression of respiratory chain complex subunits. Finally, the inhibitory effects of calcitriol were also observed on viability of human primary MPM cells. Collectively, these results indicate a novel anticancer role for calcitriol in MPM, suggesting potential for vitamin D derivatives, alone or in combination with chemotherapy, in the treatment of this malignancy.}, }
@article {pmid33119974, year = {2020}, author = {Barbieri, PG and Mirabelli, D and Madeo, E and Somigliana, A}, title = {[Asbestos exposure and related diseases among friction products workers (1971-2016)].}, journal = {Giornale italiano di medicina del lavoro ed ergonomia}, volume = {42}, number = {3}, pages = {145-152}, pmid = {33119974}, issn = {1592-7830}, abstract = {SUMMARY: Worldwide studies have been published on the mortality of workers employed in asbestos-based materials for the production of clutches and brakes. However no one of these studies is related to Italian cases. Furthermore, not even surveys have been conducted in Italy to characterize the correlation between asbestos exposures and the possible occurring of asbestos-related disease. Our objectives are the following: i) to assess and quantify the asbestos exposure cases, ii) to describe the nature and the frequency of asbestos-related diseases among blue collar employees of an important factory producing brakes and clutches with chrysotile asbestos content from 1971 to 1993 and iii) to provide preliminary data on cumulative asbestos exposure estimated using lung fibre burden analysis. Critical appraisal of airborne asbestos fibre measurements and identification of cases of asbestos-related diseases between the blue collar employees, either notified to the local health authority or recovered from the Italian national Mesothelioma registry was investigated. Lung fibre burden analysis using the lung tissue samples from two deceased blue collar employees was also performed. Airborne asbestos fibre measurements (carried out in 1982) suggested asbestos fibres average concentrations of about 0.3 f/ml, while all 1992 measurements showed results below 0.1 f/ml. Furthermore, since 1988, we identified four cases of pleural plaques, three cases of asbestosis and seven cases of lung cancer. No case of malignant mesothelioma was found. In both lung cancer cases, analysed to measure the lung fibre burden, commercial amphiboles were absent or in limited concentration but chrysotile and, especially, tremolite asbestos were present in noticeable amount. In conclusion, since 1971 and up to early 1980s, exposure to chrysotile asbestos and talc, likely contaminated by tremolite, had been significant and comparable to levels causing asbestosis long-term risk. No case of malignant mesothelioma was found, that is consistent with the absence of amphiboles and with the lower risk of mesothelioma associated with the chrysotile asbestos. However a subset of the blue collar employees, the ones employed later on, could still have not reached the full risk condition, and so being still at risk of developing malignant mesothelioma. In the two lung cancer cases studied, the lung fibre burden was essentially made of chrysotile and tremolite. Lastly, lung cancer occurrence in the population of blue collar employees has been likely underestimated and the correct determination of lung cancer risk should be done through the mortality analysis of this population.}, }
@article {pmid33093002, year = {2020}, author = {Brandi, G and Deserti, M and Palloni, A and Turchetti, D and Zuntini, R and Pedica, F and Frega, G and De Lorenzo, S and Abbati, F and Rizzo, A and Di Marco, M and Massari, F and Tavolari, S}, title = {Intrahepatic cholangiocarcinoma development in a patient with a novel BAP1 germline mutation and low exposure to asbestos.}, journal = {Cancer genetics}, volume = {248-249}, number = {}, pages = {57-62}, doi = {10.1016/j.cancergen.2020.10.001}, pmid = {33093002}, issn = {2210-7762}, mesh = {Asbestos/*adverse effects ; Bile Duct Neoplasms/etiology/*pathology ; *Carcinogens ; Cholangiocarcinoma/etiology/*pathology ; Female ; *Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Middle Aged ; Prognosis ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BRCA1 associated protein-1 (BAP1) germline mutations define a novel hereditary cancer syndrome, namely BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by an increased susceptibility to develop different cancer types, including mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and basal cell and squamous cell carcinoma. Currently, the role of BAP1 germline mutations in intrahepatic cholangiocarcinoma (iCCA) pathogenesis is less known. Here we report the first clinical case of a female patient who developed an iCCA when she was 47-years-old and was found to carry a novel germline mutation at a splicing site of exon 4 in BAP1 gene (NM_004656.4: c.255_255+6del). An accurate anamnesis revealed the absence of risk factors linked to iCCA development, except for a low occupational exposure to asbestos. In tumor tissue, BAP1 sequencing, multiplex ligation-dependent probe amplification and immunoistochemistry showed the loss of heterozygosity and lack of nuclear expression, suggesting that BAP1 wild-type allele and functional protein were lost in cancer cells, in line with the classical two-hit model of tumor suppressor genes. Further studies are needed to confirm whether iCCA may be included into BAP1-TPDS cancer phenotypes and whether minimal asbestos exposure may facilitate the development of this malignancy in individuals carrying BAP1 germline mutations.}, }
@article {pmid33087407, year = {2020}, author = {Wong, JYY and Rice, C and Blair, A and Silverman, DT}, title = {Mesothelioma risk among those exposed to chrysotile asbestos only and mixtures that include amphibole: a case-control study in the USA, 1975-1980.}, journal = {Occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1136/oemed-2020-106665}, pmid = {33087407}, issn = {1470-7926}, abstract = {OBJECTIVES: Occupational asbestos exposure is causally linked to mesothelioma. However, whether exposure to only chrysotile asbestos is associated with mesothelioma risk, and the heterogeneity in risk by different fibre types/lengths remains unclear. We investigated whether mesothelioma risk differs among workers exposed to only chrysotile asbestos compared with chrysotile and ≥1 amphibole (ie, amosite, tremolite, anthophyllite and crocidolite) over the working lifetime.<br><br>METHODS: We analysed next-of-kin interview data including occupational histories for 580 white men (176 cases and 404 controls) from a case-control study of mesothelioma conducted in the USA in 1975-1980. Asbestos exposure was determined by an occupational hygienist using a job-exposure matrix and exposure categories included chrysotile only and nine chrysotile-amphibole mixtures. Logistic regression models were used to estimate the ORs and 95% CIs of mesothelioma, comparing each asbestos category to the unexposed group, adjusted for age at death and data source. Analysis of contrasts was used to assess overall heterogeneity and pair-wise differences in risk.<br><br>RESULTS: Exposure to long and short chrysotile only was associated with increased mesothelioma risk compared with the unexposed (OR=3.8 (95% CI 1.3 to 11.2)). The complex mixture of extra-long amosite, short and long chrysotile, tremolite and anthophyllite was associated with the highest risk (OR=12.8 (95% CI 4.1 to 40.2)). There was evidence for overall heterogeneity among the asbestos exposure categories (p heterogeneity=0.02). However, the lower risk observed for exposure to chrysotile only compared with the complex mixture was not significant (p difference=0.10).<br><br>CONCLUSIONS: Our findings suggest that policies aimed at regulating asbestos should target both pure chrysotile and mixtures that include amphibole.}, }
@article {pmid33085641, year = {2020}, author = {Piber, P and Vavpetic, N and Goricar, K and Dolzan, V and Kovac, V and Franko, A}, title = {The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma.}, journal = {Radiology and oncology}, volume = {54}, number = {4}, pages = {429-436}, pmid = {33085641}, issn = {1581-3207}, abstract = {Background Asbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM. Subjects and methods In total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis. Results We found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13-0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14-0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28-0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050). Conclusions Our findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.}, }
@article {pmid33069179, year = {2020}, author = {Janošíková, M and Nakládalová, M and Štěpánek, L and Boriková, A and Vildová, H and Fošum, M}, title = {Occurrence of asbestos-related occupational diseases in the Czech Republic in the last 20 years.}, journal = {Central European journal of public health}, volume = {28 Suppl}, number = {}, pages = {S37-S42}, doi = {10.21101/cejph.a6297}, pmid = {33069179}, issn = {1210-7778}, mesh = {*Asbestos/toxicity ; Czech Republic/epidemiology ; Humans ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/epidemiology ; Retrospective Studies ; }, abstract = {OBJECTIVES: Asbestos-related diseases are still a current problem worldwide. What is their occurrence in the Czech Republic? The answer is the subject of this study, which aims to provide a general and regional overview of the situation over the last 20 years with a more detailed focus on mesothelioma, the development of which is highly associated with asbestos exposure and the issue of their recognition as an occupational disease.<br><br>METHODS: In its retrospective reviews, the study is based on analyses of data from the Institute of Health Information and Statistics of the Czech Republic and data from the Czech National Cancer Registry, which also interconnects.<br><br>RESULTS: In the last 20 years, 512 new cases of occupational diseases from asbestos have been reported, namely 228 cases of pleural thickening, 133 mesotheliomas, 92 asbestoses, and 59 cases of lung cancer. In the last 5 years, mesotheliomas (n = 39) predominated among the reported diseases with a 45% proportion in the total number of 86 cases. The trend in their incidence, as the only one among asbestos-related diseases, is not declining. There was a significant difference in the overall incidence of mesothelioma in a general population and the incidence of occupational mesotheliomas. At the national level, occupational aetiology was acknowledged in only 11.3% of cases of mesothelioma on average. The highest proportion of occupational mesotheliomas and the highest incidence of all asbestos-related diseases were found in regions where the largest asbestos processing plants were located.<br><br>CONCLUSION: The authors emphasize the importance of work history for the diagnostic process of asbestos-related diseases and also the need to perform follow-up examinations for their early detection.}, }
@article {pmid33065463, year = {2020}, author = {Fusco, N and Vaira, V and Righi, I and Sajjadi, E and Venetis, K and Lopez, G and Cattaneo, M and Castellani, M and Rosso, L and Nosotti, M and Clerici, M and Ferrero, S}, title = {Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {150}, number = {}, pages = {53-61}, doi = {10.1016/j.lungcan.2020.09.026}, pmid = {33065463}, issn = {1872-8332}, abstract = {Malignant pleural mesothelioma (MPM) is a rare tumor with an extremely poor prognosis. Its pathogenesis is related to an immune response against asbestos fibers. The T-lymphocytes, including CD8POS and CD4POS cells, are an important part of the MPM immune microenvironment, and likely contribute to the therapy resistance observed in these tumors. Here, we sought to characterize the MPM-specific lymphocytes subpopulations within the tumor immune microenvironment to identify novel clinically relevant immunologic subtypes of tumors. Representative formalin-fixed, paraffin-embedded (FFPE) tissue blocks of 88 MPMs were included in tissue microarrays and subjected to tumor-infiltrating lymphocytes (TILs) quantification and subtyping by immunohistochemistry (IHC) with antibodies specific for CD4, CD8, and CD19. Further, PD-L1 (clone 22C3) expression was assessed by IHC as a combined positive score (CPS). Our data show that PD-L1 expression by tumor cells or the presence of a sarcomatoid component is related to increased stromal TILs presence in MPM. Survival analyses showed that low CD4POS and high CD8POS stromal TILs are associated with poor patients' survival. In MPMs with PD-L1 CPS > 1, stromal CD8HIGH was a poor prognostic factor, akin stromal CD4POS peritumoral TILs correlated with a worse prognosis. Furthermore, we demonstrated that a high CD4POS/CD8POS ratio in the tumor immune microenvironment is an independent prognostic factor for survival. Finally, we provided evidence that the characterization of the stromal immune landscape of MPM predicts responses to chemotherapy in subgroups of MPM. The results of this study provide novel insights into the clinical scenario of immune-related biomarkers in MPM.}, }
@article {pmid33055488, year = {2020}, author = {Sekine, I and Yamamoto, Y and Suzuki, T and Suzuki, H}, title = {Malignant Pleural Mesothelioma in Patients Who Previously Received Radiotherapy for their First Malignant Tumor.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {}, number = {}, pages = {}, doi = {10.2169/internalmedicine.6016-20}, pmid = {33055488}, issn = {1349-7235}, }
@article {pmid33055477, year = {2020}, author = {Nakashima, K and Demura, Y and Oi, M and Tabata, M and Tada, T and Shiozaki, K and Akai, M and Ishizuka, T}, title = {The Association between Malignant Pleural Mesothelioma and Thoracic Radiation Therapy for Hodgkin's Lymphoma: The First Case Report in Japan.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {}, number = {}, pages = {}, doi = {10.2169/internalmedicine.5134-20}, pmid = {33055477}, issn = {1349-7235}, abstract = {Malignant pleural mesothelioma (MPM) is mostly observed in patients with a history of asbestos exposure. Although other causes are rare, there are several reports of MPM induced by therapeutic radiation, mainly in Europe and North America. However, no such case has been reported in Japan. We herein report a 50-year-old Japanese woman who developed MPM 25 years after thoracic radiation therapy for Hodgkin's lymphoma. The patient had no history of exposure to asbestos; therefore, her history of radiation therapy was considered to be the cause of MPM. Clinicians should consider secondary MPM in patients with a history of thoracic radiation therapy.}, }
@article {pmid33054855, year = {2020}, author = {Saleh, DM and Alexander, WT and Numano, T and Ahmed, OHM and Gunasekaran, S and Alexander, DB and Abdelgied, M and El-Gazzar, AM and Takase, H and Xu, J and Naiki-Ito, A and Takahashi, S and Hirose, A and Ohnishi, M and Kanno, J and Tsuda, H}, title = {Comparative carcinogenicity study of a thick, straight-type and a thin, tangled-type multi-walled carbon nanotube administered by intra-tracheal instillation in the rat.}, journal = {Particle and fibre toxicology}, volume = {17}, number = {1}, pages = {48}, pmid = {33054855}, issn = {1743-8977}, abstract = {BACKGROUND: Multi-walled carbon nanotubes can be divided into two general subtypes: tangled and straight. MWCNT-N (60 nm in diameter) and MWCNT-7 (80-90 nm in diameter) are straight-type MWCNTs, and similarly to asbestos, both are carcinogenic to the lung and pleura when administered to rats via the airway. Injection of straight-type MWCNTs into the peritoneal cavity also induces the development of mesothelioma, however, injection of tangled-type MWCNTs into the peritoneal cavity does not induce carcinogenesis. To investigate these effects in the lung we conducted a 2-year comparative study of the potential carcinogenicities of a straight-type MWCNT, MWCNT-A (approximately 150 nm in diameter), and a tangled-type MWCNT, MWCNT-B (7.4 nm in diameter) after administration into the rat lung. Crocidolite asbestos was used as the reference material, and rats administered vehicle were used as the controls. Test materials were administered by intra-Tracheal Intra-Pulmonary Spraying (TIPS) once a week over a 7 week period (8 administrations from day 1 to day 50), followed by a 2-year observation period without further treatment. Rats were administered total doses of 0.5 or 1.0 mg MWCNT-A and MWCNT-B or 1.0 mg asbestos.<br><br>RESULTS: There was no difference in survival between any of the groups. The rats administered MWCNT-A or asbestos did not have a significant increase in bronchiolo-alveolar hyperplasia or tumors in the lung. However, the rats administered MWCNT-B did have significantly elevated incidences of bronchiolo-alveolar hyperplasia and tumors in the lung: the incidence of bronchiolo-alveolar hyperplasia was 0/20, 6/20, and 9/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively, and the incidence of adenoma and adenocarcinoma combined was 1/19, 5/20, and 7/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively. Malignant pleural mesothelioma was not induced in any of the groups.<br><br>CONCLUSIONS: The results of this initial study indicate that tangled-type MWCNT-B is carcinogenic to the rat lung when administered via the airway, and that straight-type MWCNT-A did not have higher carcinogenic potential in the rat lung than tangled-type MWCNT-B.}, }
@article {pmid33050791, year = {2020}, author = {Hariharan, A and Sun, S and Wipplinger, M and Felley-Bosco, E}, title = {RNA editing in mesothelioma: a look forward.}, journal = {Open biology}, volume = {10}, number = {10}, pages = {200112}, pmid = {33050791}, issn = {2046-2441}, abstract = {RNA editing is a post-transcriptional process increasing transcript diversity, thereby regulating different biological processes. We recently observed that mutations resulting from RNA editing due to hydrolytic deamination of adenosine increase during the development of mesothelioma, a rare cancer linked to chronic exposure to asbestos. This review gathers information from the published literature and public data mining to explore several aspects of RNA editing and their possible implications for cancer growth and therapy. We address possible links between RNA editing and particular types of mesothelioma genetic and epigenetic alterations and discuss the relevance of an edited substrate in the context of current chemotherapy or immunotherapy.}, }
@article {pmid33049597, year = {2020}, author = {Orbach, D and André, N and Brecht, IB and López Almaraz, R and Ben-Ami, T and Vermersch, S and Carton, M and Virgone, C and Bisogno, G and Schneider, DT and Bajciova, V and Reguerre, Y and Galateau-Salle, F and Stachowicz-Stencel, T and Dvir, R and Rees, H and Bien, E and Ferrari, A and Ben Arush, M}, title = {Mesothelioma in children and adolescents: the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) contribution.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {140}, number = {}, pages = {63-70}, doi = {10.1016/j.ejca.2020.09.011}, pmid = {33049597}, issn = {1879-0852}, abstract = {INTRODUCTION: Very little is known about the characteristics of mesothelial tumours in the paediatric population. In adults with malignant mesothelioma, the pemetrexed-based regimen with cytoreductive surgery (CRS) is a standard of care in limited tumours, but long-term survival is uncommon.<br><br>MATERIAL AND METHODS: The European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) retrospectively reviewed children, adolescents and young adults (≤21 year) diagnosed with mesothelial tumours treated between 1987 and 2018.<br><br>RESULTS: Thirty-three patients were identified, 15 male and 18 female patients. One patient's exposure to asbestos was documented. Primary tumour was mainly in the peritoneum (23 patients). Histology was multicystic mesothelioma of the peritoneum (MCM) (six patients) or malignant mesothelioma (MM) (27 patients). Among MM, the first-line treatment comprised preoperative chemotherapy (14 cases), surgery only (three cases), chemotherapy only (five cases), adjuvant chemotherapy (three cases) or palliative treatment (two cases). The response rate to cisplatin-pemetrexed was 50% (6/12 cases). CRS with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was performed in 19 patients (upfront in three, after neoadjuvant therapy in 12, or after tumour progression in six patients, including three twice). After a median follow-up of 6.7 years (range, 0-20), five-year overall and event-free survivals were 82.3% (95% CI, confidential interval ((CI), 67.8-99.9) and 45.1% (95% CI, 28.4-71.7), respectively. All patients with MCM are alive after surgery (five patients) and CRS-HIPEC (one patient).<br><br>CONCLUSIONS: Paediatric mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures, more peritoneal primary, and a better outcome. The cisplatin-pemetrexed regimen showed promising efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC.}, }
@article {pmid33045471, year = {2020}, author = {Duong, BTV and Wu, L and Green, BJ and Bavaghar-Zaeimi, F and Wang, Z and Labib, M and Zhou, Y and Cantu, FJP and Jeganathan, T and Popescu, S and Pantea, J and de Perrot, M and Kelley, SO}, title = {A liquid biopsy for detecting circulating mesothelial precursor cells: A new biomarker for diagnosis and prognosis in mesothelioma.}, journal = {EBioMedicine}, volume = {61}, number = {}, pages = {103031}, doi = {10.1016/j.ebiom.2020.103031}, pmid = {33045471}, issn = {2352-3964}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer related to asbestos exposure. Early diagnosis is challenging due to generic symptoms and a lack of biomarkers. We previously demonstrated that mesothelial precursor cells (MPC) characterized by mesothelin (MSLN)+CD90+CD34+ could be implicated in the development of mesothelioma after asbestos exposure. Here, we aimed to determine the clinical significance of detecting MPC in blood for early-stage diagnosis and prognosis of mesothelioma.<br><br>METHODS: Due to the rarity of MPC in blood, it is challenging to identify this cell population using conventional techniques. Hence, we have developed a microfluidic liquid biopsy platform called MesoFind that utilizes an immunomagnetic, mesothelin capture strategy coupled with immunofluorescence to identify rare populations of cells at high sensitivity and precision. To validate our technique, we compared this approach to flow cytometry for the detection of MPC in murine blood and lavage samples. Upon successful validation of the murine samples, we then proceeded to examine circulating MPC in 23 patients with MPM, 23 asbestos-exposed individuals (ASB), and 10 healthy donors (HD) to evaluate their prognostic and diagnostic value.<br><br>FINDING: MPC were successfully detected in the blood of murine samples using MesoFind but were undetectable with flow cytometry. Circulating MPC were significantly higher in patients with epithelioid MPM compared to HD and ASB. The MPC subpopulation, MSLN+ and CD90+, were upregulated in ASB compared to HD suggesting an early role in pleural damage from asbestos. The MPC subpopulation, MSLN+ and CD34+, in contrast, were detected in advanced MPM and associated with markers of poor prognosis, suggesting a predominant role during cancer progression.<br><br>INTERPRETATION: The identification of circulating MPC presents an attractive solution for screening and early diagnosis of epithelioid mesothelioma. The presence of different subtypes of MPC have a prognostic value that could be of assistance with clinical decisions in patients with MPM.<br><br>FUNDING: Princess Margaret Hospital Foundation Mesothelioma Research Fund, Toronto General &amp; Western Hospital Foundation.}, }
@article {pmid33040390, year = {2021}, author = {Korchevskiy, A}, title = {Using benchmark dose modeling for the quantitative risk assessment: Carbon nanotubes, asbestos, glyphosate.}, journal = {Journal of applied toxicology : JAT}, volume = {41}, number = {1}, pages = {148-160}, doi = {10.1002/jat.4063}, pmid = {33040390}, issn = {1099-1263}, support = {//Chemistry &amp; Industrial Hygiene, Inc/ ; }, abstract = {Benchmark dose method is one of the most famous quantitative approaches available for toxicological risks prediction. However, it is not fully clear how occupational health professionals can use it for specific workplace scenarios requiring carcinogen risk assessment. The paper explores the hypothesis that benchmark dose method allows to effectively approximate dose-response data on carcinogenic response, providing reasonable estimations of risks in the situations when a choice between more complex models is not warranted for practical purposes. Three case studies were analyzed for the agents with different levels of scientific confidence in human carcinogenicity: carbon nanotubes, amosite asbestos, and glyphosate. For each agent, a critical study was determined, and a dose-response slope factor was quantified, based on the weighted average lower bound benchmark dose. The linear slope factors of 0.111 lifetime excess cases of lung carcinoma per mg/m3 of MWCNT-7 (in rats exposure equivalent), 0.009 cases of mesothelioma per f/cc-years of cumulative exposure to amosite asbestos, and 0.000094 cases of malignant lymphoma per mg/kg/day of glyphosate (in mice equivalent) were determined. The correlations between the proposed linear predictive models and observed data points were R = 0.96 (R2 = 0.92) for carbon nanotubes, R = 0.97 (R2 = 0.95) for amosite asbestos, and R = 0.89 (R2 = 0.79) for glyphosate. In all three cases, the linear extrapolation yielded comparable level of risk estimations with the &quot;best fit&quot; nonlinear model; for nanoparticles and amosite asbestos, linear estimations were more conservative. By performing a simulation study, it was demonstrated that a weighted average benchmark dose expressed the highest correlation with multistage and quantal-linear models.}, }
@article {pmid33037108, year = {2021}, author = {Slomovitz, B and de Haydu, C and Taub, M and Coleman, RL and Monk, BJ}, title = {Asbestos and ovarian cancer: examining the historical evidence.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {31}, number = {1}, pages = {122-128}, doi = {10.1136/ijgc-2020-001672}, pmid = {33037108}, issn = {1525-1438}, abstract = {Asbestos recently returned to the spotlight when Johnson &amp; Johnson halted sales of baby powder due to lawsuits claiming that the talc in baby powder may have been contaminated with asbestos, which has been linked to the risk of ovarian cancer development. Although talc and asbestos have some structural similarities, only asbestos is considered causally associated with ovarian cancer by the WHO's International Agency for Research on Cancer. While it is useful to understand the types and properties of asbestos and its oncologic biology, the history of its association with ovarian cancer is largely based on retrospective observational studies in women working in high asbestos exposure environments. In reviewing the literature, it is critical to understand the distinction between associative risk and causality, and to examine the strength of association in the context of how the diagnosis of ovarian cancer is made and how the disease should be distinguished from a similar appearing but unrelated neoplasm, malignant mesothelioma. Based on contextual misinterpretation of these factors, it is imperative to question the International Agency for Research on Cancer's assertion that asbestos has a clear causal inference to ovarian cancer. This has important clinical implications in the way patients are conceivably counseled and provides motivation to continue research to improve the understanding of the association between asbestos and ovarian cancer.}, }
@article {pmid33036536, year = {2020}, author = {Song, PP and Sun, XW and Zhang, SQ and Gao, Y and Zhang, H and Chen, YX}, title = {[Clinical analysis of 30 cases with asbestos-related occupational tumors].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {38}, number = {9}, pages = {693-695}, doi = {10.3760/cma.j.cn121094-20190930-00460}, pmid = {33036536}, issn = {1001-9391}, support = {2018-WJZD058//Medical Research Guidance Plan for Qingdao in 2018/ ; }, mesh = {*Asbestos/toxicity ; Humans ; *Lung Neoplasms/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/epidemiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms ; Tomography, X-Ray Computed ; }, abstract = {Asbestos is classified as a Class 1 carcinogen by the International Cancer Organization (IARC) , and almost all types of asbestos are carcinogenic. The clinical data of 30 asbestos-induced occupational tumor patients in Qingdao city from January 2002 to May 2019 were analyzed, including 24 cases of asbestos-induced lung cancer and 6 cases of asbestos-induced malignant mesothelioma. Mesothelioma was significantly worse than lung cancer in terms of malignancy, the survival time of patients is shorter, and the mortality rate was higher. Both its diagnostic methods and treatment methods should be improved. The high incidence of asbestos-caused tumors is coming. It is recommended that workers exposed to asbestos dust should undergo regular chest CT examinations for early detection, early diagnosis and early treatment.}, }
@article {pmid33036531, year = {2020}, author = {Jiang, ZQ and Shao, DC and Cheng, YR and Miao, C and Chai, JR and Xu, CM and Yu, M and Wang, J and Li, T and Chen, JQ}, title = {[Detection and comparison of fiber count concentration in processing environment of asbestos and man-made mineral fiber].}, journal = {Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases}, volume = {38}, number = {9}, pages = {675-678}, doi = {10.3760/cma.j.cn121094-20191128-00546}, pmid = {33036531}, issn = {1001-9391}, mesh = {*Asbestos/analysis ; China ; Dust/analysis ; Humans ; *Mesothelioma ; Mineral Fibers/analysis ; }, abstract = {Objective: To connect with the measurement data of asbestos dust fiber concentration in foreign countries, improve the accuracy of asbestos fiber detection in China, and understand the dust exposure in the working environment of asbestos and man-made mineral fiber production and processing sites in Zhejiang Province. The fiber count concentrations of working environment in glass fiber, ceramic fiber and asbestos processing plants were measured and compared. Methods: The dust concentration in the working environment of two glass fiber factories, one ceramic fiber factory and eight asbestos products processing factories was measured. The total dust mass concentration was measured according to GBZ/T 192.1-2007, and the fiber count concentration was measured by phase contrast microscope. Kruskal Wallis was used to test and compare the dust concentration in the working environment of each post. The correlation between asbestos mass concentration and fiber count concentration was analyzed by Spearman correlation. Results: Under the phase contrast microscope, there were many short and fine asbestos fibers in the field of vision, and there were many impurities around. The average dust concentration of asbestos processing plant was 3.2 f/ml, and the dust concentration of cotton ginning was the highest (6.68 f/ml) . There was a significantly positive correlation between asbestos fiber count concentration and mass concentration (r=0.535, P=0.033) . The average fiber count concentration of glass fiber factory was 0.001 f/ml, and the highest was 0.005 f/ml. The average fiber count concentration of ceramic fiber factory was 0.001 f/ml, and the highest was 0.006 f/ml. Conclusion: The fiber count concentration in the working environment of asbestos factory in Zhejiang Province is obviously over the standard, which is one of the important reasons for the high incidence of mesothelioma in this area. Short and small asbestos fibers are easy to be ignored when counting. It is necessary to improve the actual operation process of fiber counting to form a laboratory standard in China.}, }
@article {pmid33032525, year = {2020}, author = {Kumagai-Takei, N and Nishimura, Y and Maeda, M and Hayashi, H and Matsuzaki, H and Lee, S and Yoshitome, K and Ito, T and Otsuki, T}, title = {Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes.}, journal = {Environmental health and preventive medicine}, volume = {25}, number = {1}, pages = {59}, pmid = {33032525}, issn = {1347-4715}, support = {H18-1-3-3-1//Japan Science and Technology Agency/ ; 19659153//Japan Society for the Promotion of Science/ ; 20390178//Japan Society for the Promotion of Science/ ; 20890270//Japan Society for the Promotion of Science/ ; 21659161//Japan Society for the Promotion of Science/ ; 23790679//Japan Society for the Promotion of Science/ ; 25860470//Japan Society for the Promotion of Science/ ; 16K09114//Japan Society for the Promotion of Science/ ; Tokutei Kenkyu Josei I, 2008//Takeda Science Foundation/ ; 21-107//Kawasaki Medical School/ ; 21-401//Kawasaki Medical School/ ; 20-411I//Kawasaki Medical School/ ; 22-A29//Kawasaki Medical School/ ; 23B66//Kawasaki Medical School/ ; 23P3//Kawasaki Medical School/ ; 26B39//Kawasaki Medical School/ ; 29B051//Kawasaki Medical School/ ; Kyoiku Kenkyu Josei, 2009//The Kawasaki Foundation for Medical Science and Medical Welfare/ ; Kenkyu Josei, 2009//The Ryobi Teien Memory Foundation/ ; Tokubetsu Dengen Syozai Ken Kagaku Gijyutsu Sinkou Jigyou Kenkyu Itaku, 2010-2012//Okayama prefecture/ ; }, mesh = {Asbestos/*toxicity ; Asbestos, Serpentine/toxicity ; Cell Differentiation/*drug effects ; Cell Proliferation/*drug effects ; Humans ; Lung Neoplasms/*immunology ; Mesothelioma/*immunology ; Mesothelioma, Malignant ; T-Lymphocytes, Cytotoxic/*drug effects/immunology ; }, abstract = {Asbestos exposure is known to cause malignant mesothelioma, which is associated with poor prognosis. We focused on and examined the effect of asbestos exposure on the differentiation and function of cytotoxic T lymphocytes (CTLs). CTLs have the ability to specifically attack tumor cells after being differentiated from naïve CD8+ T cells following antigen stimulation. Exposure to chrysotile B asbestos suppressed the differentiation of CTLs during the mixed lymphocyte reaction (MLR) and was associated with a decrease in proliferation of CD8+ T cells. Additionally, in an effort to investigate the mechanism associated with suppressed CTL differentiation upon exposure to asbestos, we focused on IL-2, a cytokine involved in T cell proliferation. Our findings indicated that insufficient levels of IL-2 are not the main cause for the suppressed induction of CTLs by asbestos exposure, although they suggest potential improvement in the suppressed CTL function. Furthermore, the functional properties of peripheral blood CD8+ lymphocytes from asbestos-exposed individuals with pleural plaque (PP) and patients with malignant mesothelioma (MM) were examined. MM patients showed lower perforin levels in CD8+ lymphocytes following stimulation compared with PP-positive individuals. The production capacity of IFN-γ in the MM group tended to be lower compared with healthy volunteers or PP-positive individuals. In an effort to determine whether chronic and direct asbestos exposure affected the function of CD8+ T cells, cultured human CD8+ T cells were employed as an in vitro model and subjected to long-term exposure to chrysotile (CH) asbestos. This resulted in decreased levels of intracellular perforin and secreted IFN-γ. Those findings underlie the possibility that impaired CD8+ lymphocyte function is caused by asbestos exposure, which fail to suppress the development of MM. Our studies therefore reveal novel effects of asbestos exposure on CTLs, which might contribute towards the development and implementation of an effective strategy for the prevention and cure of malignant mesothelioma.}, }
@article {pmid33032291, year = {2020}, author = {Zhang, X and Yang, L and Chen, W and Kong, M}, title = {Identification of Potential Hub Genes and Therapeutic Drugs in Malignant Pleural Mesothelioma by Integrated Bioinformatics Analysis.}, journal = {Oncology research and treatment}, volume = {43}, number = {12}, pages = {656-671}, doi = {10.1159/000510534}, pmid = {33032291}, issn = {2296-5262}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is closely linked to asbestos exposure and is an extremely aggressive tumor with poor prognosis.<br><br>OBJECTIVE: Our study aimed to elucidate hub genes and potential drugs in MPM by integrated bioinformatics analysis.<br><br>METHODS: GSE42977 was download from the Gene Expression Omnibus (GEO) database; the differentially expressed genes (DEGs) with adj.p value <0.05 and |logFC| ≥2 were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by DAVID database. The STRING database was used to construct a protein-protein interaction network, and modules analysis and hub genes acquisition were performed by Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to assess the impact of hub genes on the prognosis of MPM patients. The Drug-Gene Interaction database (DGIdb) was used to select the related drugs.<br><br>RESULTS: A total of 169 upregulated and 70 downregulated DEGs were identified. These DEGs are enriched in the pathway of extracellular matrix-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and PPAR signaling pathway. Finally, 10 hub genes (CDC20, CDK1, UBE2C, TOP2A, CCNB2, NUSAP1, KIF20A, AURKA, CEP55, and ASPM) were identified, which are considered to be closely related to the poor prognosis of MPM. In addition, 119 related drugs that may have a therapeutic effect on MPM were filtered out.<br><br>CONCLUSION: These discovered genes and small-molecule drugs provide some new ideas for further research on MPM.}, }
@article {pmid33020398, year = {2020}, author = {Iannuzzi, CA and Indovina, P and Forte, IM and Di Somma, S and Malfitano, AM and Bruno, M and Portella, G and Pentimalli, F and Giordano, A}, title = {Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines.}, journal = {International journal of molecular sciences}, volume = {21}, number = {19}, pages = {}, pmid = {33020398}, issn = {1422-0067}, abstract = {Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, for which no therapy proves to be effective. We have recently shown that the oncolytic adenovirus dl922-947 had antitumor effects in MM cell lines and murine xenografts. Previous studies demonstrated that dl922-947-induced host cell cycle checkpoint deregulation and consequent DNA lesions associated with the virus efficacy. However, the cellular DNA damage response (DDR) can counteract this virus action. Therefore, we assessed whether AZD1775, an inhibitor of the G2/M DNA damage checkpoint kinase WEE1, could enhance MM cell sensitivity to dl922-947. Through cell viability assays, we found that AZD1775 synergized with dl922-947 selectively in MM cell lines and increased dl922-947-induced cell death, which showed hallmarks of apoptosis (annexinV-positivity, caspase-dependency, BCL-XL decrease, chromatin condensation). Predictably, dl922-947 and/or AZD1775 activated the DDR, as indicated by increased levels of three main DDR players: phosphorylated histone H2AX (γ-H2AX), phospho-replication protein A (RPA)32, phospho-checkpoint kinase 1 (CHK1). Dl922-947 also increased inactive Tyr-15-phosphorylated cyclin-dependent kinase 1 (CDK1), a key WEE1 substrate, which is indicative of G2/M checkpoint activation. This increase in phospho-CDK1 was effectively suppressed by AZD1775, thus suggesting that this compound could, indeed, abrogate the dl922-947-induced DNA damage checkpoint in MM cells. Overall, our data suggest that the dl922-947-AZD1775 combination could be a feasible strategy against MM.}, }
@article {pmid33014860, year = {2020}, author = {Rozitis, E and Johnson, B and Cheng, YY and Lee, K}, title = {The Use of Immunohistochemistry, Fluorescence in situ Hybridization, and Emerging Epigenetic Markers in the Diagnosis of Malignant Pleural Mesothelioma (MPM): A Review.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {1742}, pmid = {33014860}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos related disease that is generally considered to be difficult to diagnose, stage and treat. The diagnostic process is continuing to evolve and requires highly skilled pathology input, and generally an extensive list of biomarkers for definitive diagnosis. Diagnosis of MPM requires histological evidence of invasion by malignant mesothelial cells often confirmed by various immunohistochemical biomarkers in order to separate it from pleural metastatic carcinoma. Often when invasion of neoplastic mesothelial cells into adjacent tissue is not apparent, further immunohistochemical testing - namely BAP1 and MTAP, as well as FISH testing for loss of p16 (CDKN2A) are used to separate reactive mesothelial proliferation due to benign processes, from MPM. Various combinations of these markers, such as BAP1 and/or MTAP immunohistochemistry alongside FISH testing for loss of p16, have shown excellent sensitivity and specificity in the diagnosis of MPM. Additionally, over the recent years, research into epigenetic marker use in the diagnosis of MPM has gained momentum. Although still in their research stages, various markers in DNA methylation, long non-coding RNA, micro RNA, circular RNA, and histone modifications have all been found to support diagnosis of MPM with generally good sensitivity and specificity. Many of these studies are however, limited by small sample sizes or other study limitations and further research into the area would be beneficial. Epigenetic markers show promise for use in the future to facilitate the diagnosis of MPM.}, }
@article {pmid33012432, year = {2020}, author = {Ripley, RT}, title = {Extended Pleurectomy and Decortication for Malignant Pleural Mesothelioma.}, journal = {Thoracic surgery clinics}, volume = {30}, number = {4}, pages = {451-460}, doi = {10.1016/j.thorsurg.2020.07.002}, pmid = {33012432}, issn = {1558-5069}, abstract = {Extended pleurectomy and decortication (ePD) is a difficult operation performed for the surgical resection of malignant pleural mesothelioma that can achieve a macroscopic complete resection with preservation of the lung. With lower perioperative mortality, similar long-term survival, and better tolerance in patients with lower performance status, ePD has become the preferred operation rather than extrapleural pneumonectomy despite lack of a direct comparison. As ePD has become more popular, international collaboration is underway to create surgical guidelines based on collection of operative data. These efforts will improve the safety and standardization of this operation.}, }
@article {pmid33012429, year = {2020}, author = {Pass, HI and Alimi, M and Carbone, M and Yang, H and Goparaju, CM}, title = {Mesothelioma Biomarkers: Discovery in Search of Validation.}, journal = {Thoracic surgery clinics}, volume = {30}, number = {4}, pages = {395-423}, doi = {10.1016/j.thorsurg.2020.08.001}, pmid = {33012429}, issn = {1558-5069}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm that can only be treated successfully when correctly diagnosed and treated early. The asbestos-exposed population is a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. We review recent work with biomarker development in MPM and literature of the last 20 years on the most promising blood- and tissue-based biomarkers. Proteomic, genomic, and epigenomic platforms are covered. SMRP is the only validated blood-based biomarker with diagnostic, monitoring and prognostic value. To strengthen development and testing of MPM biomarkers, cohorts for validation must be established by enlisting worldwide collaborations.}, }
@article {pmid33012428, year = {2020}, author = {Wadowski, B and De Rienzo, A and Bueno, R}, title = {The Molecular Basis of Malignant Pleural Mesothelioma.}, journal = {Thoracic surgery clinics}, volume = {30}, number = {4}, pages = {383-393}, doi = {10.1016/j.thorsurg.2020.08.005}, pmid = {33012428}, issn = {1558-5069}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy of the pleural lining associated with asbestos exposure in greater than 80% of cases. It is characterized by molecular heterogeneity both between patients and within individual tumors. Next-generation sequencing technology and novel computational techniques have resulted in a greater understanding of the epigenetic, genetic, and transcriptomic hallmarks of MPM. This article reviews these features and discusses the implications of advances in MPM molecular biology in clinical practice.}, }
@article {pmid32999071, year = {2020}, author = {Xue, J and Patergnani, S and Giorgi, C and Suarez, J and Goto, K and Bononi, A and Tanji, M and Novelli, F and Pastorino, S and Xu, R and Caroccia, N and Dogan, AU and Pass, HI and Tognon, M and Pinton, P and Gaudino, G and Mak, TW and Carbone, M and Yang, H}, title = {Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {41}, pages = {25543-25552}, pmid = {32999071}, issn = {1091-6490}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; R01 CA237235/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Asbestos/*adverse effects ; Autophagy/*drug effects ; Cell Transformation, Neoplastic/*chemically induced ; Cells, Cultured ; Epithelial Cells/cytology/metabolism ; HMGB1 Protein/*metabolism ; Humans ; Male ; Mesothelioma/*metabolism ; Mice ; Mice, Knockout ; Middle Aged ; Occupational Exposure ; }, abstract = {Asbestos causes malignant transformation of primary human mesothelial cells (HM), leading to mesothelioma. The mechanisms of asbestos carcinogenesis remain enigmatic, as exposure to asbestos induces HM death. However, some asbestos-exposed HM escape cell death, accumulate DNA damage, and may become transformed. We previously demonstrated that, upon asbestos exposure, HM and reactive macrophages releases the high mobility group box 1 (HMGB1) protein that becomes detectable in the tissues near asbestos deposits where HMGB1 triggers chronic inflammation. HMGB1 is also detectable in the sera of asbestos-exposed individuals and mice. Searching for additional biomarkers, we found higher levels of the autophagy marker ATG5 in sera from asbestos-exposed individuals compared to unexposed controls. As we investigated the mechanisms underlying this finding, we discovered that the release of HMGB1 upon asbestos exposure promoted autophagy, allowing a higher fraction of HM to survive asbestos exposure. HMGB1 silencing inhibited autophagy and increased asbestos-induced HM death, thereby decreasing asbestos-induced HM transformation. We demonstrate that autophagy was induced by the cytoplasmic and extracellular fractions of HMGB1 via the engagement of the RAGE receptor and Beclin 1 pathway, while nuclear HMGB1 did not participate in this process. We validated our findings in a novel unique mesothelial conditional HMGB1-knockout (HMGB1-cKO) mouse model. Compared to HMGB1 wild-type mice, mesothelial cells from HMGB1-cKO mice showed significantly reduced autophagy and increased cell death. Autophagy inhibitors chloroquine and desmethylclomipramine increased cell death and reduced asbestos-driven foci formation. In summary, HMGB1 released upon asbestos exposure induces autophagy, promoting HM survival and malignant transformation.}, }
@article {pmid32988786, year = {2020}, author = {Cattaneo, M and Mendogni, P and Damarco, F and Tosi, D}, title = {Spontaneous diaphragmatic rupture following neoadjuvant chemotherapy and cytoreductive surgery in malignant pleural mesothelioma: A case report and review of the literature.}, journal = {International journal of surgery case reports}, volume = {77S}, number = {}, pages = {S85-S87}, doi = {10.1016/j.ijscr.2020.09.073}, pmid = {32988786}, issn = {2210-2612}, abstract = {INTRODUCTION: Diaphragmatic rupture (DR) is an acquired diaphragmatic defect that can cause herniation of abdominal organs into the chest. It is usually a trauma-related lesion, but rarely it can occur spontaneously. Every DR with abdominal herniation should be considered a surgical emergency.<br><br>PRESENTATION OF CASE: A 61-year-old male patient, with previous exposure to asbestos, was diagnosed of Stage Ib malignant pleural mesothelioma (MPM). He underwent neo-adjuvant chemotherapy (three cycle of cisplatin-pemetrexed combination) and a cytoreductive surgery with pleurectomy/decortication. Post-operative course was characterized by prolonged air-leakage (PAL). After three months, during a follow-up CT-scan, a spontaneous diaphragmatic rupture (SDR) with gastric herniation was detected and treated by a laparascopic diaphragmatic repair and suture.<br><br>DISCUSSION: Spontaneous diaphragmatic rupture (SDR) is an extremely rare injury of the diaphragm (less than 1% of all DR). In this case, potential predisposing factors for SDR could be: presence of diaphragmatic &quot;locus minoris resistentiae&quot; due to thinning of the diaphragm and increase tissue fragility after neo-adjuvant chemotherapy and diaphragmatic pleural stripping; increased thoraco-abdominal pressure gradient due to PAL and residual pleural space. Thus, we confirmed the feasibility and safety of the laparoscopic approach.<br><br>CONCLUSION: We highlight the multifactor etiopathology, the challenging diagnosis and the importance of a prompt treatment of SDR.}, }
@article {pmid32977478, year = {2020}, author = {Kumagai-Takei, N and Lee, S and Srinivas, B and Shimizu, Y and Sada, N and Yoshitome, K and Ito, T and Nishimura, Y and Otsuki, T}, title = {The Effects of Asbestos Fibers on Human T Cells.}, journal = {International journal of molecular sciences}, volume = {21}, number = {19}, pages = {}, pmid = {32977478}, issn = {1422-0067}, abstract = {Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos fibers on immunocompetent cells, however, have not been well studied. Asbestos physically comprises a fibrous substance, which differs from silica particles which are a particulate substance, although chemically it is a mineral silicate. Since silicosis patients previously exposed to silica particles often suffer from lung and autoimmune diseases, it is clear that silica exposure impairs immune tolerance. Similarly, asbestos may alter the immune system in asbestos-exposed individuals. Given that malignant tumors can result following exposure to asbestos, the attenuation of anti-tumor immunity in cases of asbestos exposure is an important area of investigation. We observed the effect of asbestos fibers on T lymphocytes, such as CD8+ cytotoxic T lymphocytes (CTLs), CD4+ helper T (Th), and regulatory T (Treg) cells, and showed that anti-tumor immunity was attenuated, as demonstrated in a system that stimulates fresh cells isolated from peripheral blood in vitro and a system that is continuously exposed to a cell line. In this manuscript, we introduce the experiments and results of studies on CTLs, as well as Th and Treg cells, and discuss how future changes in immunocompetent cells induced by asbestos fibers can be clinically linked.}, }
@article {pmid32971078, year = {2020}, author = {Lysaniuk, B and Cely-García, MF and Mazzeo, A and Marsili, D and Pasetto, R and Comba, P and Ramos-Bonilla, JP}, title = {Where are the landfilled zones? Use of historical geographic information and local spatial knowledge to determine the location of underground asbestos contamination in Sibaté (Colombia).}, journal = {Environmental research}, volume = {191}, number = {}, pages = {110182}, doi = {10.1016/j.envres.2020.110182}, pmid = {32971078}, issn = {1096-0953}, abstract = {INTRODUCTION: Sibaté is a municipality located in the central region of Colombia, where the first asbestos-cement facility of the country has been in operation since 1942. Both a malignant pleural mesothelioma cluster and landfilled zones with the presence of an underground friable asbestos layer have been identified in Sibaté. There is still limited knowledge regarding the history of the construction of landfilled zones, and what kinds of materials were deposited. The current study aims to improve our understanding of the history and characteristics of the landfilled zones present in Sibaté.<br><br>METHODS: Two participatory workshops with inhabitants of Sibaté were conducted to determine when the landfilled zones were built and their location. Information collected in participatory workshops was crossed with both topographic maps and aerial photographs, giving special attention to zones within the urban area of the municipality that in the past were inundated with water from El Muña Reservoir. An opportunistic soil sampling campaign was conducted in suspected landfilled zones that had not been previously sampled, during the replacement of pipelines of the drainage system ordered by the municipality.<br><br>RESULTS: The analysis of historical topographic maps, combined with the interpretation of aerial photographs, confirmed the disposal of residues in areas that were previously inundated with water from El Muña Reservoir, creating landfilled zones in the urban area of Sibaté. On top of these landfilled zones, a football stadium and a football field with an athletic track were built. The location of landfilled zones identified using geographic analysis was similar to the location identified analyzing maps constructed by inhabitants of Sibaté in participatory workshops. The four soil samples collected during an opportunistic sampling campaign confirmed the presence in new locations of the underground friable asbestos layer discovered in previous studies.<br><br>DISCUSSION: Based on the extension of the landfilled zones, the presence of friable asbestos in these areas, and the close proximity to a school and residential dwellings, there could have been major dispersion events of asbestos fibers in the urban area of Sibaté during the disposal of residue materials and the construction of the landfilled zones. Thus, important asbestos exposures may have occurred among residents of Sibaté, which is aggravated by the fact that during those years, more than 50% of the population of Sibaté was 25 years old or younger. Although the results of the current study improved our understanding of the processes and chronology associated with the landfilled zones, the uncertainty regarding their exact location remains significant. It is important to continue investigating the adverse health effects resulting from this potential asbestos exposure source.}, }
@article {pmid32967259, year = {2020}, author = {Chimed-Ochir, O and Arachi, D and Driscoll, T and Lin, RT and Takala, J and Takahashi, K}, title = {Burden of Mesothelioma Deaths by National Income Category: Current Status and Future Implications.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {18}, pages = {}, pmid = {32967259}, issn = {1660-4601}, mesh = {Asbestos/toxicity ; Global Health ; Humans ; *Income ; *Mesothelioma/economics/mortality ; Reproducibility of Results ; }, abstract = {Background: This study compares estimates of the global-level mesothelioma burden with a focus on how existing national mortality data were utilized and further assesses the interrelationship of country-level mesothelioma burden and asbestos use with national income status. Methods: Country-level mesothelioma deaths in the WHO Mortality Database as of December 2019 were analyzed by national income category of countries in terms of data availability and reliability. Numbers of mesothelioma deaths from the study of Odgerel et al. were reanalyzed to assess country-level mesothelioma death burdens by national income status. Results: Among 80 high-income countries, 54 (68%) reported mesothelioma to the WHO and 26 (32%) did not, and among 60 upper middle-income countries, the respective numbers (proportions) were 39 (65%) countries and 21 (35%) countries, respectively. In contrast, among 78 low- and lower middle-income countries, only 11 (14%) reported mesothelioma deaths while 67 (86%) did not. Of the mesothelioma deaths, 29,854 (78%) were attributed to high- and upper middle-income countries, and 8534 (22%) were attributed to low- and lower middle- income countries. Conclusions: The global mesothelioma burden, based on reported numbers, is currently shouldered predominantly by high-income countries; however, mesothelioma burdens will likely manifest soon in upper middle-income and eventually in low and lower middle-income countries.}, }
@article {pmid32966235, year = {2020}, author = {Cheng, TJ and More, SL and Maddaloni, MA and Fung, ES}, title = {Evaluation of potential gastrointestinal carcinogenicity associated with the ingestion of asbestos.}, journal = {Reviews on environmental health}, volume = {}, number = {}, pages = {}, doi = {10.1515/reveh-2020-0061}, pmid = {32966235}, issn = {2191-0308}, abstract = {The inhalation of asbestos, depending on the fiber type and dose, may be associated with the development of mesothelioma and other asbestos-related diseases. However, little is known about the potential adverse effects associated with the ingestion of asbestos. Evidence of asbestos fibers released from asbestos-cement pipes used in water distribution systems has led to concerns of potentially contaminated drinking water. The purpose of this study is to determine whether ingestion of asbestos fibers may lead to cancerous effects on the gastrointestinal (GI) tract. Data from animal and human studies were analyzed using a weight-of-evidence approach to evaluate the potential risk of GI cancers associated with asbestos ingestion. Seventeen human and 23 animal studies were identified and evaluated in this study. Animal studies were conducted in multiple species with inconsistent dosing protocols. Overall, animal studies reported that the asbestos fibers, irrespective of fiber type and dose, failed to produce any definitive GI carcinogenic effect. The 17 identified human epidemiological studies reported the ingestion of asbestos-contaminated water with concentrations from 1 to 71,350 million fibers per liter (MFL). A majority of the epidemiology studies reported statistically significant increases in multiple GI-specific cancers. However, these findings are confounded due to several critical study limitations including flawed study design, small sample size, selection bias, lack of individual exposure history, lack of adequate latency, and the inability to account for confounders including occupational history, diet, and smoking history. Based on our weight-of-evidence assessment, there is insufficient evidence of causality between the ingestion of asbestos and an increased incidence of GI cancers.}, }
@article {pmid32963780, year = {2020}, author = {Ohnishi, Y and Fujii, T and Sakamoto, T and Watanabe, M and Motohashi, T and Kubo, H and Nakajima, M}, title = {Malignant mesothelioma metastatic to the oral region and latest topics (Review).}, journal = {Molecular and clinical oncology}, volume = {13}, number = {5}, pages = {61}, pmid = {32963780}, issn = {2049-9450}, abstract = {Malignant mesothelioma (MM) is a rare neoplasm with poor prognosis that usually develops after exposure to asbestos, and is characterised by aggressive local invasion and metastatic spread. While metastasis to the oral cavity is very rare, a total of 23 cases of MM metastasising to the oral cavity were identifed. Among those, the tongue was the most common site of metastasis (39.1%), and frequently involved the epithelioid MM cell type. Recent studies have elucidated the mechanisms underlying the development of MM. Chronic inflammation has been implicated in promoting MM growth and was shown to play a key role by driving the release of high mobility group box protein 1 following asbestos deposition. Inherited heterozygous germline mutations in the deubiquitylase BRCA-associated protein 1 were shown to increase the incidence of MM in some families. Infection by the simian virus 40 was also found to be associated with the occurrence of MM. Moreover, the increasing incidence rates of MM, together with its propensity to metastasise to the oral cavity, indicate that clinicians and pathologists should be highly aware of this disease. Furthermore, identification of novel serum biomarkers would enable better screening and treatment of MM, and improve the survival outcomes.}, }
@article {pmid32944078, year = {2020}, author = {Wahlbuhl, E and Liehr, T and Rincic, M and Azawi, S}, title = {Cytogenomic characterization of three murine malignant mesothelioma tumor cell lines.}, journal = {Molecular cytogenetics}, volume = {13}, number = {}, pages = {43}, pmid = {32944078}, issn = {1755-8166}, abstract = {Background: Malignant mesothelioma (MM) is a rare aggressive cancer primary located in pleura and lung. MMs can be divided into biphasic, epithelioid and sarcomatoid subtypes. In majority of cases MMs are induced by asbestos fiber exposure. As latency period after asbestos exposure ranges between ~ 10 and 60 years MMs are mainly observed in elder people. Human MM, being a rare tumor type, lacks detailed cytogenetic data, while molecular genetic studies have been undertaken more frequently. However, murine MM cell lines are also regularly applied to get more insight into MM biology and to test new therapy strategies.<br><br>Results: Here the murine MM cell lines AB1, AB22 and AC29 were studied by molecular cytogenetics and molecular karyotyping. Interestingly, yet there were no genetic or genomic studies undertaken for these already in 1992 established cell lines. The obtained data on genomic imbalances in these murine cell lines was translated into the human genome as previously reported based on human and murine genomic browsers.<br><br>Conclusions: It turned out that all three cell lines showed high similarities in copy number variants as observed typically in human MM. Also, all three cell lines were most similar to human epithelioid MMs, and should be used as models therefore.}, }
@article {pmid32933580, year = {2020}, author = {Fisher, SA and Peddle-McIntyre, CJ and Burton, K and Newton, RU and Marcq, E and Lake, RA and Nowak, AK}, title = {Voluntary exercise in mesothelioma: effects on tumour growth and treatment response in a murine model.}, journal = {BMC research notes}, volume = {13}, number = {1}, pages = {435}, pmid = {32933580}, issn = {1756-0500}, support = {CRE APP1107043//National Health and Medical Research Council/ ; Health Research Fund//Slater &amp; Gordon/ ; KotK_UA/2018/11519/1//Kom Op Tegen Kanker (Stand Up to Cancer)/ ; hShort-Term Research Fellowship April 2019//European Respiratory Society-ERS/ ; }, abstract = {OBJECTIVE: There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen-induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma.<br><br>RESULTS: Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, non-asbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some pre-clinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.}, }
@article {pmid32929059, year = {2020}, author = {Costa, C and Indovina, P and Mattioli, E and Forte, IM and Iannuzzi, CA and Luzzi, L and Bellan, C and De Summa, S and Bucci, E and Di Marzo, D and De Feo, M and Mutti, L and Pentimalli, F and Giordano, A}, title = {P53-regulated miR-320a targets PDL1 and is downregulated in malignant mesothelioma.}, journal = {Cell death &amp; disease}, volume = {11}, number = {9}, pages = {748}, doi = {10.1038/s41419-020-02940-w}, pmid = {32929059}, issn = {2041-4889}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer, related to asbestos exposure, which has a dismal prognosis. MPM diagnosis is late and often challenging, suggesting the need to identify more reliable molecular biomarkers. Here, we set out to identify differentially expressed miRNAs in epithelioid, biphasic, and sarcomatoid MPMs versus normal mesothelium and explored specific miRNA contribution to mesothelial tumorigenesis. We screened an LNA™-based miRNA-microrray with 14 formalin-fixed paraffin-embedded (FFPE) MPMs and 6 normal controls. Through real-time qRT-PCR we extended the analysis of a miRNA subset and further investigated miR-320a role through state-of-the-art techniques. We identified 16 upregulated and 32 downregulated miRNAs in MPMs versus normal tissue, including the previously identified potential biomarkers miR-21, miR-126, miR-143, miR-145. We showed in an extended series that miR-145, miR-10b, and miR-320a levels can discriminate tumor versus controls with high specificity and sensitivity. We focused on miR-320a because other family members were found downregulated in MPMs. However, stable miR-320a ectopic expression induced higher proliferation and migration ability, whereas miR-320a silencing reduced these processes, not supporting a classic tumor-suppressor role in MPM cell lines. Among putative targets, we found that miR-320a binds the 3'-UTR of the immune inhibitory receptor ligand PDL1 and, consistently, miR-320a modulation affects PDL1 levels in MPM cells. Finally, we showed that p53 over-expression induces the upregulation of miR-320a, along with miR-200a and miR-34a, both known to target PDL1, and reduces PDL1 levels in MPM cells. Our data suggest that PDL1 expression might be due to a defective p53-regulated miRNA response, which could contribute to MPM immune evasion or tumorigenesis through tumor-intrinsic roles.}, }
@article {pmid32927122, year = {2021}, author = {Reardon, ES and Shukla, V and Xi, S and Gara, SK and Liu, Y and Straughan, D and Zhang, M and Hong, JA and Payabyab, EC and Kumari, A and Richards, WG and De Rienzo, A and Hassan, R and Miettinen, M and Xi, L and Raffeld, M and Uechi, LT and Li, X and Wang, R and Chen, H and Hoang, CD and Bueno, R and Schrump, DS}, title = {UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {16}, number = {1}, pages = {89-103}, pmid = {32927122}, issn = {1556-1380}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; ZIA BC011115/ImNIH/Intramural NIH HHS/United States ; }, abstract = {INTRODUCTION: Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) encodes a master regulator of DNA methylation that has emerged as an epigenetic driver in human cancers. To date, no studies have evaluated UHRF1 expression in malignant pleural mesothelioma (MPM). This study was undertaken to explore the therapeutic potential of targeting UHRF1 in MPM.<br><br>METHODS: Microarray, real-time quantitative reverse transcription-polymerase chain reaction, immunoblot, and immunohistochemistry techniques were used to evaluate UHRF1 expression in normal mesothelial cells (NMCs) cultured with or without asbestos, MPM lines, normal pleura, and primary MPM specimens. The impact of UHRF1 expression on MPM patient survival was evaluated using two independent databases. RNA-sequencing, proliferation, invasion, and colony formation assays, and murine xenograft experiments were performed to evaluate gene expression and growth of MPM cells after biochemical or pharmacologic inhibition of UHRF1 expression.<br><br>RESULTS: UHRF1 expression was significantly higher in MPM lines and specimens relative to NMC and normal pleura. Asbestos induced UHRF1 expression in NMC. The overexpression of UHRF1 was associated with decreased overall survival in patients with MPM. UHRF1 knockdown reversed genomewide DNA hypomethylation, and inhibited proliferation, invasion, and clonogenicity of MPM cells, and growth of MPM xenografts. These effects were phenocopied by the repurposed chemotherapeutic agent, mithramycin. Biochemical or pharmacologic up-regulation of p53 significantly reduced UHRF1 expression in MPM cells. RNA-sequencing experiments exhibited the pleiotropic effects of UHRF1 down-regulation and identified novel, clinically relevant biomarkers of UHRF1 expression in MPM.<br><br>CONCLUSIONS: UHRF1 is an epigenetic driver in MPM. These findings support the efforts to target UHRF1 expression or activity for mesothelioma therapy.}, }
@article {pmid32922794, year = {2020}, author = {Tada, Y and Tagawa, M and Yusa, T and Yatomi, M and Shimomura, I and Suzuki, T and Takeshita, Y and Sato, T and Shimada, H and Hiroshima, K}, title = {Diffuse pleural thickening and thoracic contraction: An indistinguishable case from malignant pleural mesothelioma.}, journal = {SAGE open medical case reports}, volume = {8}, number = {}, pages = {2050313X20948716}, pmid = {32922794}, issn = {2050-313X}, abstract = {The differential diagnosis of reactive mesothelial hyperplasia and mesothelioma is difficult. We present a rare case of diffuse pleural thickening with thoracic contraction that was indistinguishable from mesothelioma. A 66-year-old woman with no history of asbestos exposure visited our hospital with a complaint of dyspnea. The clinical findings included circumferential pleural thickening on chest computed tomography image and a high concentration of hyaluronic acid in the pleural fluid. Pleural biopsies obtained by thoracoscopy under local anesthesia were pathologically consistent with mesothelioma, but the patient refused to take any kind of mesothelioma treatments. Four months later, she consented to a surgical pleural biopsy under general anesthesia to obtain larger tissue samples, which included typical proliferating polygonal cells positive for CAM5.2, calretinin, WT-1, D2-40, CK5/6, epithelial membrane antigen, and glucose transporter-1 and negative for carcinoembryonic antigen, BerEP4, and MOC31. The analysis was consistent with diagnosis of epithelioid mesothelioma. Fluorescence in situ hybridization, however, showed the presence of p16 gene, and the expression of BRCA1-associated protein-1 was detected by immunohistochemistry. Our final diagnosis was diffuse pleural thickening unrelated to asbestos exposure. Differential diagnosis of diffuse pleural thickening and malignant mesothelioma is thus difficult and routine immunohistochemical examinations are often insufficient for accurate diagnosis. Multiple diagnostic methods are required for correct diagnosis in a clinically marginal case.}, }
@article {pmid32911426, year = {2020}, author = {Lam, SK and Yan, S and Xu, S and Ho, JC}, title = {Targeting polyamine as a novel therapy in xenograft models of malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {148}, number = {}, pages = {138-148}, doi = {10.1016/j.lungcan.2020.08.016}, pmid = {32911426}, issn = {1872-8332}, abstract = {INTRODUCTION: Inhalation of asbestos fibers is the key culprit in malignant pleural mesothelioma (MPM). Although the import and use of asbestos have been restricted, the incidence of MPM continues to increase globally due to the prolonged lag time in malignant transformation. The development of a novel adjuvant therapy for the minority of individuals with resectable early-stage disease and effective treatment for those with unresectable MPM are urgently needed. Our preliminary data revealed that ornithine decarboxylase (ODC) is highly expressed in MPM xenografts. This study aimed to determine the treatment effects of α-difluoromethylornithine (DFMO), a specific ODC inhibitor, in MPM xenografts.<br><br>RESULTS: In an &quot;extended adjuvant DFMO treatment&quot; setting, nude mice were fed with DFMO for 7 days prior to inoculation of 200,000 cells. DFMO suppressed tumor growth and increased median survival in both xenografts. In H226 xenograft, 43 % of treated mice had not reached the humane endpoint by day 132, mimicking long-term survival. DFMO decreased spermidine, increased nitrotyrosine and activated apoptosis in both xenografts. Furthermore, increase in nitrosocysteine, intratumoral IL-6, keratinocyte chemoattractant and TNFα, DNA lesion and inhibition of the Akt/mTOR pathway were induced by DFMO in H226 xenograft. In &quot;DFMO treatment&quot; setting, 107 cells were inoculated into nude mice and DFMO treatment commenced when tumor size reached ∼50-100 mm3. DFMO also suppressed tumor growth by similar mechanisms. Supplementation with spermidine reversed the therapeutic effect of DFMO. DFMO increased actin nitration at tyrosine 53 and inhibited actin polymerization.<br><br>CONCLUSION: DFMO is preclinically effective in treating MPM.}, }
@article {pmid32892058, year = {2020}, author = {Fuso Nerini, I and Roca, E and Mannarino, L and Grosso, F and Frapolli, R and D'Incalci, M}, title = {Is DNA repair a potential target for effective therapies against malignant mesothelioma?.}, journal = {Cancer treatment reviews}, volume = {90}, number = {}, pages = {102101}, doi = {10.1016/j.ctrv.2020.102101}, pmid = {32892058}, issn = {1532-1967}, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Clinical Trials, Phase II as Topic ; DNA Damage ; *DNA Repair ; Humans ; Mesothelioma, Malignant/*drug therapy/*genetics ; Mutation ; Poly(ADP-ribose) Polymerase Inhibitors/administration &amp; dosage/*pharmacology/therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy mainly caused by asbestos exposure. Germinal and acquired mutations in genes of DNA repair pathways, in particular of homologous recombination repair, are frequent in MPM. Here we overview the available experimental data suggesting that an impaired DNA repair system affects MPM pathogenesis by leaving lesions through the genome unresolved. DNA repair defects represent a vulnerability of MPM, and it seems plausible to propose that leveraging these deficiencies could have therapeutic potential for patients with MPM, for whom there is an urgent need of more effective therapies.}, }
@article {pmid32888937, year = {2020}, author = {Prabhakaran, S and Hocking, A and Kim, C and Hussey, M and Klebe, S}, title = {The potential utility of GATA binding protein 3 for diagnosis of malignant pleural mesotheliomas.}, journal = {Human pathology}, volume = {105}, number = {}, pages = {1-8}, doi = {10.1016/j.humpath.2020.08.005}, pmid = {32888937}, issn = {1532-8392}, abstract = {Malignant pleural mesothelioma is associated with asbestos exposure and poor outcomes. The usefulness of immunohistochemistry for diagnosis of sarcomatoid mesothelioma, especially the desmoplastic type, is limited, and more effective markers are required. GATA binding protein 3 (GATA3) has been suggested as a diagnostic marker for sarcomatoid mesothelioma. The potential usefulness of GATA3 for prognostication and its clinical and pathological correlations in different subtypes of mesothelioma have not been evaluated. We investigated the immunohistochemical labeling and associations for GATA3, BRCA1-associated protein 1 (BAP1), and Ki67 labeling in three major histological types of pleural malignant mesotheliomas. We examined 149 clinically annotated malignant mesotheliomas and assessed associations of GATA3 expression with clinical variables and prognosis. In addition, we labeled 10 cases of fibrous pleuritis with GATA3, all of which were negative. GATA3 was positive in 75 of 149 (50%) mesotheliomas, with the highest incidence of labeling seen in the sarcomatoid subtype (73%), compared with the biphasic (50%) and epithelioid (40%), mesotheliomas. A total of eight desmoplastic mesotheliomas showed labeling with GATA3. Patients whose tumors had sarcomatoid histology showed poorer survival than those with the other subtypes (p < 0.001), but overall GATA3 labeling did not have a statistically significant association with survival (p = 0.602). There was no association of GATA3 labeling and BAP1 status or Ki67 index. Our study includes the largest cohort of mesotheliomas that has been labeled for GATA3 to date. GATA3 is a useful marker for sarcomatoid mesothelioma, including the desmoplastic subtype. Discordance in GATA3 and BAP1 labeling of epithelioid and sarcomatoid components in the biphasic subtype is not uncommon.}, }
@article {pmid32888453, year = {2020}, author = {Nowak, AK and Lesterhuis, WJ and Kok, PS and Brown, C and Hughes, BG and Karikios, DJ and John, T and Kao, SC and Leslie, C and Cook, AM and Pavlakis, N and Briscoe, K and O'Byrne, KJ and Karapetis, CS and Lam, WS and Langford, A and Yip, S and Stockler, MR}, title = {Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in.}, journal = {The Lancet. Oncology}, volume = {21}, number = {9}, pages = {1213-1223}, doi = {10.1016/S1470-2045(20)30462-9}, pmid = {32888453}, issn = {1474-5488}, mesh = {Adolescent ; Adult ; Aged ; Antibodies, Anti-Idiotypic/administration &amp; dosage/adverse effects ; Antibodies, Monoclonal/*administration &amp; dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/adverse effects ; Australia/epidemiology ; B7-H1 Antigen/antagonists &amp; inhibitors/genetics ; Cisplatin/*administration &amp; dosage/adverse effects ; Female ; Humans ; Lung Neoplasms/*drug therapy/genetics/immunology/pathology ; Male ; Mesothelioma/*drug therapy/genetics/immunology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration &amp; dosage/adverse effects ; Pleural Neoplasms/*drug therapy/genetics/immunology/pathology ; Progression-Free Survival ; }, abstract = {BACKGROUND: There is a strong unmet need to improve systemic therapy in mesothelioma. Chemotherapy with cisplatin and pemetrexed improves survival in malignant pleural mesothelioma, and immune checkpoint inhibitors are an emerging treatment in this disease. We aimed to evaluate the activity of durvalumab, an anti-PD-L1 antibody, given during and after first-line chemotherapy with cisplatin and pemetrexed in patients with advanced malignant pleural mesothelioma.<br><br>METHODS: DREAM was a multicentre, single-arm, open-label, phase 2 trial done in nine hospitals in Australia. Eligible patients were aged 18 years or older and had histologically confirmed malignant pleural mesothelioma considered unsuitable for cancer-directed surgery, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease as per the modified Response Evaluation Criteria in Solid Tumors version 1.0 (mRECIST) for mesothelioma that was previously untreated with systemic therapy. All histological subtypes were eligible. The first six participants were treated for two cycles in a safety run-in. All participants received cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and durvalumab 1125 mg intravenously on day 1 of a 3-weekly schedule for a maximum of six cycles. Change from cisplatin to carboplatin with an area under the curve of 5 was permitted. Durvalumab was continued for a maximum of 12 months. The primary endpoint was progression-free survival at 6 months, measured according to mRECIST for malignant pleural mesothelioma and analysed in the intention-to-treat population. Safety analyses included all participants who receive at least one dose of any study drug. This study is registered with the Australia New Zealand Clinical Trials Registry, ACTRN12616001170415.<br><br>FINDINGS: Between Dec 28, 2016, and Sept 27, 2017, 55 participants were enrolled. 54 patients were eligible and were followed up for a median of 28·2 months (IQR 26·5-30·2). 31 (57%; 95% CI 44-70) of 54 patients were alive and progression-free at 6 months. The most common grade 3-4 adverse events were neutropenia (seven [13%] patients), nausea (six [11%]), and anaemia (four [7%]). A total of 60 serious adverse events occurred in 29 participants, five of which were considered possibly related to durvalumab. Five patients died during the study treatment; none of these five deaths were attributed to study treatment.<br><br>INTERPRETATION: The combination of durvalumab, cisplatin, and pemetrexed has promising activity and an acceptable safety profile that warrants further investigation in a randomised phase 3 trial.<br><br>FUNDING: AstraZeneca.}, }
@article {pmid32887638, year = {2020}, author = {Dell'Anno, I and Barone, E and Mutti, L and Rassl, DM and Marciniak, SJ and Silvestri, R and Landi, S and Gemignani, F}, title = {Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report).}, journal = {Journal of translational medicine}, volume = {18}, number = {1}, pages = {341}, pmid = {32887638}, issn = {1479-5876}, support = {/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the pleura, mainly related to asbestos exposure. As in other solid tumors, malignant cells exhibit high glucose uptake and glycolytic rates with increased lactic acid efflux into the interstitial space. Lactate transport into and out of cells, crucial to maintaining intracellular pH homeostasis and glycolysis, is carried out by monocarboxylate transporters (MCTs) and the chaperone basigin (CD147). We set out to examine the clinical significance of basigin, MCT1 and MCT4 in the context of MPM and to evaluate their expression in relation to the evolution of the disease.<br><br>METHODS: We used immunohistochemistry to measure the expression of basigin, MCT1 and MCT4 in a cohort of 135 individuals with MPM compared to a series of 15 non-MPM pleura specimens. Moreover, by Kaplan-Meier and Cox analyses we evaluated whether an expression over the average of these markers could be associated with the patients' overall survival (OS).<br><br>RESULTS: We detected positive staining of basigin, MCT1, and MCT4 in most MPM specimens. In particular, MCT4 was always positive in malignant tissues but undetectable in the 4 normal pleural specimens incorporated within the tissue microarray. This was confirmed in the additional series of 15 normal pleural samples. Moreover, MCT4 expression was significantly associated with reduced OS.<br><br>CONCLUSION: In this study, the tissue expression of basigin did not prove to be exploitable as a diagnostic or prognostic marker for MPM patients. The expression of MCT1 was not informative either, being tightly correlated with that of basigin. However, the expression of MCT4 showed promise as a diagnostic/therapeutic and prognostic biomarker.}, }
@article {pmid32882916, year = {2020}, author = {Cakiroglu, E and Senturk, S}, title = {Genomics and Functional Genomics of Malignant Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32882916}, issn = {1422-0067}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the mesothelial cells lining the pleural surface of the chest wall and lung. The etiology of MPM is strongly associated with prior exposure to asbestos fibers, and the median survival rate of the diagnosed patients is approximately one year. Despite the latest advancements in surgical techniques and systemic therapies, currently available treatment modalities of MPM fail to provide long-term survival. The increasing incidence of MPM highlights the need for finding effective treatments. Targeted therapies offer personalized treatments in many cancers. However, targeted therapy in MPM is not recommended by clinical guidelines mainly because of poor target definition. A better understanding of the molecular and cellular mechanisms and the predictors of poor clinical outcomes of MPM is required to identify novel targets and develop precise and effective treatments. Recent advances in the genomics and functional genomics fields have provided groundbreaking insights into the genomic and molecular profiles of MPM and enabled the functional characterization of the genetic alterations. This review provides a comprehensive overview of the relevant literature and highlights the potential of state-of-the-art genomics and functional genomics research to facilitate the development of novel diagnostics and therapeutic modalities in MPM.}, }
@article {pmid32881200, year = {2020}, author = {Mori, D and Kido, S and Hiraki, M and Sumi, K and Ureshino, N and Masuda, M and Nabeshima, K and Akashi, M}, title = {Peritoneal adenomatoid (microcystic) mesothelioma.}, journal = {Pathology international}, volume = {70}, number = {11}, pages = {876-880}, doi = {10.1111/pin.13006}, pmid = {32881200}, issn = {1440-1827}, abstract = {There are several reports of pleural adenomatoid (microcystic) mesothelioma, but peritoneal adenomatoid mesothelioma is extremely rare. A 64-year-old Japanese woman presented with no symptoms and no asbestos exposure history. An abdominal computed tomography scan revealed multiple hypervascular masses on the liver surface, pelvic cavity and anterior peritoneum. Over 10 pieces of the multiple resected tumors showed numerous microcysts composed of a bland mesothelial cell background with rich capillary vessels. Focally, atypical cells with bizarre nuclei with prominent nucleoli were observed. Adenomatoid mesothelioma was suspected based on histochemical, immunohistochemical and fluorescence in situ hybridization findings. The tumors relapsed 4 years later and metastasized to the lung, but the patient remains alive 7 years after the first tumor resection surgery. Although the prognosis of adenomatoid mesothelioma of pleural origin is poor, the progression of this peritoneal case is slow.}, }
@article {pmid32875620, year = {2020}, author = {Petrof, O and Neyens, T and Nuyts, V and Nackaerts, K and Nemery, B and Faes, C}, title = {On the impact of residential history in the spatial analysis of diseases with a long latency period: A study of mesothelioma in Belgium.}, journal = {Statistics in medicine}, volume = {39}, number = {26}, pages = {3840-3866}, doi = {10.1002/sim.8697}, pmid = {32875620}, issn = {1097-0258}, support = {12S7217N//Fonds Wetenschappelijk Onderzoek/ ; }, abstract = {Mesothelioma is a rare cancer caused by exposure to asbestos. Belgium has a known long history of asbestos production, resulting in one of the highest mesothelioma mortality rates worldwide. While the production of asbestos has stopped completely, the long latency period of mesothelioma, which can fluctuate between 20 and 40 years after exposure, causes incidences still to be frequent. Mesothelioma's long incubation time affects our assessment of its geographical distribution as well. Since patients' residential locations are likely to change a number of times throughout their lives, the location where the patients develop the disease is often far from the location where they were exposed to asbestos. Using the residential history of patients, we propose the use of a convolution multiple membership model (MMM), which includes both a spatial conditional autoregressive and an unstructured random effect. Pancreatic cancer patients are used as a control population, reflecting the population at risk for mesothelioma. Results show the impact of the residential mobility on the geographical risk estimation, as well as the importance of acknowledging the latency period of a disease. A simulation study was conducted to investigate the properties of the convolution MMM. The robustness of the results for the convolution MMM is assessed via a sensitivity analysis.}, }
@article {pmid32869268, year = {2020}, author = {Sayan, M and Mamidanna, S and Fuat Eren, M and Daliparty, V and Zoto Mustafayev, T and Nelson, C and Ohri, N and Jabbour, SK and Guven Mert, A and Atalar, B}, title = {New horizons from novel therapies in malignant pleural mesothelioma.}, journal = {Advances in respiratory medicine}, volume = {88}, number = {4}, pages = {343-351}, doi = {10.5603/ARM.a2020.0103}, pmid = {32869268}, issn = {2543-6031}, abstract = {Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.}, }
@article {pmid32863225, year = {2020}, author = {Ito, F and Yanatori, I and Maeda, Y and Nimura, K and Ito, S and Hirayama, T and Nagasawa, H and Kohyama, N and Okazaki, Y and Akatsuka, S and Toyokuni, S}, title = {Asbestos conceives Fe(II)-dependent mutagenic stromal milieu through ceaseless macrophage ferroptosis and β-catenin induction in mesothelium.}, journal = {Redox biology}, volume = {36}, number = {}, pages = {101616}, doi = {10.1016/j.redox.2020.101616}, pmid = {32863225}, issn = {2213-2317}, abstract = {Asbestos is still a social burden worldwide as a carcinogen causing malignant mesothelioma. Whereas recent studies suggest that local iron reduction is a preventive strategy against carcinogenesis, little is known regarding the cellular and molecular mechanisms surrounding excess iron. Here by differentially using high-risk and low-risk asbestos fibers (crocidolite and anthophyllite, respectively), we identified asbestos-induced mutagenic milieu for mesothelial cells. Rat and cell experiments revealed that phagocytosis of asbestos by macrophages results in their distinctive necrotic death; initially lysosome-depenent cell death and later ferroptosis, which increase intra- and extra-cellular catalytic Fe(II). DNA damage in mesothelial cells, as assessed by 8-hydroxy-2'-deoxyguanosine and γ-H2AX, increased after crocidolite exposure during regeneration accompanied by β-catenin activation. Conversely, β-catenin overexpression in mesothelial cells induced higher intracellular catalytic Fe(II) with increased G2/M cell-cycle fraction, when p16INK4A genomic loci localized more peripherally in the nucleus. Mesothelial cells after challenge of H2O2 under β-catenin overexpression presented low p16INK4A expression with a high incidence of deletion in p16INK4A locus. Thus, crocidolite generated catalytic Fe(II)-rich mutagenic environment for mesothelial cells by necrotizing macrophages with lysosomal cell death and ferroptosis. These results suggest novel molecular strategies to prevent mesothelial carcinogenesis after asbestos exposure.}, }
@article {pmid32849853, year = {2020}, author = {Bai, Y and Wang, X and Hou, J and Geng, L and Liang, X and Ruan, Z and Guo, H and Nan, K and Jiang, L}, title = {Identification of a Five-Gene Signature for Predicting Survival in Malignant Pleural Mesothelioma Patients.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {899}, pmid = {32849853}, issn = {1664-8021}, abstract = {Malignant pleural mesothelioma (MPM), predominantly caused by asbestos exposure, is a highly aggressive cancer with poor prognosis. The staging systems currently used in clinics is inadequate in evaluating the prognosis of MPM. In this study, a five-gene signature was developed and enrolled into a prognostic risk score model by LASSO Cox regression analysis based on two expression profiling datasets (GSE2549 and GSE51024) from Gene Expression Omnibus (GEO). The five-gene signature was further validated using the Cancer Genome Atlas (TCGA) MPM dataset. Univariate and multivariate Cox analyses proved that the five-gene signature was an independent prognostic factor for MPM. The signature remained statistically significant upon stratification by Brigham stage, AJCC stage, gender, tumor size, and lymph node status. Time-dependent receiver operating characteristic (ROC) curve indicated good performance of our model in predicting 1- and 2-years overall survival in MPM patients. The C-index was 0.784 for GSE2549 and 0.753 for the TCGA dataset showing moderate predictive accuracy of our model. Furthermore, Gene Set Enrichment Analysis suggested that the five-gene signature was related to pathways resulting in MPM tumor progression. Together, we have established a five-gene signature significantly associated with prognosis in MPM patients. Hence, the five-genes signature may serve as a potentially useful prognostic tool for MPM patients.}, }
@article {pmid32847019, year = {2020}, author = {Airoldi, C and Ferrante, D and Mirabelli, D and Azzolina, D and Magnani, C}, title = {Evaluation of Nonresponse Bias in a Case-Control Study of Pleural Mesothelioma.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {17}, pages = {}, pmid = {32847019}, issn = {1660-4601}, mesh = {Aged ; Aged, 80 and over ; *Asbestos ; Bias ; Case-Control Studies ; Female ; Humans ; Male ; *Mesothelioma ; Middle Aged ; *Occupational Exposure ; *Pleural Neoplasms ; }, abstract = {Nonparticipation limits the power of epidemiological studies, and can cause bias. In a case-control study on pleural malignant mesothelioma (MM), we found low participation in interviews (63%) among controls. Our goal was to characterize nonresponder controls and assess nonresponse bias in our study. We selected all nonresponder controls (204) and a random sample of responder controls (174). Data were obtained linking hospital admissions and town registrars, and concordance between sources was assessed. Nonresponse bias was evaluated using a logistic regression model applying the inverse probability weighting approach. The odds ratio (OR) for the status of the respondents was 0.61 (95% confidence interval (CI): 0.33-1.16) for controls aged 61-70, 0.37 (CI: 0.20-0.66) for those aged 71-80, and 0.40 (CI: 0.20-0.80) for those aged above 80 (reference group: ≤60 years). Controls with low education level had lower OR (0.47; CI: 0.26-0.84). After adjustment, the ORs for MM by categories of cumulative exposure to asbestos were similar to the unadjusted results, ranging from 4.6 (CI: 1.8-11.7) for cumulative exposures between 0.1 and 1 f/mL-y to 57.5 (CI: 20.2-163.9) above 10 f/mL-y. Responder controls were younger and had higher education level. Nevertheless, there was little evidence of bias from nonresponse in the risk estimates of MM.}, }
@article {pmid32826527, year = {2020}, author = {Mujahed, T and Tazelaar, HD and Sukov, WR and Halling, KC and Davila, JI and Glass, C and Pavlisko, EN and Strickland, KC and Roggli, V and Haque, M and Mneimneh, W and Carter, E and Galateau-Salle, F and Glidden, D and Garcia-Kennedy, R and Larsen, BT}, title = {Malignant Peritoneal Mesothelioma Arising in Young Adults With Long-standing Indwelling Intra-abdominal Shunt Catheters.}, journal = {The American journal of surgical pathology}, volume = {}, number = {}, pages = {}, doi = {10.1097/PAS.0000000000001574}, pmid = {32826527}, issn = {1532-0979}, abstract = {Only 50% to 70% of patients with mesothelioma report asbestos exposure. Other exposures (eg, radiation) play a role in some cases, but some patients have no obvious cause. We describe a series of patients with long-standing indwelling intra-abdominal shunt catheters who developed malignant peritoneal mesothelioma, suggesting a novel association. We identified 7 patients who had shunts and subsequently developed mesothelioma (5 women; median age: 31 y, range: 18 to 45 y). Clinical history and pathology materials were reviewed, and RNA sequencing was performed. Clinical presentations varied; 6 patients had hydrocephalus and a ventriculoperitoneal shunt, and 1 patient had portal hypertension and a portoatrial shunt. The median duration of shunt therapy in 5 cases was 29 years (range: 12 to 35 y); the remaining 2 patients also had shunts for many years, but specific details were unavailable. Two patients had radiotherapy for malignancies in childhood. One had an alleged exposure to asbestos and 1 had prior exposure to talc. The rest had no known risk factors. Histologically, all tumors were purely epithelioid. Treatments included surgical debulking, chemotherapy, and palliative care. All 7 died of disease (median survival: 7 mo, range: 1 to 18 mo). Molecular testing showed loss of NF2 and CDKN2A/B and a BAP1 mutation in 1 case, and no genomic alterations associated with mesothelioma in 2 cases. Peritoneal mesothelioma may represent a complication of long-standing indwelling shunt catheters. The mechanism is unknown, but chronic peritoneal irritation may play a role. Albeit rare, mesothelioma should be considered in patients with a shunt who present with new ascites.}, }
@article {pmid32823952, year = {2020}, author = {Johnson, TG and Schelch, K and Lai, K and Marzec, KA and Kennerson, M and Grusch, M and Reid, G and Burgess, A}, title = {YB-1 Knockdown Inhibits the Proliferation of Mesothelioma Cells through Multiple Mechanisms.}, journal = {Cancers}, volume = {12}, number = {8}, pages = {}, pmid = {32823952}, issn = {2072-6694}, support = {IIRS-18-103//National Breast Cancer Foundation/ ; T 1062 Firnberg Program//Austrian Science Fund/ ; }, abstract = {Y-box binding protein-1 (YB-1) is a multifunctional oncoprotein that has been shown to regulate proliferation, invasion and metastasis in a variety of cancer types. We previously demonstrated that YB-1 is overexpressed in mesothelioma cells and its knockdown significantly reduces tumour cell proliferation, migration, and invasion. However, the mechanisms driving these effects are unclear. Here, we utilised an unbiased RNA-seq approach to characterise the changes to gene expression caused by loss of YB-1 knockdown in three mesothelioma cell lines (MSTO-211H, VMC23 and REN cells). Bioinformatic analysis showed that YB-1 knockdown regulated 150 common genes that were enriched for regulators of mitosis, integrins and extracellular matrix organisation. However, each cell line also displayed unique gene expression signatures, that were differentially enriched for cell death or cell cycle control. Interestingly, deregulation of STAT3 and p53-pathways were a key differential between each cell line. Using flow cytometry, apoptosis assays and single-cell time-lapse imaging, we confirmed that MSTO-211H, VMC23 and REN cells underwent either increased cell death, G1 arrest or aberrant mitotic division, respectively. In conclusion, this data indicates that YB-1 knockdown affects a core set of genes in mesothelioma cells. Loss of YB-1 causes a cascade of events that leads to reduced mesothelioma proliferation, dependent on the underlying functionality of the STAT3/p53-pathways and the genetic landscape of the cell.}, }
@article {pmid32823056, year = {2020}, author = {Torres-Roman, JS and Gomez-Rubio, V and Sanchez-Trujillo, L and Delgado-Rosas, E and Puche-Vergara, F and Sanz-Anquela, JM and Ortega, MA}, title = {Geographic study of mortality due to mesothelioma in Peru and its evolution.}, journal = {Cancer epidemiology}, volume = {68}, number = {}, pages = {101791}, doi = {10.1016/j.canep.2020.101791}, pmid = {32823056}, issn = {1877-783X}, abstract = {BACKGROUND: Peru has a public health problem because of asbestos imports. We analyzed the mortality trends for mesothelioma in Peru and its provinces from 2005 to 2014 and estimated their relationship with the amount of asbestos imported previously.<br><br>METHODS: We computed age-standardized mortality rates (ASMRs) per 100,000 population (direct method and SEGI world standard population reference), and the standardized mortality ratio (SMR). The relationship between the amount of asbestos imported annually along the period 1965-2010 and the number of mesothelioma deaths per year from 2005 to 2014 was estimated by log-linear Poisson regression models and Pearson correlation calculations.<br><br>RESULTS: After correcting the number of deaths, Peru registered 428 cases (or 430 when corrected cases are rounded by sex) between 2005 and 2014. The highest ASMRs were in Arequipa and Callao (range: 0.40-0.41/100,000 population), followed by Huancavelica (0.36/100,000 population). This translates into approximately one death per each 68-111 of asbestos tons imported. The latency period for the higher level of positive correlation found was 8 years (r = 0.8). Male female sex ratio was lower in provinces such as Junin and Hunacavelica with geological asbestos risk.<br><br>CONCLUSIONS: Two patterns of mesothelioma risk have been detected, occupational and environmental. During the 2002-2006 years, Peru increased the asbestos use. If crocidolite imports were also increased, this could be behind the 8 years latency period detected. Peru should boost strategies towards the total ban of all forms of asbestos.}, }
@article {pmid32816595, year = {2020}, author = {Johnson, NF}, title = {Inhalation Toxicity of Talc.}, journal = {Journal of aerosol medicine and pulmonary drug delivery}, volume = {}, number = {}, pages = {}, doi = {10.1089/jamp.2020.1609}, pmid = {32816595}, issn = {1941-2703}, abstract = {Respirable talc powder (RTP) is a complex mineral mixture of talc along with accessory minerals, including tremolite, anthophyllite, quartz, magnesite, dolomite, antigorite, lizardite, and chlorite. The industrial mining, milling, and processing of talc ore is associated with elevated incidences of fibrotic and neoplastic diseases, which are also seen among workers exposed to RTP in secondary industries and individuals using processed cosmetic talc for personal use. There is controversial evidence of a link between the talc-induced lung diseases and a potential contamination with asbestos fibers. This controversy is fueled by inadequate exposure data and the complex mineralogy and terminology of the accessory minerals. Talc aerosols exhibit a wide range of mineral habits, including particulates and fibrous structures that have dimensional and compositional characteristics related to the development of asbestos-related lung disease. The inhalation toxicology of RTP is based on the analysis of occupational hygiene and animal inhalation studies conducted between the 1940s and the 1990s and more recent mechanistic studies conducted both in vivo and in vitro. The review of talc toxicity studies reveals that the occupational studies provide only equivocal links between any of the components of the aerosols and the development of pulmonary cancer; however, there is substantial evidence of an association between the aerosols and pleural and pulmonary fibrosis and the development of nonmalignant respiratory disease. The animal inhalation and implantation studies appear to be less than optimal, which also appears to be true for the in vivo and in vitro studies. The mechanistic studies have identified the key pathogenic characteristics of asbestos to be long and thin fibers that are durable in lung tissues and fluids. Talc toxicity studies show that talc particles and fibers are durable and can remain in the lung for up to 40 years after the end of exposure. This extended tissue residence is considered to constitute a continuing tissue exposure that is capable of inducing the documented inflammatory and proliferative response. There is less consensus as to whether there is a threshold fiber length effect, as long, thin fibers (>5 μm) form only a small fraction of talc aerosols and the possible role of fibers >5 μm in the translocation from the lung to the pleura and their association with pleural fibrotic and carcinogenic lesions. Long, thin fibers are preferentially deposited in hot spots in the lung, such as airway bifurcations, areas typically associated with the development of lung cancer. The platy structures typical of talc can form oblate structures behaving more as fibers in the air stream, and these have also been shown to deposit preferentially in such locations. The review of the inhalation toxicity of talc provides a plausible explanation for the carcinogenic potential of RTP.}, }
@article {pmid32815857, year = {2020}, author = {Alpert, N and van Gerwen, M and Flores, R and Taioli, E}, title = {Gender Differences in Outcomes of Patients With Mesothelioma.}, journal = {American journal of clinical oncology}, volume = {43}, number = {11}, pages = {792-797}, pmid = {32815857}, issn = {1537-453X}, support = {P30 CA196521/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma, Malignant/*mortality ; Middle Aged ; Pleural Neoplasms/*mortality ; *Sex Characteristics ; Survival Rate ; Treatment Outcome ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Mesothelioma is a rare and deadly form of cancer, linked to asbestos exposure. Although the United Kingdom has banned asbestos, the incidence rate remains high. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the United Kingdom.<br><br>MATERIALS AND METHODS: Pleural mesothelioma cases from 2005 to 2014 were extracted from the United Kingdom Lung Cancer Dataset. Multivariable logistic regression was used to assess the clinical and demographic factors associated with gender. A multivariable Cox proportional hazards model and propensity matching methods were used to assess gender differences in overall survival while accounting for potential confounders.<br><br>RESULTS: There were 8479 (87.8%) male and 1765 (17.2%) female individuals included in the analysis. Female individuals were significantly younger, with more epithelial histology than male individuals. Female individuals had significantly better overall survival (adjusted hazard ratio, 0.85, 95% confidence interval, 0.81-0.90). Results remained similar when stratifying by age and performance status, and when limiting to patients with epithelial histology.<br><br>CONCLUSIONS: The study increases knowledge about gender differences in mesothelioma survival and is the first to directly examine this in the United Kingdom. It further disentangles the effects of age, histology, and health status. Increased estrogen may improve survival and could provide a potential target for future therapies.}, }
@article {pmid32811344, year = {2020}, author = {Barbieri, PG and Mirabelli, D}, title = {Diagnosis of lung cancer: a necropsy-based study of 128 cases (1997-2016).}, journal = {Tumori}, volume = {}, number = {}, pages = {300891620949665}, doi = {10.1177/0300891620949665}, pmid = {32811344}, issn = {2038-2529}, abstract = {BACKGROUND: The diagnosis of lung cancer (LC) may be difficult to make in the elderly. We report on the diagnostic elements available in life in an LC necropsy case series of asbestos-exposed workers and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices.<br><br>METHODS: We reviewed pathologic and clinical records of an unselected series of autopsies (1997-2016) in patients with LC employed in the Monfalcone shipyards. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings.<br><br>RESULTS: Data on 128 autopsy-confirmed LC cases were available; in life, 119 had been diagnosed as LC. Among these, 49 had histologic confirmation of diagnosis (17 with immunophenotyping); histology had been negative in 4. Cytology had been the main positive finding and the basis for diagnosis in 24 cases, but had been negative in 13. Chest computed tomography had been the basis for diagnosis in 45; in 18 cases, it had been negative. Nine patients had received a diagnosis different from LC, among whom 4 had been suspected to have malignant pleural mesothelioma by chest computed tomography. Pleural plaques were found in 124 and histologic asbestosis in 46 cases.<br><br>CONCLUSIONS: Autopsies confirmed all LC diagnoses received in life, including 46 that would have been considered only possible LC based on clinical workup. The overall survival in this case series was poor. The high prevalence of pleural plaques and asbestosis suggest severity of asbestos exposures.}, }
@article {pmid32787452, year = {2020}, author = {Uhlenhopp, DJ and Saliares, A and Gaduputi, V and Sunkara, T}, title = {An Unpleasant Surprise: Abdominal Presentation of Malignant Mesothelioma.}, journal = {Journal of investigative medicine high impact case reports}, volume = {8}, number = {}, pages = {2324709620950121}, pmid = {32787452}, issn = {2324-7096}, abstract = {Malignant mesothelioma is an aggressive cancer associated with asbestos exposure with median survival time of 8 to 14 months following diagnosis. Given that mesothelial cells also line the peritoneum and pericardium, malignant mesothelioma can present in unusual sites and in patients with nonrespiratory complaints. A 73-year-old male presented to the emergency department for worsening intermittent diffuse abdominal pain for the past 3 months with associated unintentional 40-pound weight loss, early satiety, and diarrhea. He denied exposure to asbestos. Computed tomography imaging revealed multiple masses concerning for malignancy including the primary retroperitoneal mass, a mass involving the terminal ileum, and a mass in the right upper lung. Esophagogastroduodenoscopy demonstrated significant mass effect within the stomach without signs of endoluminal infiltration. Computed tomography-guided biopsy of the retroperitoneal abdominal and intramuscular paraspinal masses was performed. Stage IV epithelioid mesothelioma was confirmed when hematoxylin and eosin staining revealed pleomorphic malignancy nuclei containing a vesicular chromatin pattern and prominent nucleoli and immunohistochemical staining was positive for CK Oscar, cytokeratin 7, GATA3, calretinin, EMA, and CK5/6. He was started on cisplatin, pemetrexed, and bevacizumab but developed severe abdominal pain with pneumoperitoneum and bowel perforation 1 month later and expired shortly thereafter. To our knowledge, this represents a highly atypical presentation of malignant mesothelioma considering the involvement of the retroperitoneum with diffuse lesions in the abdominopelvic cavity and thorax (sparing the lung pleurae). This case also calls attention to the occurrence of malignant mesothelioma in patients without known asbestos exposure and the crucial role of pathology in diagnosing atypical presentations.}, }
@article {pmid32783735, year = {2020}, author = {Rosner, D and Markowitz, G}, title = {Baby Powders and the Precautionary Principle.}, journal = {American journal of public health}, volume = {110}, number = {9}, pages = {1378-1379}, doi = {10.2105/AJPH.2020.305839}, pmid = {32783735}, issn = {1541-0048}, mesh = {Asbestos/*adverse effects ; Consumer Product Safety ; Female ; Humans ; Mesothelioma/chemically induced/prevention &amp; control ; Ovarian Neoplasms/chemically induced/prevention &amp; control ; Powders/adverse effects/chemistry ; Risk Factors ; Talc/*adverse effects/chemistry ; }, }
@article {pmid32769428, year = {2021}, author = {Malpica, A and Euscher, ED and Marques-Piubelli, ML and Ferrufino-Schmidt, MC and Miranda, RN and Sams, R and Royal, RE and Raghav, KPS and Fournier, KF and Ramalingam, P}, title = {Malignant Mesothelioma of the Peritoneum in Women: A Clinicopathologic Study of 164 Cases.}, journal = {The American journal of surgical pathology}, volume = {45}, number = {1}, pages = {45-58}, doi = {10.1097/PAS.0000000000001545}, pmid = {32769428}, issn = {1532-0979}, abstract = {Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin-stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirect exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients' treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgical treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively.}, }
@article {pmid32769345, year = {2020}, author = {Kazaz, IO and Teoman, AS and Mungan, S}, title = {Mesothelioma of the tunica vaginalis testis: A case report.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {63}, number = {3}, pages = {475-477}, doi = {10.4103/IJPM.IJPM_780_18}, pmid = {32769345}, issn = {0974-5130}, abstract = {Primary mesotheliomas of the tunica vaginalis testis are very rare malignant tumors. They are generally associated with exposure to asbestos. They may manifest as hydrocele, testis tumor, inguinal hernia, or epididymitis. After differential diagnosis, treatment is primarily surgical. Adjuvant therapeutic methods for mesotheliomas of the tunica vaginalis testis, with their high mortality, are controversial. Here, we present a mesothelioma case derived from tunica vaginalis testis acting as long-term pyocele with no known asbestos exposure.}, }
@article {pmid32764839, year = {2020}, author = {Wang, Q and Wang, Q and Zhao, Z and Alexander, DB and Zhao, D and Xu, J and Tsuda, H}, title = {Pleural translocation and lesions by pulmonary exposed multi-walled carbon nanotubes.}, journal = {Journal of toxicologic pathology}, volume = {33}, number = {3}, pages = {145-151}, pmid = {32764839}, issn = {0914-9198}, abstract = {Carbon nanotubes (CNTs) are recently developed tubular nanomaterials, with diameters ranging from a few nanometers to tens of nanometers, and the length reaching up to several micrometers. They can be either single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs). Due to their nano-scaled structure, CNTs have a unique set of mechanical, electrical, and chemical properties that make them useful in information technologies, optoelectronics, energy technologies, material sciences, medical technologies, and other fields. However, with the wide application and increasing production of CNTs, their potential risks have led to concerns regarding their impact on environment and health. The shape of some types of CNTs is similar to asbestos fibers, which suggests that these CNTs may cause characteristic pleural diseases similar to those found in asbestos-exposed humans, such as pleural plaques and malignant mesothelioma. Experimental data indicate that CNTs can induce lung and pleural lesions, inflammation, pleural fibrosis, lung tumors, and malignant mesothelioma upon inhalation in the experimental animals. In this review, we focus on the potential of MWCNTs to induce diseases similar to those by asbestos, molecular and cellular mechanisms associated with these diseases, and we discuss a method for evaluating the pleural toxicity of MWCNTs.}, }
@article {pmid32760782, year = {2020}, author = {Plesker, R and Köhler, K and von Gerlach, S and Boller, K and Vogt, M and Feder, IS}, title = {Reactive mesothelial hyperplasia mimicking mesothelioma in an African green monkey (Chlorocebus aethiops).}, journal = {Primate biology}, volume = {7}, number = {1}, pages = {5-12}, pmid = {32760782}, issn = {2363-4715}, abstract = {A spontaneous reactive mesothelial hyperplasia occurred in a female, 15.7-year-old African green monkey (grivet; Chlorocebus aethiops). At necropsy, massive effusions were found in the abdomen, the thorax, and the pericardium. Additionally, multiple small, beige-gray nodules were detected on the serosal surfaces of the abdominal organs. Histopathologically, the mesothelial cells resembled the epithelioid subtype of a mesothelioma, but no infiltrative or invasive growth could be demonstrated. The mesothelial cells on the thoracis, liver, and intestinal serosa were accompanied by chronic serositis. Mesothelial cells expressed cytokeratin, vimentin, calretinin, desmin, Wilms Tumor 1 (WT-1) protein, and epithelial membrane antigen (EMA). Cells were negative for carcinoembryonic antigen (CEA), cluster of differentiation 15 (CD15), and podoplanin. Ultrastructurally, cells revealed a moderate amount of microvilli of medium length, perinuclear tonofilament bundles, and long desmosomes. In fluorescence in situ hybridization (FISH) for the detection of characteristic gene loss (p16; CDKN2A), NF2, and MTAP, no deletions were detected. No asbestos fibers and no presence of Simian virus 40 antigen (SV40) could be demonstrated.}, }
@article {pmid32759747, year = {2020}, author = {Marzullo, A and Serio, G and Pezzuto, F and Fortarezza, F and Cazzato, G and Caporusso, C and Lettini, T and Cavone, D and Delfino, MC and Vimercati, L}, title = {A Single Liver Metastasis from Pleural Biphasic Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {10}, number = {8}, pages = {}, pmid = {32759747}, issn = {2075-4418}, abstract = {Virtually any malignancy can metastasize to the liver. Large solitary metastases are rare and can be difficult to distinguish from primary tumors. Malignant mesothelioma is often considered as a locally invasive cancer but tumor dissemination to extra-thoracic sites is possible, and the liver can be involved. Herein, we present a rare case of pleural mesothelioma with a solitary large liver metastasis diagnosed postmortem in a ninety-two-year-old man with 35 years of exposure to asbestos. Results of immunohistochemical staining of the pleural and liver tumor were similar, both positive for low-molecular weight keratins, calretinin, vimentin, and podoplanin, and negative for Claudin-4, TTF1, CEA, BerEP4, CK7, CK19, CK20, BAP1, Hep Par1, p40, and WT1. Fluorescent in-situ hybridization (FISH) for p16/CDKN2A was also performed and a homozygous deletion was detected in both tumors, supporting the diagnosis of mesothelioma. Reporting this case, we would like to point out that extra-thoracic dissemination from pleural mesothelioma, even if exceptional, can occur. In cases where differential diagnoses are challenging, the value of ancillary techniques and a practical approach to diagnostic work-up is of primary importance.}, }
@article {pmid32755622, year = {2020}, author = {Luo, Y and Deng, J and Cui, Y and Li, T and Bai, J and Huang, L and Sun, Y and Dong, F and Zhang, Q}, title = {Long-term instillation to four natural representative chrysotile of China induce the inactivation of P53 and P16 and the activation of C-JUN and C-FOS in the lung tissues of Wistar rats.}, journal = {Toxicology letters}, volume = {333}, number = {}, pages = {140-149}, doi = {10.1016/j.toxlet.2020.07.033}, pmid = {32755622}, issn = {1879-3169}, mesh = {Animals ; Asbestos, Serpentine/chemistry/*toxicity ; Bronchoalveolar Lavage Fluid/cytology ; China ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Cytokines/metabolism ; Environmental Pollutants/chemistry/*toxicity ; Gene Expression/drug effects ; Inhalation Exposure/adverse effects ; JNK Mitogen-Activated Protein Kinases/genetics/*metabolism ; Leukocyte Count ; Leukocytes/cytology/drug effects ; Lung/*drug effects/immunology/metabolism/pathology ; Male ; Mineral Fibers/toxicity ; Proto-Oncogene Proteins c-fos/genetics/*metabolism ; Rats, Wistar ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Chrysotile is the only type of asbestos still widely exploited, and all kinds of asbestos including chrysotile was classified as a group I carcinogen by the IARC. There is a wealth of evidence that chrysotile can cause a range of cancers, including cancer of the lung, larynx, ovary, and mesothelioma. As the second largest chrysotile producer, China is at great risk of occupational exposure. Moreover, our previous experiment and some other studies have shown that the toxicity of mineral fibre from various mining areas may be different. To explore the oncogenic potential of chrysotile from different mining areas of China, Wistar rats were administered 0.5 mL chrysotile asbestos suspension of 2.0 mg/mL (from Akesai, Gansu; Mangnai, Qinghai; XinKang, Sichuan; and Shannan, Shaanxi) dissolved in saline by intratracheal instillation once-monthly and were sacrificed at 1 mo, 6 mo, and 12 mo. Our results found that chrysotile caused lung inflammation and lung tissue damage. Moreover, prolonged exposure of chrysotile can induce inactivation of the tumor suppressor gene P53 and P16 and activation of the protooncogene C-JUN and C-FOS both in the messenger RNA and protein level. In addition, chrysotile from Shannan and XinKang has a stronger effect which may link to cancer than that from Akesai and Mangnai.}, }
@article {pmid32732250, year = {2020}, author = {Cerciello, F and Choi, M and Sinicropi-Yao, SL and Lomeo, K and Amann, JM and Felley-Bosco, E and Stahel, RA and Robinson, BWS and Creaney, J and Pass, HI and Vitek, O and Carbone, DP}, title = {Verification of a Blood-Based Targeted Proteomics Signature for Malignant Pleural Mesothelioma.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {29}, number = {10}, pages = {1973-1982}, pmid = {32732250}, issn = {1538-7755}, support = {U01 CA111295/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: We have verified a mass spectrometry (MS)-based targeted proteomics signature for the detection of malignant pleural mesothelioma (MPM) from the blood.<br><br>METHODS: A seven-peptide biomarker MPM signature by targeted proteomics in serum was identified in a previous independent study. Here, we have verified the predictive accuracy of a reduced version of that signature, now composed of six-peptide biomarkers. We have applied liquid chromatography-selected reaction monitoring (LC-SRM), also known as multiple-reaction monitoring (MRM), for the investigation of 402 serum samples from 213 patients with MPM and 189 cancer-free asbestos-exposed donors from the United States, Australia, and Europe.<br><br>RESULTS: Each of the biomarkers composing the signature was independently informative, with no apparent functional or physical relation to each other. The multiplexing possibility offered by MS proteomics allowed their integration into a single signature with a higher discriminating capacity than that of the single biomarkers alone. The strategy allowed in this way to increase their potential utility for clinical decisions. The signature discriminated patients with MPM and asbestos-exposed donors with AUC of 0.738. For early-stage MPM, AUC was 0.765. This signature was also prognostic, and Kaplan-Meier analysis showed a significant difference between high- and low-risk groups with an HR of 1.659 (95% CI, 1.075-2.562; P = 0.021).<br><br>CONCLUSIONS: Targeted proteomics allowed the development of a multianalyte signature with diagnostic and prognostic potential for MPM from the blood.<br><br>IMPACT: The proteomic signature represents an additional diagnostic approach for informing clinical decisions for patients at risk for MPM.}, }
@article {pmid32731396, year = {2020}, author = {Javadi, J and Dobra, K and Hjerpe, A}, title = {Multiplex Soluble Biomarker Analysis from Pleural Effusion.}, journal = {Biomolecules}, volume = {10}, number = {8}, pages = {}, pmid = {32731396}, issn = {2218-273X}, support = {CAN 2018/653//Cancerfonden/International ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.}, }
@article {pmid32727552, year = {2020}, author = {Lehnert, M and Weber, DG and Taeger, D and Raiko, I and Kollmeier, J and Stephan-Falkenau, S and Brüning, T and Johnen, G and , }, title = {Determinants of plasma calretinin in patients with malignant pleural mesothelioma.}, journal = {BMC research notes}, volume = {13}, number = {1}, pages = {359}, pmid = {32727552}, issn = {1756-0500}, support = {IN-1214264//Ruhr-Universität Bochum/ ; }, abstract = {OBJECTIVE: Calretinin is a well-known immunohistochemical tissue marker in the diagnosis of malignant mesothelioma. Promising results also indicate the use in early detection. In the present cross-sectional survey, correlations of calretinin plasma levels with clinical features were investigated. Plasma samples of 60 patients with malignant pleural mesothelioma (MPM) and 111 cancer-free controls formerly exposed to asbestos were compared. Calretinin concentrations were determined in plasma using an enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: The median concentration was higher in MPM patients than in controls (0.79 vs. 0.23 ng/ml; p < 0.0001). Patients with epithelioid MPM or biphasic MPM had higher calretinin plasma levels than patients with sarcomatoid MPM. Strong expression of calretinin in the tumor tissue was associated with higher plasma levels. Preoperative patients showed higher levels of calretinin than patients after thoracic surgery (1.20 vs. 0.67 ng/ml; p = 0.096). The suitability of plasma calretinin has been confirmed as a tumor marker in the differential diagnosis of epithelioid MPM. The value of plasma calretinin for therapy monitoring or as a prognostic marker should be further investigated.}, }
@article {pmid32726334, year = {2020}, author = {Schüz, J and Bukhtiyarov, I and Olsson, A and Moissonnier, M and Ostroumova, E and Feletto, E and Schonfeld, SJ and Byrnes, G and Tskhomariia, I and McCormack, V and Straif, K and Kashanskiy, S and Morozova, T and Kromhout, H and Kovalevskiy, E}, title = {Occupational cohort study of current and former workers exposed to chrysotile in mine and processing facilities in Asbest, the Russian Federation: Cohort profile of the Asbest Chrysotile Cohort study.}, journal = {PloS one}, volume = {15}, number = {7}, pages = {e0236475}, pmid = {32726334}, issn = {1932-6203}, mesh = {Adult ; Asbestos/adverse effects ; Asbestos, Serpentine/*adverse effects ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/chemically induced/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology/pathology ; Occupational Exposure/*adverse effects ; Russia/epidemiology ; }, abstract = {A historical cohort study in workers occupationally exposed to chrysotile was set up in the town of Asbest, the Russian Federation, to study their cause-specific mortality, with a focus on cancer. Chrysotile has different chemical and physical properties compared with other asbestos fibres; therefore it is important to conduct studies specifically of chrysotile and in different geographical regions to improve the knowledge about its carcinogenicity. Setting was the town of Asbest, Sverdlovsk oblast, the Russian Federation. Participants were all current and former employees with at least one year of employment between 1/1/1975 and 31/12/2010 in the mine, enrichment factories, auto-transport and external rail transportation departments, the central laboratory, and the explosives unit of the company. Of the 35,837 cohort members, 12,729 (35.5%) had died (2,373 of them of cancer, including 10 of mesothelioma), 18,799 (52.5%) were known to be alive at the end of the observation period (2015), and 4,309 (12.0%) were censored before the end of 2015. Mean follow-up duration was 21.7 years in men and 25.9 years in women. The mean age at death was 59.4 years in men and 66.5 years in women. This is the largest occupational cohort of chrysotile workers to date, and the only one with a large proportion of exposed female workers.}, }
@article {pmid32723839, year = {2020}, author = {Kwak, K and Paek, D and Zoh, KE}, title = {Author's response to 'Re: Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis by Kwak et al'.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {9}, pages = {656-657}, doi = {10.1136/oemed-2020-106737}, pmid = {32723839}, issn = {1470-7926}, mesh = {*Asbestos/adverse effects ; *Colonic Neoplasms ; *Colorectal Neoplasms ; Humans ; *Mesothelioma ; }, }
@article {pmid32710945, year = {2020}, author = {Gandhi, M and Nair, S}, title = {New vistas in malignant mesothelioma: MicroRNA architecture and NRF2/MAPK signal transduction.}, journal = {Life sciences}, volume = {257}, number = {}, pages = {118123}, doi = {10.1016/j.lfs.2020.118123}, pmid = {32710945}, issn = {1879-0631}, mesh = {Animals ; Biomarkers, Tumor ; Humans ; Lung Neoplasms/*metabolism ; *MAP Kinase Signaling System ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; MicroRNAs/*metabolism ; NF-E2-Related Factor 2/*metabolism ; }, abstract = {Malignant mesothelioma (MM) is a cancer of the mesothelial lining of the pleura, peritoneum, pericardium and testes. The most common form is asbestos-linked MM that is etiologically linked to repeated asbestos exposure with a long latency period, although non-asbestos MM has also been reported. Late diagnosis, poor survival rates, lack of diagnostic and prognostic markers act as major impediments in the clinical management of MM. Despite advances in immune checkpoint inhibition and CAR T-cell-based therapies, MM which is of different histologic subtypes remains challenging to treat. We review microRNAs (miRNAs) and the miRNA interactome implicated in MM which can be useful as circulating miRNA biomarkers for early diagnosis of MM and as biomarkers for prognostication in MM. Further, we underscore the relevance of the NRF2/MAPK signal transduction pathway that has been implicated in MM which may be useful as druggable targets or as biomarkers of predictive response. In addition, since MM is driven partly by inflammation, we elucidate chemopreventive phytochemicals that are beneficial in MM, either via crosstalk with the NRF2/MAPK pathway or via concerted anticancer mechanisms, and may be of benefit as adjuvants in chemotherapy. Taken together, a multifactorial approach comprising identification of miRNA target hubs and NRF2/MAPK biomarkers along with appropriately designed clinical trials may enable early detection and faster intervention in MM translating into better patient outcomes for this aggressive cancer.}, }
@article {pmid32709739, year = {2020}, author = {Boffetta, P}, title = {Re: Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis by Kwak et al.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {9}, pages = {655}, doi = {10.1136/oemed-2020-106588}, pmid = {32709739}, issn = {1470-7926}, mesh = {*Asbestos/adverse effects ; *Colonic Neoplasms ; *Colorectal Neoplasms/etiology ; Humans ; *Mesothelioma ; }, }
@article {pmid32708306, year = {2020}, author = {Bonelli, M and Terenziani, R and Zoppi, S and Fumarola, C and La Monica, S and Cretella, D and Alfieri, R and Cavazzoni, A and Digiacomo, G and Galetti, M and Petronini, PG}, title = {Dual Inhibition of CDK4/6 and PI3K/AKT/mTOR Signaling Impairs Energy Metabolism in MPM Cancer Cells.}, journal = {International journal of molecular sciences}, volume = {21}, number = {14}, pages = {}, pmid = {32708306}, issn = {1422-0067}, support = {N/A//Associazione Augusto per la Vita (Novellara, RE)/ ; N/A//CHIESI Farmaceutici S.p.A. (Parma)/ ; N/A//Transfer Oil S.p.A. (Colorno, PR)/ ; N/A//Famiglia Gigetto Furlotti (Parma)/ ; N/A//A.VO.PRO.RI.T. (Parma)/ ; N/A//Ing. Marco Nocivelli, EPTA S.p.A (Milano)/ ; 2018.0184//Fondazione CARIPARMA/ ; }, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated to asbestos exposure. One of the most frequent genetic alteration in MPM patients is CDKN2A/ARF loss, leading to aberrant activation of the Rb pathway. In MPM cells, we previously demonstrated the therapeutic efficacy of targeting this signaling with the CDK4/6 inhibitor palbociclib in combination with PI3K/mTOR inhibitors. Here, we investigated whether such combination may have an impact on cell energy metabolism. Methods: The study was performed in MPM cells of different histotypes; metabolic analyses were conducted by measuring GLUT-1 expression and glucose uptake/consumption, and by SeaHorse technologies. Results: MPM cell models differed for their ability to adapt to metabolic stress conditions, such as glucose starvation and hypoxia. Independently of these differences, combined treatments with palbociclib and PI3K/mTOR inhibitors inhibited cell proliferation more efficaciously than single agents. The drugs alone reduced glucose uptake/consumption as well as glycolysis, and their combination further enhanced these effects under both normoxic and hypoxic conditions. Moreover, the drug combinations significantly impaired mitochondrial respiration as compared with individual treatments. These metabolic effects were mediated by the concomitant inhibition of Rb/E2F/c-myc and PI3K/AKT/mTOR signaling. Conclusions: Dual blockade of glycolysis and respiration contributes to the anti-tumor efficacy of palbociclib-PI3K/mTOR inhibitors combination.}, }
@article {pmid32700418, year = {2020}, author = {Voloaca, OM and Greenhalgh, CJ and Cole, LM and Clench, MR and Managh, AJ and Haywood-Small, SL}, title = {Laser ablation inductively coupled plasma mass spectrometry as a novel clinical imaging tool to detect asbestos fibres in malignant mesothelioma.}, journal = {Rapid communications in mass spectrometry : RCM}, volume = {34}, number = {21}, pages = {e8906}, doi = {10.1002/rcm.8906}, pmid = {32700418}, issn = {1097-0231}, abstract = {RATIONALE: Malignant pleural mesothelioma is an extremely aggressive and incurable malignancy associated with prior exposure to asbestos fibres. Difficulties remain in relation to early diagnosis, notably due to impeded identification of asbestos in lung tissue. This study describes a novel laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging approach to identify asbestos within mesothelioma models with clinical significance.<br><br>METHODS: Human mesothelioma cells were exposed to different types of asbestos fibres and prepared on plastic slides for LA-ICP-MS analysis. No further sample preparation was required prior to analysis, which was performed using an NWR Image 266 nm laser ablation system coupled to an Element XR sector-field ICP mass spectrometer, with a lateral resolution of 2 μm. Data was processed using LA-ICP-MS ImageTool v1.7 with the final graphic production made using DPlot software.<br><br>RESULTS: Four different mineral fibres were successfully identified within the mesothelioma samples based on some of the most abundant elements that make up these fibres (Si, Mg and Fe). Using LA-ICP-MS as an imaging tool provided information on the spatial distribution of the fibres at cellular level, which is essential in asbestos detection within tissue samples. Based on the metal counts generated by the different types of asbestos, different fibres can be identified based on shape, size, and elemental composition. Detection of Ca was attempted but requires further optimisation.<br><br>CONCLUSIONS: Detection of asbestos fibres in lung tissues is very useful, if not necessary, to complete the pathological dt9iagnosis of asbestos-related malignancies in the medicolegal field. For the first time, this study demonstrates the successful application of LA-ICP-MS imaging to identify asbestos fibres and other mineral fibres within mesothelioma samples. Ultimately, high-resolution, fast-speed LA-ICP-MS analysis has the potential to be integrated into clinical workflow to aid earlier detection and stratification of mesothelioma patient samples.}, }
@article {pmid32699075, year = {2020}, author = {Pass, HI and Alimi, M and Carbone, M and Yang, H and Goparaju, CM}, title = {Mesothelioma Biomarkers: A Review Highlighting Contributions from the Early Detection Research Network.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {29}, number = {12}, pages = {2524-2540}, doi = {10.1158/1055-9965.EPI-20-0083}, pmid = {32699075}, issn = {1538-7755}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm, which can be treated successfully only if correctly diagnosed and treated in early stages. The asbestos-exposed population serves as a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. This review details the recent work with biomarker development in MPM and the contributions of the NCI Early Detection Research Network Biomarker Developmental Laboratory of NYU Langone Medical Center. The literature of the last 20 years was reviewed to comment on the most promising of the blood- and tissue-based biomarkers. Proteomic, genomic, and epigenomic platforms as well as novel studies such as &quot;breath testing&quot; are covered. Soluble mesothelin-related proteins (SMRP) have been characterized extensively and constitute an FDA-approved biomarker in plasma with diagnostic, monitoring, and prognostic value in MPM. Osteopontin is found to be a valuable prognostic biomarker for MPM, while its utility in diagnosis is slightly lower. Other biomarkers, such as calretinin, fibulin 3, and High-Mobility Group Box 1 (HMGB1), remain under study and need international validation trials with large cohorts of cases and controls to demonstrate any utility. The EDRN has played a key role in the development and testing of MPM biomarkers by enlisting collaborations all over the world. A comprehensive understanding of previously investigated biomarkers and their utility in screening and early diagnosis of MPM will provide guidance for further future research.See all articles in this CEBP Focus section, &quot;NCI Early Detection Research Network: Making Cancer Detection Possible.&quot;}, }
@article {pmid32691574, year = {2020}, author = {Loreto, C and Ledda, C and Tumino, R and Lombardo, C and Vitale, E and Filetti, V and Caltabiano, R and Rapisarda, V}, title = {Activation of caspase-3 in malignant mesothelioma induced by asbestiform fiber: an in vivo study.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {34}, number = {3}, pages = {1163-1166}, doi = {10.23812/19-441-L-50}, pmid = {32691574}, issn = {0393-974X}, mesh = {Caspase 3/genetics ; Humans ; Italy ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; }, }
@article {pmid32683434, year = {2020}, author = {Brook, MS and Black, PM and Salmond, J and Dirks, KN and Berry, TA and Steinhorn, G}, title = {Erionite in Auckland bedrock and malignant mesothelioma: an emerging public and occupational health hazard?.}, journal = {The New Zealand medical journal}, volume = {133}, number = {1518}, pages = {73-78}, pmid = {32683434}, issn = {1175-8716}, mesh = {Humans ; Incidence ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; Mesothelioma, Malignant ; New Zealand/epidemiology ; Occupational Exposure/*adverse effects ; *Occupational Health ; *Public Health ; Zeolites/*adverse effects ; }, abstract = {Overseas, emerging research has shown that where erionite is present in bedrock as a zeolite, and then subsequently disturbed and blown into the atmosphere, resulting exposure is associated with health effects similar to those caused by asbestos, including malignant mesothelioma (MM). Erionite-induced MM is thought to be particularly prevalent in the construction and quarrying industries, in regions where rock containing erionite is disturbed. In 2015, the then Government Chief Scientist, Sir Peter Gluckman, reported that erionite was a more potent carcinogen than asbestos, and more recent studies have established its presence in the Auckland Region. However, globally at present, there are no established occupational exposure limits for erionite, standard sampling and analytical methods or exposure mitigation guidelines. Given the many major construction projects being carried out in Auckland at the present time, which involve the removal of large quantities of bedrock containing erionite, an assessment of the health risks such activities pose to the public is needed.}, }
@article {pmid32682370, year = {2020}, author = {Cheng, L and Li, N and Xu, XL and Mao, WM}, title = {Progress in the Understanding of the Immune Microenvironment and Immunotherapy in Malignant Pleural Mesothelioma.}, journal = {Current drug targets}, volume = {21}, number = {15}, pages = {1606-1612}, doi = {10.2174/1389450121666200719011234}, pmid = {32682370}, issn = {1873-5592}, abstract = {Malignant pleural mesothelioma (MPM) is a remarkably aggressive thoracic malignancy with a limited survival of only 5-12 months. However, MPM still remains unresponsive to conventional standards of treatment, including pleurectomy and decortication, extrapleural pneumonectomy for resectable disease with or without chemotherapy, and/or radiation therapy. The mechanism of carcinogenesis has not been fully elucidated, although approximately 80% of cases can still be linked to asbestos exposure. The tumor immune microenvironment (TME) has been proven to play an important role in MPM pathogenesis and treatment outcomes. Several molecular pathways have been implicated in the MPM tumor microenvironment, such as angiogenesis, apoptosis, cell cycle regulation, and stromal processes. Immunotherapy has already shown promising results in other thoracic solid tumors, such as non-small-cell lung cancer (NSCLC). However, immunotherapy has shown less convincing results in MPM than in melanoma and NSCLC. A multicenter, randomized trial (DETERMINE) proved that immune checkpoint inhibition using tremelimumab, an anti-cytotoxic T lymphocyteassociated protein 4 (CTLA-4) antibody, failed to improve median overall survival. Therefore, it is important to explore the relationship between the characteristics of the tumor microenvironment and immunotherapy. Here, we review the heterogeneity of the TME and the progress in the understanding of the immune microenvironment and immunotherapy in MPM to explore the mechanisms of resistance to immunotherapy.}, }
@article {pmid32682189, year = {2020}, author = {Remon, J and Nadal, E and Dómine, M and Ruffinelli, J and García, Y and Pardo, JC and López, R and Cilleruelo, A and García-Campelo, R and Martín, P and Juan, O and González-Larriba, JL and Provencio, M and Olmedo, E and Ponce, S and Cumplido, D and Barenys, C and Majem, M and Massutti, B and Rodriguez-Abreu, D and Porta, R and Sala, MA and Martinez-Kareaga, M and Lianes, P and Reguart, N}, title = {Malignant pleural mesothelioma: Treatment patterns and outcomes from the Spanish Lung Cancer Group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {147}, number = {}, pages = {83-90}, doi = {10.1016/j.lungcan.2020.06.034}, pmid = {32682189}, issn = {1872-8332}, abstract = {BACKGROUND: Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain.<br><br>MATERIAL AND METHODS: Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments.<br><br>RESULTS: A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1-14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7-57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8-16.0 months), reaching 20.2 months (95 % CI, 17.2-23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy.<br><br>CONCLUSIONS: Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.}, }
@article {pmid32676359, year = {2020}, author = {Hjerpe, A and Abd Own, S and Dobra, K}, title = {Integrative approach to cytologic and molecular diagnosis of malignant pleural mesothelioma.}, journal = {Translational lung cancer research}, volume = {9}, number = {3}, pages = {934-943}, pmid = {32676359}, issn = {2218-6751}, abstract = {The global incidence of malignant mesothelioma (MM) causes considerable disease burden, suffering and health care costs. Beside preventive measures and ban the use of asbestos, early diagnosis would largely improve the chance of curative treatment. Current histologic criteria, however, requiring presence of invasion in the surrounding fatty tissue fail to identify MM in sufficiently early stage. Unilateral accumulation of pleural effusion is one of the earliest clinical manifestations of MM that occurs in approximately 90% of the patients. Therapeutic thoracocenthesis is necessary to remove the fluid and to relieve patients' symptoms. This effusion is easily accessible and offers early and minimally invasive diagnosis by combining cytology with immunologic, molecular- and biomarker analyses. Typically, the fluid is rich in malignant cells and cell groups, but incipient stages of the disease may be difficult to recognize as the malignant cells can be masked by presence of inflammatory or reactive mesothelial cells. Recurrent, hemorrhagic and cell rich effusion should always be suspicious for MM and adequately prepared and analyzed to provide necessary information for subsequent therapy. Importantly, early detection of MM by integrating cytology and molecular approaches has high sensitivity and positive predictive value and has a major impact on patient survival. Thus, a conclusive positive MM cytology should lead to treatment without delay. This review summarizes molecular and diagnostic criteria of MM diagnosis.}, }
@article {pmid32667289, year = {2020}, author = {Świątkowska, B}, title = {[The Amiantus Program in Poland - 20 years of implementation].}, journal = {Medycyna pracy}, volume = {71}, number = {5}, pages = {595-601}, doi = {10.13075/mp.5893.00997}, pmid = {32667289}, issn = {2353-1339}, abstract = {BACKGROUND: Despite the ban on the production of asbestos-containing materials, introduced in Poland over 20 years ago, new cases of asbestos-related diseases are still being recorded. Systematic control of respiratory function in people exposed to asbestos dust is, therefore, extremely important due to the biological properties of this mineral.<br><br>MATERIAL AND METHODS: The Amiantus preventive medical examination program was undertaken in 2000 to implement the legal rights of former employees of asbestos processing plants for this type of examinations. People who have ever been employed in such factories have been authorized to use preventive medical examinations for the rest of their lives. The research is continuous, spread over time and focused, in particular, on the assessment of the respiratory system.<br><br>RESULTS: Since the beginning of the program, throughout 20 years of its implementation, 8329 people have been examined, including 5199 (62.4%) men for whom a total of 34 454 medical examinations have been carried out. During the program period, the percentage of diagnosed pathologies increased from 8% in 2000 to 25% in 2019. Overall, 2078 asbestos-related diseases were diagnosed among former employees of asbestos processing plants under the Amiantus Program, which accounted for 25% of this group. Among all diseases caused by exposure to asbestos, the most common were: asbestosis (1880 cases - 90.5%), lung cancer (121 cases - 5.8%) and pleural mesothelioma (77 cases - 3.7%). Diseases of pleura in the form of plaques and diffuse pleural thickening were diagnosed in 40% of the examined patients, while radiological pulmonary shadows affected over 65% of former employees of asbestos processing plants.<br><br>CONCLUSIONS: The Amiantus Program, thanks to the long observation period, enabled monitoring the health of former employees exposed to asbestos, and created a unique opportunity to carry out epidemiological analyzes. These studies allowed the authors to expand their knowledge of the natural history of asbestos-related diseases. Med Pr. 2020;71(5):595-601.}, }
@article {pmid32664483, year = {2020}, author = {Indovina, P and Forte, IM and Pentimalli, F and Giordano, A}, title = {Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade.}, journal = {Cancers}, volume = {12}, number = {7}, pages = {}, pmid = {32664483}, issn = {2072-6694}, support = {ID 483418//Mesothelioma Applied Research Foundation/ ; Ricerca Corrente (M4/7)//Italian Ministry of Health/ ; }, abstract = {Abstract: Malignant mesothelioma (MM) is a deadly tumor mainly caused by exposure to asbestos. Unfortunately, no current treatment is able to change significantly the natural history of the disease, which has a poor prognosis in the majority of patients. The non-receptor tyrosine kinase SRC and other SRC family kinase (SFK) members are frequently hyperactivated in many cancer types, including MM. Several works have indeed suggested that SFKs underlie MM cell proliferation, survival, motility, and invasion, overall affecting multiple oncogenic pathways. Consistently, SFK inhibitors effectively counteracted MM cancerous features at the preclinical level. Dasatinib, a multi-kinase inhibitor targeting SFKs, was also assessed in clinical trials either as second-line treatment for patients with unresectable MM or, more recently, as a neoadjuvant agent in patients with resectable MM. Here, we provide an overview of the molecular mechanisms implicating SFKs in MM progression and discuss possible strategies for a more successful clinical application of SFK inhibitors. Our aim is to stimulate discussion and further consideration of these agents in better designed preclinical and clinical studies to make the most of another class of powerful antitumoral drugs, which too often are lost in translation when applied to MM.}, }
@article {pmid32649346, year = {2020}, author = {Louw, A and Creaney, J and Thomas, A and Van Vliet, C and Harvey, NT and Wood, BA and Mesbah Ardakani, N}, title = {Histologically Diverse BAP1-Deficient Melanocytic Tumors in a Patient With BAP1 Tumor Predisposition Syndrome.}, journal = {The American Journal of dermatopathology}, volume = {42}, number = {11}, pages = {872-875}, doi = {10.1097/DAD.0000000000001719}, pmid = {32649346}, issn = {1533-0311}, abstract = {BRCA1-associated protein-1 (BAP1)-deficient cutaneous tumors are common in patients with BAP1 tumor predisposition syndrome, frequently presenting before other associated neoplasms, and can serve as an early marker to identify individuals with this disease. The typical lesions are dermal based and composed of a combination of larger epithelioid melanocytes with abundant glassy cytoplasm and smaller cells resembling those of a conventional nevus. There is often a component of interspersed lymphocytes. However, BAP1-deficient melanocytic tumors can show a spectrum of histologic appearances, ranging from lesions with pure epithelioid, pure conventional nevus, or rhabdoid cells and tumors with an intraepidermal component. To demonstrate such morphologic variation, we present a case of a 50-year-old woman with multiple histologically diverse BAP1-deficient melanocytic tumors and germline BAP1 mutation, identified after a diagnosis of pleural mesothelioma. We also discuss the pathogenesis and potential histopathological and clinical indications of germline versus sporadic etiology in the assessment of BAP1-deficient melanocytic tumors.}, }
@article {pmid32648970, year = {2020}, author = {Schüz, J and Kromhout, H}, title = {Re Ferrante et al (2020). Mortality and mesothelioma incidence among chrysotile asbestos miners in Balangero, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {63}, number = {9}, pages = {834-835}, doi = {10.1002/ajim.23154}, pmid = {32648970}, issn = {1097-0274}, mesh = {Asbestos, Serpentine ; Cohort Studies ; Humans ; Incidence ; Italy ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid32648944, year = {2020}, author = {Ferrante, D and Mirabelli, D and Silvestri, S and Azzolina, D and Giovannini, A and Tribaudino, P and Magnani, C}, title = {Ferrante et al respond.}, journal = {American journal of industrial medicine}, volume = {63}, number = {9}, pages = {836-837}, doi = {10.1002/ajim.23153}, pmid = {32648944}, issn = {1097-0274}, mesh = {*Asbestos, Serpentine ; Cohort Studies ; Humans ; Incidence ; Italy ; *Mesothelioma ; }, }
@article {pmid32633902, year = {2020}, author = {Maat, A and Abdullah, S and Schouten, G and Cornelissen, R and Bogers, A and Mahtab, E}, title = {Video-assisted biopsy and talc pleurodesis for malignant pleural mesothelioma.}, journal = {Multimedia manual of cardiothoracic surgery : MMCTS}, volume = {2020}, number = {}, pages = {}, doi = {10.1510/mmcts.2020.038}, pmid = {32633902}, issn = {1813-9175}, mesh = {Aged ; Humans ; Image-Guided Biopsy/*methods ; *Lung Neoplasms/pathology/physiopathology/therapy ; Male ; *Mesothelioma/pathology/physiopathology/therapy ; Mesothelioma, Malignant ; Pleural Effusion, Malignant/etiology/prevention &amp; control ; Pleurodesis/*methods ; Thoracic Surgery, Video-Assisted/*methods ; }, abstract = {Malignant pleural mesothelioma is a disease of the pleural cavity that is strongly associated with asbestos exposure. In most cases it carries a poor prognosis. Patients often present with respiratory symptoms, caused by pleural effusion. Treatment, preferably in a multimodal setting, cannot provide cure, but can prolong survival and improve quality of life in selected cases. Prior to eventual cytoreductive surgery, surgical intervention can provide histopathological proof of disease, and symptoms can be controlled with talc pleurodesis. We present the case of a 67-year-old patient with malignant pleural mesothelioma who underwent video-assisted thoracoscopic biopsy and talc pleurodesis, and demonstrate our technique with a video tutorial showing how we performed the procedure.}, }
@article {pmid32631013, year = {2020}, author = {Fazzo, L and Cernigliaro, A and De Santis, M and Quattrone, G and Bruno, C and Zona, A and Tumino, R and Cascone, G and Scondotto, S and Comba, P}, title = {Occupational cohort study of asbestos-cement workers in a contaminated site in Sicily (Italy).}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {2-3}, pages = {137-144}, doi = {10.19191/EP20.2-3.P137.036}, pmid = {32631013}, issn = {1120-9763}, abstract = {OBJECTIVES: to analyse the asbestos-related diseases risk among the former workers of Sacelit asbestos-cement plant, operating in San Filippo del Mela (Sicily: 1958- 1993).<br><br>DESIGN: cohort study.<br><br>SETTING AND PARTICIPANTS: 228 subjects were employed in Sacelit from 1958 to 1993. Due to the available observation periods, the analyses of the different outcomes were performed for the subjects alive at the beginning of the respective follow up periods: mortality (1986-2018) was analysed for 204 subjects (177 men, 27 women), hospitalization (2001-2016) for 164 workers (139 men, 25 women) and the incidence of mesothelioma (1998-2016) was estimated for 178 subjects (153 men, 25 women).<br><br>MAIN OUTCOMES MEASURES: mortality (Standardized Mortality Ratio: SMR) and hospitalization (Standardized Hospitalization Ratio: SHR) from specific diseases were analysed. Incidence (Standardized Incidence Ratio: SIR) of mesothelioma cases was detected, also. SMR (1986-2014), SHR (2001-2016) and SIR (1998-2016), with 95% Confidence Intervals, were computed with respect to the regional rates, with STATA11.<br><br>RESULTS: in the men cohort, mortality from lung (17 cases, SMR 2.83) and pleural cancers (5 cases, SMR 30) and from asbestosis (15 cases, SMR 1,930) was in excess. The risk of hospitalization was in excess, in both genders, from lung cancer (men: 6 cases, SHR 4.1; women: 2 cases, SHR 8.6) and asbestosis (men: 17 cases, SHR 1,304; women: 6 cases, SHR 2,455). The incidence of mesothelioma was in excess in men (5 cases, SIR 23.9); no female cases of mesothelioma were observed.<br><br>CONCLUSIONS: a high occurrence of asbestos-related diseases in the cohort, particularly among men, was observed. The excess of hospitalization from asbestosis and lung cancer was highlighted also in women. The prosecution of the on-going health surveillance plan is particularly appropriated.}, }
@article {pmid32626907, year = {2021}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Comments on a recent case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {47}, number = {1}, pages = {85-86}, doi = {10.5271/sjweh.3909}, pmid = {32626907}, issn = {1795-990X}, abstract = {As the first case-control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis (mTVT), the paper by Marinaccio et al (1) is potentially an important epidemiologic contribution. A careful review of the paper, however, raises a number of methodological issues. Any case-control study can be viewed as being nested within a conceptual cohort, with controls being sampled from the at-risk cohort as cases arise over time. This view of case-control studies leads to the concept of incidence-density sampling of controls (eg, 2, 3). For Marinaccio et al (1) this would mean that, as cases were registered over the study period, each would be matched to an individual control or set of controls of the same gender, age, and region of the country (since asbestos exposure varies by time and region [4]). For example, if a case were 50 years old in 1995, then any matched control should be close to age 50 in 1995 and of the same gender and from the same region as the case. Matching for age in this fashion automatically results in matching for year of birth, which is essential in this context because birth-cohort effects are determinants of asbestos exposure and mesothelioma incidence (eg, 5-8). If Marinaccio et al (1) used this scheme for age-matching, one would expect to see similar distributions of cases (table 1) and controls (table S3 in the supplemental material) by period of birth. Among males, however, the distributions of mesothelioma cases (whether pericardial or mTVT) and controls by period of birth are clearly different (P<0.001). Among females, the distributions of cases of pericardial mesothelioma and controls by birth year are less dissimilar (P≈0.05). Thus, the female cases of pericardial mesothelioma are better matched to controls on year of birth than are male cases of either mTVT or pericardial mesothelioma. We note also that the distributions of male and female controls by year of birth are distinctly different (P<0.002), whereas the birth-year distributions of cases of mesothelioma by site and gender are not (P≈0.8). In the Marinaccio et al (1) sensitivity analysis restricted to subjects born before 1950, the distributions of cases and controls by period of birth remain significantly different. Therefore, based on the reported evidence, cases and controls were not matched on birth cohort, thereby possibly biasing the results. Similarly, bias may result from the lack of matching on geographic region; while cases were registered from across Italy, controls were selected from only six regions. Although a sensitivity analysis restricted cases and controls to those from only the six regions, a comparison of tables S1 and S3 indicates that the regional distribution of controls is different from that of person-time observed; that is, the controls do not appear to be representative of the underlying population at risk by region. The second major issue of concern has to do with ascertainment of asbestos exposure. Information on exposure for the cases was presumably obtained at the time of registration. The two sets of controls, obtained from previously unpublished case-control studies, were interviewed during 2014-2015 and 2014-2016; that is, many years after the exposure for most cases was ascertained (1993-2015). Few other details of the control groups are provided, except that participation by one set of controls was <50%, raising additional concerns about selection bias. For details on the second set of controls, Marinaccio et al (1) reference a paper by Brandi et al (9). On review of that paper, however, we found no description of the control group, only references to three earlier papers. Marinaccio et al (1) present analyses only with both sets of controls combined; to evaluate potential sources of bias from the use of different sets of controls, they should also report results using each set of controls separately. The authors also did not detail their methods of exposure classification. For example, what does probable or possible exposure mean? The authors should at least present separate analyses of definite occupational exposure. Eighty cases of mTVT were registered, but only 68 were included in the analyses. Information on the 12 omitted cases (eg, age, year of birth, and region) would be helpful. Marinaccio et al (1) did not provide clear information on what occupations and/or industries they considered as exposed to asbestos. In an earlier study, Marinaccio et al (10) remarked on the absence of pericardial mesothelioma and mTVT in industries with the highest exposures to asbestos, saying, &quot;[t]he absence of exposures in the shipbuilding, railway and asbestos-cement industries … for all the 67 pericardial and testicular cases is noteworthy but not easy to interpret.&quot; By contrast, Marinaccio et al (1) stated, &quot;[t]he economic sectors more frequently associated with asbestos exposure were construction, steel mills, metal-working industry, textile industry and agriculture.&quot; The possibility of exposure in the &quot;agriculture economic sector&quot; was not mentioned in Marinaccio et al (10) and appears not to have been considered in previous epidemiologic studies in Italy. In general, epidemiologic studies indicate that farmers and agricultural workers are not at increased risk of developing mesothelioma (eg, 11-17). The fact that few, if any, cases of mTVT and pericardial mesothelioma occurred in industries traditionally associated with high asbestos exposure raises the possibility that the results of Marinaccio et al (1) are attributable to deficiencies in study design, very possibly bias in the selection of controls, and deficiencies in exposure assessment and classification as described above, leading to a spurious association of occupational exposure with mTVT and male pericardial mesothelioma. Conflict of interest This research has received no outside funding. All authors are employees of Exponent, Inc., an international scientific and engineering consulting company. All authors have worked as both consulting and testifying experts in litigation matters related to asbestos exposure and asbestos-related disease. References 1. Marinaccio A, Consonni D, Mensi C, Mirabelli D, Migliore E, Magnani C et al.; ReNaM Working Group. Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks. Scand J Work Environ Health. 2020;46(6):609-617. https://doi.org/10.5271/sjweh.3895. 2. Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 2008; Philadelphia: Wolters Kluwer/Lippincott Williams &amp; Wilkins. 3. Richardson DB. An incidence density sampling program for nested case-control analyses. Occup Environ Med 2004 Dec;61(12):e59. https://doi.org/10.1136/oem.2004.014472. 4. Marinaccio A, Binazzi A, Marzio DD, Scarselli A, Verardo M, Mirabelli D et al.; ReNaM Working Group. Pleural malignant mesothelioma epidemic: incidence, modalities of asbestos exposure and occupations involved from the Italian National Register. Int J Cancer 2012 May;130(9):2146-54. https://doi.org/10.1002/ijc.26229. 5. La Vecchia C, Decarli A, Peto J, Levi F, Tomei F, Negri E. An age, period and cohort analysis of pleural cancer mortality in Europe. Eur J Cancer Prev 2000 Jun;9(3):179-84. https://doi.org/10.1097/00008469-200006000-00005. 6. Price B, Ware A. Mesothelioma trends in the United States: an update based on Surveillance, Epidemiology, and End Results Program data for 1973 through 2003. Am J Epidemiol 2004 Jan;159(2):107-12. https://doi.org/10.1093/aje/kwh025. 7. Moolgavkar SH, Meza R, Turim J. Pleural and peritoneal mesotheliomas in SEER: age effects and temporal trends, 1973-2005. Cancer Causes Control 2009 Aug;20(6):935-44. https://doi.org/10.1007/s10552-009-9328-9. 8. Moolgavkar SH, Chang ET, Mezei G, Mowat FS. Chapter 3. Epidemiology of mesothelioma. In Testa JR. Asbestos and mesothelioma; 2017. pp. 43-72. Cham, Switzerland: Springer International Publishing. 9. Brandi G, Di Girolamo S, Farioli A, de Rosa F, Curti S, Pinna AD et al. Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis. Cancer Causes Control 2013 May;24(5):911-8. https://doi.org/10.1007/s10552-013-0167-3. 10. Marinaccio A, Binazzi A, Di Marzio D, Scarselli A, Verardo M, Mirabelli D et al. Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the Italian national register. Occup Environ Med 2010 Nov;67(11):760-5. https://doi.org/10.1136/oem.2009.051466. 11. Teschke K, Morgan MS, Checkoway H, Franklin G, Spinelli JJ, van Belle G et al. Mesothelioma surveillance to locate sources of exposure to asbestos. Can J Public Health 1997 May-Jun;88(3):163-8. https://doi.org/10.1007/BF03403881. 12. Bouchardy C, Schüler G, Minder C, Hotz P, Bousquet A, Levi F et al. Cancer risk by occupation and socioeconomic group among men--a study by the Association of Swiss Cancer Registries. Scand J Work Environ Health 2002;28(1 Suppl 1):1-88. 13. Hemminki K, Li X. Time trends and occupational risk factors for pleural mesothelioma in Sweden. J Occup Environ Med 2003a Apr;45(4):456-61. https://doi.org/10.1097/01.jom.0000058341.05741.7e. 14. Hemminki K, Li X. Time trends and occupational risk factors for peritoneal mesothelioma in Sweden. J Occup Environ Med 2003b Apr;45(4):451-5. https://doi.org/10.1097/01.jom.0000052960.59271.d4. 15. Pukkala E, Martinsen JI, Lynge E, Gunnarsdottir HK, Sparén P, Tryggvadottir L et al. Occupation and cancer - follow-up of 15 million people in five Nordic countries. Acta Oncol 2009;48(5):646-790. https://doi.org/10.1080/02841860902913546. 16. Rolland P, Gramond C, Berron H, Ducamp S, Imbernon E, Goldberg M et al. Mesotheliome pleural: Professions et secteurs d'activite a risque chez les hommes [Pleural mesothelioma: Professions and occupational areas at risk among humans]. 2005; Institut de Veille Sanitaire, Departement Sante Travai, Saint-Maurice, France. 17. Rolland P, Gramond C, Lacourt A, Astoul P, Chamming's S, Ducamp S et al. PNSM Study Group. Occupations and industries in France at high risk for pleural mesothelioma: A population-based case-control study (1998-2002). Am J Ind Med 2010 Dec;53(12):1207-19. https://doi.org/10.1002/ajim.20895.}, }
@article {pmid32624414, year = {2020}, author = {Paajanen, J and Laaksonen, S and Ilonen, I and Vehmas, T and Mäyränpää, MI and Sutinen, E and Kettunen, E and Salo, JA and Räsänen, J and Wolff, H and Myllärniemi, M}, title = {Clinical Features in Patients With Malignant Pleural Mesothelioma With 5-Year Survival and Evaluation of Original Diagnoses.}, journal = {Clinical lung cancer}, volume = {21}, number = {6}, pages = {e633-e639}, doi = {10.1016/j.cllc.2020.05.020}, pmid = {32624414}, issn = {1938-0690}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a fatal malignancy strongly associated with previous asbestos exposure. Overall survival remains dismal, partly owing to poor response to available treatment. The aims of this study were to evaluate diagnostic accuracy in a group of patients with MPM with an unusually long survival time and to assess the factors related to this prolonged survival.<br><br>MATERIALS AND METHODS: Forty-three patients with overall survival exceeding 5 years were accepted to the long-term survivor (LTS) group, and these patients were compared with 84 patients with epithelial MPM. Data were collected from various national registries and electronic medical records. In addition, all available histopathologic diagnostic samples and computed tomography studies were re-evaluated by experienced specialists.<br><br>RESULTS: Our study showed a good diagnostic accuracy, with only 1 (0.5%) patient having an incorrect MPM diagnosis. Two (0.9%) localized malignant mesotheliomas and 2 (0.9%) well-differentiated papillary mesotheliomas were also found. LTS patients were younger, more frequently female, had a better performance status at time of diagnosis, and had less evidence of prior asbestos exposure. In multivariate analysis, we showed tumor size, Eastern Cooperative Oncology Group performance status, and first-line treatment (both surgery and chemotherapy) to be associated with survival time.<br><br>CONCLUSION: We confirmed the diagnosis of MPM in an overwhelming majority of patients in the LTS group. An epithelial subtype of MPM behaving clinically more indolently seems to exist, but further tumor and genetic characterization is needed. The prolonged survival time is most likely explained by a combination of tumor-, patient-, and treatment-related factors.}, }
@article {pmid32604114, year = {2020}, author = {Xu, T and Hu, J and Zhang, X and Cao, J and Chen, Y}, title = {A Case of Localized Malignant Peritoneal Mesothelioma Evaluated by 18F-FDG PET/CT.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {11}, pages = {890-891}, doi = {10.1097/RLU.0000000000003158}, pmid = {32604114}, issn = {1536-0229}, mesh = {Aged ; Female ; *Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*diagnostic imaging/pathology ; Mesothelioma/*diagnostic imaging/pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnostic imaging/pathology ; *Positron Emission Tomography Computed Tomography ; Prognosis ; }, abstract = {Localized malignant mesothelioma is rare. The prognosis is generally more favorable for this condition than for diffuse malignant mesothelioma. An elderly woman recently complained of abdominal pain, fever, and weight loss. She had no history of asbestos exposure. Her serum CEA level was elevated. Plain CT revealed a mass under the left diaphragm, with liquefaction and necrosis. A contrast-enhanced scan showed circular enhancement of the mass. A subsequent biopsy of the mass revealed a poorly differentiated carcinoma. PET/CT showed a significant FDG-avid subphrenic mass without any indications of metastasis. Postoperative pathological and immunohistochemical examination confirmed a case of malignant mesothelioma.}, }
@article {pmid32602389, year = {2020}, author = {Boice, JD and Cohen, SS and Mumma, MT and Chen, H and Golden, AP and Beck, HL and Till, JE}, title = {Mortality among U.S. military participants at eight aboveground nuclear weapons test series.}, journal = {International journal of radiation biology}, volume = {}, number = {}, pages = {1-22}, doi = {10.1080/09553002.2020.1787543}, pmid = {32602389}, issn = {1362-3095}, abstract = {BACKGROUND: Approximately 235,000 military personnel participated at one of 230 U.S. atmospheric nuclear weapons tests from 1945 through 1962. At the Nevada Test Site (NTS), the atomic veterans participated in military maneuvers, observed nuclear weapons tests, or provided technical support. At the Pacific Proving Ground (PPG), they served aboard ships or were stationed on islands during or after nuclear weapons tests.<br><br>MATERIAL AND METHODS: Participants at seven test series, previously studied with high-quality dosimetry and personnel records, and the first test at TRINITY formed the cohort of 114,270 male military participants traced for vital status from 1945 through 2010. Dose reconstructions were based on Nuclear Test Personnel Review records, Department of Defense. Standardized mortality ratios (SMR) and Cox and Poisson regression models were used in the analysis.<br><br>RESULTS: Most atomic veterans were enlisted men, served in the Navy at the PPG, and were born before 1930. Vital status was determined for 96.8% of the veterans; 60% had died. Enlisted men had significantly high all-causes mortality SMR (1.06); officers had significantly low all-causes mortality SMR (0.71). The pattern of risk over time showed a diminution of the 'healthy soldier effect': the all-causes mortality SMR after 50 years of follow-up was 1.00. The healthy soldier effect for all cancers also diminished over time. The all-cancer SMR was significantly high after 50 years (SMR 1.10) primarily from smoking-related cancers, attributed in part to the availability of cigarettes in military rations. The highest SMR was for mesothelioma (SMR 1.56) which was correlated with asbestos exposure in naval ships. Prostate cancer was significantly high (SMR 1.13). Ischemic heart disease was significantly low (SMR 0.84). Estimated mean doses varied by organ were low; e.g., the mean red bone marrow dose was 6 mGy (maximum 108 mGy). Internal cohort dose-response analyses provided no evidence for increasing trends with radiation dose for leukemia (excluding chronic lymphocytic leukemia (CLL)) [ERR (95% CI) per 100 mGy -0.37 (-1.08, 0.33); n = 710], CLL, myelodysplastic syndrome, multiple myeloma, ischemic heart disease, or cancers of the lung, prostate, breast, and brain.<br><br>CONCLUSION: No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65 years. The 95% confidence limits were narrow and excluded mortality risks per unit dose that are two to four times higher than those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships.}, }
@article {pmid32600665, year = {2020}, author = {Marinaccio, A and Gariazzo, C and Di Marzio, D and Iavicoli, S and , }, title = {Predictors of filing claims and receiving compensation in malignant mesothelioma patients.}, journal = {Health policy (Amsterdam, Netherlands)}, volume = {124}, number = {9}, pages = {1032-1040}, doi = {10.1016/j.healthpol.2020.06.005}, pmid = {32600665}, issn = {1872-6054}, abstract = {Although the predominant occupation origin of mesothelioma is well known, determinant factors involved in filing compensation are scarcely investigated. A linkage between incident mesothelioma cases collected by Italian mesothelioma register (ReNaM) and compensation claims and assignment by Italian national insurance Institute (INAIL) has been conducted for cases diagnosed in the period 2010-2015 and occupational exposure to asbestos. Logistic regression models and decision tree models have been used to identify demographic, diagnostic and anamnestic factors significant for filing and receiving compensation. We have included in the analyses 5019 mesothelioma cases, and among them, 3321 (66.2 %) were found in INAIL archives as mesothelioma cases who fil claims for compensation. The modalities of asbestos exposure, sector of working activities and job type are crucial factors. Furthermore, gender, age at diagnosis, area of residence have been found to be significant predictors of probability to fil claims. Relative risks to fil claims were obtained for the above determinants and conditions to maximize the probability to obtain compensation identified. Our findings demonstrate that there is a need to enforce policies for improving awareness of the occupational origin for mesothelioma cases. Stakeholders, occupational health and safety institutions can play an important role for improving the sensitization regarding the rights of compensation benefits, ensuring the equity and the effectiveness of insurance, welfare and public health systems.}, }
@article {pmid32596966, year = {2020}, author = {Sherborne, V and Seymour, J and Taylor, B and Tod, A}, title = {What are the psychological effects of mesothelioma on patients and their carers? A scoping review.}, journal = {Psycho-oncology}, volume = {29}, number = {10}, pages = {1464-1473}, doi = {10.1002/pon.5454}, pmid = {32596966}, issn = {1099-1611}, mesh = {*Adaptation, Psychological ; Caregivers/*psychology ; Emotions ; Female ; Humans ; Male ; Mental Health ; Mesothelioma, Malignant/*psychology ; Palliative Care ; *Psychological Distress ; Quality of Life/*psychology ; Stress, Psychological ; Uncertainty ; }, abstract = {OBJECTIVE: Despite recent advances in research, malignant mesothelioma remains an incurable and devastating disease, typically bringing shock and emotional distress to patients and carers. Little research has addressed the psychological impact on either group. This scoping review examines the current state of evidence on the psychological effects of mesothelioma on patients and carers, and identifies areas for further research.<br><br>METHODS: We searched PubMed, PsychINFO, CINAHL, the Cochrane Library and Web of Science for English-language peer-reviewed research articles published 1981 to 2019 reporting studies focussing on the psychological effects of mesothelioma on patients and carers. Following data extraction and quality appraisal, reflexive thematic analysis was used to identify themes.<br><br>RESULTS: Seventeen articles met the inclusion criteria. Carers' experiences were generally amalgamated with patients'. Three themes were developed. The Passing of Time included the importance of timing of interventions; delays in the medical journey; awareness of different time-phases in mesothelioma; and uncertainty/certainty. Dealing with Difficult Feelings reflected ubiquitous negative emotions, feelings about identity and states of being and associated coping strategies. Craving Good Communication covered issues related to sharing of information and to positive/negative aspects of communication.<br><br>CONCLUSIONS: Though limited, the evidence indicates that mesothelioma, with its high symptom-burden, incurability, rarity and asbestos-related causation, leads to complex and inter-relating psychological effects on patients and carers. These effects are both negative and positive. The sparse literature gives a partial picture and demonstrates an urgent need for more nuanced research. Studies exploring the experiences of specific groups are recommended, with particular attention required to carers.}, }
@article {pmid32583627, year = {2020}, author = {Shinozaki-Ushiku, A and Kohsaka, S and Kage, H and Oda, K and Miyagawa, K and Nakajima, J and Aburatani, H and Mano, H and Ushiku, T}, title = {Genomic profiling of multiple primary cancers including synchronous lung adenocarcinoma and bilateral malignant mesotheliomas: Identification of a novel BAP1 germline variant.}, journal = {Pathology international}, volume = {70}, number = {10}, pages = {775-780}, doi = {10.1111/pin.12977}, pmid = {32583627}, issn = {1440-1827}, support = {JP19kk0205016//Japan Agency for Medical Research and Development/ ; //Sysmex Corporation/ ; }, abstract = {We report a case with a rare combination of synchronous lung adenocarcinoma and bilateral malignant pleural mesotheliomas in a 70-year-old male without asbestos exposure. He metachronously developed peritoneal malignant mesothelioma, intrahepatic cholangiocarcinoma, urothelial carcinoma of the bladder and prostatic adenocarcinoma. Immunohistochemistry revealed complete loss of BAP1 expression in all seven lesions. Targeted next generation sequencing using Todai OncoPanel identified a novel germline variant (c.1565_1566del, p.P522Rfs*14) of BAP1. Additionally, different nonsynonymous somatic mutations of BAP1 were identified in four lesions including lung adenocarcinoma, malignant pleural and peritoneal mesotheliomas, and bladder cancer. The remaining two lesions had different somatic mutations in genes other than BAP1. Multiple BAP1-deficient cancers that developed in a single patient suggest the newly identified germline variant of BAP1 gene to be pathogenic and this case expands the clinical spectrum of BAP1-tumor predisposition syndrome. Screening for BAP1 status is highly recommended in cases with a similar combination of cancers.}, }
@article {pmid32581164, year = {2020}, author = {Ide, Y and Yuki, T and Taooka, Y and Higashi, Y and Tachiyama, Y}, title = {Malignant Peritoneal Mesothelioma Presenting with Polymyalgia Rheumatica-like Syndrome.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {59}, number = {20}, pages = {2629-2632}, pmid = {32581164}, issn = {1349-7235}, abstract = {A 30-year-old man was admitted to our hospital because of pain in his proximal extremities. The pain mimicked polymyalgia rheumatica (PMR) and it temporarily improved by a low dose of glucocorticoids, but his symptoms relapsed many times. After six years of glucocorticoid treatment, he developed abdominal pain and ascites, for which he was diagnosed with malignant peritoneal mesothelioma (MPM). His PMR-like symptoms improved with cytoreductive surgery and chemotherapy for MPM. Finally, we diagnosed this PMR-like syndrome to be paraneoplastic syndrome with MPM. Although cases of MPM complicated by PMR-like syndrome are rare, MPM should be taken into account in the differential diagnosis.}, }
@article {pmid32581053, year = {2020}, author = {Blondy, T and d'Almeida, SM and Briolay, T and Tabiasco, J and Meiller, C and Chéné, AL and Cellerin, L and Deshayes, S and Delneste, Y and Fonteneau, JF and Boisgerault, N and Bennouna, J and Grégoire, M and Jean, D and Blanquart, C}, title = {Involvement of the M-CSF/IL-34/CSF-1R pathway in malignant pleural mesothelioma.}, journal = {Journal for immunotherapy of cancer}, volume = {8}, number = {1}, pages = {}, pmid = {32581053}, issn = {2051-1426}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The tumor microenvironment content, particularly the presence of macrophages, was described as crucial for the development of the disease. This work aimed at studying the involvement of the M-CSF (CSF-1)/IL-34/CSF-1R pathway in the formation of macrophages in MPM, using samples from patients.<br><br>METHODS: Pleural effusions (PEs), frozen tumors, primary MPM cells and MPM cell lines used in this study belong to biocollections associated with clinical databases. Cytokine expressions were studied using real-time PCR and ELISA. The Cancer Genome Atlas database was used to confirm our results on an independent cohort. An original three-dimensional (3D) coculture model including MPM cells, monocytes from healthy donors and a tumor antigen-specific cytotoxic CD8 T cell clone was used.<br><br>RESULTS: We observed that high interleukin (IL)-34 levels in PE were significantly associated with a shorter survival of patients. In tumors, expression of CSF1 was correlated with 'M2-like macrophages' markers, whereas this was not the case with IL34 expression, suggesting two distinct modes of action of these cytokines. Expression of IL34 was higher in MPM cells compared with primary mesothelial cells. Particularly, high expression of IL34 was observed in MPM cells with an alteration of CDKN2A. Finally, using 3D coculture model, we demonstrated the direct involvement of MPM cells in the formation of immunosuppressive macrophages, through activation of the colony stimulating factor-1 receptor (CSF1-R) pathway, causing the inhibition of cytotoxicity of tumor antigen-specific CD8+ T cells.<br><br>CONCLUSIONS: The M-CSF/IL-34/CSF-1R pathway seems strongly implicated in MPM and could constitute a therapeutic target to act on immunosuppression and to support immunotherapeutic strategies.}, }
@article {pmid32571118, year = {2020}, author = {Ierardi, AM and Marsh, GM}, title = {Absence of mesothelioma risk maintained in an expanded international cohort of cosmetic talc miners and millers.}, journal = {Inhalation toxicology}, volume = {32}, number = {6}, pages = {257-264}, doi = {10.1080/08958378.2020.1781304}, pmid = {32571118}, issn = {1091-7691}, abstract = {Objectives: Based on novel information for the Vermont cosmetic talc miner/miller cohort, including a reported case of mesothelioma, we sought to update our prior pooled statistical power analyses of mesothelioma incidence among European cosmetic talc miners/millers. With the inclusion of the Vermont cohort, we expanded our pooled analysis by 17,170 person-years of observation.Methods: Cosmetic talc miner/miller cohort studies conducted in Italy, Norway, France, Austria, and Vermont were pooled. The expected numbers of mesothelioma cases for each cohort as reported in these studies were used. Our statistical power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities.Results: A total of 130,514 person-years of observation was generated across the five cohorts. One case of mesothelioma was observed (in the Vermont cohort), while approximately 3.34 cases (a mid-value estimate) were expected overall. Thus, we found that the pooled cohorts had 59% and 78% power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. The work history characteristics of the one mesothelioma case, which included mention of prior asbestos exposure on the case's death certificate, do not support a causal link with cosmetic talc exposure.Conclusions: Despite the recent finding of one case of mesothelioma in the Vermont cohort (a case unlikely related to talc exposure), we continue to conclude that the epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that cosmetic talc exposures are associated with an increased risk of pleural mesothelioma.}, }
@article {pmid32560575, year = {2020}, author = {Panou, V and Røe, OD}, title = {Inherited Genetic Mutations and Polymorphisms in Malignant Mesothelioma: A Comprehensive Review.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, pmid = {32560575}, issn = {1422-0067}, abstract = {Malignant mesothelioma (MM) is mainly caused by air-born asbestos but genetic susceptibility is also suspected to be a risk factor. Recent studies suggest an increasing number of candidate genes that may predispose to MM besides the well-characterized BRCA1-associated protein-1 gene. The aim of this review is to summarize the most important studies on germline mutations for MM. A total of 860 publications were retrieved from Scopus, PubMed and Web of Science, of which 81 met the inclusion criteria and were consider for this review. More than 50% of the genes that are reported to predispose to MM are involved in DNA repair mechanisms, and the majority of them have a role in the homologous recombination pathway. Genetic alterations in tumor suppressor genes involved in chromatin, transcription and hypoxia regulation have also been described. Furthermore, we identified several single nucleotide polymorphisms (SNPs) that may promote MM tumorigenesis as a result of an asbestos-gene interaction, including SNPs in DNA repair, carcinogen detoxification and other genes previously associated with other malignancies. The identification of inherited mutations for MM and an understanding of the underlying pathways may allow early detection and prevention of malignancies in high-risk individuals and pave the way for targeted therapies.}, }
@article {pmid32560553, year = {2020}, author = {Bonafede, M and Granieri, A and Binazzi, A and Mensi, C and Grosso, F and Santoro, G and Franzoi, IG and Marinaccio, A and Guglielmucci, F}, title = {Psychological Distress after a Diagnosis of Malignant Mesothelioma in a Group of Patients and Caregivers at the National Priority Contaminated Site of Casale Monferrato.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {12}, pages = {}, pmid = {32560553}, issn = {1660-4601}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Asbestos/adverse effects ; Asbestosis/diagnosis/epidemiology/etiology/psychology ; Carcinogens ; Caregivers/*psychology/statistics &amp; numerical data ; Cross-Sectional Studies ; Depression/epidemiology/etiology/psychology ; Environmental Exposure/statistics &amp; numerical data ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology/*psychology ; Middle Aged ; Occupational Diseases/diagnosis/*epidemiology/etiology/*psychology ; *Psychological Distress ; Registries/statistics &amp; numerical data ; Risk Factors ; Stress Disorders, Post-Traumatic/epidemiology/etiology/psychology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Patients of malignant mesothelioma (MM) and their caregivers face significant physical and psychological challenges. The purpose of the present study is to examine the emotional impact after the diagnosis of MM in a group of patients and familial caregivers in a National Priority Contaminated Site (NPCS).<br><br>METHODS: A sample of 108 patients and 94 caregivers received a sociodemographic/clinical questionnaire, the Beck Depression Inventory II, the Davidson Trauma Scale, the Coping Orientation to the Problems Experienced-New Italian Version, and the Defense style questionnaire. The risk of depressive and post-traumatic stress disorder (PTSD) symptoms in relation to the strategies of coping and defense mechanisms was estimated in patients and caregivers separately by logistic regression models.<br><br>RESULTS: For patients, a high risk of depression was associated with high usage of Defense Style Questionnaire (DSQ) Isolation (OR: 53.33; 95% CI: 3.22-882.30; p = 0.01) and DSQ Somatization (OR: 16.97; 95% CI: 1.04-275.90; p = 0.05). Other significant risks emerged for some coping strategies and some defenses regarding both depression and trauma in patients and caregivers.<br><br>CONCLUSIONS: This research suggests that for both patients and caregivers unconscious adaptive processes have a central role in dealing with overwhelming feelings related to the disease.}, }
@article {pmid32553000, year = {2020}, author = {Musk, AW and de Klerk, N and Reid, A and Hui, J and Franklin, P and Brims, F}, title = {Asbestos-related diseases.}, journal = {The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease}, volume = {24}, number = {6}, pages = {562-567}, doi = {10.5588/ijtld.19.0645}, pmid = {32553000}, issn = {1815-7920}, abstract = {Knowledge of asbestos-related diseases has been accumulating for over one hundred years as the industrial value of asbestos was recognised for the strength of its fibres and their resistance to destruction, resulting in increasing production and use until the multiple health effects have become apparent. Deposition in the lung parenchyma results in an inflammatory/progressively fibrotic response, with impaired gas exchange and reduced lung compliance ('asbestosis'), causing progressive dyspnoea and respiratory failure for which only palliation is indicated, although anti-fibrotic agents used for idiopathic usual interstitial pneumonitis remain to be evaluated. Benign pleural effusion, diffuse pleural fibrosis (occasionally with associated rolled atelectasis) and pleural plaques are the non-malignant pleural diseases that result from fibres reaching the pleura. But the main issues that led to the ban on asbestos in industry are those of malignancy: lung cancer, malignant mesothelioma (MM) of the pleura and MM of the peritoneum. Bronchogenic carcinoma risk from asbestos exposure is dose-dependent and multiplies the risk attributable to tobacco smoking. The principles of treatment are as for all cases of lung cancer. Low-dose computed tomography screening of exposed people can detect early-stage, non-small cell cancers, with improved survival. The amphibole varieties of asbestos are much more potent causes of MM than chrysotile, and the risk increases exponentially for 40-50 years following first exposure. As MM is non-resectable and poorly responsive to chemotherapy and radiotherapy, curative treatment is not possible and screening not justified.}, }
@article {pmid32549902, year = {2020}, author = {Frank, AL}, title = {Global use of asbestos - legitimate and illegitimate issues.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {15}, number = {}, pages = {16}, pmid = {32549902}, issn = {1745-6673}, abstract = {Background: Exposure to asbestos causes non-malignant and malignant diseases including asbestosis, lung cancer, and mesothelioma. The modern history of such diseases goes back more than a century.<br><br>Main text: While much is known about the ability of asbestos to cause disease, the carcinogenic mechanism is not yet understood. Continuing legitimate scientific questions include such issues as potential differential toxicity and carcinogenicity of different fiber types. Illegitimate issues include the supposed &quot;safe&quot; use of asbestos, and the chrysotile hypothesis.<br><br>Conclusion: Asbestos disease issues are highly politicized and vested economic interests perpetuate false issues regarding the hazards of asbestos.}, }
@article {pmid32549782, year = {2020}, author = {Franko, A and Goricar, K and Kovac, V and Dodic-Fikfak, M and Dolzan, V}, title = {NLRP3 and CARD8 polymorphisms influence risk for asbestos-related diseases.}, journal = {Journal of medical biochemistry}, volume = {39}, number = {1}, pages = {91-99}, pmid = {32549782}, issn = {1452-8258}, abstract = {Background: This study aimed to investigate the association between NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms and the risk of developing pleural plaques, asbestosis, and malignant mesothelioma (MM), and to study the influence of the interactions between polymorphisms and asbestos exposure on the risk of developing these diseases.<br><br>Methods: The case-control study included 416 subjects with pleural plaques, 160 patients with asbestosis, 154 subjects with MM and 149 subjects with no asbestos disease. The NLRP3 rs35829419 and CARD8 rs2043211 polymorphisms were determined using real-time PCR-based methods. In the statistical analysis, standard descriptive statistics was followed by univariate and multivariate logistic regression modelling.<br><br>Results: Asbestos exposure (medium and high vs low) was associated with the risk for each studied asbestos-related disease. An increased risk of pleural plaques was found for CARD8 rs2043211 at + TT genotypes (OR = 1.48, 95% CI 1.01-2.16, p = 0.042). When the analysis was performed for MM patients as cases, and pleural plaques patients as controls, a decreased MM risk was observed for carriers of CARD8 rs2043211 TT genotype (OR = 0.52, 95% CI 0.27-1.00, p = 0.049). The interactions between NLRP3 rs35829419 and CARD8 rs2043211 genotypes did not influence the risk of any asbestos-related disease. However, when testing interactions with asbestos exposure, a decreased risk of asbestosis was found for NLRP3 CA+AA genotypes (OR = 0.09, 95% CI 0.01-0.60, p = 0.014).<br><br>Conclusions: The results of our study suggest that NLRP3 and CARD8 polymorphisms could affect the risk of asbestos-related diseases.}, }
@article {pmid32535843, year = {2020}, author = {Shibata, R and Ozaki, T and Tada, K and Aoyama, T and Watanabe, M and Himuro, N and Takahashi, K and Ito, K and Yasuno, T and Miyake, K and Masutani, K and Uesugi, N and Nabeshima, K and Nakashima, H}, title = {Secondary renal amyloidosis associated with asbestos-related pleuropulmonary diseases.}, journal = {CEN case reports}, volume = {9}, number = {4}, pages = {385-391}, pmid = {32535843}, issn = {2192-4449}, abstract = {Here, we present a 67-year-old Japanese man who developed insidious-onset nephrotic syndrome. He had a history of occupational asbestos exposure for about 8 years during his 30s, and was found to have pleural effusion 3 years before his present illness. At that time, repeated cytology testing of his pleural effusion found no malignant cells, and pleural biopsy found fibrous pleuritis without evidence of malignant mesothelioma. Percutaneous kidney biopsy found massive deposits of AA-type amyloid in the glomeruli, small arteries, and medulla. Computed tomography showed a calcified mass in the right lower lung that was positive for 67Ga uptake, but transbronchial lung biopsy and bronchoalveolar lavage found no evidence of malignancy. He was diagnosed with rounded atelectasis and diffuse pleural thickening. As these benign asbestos-related diseases have no standard treatment, we administered low-dose angiotensin II receptor blocker to preserve kidney function. Unfortunately, his nephrotic syndrome persists, with progressive chronic kidney failure. Kidney involvement in patients with asbestos-related disease is rare. To our knowledge, this is the first case to present with secondary amyloidosis. Kidney biopsy should be considered for patients with existing asbestos-related pleuropulmonary diseases who have urinary abnormalities or renal dysfunction, to clarify the incidence and pathophysiology of renal manifestations.}, }
@article {pmid32530527, year = {2020}, author = {Horio, D and Minami, T and Kitai, H and Ishigaki, H and Higashiguchi, Y and Kondo, N and Hirota, S and Kitajima, K and Nakajima, Y and Koda, Y and Fujimoto, E and Negi, Y and Niki, M and Kanemura, S and Shibata, E and Mikami, K and Takahashi, R and Yokoi, T and Kuribayashi, K and Kijima, T}, title = {Tumor-associated macrophage-derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma.}, journal = {Cancer science}, volume = {111}, number = {8}, pages = {2895-2906}, doi = {10.1111/cas.14523}, pmid = {32530527}, issn = {1349-7006}, support = {18K08161//Japan Society for the Promotion of Science/ ; 18K15962//Japan Society for the Promotion of Science/ ; 18K15963//Japan Society for the Promotion of Science/ ; 20K08555//Japan Society for the Promotion of Science/ ; }, mesh = {Aged ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Asbestos/toxicity ; Biopsy ; Cell Line, Tumor ; Cisplatin/pharmacology/therapeutic use ; Female ; Humans ; Inflammasomes/metabolism ; Interleukin-1beta/*metabolism ; Macrophages/drug effects/*metabolism ; Male ; Mesothelioma, Malignant/chemically induced/drug therapy/mortality/*pathology ; Middle Aged ; Pemetrexed/pharmacology/therapeutic use ; Pleura/*pathology ; Receptors, Interleukin-1 Type I/*metabolism ; Spheroids, Cellular ; Tumor Microenvironment/drug effects ; Up-Regulation ; }, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive malignant neoplasm. Due to the difficulty of achieving curative surgical resection in most patients with MPM, a combination chemotherapy of cisplatin and pemetrexed has been the only approved regimen proven to improve the prognosis of MPM. However, the median overall survival time is at most 12 mo even with this regimen. There has been therefore a pressing need to develop a novel chemotherapeutic strategy to bring about a better outcome for MPM. We found that expression of interleukin-1 receptor (IL-1R) was upregulated in MPM cells compared with normal mesothelial cells. We also investigated the biological significance of the interaction between pro-inflammatory cytokine IL-1β and the IL-1R in MPM cells. Stimulation by IL-1β promoted MPM cells to form spheroids along with upregulating a cancer stem cell marker CD26. We also identified tumor-associated macrophages (TAMs) as the major source of IL-1β in the MPM microenvironment. Both high mobility group box 1 derived from MPM cells and the asbestos-activated inflammasome in TAMs induced the production of IL-1β, which resulted in enhancement of the malignant potential of MPM. We further performed immunohistochemical analysis using clinical MPM samples obtained from patients who were treated with the combination of platinum plus pemetrexed, and found that the overexpression of IL-1R tended to correlate with poor overall survival. In conclusion, the interaction between MPM cells and TAMs through a IL-1β/IL-1R signal could be a promising candidate as the target for novel treatment of MPM (Hyogo College of Medicine clinical trial registration number: 2973).}, }
@article {pmid32528683, year = {2020}, author = {Amore, D and Massa, S and Caterino, U and Casazza, D and Palma, A and Curcio, C}, title = {Mediastinal malignant mesothelioma discovered in a patient with dysphagia.}, journal = {Respirology case reports}, volume = {8}, number = {6}, pages = {e00592}, doi = {10.1002/rcr2.592}, pmid = {32528683}, issn = {2051-3380}, abstract = {A mediastinal mass in patients with a history of asbestos exposure should raise the suspicion of malignant mesothelioma.}, }
@article {pmid32526494, year = {2020}, author = {Catelan, D and Consonni, D and Biggeri, A and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Estimate of environmental and occupational components in the spatial distribution of malignant mesothelioma incidence in Lombardy (Italy).}, journal = {Environmental research}, volume = {188}, number = {}, pages = {109691}, doi = {10.1016/j.envres.2020.109691}, pmid = {32526494}, issn = {1096-0953}, mesh = {*Asbestos/toxicity ; Bayes Theorem ; Environmental Exposure ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Exposure ; Registries ; }, abstract = {INTRODUCTION: Measuring and mapping the occurrence of malignant mesothelioma (MM) is a useful means to monitor the impact of past asbestos exposure and possibly identify previously unknown sources of asbestos exposure.<br><br>OBJECTIVE: Our goal is to decompose the observed spatial pattern of incidence of MM in the Lombardy region (Italy) in gender-specific components linked to occupational exposure and a shared component linked to environmental exposure.<br><br>MATERIALS AND METHODS: We selected from the Lombardy Region Mesothelioma Registry (RML) all incident cases of MM (pleura, peritoneum, pericardium, and tunica vaginalis testis) with first diagnosis in the period 2000-2016. We mapped at municipality level crude incidence rates and smoothed rates using the Besag York and Mollié model separately for men and women. We then decomposed the spatial pattern of MM in gender-specific occupational components and a shared environmental component using a multivariate hierarchical Bayesian model.<br><br>RESULTS: We globally analyzed 6226 MM cases, 4048 (2897 classified as occupational asbestos exposure at interview) in men and 2178 (780 classified as occupational asbestos exposure at interview) in women. The geographical analysis showed a strong spatial pattern in the distribution of incidence rates in both genders. The multivariate hierarchical Bayesian model decomposed the spatial pattern in occupational and environmental components and consistently identified some known occupational and environmental hot spots. Other areas at high risk for MM occurrence were highlighted, contributing to better characterize environmental exposures from industrial sources and suggesting a role of natural sources in the Alpine region.<br><br>CONCLUSION: The spatial pattern highlights areas at higher risk which are characterized by the presence of industrial sources - asbestos-cement, metallurgic, engineering, textile industries - and of natural sources in the Alpine region. The multivariate hierarchical Bayesian model was able to disentangle the geographical distribution of MM cases in two components interpreted as occupational and environmental.}, }
@article {pmid32517259, year = {2020}, author = {Staumont, B and Jamakhani, M and Costa, C and Vandermeers, F and Sriramareddy, SN and Redouté, G and Mascaux, C and Delvenne, P and Hubert, P and Safari, R and Willems, L}, title = {TGFα Promotes Chemoresistance of Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {12}, number = {6}, pages = {}, pmid = {32517259}, issn = {2072-6694}, support = {CDR//Fonds De La Recherche Scientifique - FNRS/ ; Télévie//Fonds De La Recherche Scientifique - FNRS/ ; Asbestos grants//Belgian Foundation against Cancer/ ; }, abstract = {Background: There is no standard chemotherapy for refractory or relapsing malignant pleural mesothelioma (MPM). Our previous reports nevertheless indicated that a combination of an anthracycline (doxorubicin) and a lysine deacetylase inhibitor (valproic acid, VPA) synergize to induce the apoptosis of MPM cells and reduce tumor growth in mouse models. A Phase I/II clinical trial indicated that this regimen is a promising therapeutic option for a proportion of MPM patients. Methods: The transcriptomes of mesothelioma cells were compared after Illumina HiSeq 4000 sequencing. The expression of differentially expressed genes was inhibited by RNA interference. Apoptosis was determined by cell cycle analysis and Annexin V/7-AAD labeling. Protein expression was assessed by immunoblotting. Preclinical efficacy was evaluated in BALB/c and NOD-SCID mice. Results: To understand the mechanisms involved in chemoresistance, the transcriptomes of two MPM cell lines displaying different responses to VPA-doxorubicin were compared. Among the differentially expressed genes, transforming growth factor alpha (TGFα) was associated with resistance to this regimen. The silencing of TGFα by RNA interference correlated with a significant increase in apoptosis, whereas the overexpression of TGFα desensitized MPM cells to the apoptosis induced by VPA and doxorubicin. The multi-targeted inhibition of histone deacetylase (HDAC), HER2 and TGFα receptor (epidermal growth factor receptor/EGFR) improved treatment efficacy in vitro and reduced tumor growth in two MPM mouse models. Finally, TGFα expression but not EGFR correlated with patient survival. Conclusions: Our data show that TGFα but not its receptor EGFR is a key factor in resistance to MPM chemotherapy. This observation may contribute to casting light on the promising but still controversial role of EGFR signaling in MPM therapy.}, }
@article {pmid32515059, year = {2020}, author = {Orriols, R and Tarrés, J and Albertí-Casas, C and Rosell-Murphy, M and Abós-Herràndiz, R and Canela-Soler, J}, title = {Malignant asbestos-related disease in a population exposed to asbestos.}, journal = {American journal of industrial medicine}, volume = {63}, number = {9}, pages = {796-802}, doi = {10.1002/ajim.23141}, pmid = {32515059}, issn = {1097-0274}, abstract = {OBJECTIVES: The first asbestos fiber cement plant in Spain operated in Cerdanyola, in the Barcelona metropolitan area, between 1907 and 1997. We describe clinical and epidemiological characteristics of patients diagnosed with the malignant asbestos-related disease (ARD) in the area of the plant between 2007 and 2016.<br><br>METHODS: A prospective, descriptive study was undertaken in the 12 municipalities of the county of Barcelona most proximate to the plant. We describe malignant ARD cases by time of diagnosis, source of exposure, periods of exposure and latency, and distribution by sex. Cumulative incidence and age-standardized incidence rates (ASIR) are calculated.<br><br>RESULTS: Of 477 patients diagnosed with ARD between 2007 and 2016, 128 (26%) presented with asbestos-associated malignancy. Pleural mesothelioma was noted in 105 patients (82.0%) with a linear trend Z-score of -0.2 (NS) in men and 2.7 (P < .01) in women. The highest ASIRs for malignant ARD (6.1/100 000 residents/year; 95% confidence interval [CI], 2.2-13.3) and pleural mesothelioma (4.8/100 000 residents/year; 95% CI, 1.5-11.6) occurred in municipalities closest to the focal point of contamination. The origin of malignant ARD was nonoccupational in 32.2% of men and 81.6% of women (P < .001).<br><br>CONCLUSIONS: More than 20 years after the closure of the fiber cement plant, the grave consequences of exposure to asbestos remain. The detection of cases of pleural mesothelioma in men seems to have plateaued whereas in women an ascending trend continues, which principally has its origin in nonoccupational exposures.}, }
@article {pmid32509926, year = {2020}, author = {Marques de Sousa, S and Pereira, F and Duarte, M and Marques, M and Vázquez, D and Marques, C}, title = {Malignant Peritoneal Mesothelioma as a Rare Cause of Dyspeptic Complaints and Ascites: A Diagnostic Challenge.}, journal = {GE Portuguese journal of gastroenterology}, volume = {27}, number = {3}, pages = {197-202}, pmid = {32509926}, issn = {2341-4545}, abstract = {Introduction: Malignant peritoneal mesothelioma (MPM) is a rare malignancy of the mesothelial cells in the peritoneum. The best-defined risk factor is asbestos exposure, but germline mutations in BAP1 also increase susceptibility to this tumor. The diagnosis of MPM is challenging since clinical manifestations are often nonspecific.<br><br>Case Presentation: We describe a case of MPM in a 53-year-old former construction worker with prior asbestos exposure. The clinical presentation was a 3-month history of dyspeptic complaints. As initial workup, abdominal ultrasound and upper gastrointestinal endoscopy were performed. Chronic gastritis due to Helicobacter pylori was detected, which was promptly treated but without symptom relief. Abdominal ultrasound showed small volume ascites with hyperechogenic foci, which was later confirmed on computed tomography scan showing the presence of peritoneal nodules in the greater omentum and mesentery. A thorough investigation was conducted based on the suspicion of peritoneal carcinomatosis. A non-peritoneal primary tumor was not found. Ascitic cytology and immunocytochemical studies were suggestive of mesothelioma. He underwent exploratory laparotomy and inoperable peritoneal disease was observed. Peritoneal biopsy confirmed epithelioid-type MPM. Systemic therapy was initiated with platinum plus pemetrexed with good response. The last follow-up was 38 months after the diagnosis.<br><br>Discussion/Conclusion: The diagnosis of MPM is challenging since it requires a high degree of suspicion. MPM has a poor prognosis. The standard of treatment recommended is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. For those who are inoperable, systemic therapy with pemetrexed-cisplatin combination is the alternative. Given the infrequency of disease, it is imperative to ensure patient participation in clinical trials with the purpose of treatment standardization.}, }
@article {pmid32492522, year = {2020}, author = {Marsh, GM and Ierardi, AM}, title = {Confidence interval function analysis to evaluate the risk of mesothelioma among an expanded international cohort of cosmetic talc miners and millers.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {115}, number = {}, pages = {104696}, doi = {10.1016/j.yrtph.2020.104696}, pmid = {32492522}, issn = {1096-0295}, abstract = {We used pooled data from international cosmetic talc miner/miller cohorts to determine whether hypothesized increased mesothelioma risks are consistent with the observed data. We evaluated the confidence interval function for the observed pooled mesothelioma SMRs (observed = 1; expected = 3.17, 3.34, or 3.60), and calculated the value of α for the upper 100(1 - 2α)% confidence limit that equals various SMRs of interest (1.5, 2.0, 2.5, 3.0). Using the mid-value estimate of expected number of cases (3.34), the probability (α) that the true mesothelioma SMR is at or above 2.0, or at or above 3.0 is 0.0096 and 0.0005, respectively. Thus, a mesothelioma SMR ≥2.0 is not compatible with the observed pooled data, providing further support for our conclusion that cosmetic talc exposure is not associated with an elevated risk of mesothelioma.}, }
@article {pmid32489446, year = {2020}, author = {Alghamdi, ZM and Othman, SA and Al-Yousef, MJ and AlFadel, BZ}, title = {Intrapulmonary location of benign solitary fibrous tumor.}, journal = {Annals of thoracic medicine}, volume = {15}, number = {2}, pages = {98-101}, pmid = {32489446}, issn = {1817-1737}, abstract = {Intrapulmonary solitary fibrous tumors (SFTs) are sporadic mesenchymal neoplasms that typically arise from visceral or parietal pleura. While accounting for <5% of all pleural tumors, SFTs are known to occur in nearly all bodily organs, including nasopharynx, bladder, prostate, soft tissue of neck, buttocks, extremities, and abdominal wall. Such tumors have been previously designated localized fibrous mesothelioma or pleural fibroma. SFTs have no genetic basis and are unrelated to environmental factors such as tobacco smoking or asbestos exposure. Herein, we describe a 24-year-old woman whose clinical presentation mimicked atypical carcinoid tumor. A diagnosis of intrapulmonary SFT was achieved by surgical resection.}, }
@article {pmid32475021, year = {2020}, author = {Korša, L and Lukač, A and Kovačević, L and Bilić, I and Prutki, M and Marušić, Z}, title = {Breast metastasis as the initial presentation of malignant pleural mesothelioma.}, journal = {The breast journal}, volume = {26}, number = {10}, pages = {2063-2064}, doi = {10.1111/tbj.13898}, pmid = {32475021}, issn = {1524-4741}, abstract = {Metastatic involvement of the breast is far less common than primary breast carcinoma, comprising 0.5%-6.6% of all breast malignancies. Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with higher incidence among men, particularly smokers, strongly associated with asbestos exposure. The epithelioid type of MPM can represent a diagnostic pitfall in this setting, as it shows similar histologic features to primary breast carcinoma as well as other metastatic epithelioid malignancies. We report a rare case of breast metastasis of malignant pleural mesothelioma in a 61-year-old female.}, }
@article {pmid32472158, year = {2020}, author = {Greimelmaier, K and Wohlschläger, J and Probst, A and Hager, T and Wardelmann, E and Werlein, C and Jonigk, D and Müller, KM}, title = {[Mesothelial proliferation of the tunica vaginalis testis].}, journal = {Der Pathologe}, volume = {41}, number = {4}, pages = {406-410}, doi = {10.1007/s00292-020-00797-6}, pmid = {32472158}, issn = {1432-1963}, mesh = {Cell Proliferation ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; *Lung Neoplasms/diagnosis ; Male ; *Mesothelioma/diagnosis ; *Testicular Neoplasms/pathology ; Testis ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {Proliferative changes seen in reactive mesothelial hyperplasia of a hydrocele sac may mimic malignant mesothelioma. There is no immunohistochemical staining that reliably separates benign from malignant mesothelial proliferations. However, the combined analysis of BAP1 by immunohistochemistry and CDKN2A by FISH has been reported to yield both a high specificity and sensitivity in this differential diagnosis. In addition, the evaluation of risk factors such as asbestos exposure or prior traumata may be helpful for the correct diagnosis. Exclusion of stromal invasion, which is diagnostic for malign mesothelioma, is of utmost importance. Therefore, extended histological workup is essential.}, }
@article {pmid32435497, year = {2020}, author = {Weber, DG and Casjens, S and Brik, A and Raiko, I and Lehnert, M and Taeger, D and Gleichenhagen, J and Kollmeier, J and Bauer, TT and Brüning, T and Johnen, G and , }, title = {Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies.}, journal = {Biomarker research}, volume = {8}, number = {}, pages = {15}, pmid = {32435497}, issn = {2050-7771}, abstract = {Background: For the detection of malignant mesothelioma additional markers are needed besides the established panel consisting of calretinin and mesothelin. The aim of this study was the identification and verification of long non-coding RNAs (lncRNAs) as complementing circulating markers.<br><br>Methods: Candidate lncRNAs were identified in silico using previously published RNA expression profiles and verified using quantitative PCR (qPCR) in mesothelioma cell lines as well as human plasma samples from mesothelioma patients and asbestos-exposed controls.<br><br>Results: GAS5 (growth arrest-specific transcript 5) as a single marker is marked by a low sensitivity of 14%, but the combination of GAS5 with calretinin and mesothelin increased the panel's sensitivity from 64 to 73% at a predefined specificity of 97%. Circulating GAS5 is not affected by pleurectomy before blood collection, age, or smoking status.<br><br>Conclusions: GAS5 is verified as an appropriate circulating marker for the supplement of calretinin and mesothelin to detect malignant mesothelioma. Although the sensitivity of GAS5 is too low for the use as a single marker, the addition of GAS5 as a third marker improves the performance of the established marker panel. The benefit of GAS5 for the detection of malignant mesothelioma at early stages needs to be validated in a prospective study.}, }
@article {pmid32429446, year = {2020}, author = {Di Gilio, A and Catino, A and Lombardi, A and Palmisani, J and Facchini, L and Mongelli, T and Varesano, N and Bellotti, R and Galetta, D and de Gennaro, G and Tangaro, S}, title = {Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways.}, journal = {Cancers}, volume = {12}, number = {5}, pages = {}, pmid = {32429446}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm, mainly caused by asbestos exposure, with a high mortality rate. The management of patients with MPM is controversial due to a long latency period between exposure and diagnosis and because of non-specific symptoms generally appearing at advanced stage of the disease. Breath analysis, aimed at the identification of diagnostic Volatile Organic Compounds (VOCs) pattern in exhaled breath, is believed to improve early detection of MPM. Therefore, in this study, breath samples from 14 MPM patients and 20 healthy controls (HC) were collected and analyzed by Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC/MS). Nonparametric test allowed to identify the most weighting variables to discriminate between MPM and HC breath samples and multivariate statistics were applied. Considering that MPM is an aggressive neoplasm leading to a late diagnosis and thus the recruitment of patients is very difficult, a promising data mining approach was developed and validated in order to discriminate between MPM patients and healthy controls, even if no large population data are available. Three different machine learning algorithms were applied to perform the classification task with a leave-one-out cross-validation approach, leading to remarkable results (Area Under Curve AUC = 93%). Ten VOCs, such as ketones, alkanes and methylate derivates, as well as hydrocarbons, were able to discriminate between MPM patients and healthy controls and for each compound which resulted diagnostic for MPM, the metabolic pathway was studied in order to identify the link between VOC and the neoplasm. Moreover, five breath samples from asymptomatic asbestos-exposed persons (AEx) were exploratively analyzed, processed and tested by the validated statistical method as blinded samples in order to evaluate the performance for the early recognition of patients affected by MPM among asbestos-exposed persons. Good agreement was found between the information obtained by gold-standard diagnostic methods such as computed tomography CT and model output.}, }
@article {pmid32392897, year = {2020}, author = {Abbott, DM and Bortolotto, C and Benvenuti, S and Lancia, A and Filippi, AR and Stella, GM}, title = {Malignant Pleural Mesothelioma: Genetic and Microenviromental Heterogeneity as an Unexpected Reading Frame and Therapeutic Challenge.}, journal = {Cancers}, volume = {12}, number = {5}, pages = {}, pmid = {32392897}, issn = {2072-6694}, abstract = {Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a rare disease with a global incidence in countries like Italy of about 1.15 per 100,000 inhabitants. Malignant Pleural Mesothelioma (MPM) is the most common form of mesothelioma, accounting for approximately 80% of disease. Although rare in the global population, mesothelioma is linked to industrial pollutants and mineral fiber exposure, with approximately 80% of cases linked to asbestos. Due to the persistent asbestos exposure in many countries, a worldwide progressive increase in MPM incidence is expected for the current and coming years. The tumor grows in a loco-regional pattern, spreading from the parietal to the visceral pleura and invading the surrounding structures that induce the clinical picture of pleural effusion, pain and dyspnea. Distant spreading and metastasis are rarely observed, and most patients die from the burden of the primary tumor. Currently, there are no effective treatments for MPM, and the prognosis is invariably poor. Some studies average the prognosis to be roughly one-year after diagnosis. The uniquely poor mutational landscape which characterizes MPM appears to derive from a selective pressure operated by the environment; thus, inflammation and immune response emerge as key players in driving MPM progression and represent promising therapeutic targets. Here we recapitulate current knowledge on MPM with focus on the emerging network between genetic asset and inflammatory microenvironment which characterize the disease as amenable target for novel therapeutic approaches.}, }
@article {pmid32383566, year = {2020}, author = {Kilitci, A and Uygun, N and Emir, ML}, title = {Sarcomatoid Type of Paratesticular Malignant Mesothelioma in a Dry-Cleaning Worker Exposed to Asbestos and Diagnostic Value of WT-1.}, journal = {Puerto Rico health sciences journal}, volume = {39}, number = {1}, pages = {39-44}, pmid = {32383566}, issn = {2373-6011}, abstract = {Of the 3 major histologic types of malignant paratesticular mesothelioma (MPM) (epithelial, sarcomatoid, and biphasic), many cases of epithelial and biphasic mesothelioma have been reported in the literature. Pure sarcomatoid MPM is the least common but the most aggressive of the 3 major histologic types of mesothelioma cells. It is limited to only 2 cases in the literature The sarcomatoid type of MPM can be confused clinically and histologically with true sarcomas because it is rarely seen. We present a case who had been exposed to asbestos for years due to his involvement in the dry-cleaning industry and who was diagnosed with the sarcomatoid type of MPM but had a relatively prolonged survival not usually seen with this tumor. This report also emphasizes the significance of an immunohistochemical examination, focusing especially on the diagnostic role of WT-1.}, }
@article {pmid32382335, year = {2020}, author = {Zhang, G and Yang, DL and Zheng, G and Liang, Y}, title = {Survivin expression as an independent predictor of overall survival in malignant peritoneal mesothelioma.}, journal = {Oncology letters}, volume = {19}, number = {6}, pages = {3871-3880}, pmid = {32382335}, issn = {1792-1074}, abstract = {Malignant peritoneal mesothelioma (MPeM) is an incurable cancer strongly associated with asbestos exposure and characterised by poor prognosis. The aim of the present study was to elucidate the prognostic and predictive value of CD146 and survivin expression in MPeM. Diagnostic biopsies from 60 patients with MPeM were collected and analysed for CD146, survivin and Ki-67 expression using immunohistochemistry. Complete clinical and follow-up information was obtained from patients' records. CD146 was expressed in 31/60 MPeM specimens and survivin in 34/60 specimens, with both expression levels being significantly associated with the Ki-67 labelling index (Ki-67LI). Kaplan-Meier and univariate Cox regression analyses revealed that a lower peritoneal cancer index (PCI), tumour-directed treatment, stage I, lower Ki-67LI and lower CD146 and survivin expression had a statistically positive effect on overall survival (OS). Cox regression analysis revealed that PCI [hazard ratio (HR)=1.99; 95% CI, 1.04-3.83; P=0.038], survivin (HR=1.47; 95% CI, 1.03-2.10; P=0.034) and treatment protocol including intraperitoneal chemotherapy (HR=0.28; 95% CI, 0.14-0.57; P=0.013) and systemic chemotherapy (HR=0.13; 95% CI, 0.04-0.42; P=0.013) retained independent prognostic significance for OS. All of these were included in the nomogram. Calibration curves showed good agreement between nomogram-predicted and observed survival. The C-index of the nomogram for predicting OS was 0.77. A lower PCI, intraperitoneal chemotherapy, systemic chemotherapy and a lower level of survivin were powerful prognostic markers in patients with MPeM. The proposed nomogram provides individual survival prediction for patients with MPeM.}, }
@article {pmid32374117, year = {2020}, author = {Barbieri, PG and Calisti, R and Silvestri, S and Calabresi, C and Consonni, D and Angelini, A and Carnevale, F and Cavariani, F and Sala, O}, title = {[About the asbestos and the Position Paper on asbestos of the Italian Society of Occupational Medicine].}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {1}, pages = {73-83}, doi = {10.19191/EP20.1.P073.019}, pmid = {32374117}, issn = {1120-9763}, mesh = {*Asbestos ; Asbestosis/epidemiology ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology ; Occupational Diseases/*epidemiology ; Occupational Exposure ; }, abstract = {The SIML Position Paper dedicated to asbestos (PPA) is addressed (mainly) to competent practitioners (CP) for the purposes to provide a guidance about a set of items classified as markedly interesting: the actuality of asbestos exposure and the evaluation of the related risk; the diagnosis of the asbestos related diseases; the shape of the risk functions (namely about mesotheliomas); the causal relationship between exposure and disease; the medical surveillance of the workers currently and previously exposed. The scientific literature doesn't acknowledge the idea that nowadays in Italy the frequency of pleural mesotheliomas deriving from environmental asbestos from outdoor sources exposures is really a relevant item. Inside the SIML PPA the chapter concerning industrial hygiene and environmental monitoring themes shows inaccuracies and deficiencies, so resulting of scarce utility for the CPs that should be called for a more cooperative role in front of the employers. The arguments of the diagnosis of the asbestos related diseases is developed with an undue emphasis upon the differential histological diagnosis of asbestosis and, especially, of pleural mesothelioma: nosographic aspects that hardly are posed to the attention of the CP. A similar emphasis is posed towards the shape of the risk function for pleural mesothelioma, a theme absent from the current practice of the CP such as of other occupational practitioners. In conclusion, next to themes of undoubted interest for the PC, the SIML PPA dwells on the scrutiny of some topics representing critical elements of the current contrast between consultants and valuers in the context of criminal prosecutions: subjects having forensic relevance but far from the &quot;application actuality&quot; for the CP invoked in the PPA. A greater transparency, last but not least, was to have been posed, inside the SIML PPA, in the disclosure of the conflict of interests (COIs) of some Authors, declaring their consultancy in favour of companies.}, }
@article {pmid32374111, year = {2020}, author = {Marinaccio, A and Corfiati, M and Binazzi, A and Di Marzio, D and Bonafede, M and Verardo, M and Migliore, E and Gennaro, V and Mensi, C and Schallemberg, G and Mazzoleni, G and Fedeli, U and Negro, C and Romanelli, A and Chellini, E and Grappasonni, I and Pascucci, C and Madeo, G and Romeo, E and Trafficante, L and Carrozza, F and Angelillo, IF and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and , }, title = {The epidemiological surveillance of malignant mesothelioma in Italy (1993-2015): methods, findings, and research perspectives.}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {1}, pages = {23-30}, doi = {10.19191/EP20.1.P023.014}, pmid = {32374111}, issn = {1120-9763}, mesh = {Adult ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*epidemiology ; Middle Aged ; Occupational Diseases/epidemiology ; Occupational Exposure/statistics &amp; numerical data ; Population Surveillance ; Registries ; }, abstract = {BACKGROUND: as a legacy of the large asbestos consumption until the definitive ban in 1992, Italy had to tackle a real epidemic of asbestos related diseases. The Italian National Registry of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with a regional structure. Aims, assignments and territorial network of ReNaM are described, as well as data collection, recording and coding procedures.<br><br>OBJECTIVES: to describe the Italian epidemiological surveillance system of mesothelioma incidence, to provide updated data about occurrence of malignant mesothelioma in Italy, and to discuss goals, attainments, and expectations of registering occupational cancer.<br><br>DESIGN: analysis of data by malignant mesothelioma incident cases surveillance system.<br><br>SETTING AND PARTICIPANTS: Italy, network of regional surveillance system, all Italian regions.<br><br>MAIN OUTCOME MEASURES: a Regional Operating Centre (COR) is currently established in all the Italian regions, actively searching incident malignant mesothelioma cases from health care institutions. Occupational history, lifestyle habits, and residential history are obtained using a standardized questionnaire, administered to the subject or to the next of kin by a trained interviewer. The extent of dataset, epidemiological parameters, and occupations involved are reported updated at 31.12.2016, and standardized incidence rates are calculated.<br><br>RESULTS: at December 2016, ReNaM has collected 27,356 malignant mesothelioma cases, referring to the period of incidence between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of defined cases (14,818).<br><br>CONCLUSIONS: the Italian experience shows that epidemiological systematic surveillance of asbestos related diseases incidence has a key importance for assessing and monitoring the public health impact of occupational and/or environmental hazards, programming preventive interventions, including remediation plans and information campaigns, and supporting the efficiency of insurance and welfare system. Monitoring the incidence of malignant mesothelioma through a specialized cancer registry is essential to follow-up the health effects of changing modalities and extent of occupational exposures over years and of environmental contamination. Such consolidated surveillance system is recommended also for occupational cancers with low aetiological fraction.}, }
@article {pmid32369821, year = {2020}, author = {Campanella, NC and Silva, EC and Dix, G and de Lima Vazquez, F and Escremim de Paula, F and Berardinelli, GN and Balancin, M and Chammas, R and Mendoza Lopez, RV and Silveira, HCS and Capelozzi, VL and Reis, RM}, title = {Mutational Profiling of Driver Tumor Suppressor and Oncogenic Genes in Brazilian Malignant Pleural Mesotheliomas.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {87}, number = {3}, pages = {208-216}, doi = {10.1159/000507373}, pmid = {32369821}, issn = {1423-0291}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly lethal disease comprising a heterogeneous group of tumors with challenging to predict biological behavior. The diagnosis is complex, and the histologic classification includes 2 major subtypes of MPM: epithelioid (∼60% of cases) and sarcomatous (∼20%). Its identification depends upon pathological investigation supported by clinical and radiological evidence and more recently ancillary molecular testing. Treatment options are currently limited, with no known targeted therapies available.<br><br>OBJECTIVES: To elucidate the mutation profile of driver tumor suppressor and oncogenic genes in a cohort of Brazilian patients.<br><br>METHODS: We sequenced 16 driver genes in a series of 43 Brazilian malignant mesothelioma (MM) patients from 3 distinct Brazilian centers. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor tissue blocks, and the TERT promoter region was amplified by PCR followed by direct capillary sequencing. The Illumina TruSight Tumor 15 was used to evaluate 250 amplicons from 15 genes associated with solid tumors (AKT1, GNA11, NRAS, BRAF, GNAQ, PDGFRA, EGFR, KIT, PIK3CA, ERBB2, KRAS, RET, FOXL2, MET,and TP53). Library preparation with the TruSight Tumor 15 was performed before sequencing at the MiSeq platform. Data analysis was performed using Sophia DDM software.<br><br>RESULTS: Out of 43 MPM patients, 38 (88.4%) were epithelioid subtype and 5 (11.6%) were sarcomatoid histotype. Asbestos exposure was present in 15 (39.5%) patients with epithelioid MPM and 3 (60%) patients with sarcomatoid MPM. We found a TERT promoter mutation in 11.6% of MM, and the c.-146C>T mutation was the most common event. The next-generation sequencing was successful in 33 cases. A total of 18 samples showed at least 1 pathogenic, with a median of 1.8 variants, ranging from 1 to 6. The most mutated genes were TP53 and ERBB2 with 7 variants each, followed by NRAS BRAF, PI3KCA, EGFR and PDGFRA with 2 variants each. KIT, AKT1, and FOXL2 genes exhibited 1 variant each. Interestingly, 2 variants observed in the PDGFRA gene are classic imatinib-sensitive therapy.<br><br>CONCLUSIONS: We concluded that Brazilian MPM harbor mutation in classic tumor suppressor and oncogenic genes, which might help in the guidance of personalized treatment of MPM.}, }
@article {pmid32367143, year = {2020}, author = {Fadel, M and Evanoff, BA and Andersen, JH and d'Errico, A and Dale, AM and Leclerc, A and Descatha, A}, title = {Not just a research method: If used with caution, can job-exposure matrices be a useful tool in the practice of occupational medicine and public health?.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {46}, number = {5}, pages = {552-553}, doi = {10.5271/sjweh.3900}, pmid = {32367143}, issn = {1795-990X}, mesh = {*Asbestos ; France ; Humans ; Occupational Exposure/*analysis ; *Occupational Medicine ; Occupations ; Public Health ; }, abstract = {The recent editorial by Dr Susan Peters &quot;Although a valuable method in occupational epidemiology, job-exposure matrices are no magic fix&quot; ably describes the strengths and limitations of job-exposure matrix (JEM) approaches in occupational epidemiology research (1). In addition to their use in research, we would like to add that JEM may also be of use in compensation and surveillance efforts in occupational health. JEM could assist the compensation process by supporting the assessment of relevant exposures related to specific health conditions (2). The potential usefulness of a JEM as a decision tool for compensation of work-related musculoskeletal disorders has been examined (3). Because occupational diseases are often under-recognized, another practical application is using a JEM to screen for occupational exposures as part of health surveillance. Use of JEM to screen for asbestos and wood dust exposure in the clinical setting has shown promising results (4-6). By summarizing multiple exposures at a job level (7), JEM may also assist policy-makers in setting priorities for hazards and controls at work, as well as occupational practitioners to target prevention efforts and direct the conduct of more precise exposure measures to particular jobs. Sharing JEM across different countries may be useful in providing estimates of exposures across larger populations to calculate global burden of disease related to occupational exposure. The JEMINI (JEM InterNatIonal) initiative was launched to explore the possibility of developing international JEM that could be used across countries (8). Beginning with physical (biomechanical) exposures, this open group has started homogenizing job coding systems and comparing some available JEM. Estimating differences in the level of exposure between countries will require much more work, without guaranteed success. As Peters mentioned, many limitations exist in the use of JEM. Users of JEM must consider the source of exposure data - expert assessments, data collected from individual workers, or environmental sampling. The coding of occupations is time consuming and can introduce error (9), and more testing of and comparison with automated job coding systems is needed (10). JEM reflect an &quot;average&quot; level of exposure within a job at the expense of individual variation. At population level, JEM can offer a useful estimate of exposures. If used at an individual level in a clinical or compensation setting, JEM cannot replace the professionals involved in exposure assessment but may help them focus their action more effectively on complex situations that require their expertise. In conclusion, these JEM developed for research might also be used as a public health tool, provided that their limitations are properly taken into account. References 1. Peters S. Although a valuable method in occupational epidemiology, job-exposure matrices are no magic fix. Scand J Work Environ Health 2020;46:2314. https://doi.org/10.5271/sjweh.3894 2. Kerbrat J, Descatha A. (The recognition of health consequences of difficult working conditions in France and its evaluation with the use of a job-exposure matrix). Arch Mal Prof Environ. 2018;79:493500. https://doi.org/10.1016/j.admp.2017.12.001 3. Fadel M, Valter R, Quignette A, Descatha A. Usefulness of a job-exposure matrix « MADE » as a decision tool for compensation of work-related musculoskeletal disorders. Eur J Public Health 2019;29:86870. https://doi.org/10.1093/eurpub/cky274 4. Lorentz E, Despreaux T, Quignette A, Chinet T, Descatha A. (Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma). Rev Mal Respir. 2019;36:108895. https://doi.org/10.1016/j.rmr.2019.08.006 5. Imbernon E, Goldberg M, Spyckerell Y, Steinmetz J, Bonenfant S, Fournier B. (Use of a job-exposure matrix for the screening of occupational exposure to asbestos). Rev Epidemiol Sante Publique 2004;52:717. https://doi.org/10.1016/S0398-7620(04)99018-9 6. Carton M, Bonnaud S, Nachtigal M, Serrano A, Carole C, Bonenfant S, et al. Post-retirement surveillance of workers exposed to asbestos or wood dust: first results of the French national SPIRALE Program. Epidemiol Prev. 2011;35:31523. 7. Guéguen A, Goldberg M, Bonenfant S, Martin JC. Using a representative sample of workers for constructing the SUMEX French general population based job-exposure matrix. Occup Environ Med. 2004;61:58693. https://doi.org/10.1136/oem.2003.010660 8. Descatha A, Evanoff BA, Andersen JH, Fadel M, Ngabirano L, Leclerc A, et al. JEMINI (Job Exposure Matrix InterNatIonal) Initiative: a Utopian Possibility for Helping Occupational Exposure Assessment All Around the World? J Occup Environ Med. 2019;61:e3201. https://doi.org/10.1097/JOM.0000000000001631 9. Petersen SB, Flachs EM, Svendsen SW, Marott JL, Budtz-Jørgensen E, Hansen J, et al. Influence of errors in job codes on job exposure matrix-based exposure assessment in the register-based occupational cohort DOC*X. Scand J Work Environ Health 2020;46:25967. https://doi.org/10.5271/sjweh.3857 10. Buckner-Petty S, Dale AM, Evanoff BA. Efficiency of autocoding programs for converting job descriptors into standard occupational classification (SOC) codes. Am J Ind Med. 2019;62:5968. https://doi.org/10.1002/ajim.22928.}, }
@article {pmid32364316, year = {2020}, author = {Trama, A and Proto, C and Signorelli, D and Garassino, MC and Lo Russo, G and Ganzinelli, M and Prelaj, A and Mensi, C and Gangemi, M and Gennaro, V and Chellini, E and Caldarella, A and Angelillo, IF and Ascoli, V and Pascucci, C and Tagliabue, G and Cusimano, R and Bella, F and Falcini, F and Merler, E and Masanotti, G and Ziino, A and Michiara, M and Gola, G and Storchi, C and Mangone, L and Vitale, MF and Cirilli, C and Tumino, R and Scuderi, T and Fanetti, AC and Piffer, S and Tiseo, M and Gatta, G and Botta, L and , }, title = {Treatment patterns among patients with malignant pleural mesothelioma: An Italian, population-based nationwide study.}, journal = {Thoracic cancer}, volume = {11}, number = {6}, pages = {1661-1669}, pmid = {32364316}, issn = {1759-7714}, support = {NA//Associazione Italiana Esposti Amianto (Italian Association of Asbestos Expositions AIEA)/International ; Investigator Grant - IG 2012 number 13534, year 20//Associazione Italiana per la Ricerca sul Cancro (Italian Association for cancer research-AIRC)/International ; RF-INT- 201241451, year 2008//Italian Ministry of Health/International ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. Centralization of rare cancer in dedicated centers is recommended to ensure expertise, multidisciplinarity and access to innovation. In Italy, expert centers for MPM have not been identified in all regions. We aimed to describe the treatment patterns among MPM patients across different Italian regions and to identify factors associated with the treatment patterns across the regions.<br><br>METHODS: We performed an observational study on a random sample of 2026 MPM patients diagnosed in 2003-2008. We included 26 population-based registries covering 70% of the Italian population. To identify factors associated with treatment patterns, across the different regions, we fitted a multinomial logistic regression model adjusted by age, sex, stage, histology and hospital with thoracic surgical department.<br><br>RESULTS: MPM patients mostly received chemotherapy alone (41%) or no cancer-directed therapy (36%) especially the older patients. The first course of treatment for MPM patients differed across regions. Patients from Piedmont, Liguria and Campania were more likely to receive no cancer-directed therapy; those living in Tuscany and Sicily were more likely to get surgery; patients from Marche and Lazio were more likely to receive chemotherapy. These differences were not explained by age, sex, stage, histology and availability of a thoracic surgery department.<br><br>CONCLUSIONS: There is limited expertise available and lack of a network able to maximize the expertise available may contribute to explaining the results of our study. Our findings support the need to ensure the appropriate care of all MPM patients in reorganizing the health care services.<br><br>KEY POINTS: Significant findings of the study: MPM patients mostly received chemotherapy alone or no cancer-directed therapy especially the older patients. The first course of treatment for MPM patients differed across Italian regions.<br><br>WHAT THIS STUDY ADDS: Differences in MPM clinical management are not explained by the age, stage, histology nor by the availability of a thoracic surgery department. Limited expertise for MPM contribute to explaining the unequal access to appropriate care for MPM patients in Italy.}, }
@article {pmid32354783, year = {2020}, author = {Dyer, C}, title = {Doctor with mesothelioma wins settlement for asbestos exposure in late 1990s.}, journal = {BMJ (Clinical research ed.)}, volume = {369}, number = {}, pages = {m1783}, doi = {10.1136/bmj.m1783}, pmid = {32354783}, issn = {1756-1833}, }
@article {pmid32352426, year = {2020}, author = {Angelini, A and Chellini, E and Parducci, D and Puccetti, M and Mauro, L}, title = {.}, journal = {La Medicina del lavoro}, volume = {111}, number = {2}, pages = {126-132}, doi = {10.23749/mdl.v111i2.8837}, pmid = {32352426}, issn = {0025-7818}, mesh = {*Asbestos/toxicity ; Humans ; *Lung Neoplasms/epidemiology ; *Mesothelioma/epidemiology ; Occupational Diseases ; *Occupational Exposure ; *Pleural Neoplasms/epidemiology ; }, abstract = {BACKGROUND: The Tuscan Regional Operating Center (ROC) of Malignant Mesotheliomas has identified a cluster of 11 cases of malignant mesothelioma occurred in a textile plant manufacturing sewing thread. Using the common research method, the ROC had not previously been able to identify the specific sources of asbestos exposure causing such a large cluster.<br><br>OBJECTIVES: The ROC's objective was to review all cases of the cluster and to better identify their occupational asbestos exposures.<br><br>METHODS: The cases' occupational histories of asbestos exposure have been reviewed, using information deriving from the annual reports sent to the Tuscany Region since 1988 by all the asbestos removal companies according to the Law no. 257/1992, article 9, and from interviews to former employees of the plant.<br><br>RESULTS: The work cycle has been reconstructed and enriched with the new information about the asbestos presence and its uses in the plant. The eleven cases were all reclassified as &quot;certainly occupational exposed&quot; given that the new collected information depicted a widespread asbestos pollution of the workplace during the period of employment of all cases.<br><br>CONCLUSIONS: Using different sources of information, in addition to those traditionally collected through questionnaires, to reconstruct past asbestos exposuresallowed us to clarify the existence of the cluster of mesothelioma cases and the highest level of occupational asbestos exposure was attributed to all cases with consequent activation of the medico-legal procedure.}, }
@article {pmid32345664, year = {2020}, author = {Lacerenza, S and Ciregia, F and Giusti, L and Bonotti, A and Greco, V and Giannaccini, G and D'Antongiovanni, V and Fallahi, P and Pieroni, L and Cristaudo, A and Lucacchini, A and Mazzoni, MR and Foddis, R}, title = {Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome.}, journal = {Cancer genomics &amp; proteomics}, volume = {17}, number = {3}, pages = {225-236}, pmid = {32345664}, issn = {1790-6245}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Cell Line, Tumor ; Female ; GPI-Linked Proteins/blood ; Humans ; Lung Neoplasms/*blood/pathology ; Male ; Mesothelioma/*blood/pathology ; Mesothelioma, Malignant ; Middle Aged ; Oxidoreductases Acting on Sulfur Group Donors/blood ; Pleural Neoplasms/*blood/pathology ; Proteome/*metabolism ; ROC Curve ; Saposins/blood ; Secretory Pathway ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) a rare neoplasm linked to asbestos exposure is characterized by a poor prognosis. Soluble mesothelin is currently considered the most specific diagnostic biomarker. The aim of the study was to identify novel biomarkers by proteomic analysis of two MPM cell lines secretome.<br><br>MATERIALS AND METHODS: The protein patterns of MPM cells secretome were examined and compared to a non-malignant mesothelial cell line using two-dimensional gel electrophoresis coupled to mass spectrometry. Serum levels of candidate biomarkers were determined in MPM patients and control subjects.<br><br>RESULTS: Two up-regulated proteins involved in cancer biology, prosaposin and quiescin Q6 sulfhydryl oxidase 1, were considered candidate biomarkers. Serum levels of both proteins were significantly higher in MPM patients than control subjects. Combining the data of each receiver-operating characteristic analysis predicted a good diagnostic accuracy.<br><br>CONCLUSION: A panel of the putative biomarkers represents a promising tool for MPM diagnosis.}, }
@article {pmid32330840, year = {2020}, author = {Ahmadzada, T and Kao, S and Reid, G and Clarke, S and Grau, GE and Hosseini-Beheshti, E}, title = {Extracellular vesicles as biomarkers in malignant pleural mesothelioma: A review.}, journal = {Critical reviews in oncology/hematology}, volume = {150}, number = {}, pages = {102949}, doi = {10.1016/j.critrevonc.2020.102949}, pmid = {32330840}, issn = {1879-0461}, mesh = {Biomarkers ; *Cell-Derived Microparticles ; *Exosomes ; *Extracellular Vesicles ; Humans ; *Mesothelioma ; }, abstract = {Extracellular vesicles (EV) are secreted by all cells, including cancer cells, as a mode of intercellular transport and communication. The main types of EV known to date include exosomes, microvesicles and apoptotic bodies, as well as oncosomes and large oncosomes, which are specific to cancer cells. These different EV populations carry specific cargo from one cell to another to stimulate a specific response. They can be found in all body fluids and can be detected in liquid biopsies. EV released from mesothelioma cells can reveal important information about the molecules and signalling pathways involved in the development and progression of the tumour. The presence of tumour-derived EV in circulating body fluids makes them potential novel biomarkers for early diagnosis, prognostication and surveillance of cancer. In this review, we explore the characteristics and functional roles of EV reported in the literature, with a focus on their role in malignant pleural mesothelioma.}, }
@article {pmid32330788, year = {2020}, author = {Filetti, V and Falzone, L and Rapisarda, V and Caltabiano, R and Eleonora Graziano, AC and Ledda, C and Loreto, C}, title = {Modulation of microRNA expression levels after naturally occurring asbestiform fibers exposure as a diagnostic biomarker of mesothelial neoplastic transformation.}, journal = {Ecotoxicology and environmental safety}, volume = {198}, number = {}, pages = {110640}, doi = {10.1016/j.ecoenv.2020.110640}, pmid = {32330788}, issn = {1090-2414}, mesh = {Adult ; Asbestos/*toxicity ; Asbestos, Amphibole/*toxicity ; Biomarkers/analysis ; Cell Line ; Cell Transformation, Neoplastic/*chemically induced ; *Environmental Exposure ; Epithelium/*drug effects ; Female ; Gene Expression Profiling ; Humans ; Male ; MicroRNAs/*genetics ; Middle Aged ; Neoplasms, Mesothelial/*chemically induced/diagnosis ; Sicily ; }, abstract = {Fluoro-edenite (FE) is a silicate mineral identified in the lava products of Monte Calvario from stone quarries located in the southeast of Biancavilla, a small city of the Etnean volcanic complex (Sicily, Italy). Inhalation of FE fibers has been associated with a higher incidence of Malignant Mesothelioma (MM), a highly aggressive neoplasm of the serosal membranes lining the pleural cavity. Only 5% of MM patients are diagnosed at an early stage and the median survival is approximate 6-12 months. Many diagnostic biomarkers have been proposed for MM. Several studies demonstrated that microRNAs (miRNAs) may be used as good non-invasive diagnostics, as well as prognostic biomarkers for various human diseases, including cancer. On these bases, the aim of the present study was to identify a set of miRNAs involved in the development and progression of MM and potentially used as diagnostic biomarkers. For these purposes, in silico analyses were performed on healthy/exposed to asbestos fibers subjects vs. patients with MM. These analyses revealed a set of miRNAs strictly involved in MM by merging the lists of miRNAs found differentially expressed in the three miRNA expression datasets analyzed. The result of these computational evaluations allowed the execution of functional in vitro experiments performed on normal pleural mesothelial cell line (MeT-5A) and MM cell line (JU77) in order to test the carcinogenetic effects and epigenetic modulation induced by FE exposure. The in vitro results showed that the expression levels of hsa-miR-323a-3p vary significantly in both supernatant- and cell-derived miRNAs derived from treated and untreated cells. Secreted and cellular hsa-miR-101-3p in MeT-5A treated with FE fibers and JU77 cells showed different trends of expression. As regard hsa-miR-20b-5p, there was no differential expression between secreted and cellular hsa-miR-20b-5p. This miRNA has been shown a significant up-regulation in JU77 cells vs. control and treated MeT-5A. As a future plan, translational analyses will be performed on a subset of patients chronically exposed to FE fibers to further verify the clinical role of such miRNAs in high-risk individuals and their possible use as biomarkers of FE exposure or MM early onset.}, }
@article {pmid32328661, year = {2020}, author = {Girardi, P and Merler, E and Ferrante, D and Silvestri, S and Chellini, E and Angelini, A and Luberto, F and Fedeli, U and Oddone, E and Vicentini, M and Barone-Adesi, F and Cena, T and Mirabelli, D and Mangone, L and Roncaglia, F and Sala, O and Menegozzo, S and Pirastu, R and Azzolina, D and Tunesi, S and Miligi, L and Perticaroli, P and Pettinari, A and Cuccaro, F and Nannavecchia, AM and Bisceglia, L and Marinaccio, A and Pavone, VLM and Magnani, C}, title = {Factors Affecting Asbestosis Mortality Among Asbestos-Cement Workers in Italy.}, journal = {Annals of work exposures and health}, volume = {64}, number = {6}, pages = {622-635}, doi = {10.1093/annweh/wxaa037}, pmid = {32328661}, issn = {2398-7316}, abstract = {OBJECTIVES: This study was performed with the aim of investigating the temporal patterns and determinants associated with mortality from asbestosis among 21 cohorts of Asbestos-Cement (AC) workers who were heavily exposed to asbestos fibres.<br><br>METHODS: Mortality for asbestosis was analysed for a cohort of 13 076 Italian AC workers (18.1% women). Individual cumulative asbestos exposure index was calculated by factory and period of work weighting by the different composition of asbestos used (crocidolite, amosite, and chrysotile). Two different approaches to analysis, based on Standardized Mortality Ratios (SMRs) and Age-Period-Cohort (APC) models were applied.<br><br>RESULTS: Among the considered AC facilities, asbestos exposure was extremely high until the end of the 1970s and, due to the long latency, a peak of asbestosis mortality was observed after the 1990s. Mortality for asbestosis reached extremely high SMR values [SMR: males 508, 95% confidence interval (CI): 446-563; females 1027, 95% CI: 771-1336]. SMR increased steeply with the increasing values of cumulative asbestos exposure and with Time Since the First Exposure. APC analysis reported a clear age effect with a mortality peak at 75-80 years; the mortality for asbestosis increased in the last three quintiles of the cumulative exposure; calendar period did not have a significant temporal component while the cohort effect disappeared if we included in the model the cumulative exposure to asbestos.<br><br>CONCLUSIONS: Among heaviest exposed workers, mortality risk for asbestosis began to increase before 50 years of age. Mortality for asbestosis was mainly determined by cumulative exposure to asbestos.}, }
@article {pmid32326213, year = {2020}, author = {Cellai, F and Bonassi, S and Cristaudo, A and Bonotti, A and Neri, M and Ceppi, M and Bruzzone, M and Milić, M and Munnia, A and Peluso, M}, title = {Chromatographic Detection of 8-Hydroxy-2'-Deoxyguanosine in Leukocytes of Asbestos Exposed Workers for Assessing Past and Recent Carcinogen Exposures.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {10}, number = {4}, pages = {}, pmid = {32326213}, issn = {2075-4418}, support = {NA//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; NA//Regione Toscana/ ; }, abstract = {Asbestos fibers include a group of silicate minerals that occur in the environment and are widely employed in occupational settings. Asbestos exposure has been associated to various chronic diseases; such as pulmonary fibrosis; mesothelioma; and lung cancer; often characterized by a long period of latency. Underlying mechanisms that are behind the carcinogenic effect of asbestos have not been fully clarified. Therefore; we have conducted an epidemiological study to evaluate the relationship between 8-hydroxy-2'-deoxyguanosine (8-oxodG), one of the most reliable biomarkers of oxidative stress and oxidative DNA damage; and asbestos exposure in the peripheral blood of residents in Tuscany and Liguria regions; Italy; stratified by occupational exposure to this carcinogen. Levels of 8-oxodG were expressed such as relative adduct labeling (RAL); the frequency of 8-oxodG per 105 deoxyguanosine was significantly higher among exposed workers with respect to the controls; i.e., 3.0 ± 0.2 Standard Error (SE) in asbestos workers versus a value of 1.3 ± 0.1 (SE) in unexposed controls (p < 0.001). When the relationship with occupational history was investigated; significant higher levels of 8-oxodG were measured in current and former asbestos workers vs. healthy controls; 3.1 ± 0.3 (SE) and 2.9 ± 0.2 (SE), respectively. After stratification for occupational history; a significant 194% excess of adducts was found in workers with 10 or more years of past asbestos exposure (p < 0.001). 8-oxodG can be used for medical surveillance programs of cohorts of workers with past and recent exposures to carcinogens for the identification of subjects requiring a more intense clinical surveillance.}, }
@article {pmid32318342, year = {2020}, author = {Ferrari, L and Carugno, M and Mensi, C and Pesatori, AC}, title = {Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {445}, pmid = {32318342}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer, which originates from the mesothelial cells of the pleura and is associated with asbestos exposure. In light of its aggressive nature, late diagnosis and dismal prognosis, there is an urgent need for identification of biomarkers in easily accessible samples (such as blood) for early diagnosis of MPM. In the last 10 years, epigenetic markers, such as DNA methylation and microRNAs (miRNAs), have gained popularity as possible early diagnostic and prognostic biomarkers in cancer research. The aim of this review is to provide a critical analysis of the current evidences on circulating epigenetic biomarkers for MPM and on their translational potential to the clinical practice for early diagnosis and for prognosis.}, }
@article {pmid32312030, year = {2020}, author = {Loreto, C and Caltabiano, R and Graziano, ACE and Castorina, S and Lombardo, C and Filetti, V and Vitale, E and Rapisarda, G and Cardile, V and Ledda, C and Rapisarda, V}, title = {Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1.}, journal = {European journal of histochemistry : EJH}, volume = {64}, number = {2}, pages = {}, pmid = {32312030}, issn = {2038-8306}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Asbestosis/*physiopathology ; Female ; Fibroblasts/drug effects ; Heme Oxygenase-1/*metabolism ; Humans ; Immunohistochemistry ; Inflammation/physiopathology ; Lung/*drug effects/pathology ; Macrophage Migration-Inhibitory Factors/*metabolism ; Male ; Sheep ; }, abstract = {Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 μg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.}, }
@article {pmid32308151, year = {2020}, author = {Sturchio, E and Berardinelli, MG and Boccia, P and Zanellato, M and Gioiosa, S}, title = {MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma.}, journal = {Archives of environmental &amp; occupational health}, volume = {75}, number = {8}, pages = {471-482}, doi = {10.1080/19338244.2020.1747966}, pmid = {32308151}, issn = {2154-4700}, mesh = {Animals ; Asbestos/toxicity ; Biomarkers, Tumor/analysis ; Humans ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mesothelioma, Malignant ; MicroRNAs/*analysis ; Occupational Exposure/adverse effects ; Predictive Value of Tests ; Prognosis ; }, abstract = {Malignant mesothelioma is an aggressive tumor resistant to current therapies with a latency period ranging between 20 and 60 years, caused by inhalation of asbestos fibers, that continues to represent a social and healthcare issue. The high percentage of people exposed to asbestos for professional or environmental reasons is associated with the high biopersistence of its fibers and with its widespread use in the last century. Approximately 20-40% of men report an occupational history that might have caused the workplace exposure (criteria Helsinki, 1997). Some authors are evaluating the possible use of bioindicators as a screening and early diagnosis tool. In this regard, the use of microRNAs has been proposed as powerful diagnostic and prognostic biomarkers for many tumors and human diseases. This review focuses on the current state of knowledge on the key role of microRNAs expression as new malignant mesothelioma biomarkers, in early clinical diagnostic applications.}, }
@article {pmid32301278, year = {2020}, author = {Barbarino, M and Cesari, D and Bottaro, M and Luzzi, L and Namagerdi, A and Bertolino, FM and Bellan, C and Proietti, F and Somma, P and Micheli, M and de Santi, MM and Guazzo, R and Mutti, L and Pirtoli, L and Paladini, P and Indovina, P and Giordano, A}, title = {PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach.}, journal = {Journal of cellular and molecular medicine}, volume = {24}, number = {10}, pages = {5565-5577}, pmid = {32301278}, issn = {1582-4934}, support = {483418//Mesothelioma Applied Research Foundation/ ; }, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.}, }
@article {pmid32290540, year = {2020}, author = {Vimercati, L and Cavone, D and Delfino, MC and Caputi, A and De Maria, L and Sponselli, S and Corrado, V and Ferri, GM and Serio, G}, title = {Asbestos Air Pollution: Description of a Mesothelioma Cluster Due to Residential Exposure from an Asbestos Cement Factory.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {8}, pages = {}, pmid = {32290540}, issn = {1660-4601}, mesh = {Aged ; *Air Pollution ; *Asbestos/toxicity ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/chemically induced/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; Middle Aged ; *Occupational Exposure/adverse effects ; }, abstract = {The study describes a cluster of 71 malignant mesothelioma cases among Bari residents without asbestos exposure other than residential exposure. This small cohort, as expected, was composed of a majority of females (56.34%) with a M/F ratio of 0.8, ages ≤ 65 years old (52.11%) and the epithelioid morphological type (78.87%). Sixty-four subjects (90.14%) lived between 10 m and 1000 m from the asbestos cement factory (Fibronit), and the latency length was longer than 55 years for 25 subjects (35.21%). The adjusted risk (adjusted OR) of observing the epithelial form of mesothelioma among subjects living at small distances from Fibronit was high (OR = 1.870 (0.353-9.905)) for people living 550-1000 m from the site and for those living less than 550 m from the site (OR = 1.470 (0.262-8.248)). Additionally, the subjects with a high length of exposure showed a relevant risk of epithelioid mesothelioma both for 21-40 years of exposure (OR = 2.027 (0.521-7.890)) and more than 40 years of exposure (OR = 2.879 (0.651-12.736)). All of the estimates were high but not significant because this transitional study has a typically low power. The adjustment for latency showed the same trend. Using detailed information collected by the regional mesothelioma registry, this study provided evidence of a continuing health impact of the Fibronit asbestos cement factory in Bari on the resident population.}, }
@article {pmid32282287, year = {2020}, author = {Metintas, S and Ak, G and Metintas, M}, title = {Potential years of life and productivity loss due to malignant mesothelioma in Turkey.}, journal = {Archives of environmental &amp; occupational health}, volume = {75}, number = {8}, pages = {464-470}, doi = {10.1080/19338244.2020.1747380}, pmid = {32282287}, issn = {2154-4700}, mesh = {Adult ; *Efficiency ; Female ; Humans ; *Life Expectancy ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; Mortality/*trends ; Population Surveillance ; Risk Assessment ; Risk Factors ; Turkey/epidemiology ; }, abstract = {The study aimed to calculate years of life lost (YLL) and years of potential life lost (YPLL) due to malignant mesothelioma (MM) in Turkey. YLL was computed by estimating the difference between age at death due to MM and the expected death age. To calculate YPLL, all deaths above 65 years (retirement age) were disregarded. Of the 5,617 deaths due to MM in the study period, 3,241 (57.70%) were male and 2,376 (42.30%) were female. The median YLL and YPLL were 16.58 and 25.13 for males and 19.83 and 28.50 years for females. YLL and YPLL were shorter in males than females (p < 0.001). Premature mortality cost per death was $ 45,963.57 (2.23 times higher for males). MM is associated with high YLL, YPLL and economic burden in a country with environmental asbestos exposure in the rural areas.}, }
@article {pmid32253443, year = {2020}, author = {Marinaccio, A and Consonni, D and Mensi, C and Mirabelli, D and Migliore, E and Magnani, C and Di Marzio, D and Gennaro, V and Mazzoleni, G and Girardi, P and Negro, C and Romanelli, A and Chellini, E and Grappasonni, I and Madeo, G and Romeo, E and Ascoli, V and Carrozza, F and Angelillo, IF and Cavone, D and Tumino, R and Melis, M and Curti, S and Brandi, G and Mattioli, S and Iavicoli, S and , }, title = {Association between asbestos exposure and pericardial and tunica vaginalis testis malignant mesothelioma: a case-control study and epidemiological remarks.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {46}, number = {6}, pages = {609-617}, doi = {10.5271/sjweh.3895}, pmid = {32253443}, issn = {1795-990X}, abstract = {Objectives The purposes of this study are to describe the epidemiology of pericardial and tunica vaginalis testis mesothelioma and assess the role of asbestos exposure for these rare diseases. Methods Based on incident pericardial and tunica vaginalis testis mesothelioma cases collected from the Italian national mesothelioma registry (ReNaM) in the period 1993-2015, incidence rates, survival median period and prognostic factors have been evaluated. A case-control study has been performed to analyze the association with asbestos exposure (occupational and non-occupational) for these diseases. Results Between 1993 and 2015, 58 pericardial (20 women and 38 men) and 80 tunica vaginalis testis mesothelioma cases have been registered with a mean annual standardized (world standard population as reference) incidence rates of 0.049 (per million) in men and 0.023 in women for the pericardial site, and 0.095 for tunica vaginalis testis mesothelioma. Occupational exposure to asbestos was significantly associated with the risk of the diseases [odds ratio (OR) 3.68, 95% confidence interval (CI) 1.85-7.31 and OR 3.42, 95% CI 1.93-6.04 in pericardial and tunica vaginalis testis mesothelioma, respectively]. The median survival was 2.5 months for pericardial and 33.0 months for tunica vaginalis testis mesotheliomas. Age was the main predictive factor for survival for both anatomical sites. Conclusions For the first time in an analytical study, asbestos exposure was associated with pericardial and tunica vaginalis testis mesothelioma risk, supporting the causal role of asbestos for all anatomical sites. The extreme rarity of the diseases, the poor survival and the prognostic role of age have been confirmed based on population and nationwide mesothelioma registry data.}, }
@article {pmid32249197, year = {2020}, author = {Lau, B and Boyer, M and Lee, JH and Kao, S}, title = {Clinical Trials Eligibility of Patients With Malignant Pleural Mesothelioma: Use of Novel Therapies and Outcomes.}, journal = {Clinical lung cancer}, volume = {21}, number = {4}, pages = {378-383.e1}, doi = {10.1016/j.cllc.2020.01.007}, pmid = {32249197}, issn = {1938-0690}, abstract = {INTRODUCTION: Studies of bevacizumab and pembrolizumab in the treatment of malignant pleural mesothelioma suggest anticancer efficacy; clinical trial populations are not reflective of real-world patients. We aimed to determine the proportion of real-world patients who would be eligible for trials, identify patients who participated in clinical trials, and examine treatment and outcome data.<br><br>PATIENTS AND METHODS: Consecutive patients with unresectable malignant pleural mesothelioma seen at our center from January 2012 to July 2018 were assessed with regards to their eligibility for Mesothelioma Avastin Cisplatin Study (MAPS) and KEYNOTE-028 clinical trials. Prognostic information, treatment use, and overall survival (OS) data were also collected.<br><br>RESULTS: A total of 133 patients were included: 50% and 37%, respectively, did not meet trial eligibility for MAPS or KEYNOTE-028, most commonly owing to age ≥75 (23%), Eastern Cooperative Oncology Group performance status of ≥2 (21%), concomitant medication (21%), or comorbidity (12%). MAPS eligibility did not correlate with use of bevacizumab (P = .30) or improved OS (P = .87). Eligibility for KEYNOTE-028 correlated with pembrolizumab use (P < .001), but not improved OS (P = .21). Patients who received an investigational anticancer therapy on any clinical trial had improved OS: 32.4 (95% CI, 23.9-40.9) months versus 20.5 (95% CI, 15.8-25.3) months (P = .01).<br><br>CONCLUSION: Only ≤63% of our patients were eligible for these trials, highlighting the differences between real-world patients and the highly select trial population. Our patients who participated in clinical trials had superior OS, further emphasizing the selection bias in the trial population.}, }
@article {pmid32248600, year = {2020}, author = {Okazaki, Y and Chew, SH and Nagai, H and Yamashita, Y and Ohara, H and Jiang, L and Akatsuka, S and Takahashi, T and Toyokuni, S}, title = {Overexpression of miR-199/214 is a distinctive feature of iron-induced and asbestos-induced sarcomatoid mesothelioma in rats.}, journal = {Cancer science}, volume = {111}, number = {6}, pages = {2016-2027}, pmid = {32248600}, issn = {1349-7006}, support = {//Ministry of Education, Culture, Sports, Science and Technology/ ; Young Scientist (B)(23790440)//Japan Society for the Promotion of Science/ ; Young Scientist (B)(25860292)//Japan Society for the Promotion of Science/ ; JP17H04064//JSPS Kakenhi/ ; JP19H05462//JSPS Kakenhi/ ; JPMJCR19H4//JST CREST/ ; }, mesh = {Animals ; Asbestos/toxicity ; Cell Line ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Iron/toxicity ; Lung Neoplasms/genetics/metabolism/*pathology ; Mesothelioma/genetics/metabolism/*pathology ; Mesothelioma, Malignant ; MicroRNAs/*biosynthesis ; Peritoneal Neoplasms/genetics/metabolism/*pathology ; Rats ; Twist-Related Protein 1/*biosynthesis ; }, abstract = {Malignant mesothelioma (MM) is one of the most lethal tumors in humans. The onset of MM is linked to exposure to asbestos, which generates reactive oxygen species (ROS). ROS are believed to be derived from the frustrated phagocytosis and the iron in asbestos. To explore the pathogenesis of MM, peritoneal MM was induced in rats by the repeated intraperitoneal injection of iron saccharate and nitrilotriacetate. In the present study, we used microarray techniques to screen the microRNA (miR) expression profiles of these MM. We observed that the histological subtype impacted the hierarchical clustering of miR expression profiles and determined that miR-199/214 is a distinctive feature of iron saccharate-induced sarcomatoid mesothelioma (SM). Twist1, a transcriptional regulator of the epithelial-mesenchymal transition, has been shown to activate miR-199/214 transcription; thus, the expression level of Twist1 was examined in iron-induced and asbestos-induced mesotheliomas in rats. Twist1 was exclusively expressed in iron saccharate-induced SM but not in the epithelioid subtype. The Twist1-miR-199/214 axis is activated in iron saccharate-induced and asbestos-induced SM. The expression levels of miR-214 and Twist1 were correlated in an asbestos-induced MM cell line, suggesting that the Twist1-miR-199/214 axis is preserved. MeT5A, an immortalized human mesothelial cell line, was used for the functional analysis of miR. The overexpression of miR-199/214 promoted cellular proliferation, mobility and phosphorylation of Akt and ERK in MeT5A cells. These results indicate that miR-199/214 may affect the aggressive biological behavior of SM.}, }
@article {pmid32242530, year = {2020}, author = {Ramos-Bonilla, JP and Marsili, D and Comba, P}, title = {Epidemiological research as a driver of prevention: the Sibaté study. Commentary.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {56}, number = {1}, pages = {6-9}, doi = {10.4415/ANN_20_01_03}, pmid = {32242530}, issn = {2384-8553}, abstract = {Although asbestos exposure and risks can be prevented, only five countries in Latin America have banned asbestos, including Colombia. Beginning in 2011, a collaboration between the Istituto Superiore di Sanità in Italy and Universidad de los Andes in Colombia was established, bringing together relevant expertise aiming to improve our understanding of the asbestos problem. An important result of this collaboration was a recently published study conducted in Sibaté, Colombia, a municipality where an asbestos-cement facility has operated since 1942. The evidence collected suggests the presence of a mesothelioma cluster in Sibaté. Landfilled zones with an underground layer of friable asbestos were also discovered in the urban area of the municipality. The importance of this type of collaboration can go beyond understanding the impact of asbestos at the local level, which is crucial, and may also contribute in solving unanswered questions of the problem in countries that banned asbestos decades ago.}, }
@article {pmid32223452, year = {2020}, author = {van Zandwijk, N and Reid, G and Frank, AL}, title = {Asbestos-related cancers: the 'Hidden Killer' remains a global threat.}, journal = {Expert review of anticancer therapy}, volume = {20}, number = {4}, pages = {271-278}, doi = {10.1080/14737140.2020.1745067}, pmid = {32223452}, issn = {1744-8328}, abstract = {Introduction: Asbestos, the most frequent cause of occupational cancer, continues to be consumed on a massive scale, with millions of people exposed on a daily basis. This review explains why we have failed in curtailing the silent epidemic of asbestos-related disease and why the numbers of asbestos victims are likely to remain high. Emerging and developed countries have to be reminded that asbestos exposure has yet to become a problem of the past. The worldwide spread of asbestos, followed by the surge of asbestos-related cancers, resembles the lung cancer epidemic caused by smoking and stimulated by manufacturers.Areas covered: Underreporting of malignant mesothelioma and asbestos-induced lung cancer, frequently-used arguments in the amphibole/chrysotile debate and the conclusion from bona-fide research organizations, that all forms of asbestos are carcinogenic, are reviewed. Special attention is paid to the consequences of ubiquitous environmental asbestos and the 'changing face' of malignant mesothelioma in countries with heavy asbestos use in the past.Expert opinion: Experts in oncology, respiratory medicine, occupational and public health, and basic researchers must take responsibility and acknowledge the ongoing silent epidemic of asbestos-related diseases. The call for a world-wide asbestos ban is more urgent than ever.}, }
@article {pmid32213537, year = {2020}, author = {Hoon, SN and Fyfe, K and Peddle-McIntyre, CJ and Bowyer, S and Hawkins, F and Jeffery, E and Chih, HJ and Creaney, J and Nowak, A and Brims, F}, title = {Randomised placebo-controlled cross-over study examining the role of anamorelin in mesothelioma (The ANTHEM study): rationale and protocol.}, journal = {BMJ open respiratory research}, volume = {7}, number = {1}, pages = {}, doi = {10.1136/bmjresp-2019-000551}, pmid = {32213537}, issn = {2052-4439}, abstract = {INTRODUCTION: Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia.<br><br>METHODS AND ANALYSIS: A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients will be randomised. Primary outcome is change in ASM relative to height measured by dual energy X-ray absorptiometry at end of period 1. Secondary outcomes include cancer-specific and cachexia-related QoL, objective physical activity, dietary intake and adverse events. Eligible patients will have confirmed MM, Eastern Cooperative Oncology Group 0-2, expected survival >3 months and cachexia (defined as >5% weight loss in 6 months or body mass index <20 kg/m2 with weight loss >2%).<br><br>ETHICS AND DISSEMINATION: Ethical approval has been granted. Results will be reported in peer-reviewed publications.<br><br>TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (U1111-1240-6828).}, }
@article {pmid32208261, year = {2020}, author = {Neitzel, RL and Sayler, SK and Demond, AH and d'Arcy, H and Garabrant, DH and Franzblau, A}, title = {Measurement of asbestos emissions associated with demolition of abandoned residential dwellings.}, journal = {The Science of the total environment}, volume = {722}, number = {}, pages = {137891}, doi = {10.1016/j.scitotenv.2020.137891}, pmid = {32208261}, issn = {1879-1026}, support = {P30 ES017885/ES/NIEHS NIH HHS/United States ; }, abstract = {Many cities are revitalizing their urban cores through the demolition of abandoned residential dwellings (ARDs). However, data regarding the emissions of asbestos during such an operation are sparse. We measured airborne asbestos emissions from emergency demolitions (demolitions on structures deemed too dangerous to enter and remove asbestos) of ARDs in Detroit. High-flow air sampling was conducted during ARD demolitions. Air samples were analyzed using Phased Contrast Microscopy (PCM), and a subset using Transmission Electron Microscopy (TEM). One hundred and one air samples were collected on 25 emergency demolitions. Fifty-four of the 101 PCM samples (53%) exceeded the limit of detection (LOD). However, only 2 of 46 TEM samples (4%) exceeded the LOD for asbestos; these latter samples were from two different demolitions and each contained a single chrysotile asbestos fiber. Using conservative exposure assumptions and commonly-accepted risk estimation formulae, we estimated the lifetime risk of mesothelioma and lung cancer combined to be less than one case per one million people. Emissions of airborne asbestos during emergency (unabated) ARD demolition operations appear to be negligible. As a result, the associated health risk for asbestos-related disease is also negligible. Reconsideration of current regulatory mandates for asbestos abatement in ARDs may be warranted.}, }
@article {pmid32206576, year = {2020}, author = {Gray, SG and Mutti, L}, title = {Immunotherapy for mesothelioma: a critical review of current clinical trials and future perspectives.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S100-S119}, pmid = {32206576}, issn = {2218-6751}, abstract = {At the clinical level the role of immunotherapy in cancer is currently at a pivotal point. Therapies such as checkpoint inhibitors are being approved at many levels in cancers such as non-small cell lung cancer (NSCLC). Mesothelioma is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Various clinical trials for checkpoint inhibitors have been conducted in this rare disease, and suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer. Most recently approved as a salvage therapy in mesothelioma was granted in Japan, regulatory approval for their use in the clinic elsewhere lags. In this article we review the current pertinent clinical trials of immunotherapies in malignant mesothelioma, discuss the current issues that may affect the clinical outcomes of such therapies and further evaluate potential candidate new avenues that may become future targets for immunotherapy in this cancer.}, }
@article {pmid32206572, year = {2020}, author = {Yoshikawa, Y and Emi, M and Nakano, T and Gaudino, G}, title = {Mesothelioma developing in carriers of inherited genetic mutations.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S67-S76}, pmid = {32206572}, issn = {2218-6751}, abstract = {Malignant mesothelioma is associated with the exposure to asbestos fibers. Recent discovery of the BAP1 cancer syndrome, a Mendelian disorder with high-penetrance autosomal dominant inheritance fostered the genotyping for nucleotide-level or larger structural alteration of germline DNA. Inherited heterozygous mutations of the BAP1 gene increase the susceptibility to carcinogenic fibers, leading to a concept of gene x environment interaction (GxE) as a pathogenetic mechanism of mesothelioma. Several studies on cohorts of unselected patients with mesothelioma or on familial/early-onset cohorts of mesothelioma cases converged on BAP1 as the more frequent germline mutated gene, followed by other genes involved in DNA repair and homologous recombination. Evidence has been emerging that patients with mesothelioma carrying germline mutations of BAP1 and of other genes, such as those involved in DNA repair and tumor suppressor genes, have better prognosis and higher chemosensitivity when compared with patients with germline wildtype Bap1. We report here a germline genomic analysis targeted 22 genes in a cohort of 101 Japanese patients irrespective of asbestos exposure, age at diagnosis, or personal or family history of cancer. By comparing the results with the Human Genetic Variation Database (HGVD) and the Genome Aggregation Database (gnomAD) we selected rare germline variants with a Combined Annotation Dependent Depletion (CADD) >20. We show here that 31 of 101 subjects were carrying 25 rare variants in 14 genes, neither reported in the HGVD nor in the gnomAD database for 14/25 variants. Besides pathogenic variants of BAP1, rare missense variants were found in genes encoding lysine-specific histone methyltransferase SETD2 and SETDB1 and genes encoding subunits of the mSWI/SNF chromatin remodeling complex. The complete scenario of the genetic background consisting of pathogenic germline variants required for the predisposition and GxE for pathogenesis of mesothelioma appears complex, and further large-scale studies are warranted.}, }
@article {pmid32206570, year = {2020}, author = {Carbone, M and Gazdar, A and Butel, JS}, title = {SV40 and human mesothelioma.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S47-S59}, pmid = {32206570}, issn = {2218-6751}, abstract = {Simian virus 40 (SV40) is a DNA tumor virus capable of infecting and transforming human mesothelial (HM) cells in vitro. Hamsters injected intracardially to expose most tissue types to SV40 preferentially develop mesotheliomas. In humans, asbestos is the main cause of mesothelioma, and asbestos and SV40 are co-carcinogens in transforming HM cells in tissue culture and in causing mesothelioma in hamsters. Laser microdissection experiments conducted in the laboratory of Adi Gazdar demonstrated that SV40 was present specifically in the malignant mesothelioma cells and not in nearby stromal cells. Further experiments demonstrated that SV40 remains episomal in HM cells and astrocytes because of the production of a long antisense RNA that represses viral capsid protein production. Thus, the potent SV40 oncoprotein, T-antigen (Tag), is expressed, but because the capsid proteins are not produced, the cells are not lysed and, instead, become transformed. Together this evidence suggests that SV40 may contribute to the development of mesotheliomas in humans. However, epidemiological evidence to support this hypothesis is lacking. This chapter also summarizes the introduction of SV40, a monkey virus, into the human population as an unrecognized contaminant of early poliovaccines. In addition to mesotheliomas, SV40 now is linked with brain cancers, osteosarcomas, and lymphomas in humans. Explanations are provided for the apparent geographic variations in SV40 prevalence and for controversies about the role of SV40 in human cancer.}, }
@article {pmid32206569, year = {2020}, author = {Gaudino, G and Xue, J and Yang, H}, title = {How asbestos and other fibers cause mesothelioma.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S39-S46}, pmid = {32206569}, issn = {2218-6751}, abstract = {Mesothelioma has long been associated with the exposure to asbestos, which was largely used in manufacturing activities. Toxicology studies in vitro and in vivo demonstrated that asbestos fibers were carcinogenic, and epidemiology studies revealed that asbestos exposure was paralleled by the increase in the incidence of mesothelioma and related mortality rates. More recently, the role of chronic inflammation and the molecular mechanisms involved in carcinogenesis by mineral fibers were elucidated following the discovery of the roles of HMGB1 and inflammasome. A change of paradigm was the discovery of a prevalence of mesotheliomas attributable to inherited mutations of cancer susceptibility genes. The discovery of BAP1 as a predisposition gene for the development of familial mesothelioma and other cancers implemented genome studies in patients with mesothelioma and routine clinical surveys in individuals at risk to identify germline mutations associated with cancers included in the BAP1 syndrome. A further progress in the approach to asbestos-related malignancy was the adoption of combined genetics and environmental analyses according to the model of gene-environment (GxE) interactions. This review aims at updating on the most recently discovered mechanisms of tumorigenesis and the pivotal role of GxE interactions.}, }
@article {pmid32206568, year = {2020}, author = {Alpert, N and van Gerwen, M and Taioli, E}, title = {Epidemiology of mesothelioma in the 21st century in Europe and the United States, 40 years after restricted/banned asbestos use.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S28-S38}, pmid = {32206568}, issn = {2218-6751}, abstract = {Research has established a strong association between asbestos exposure and malignant mesothelioma, a deadly form of cancer. Since the early 1980's many countries have restricted or banned the production of asbestos, leading to a decline of occupational asbestos exposure in many industrialized countries. However, some countries continue to use asbestos, and worldwide rates of mesothelioma are still increasing. Because of the long latency between exposure and mesothelioma occurrence and the persistence of environmental exposure, incidence rates (IR) may decrease very slowly for several years ahead. In this review, we examine estimates of asbestos consumption before widespread asbestos regulations and the trends in incidence and mortality rates, as well as changes over time for the United States and Europe. In some countries with earlier asbestos restrictions, mesothelioma incidence has been in a modest decline over time. However, asbestos exposure is still a burden worldwide and legislative action is needed to obtain a full ban. The pattern of mesothelioma is shifting from a mostly male disease to a disease that affects females as well in substantial numbers. Studies on unknown sources of asbestos exposure, of other sources of natural exposure to asbestos and asbestos-like fibers, as well as of individual genetic susceptibility to asbestos fibers are needed.}, }
@article {pmid32206566, year = {2020}, author = {Carbone, M}, title = {This special volume of mesothelioma is dedicated to my friend Adi Gazdar.}, journal = {Translational lung cancer research}, volume = {9}, number = {Suppl 1}, pages = {S1-S2}, doi = {10.21037/tlcr.2020.01.15}, pmid = {32206566}, issn = {2218-6751}, }
@article {pmid32187018, year = {2020}, author = {Goricar, K and Kovac, V and Dodic-Fikfak, M and Dolzan, V and Franko, A}, title = {Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {54}, number = {1}, pages = {86-95}, pmid = {32187018}, issn = {1581-3207}, abstract = {Background Asbestos exposure is associated with increased risk of several diseases, including malignant mesothelioma (MM). Cell surface glycoprotein mesothelin is overexpressed in MM and serum soluble mesothelin-related peptides (SMRP) were already proposed as a diagnostic or prognostic biomarker in MM. However, interindividual variability in serum SMRP levels limits the clinical usefulness. Our primary objective was to investigate the influence of MSLN rs1057147 on serum SMRP levels in asbestos-exposed subjects and patients with asbestos-related diseases as well as on survival in MM. Subjects and methods Among 782 asbestos-exposed subjects and patients with asbestos-related diseases, 154 had MM. Serum SMRP levels were determined using sandwich enzyme-linked immunosorbent assay. All subjects were genotyped for MSLN rs1057147 polymorphism using competitive allele-specific polymerase chain reaction. Nonparametric tests, logistic and Cox regression were used in statistical analysis to compare different subject groups. Results MM patients had significantly higher SMRP levels than all other subjects (p < 0.001). Compared to wild-type MSLN rs1057147 genotype, both heterozygotes and carriers of two polymorphic alleles had significantly higher SMRP levels among subjects without MM (p < 0.001), but not in MM patients (p = 0.424). If genotype information was included, specificity of SMRP increased from 88.5% to 92.7% for the optimal cutoff value. Overall survival was significantly shorter in MM patients carrying at least one polymorphic rs1057147 allele (HR = 1.72, 95% CI = 1.15-2.55, p = 0.008). Conclusions MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of MM patients. Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients.}, }
@article {pmid32183600, year = {2020}, author = {Funahashi, S and Okazaki, Y and Akatsuka, S and Takahashi, T and Sakumi, K and Nakabeppu, Y and Toyokuni, S}, title = {Mth1 deficiency provides longer survival upon intraperitoneal crocidolite injection in female mice.}, journal = {Free radical research}, volume = {54}, number = {2-3}, pages = {195-205}, doi = {10.1080/10715762.2020.1743285}, pmid = {32183600}, issn = {1029-2470}, mesh = {Animals ; Asbestos, Crocidolite/*adverse effects/*metabolism ; DNA Repair Enzymes/*deficiency ; Female ; Injections, Intraperitoneal/*methods ; Mice ; Phosphoric Monoester Hydrolases/*deficiency ; }, abstract = {Exposure to asbestos fiber is central to mesothelial carcinogenesis. Recent sequencing studies on human and rodent malignant mesothelioma (MM) revealed frequently mutated genes, including CDKN2A, BAP1 and NF2. Crocidolite directly or indirectly catalyses the generation of hydroxyl radicals, which appears to be the major driving force for mesothelial mutations. DNA base modification is an oxidative DNA damage mechanism, where 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the most abundant modification both physiologically and pathologically. Multiple distinct mechanisms work together to decrease the genomic level of 8-OHdG through the enzymatic activities of Mutyh, Ogg1 and Mth1. Knockout of one or multiple enzymes is not lethal but increases the incidence of tumors. Here, we used single knockout (KO) mice to test whether the deficiency of these three genes affects the incidence and prognosis of asbestos-induced MM. Intraperitoneal injection of 3 mg crocidolite induced MM at a fraction of 14.8% (4/27) in Mth1 KO, 41.4% (12/29) in Mutyh KO and 24.0% (6/25) in Ogg1 KO mice, whereas 31.7% (20/63) induction was observed in C57BL/6 wild-type (Wt) mice. The lifespan of female Mth1 KO mice was longer than that of female Wt mice (p = 0.0468). Whole genome scanning of MM with array-based comparative genomic hybridization revealed rare genomic alterations compared to MM in rats and humans. These results indicate that neither Mutyh deficiency nor Ogg1 deficiency promotes crocidolite-induced MM in mice, but the sanitizing nucleotide pool with Mth1 is advantageous in crocidolite-induced mesothelial carcinogenesis.}, }
@article {pmid32183579, year = {2020}, author = {Roggli, VL and Carney, JM and Sporn, TA and Pavlisko, EN}, title = {Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation.}, journal = {Ultrastructural pathology}, volume = {44}, number = {2}, pages = {211-218}, doi = {10.1080/01913123.2020.1737286}, pmid = {32183579}, issn = {1521-0758}, abstract = {Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients. Asbestos bodies were counted by light microscopy and mineral fiber concentrations for fibers 5 µm or greater in length were determined by scanning electron microscopy equipped with an energy dispersive spectrometer. The values were compared with 20 previously published controls. Among 609 patients with mesothelioma, talc fibers were detected in 375 (62%) and exceeded our control values in 65 (11%). Elevated talc levels were found in 48/524 men (9.2%) and 17/85 women (20%). Parietal pleural plaques were identified in 30/51 informative cases (59%) and asbestosis in 5/62 informative cases (8%). Commercial amphiboles (amosite and/or crocidolite) were elevated in 52/65 (80%) and noncommercial amphiboles (tremolite, actinolite or anthophyllite) in 41/65 (63%). Both were elevated in 34/65 (52%). Asbestos body counts by light microscopy were elevated in 53/64 informative cases (83%). A history of working in industries associated with asbestos exposure and increased mesothelioma risk was identified in 36/48 cases in men, and a history of exposure as household contacts of an occupationally exposed individual was identified in 12/17 cases in women. We conclude that among patients with mesothelioma, the vast majority have talc levels indistinguishable from background. Of the remaining 11% with elevated talc levels, the vast majority (80%) have elevated levels of commercial amphibole fibers.}, }
@article {pmid32175619, year = {2020}, author = {Emory, TS and Maddox, JC and Kradin, RL}, title = {Malignant mesothelioma following repeated exposures to cosmetic talc: A case series of 75 patients.}, journal = {American journal of industrial medicine}, volume = {63}, number = {6}, pages = {484-489}, pmid = {32175619}, issn = {1097-0274}, abstract = {BACKGROUND: Asbestos is the primary known cause of malignant mesothelioma. Some cosmetic talc products have been shown to contain asbestos. Recently, repeated exposures to cosmetic talc have been implicated as a cause of mesothelioma.<br><br>METHODS: Seventy-five individuals (64 females; 11 males) with malignant mesothelioma, whose only known exposure to asbestos was repeated exposures to cosmetic talcum powders, were reviewed in medical-legal consultation. Out of the 75 cases, 11 were examined for asbestiform fibers.<br><br>RESULTS: All subjects had pathologically confirmed malignant mesothelioma. The mean age at diagnosis was 61 ± 17 years. The mean latency from exposure to diagnosis was 50 ± 13 years. The mean exposure duration was 33 ± 16 years. Four mesotheliomas (5%) occurred in individuals working as barbers/cosmetologists, or in a family member who swept the barber shop. Twelve (16%) occurred in individuals less than 45 years old (10 females; 2 males). Forty-eight mesotheliomas were pleural (40 females; 8 males), 23 were peritoneal (21 females; 2 males). Two presented with concomitant pleural and peritoneal disease. There was one pericardial, and one testicular mesothelioma. The majority (51) were of the epithelioid histological subtype, followed by 13 biphasic, 8 sarcomatoid, 2 lymphohistiocytoid, and 1 poorly differentiated. Of the 11 individuals whose nontumorous tissues were analyzed for the presence of asbestiform fibers, all showed the presence of anthophyllite and/or tremolite asbestos.<br><br>CONCLUSIONS: Mesotheliomas can develop following exposures to cosmetic talcum powders. These appear to be attributable to the presence of anthophyllite and tremolite contaminants in cosmetic talcum powder.}, }
@article {pmid32169964, year = {2020}, author = {Napolitano, A and Antoine, DJ and Pellegrini, L and Baumann, F and Pagano, I and Pastorino, S and Goparaju, CM and Prokrym, K and Canino, C and Pass, HI and Carbone, M and Yang, H}, title = {Expression of Concern: HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {26}, number = {6}, pages = {1529}, doi = {10.1158/1078-0432.CCR-20-0338}, pmid = {32169964}, issn = {1557-3265}, }
@article {pmid32156681, year = {2020}, author = {Viscardi, G and Di Liello, R and Morgillo, F}, title = {How I treat malignant pleural mesothelioma.}, journal = {ESMO open}, volume = {4}, number = {Suppl 2}, pages = {}, pmid = {32156681}, issn = {2059-7029}, mesh = {Humans ; Lung Neoplasms/*pathology/*therapy ; Mesothelioma/*pathology/*therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*therapy ; }, abstract = {Malignant pleural mesothelioma is a rare and aggressive malignancy mostly associated with occupational asbestos exposure. Prognosis is poor and only highly selected patients may benefit from aggressive surgical management, also as part of a multimodal approach. In advanced disease, the combination of pemetrexed and platinum remains the only established treatment, while efficacy evidence of second line chemotherapy is lacking. Thus, a deeper knowledge of biology of the disease and more effective treatments are urgently needed. Refer to specialised centres with multidisciplinary expertise is mandatory, as well as inclusion of patients in clinical trials is advisable whenever possible. In all stages of disease focus on symptoms control is paramount.}, }
@article {pmid32142836, year = {2020}, author = {Paajanen, J and Laaksonen, S and Kettunen, E and Ilonen, I and Vehmas, T and Salo, J and Räsänen, J and Sutinen, E and Ollila, H and Mäyränpää, MI and Myllärniemi, M and Wolff, H}, title = {Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival.}, journal = {Human pathology}, volume = {98}, number = {}, pages = {110-119}, doi = {10.1016/j.humpath.2020.02.007}, pmid = {32142836}, issn = {1532-8392}, mesh = {Epithelioid Cells/*pathology ; Female ; Humans ; Lung Neoplasms/mortality/*pathology/surgery ; Male ; Mesothelioma/mortality/*pathology/surgery ; Mesothelioma, Malignant ; Necrosis ; Neoplasm Grading ; Pleural Neoplasms/mortality/*pathology/surgery ; Time Factors ; Treatment Outcome ; }, abstract = {Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, wherein the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. To study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival more than five years (LTSs) and compared the findings with 84 tumors from a reference group (RG) with average survival. We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n = 34, 90%) and a tubulopapillary growth pattern (n = 30, 70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n = 49, 61%) and solid growth pattern (n = 59, 70%) were more frequent in the RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (P < 0.001) and the presence of necrosis (P = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival: exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (P < 0.001) and presence of exophytic polypoid growth (P = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis.}, }
@article {pmid32133285, year = {2020}, author = {Nowak, AK and Brosseau, S and Cook, A and Zalcman, G}, title = {Antiangiogeneic Strategies in Mesothelioma.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {126}, pmid = {32133285}, issn = {2234-943X}, abstract = {There is a strong rationale for inhibiting angiogenesis in mesothelioma. Vascular endothelial growth factor (VEGF) is an autocrine growth factor in mesothelioma and a potent mitogen for mesothelial cells. Further, the abnormal tumor vasculature promotes raised interstitial pressure and hypoxia, which may be detrimental to both penetration and efficacy of anticancer agents. Antiangiogenic agents have been trialed in mesothelioma for close to two decades, with early phase clinical trials testing vascular targeting agents, the VEGF-A targeting monoclonal antibody bevacizumab, and numerous tyrosine kinase inhibitors, many with multiple targets. None of these have shown efficacy which has warranted further development as single agents in any line of therapy. Whilst a randomized phase II trial combining the multitargeted tyrosine kinase inhibitor nintedanib with platinum/pemetrexed chemotherapy was positive, these results were not confirmed in a subsequent phase III study. The combination of cisplatin and pemetrexed with bevacizumab, in appropriately selected patients, remains the only anti-angiogenic combination showing efficacy in mesothelioma. Extensive efforts to identify biomarkers of response have not yet been successful.}, }
@article {pmid32123850, year = {2019}, author = {Fan, X and McLaughlin, C and Robinson, C and Ravasini, J and Schelch, K and Johnson, T and van Zandwijk, N and Reid, G and George, AM}, title = {Zeolites ameliorate asbestos toxicity in a transgenic model of malignant mesothelioma.}, journal = {FASEB bioAdvances}, volume = {1}, number = {9}, pages = {550-560}, pmid = {32123850}, issn = {2573-9832}, abstract = {Malignant mesothelioma (MM) is an almost invariably fatal cancer caused by asbestos exposure. The toxicity of asbestos fibers is related to their physicochemical properties and the generation of free radicals. We set up a pilot study to investigate the potential of the zeolite clinoptilolite to counteract the asbestos carcinogenesis by preventing the generation of reactive nitrogen and oxygen radicals. In cell culture experiments, clinoptilolite prevented asbestos-induced cell death, reactive oxygen species production, DNA degradation, and overexpression of genes known to be up-regulated by asbestos. In an asbestos-induced transgenic mouse model of MM, mice were injected intraperitoneal injections with blue asbestos, with or without clinoptilolite, and monitored for 30 weeks. By the end of the trial all 13 mice injected with asbestos alone had reached humane end points, whereas only 7 of 29 mice receiving crocidolite and clinoptilolite reached a similar stage of disease. Post-mortem examination revealed pinpoint mesothelioma-like tumors in affected mice, and the absence of tumor formation in surviving mice. Interestingly, the macrophage clearance system, which was largely suppressed in asbestos-treated mice, exhibited evidence of increased phagocytosis in mice treated with asbestos and clinoptilolite. Our study suggests that inhibiting the asbestos-induced generation of reactive oxygen species and stimulating the macrophage system may represent a pathway to amelioration of asbestos-induced toxicity. Additional studies are warranted to explore the underlying mechanisms responsible for our observations.}, }
@article {pmid32117755, year = {2020}, author = {Reid, G and Johnson, TG and van Zandwijk, N}, title = {Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {105}, pmid = {32117755}, issn = {2234-943X}, abstract = {microRNAs (miRNAs) are an important class of non-coding RNA that post-transcriptionally regulate the expression of most protein-coding genes. Their aberrant expression in tumors contributes to each of the hallmarks of cancer. In malignant pleural mesothelioma (MPM), in common with other tumor types, changes in miRNA expression are characterized by a global downregulation, although elevated levels of some miRNAs are also found. While an increasing number of miRNAs exhibit altered expression in MPM, relatively few have been functionally characterized. Of a growing number with tumor suppressor activity in vitro, miR-16, miR-193a, and miR-215 were also shown to have tumor suppressor activity in vivo. In the case of miR-16, the significant inhibitory effects on tumor growth following targeted delivery of miR-16-based mimics in a xenograft model was the basis for a successful phase I clinical trial. More recently overexpressed miRNAs with oncogenic activity have been described. Many of these changes in miRNA expression are related to the characteristic loss of tumor suppressor pathways in MPM tumors. In this review we will highlight the studies providing evidence for therapeutic effects of modulating microRNA levels in MPM, and discuss these results in the context of emerging approaches to miRNA-based therapy.}, }
@article {pmid32117751, year = {2020}, author = {Testa, JR and Berns, A}, title = {Preclinical Models of Malignant Mesothelioma.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {101}, pmid = {32117751}, issn = {2234-943X}, abstract = {Rodent models of malignant mesothelioma help facilitate the understanding of the biology of this highly lethal cancer and to develop and test new interventions. Introducing the same genetic lesions as found in human mesothelioma in mice results in tumors that show close resemblance with the human disease counterpart. This includes the extensive inflammatory responses that characterize human malignant mesothelioma. The relatively fast development of mesothelioma in mice when the appropriate combination of lesions is introduced, with or without exposure to asbestos, make the autochthonous models particularly useful for testing new treatment strategies in an immunocompetent setting, whereas Patient-Derived Xenograft models are particularly useful to assess effects of inter- and intra-tumor heterogeneity and human-specific features of mesothelioma. It is to be expected that new insights obtained by studying these experimental systems will lead to new more effective treatments for this devastating disease.}, }
@article {pmid32114955, year = {2020}, author = {Kim, K and Ko, Y and Oh, H and Ha, M and Kang, J and Kwon, EJ and Kang, JW and Kim, Y and Heo, HJ and Kim, G and Kim, JW and Kim, YH}, title = {MicroRNA-98 is a prognostic factor for asbestos-induced mesothelioma.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {83}, number = {3}, pages = {126-134}, doi = {10.1080/15287394.2020.1734891}, pmid = {32114955}, issn = {1528-7394}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor ; Carcinogens/*toxicity ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Mesothelioma/chemically induced/*diagnosis ; MicroRNAs/genetics/*metabolism ; Middle Aged ; }, abstract = {Malignant pleural mesothelioma (MPM) is a type of cancer characterized by a short survival time and poor prognosis. Malignant pleural mesothelioma is most frequently associated with exposure to asbestos and other elongated mineral fibers. The aim of this study was to examine molecular differences between asbestos-exposed and non-exposed MPM patients and assess prognostic significances of molecular factors. Clinical and genetic data were downloaded from Cancer Genome Atlas. To identify the molecular differences, Significant Analysis of Microarray method was used. Prognostic significances of differentially expressed genes were confirmed by using Kaplan-Meier curve with the Log-Rank test. Although mRNAs did not exhibit any significant differences between the two patient groups, nine miRNAs were found to be down-regulated in the asbestos-exposed group. The top five pathways most relevant to the selected miRNAs were extracted through pathway enrichment analysis. Survival analysis revealed that high expression of only hsa-miR-98 was significantly associated with poor prognosis in patients with asbestos-exposed MPM. Evidence suggests that management of the aggressiveness and progression of asbestos-induced MPM may require high levels of hsa-miR-98 due to its tumor-suppressive role. This study might be helpful in enhancing our understanding of the biological mechanisms underlying asbestos-induced MPM and for acquiring greater insights into targeted therapy.Abbreviations: FDR: false discovery rate; MM: malignant mesothelioma; MPM: malignant pleural mesothelioma; mRNA: messenger RNA; miRNA: microRNA; SAM: significance analysis of microarrays; TCGA: the cancer genome atlas.}, }
@article {pmid32106829, year = {2020}, author = {Drevinskaite, M and Patasius, A and Kevlicius, L and Mickys, U and Smailyte, G}, title = {Malignant mesothelioma of the tunica vaginalis testis: a rare case and review of literature.}, journal = {BMC cancer}, volume = {20}, number = {1}, pages = {162}, pmid = {32106829}, issn = {1471-2407}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Biopsy ; Cisplatin/therapeutic use ; Deoxycytidine/analogs &amp; derivatives/therapeutic use ; Disease Progression ; Fatal Outcome ; Humans ; Lung Neoplasms/complications/*diagnosis/therapy ; Lymphadenopathy ; Male ; Mesothelioma/complications/*diagnosis/therapy ; Mesothelioma, Malignant ; Orchiectomy ; Pemetrexed/therapeutic use ; Prognosis ; Testicular Hydrocele/etiology/*surgery ; Testicular Neoplasms/complications/*diagnosis/therapy ; }, abstract = {BACKGROUND: Malignant mesothelioma of the tunica vaginalis is a rare tumour which comprises less than 1% of all mesotheliomas.<br><br>CASE PRESENTATION: 69-years old patient with painful hard mass and hydrocele in the right scrotum to whom a right hydrocelectomy was performed. Any history of scrotal trauma or exposure to asbestos was not present. Excisional biopsy revealed a multinodular tumour with focal areas of necrosis and infiltrative growth. According to morphological and immunohistochemical findings, diagnosis of malignant biphasic mesothelioma of the tunica vaginalis testis was made. Two months after hydrocelectomy, right inguinal orchidectomy was performed. Post-surgical whole body CT scan revealed paraaortic and pararenal lymphadenopathy, likely to be metastatic. Adjuvant treatment with 6 cycles of cisplatin and pemetrexed was applied. After 3 cycles of chemotherapy, CT scan showed progression and the treatment was changed to gemcitabine 1 month after.<br><br>CONCLUSIONS: Although malignant mesothelioma of the tunica vaginalis is a rare malignancy, it poses a diagnostic challenge which can mimic common inguinal or scrotal diseases such as hydrocele. Despite aggressive surgical procedures or adjuvant therapies, the prognosis remains poor.}, }
@article {pmid32083805, year = {2020}, author = {Quetel, L and Meiller, C and Assié, JB and Blum, Y and Imbeaud, S and Montagne, F and Tranchant, R and de Wolf, J and Caruso, S and Copin, MC and Hofman, V and Gibault, L and Badoual, C and Pintilie, E and Hofman, P and Monnet, I and Scherpereel, A and Le Pimpec-Barthes, F and Zucman-Rossi, J and Jaurand, MC and Jean, D}, title = {Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival.}, journal = {Molecular oncology}, volume = {14}, number = {6}, pages = {1207-1223}, pmid = {32083805}, issn = {1878-0261}, abstract = {Development of precision medicine for malignant pleural mesothelioma (MPM) requires a deep knowledge of tumor heterogeneity. Histologic and molecular classifications and histo-molecular gradients have been proposed to describe heterogeneity, but a deeper understanding of gene mutations in the context of MPM heterogeneity is required and the associations between mutations and clinical data need to be refined. We characterized genetic alterations on one of the largest MPM series (266 tumor samples), well annotated with histologic, molecular and clinical data of patients. Targeted next-generation sequencing was performed focusing on the major MPM mutated genes and the TERT promoter. Molecular heterogeneity was characterized using predictors allowing classification of each tumor into the previously described molecular subtypes and the determination of the proportion of epithelioid-like and sarcomatoid-like components (E/S.scores). The mutation frequencies are consistent with literature data, but this study emphasized that TERT promoter, not considered by previous large sequencing studies, was the third locus most affected by mutations in MPM. Mutations in TERT promoter, NF2, and LATS2 were more frequent in nonepithelioid MPM and positively associated with the S.score. BAP1, NF2, TERT promoter, TP53, and SETD2 mutations were enriched in some molecular subtypes. NF2 mutation rate was higher in asbestos unexposed patient. TERT promoter, NF2, and TP53 mutations were associated with a poorer overall survival. Our findings lead to a better characterization of MPM heterogeneity by identifying new significant associations between mutational status and histologic and molecular heterogeneity. Strikingly, we highlight the strong association between new mutations and overall survival.}, }
@article {pmid32082887, year = {2019}, author = {Döngel, İ and Akbaş, A and Benli, İ and Bayram, M}, title = {Comparison of serum biochemical markers in patients with mesothelioma and pleural plaques versus healthy individuals exposed to environmental asbestos.}, journal = {Turk gogus kalp damar cerrahisi dergisi}, volume = {27}, number = {3}, pages = {374-380}, pmid = {32082887}, issn = {1301-5680}, abstract = {Background: In this study, we aimed to compare serum biochemical markers in patients with malignant pleural mesothelioma and pleural plaques versus healthy individuals exposed to environmental asbestos.<br><br>Methods: Between September 01, 2010 and March 31, 2011, a total of 540 participants (354 males, 186 females; mean age 61.4 years; range, 35 to 89 years) were included in the study. The participants were divided into four groups as follows: (1) patients with pleural plaques (n=277); (2) healthy individuals with normal chest X-rays who were exposed to environmental asbestos (n=121); (3) healthy individuals with normal chest X-rays who were not exposed to environmental asbestos (n=118); and (4) patients with malignant pleural mesothelioma (n=24). Serum levels of carcinoembryonic antigen, cancer antigen 125, 15-3, 19-9, free T3, free T4, thyroidstimulating hormone, vitamin B12, folate, and ferritin were measured.<br><br>Results: Serum cancer antigen 125, 15-3, folic acid, vitamin B12, and ferritin levels were higher with lower free T3 levels in Group 4 than the other groups. The areas under the curve for cancer antigen 125 and 15-3 were 0.78 and 0.67, respectively in the differential diagnosis of mesothelioma from other pathologies (p<0.001 for both). Optimal limits of these biomarkers were 13.63 and 18.43 ng/mL, respectively with 83% and 75% sensitivity and 69% and 48% specificity, respectively.<br><br>Conclusion: The combination or individual use of serum cancer antigen 125, 15-3, folic acid, vitamin B12, and ferritin levels may be helpful for early diagnosis and treatment of malignant pleural mesothelioma.}, }
@article {pmid32081346, year = {2020}, author = {Sinha, S and Swift, AJ and Kamil, MA and Matthews, S and Bull, MJ and Fisher, P and De Fonseka, D and Saha, S and Edwards, JG and Johns, CS}, title = {The role of imaging in malignant pleural mesothelioma: an update after the 2018 BTS guidelines.}, journal = {Clinical radiology}, volume = {75}, number = {6}, pages = {423-432}, doi = {10.1016/j.crad.2019.12.001}, pmid = {32081346}, issn = {1365-229X}, mesh = {Diagnostic Imaging/*standards ; Early Detection of Cancer ; Humans ; Mesothelioma, Malignant/*diagnostic imaging/pathology ; Neoplasm Staging ; Pleural Neoplasms/*diagnostic imaging/pathology ; *Practice Guidelines as Topic ; Societies, Medical ; }, abstract = {Malignant pleural mesothelioma (MPM) is a primary malignancy of the pleura and is associated with a poor outcome. The symptoms and signs of malignant mesothelioma present late in the natural history of the disease and are non-specific, making the diagnosis challenging and imaging key. In 2018, the British Thoracic Society (BTS) updated the guideline on diagnosis, staging, and follow-up of patients with MPM. These recommendations are discussed in this review of the current literature on imaging of MPM. It is estimated MPM will continue to cause serious morbidity and mortality in the UK late into the 21st century, and internationally, people continue to be exposed to asbestos. We aim to update the reader on current and future imaging strategies, which could aid early diagnosis of pleural malignancy and provide an update on staging and assessment of tumour response.}, }
@article {pmid32080953, year = {2020}, author = {Okazaki, Y and Misawa, N and Akatsuka, S and Kohyama, N and Sekido, Y and Takahashi, T and Toyokuni, S}, title = {Frequent homozygous deletion of Cdkn2a/2b in tremolite-induced malignant mesothelioma in rats.}, journal = {Cancer science}, volume = {111}, number = {4}, pages = {1180-1192}, pmid = {32080953}, issn = {1349-7006}, support = {JP17H04064 and JP19H05462//Japan Society for the Promotion of Science/ ; JP25860292//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Comparative Genomic Hybridization ; Cyclin-Dependent Kinase Inhibitor p15/*genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; Homozygote ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Rats ; Risk Factors ; Sequence Deletion/genetics ; }, abstract = {The onset of malignant mesothelioma (MM) is linked to exposure to asbestos fibers. Asbestos fibers are classified as serpentine (chrysotile) or amphibole, which includes the crocidolite, amosite, anthophyllite, tremolite, and actinolite types. Although few studies have been undertaken, anthophyllite has been shown to be associated with mesothelioma, and tremolite, a contaminant in talc and chrysotile, is a risk factor for carcinogenicity. Here, after characterizing the length and width of these fibers by scanning electron microscopy, we explored the cytotoxicity induced by tremolite and anthophyllite in cells from an immortalized human mesothelial cell line (MeT5A), murine macrophages (RAW264.7), and in a rat model. Tremolite and short anthophyllite fibers were phagocytosed and localized to vacuoles, whereas the long anthophyllite fibers were caught on the pseudopod of the MeT5A and Raw 264.7 cells, according to transmission electron microscopy. The results from a 2-day time-lapse study revealed that tremolite was engulfed and damaged the MeT5A and RAW264.7 cells, but anthophyllite was not cytotoxic to these cells. Intraperitoneal injection of tremolite in rats induced diffuse serosal thickening, whereas anthophyllite formed focal fibrosis and granulomas on peritoneal serosal surfaces. Furthermore, the loss of Cdkn2a/2b, which are the most frequently lost foci in human MM, were observed in 8 cases of rat MM (homozygous deletion [5/8] and loss of heterozygosity [3/8]) by array-based comparative genomic hybridization techniques. These results indicate that tremolite initiates mesothelial injury and persistently frustrates phagocytes, causing subsequent peritoneal fibrosis and MM. The possible mechanisms of carcinogenicity based on fiber diameter/length are discussed.}, }
@article {pmid32077824, year = {2020}, author = {Loreto, C and Lombardo, C and Caltabiano, R and Ledda, C and Hagnas, M and Filetti, V and Rapisarda, V}, title = {An In vivo Immunohistochemical Study on MacroH2A.1 in Lung and Lymph-Node Tissues Exposed to an Asbestiform Fiber.}, journal = {Current molecular medicine}, volume = {20}, number = {8}, pages = {653-660}, doi = {10.2174/1566524020666200220130023}, pmid = {32077824}, issn = {1875-5666}, abstract = {AIMS: The aim of this study was to investigate MacroH2A.1 immunoexpression in tissues of sheep exposed to FE.<br><br>BACKGROUND: The correlation between asbestiform fibers, lung cancer, pleural mesothelioma, and other lung diseases is already well established as the pathophisiological pathophysiological respiratory mechanisms involved by inhalation of Fluoro-edenite (FE). The latter is represented by cell proliferation and inducing the release of growth factors, cytokines, and reactive oxygen and nitrite species, with DNA damage that causes chronic inflammation and carcinogenesis. MacroH2A.1, and histone variant, seems to play a role in sensing the metabolic state of the cell and linking it with chromatin. Physiologically, MacroH2A.1 is expressed at low levels in stem cells and it became upregulated during differentiation, preventing reprogramming of induced pluripotent stem cells and after nuclear transfer. In particular, MacroH2A.1 has been shown to explicate a potent antitumor mechanism in vivo as it results upregulated in senescent cells determining a permanent growth-arrest.<br><br>OBJECTIVE: Evaluate the possible role of the histone variant in the organism in response to deep insight understanding the mechanisms of toxicity and the cellular response to FE.<br><br>METHODS: Lung and lymph nodes of exposed sheep were selected. Samples were processed for histological and immunihistochemical immunohistochemical evaluations. Densitometric, morphometric, and statistical analysis analyses were conducted.<br><br>RESULTS: Tissue sections of FE exposed sheep demonstrated overexpression of MacroH2A.1 vs unexposed samples. The data suggest an involvement of these this molecule in the cellular response triggered by FE directed exposure.<br><br>CONCLUSION: In this contest, MacroH2A.1 overexpression supports its function as an epigenetic stabilizer that helps to establish and maintain differentiated states.}, }
@article {pmid32065212, year = {2020}, author = {Barbieri, PG and Somigliana, A and Chen, Y and Consonni, D and Vignola, R and Finotto, L}, title = {Lung Asbestos Fibre Burden and Pleural Mesothelioma in Women with Non-occupational Exposure.}, journal = {Annals of work exposures and health}, volume = {64}, number = {3}, pages = {297-310}, doi = {10.1093/annweh/wxaa009}, pmid = {32065212}, issn = {2398-7316}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) due to environmental and familial (domestic) asbestos exposure is well recognized. However, information on cumulative asbestos dose in subjects affected by MPM is limited.<br><br>OBJECTIVES: To evaluate the residual lung asbestos fibre and asbestos body burden in women with MPM with past environmental and/or familial asbestos exposure.<br><br>METHODS: We collected lung samples from autopsies regarding 15 non-occupationally asbestos-exposed MPM cases, divided in three groups: (i) familial exposure from the Fincantieri shipyards in Monfalcone (No. 7), (ii) environmental and familial asbestos exposure from the asbestos-cement plant Fibronit in Broni (No. 6), and (iii) environmental exposure from the Fibronit plant (No. 2). Asbestos body (AB) and fibres (AF) per gram of dry lung tissue were counted by optical and scanning electron microscopy, respectively, and expressed as geometric means and standard deviations (GM, GSD).<br><br>RESULTS: GM/GSD of AB counts were 6123/9.6 (Group 1), 13 800/10.4 (Group 2), and 8400/1.1 (Group 3); GM/GSD of AF were 0.6/2.1 (Group 1), 7.9/2.1 (Group 2), and 6.0/2.3 (Group 3) million. Pleural plaques were observed in 12 cases.<br><br>CONCLUSIONS: Exclusive familial exposure to asbestos determined cumulative doses close to those observed in moderate occupational exposure circumstances. Our results also suggest that combined environmental and familial exposures may cause unexpectedly high cumulative fibre doses.}, }
@article {pmid32054819, year = {2020}, author = {, }, title = {Global and regional burden of cancer in 2016 arising from occupational exposure to selected carcinogens: a systematic analysis for the Global Burden of Disease Study 2016.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {3}, pages = {151-159}, pmid = {32054819}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Carcinogens ; Disabled Persons/statistics &amp; numerical data ; Female ; Global Burden of Disease/*statistics &amp; numerical data/*trends ; Global Health/statistics &amp; numerical data/trends ; Humans ; *Life Expectancy ; Lung Neoplasms/mortality ; Male ; Mesothelioma ; Mesothelioma, Malignant ; Middle Aged ; Neoplasms/*epidemiology/mortality ; Occupational Diseases/epidemiology ; Occupational Exposure/adverse effects/*statistics &amp; numerical data ; Quality-Adjusted Life Years ; Risk Assessment ; Risk Factors ; Sex Distribution ; Socioeconomic Factors ; Young Adult ; }, abstract = {OBJECTIVES: This study provides a detailed analysis of the global and regional burden of cancer due to occupational carcinogens from the Global Burden of Disease 2016 study.<br><br>METHODS: The burden of cancer due to 14 International Agency for Research on Cancer Group 1 occupational carcinogens was estimated using the population attributable fraction, based on past population exposure prevalence and relative risks from the literature. The results were used to calculate attributable deaths and disability-adjusted life years (DALYs).<br><br>RESULTS: There were an estimated 349 000 (95% Uncertainty Interval 269 000 to 427 000) deaths and 7.2 (5.8 to 8.6) million DALYs in 2016 due to exposure to the included occupational carcinogens-3.9% (3.2% to 4.6%) of all cancer deaths and 3.4% (2.7% to 4.0%) of all cancer DALYs; 79% of deaths were of males and 88% were of people aged 55 -79 years. Lung cancer accounted for 86% of the deaths, mesothelioma for 7.9% and laryngeal cancer for 2.1%. Asbestos was responsible for the largest number of deaths due to occupational carcinogens (63%); other important risk factors were secondhand smoke (14%), silica (14%) and diesel engine exhaust (5%). The highest mortality rates were in high-income regions, largely due to asbestos-related cancers, whereas in other regions cancer deaths from secondhand smoke, silica and diesel engine exhaust were more prominent. From 1990 to 2016, there was a decrease in the rate for deaths (-10%) and DALYs (-15%) due to exposure to occupational carcinogens.<br><br>CONCLUSIONS: Work-related carcinogens are responsible for considerable disease burden worldwide. The results provide guidance for prevention and control initiatives.}, }
@article {pmid32050546, year = {2020}, author = {Töreyin, ZN and Ghosh, M and Göksel, Ö and Göksel, T and Godderis, L}, title = {Exhaled Breath Analysis in Diagnosis of Malignant Pleural Mesothelioma: Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {3}, pages = {}, pmid = {32050546}, issn = {1660-4601}, mesh = {*Asbestos ; *Biomarkers, Tumor/analysis ; *Breath Tests ; Exhalation ; Humans ; *Mesothelioma/diagnosis ; Prospective Studies ; *Volatile Organic Compounds ; }, abstract = {Malignant pleural mesothelioma (MPM) is mainly related to previous asbestos exposure. There is still dearth of information on non-invasive biomarkers to detect MPM at early stages. Human studies on exhaled breath biomarkers of cancer and asbestos-related diseases show encouraging results. The aim of this systematic review was to provide an overview on the current knowledge about exhaled breath analysis in MPM diagnosis. A systematic review was conducted on MEDLINE (PubMed), EMBASE and Web of Science databases to identify relevant studies. Quality assessment was done by the Newcastle-Ottawa Scale. Six studies were identified, all of which showed fair quality and explored volatile organic compounds (VOC) based breath profile using Gas Chromatography Coupled to Mass Spectrometry (GC-MS), Ion Mobility Spectrometry Coupled to Multi-capillary Columns (IMS-MCC) or pattern-recognition technologies. Sample sizes varied between 39 and 330. Some compounds (i.e, cyclohexane, P3, P5, P50, P71, diethyl ether, limonene, nonanal, VOC IK 1287) that can be indicative of MPM development in asbestos exposed population were identified with high diagnostic accuracy rates. E-nose studies reported breathprints being able to distinguish MPM from asbestos exposed individuals with high sensitivity and a negative predictive value. Small sample sizes and methodological diversities among studies limit the translation of results into clinical practice. More prospective studies with standardized methodologies should be conducted on larger populations.}, }
@article {pmid32050285, year = {2020}, author = {Habbel, VSA and Mahler, EA and Feyerabend, B and Oldhafer, KJ and Lipp, MJ}, title = {[Diffuse malignant peritoneal mesothelioma (DMPM) - a rare diagnosis].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {58}, number = {2}, pages = {146-151}, doi = {10.1055/a-1083-6962}, pmid = {32050285}, issn = {1439-7803}, mesh = {Antineoplastic Agents/*administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols ; Combined Modality Therapy ; *Cytoreduction Surgical Procedures/methods ; Female ; Humans ; Hyperthermia, Induced/*methods ; Male ; Mesothelioma/drug therapy/mortality/surgery/*therapy ; Peritoneal Neoplasms/drug therapy/mortality/surgery/*therapy ; Prognosis ; Survival Rate ; }, abstract = {Diffuse malignant peritoneal mesothelioma (DMPM) is a rare diagnosis, found more frequently in men than in women. Symptoms are unspecific abdominal disorders making that diagnosis difficult to set. Causes of DMPM are yet to be discovered in entirety. Asbestos exposure is the reason for approximately 7 % of all peritoneal mesotheliomas. Until the evaluation of systematic cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) DMPM was a fatal diagnosis with a median overall survival (OS) of 4-13 months. The prognosis of DMPM dramatically improved with implementation of CRS and HIPEC to an OS of 30-92 month nowadys. CRS and HIPEC were performed in this case.}, }
@article {pmid32050148, year = {2020}, author = {Singh, R and Cherrie, JW and Rao, B and Asolekar, SR}, title = {Assessment of the future mesothelioma disease burden from past exposure to asbestos in ship recycling yards in India.}, journal = {International journal of hygiene and environmental health}, volume = {225}, number = {}, pages = {113478}, doi = {10.1016/j.ijheh.2020.113478}, pmid = {32050148}, issn = {1618-131X}, mesh = {Adult ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Humans ; India ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Recycling ; *Ships ; Young Adult ; }, abstract = {The recycling of end-of-life vessels is a complex activity that generates an enormous amount of hazardous waste, including asbestos-containing materials (ACM). Efforts by the Government of India to comply with national and international regulations and improved standard operating procedures are expected to lower the exposure risk of the workforce to hazardous substances, including asbestos. The current workers are likely to face lesser risks than did those exposed in the past. The present study assesses the health risks from past exposure of asbestos for those workers engaged in handling and removing ACM in ship recycling yards before environmentally sound recycling of obsolete ships was introduced in the early 2000s. Estimates were made of the number of workers exposed, and the intensity of exposure and these data were used to estimate the likely number of mesothelioma deaths in the future. It was estimated that nearly 15% of the total workforce engaged in ship recycling will suffer from mesothelioma which translates to about 4,513 mesothelioma deaths among the total of 31,000 workers estimated to be ever employed in the yards from 1994 till 2002. Recommendations are made for a practical approach to the safe handling of ACMs in Indian ship recycling yards.}, }
@article {pmid32041759, year = {2020}, author = {Ahmed, ST and Barvo, M and Kamath, N and Alweis, R}, title = {Acute popliteal thrombus workup leads to discovery of primary peritoneal mesothelioma in the absence of any known asbestos exposure.}, journal = {BMJ case reports}, volume = {13}, number = {2}, pages = {}, doi = {10.1136/bcr-2019-232812}, pmid = {32041759}, issn = {1757-790X}, mesh = {Abdomen/diagnostic imaging ; Aged ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos ; Ascites/diagnostic imaging ; Biopsy, Large-Core Needle ; Carboplatin/therapeutic use ; Diagnosis, Differential ; Emergency Service, Hospital ; Humans ; Lung Neoplasms/*diagnosis/drug therapy ; Male ; Mesothelioma/*diagnosis/drug therapy ; Mesothelioma, Malignant ; Pelvis/diagnostic imaging ; Pemetrexed/therapeutic use ; Peritoneal Neoplasms/*diagnosis/drug therapy ; Popliteal Artery/surgery ; Positron Emission Tomography Computed Tomography ; Thrombosis/surgery ; }, abstract = {A 75-year-old man presented to the emergency department with 1-day history of right lower limb pain and 3-month history of vague abdominal pain. In the emergency department a thrombus was discovered in the right popliteal artery. CT scan of the abdomen and pelvis revealed high-density material in the pelvis, multiple hypodensities on the liver, ascites with omental nodularity, and high-density material along the stomach wall. He underwent thrombectomy and was started on anticoagulation therapy. The core needle biopsy revealed primary omental mesothelioma. There was no history of any known asbestos exposure. He also had to undergo therapeutic paracentesis twice due to abdominal distension. Mesothelioma treatment of carboplatin and pemetrexed was started, and the patient is currently receiving this chemotherapy treatment regimen.}, }
@article {pmid32041124, year = {2020}, author = {Airoldi, C and Ferrante, D and Miligi, L and Piro, S and Stoppa, G and Migliore, E and Chellini, E and Romanelli, A and Sciacchitano, C and Mensi, C and Cavone, D and Romeo, E and Massari, S and Marinaccio, A and Magnani, C}, title = {Estimation of Occupational Exposure to Asbestos in Italy by the Linkage of Mesothelioma Registry (ReNaM) and National Insurance Archives. Methodology and Results.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {3}, pages = {}, pmid = {32041124}, issn = {1660-4601}, mesh = {Asbestos/*adverse effects ; Humans ; Industry ; Italy ; Mesothelioma/*chemically induced ; National Health Programs ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {The identification and monitoring of occupational cancer is an important aspect of occupational health protection. The Italian law on the protection of workers (D. Leg. 81/2008) includes different cancer monitoring systems for high and low etiologic fraction tumors. Record linkage between cancer registries and administrative data is a convenient procedure for occupational cancer monitoring. We aim to: (i) Create a list of industries with asbestos exposure and (ii) identify cancer cases who worked in these industries. The Italian National Mesothelioma Registry (ReNaM) includes information on occupational asbestos exposure of malignant mesothelioma (MM) cases. We developed using data from seven Italian regions a methodology for listing the industries with potential exposure to asbestos linking ReNaM to Italian National Social Security Institute (INPS) data. The methodology is iterative and adjusts for imprecision and inaccuracy in reporting firm names at interview. The list of asbestos exposing firms was applied to the list of cancer cases (all types associated or possibly associated with asbestos according to International Agency for Research on Cancer (IARC) monograph 100C) in two Italian regions for the indication of possible asbestos exposure. Eighteen percent of the cancer cases showed at least one work period in firms potentially exposing to asbestos, 48% of which in regions different from where the cases lived at diagnosis. The methodology offers support for the preliminary screening of asbestos exposing firms in the occupational history of cancer cases.}, }
@article {pmid32040984, year = {2020}, author = {Wylie, AG and Korchevskiy, A and Segrave, AM and Duane, A}, title = {Modeling mesothelioma risk factors from amphibole fiber dimensionality: mineralogical and epidemiological perspective.}, journal = {Journal of applied toxicology : JAT}, volume = {40}, number = {4}, pages = {515-524}, doi = {10.1002/jat.3923}, pmid = {32040984}, issn = {1099-1263}, abstract = {Amphiboles are common rock-forming minerals but when they form asbestos, they are known carcinogens. Mesothelioma mortality among miners and millers per the unit of asbestiform amphibole exposure varies significantly across cohorts when asbestos exposure measurements are based on the membrane filter method. Because the cohorts were exposed to different occurrences of asbestiform amphibole, variance in mesothelioma potency (RM) among cohorts is likely due to differences in exposure characteristics not reflected by the membrane filter method. In this paper using both linear and nonlinear models we correlate RM from four mining and milling cohorts with two-dimensional parameters of the exposure. The parameters are based on the proportion of elongated minerals that are >5 μm in length from each occurrence that also have either (a) width ≤ 0.15 μm, or (b) width ≤ 0.25 μm. Based on the models we derived, it was possible to quantify RM for the occurrences of asbestiform amphibole associated with mesothelioma excess but for which epidemiologically based RM has not been published. It was demonstrated that modeled RM for amphibole occurrences in nonasbestiform habits are lower (fibrous glaucophane) or not significant (cleavage fragments). The results of the study can be used in a risk assessment of elongated mineral particles and have implications for public policy and regulations.}, }
@article {pmid32039010, year = {2019}, author = {Nicolini, F and Bocchini, M and Bronte, G and Delmonte, A and Guidoboni, M and Crinò, L and Mazza, M}, title = {Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1519}, pmid = {32039010}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CAR-T cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and on-going clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management.}, }
@article {pmid32035500, year = {2020}, author = {Pais, A and Pinto, N and Cardoso, J and Fernandes, M and Coutinho, AI and Oliveira, AS and Carvalho, L and Bárbara, C}, title = {[Diffuse Intraparenchymal Mesothelioma: An Atypical Presentation].}, journal = {Acta medica portuguesa}, volume = {33}, number = {2}, pages = {143-146}, doi = {10.20344/amp.11406}, pmid = {32035500}, issn = {1646-0758}, mesh = {Asbestosis/*diagnosis ; Diagnosis, Differential ; Humans ; Male ; Mesothelioma, Malignant/*diagnosis ; Middle Aged ; Occupational Diseases/*diagnosis ; Pleural Neoplasms/*diagnosis ; }, abstract = {Pleural mesothelioma is a disease associated with exposure to asbestos. Although rare, it is the most common malignant pleural neoplasm. It is difficult to diagnose and it has a poor prognosis. We report the case of a 62-year-old male patient with a history of prolonged occupational exposure to asbestos, with dyspnea for minor exertion and productive cough, for several months. Imaging studies revealed extensive interstitial involvement with marked thickening of the interlobular and centrilobular septa and tenuous pleural involvement. Several differential diagnoses were considered such as, asbestosis, cryptogenic organizing pneumonia, desquamative interstitial pneumonia, pleuropulmonary metastases, and/or bronchopulmonary infection, but the histological and immunohistochemical results were compatible with pleural mesothelioma - a rare malignant neoplasm, with pleural origin, with a high mortality rate.}, }
@article {pmid32033249, year = {2020}, author = {Aoki, K and Saito, N}, title = {Biocompatibility and Carcinogenicity of Carbon Nanotubes as Biomaterials.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {32033249}, issn = {2079-4991}, abstract = {With the development of nanotechnology in recent years, there have been concerns about the health effects of nanoparticles. Carbon nanotubes (CNTs) are fibrous nanoparticles with a micro-sized length and nano-sized diameter, which exhibit excellent physical properties and are widely studied for their potential application in medicine. However, asbestos has been historically shown to cause pleural malignant mesothelioma and lung cancer by inhalation exposure. Because carbon nanotubes are also fibrous nanotubes, some have raised concerns about its possible carcinogenicity. We have reported that there is no clear evidence of carcinogenicity by local and intravenous administration of multi-walled CNTs to cancer mice models. We firmly believe that CNTs can be a safe, new, and high-performance biomaterials by controlling its type, site of administration, and dosage.}, }
@article {pmid32021524, year = {2020}, author = {Cheng, YY and Rath, EM and Linton, A and Yuen, ML and Takahashi, K and Lee, K}, title = {The Current Understanding Of Asbestos-Induced Epigenetic Changes Associated With Lung Cancer.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {11}, number = {}, pages = {1-11}, pmid = {32021524}, issn = {1179-2728}, abstract = {Asbestos is a naturally occurring mineral consisting of extremely fine fibres that can become trapped in the lungs after inhalation. Occupational and environmental exposures to asbestos are linked to development of lung cancer and malignant mesothelioma, a cancer of the lining surrounding the lung. This review discusses the factors that are making asbestos-induced lung cancer a continuing problem, including the extensive historic use of asbestos and decades long latency between exposure and disease development. Genomic mutations of DNA nucleotides and gene rearrangements driving lung cancer are well-studied, with biomarkers and targeted therapies already in clinical use for some of these mutations. The genes involved in these mutation biomarkers and targeted therapies are also involved in epigenetic mechanisms and are discussed in this review as it is hoped that identification of epigenetic aberrations in these genes will enable the same gene biomarkers and targeted therapies to be used. Currently, understanding of how asbestos fibres trapped in the lungs leads to epigenetic changes and lung cancer is incomplete. It has been shown that oxidoreduction reactions on fibre surfaces generate reactive oxygen species (ROS) which in turn damage DNA, leading to genetic and epigenetic alterations that reduce the activity of tumour suppressor genes. Epigenetic DNA methylation changes associated with lung cancer are summarised in this review, and some of these changes will be due to asbestos exposure. So far, little research has been carried out to separate the asbestos driven epigenetic changes from those due to non-asbestos causes of lung cancer. Asbestos-associated lung cancers exhibit less methylation variability than lung cancers in general, and in a large proportion of samples variability has been found to be restricted to promoter regions. Epigenetic aberrations in cancer are proving to be promising biomarkers for diagnosing cancers. It is hoped that further understanding of epigenetic changes in lung cancer can result in useful asbestos-associated lung cancer biomarkers to guide treatment. Research is ongoing into the detection of lung cancer epigenetic alterations using non-invasive samples of blood and sputum. These efforts hold the promise of non-invasive cancer diagnosis in the future. Efforts to reverse epigenetic aberrations in lung cancer by epigenetic therapies are ongoing but have not yet yielded success.}, }
@article {pmid32006662, year = {2020}, author = {Gaetani, S and Monaco, F and Alessandrini, F and Tagliabracci, A and Sabbatini, A and Bracci, M and Valentino, M and Neuzil, J and Amati, M and Santarelli, L and Tomasetti, M}, title = {Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {121}, number = {}, pages = {105700}, doi = {10.1016/j.biocel.2020.105700}, pmid = {32006662}, issn = {1878-5875}, mesh = {Aged ; Asbestos/*adverse effects ; Carcinogens/*chemistry ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; MicroRNAs/*metabolism ; }, abstract = {MiR-222 and miR-126 are associated with asbestos exposure and the ensuing malignancy, but the mechanism(s) of their regulation remain unclear. We evaluated the mechanism by which asbestos regulates miR-222 and miR-126 expression in the context of cancer etiology. An 'in vitro' model of carcinogen-induced cell transformation was used based on exposing bronchial epithelium BEAS-2B cells to three different carcinogens including asbestos. Involvement of the EGFR pathway and the role of epigenetics have been investigated in carcinogen-transformed cells and in malignant mesothelioma, a neoplastic disease associated with asbestos exposure. Increased expression of miR-222 and miR-126 were found in asbestos-transformed cells, but not in cells exposed to arsenic and chrome. Asbestos-mediated activation of the EGFR pathway and macrophages-induced inflammation resulted in miR-222 upregulation, which was reversed by EGFR inhibition. Conversely, asbestos-induced miR-126 expression was affected neither by EGFR modulation nor inflammation. Rather than methylation of the miR-126 host gene EGFL7, epigenetic mechanism involving DNMT1- and PARP1-mediated chromatin remodeling was found to upregulate of miR-126 in asbestos-exposed cells, while miR-126 was downregulated in malignant cells. Analysis of MM tissue supported the role of PARP1 in miR-126 regulation. Therefore, activation of the EGFR pathway and the PARP1-mediated epigenetic regulation both play a role in asbestos-induced miRNA expression, associated with in asbestos-induced carcinogenesis and tumor progression.}, }
@article {pmid32005436, year = {2020}, author = {Fels Elliott, DR and Jones, KD}, title = {Diagnosis of Mesothelioma.}, journal = {Surgical pathology clinics}, volume = {13}, number = {1}, pages = {73-89}, doi = {10.1016/j.path.2019.10.001}, pmid = {32005436}, issn = {1875-9157}, mesh = {Biopsy ; Humans ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/*diagnosis/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Mesothelioma/*diagnosis/diagnostic imaging/pathology ; Radiography ; Tomography, X-Ray Computed ; }, abstract = {Mesothelioma is a rare neoplasm that arises from mesothelial cells lining body cavities including the pleura, pericardium, peritoneum, and tunica vaginalis. Most malignant mesotheliomas occur in the chest and are frequently associated with a history of asbestos exposure. The diagnosis of malignant mesothelioma is challenging and fraught with pitfalls, particularly in small biopsies. This article highlights what the pathologist needs to know regarding the clinical and radiographic presentation of mesothelioma, histologic features including subtypes and variants, and recent advances in immunohistochemical markers and molecular testing.}, }
@article {pmid32002299, year = {2020}, author = {Ma, S and Chee, J and Fear, VS and Forbes, CA and Boon, L and Dick, IM and Robinson, BWS and Creaney, J}, title = {Pre-treatment tumor neo-antigen responses in draining lymph nodes are infrequent but predict checkpoint blockade therapy outcome.}, journal = {Oncoimmunology}, volume = {9}, number = {1}, pages = {1684714}, pmid = {32002299}, issn = {2162-4011}, abstract = {Immune checkpoint blockade (ICPB) is a powerfully effective cancer therapy in some patients. Tumor neo-antigens are likely main targets for attack but it is not clear which and how many tumor mutations in individual cancers are actually antigenic, with or without ICPB therapy and their role as neo-antigen vaccines or as predictors of ICPB responses. To examine this, we interrogated the immune response to tumor neo-antigens in a murine model in which the tumor is induced by a natural human carcinogen (i.e. asbestos) and mimics its human counterpart (i.e. mesothelioma). We identified and screened 33 candidate neo-antigens, and found T cell responses against one candidate in tumor-bearing animals, mutant UQCRC2. Interestingly, we found a high degree of inter-animal variation in the magnitude of neo-antigen responses in otherwise identical mice. ICPB therapy with Cytotoxic T-lymphocyte-associated protein (CTLA-4) and α-glucocorticoid-induced TNFR family related gene (GITR) in doses that induced tumor regression, increased the magnitude of responses and unmasked functional T cell responses against another neo-antigen, UNC45a. Importantly, the magnitude of the pre-treatment draining lymph node (dLN) response to UNC45a closely corresponded to ICPB therapy outcomes. Surprisingly however, boosting pre-treatment UNC45a-specific T cell numbers did not improve response rates to ICPB. These observations suggest a novel biomarker approach to the clinical prediction of ICPB response and have important implications for the development of neo-antigen vaccines.}, }
@article {pmid32002298, year = {2020}, author = {Sneddon, S and Rive, CM and Ma, S and Dick, IM and Allcock, RJN and Brown, SD and Holt, RA and Watson, M and Leary, S and Lee, YCG and Robinson, BWS and Creaney, J}, title = {Identification of a CD8+ T-cell response to a predicted neoantigen in malignant mesothelioma.}, journal = {Oncoimmunology}, volume = {9}, number = {1}, pages = {1684713}, pmid = {32002298}, issn = {2162-4011}, abstract = {Neoantigens present unique and specific targets for personalized cancer immunotherapy strategies. Given the low mutational burden yet immunotherapy responsiveness of malignant mesothelioma (MM) when compared to other carcinogen-induced malignancies, identifying candidate neoantigens and T cells that recognize them has been a challenge. We used pleural effusions to gain access to MM tumor cells as well as immune cells in order to characterize the tumor-immune interface in MM. We characterized the landscape of potential neoantigens from SNVs identified in 27 MM patients and performed whole transcriptome sequencing of cell populations from 18 patient-matched pleural effusions. IFNγ ELISpot was performed to detect a CD8+ T cell responses to predicted neoantigens in one patient. We detected a median of 68 (range 7-258) predicted neoantigens across the samples. Wild-type non-binding to mutant binding predicted neoantigens increased risk of death in a model adjusting for age, sex, smoking status, histology and treatment (HR: 33.22, CI: 2.55-433.02, p = .007). Gene expression analysis indicated a dynamic immune environment within the pleural effusions. TCR clonotypes increased with predicted neoantigen burden. A strong activated CD8+ T-cell response was identified for a predicted neoantigen produced by a spontaneous mutation in the ROBO3 gene. Despite the challenges associated with the identification of bonafide neoantigens, there is growing evidence that these molecular changes can provide an actionable target for personalized therapeutics in difficult to treat cancers. Our findings support the existence of candidate neoantigens in MM despite the low mutation burden of the tumor, and may present improved treatment opportunities for patients.}, }
@article {pmid31977466, year = {2020}, author = {Fernández-Rodríguez, P and Martín-Marcuartu, JJ and Acevedo Báñez, I and Masero Carretero, JM and Jiménez-Hoyuela García, JM}, title = {99mTc-HDP Bone Scintigraphy, SPECT/CT, and 18F-FDG PET/CT Diagnosis Imaging of Incidental Pleural Mesothelioma in a Patient With Biochemical Recurrences of Prostate Cancer: Is it Really a Coincidence?.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {3}, pages = {e148-e150}, doi = {10.1097/RLU.0000000000002908}, pmid = {31977466}, issn = {1536-0229}, mesh = {Aged ; Diphosphonates ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/complications/*diagnostic imaging ; Male ; Mesothelioma/complications/*diagnostic imaging ; Mesothelioma, Malignant ; Organotechnetium Compounds ; Pleural Neoplasms/complications/*diagnostic imaging ; *Positron Emission Tomography Computed Tomography ; Prostatic Neoplasms/blood/*complications ; Radiopharmaceuticals ; *Single Photon Emission Computed Tomography Computed Tomography ; }, abstract = {We present the case of a 69-year-old man with history of prostate carcinoma treated with prostatectomy and subsequently with external beam radiotherapy and hormone therapy because of biochemical recurrences. More than 10 years after the diagnosis, follow-up Tc-HDP bone scans and SPECT/CT images demonstrated an incidental diagnosis of osteoblastic pleural plaques that quickly evolve to mesothelioma. PET/CT achieved the definitive diagnosis by guiding the biopsy to the highest and most accessible focus of glucidic hypermetabolism. Our case report raises the association between prostate cancer patients treated with external beam radiotherapy and the development of pleural mesothelioma despite having no history of exposure to asbestos.}, }
@article {pmid31967100, year = {2019}, author = {Vimercati, L and Cavone, D and Mansi, F and Cannone, ESS and DE Maria, L and Caputi, A and Delfino, MC and Serio, G}, title = {Health impact of exposure to asbestos in polluted area of Southern Italy.}, journal = {Journal of preventive medicine and hygiene}, volume = {60}, number = {4}, pages = {E407-E418}, pmid = {31967100}, issn = {2421-4248}, mesh = {*Asbestos ; Asbestosis/epidemiology/*mortality ; Cardiovascular Diseases/mortality ; Cause of Death ; *Environmental Exposure ; *Environmental Pollution ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/mortality ; Mesothelioma/epidemiology/*mortality ; Neoplasms/epidemiology/mortality ; *Occupational Exposure ; Peritoneal Neoplasms/epidemiology/mortality ; Personal Protective Equipment ; Pleural Neoplasms/epidemiology/*mortality ; }, abstract = {The three main sources of asbestos pollution in the city of Bari, Puglia, the former Fibronit asbestos factory, the Torre Quetta beach, the former Rossani barracks and the history of their reclamation are described. The results of cohort studies on factory workers and case-control studies on asbestos exposure to the resident population and the onset of mesothelioma are also reported. Finally, the data of the regional register of mesothelioma related to residents in the city of Bari and four new cases with environmental exposure due to the former Rossani barracks are presented.}, }
@article {pmid31965908, year = {2019}, author = {Peterson, MK and Mohar, I and Lam, T and Cook, TJ and Engel, AM and Lynch, H}, title = {Critical review of the evidence for a causal association between exposure to asbestos and esophageal cancer.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {7}, pages = {597-613}, doi = {10.1080/10408444.2019.1692190}, pmid = {31965908}, issn = {1547-6898}, mesh = {Animals ; *Asbestos ; Environmental Exposure/*statistics &amp; numerical data ; Esophageal Neoplasms/*epidemiology ; *Hazardous Substances ; Humans ; }, abstract = {Esophageal cancers comprise about 1% of all cancers diagnosed in the US but are more prevalent in other regions of the world. Several regulatory agencies have classified asbestos as a known human carcinogen, and it is linked to multiple diseases and malignancies, including lung cancer and mesothelioma. In a 2006 review of the epidemiological literature, the Institute of Medicine (IOM) did not find sufficient evidence to demonstrate a causal relationship between asbestos exposure and esophageal cancer. To reevaluate this conclusion, we performed a critical review of the animal toxicological, epidemiological, and mechanism of action literature on esophageal cancer and asbestos, incorporating studies published since 2006. Although there is some evidence in the epidemiological literature for an increased risk of esophageal cancer in asbestos-exposed occupational cohorts, these studies generally did not control for critical esophageal cancer risk factors (e.g. smoking, alcohol consumption). Furthermore, data from animal toxicological studies do not indicate that asbestos exposure increases esophageal cancer risk. Based on our evaluation of the literature, and reaffirming the IOM's findings, we conclude that there is insufficient evidence to demonstrate a causal link between asbestos exposure and esophageal cancer.}, }
@article {pmid31963601, year = {2020}, author = {Oddone, E and Bollon, J and Nava, CR and Bugani, M and Consonni, D and Marinaccio, A and Magnani, C and Barone-Adesi, F}, title = {Predictions of Mortality from Pleural Mesothelioma in Italy After the Ban of Asbestos Use.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {2}, pages = {}, pmid = {31963601}, issn = {1660-4601}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Epidemics/*statistics &amp; numerical data ; Female ; Forecasting ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Middle Aged ; }, abstract = {Even if the epidemic of malignant pleural mesothelioma (MPM) is still far from being over worldwide, the health effects of regulations banning asbestos can be evaluated in the countries that implemented them early. Estimates of MPM future burden can be useful to inform and support the implementation of anti-asbestos health policies all around the world. With this aim we described the trends of MPM deaths in Italy (1970-2014) and predicted the future number of cases in both sexes (2015-2039), with consideration of the national asbestos ban that was issued in 1992. The Italian National Statistical Institute (ISTAT) provided MPM mortality figures. Cases ranging from 25 to 89 years of age were included in the analysis. For each five-year period from 1970 to 2014, mortality rates were calculated and age-period-cohort Poisson models were used to predict future burden of MPM cases until 2039. During the period 1970-2014 a total number of 28,907 MPM deaths were observed. MPM deaths increased constantly over the study period, ranging from 1356 cases in 1970-1974 to 5844 cases in 2010-2014. The peak of MPM cases is expected to be reached in the period 2020-2024 (about 7000 cases). The decrease will be slow: about 26,000 MPM cases are expected to occur in Italy during the next 20 years (2020-2039). The MPM epidemic in Italy is far from being concluded despite the national ban implemented in 1992, and the peak is expected in 2020-2024, in both sexes. Our results are consistent with international literature.}, }
@article {pmid31929796, year = {2019}, author = {Borchert, S and Suckrau, PM and Wessolly, M and Mairinger, E and Hegedus, B and Hager, T and Herold, T and Eberhardt, WEE and Wohlschlaeger, J and Aigner, C and Bankfalvi, A and Schmid, KW and Walter, RFH and Mairinger, FD}, title = {Screening of Pleural Mesothelioma Cell Lines for Kinase Activity May Identify New Mechanisms of Therapy Resistance in Patients Receiving Platin-Based Chemotherapy.}, journal = {Journal of oncology}, volume = {2019}, number = {}, pages = {2902985}, pmid = {31929796}, issn = {1687-8450}, abstract = {Background: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumor associated with a dismal prognosis. Multimodal therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons underlying the rather poor efficacy of platinum compounds remain largely unknown. Kinase activity might influence cellular response to these regimens.<br><br>Materials and Methods: For this exploratory study, we screened MPM cell lines (NCI-H2452, NCI-H2052, and MSTO-211H) differing in response to cisplatin and benign control fibroblasts (MRC-5) for overall phosphorylation patterns as well as kinase activity with respect to cellular response to cisplatin-based therapeutics. We analysed the cell lines for cellular kinases in a high-throughput manner using the highly innovative technique PamGene. Cell state analysis including apoptosis, necrosis, and cell viability was performed by using enzyme activity and fluorescent-based assays.<br><br>Results: Cisplatin alters cellular phosphorylation patterns affecting cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis. In cisplatin-responsive cell lines, phosphorylation of AKT1 and GSK3B was decreased but could not be influenced in cisplatin-resistant NCI-H2452 cells. Cisplatin-responsive cell lines showed increased phosphorylation levels of JNK1/2/3 but decreased phosphorylation in cisplatin-resistant NCI-H2452 cells.<br><br>Conclusion: Kinase phosphorylation and activity might play a crucial role in cellular response to cytostatic agents. Cisplatin influences phosphorylation patterns with distinct features in cisplatin-resistant cells. These alterations exert a significant impact on cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis of the respective tumor cells. Based on our results, the induction of p38 or JNK1/3, or inhibition of AKT1 by, for example, BIA-6, might offer a positive synergistic effect by induction of an apoptotic response to cisplatin-based treatment, thus potentially enhancing the clinical outcome of MPM patients.}, }
@article {pmid31927297, year = {2020}, author = {Cox, LA}, title = {Nonlinear dose-time-response functions and health-protective exposure limits for inflammation-mediated diseases.}, journal = {Environmental research}, volume = {182}, number = {}, pages = {109026}, doi = {10.1016/j.envres.2019.109026}, pmid = {31927297}, issn = {1096-0953}, mesh = {*Asbestos/toxicity ; Humans ; Inflammation ; Inhalation Exposure ; *Mesothelioma ; *Occupational Exposure ; *Occupational Health ; *Silicon Dioxide/toxicity ; Threshold Limit Values ; United States ; }, abstract = {Why have occupational safety regulations in the United States not been more successful in protecting worker health from mesothelioma risks, while apparently succeeding relatively well in reducing silicosis risks? This paper briefly discusses biological bases for thresholds and nonlinearities in exposure-response functions for respirable crystalline silica (RCS) and asbestos, based on modeling a chronic inflammation mode of action (mediated by activation of the NLRP3 inflammasome, for both RCS and asbestos). It applies previously published physiologically based pharmacokinetic (PBPK) models to perform computational experiments illuminating how different time courses of exposure with the same time-weighted average (TWA) concentration affect internal doses in target tissues (lung for RCS and mesothelium for asbestos). Key conclusions are that (i) For RCS, but not asbestos, limiting average (TWA) exposure concentrations also tightly constrains internal doses and ability to trigger chronic inflammation and resulting increases in disease risks (ii) For asbestos, excursions (i.e., spikes in concentrations); and especially the times between them are crucial drivers of internal doses and time until chronic inflammation; and hence (iii) These dynamic aspects of exposure, which are not addressed by current occupational safety regulations, should be constrained to better protect worker health. Adjusting permissible average exposure concentration limits (PELs) and daily excursion limits (ELs) is predicted to have little impact on reducing mesothelioma risks, but increasing the number of days between successive excursions is predicted to be relatively effective in reducing worker risks, even if it has little or no impact on TWA average concentrations.}, }
@article {pmid31921422, year = {2020}, author = {Kim, MK and Kim, HW and Jang, M and Oh, SS and Yong, SJ and Jeong, Y and Jung, SH and Choi, JW}, title = {LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma.}, journal = {Biomarker research}, volume = {8}, number = {}, pages = {1}, pmid = {31921422}, issn = {2050-7771}, abstract = {Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database.<br><br>Methods: Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction.<br><br>Results: We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&amp;2 (LOXL1&amp; LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11).<br><br>Conclusions: LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities.}, }
@article {pmid31917456, year = {2020}, author = {Ugelvig Petersen, K and Pukkala, E and Martinsen, JI and Lynge, E and Tryggvadottir, L and Weiderpass, E and Kjærheim, K and Heikkinen, S and Hansen, J}, title = {Cancer incidence among seafarers and fishermen in the Nordic countries.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {46}, number = {5}, pages = {461-468}, doi = {10.5271/sjweh.3879}, pmid = {31917456}, issn = {1795-990X}, abstract = {Objectives Maritime workers may be exposed to several occupational hazards at sea. The aim of this study was to assess cancer incidence among seafarers and fishermen in the Nordic countries and identify patterns in morbidity in the context of existing studies in this field. Methods A cohort of 81 740 male seafarers and 66 926 male fishermen was established from census data on 15 million citizens in the five Nordic countries. Using personal identity codes, information on vital status and cancer was linked to members of the cohort from the national population and cancer registries for the follow-up period 1961-2005. Standardized incidence ratios (SIR) were calculated applying national cancer incidence rates for each country and pooling results. Results The overall incidence of cancer was increased among the male seafarers [SIR 1.22, 95% confidence interval (CI) 1.19-1.23]. Significant excesses were observed for multiple cancer sites among the seafarers, while results for the fishermen were mixed. Lip cancer incidence was increased among both maritime populations. For mesothelioma (SIR 2.17, 95% CI 1.83-2.56 seafarers) and non-melanoma skin cancer (SIR 1.23, 95% CI 1.14-1.32 seafarers), incidence was increased among the seafarers. Conclusion In our cohort, seafaring was associated with a higher overall incidence of cancer compared to the general population. While the majority of cancers could not be linked to specific occupational factors, increases in mesothelioma, lip and non-melanoma-skin cancer indicate previous exposure to asbestos, ultraviolet radiation and potentially also chemicals with dermal carcinogenic properties at sea.}, }
@article {pmid31916469, year = {2020}, author = {Dodson, RF and Poye, LW}, title = {Tissue burden evaluation of elongated mineral particles in two individuals with mesothelioma and whose work history included manufacturing tile.}, journal = {Ultrastructural pathology}, volume = {44}, number = {1}, pages = {17-31}, doi = {10.1080/01913123.2019.1709935}, pmid = {31916469}, issn = {1521-0758}, mesh = {Asbestos, Amphibole/adverse effects/*analysis ; Humans ; Male ; Mesothelioma, Malignant/*etiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology ; Talc/adverse effects/*agonists ; }, abstract = {Two cases with diagnosis of mesothelioma were referred to our laboratories with a request for tissue burden analysis in order to determine the presence of ferruginous bodies and uncoated elongated mineral particles in tissue samples. The individuals shared in common a past background of working in tile manufacturing facilities where industrial talc was used in the production of the products. Both were found to have ferruginous bodies in their lung tissues as well as elongated talc fibers/ribbons and elevated numbers of noncommercial amphiboles in their tissues. To our knowledge, this is the first report of tissue assessment for the presence of elongated mineral particles in individuals whose exposures to talc occurred were while working in the manufacture of tile products and who developed the fiber-related cancer - mesothelioma.}, }
@article {pmid31905913, year = {2019}, author = {Klebe, S and Leigh, J and Henderson, DW and Nurminen, M}, title = {Asbestos, Smoking and Lung Cancer: An Update.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {1}, pages = {}, pmid = {31905913}, issn = {1660-4601}, mesh = {Animals ; Asbestos/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Occupational Exposure ; Tobacco Smoking/*adverse effects ; }, abstract = {This review updates the scientific literature concerning asbestos and lung cancer, emphasizing cumulative exposure and synergism between asbestos exposure and tobacco smoke, and proposes an evidence-based and equitable approach to compensation for asbestos-related lung cancer cases. This update is based on several earlier reviews written by the second and third authors on asbestos and lung cancer since 1995. We reevaluated the peer-reviewed epidemiologic studies. In addition, selected in vivo and in vitro animal studies and molecular and cellular studies in humans were included. We conclude that the mechanism of lung cancer causation induced by the interdependent coaction of asbestos fibers and tobacco smoke at a biological level is a multistage stochastic process with both agents acting conjointly at all times. The new knowledge gained through this review provides the evidence for synergism between asbestos exposure and tobacco smoke in lung cancer causation at a biological level. The evaluated statistical data conform best to a multiplicative model for the interaction effects of asbestos and smoking on the lung cancer risk, with no requirement for asbestosis. Any asbestos exposure, even in a heavy smoker, contributes to causation. Based on this information, we propose criteria for the attribution of lung cancer to asbestos in smokers and non-smokers.}, }
@article {pmid31905042, year = {2019}, author = {Cox, LA}, title = {Dose-response modeling of NLRP3 inflammasome-mediated diseases: asbestos, lung cancer, and malignant mesothelioma as examples.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {7}, pages = {614-635}, doi = {10.1080/10408444.2019.1692779}, pmid = {31905042}, issn = {1547-6898}, mesh = {*Asbestos ; Carcinogens, Environmental ; *Dose-Response Relationship, Drug ; Environmental Exposure/*statistics &amp; numerical data ; Humans ; Inflammasomes ; Inflammation ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism ; Risk Assessment ; }, abstract = {Can a single fiber of amphibole asbestos increase the risk of lung cancer or malignant mesothelioma (MM)? Traditional linear no-threshold (LNT) risk assessment assumptions imply that the answer is yes: there is no safe exposure level. This paper draws on recent scientific progress in inflammation biology, especially elucidation of the activation thresholds for NLRP3 inflammasomes and resulting chronic inflammation, to model dose-response relationships for malignant mesothelioma and lung cancer risks caused by asbestos exposures. The modeling integrates a physiologically based pharmacokinetics (PBPK) front end with inflammation-driven two-stage clonal expansion (I-TSCE) models of carcinogenesis to describe how exposure leads to chronic inflammation, which in turn promotes carcinogenesis. Together, the combined PBPK and I-TSCE modeling predict that there are practical thresholds for exposure concentration below which asbestos exposure does not cause chronic inflammation in less than a lifetime, and therefore does not increase chronic inflammation-dependent cancer risks. Quantitative examples using model parameter estimates drawn from the literature suggest that practical thresholds may be within about a factor of 2 of some past exposure levels for some workers. The I-TSCE modeling framework explains previous puzzling aspects of asbestos epidemiology, such as why age at first exposure is a better predictor of lifetime MM risk than exposure duration. It may be a valuable tool for risk analysts when LNT assumptions are not justified due to inflammation response thresholds mediating dose-response relationships.}, }
@article {pmid31904012, year = {2019}, author = {Colin, DJ and Bejuy, O and Germain, S and Triponez, F and Serre-Beinier, V}, title = {Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {154}, pages = {}, doi = {10.3791/60272}, pmid = {31904012}, issn = {1940-087X}, mesh = {Animals ; Cell Line, Tumor ; Cell Proliferation ; Fluorodeoxyglucose F18/chemistry ; Humans ; Lung Neoplasms/*diagnostic imaging/metabolism/pathology ; Mesothelioma/*diagnostic imaging/metabolism/pathology ; Mesothelioma, Malignant ; Mice, Nude ; Organ Size ; Pleural Neoplasms/*diagnostic imaging/metabolism/pathology ; *Positron Emission Tomography Computed Tomography ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor arising in the mesothelium that covers the lungs, the heart, and the thoracic cavity. MPM development is mainly associated with asbestos. Treatments provide only modest survival since the median survival average is 9-18 months from the time of diagnosis. Therefore, more effective treatments must be identified. Most data describing new therapeutic targets were obtained from in vitro experiments and need to be validated in reliable in vivo preclinical models. This article describes one such reliable MPM orthotopic model obtained after injection of a human MPM cell line H2052/484 into the pleural cavity of immunodeficient athymic mice. Transplantation in the orthotopic site allows studying the progression of tumor in the natural in vivo environment. Positron emission tomography/computed tomography (PET/CT) molecular imaging using the clinical [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) radiotracer is the diagnosis method of choice for examining patients with MPM. Accordingly, [18F]FDG-PET/CT was used to longitudinally monitor the disease progression of the H2052/484 orthotopic model. This technique has a high 3R potential (Reduce the number of animals, Refine to lessen pain and discomfort, and Replace animal experimentation with alternatives) since the tumor development can be monitored non-invasively and the number of animals required could be significantly reduced. This model displays a high development rate, a rapid tumor growth, is cost-efficient and allows for rapid clinical translation. By using this orthotopic xenograft MPM model, researchers can assess biological responses of a reliable MPM model following therapeutic interventions.}, }
@article {pmid31901768, year = {2020}, author = {Lam, WS and Creaney, J and Chen, FK and Chin, WL and Muruganandan, S and Arunachalam, S and Attia, MS and Read, C and Murray, K and Millward, M and Spiro, J and Chakera, A and Gary Lee, YC and Nowak, AK}, title = {A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {140}, number = {}, pages = {87-92}, doi = {10.1016/j.lungcan.2019.12.018}, pmid = {31901768}, issn = {1872-8332}, abstract = {OBJECTIVES: Currently, there is no optimal salvage therapy for patients with malignant pleural mesothelioma (MPM) who relapse after treatment with first-line chemotherapy. In line with the strong preclinical rationale for targeting fibroblast growth factor receptor (FGFR) signalling in malignant mesothelioma, we conducted a phase II study assessing the efficacy of AZD4547, an oral tyrosine multi-kinase FGFR 1-3 inhibitor, as a second or third-line treatment.<br><br>MATERIALS AND METHODS: We conducted a single-center, open-label, single-arm phase II study of AZD4547 in eligible patients with confirmed, measurable MPM and radiological progression after first or second-line systemic chemotherapy. Patients received continuous, twice-daily oral AZD4547 on a 3-weekly cycle. The primary end point was 6-month progression free survival (PFS6). Response was assessed with CT scan every 6 weeks according to the modified RECIST criteria for mesothelioma (mRECIST) and toxicities were also assessed. The study used a Simon's two-stage design: 26 patients would be recruited to the first stage and more than 7 (27 %) of 26 patients were required to achieve PFS6 to continue to stage two, for a potential total cohort of 55 patients.<br><br>RESULTS: 3 of 24 patients (12 %) were progression-free at 6 months. Hence, the study fulfilled stopping criteria regardless of further recruitment and warranted discontinuation. The most common toxicities (across all grades) were hyperphosphatemia, xerostomia, mucositis, retinopathy, dysgeusia, and fatigue. Maximum toxicities were grade 2 or below for all patients across all cycles. There was no association between tumour BAP1 protein loss and clinical outcomes.<br><br>CONCLUSIONS: The FGFR 1-3 inhibitor AZD4547 did not demonstrate efficacy in patients with MPM who had progressed after first line treatment with platinum-based chemotherapy.}, }
@article {pmid31900296, year = {2020}, author = {Hinkamp, CA and Dalal, SN and Butt, Y and Cabo Chan, AV}, title = {Diffuse epithelioid malignant mesothelioma of the pleura presenting as a hydropneumothorax and vertebral body invasion.}, journal = {BMJ case reports}, volume = {13}, number = {1}, pages = {}, doi = {10.1136/bcr-2019-231987}, pmid = {31900296}, issn = {1757-790X}, mesh = {Aged ; Asbestos/*adverse effects ; Diagnosis, Differential ; Humans ; Hydropneumothorax/*surgery ; Lung Neoplasms/*therapy ; Male ; Mesothelioma/*therapy ; Mesothelioma, Malignant ; Neoplasm Invasiveness ; Pleural Neoplasms/*therapy ; Thoracic Neoplasms/secondary/*therapy ; }, abstract = {Malignant mesothelioma is an uncommon form of neoplastic transformation of the mesothelial cells that line the serosal surfaces of the body. It most commonly affects the pleura and is often associated with pleural effusions and pleural-based masses. The annual incidence in the United States is only 3300 cases, representing less than 0.3% of all cancers worldwide, although this is likely underestimated. We present a case of diffuse epithelioid malignant pleural mesothelioma in a patient with remote, short-term asbestos exposure complicated by recurrent left-sided hydropneumothoraces and pleural-based invasion of the T12 vertebral body, which represent two rare coexisting complications. This case illustrates the importance of maintaining a broad differential for hydropneumothorax, particularly as the risk factors may be decades removed and the degree of asbestos exposure to induce a malignant mesothelioma may be smaller than has been traditionally thought.}, }
@article {pmid31895128, year = {2020}, author = {Walters, GI}, title = {Occupational exposures and idiopathic pulmonary fibrosis.}, journal = {Current opinion in allergy and clinical immunology}, volume = {20}, number = {2}, pages = {103-111}, doi = {10.1097/ACI.0000000000000610}, pmid = {31895128}, issn = {1473-6322}, abstract = {PURPOSE OF REVIEW: A recent meta-analysis of data from international case-control studies reports a population attributable fraction of 16% for occupational factors in the cause of idiopathic pulmonary fibrosis (IPF). Smoking, genetic factors and other prevalent diseases only partly explain IPF, and so this review aims to summarize recent progress in establishing which occupational exposures are important in cause.<br><br>RECENT FINDINGS: IPF is a rare disease, although it is the commonest idiopathic interstitial pneumonia. Epidemiological study suggests that incidence of IPF is increasing, particularly in older men. There are significant associations with IPF and occupational exposures to organic dust, including livestock, birds and animal feed, metal dust, wood dust and silica/minerals. Estimates of effect vary between studies, and are influenced by the distribution of employment, study design and case definition. Inhalation of asbestos fibres is a known cause of usual interstitial pneumonia (as seen histologically in IPF), though there are significant linear relationships between asbestos consumption, and mortality from both IPF and mesothelioma, leading to the hypothesis that low-level asbestos exposure may cause IPF.<br><br>SUMMARY: Research must focus on exposure-response relationships between asbestos and other occupational inhaled hazards, and IPF. Funding bodies and policy makers should acknowledge the significant occupational burden on IPF.}, }
@article {pmid31887736, year = {2019}, author = {Totaro, M and Giorgi, S and Filippetti, E and Gallo, A and Frendo, L and Privitera, G and Baggiani, A}, title = {[Asbestos in drinking water and hazards to human health: a narrative synthesis].}, journal = {Igiene e sanita pubblica}, volume = {75}, number = {4}, pages = {303-312}, pmid = {31887736}, issn = {0019-1639}, mesh = {Asbestos/*adverse effects/toxicity ; Carcinogens ; Drinking Water/*analysis ; Environmental Exposure/*adverse effects ; Humans ; Lung Neoplasms/etiology/prevention &amp; control ; Mesothelioma/etiology/prevention &amp; control ; Water Pollutants, Chemical/*toxicity ; }, abstract = {The term asbestos refers to six unique fibrous minerals mostly used in the production of asbestos cement sheets and pipes. According to the World Health Organization and the International Agency for Research on Cancer (IARC), there exists at least &amp;quot;sufficient evidence&amp;quot; that all types of asbestos may cause cancer in humans (mesothelioma, lung cancer, laryngeal tumor and ovarian cancer). The only asbestos limit in drinking water is 7 million fiber/liter. This study is a narrative synthesis about the possible hazards to human health related to the presence of asbestos in drinking water. The various scientific studies and epidemiological reports examined highlight that there is an ongoing debate on the possible carcinogenic risk associated with asbestos exposure through ingestion. Nevertheless, considering the latency with which diseases caused by asbestos may emerge, control measures should be adopted.}, }
@article {pmid31878930, year = {2019}, author = {Vimercati, L and Cavone, D and Delfino, MC and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Response to the &quot;Letter to the Editor&quot; by Gabor Mezei et al., Comments on Vimercati et al., 2019, &quot;Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (Southern Italy) mesothelioma register&quot;.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {112}, pmid = {31878930}, issn = {1476-069X}, }
@article {pmid31878926, year = {2019}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Comments on Vimercati et al., 2019, &quot;Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (southern Italy) mesothelioma register&quot;.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {111}, pmid = {31878926}, issn = {1476-069X}, }
@article {pmid31876833, year = {2020}, author = {Kodama, E and Kodama, T and Ichikawa, T and Ikoma, H and Hashimoto, J}, title = {18F-FDG Uptake of Localized Malignant Peritoneal Mesothelioma.}, journal = {Clinical nuclear medicine}, volume = {45}, number = {2}, pages = {161-163}, doi = {10.1097/RLU.0000000000002901}, pmid = {31876833}, issn = {1536-0229}, mesh = {Aged ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*diagnostic imaging ; Male ; Mesothelioma/*diagnostic imaging ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*diagnostic imaging ; *Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals ; }, abstract = {We present 2 cases of malignant peritoneal mesothelioma (MPM) characterized by a localized solid mass without ascites and showing F-FDG uptake. A 79-year-old man with a history of asbestos exposure suffered from an epithelioid MPM originating from the hepatoduodenal ligament with FDG uptake (SUVmax 16.8). Another 80-year-old man with esophageal cancer showed desmoplastic MPM of the small bowel mesentery with FDG uptake (SUVmax 4.0). Desmoplastic MPM is more aggressive and yields poorer prognosis compared with the epithelioid type. However, the present desmoplastic MPM case showed mild FDG uptake because of rich fibrosis.}, }
@article {pmid31876584, year = {2020}, author = {Pavlisko, EN and Liu, B and Green, C and Sporn, TA and Roggli, VL}, title = {Malignant Diffuse Mesothelioma in Women: A Study of 354 Cases.}, journal = {The American journal of surgical pathology}, volume = {44}, number = {3}, pages = {293-304}, doi = {10.1097/PAS.0000000000001418}, pmid = {31876584}, issn = {1532-0979}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Carcinogens/toxicity ; Databases, Factual ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/chemically induced/diagnosis/mortality/*pathology ; Mesothelioma/chemically induced/diagnosis/mortality/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Prognosis ; Survival Analysis ; United States/epidemiology ; }, abstract = {We reviewed 354 cases of malignant diffuse mesothelioma (MM) in women from a database of 2858 histologically confirmed MM cases. There was a pleural predominance with 78% pleural MM and 22% peritoneal MM. The pleural tumors consisted of 72% epithelioid, 19% biphasic, and 9% sarcomatoid variant. The peritoneal tumors consisted of 82% epithelioid, 13% biphasic, and 5% sarcomatoid. The immunohistochemical profile was typical of what is well-accepted and previously described for MM. When examining tumor subtype and location, there was a trend toward epithelioid subtype and peritoneal location; however, this did not reach statistical significance. Age at the time of diagnosis ranged from 19 to 93 years with a mean of 60 years. The median age at time of diagnosis for pleural MM was 65 years and for peritoneal MM was 52 years. A further look at age and histologic subtype showed no statistically significant difference in age between MM subtypes. Survival was greatest for epithelioid variant, and this was magnified in the peritoneum. A majority of our cases were exposed to asbestos through a household contact. Asbestosis and parietal pleural plaque were present in 5% and 50% of cases with data, respectively. Fiber analysis data was available in 67 cases; 38 cases had elevated asbestos fiber burden, and tremolite was the most common asbestos fiber type detected. Commercial and noncommercial amphibole asbestos fibers were elevated in nearly equal numbers of cases.}, }
@article {pmid31867277, year = {2019}, author = {Chu, GJ and van Zandwijk, N and Rasko, JEJ}, title = {The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1366}, pmid = {31867277}, issn = {2234-943X}, abstract = {Although mesothelioma is the consequence of a protracted immune response to asbestos fibers and characterized by a clear immune infiltrate, novel immunotherapy approaches show less convincing results as compared to those seen in melanoma and non-small cell lung cancer. The immune suppressive microenvironment in mesothelioma is likely contributing to this therapy resistance. Therefore, it is important to explore the characteristics of the tumor microenvironment for explanations for this recalcitrant behavior. This review describes the stromal, cytokine, metabolic, and cellular milieu of mesothelioma, and attempts to make connection with the outcome of immunotherapy trials.}, }
@article {pmid31850200, year = {2019}, author = {Tomasetti, M and Gaetani, S and Monaco, F and Neuzil, J and Santarelli, L}, title = {Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1293}, pmid = {31850200}, issn = {2234-943X}, abstract = {Asbestos exposure leads to epigenetic and epigenomic modifications that, in association with ROS-induced DNA damage, contribute to cancer onset. Few miRNAs epigenetically regulated in MM have been described in literature; miR-126, however, is one of them, and its expression is regulated by epigenetic mechanisms. Asbestos exposure induces early changes in the miRNAs, which are reversibly expressed as protective species, and their inability to reverse reflects the inability of the cells to restore the physiological miRNA levels despite the cessation of carcinogen exposure. Changes in miRNA expression, which results from genetic/epigenetic changes during tumor formation and evolution, can be detected in fluids and used as cancer biomarkers. This article has reviewed the epigenetic mechanisms involved in miRNA expression in MM, focusing on their role as biomarkers of early diagnosis and therapeutic effects.}, }
@article {pmid31846450, year = {2019}, author = {Apostoli, P and Boffetta, P and Bovenzi, M and Cocco, PL and Consonni, D and Cristaudo, A and Discalzi, G and Farioli, A and Manno, M and Mattioli, S and Pira, E and Soleo, L and Taino, G and Violante, FS and Zocchetti, C}, title = {Position Paper on Asbestos of the Italian Society of Occupational Medicine.}, journal = {La Medicina del lavoro}, volume = {110}, number = {6}, pages = {459-485}, doi = {10.23749/mdl.v110i6.9022}, pmid = {31846450}, issn = {0025-7818}, mesh = {*Asbestos ; *Asbestosis ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Exposure ; *Occupational Medicine ; *Pleural Neoplasms ; Retrospective Studies ; }, abstract = {The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML's Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.}, }
@article {pmid31842309, year = {2019}, author = {Vernez, D and Duperrex, O and Herrera, H and Perret, V and Rossi, I and Regamey, F and Guillemin, M}, title = {Exposure to Amosite-Containing Ceiling Boards in a Public School in Switzerland: A Case Study.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {24}, pages = {}, pmid = {31842309}, issn = {1660-4601}, mesh = {Adolescent ; Air Pollutants/*analysis ; Air Pollution, Indoor/*analysis ; Asbestos, Amosite/*analysis ; Child ; *Construction Materials ; Dose-Response Relationship, Drug ; Environmental Monitoring ; Female ; Humans ; *Lung Neoplasms ; Male ; *Mesothelioma ; Mesothelioma, Malignant ; Risk Assessment ; Schools ; Switzerland ; }, abstract = {The measurement of an airborne concentration in Amosite fibers above 5035 F/m3 in a school prompted a retrospective quantitative health risk assessment. Dose estimates were built using air measurements, laboratory experiments, previous exposure data, and interviews. A dose response model was adapted for amosite-only exposure and adjusted for the life expectancy and lung cancer incidence in the Swiss population. The average yearly concentrations found were 52-320 F/m3. The high concentration previously observed was not representative of the average exposure in the building. Overall, the risk estimates for the different populations of the school were low and in the range of 2 × 10-6 to 3 × 10-5 for mesothelioma and 4 × 10-7 to 8 × 10-6 for lung cancer. The results evidenced however that children have to be considered at higher risk when exposed to asbestos, and that the current reference method and target values are of limited use for amphibole-only exposures. This study confirmed that quantitative health risk assessments and participatory approaches are powerful tools to support public decisions and build constructive communication between exposed people, experts, and policy-makers.}, }
@article {pmid31833271, year = {2019}, author = {Pellegrini, I and Sibille, A and Paulus, A and Vaillant, F and Radermecker, MA and Corhay, JL and Louis, R and Duysinx, B}, title = {[How I manage... Malignant pleural mesothelioma in 2019].}, journal = {Revue medicale de Liege}, volume = {74}, number = {12}, pages = {627-632}, pmid = {31833271}, issn = {0370-629X}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Bevacizumab ; Combined Modality Therapy ; Humans ; *Mesothelioma/drug therapy ; Pemetrexed ; *Pleural Neoplasms/drug therapy ; }, abstract = {Malignant pleural mesothelioma is a rare disease originating from mesothelial cells of the pleura and is related to asbestos exposure. The tumor is generally extended at the time of diagnosis and the treatment consists of a systemic palliative therapy. Radical approach is limited to very selected patients and is performed in expert centers but without validated schema. Radiotherapy alone is mainly used in palliative intent. Platinum-based chemotherapy in association with pemetrexed is the frontline standard of care and provides a 12-month overall survival. The addition of bevacizumab, an antiangiogenic drug, shows an improvement in median survival. To date, there is no second-line treatment approved for this disease and therefore inclusion in trials is recommended. Currently, various studies are investigating target therapy, immunotherapy and intrapleural perioperative treatment.}, }
@article {pmid31823764, year = {2019}, author = {Kishimoto, T and Fujimoto, N and Ebara, T and Omori, T and Oguri, T and Niimi, A and Yokoyama, T and Kato, M and Usami, I and Nishio, M and Yoshikawa, K and Tokuyama, T and Tamura, M and Yokoyama, Y and Tsuboi, K and Matsuo, Y and Xu, J and Takahashi, S and Abdelgied, M and Alexander, WT and Alexander, DB and Tsuda, H}, title = {Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {1204}, pmid = {31823764}, issn = {1471-2407}, support = {14030101-01//Ministry of Health, Labour and Welfare/ ; 13801370//Ministry of Health, Labour and Welfare/ ; 16768893//Ministry of Health, Labour and Welfare/ ; H24//Princess Takamatsu Cancer Research Fund/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestosis/blood ; Biomarkers, Tumor/blood ; Chemokine CCL2/*blood ; Disease Progression ; Female ; Healthy Volunteers ; Humans ; Lung Neoplasms/*blood/pathology ; Male ; Mesothelioma/*blood/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*blood ; Young Adult ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients.<br><br>METHODS: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA.<br><br>RESULTS: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM.<br><br>CONCLUSIONS: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.}, }
@article {pmid31821579, year = {2020}, author = {Ferrante, D and Mirabelli, D and Silvestri, S and Azzolina, D and Giovannini, A and Tribaudino, P and Magnani, C}, title = {Mortality and mesothelioma incidence among chrysotile asbestos miners in Balangero, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {63}, number = {2}, pages = {135-145}, doi = {10.1002/ajim.23071}, pmid = {31821579}, issn = {1097-0274}, support = {//This study was partially supported by Istituto Superiore di Sanità - Progetto Amianto (to C.M)/International ; }, abstract = {BACKGROUND: We studied cancer mortality and mesothelioma incidence in 974 male workers employed at least 6 months at the Balangero mine (Italy), the largest chrysotile mine in Western Europe, active from 1917 to 1985.<br><br>METHODS: Vital status as of 31 May 2013, causes of deaths and mesothelioma incidence from 1990 were ascertained. Past exposure to asbestos by working area and calendar period was estimated, based on historical data of fibers concentrations. Individual cumulative exposure was assessed by applying estimates to the job history of cohort members. Standardized mortality ratios (SMRs) for selected causes and standardized incidence ratios for malignant mesothelioma (MM) were calculated based on regional reference rates. Poisson regression analysis was used to study MM and lung cancer risk by latency, duration, and cumulative exposure.<br><br>RESULTS: Mortality was increased for all causes (SMR = 1.28; 95% confidence interval [CI] = 1.17-1.40), pleural cancer (SMR = 4.30; 95% CI = 1.58-9.37), asbestosis (SMR = 375.06; 95% CI = 262.68-519.23). An increase was also found for lung cancer (SMR = 1.14; 95% CI = 0.81-1.55) and peritoneal cancer (SMR = 3.25; 95% CI = 0.39-11.75). The risk of both pleural and peritoneal cancer mortality and of mesothelioma incidence increased with increasing cumulative exposure, duration, and latency. Poisson regression analyses showed an increase in mesothelioma risk with cumulative asbestos exposure and suggest a similar trend for lung cancer. Asbestosis mortality also increased with cumulative exposure.<br><br>CONCLUSIONS: Among Balangero chrysotile miners and millers, the occurrence of malignant and nonmalignant asbestos-related diseases was increased by exposure, with dose-response relation. The study confirms the carcinogenicity of chrysotile asbestos, in particular for pleural mesothelioma.}, }
@article {pmid31819191, year = {2020}, author = {Urso, L and Cavallari, I and Sharova, E and Ciccarese, F and Pasello, G and Ciminale, V}, title = {Metabolic rewiring and redox alterations in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {122}, number = {1}, pages = {52-61}, pmid = {31819191}, issn = {1532-1827}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Asbestos/adverse effects ; Cell Transformation, Neoplastic/metabolism ; Cisplatin/therapeutic use ; Humans ; Loss of Function Mutation ; Lung Neoplasms/drug therapy/etiology/*genetics/*metabolism ; Mesothelioma/drug therapy/etiology/*genetics/*metabolism ; Mesothelioma, Malignant ; Oxidation-Reduction ; Pleural Neoplasms/drug therapy/etiology/*genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Transforming Growth Factor beta ; Transforming Growth Factor beta1/metabolism ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in 18F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.}, }
@article {pmid31814459, year = {2019}, author = {Pfau, JC and McNew, T and Hanley, K and Swan, L and Black, B}, title = {Autoimmune markers for progression of Libby amphibole lamellar pleural thickening.}, journal = {Inhalation toxicology}, volume = {31}, number = {11-12}, pages = {409-419}, pmid = {31814459}, issn = {1091-7691}, support = {UL1 TR002319/TR/NCATS NIH HHS/United States ; }, mesh = {Antibodies, Antinuclear/metabolism ; Asbestos, Amphibole/*toxicity ; Autoantibodies/*metabolism ; Biomarkers ; Cell Line ; Collagen ; Cytokines/genetics/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Pleura/*drug effects/*pathology ; Sensitivity and Specificity ; }, abstract = {Exposure to Libby Asbestiform Amphibole (LAA) is associated with asbestos-related diseases, including mesothelioma, pulmonary carcinoma, pleural fibrosis, and systemic autoimmune diseases. The pleural fibrosis can manifest as a rapidly progressing lamellar pleural thickening (LPT), which causes thoracic pain, dyspnea, and worsening pulmonary function tests (PFT). It is refractory to treatment and frequently fatal.Objective: Because of the immune dysfunction that has been described in the LAA-exposed population and the association of pleural manifestations with the presence of autoantibodies, this study tested whether specific immunological factors were associated with progressive LPT and whether they could be used as markers of progressive disease.Methods: Subjects were placed into three study groups defined as (1) progressive LPT, (2) stable LPT, (3) no LPT. Serum samples were tested for antinuclear autoantibodies, mesothelial cell autoantibodies, anti-plasminogen antibodies, IL1 beta, and IL17; which have all been shown to be elevated in mice and/or humans exposed to LAA.Results: Group 1 had significantly higher mean values for all of the autoantibodies, but not IL1 or IL-17, compared to the control Group 3. All three autoantibody tests had high specificity but low sensitivity, but ROC area-under-the-curve values for all three antibodies were over 0.7, statistically higher than a test with no value. When all LPT subjects were combined (Progressive plus Stable), no marker had predictive value for disease.Conclusion: The data support the hypothesis that progressive LPT is associated with immunological findings that may serve as an initial screen for progressive LPT.}, }
@article {pmid31812249, year = {2020}, author = {Consonni, D and De Matteis, S and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Impact of an asbestos cement factory on mesothelioma incidence in a community in Italy.}, journal = {Environmental research}, volume = {183}, number = {}, pages = {108968}, doi = {10.1016/j.envres.2019.108968}, pmid = {31812249}, issn = {1096-0953}, mesh = {Adult ; *Asbestos/toxicity ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; *Mesothelioma/epidemiology ; *Occupational Exposure ; *Pleural Neoplasms/epidemiology ; }, abstract = {BACKGROUND: Broni is a small town (9000 inhabitants) in the province of Pavia, Lombardy, north-west Italy, where the second largest Italian asbestos cement factory (Fibronit) was in operation between 1932 and 1993. Based on Lombardy Mesothelioma Registry (RML) data (2000-2011), we previously showed a high impact of asbestos exposure on malignant mesothelioma (MM) incidence among Fibronit workers, their families, and people living in Broni and in the nearby town of Stradella (11,000 residents). Given the great concern of the community, we have recently updated the data regarding 5 more years (2012-2016).<br><br>METHODS: From the RML database we extracted subjects who ever worked in Fibronit, their family members, ever residents in Broni, and subjects living in Stradella and nearby towns at the time of diagnosis. For each type of exposure we calculated standardized incidence ratios (SIR = observed/expected cases).<br><br>RESULTS: In the period 2000-2016 we registered 56 cases (2.52 expected, SIR = 22.2), 49 men (41 pleural, 8 peritoneal MM), 7 women (5 pleural, 2 peritoneal MM) with past occupational exposure in Fibronit. Among subjects never occupationally exposed and never exposed to extra-occupational sources unrelated to Fibronit, we counted 39 cases (4.24 expected, SIR = 9.2), 10 men (all pleural MM), 29 women (28 pleural, 1 peritoneal MM) in Fibronit workers' families, 91 pleural mesothelioma cases (7.43 expected, SIR = 12.2, 31 men, 60 women), ever residents in Broni, and 25 pleural mesothelioma cases (3.05 expected, SIR = 8.2, 6 men, 19 women) living in Stradella at the time of diagnosis. The overall number of excess cases was about 194 (211 against 17.24 expected). In the remaining adjacent (No. 8) and surrounding (No. 17) municipalities (32,000 people) there were 7 cases (1 men, 6 women, 8.85 expected).<br><br>CONCLUSION: The mesothelioma burden related to the asbestos cement factory is still high on factory workers, their families, and residents in Broni and Stradella towns.}, }
@article {pmid31812210, year = {2019}, author = {Sonnick, MA and Weisman, S and Borczuk, AC and Turetz, ML}, title = {A Man in His 20s With Cough, Unilateral Pleural Effusion, and Nodular Pleural Thickening.}, journal = {Chest}, volume = {156}, number = {6}, pages = {e121-e126}, doi = {10.1016/j.chest.2019.05.040}, pmid = {31812210}, issn = {1931-3543}, mesh = {Adenocarcinoma of Lung/diagnosis ; Adult ; Asbestos ; Bartonella Infections/diagnosis ; Biopsy ; Cough/etiology ; Diagnosis, Differential ; Dyspnea/etiology ; Environmental Exposure ; Humans ; Lung Neoplasms/complications/*diagnosis/pathology ; Lymph Nodes/diagnostic imaging ; Lymphoma, Non-Hodgkin/diagnosis ; Male ; Mesothelioma/complications/*diagnosis/pathology ; Mesothelioma, Malignant ; Palatine Tonsil/diagnostic imaging ; Pleural Effusion/diagnostic imaging/etiology ; Pleural Effusion, Malignant/*diagnostic imaging/etiology ; Pleural Neoplasms/complications/*diagnosis/pathology ; Positron-Emission Tomography ; Spleen/diagnostic imaging ; Sweating ; Talc ; Thoracic Surgery, Video-Assisted ; }, abstract = {CASE PRESENTATION: A man in his 20s presented to the ED after several months of progressive dyspnea, dry cough, and night sweats. He had no chest pain, fevers, weight loss, or sick contacts. He was previously healthy and took no medications. Social history was notable for 5 pack-years of tobacco use. The patient was sexually active with male partners and had a recent partner infected with human T-lymphotropic virus. The patient worked in set design and window installations, and wore a respirator when working around solvents and resins. From ages 2 to 7 years, he frequently visited buildings at his parents' workplace that were undergoing asbestos abatement. From ages 7 to 24 years, he frequently visited pottery studios where talc-containing products were used. He frequently visited northern Massachusetts, and infections with Borrelia burgdorferi and Bartonella henselae were common in family members. His stepfather had recently been infected with Anaplasma. There was no family history of cancer.}, }
@article {pmid31807495, year = {2019}, author = {Johnson, TG and Schelch, K and Mehta, S and Burgess, A and Reid, G}, title = {Corrigendum: Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {293}, pmid = {31807495}, issn = {2296-634X}, abstract = {[This corrects the article DOI: 10.3389/fcell.2019.00221.].}, }
@article {pmid31783178, year = {2020}, author = {Mian, I and Abdullaev, Z and Morrow, B and Kaplan, RN and Gao, S and Miettinen, M and Schrump, DS and Zgonc, V and Wei, JS and Khan, J and Pack, S and Hassan, R}, title = {Anaplastic Lymphoma Kinase Gene Rearrangement in Children and Young Adults With Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {15}, number = {3}, pages = {457-461}, pmid = {31783178}, issn = {1556-1380}, support = {Z01 BC010816/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anaplastic Lymphoma Kinase/genetics ; Child ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/genetics ; Male ; *Mesothelioma/genetics ; Prospective Studies ; Receptor Protein-Tyrosine Kinases/genetics ; Young Adult ; }, abstract = {INTRODUCTION: Children and young adults diagnosed with malignant mesothelioma may have unique genetic characteristics. In this study, we evaluated for the presence of the anaplastic lymphoma kinase (ALK) translocations in these patients.<br><br>METHODS: In a prospective study of mesothelioma natural history (ClinicalTrials.gov number NCT01950572), we assessed for the presence of the ALK translocation in patients younger than 40 years, irrespective of the site of disease. The presence of this translocation was assessed by means of fluorescence in situ hybridization (FISH). If the patients tested positive for the ALK translocation, both immunohistochemistry and RNA sequencing were performed on the tumor specimen.<br><br>RESULTS: Between September 2013 and December 2018, 373 patients were enrolled in the mesothelioma natural history study, of which 32 patients were 40 years old or younger at the time of their mesothelioma diagnosis. There were 25 patients with peritoneal mesothelioma, five with pleural mesothelioma, one with pericardial mesothelioma, and one with bicompartmental mesothelioma. Presence of an ALK translocation by FISH was seen in two of the 32 patients (6%) with mesothelioma. Both patients, a 14-year-old female and a 27-year-old male, had peritoneal mesothelioma and had no history of asbestos exposure, prior radiation therapy, or predisposing germline mutations. Neither had detectable ALK expression by immunohistochemistry. RNA sequencing revealed the presence of an STRN fusion partner in the female patient but failed to identify any fusion protein in the male patient.<br><br>CONCLUSIONS: Young patients with peritoneal mesothelioma should be evaluated for the presence of ALK translocations. Presence of this translocation should be assessed by FISH and these patients could potentially benefit from tyrosine kinase inhibitors targeting ALK.}, }
@article {pmid31766522, year = {2019}, author = {Martinotti, S and Patrone, M and Moccia, F and Ranzato, E}, title = {Targeting Calcium Signalling in Malignant Mesothelioma.}, journal = {Cancers}, volume = {11}, number = {12}, pages = {}, pmid = {31766522}, issn = {2072-6694}, abstract = {Calcium ions (Ca2+) are central in cancer development and growth, serving as a major signaling system determining the cell's fate. Therefore, the investigation of the functional roles of ion channels in cancer development may identify novel approaches for determining tumor prognosis. Malignant mesothelioma is an aggressive cancer that develops from the serosal surface of the body, strictly related to asbestos exposure. The treatment of malignant mesothelioma is complex and the survival outcomes, rather than the overall survival data are, to date, disappointedly daunting. Nevertheless, conventional chemotherapy is almost ineffective. The alteration in the expression and/or activity of Ca2+ permeable ion channels seems to be characteristic of mesothelioma cells. In this review, we explore the involvement of the Ca2+toolkit in this disease. Moreover, the established sensitivity of some Ca2+channels to selective pharmacological modulators makes them interesting targets for mesothelioma cancer therapy.}, }
@article {pmid31755376, year = {2019}, author = {Celsi, F and Crovella, S and Moura, RR and Schneider, M and Vita, F and Finotto, L and Zabucchi, G and Zacchi, P and Borelli, V}, title = {Pleural mesothelioma and lung cancer: the role of asbestos exposure and genetic variants in selected iron metabolism and inflammation genes.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {82}, number = {20}, pages = {1088-1102}, doi = {10.1080/15287394.2019.1694612}, pmid = {31755376}, issn = {1528-7394}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Female ; Humans ; Inflammasomes/*genetics ; Iron/*metabolism ; Italy ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Pleural Neoplasms/chemically induced/*epidemiology ; Prevalence ; Retrospective Studies ; Risk Factors ; }, abstract = {Two of the major cancerous diseases associated with asbestos exposure are malignant pleural mesothelioma (MPM) and lung cancer (LC). In addition to asbestos exposure, genetic factors have been suggested to be associated with asbestos-related carcinogenesis and lung genotoxicity. While genetic factors involved in the susceptibility to MPM were reported, to date the influence of individual genetic variations on asbestos-related lung cancer risk is still poorly understood. Since inflammation and disruption of iron (Fe) homeostasis are hallmarks of asbestos exposure affecting the pulmonary tissue, this study aimed at investigating the association between Fe-metabolism and inflammasome gene variants and susceptibility to develop LC or MPM, by comparing an asbestos-exposed population affected by LC with an &quot;asbestos-resistant exposed population&quot;. A retrospective approach similar to our previous autopsy-based pilot study was employed in a novel cohort of autoptic samples, thus giving us the possibility to corroborate previous findings obtained on MPM by repeating the analysis in a novel cohort of autoptic samples. The protective role of HEPH coding SNP was further confirmed. In addition, the two non-coding SNPs, either in FTH1 or in TF, emerged to exert a similar protective role in a new cohort of LC exposed individuals from the same geographic area of MPM subjects. No association was found between NLRP1 and NLRP3 polymorphisms with susceptibility to develop MPM and LC. Further research into a specific MPM and LC &quot;genetic signature&quot; may be needed to broaden our knowledge of the genetic landscape attributed to result in MPM and LC.}, }
@article {pmid31743489, year = {2020}, author = {Cummings, KJ and Becich, MJ and Blackley, DJ and Deapen, D and Harrison, R and Hassan, R and Henley, SJ and Hesdorffer, M and Horton, DK and Mazurek, JM and Pass, HI and Taioli, E and Wu, XC and Zauderer, MG and Weissman, DN}, title = {Workshop summary: Potential usefulness and feasibility of a US National Mesothelioma Registry.}, journal = {American journal of industrial medicine}, volume = {63}, number = {2}, pages = {105-114}, pmid = {31743489}, issn = {1097-0274}, support = {U19 OH009077/OH/NIOSH CDC HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; //Mesothelioma Applied Research Foundation/International ; }, abstract = {The burden and prognosis of malignant mesothelioma in the United States have remained largely unchanged for decades, with approximately 3200 new cases and 2400 deaths reported annually. To address care and research gaps contributing to poor outcomes, in March of 2019 the Mesothelioma Applied Research Foundation convened a workshop on the potential usefulness and feasibility of a national mesothelioma registry. The workshop included formal presentations by subject matter experts and a moderated group discussion. Workshop participants identified top priorities for a registry to be (a) connecting patients with high-quality care and clinical trials soon after diagnosis, and (b) making useful data and biospecimens available to researchers in a timely manner. Existing databases that capture mesothelioma cases are limited by factors such as delays in reporting, deidentification, and lack of exposure information critical to understanding as yet unrecognized causes of disease. National disease registries for amyotrophic lateral sclerosis (ALS) in the United States and for mesothelioma in other countries, provide examples of how a registry could be structured to meet the needs of patients and the scientific community. Small-scale pilot initiatives should be undertaken to validate methods for rapid case identification, develop procedures to facilitate patient access to guidelines-based standard care and investigational therapies, and explore approaches to data sharing with researchers. Ultimately, federal coordination and funding will be critical to the success of a National Mesothelioma Registry in improving mesothelioma outcomes and preventing future cases of this devastating disease.}, }
@article {pmid31732616, year = {2020}, author = {Kandasamy, S and Adhikary, G and Rorke, EA and Friedberg, JS and Mickle, MB and Alexander, HR and Eckert, RL}, title = {The YAP1 Signaling Inhibitors, Verteporfin and CA3, Suppress the Mesothelioma Cancer Stem Cell Phenotype.}, journal = {Molecular cancer research : MCR}, volume = {18}, number = {3}, pages = {343-351}, pmid = {31732616}, issn = {1557-3125}, support = {R01 CA211909/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, abstract = {Mesothelioma is an aggressive cancer that has a poor prognosis. Tumors develop in the mesothelial lining of the pleural and peritoneal cavities in response to asbestos exposure. Surgical debulking followed by chemotherapy is initially effective, but this treatment ultimately selects for resistant cells that form aggressive and therapy-resistant recurrent tumors. Mesothelioma cancer stem cells (MCS) are a highly aggressive subpopulation present in these tumors that are responsible for tumor maintenance and drug resistance. In this article, we examine the impact of targeting YAP1/TAZ/TEAD signaling in MCS cells. YAP1, TAZ, and TEADs are transcriptional mediators of the Hippo signaling cascade that activate gene expression to drive tumor formation. We show that two YAP1 signaling inhibitors, verteporfin and CA3, attenuate the MCS cell phenotype. Verteporfin or CA3 treatment reduces YAP1/TEAD level/activity to suppress MCS cell spheroid formation, Matrigel invasion, migration, and tumor formation. These agents also increase MCS cell apoptosis. Moreover, constitutively active YAP1 expression antagonizes inhibitor action, suggesting that loss of YAP1/TAZ/TEAD signaling is required for response to verteporfin and CA3. These agents are active against mesothelioma cells derived from peritoneal (epithelioid) and patient-derived pleural (sarcomatoid) mesothelioma, suggesting that targeting YAP1/TEAD signaling may be a useful treatment strategy. IMPLICATIONS: These studies suggest that inhibition of YAP1 signaling may be a viable approach to treating mesothelioma.}, }
@article {pmid31727556, year = {2019}, author = {Lorentz, E and Despreaux, T and Quignette, A and Chinet, T and Descatha, A}, title = {[Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma].}, journal = {Revue des maladies respiratoires}, volume = {36}, number = {10}, pages = {1088-1095}, doi = {10.1016/j.rmr.2019.08.006}, pmid = {31727556}, issn = {1776-2588}, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Asbestos/toxicity ; Asbestosis/complications/*diagnosis/epidemiology ; Carcinoma, Bronchogenic/diagnosis/*epidemiology/etiology ; Female ; France/epidemiology ; Humans ; Lung Neoplasms/diagnosis/*epidemiology/etiology ; Male ; Mass Screening/*methods ; Mesothelioma/diagnosis/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/diagnosis ; Occupational Exposure/analysis ; Silicon Dioxide/toxicity ; Silicosis/complications/*diagnosis/epidemiology ; Surveys and Questionnaires ; Work/statistics &amp; numerical data ; }, abstract = {INTRODUCTION: In the context of underreporting of occupational diseases, the aim was to study the validity of silica and asbestos job-exposure matrices in screening occupational exposure in the field of thoracic oncology.<br><br>METHODS: Fifty patients hospitalized with primitive lung cancer or mesothelioma in a university hospital center in the Hauts-de-Seine department of France were included between November 2016 and September 2017. For each patient 1/the job history was collected, from which data was entered single-blindly into the job-exposure matrices by a resident in occupational medicine, 2/a questionnaire (Q-SPLF) was completed similarly, and 3/the patients also had a consultation with a chief resident in occupational medicine, considered the gold standard. The main outcome was the diagnostic performance of the matrices. The Q-SPLF diagnostic performance was also studied.<br><br>RESULTS: The asbestos and silica matrices had sensitivities of 100%, specificities of respectively 76.1% and 87.8%, the positive likelihood ratios were at 4.19 [2.5-6] and 8.17 [3.8-10], and the negative likelihood ratios were at 0. The Q-SPLF diagnostic performance was comparable to that of the matrices.<br><br>CONCLUSIONS: The matrices and the questionnaire have a great diagnostic performance which seems interesting for a use as a screening tool for occupational exposures. These results have yet to be confirmed by large-scale studies.}, }
@article {pmid31714372, year = {2020}, author = {Larson, TC and Williamson, L and Antao, VC}, title = {Follow-Up of the Libby, Montana Screening Cohort: A 17-Year Mortality Study.}, journal = {Journal of occupational and environmental medicine}, volume = {62}, number = {1}, pages = {e1-e6}, doi = {10.1097/JOM.0000000000001760}, pmid = {31714372}, issn = {1536-5948}, abstract = {OBJECTIVE: To evaluate mortality patterns among participants in a community-based screening program for asbestos-related disease.<br><br>METHODS: We calculated standardized mortality ratios (SMRs) and stratified results by exposure group (three occupational exposure groups, household contacts and residents without occupational asbestos exposure) and by radiographic abnormality presence.<br><br>RESULTS: All-cause mortality (15.8%; 1,429/8,043) was statistically lower than expected. Asbestosis was statistically elevated in all exposure groups. Lung cancer was moderately associated with vermiculite miner/miller employment. Mesothelioma was elevated in that same exposure group and among residents. Systemic autoimmune disease mortality was also elevated. Radiographic parenchymal abnormalities were associated with lung cancer mortality.<br><br>CONCLUSION: In addition to asbestos-related mortality in occupational exposure groups, this initial follow-up of this cohort also shows elevated mortality for some asbestos-related causes in non-occupational exposure groups.}, }
@article {pmid31713586, year = {2020}, author = {Finkelstein, MM and Meisenkothen, C}, title = {Malignant Mesothelioma Among Employees of a Connecticut Factory That Manufactured Friction Materials Using Chrysotile Asbestos: An Update.}, journal = {Annals of work exposures and health}, volume = {64}, number = {1}, pages = {106-109}, doi = {10.1093/annweh/wxz082}, pmid = {31713586}, issn = {2398-7316}, abstract = {There is an ongoing argument about the potency of chrysotile asbestos to cause malignant mesothelioma. Authors of chrysotile risk assessments have relied upon the results of an epidemiologic study, published in 1984, to state that there were no mesotheliomas found among workers at a Connecticut friction products plant. McDonald reported the first two cases in 1986. In 2010, we reported the work histories and pathologic reports of five individuals from the Connecticut plant who were diagnosed with mesothelioma. Despite this, a review of the health effects of chrysotile published in 2018 continued to state that there were no cases of mesothelioma from this plant. We report here two new cases that were diagnosed after the publication of our previous report, bringing the current total to nine cases. We also discuss the results of previously unpublished air sampling data from the plant. Chrysotile, mainly from Canada, was the only asbestos fiber type used until 1957 when some anthophyllite was added in making paper discs and bands. Beyond this original description of the anthophyllite usage from McDonald, there is a dearth of information about the amount of anthophyllite used in the plant, the frequency of its use, and the specific departments where it was used. For over 30 years in the published literature, this factory has alternatively been described as a 'chrysotile' or 'predominantly chrysotile' factory. While it is clear that some anthophyllite was used in the factory (in addition to 400 pounds of crocidolite in the laboratory), given the volume, frequency, and processes using chrysotile, it still seems satisfactory to describe this cohort as a predominantly, but not exclusively, chrysotile-exposed cohort.}, }
@article {pmid31701555, year = {2020}, author = {van Gerwen, M and Alpert, N and Flores, R and Taioli, E}, title = {An overview of existing mesothelioma registries worldwide, and the need for a US Registry.}, journal = {American journal of industrial medicine}, volume = {63}, number = {2}, pages = {115-120}, doi = {10.1002/ajim.23069}, pmid = {31701555}, issn = {1097-0274}, abstract = {The association between asbestos exposure, mainly in occupational settings, and malignant mesothelioma has been well established; this has prompted several countries to establish mesothelioma epidemiologic surveillance programs often at the request of national agencies. This review compares currently existing mesothelioma registries worldwide to develop a concept model for a US real-time case capture mesothelioma registry. Five countries were identified with a mesothelioma specific registry, including Italy, France, UK, Australia, and South Korea. All, except the UK, used interviews to collect exposure data. Linkage with the national death index was available or was in future plans for all registries. The registries have limited information on treatment, quality of life, and other patient-centered outcomes such as symptoms and pain management. To thoroughly collect exposure data, &quot;real-time&quot; enrollment is preferable; to maximize the capture of mesothelioma cases, optimal coverage, and a simplified consent process are needed.}, }
@article {pmid31693951, year = {2020}, author = {Gwenzi, W}, title = {Occurrence, behaviour, and human exposure pathways and health risks of toxic geogenic contaminants in serpentinitic ultramafic geological environments (SUGEs): A medical geology perspective.}, journal = {The Science of the total environment}, volume = {700}, number = {}, pages = {134622}, doi = {10.1016/j.scitotenv.2019.134622}, pmid = {31693951}, issn = {1879-1026}, mesh = {Africa ; Animals ; Asbestos, Serpentine ; Asbestosis ; Environmental Exposure ; *Environmental Monitoring ; Geology ; Hazardous Substances/*analysis ; Humans ; Iron ; Lung Neoplasms ; Mesothelioma ; Mesothelioma, Malignant ; Metals, Heavy ; Metals, Rare Earth ; Mining ; *Risk Assessment ; }, abstract = {Serpentinitic ultramafic geological environments (SUGEs) contain toxic geogenic contaminants (TGCs). Yet comprehensive reviews on the medical geology of SUGEs are still lacking. The current paper posits that TGCs occur widely in SUGEs, and pose human health risks. The objectives of the review are to: (1) highlight the nature, occurrence and behaviour of TGCs associated with SUGEs; (2) discuss the human intake pathways and health risks of TGCs; (4) identify the key risk factors predisposing human health to TGCs particularly in Africa; and (5) highlight key knowledge gaps and future research directions. TGCs of human health concern in SUGEs include chrysotile asbestos, toxic metals (Fe, Cr, Ni, Mn, Zn, Co), and rare earth elements. Human intake of TGCs occur via inhalation, and ingestion of contaminated drinking water, wild foods, medicinal plants, animal foods, and geophagic earths. Occupational exposure may occur in the mining, milling, sculpturing, engraving, and carving industries. African populations are particularly at high risk due to: (1) widespread consumption of wild foods, medicinal plants, untreated drinking water, and geophagic earths; (2) weak and poorly enforced environmental, occupational, and public health regulations; and (3) lack of human health surveillance systems. Human health risks of chrysotile include asbestosis, cancers, and mesothelioma. Toxic metals are redox active, thus generate reactive oxygen species causing oxidative stress. Dietary intake of iron and geophagy may increase the iron overload among native Africans who are genetically predisposed to such health risks. Synergistic interactions among TGCs particularly chrysotile and toxic metals may have adverse human health effects. The occurrence of SUGEs, coupled with the several risk factors in Africa, provides a unique and ideal setting for investigating the relationships between TGCs and human health risks. A conceptual framework for human health risk assessment and mitigation, and future research direction are highlighted.}, }
@article {pmid31690138, year = {2019}, author = {Boyles, MSP and Poland, CA and Raftis, J and Duffin, R}, title = {Assessment of the physicochemical properties of chrysotile-containing brake debris pertaining to toxicity.}, journal = {Inhalation toxicology}, volume = {31}, number = {8}, pages = {325-342}, doi = {10.1080/08958378.2019.1683103}, pmid = {31690138}, issn = {1091-7691}, mesh = {Air Pollutants, Occupational/*chemistry ; Asbestos, Serpentine/*chemistry ; Automobiles ; Humans ; Macrophages/*drug effects ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Reactive Oxygen Species/analysis ; THP-1 Cells ; }, abstract = {Grinding and drilling of chrysotile asbestos-containing brake pads during the 20th century led to release of chrysotile, resulting in varying levels of workplace exposures of mechanics. Despite exposures, excess risk of mesothelioma remains in doubt. Objectives: The toxicity of particulates is primarily derived through a combination of physicochemical properties and dose and as such this study aimed to determine properties of asbestos-containing brake debris (BD) which may influence pathogenicity and potential of mesothelioma. Materials and Methods: Chrysotile-containing brake pads were ground - to reflect occupational activities, aerosolized, and size-fractionated to isolate respirable fractions. Analysis of morphology, biodurability, surface charge, and interactions with macrophages were undertaken. Results: The respirable fraction of BD contained ∼15-17% free chrysotile fibers thereby constituting a small but relevant potential long fiber dose. Acellular biodurability studies showed rapid dissolution and fragmentation of chrysotile fibers that was consistent for pure chrysotile control and BD samples. Conclusions: The long, free, respirable chrysotile fibers were present in BD, yet were of low bio-durability; incubation in artificial lysosomal fluid led to destruction of free fibers.}, }
@article {pmid31684803, year = {2019}, author = {Waldron, T}, title = {ERA Merewether - And asbestos.}, journal = {Journal of medical biography}, volume = {}, number = {}, pages = {967772019883550}, doi = {10.1177/0967772019883550}, pmid = {31684803}, issn = {1758-1087}, abstract = {After a succession of posts and studying for the Bar, Edward Merewether joined the Medical Inspectorate of Factories in 1927. Not long thereafter he was asked to undertake a study of the effects of asbestos exposure on the lungs. His results showed that asbestos workers had a significant risk of developing pulmonary fibrosis and this resulted in the promulgation of regulations to limit exposure. Some years later, Merewether showed that asbestos workers also had a higher than expected risk of developing lung cancer, but on this occasion there was no further protective legislation, and the association was not generally accepted until some years later. Merewether's name is inextricably linked with the risks of asbestos exposure but after his death the importance of his efforts was often played down by those who wished to show that the government had not acted quickly enough, or vigorously enough to control the hazard. The contention of this paper is that these criticisms are not justified and that Merewether acted to the best of his ability, given the conditions and knowledge current at the time he was working.}, }
@article {pmid31682242, year = {2019}, author = {Świątkowska, B}, title = {[The occurrence of asbestos-related diseases among former employees of asbestos processing plants in Poland].}, journal = {Medycyna pracy}, volume = {70}, number = {6}, pages = {723-731}, doi = {10.13075/mp.5893.00890}, pmid = {31682242}, issn = {2353-1339}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*epidemiology ; Female ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects/*statistics &amp; numerical data ; Poland/epidemiology ; Population Surveillance ; }, abstract = {BACKGROUND: Despite the fact that asbestos is no longer used in production in Poland, there are still new cases of asbestos-related diseases among workers previously exposed to asbestos dust. This situation is related to the specificity of the biological activity of this mineral; the health consequences of asbestos can manifest not only during the exposure but also many years after exposure cessation. The aim of the analysis was to assess the occurrence of occupational diseases among people exposed to asbestos dust, who were examined under the Amiantus program.<br><br>MATERIAL AND METHODS: The research material consisted of the program cards filled by the doctors conducting the examinations as well as radiological images stored on the International Labour Organization form. The analysis covered 8049 people, including 37% of women surveyed in the years 2000-2017.<br><br>RESULTS: In the group of former employees of asbestos processing plants, the occupational disease was diagnosed in 1993 people (25%), including 584 women (19%). The most common was asbestosis (76% of occupational diseases) and pleural disease (17%). Malignant neoplasms accounted for 7% of all cases in this group. The analysis showed an increase in the incidence of respiratory system diseases along with the age of the surveyed persons, their seniority at asbestos processing plants and an increase in cumulative exposure. The chest radiographs revealed radiological changes among 75% of the examined cases, whereas the changes entitling to diagnose asbestosis, according to the criteria applicable in Poland, occurred in 23% of the workers. The adoption of international criteria would increase the incidence of asbestosis as an occupational disease by 19% in the study group.<br><br>CONCLUSIONS: The increase in the percentage of people with a diagnosed occupational disease provides evidence for the worsening health status of the former workers as well as a good detection of asbestos-related diseases among employees exposed to asbestos dust in the past. The results of the analysis indicate the need for undertaking a discussion in Poland on the implementation of international criteria for the diagnosis of asbestosis. Med Pr. 2019;70(6):723-31.}, }
@article {pmid31671889, year = {2019}, author = {Wörthmüller, J and Salicio, V and Oberson, A and Blum, W and Schwaller, B}, title = {Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin.}, journal = {International journal of molecular sciences}, volume = {20}, number = {21}, pages = {}, pmid = {31671889}, issn = {1422-0067}, mesh = {Antineoplastic Agents/*pharmacology ; Calbindin 2/genetics/*metabolism ; Carcinogenesis ; Carrier Proteins/metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cisplatin/*pharmacology ; Down-Regulation ; Drug Resistance, Neoplasm/*drug effects ; Epithelial-Mesenchymal Transition/drug effects ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Wnt Signaling Pathway/*drug effects ; }, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-linked neoplasm, characterized by dysregulation of signaling pathways. Due to intrinsic or acquired chemoresistance, MM treatment options remain limited. Calretinin is a Ca2+-binding protein expressed during MM tumorigenesis that activates the FAK signaling pathway, promoting invasion and epithelial-to-mesenchymal transition. Constitutive calretinin downregulation decreases MM cells' growth and survival, and impairs tumor formation in vivo. In order to evaluate early molecular events occurring during calretinin downregulation, we generated a tightly controlled IPTG-inducible expression system to modulate calretinin levels in vitro. Calretinin downregulation significantly reduced viability and proliferation of MM cells, attenuated FAK signaling and reduced the invasive phenotype of surviving cells. Importantly, surviving cells showed a higher resistance to cisplatin due to increased Wnt signaling. This resistance was abrogated by the Wnt signaling pathway inhibitor 3289-8625. In various MM cell lines and regardless of calretinin expression levels, blocking of FAK signaling activated the Wnt signaling pathway and vice versa. Thus, blocking both pathways had the strongest impact on MM cell proliferation and survival. Chemoresistance mechanisms in MM cells have resulted in a failure of single-agent therapies. Targeting of multiple components of key signaling pathways, including Wnt signaling, might be the future method-of-choice to treat MM.}, }
@article {pmid31670764, year = {2020}, author = {Musk, AWB and Reid, A and Olsen, N and Hobbs, M and Armstrong, B and Franklin, P and Hui, J and Layman, L and Merler, E and Brims, F and Alfonso, H and Shilkin, K and Sodhi-Berry, N and de Klerk, N}, title = {The Wittenoom legacy.}, journal = {International journal of epidemiology}, volume = {49}, number = {2}, pages = {467-476}, doi = {10.1093/ije/dyz204}, pmid = {31670764}, issn = {1464-3685}, abstract = {The Wittenoom crocidolite (blue asbestos) mine and mill ceased operating in 1966. The impact of this industry on asbestos-related disease in Western Australia has been immense. Use of the employment records of the Australian Blue Asbestos Company and records of the Wittenoom township residents has permitted two cohorts of people with virtually exclusive exposure to crocidolite to be assembled and studied. Follow-up of these two cohorts has been conducted through data linkage with available hospital, mortality and cancer records. The evolution of asbestos-related disease has been recorded and, with the establishment of exposure measurements, quantitative exposure-response relationships have been estimated. There has been an ongoing epidemic of mortality from lung cancer and malignant mesothelioma and, less so, from asbestosis. Wittenoom crocidolite was used extensively in asbestos-cement products in Western Australia. As a result, the state has recorded a higher malignant-mesothelioma mortality rate than in any other Australian state and in any defined general population in the world. Thus, the legacy of Wittenoom has extended beyond the mine and the town, and is still evident more than 50 years after the closure of the mine.}, }
@article {pmid31670225, year = {2019}, author = {Cinausero, M and Rihawi, K and Cortiula, F and Follador, A and Fasola, G and Ardizzoni, A}, title = {Emerging therapies in malignant pleural mesothelioma.}, journal = {Critical reviews in oncology/hematology}, volume = {144}, number = {}, pages = {102815}, doi = {10.1016/j.critrevonc.2019.102815}, pmid = {31670225}, issn = {1879-0461}, mesh = {Combined Modality Therapy ; Humans ; Immunotherapy ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer of the pleural surfaces frequently related to asbestos exposure. It is characterized by a poor prognosis even for patients treated with trimodality therapy, including surgery, chemotherapy and radiotherapy. Moreover, the majority of patients are not candidates for surgery due to disease advanced stage or medical comorbidities. For these patients, the survival rate is even lower and few therapeutic options are currently available. Nevertheless, many interesting novel approaches are under investigation, among which immunotherapy represents one of the most promising emerging strategies. In this review, we will discuss the role of new therapeutic options, particularly immunotherapy, and present the results of the most important and promising clinical trials.}, }
@article {pmid31667596, year = {2020}, author = {Minami, K and Jimbo, N and Tanaka, Y and Hokka, D and Miyamoto, Y and Itoh, T and Maniwa, Y}, title = {Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {476}, number = {3}, pages = {469-473}, pmid = {31667596}, issn = {1432-2307}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Cyclin-Dependent Kinase Inhibitor p16/analysis/genetics ; *Early Diagnosis ; Genes, p16 ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Pleural Neoplasms/*diagnosis ; Purine-Nucleoside Phosphorylase/analysis/biosynthesis ; Sequence Deletion ; }, abstract = {Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.}, }
@article {pmid31662422, year = {2019}, author = {Reynolds, CJ and Minelli, C and Darnton, A and Cullinan, P}, title = {Mesothelioma mortality in Great Britain: how much longer will dockyards dominate?.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {12}, pages = {908-912}, doi = {10.1136/oemed-2019-105878}, pmid = {31662422}, issn = {1470-7926}, support = {201291/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Female ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Mesothelioma, Malignant ; Occupational Diseases/*mortality ; *Ships ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: We aimed to investigate whether there has been a geographic shift in the distribution of mesothelioma deaths in Great Britain given the decline of shipbuilding and progressive exposure regulation.<br><br>METHODS: We calculated age-adjusted mesothelioma mortality rates and estimated rate ratios for areas with and without a dockyard. We compared spatial autocorrelation statistics (Moran's I) for age-adjusted rates at local authority district level for 2002-2008 and 2009-2015. We measured the mean distance of the deceased's postcode to the nearest dockyard at district level and calculated the association of average distance to dockyard and district mesothelioma mortality using simple linear regression for men, for 2002-2008 and 2009-2015.<br><br>RESULTS: District age-adjusted male mortality rates fell during 2002-2015 for 80 of 348 districts (23%), rose for 267 (77%) and were unchanged for one district; having one or more dockyards in a district was associated with rates falling (OR=2.43, 95% CI 1.22 to 4.82, p=0.02). The mortality rate ratio for men in districts with a dockyard, compared with those without a dockyard was 1.41 (95% CI 1.35 to 1.48, p<0.05) for 2002-2008 and 1.18 (95% CI 1.13 to 1.23, p<0.05) for 2009-2015. Spatial autocorrelation (measured by Moran's I) decreased from 0.317 (95% CI 0.316 to 0.319, p=0.001) to 0.312 (95% CI 0.310 to 0.314, p=0.001) for men and the coefficient of the association between distance to dockyard and district level age-adjusted male mortality (per million population) from -0.16 (95% CI -0.21 to -0.10, p<0.01) to -0.13 (95% CI -0.18 to -0.07, p<0.01) for men, when comparing 2002-2008 with 2009-2015.<br><br>CONCLUSION: For most districts age-adjusted mesothelioma mortality rates increased through 2002-2015 but the relative contribution from districts with a dockyard fell. Dockyards remain strongly spatially associated with mesothelioma mortality but the strength of this association appears to be falling and mesothelioma deaths are becoming more dispersed.}, }
@article {pmid31655816, year = {2020}, author = {Fortin, M and Cabon, E and Berbis, J and Laroumagne, S and Guinde, J and Elharrar, X and Dutau, H and Astoul, P}, title = {Diagnostic Value of Computed Tomography Imaging Features in Malignant Pleural Mesothelioma.}, journal = {Respiration; international review of thoracic diseases}, volume = {99}, number = {1}, pages = {28-34}, doi = {10.1159/000503239}, pmid = {31655816}, issn = {1423-0356}, abstract = {BACKGROUND: Medical history, thoracentesis, and imaging features are usually the first steps in the investigation of a possible malignant pleural effusion (MPE). Unfortunately, the diagnostic yield of thoracentesis in this situation is suboptimal even if the procedure is repeated, especially in the context of malignant pleural mesothelioma (MPM). The next step for confirming the diagnosis, if clinically appropriate, is thoracoscopy, but not all patients are fit to undergo this procedure, so the diagnosis is then based on the medical history and imaging features only.<br><br>OBJECTIVES: Our objective was to evaluate the diagnostic value of the medical history and imaging features in MPM.<br><br>METHODS: We reviewed the imaging and medical charts of 92 patients with a final diagnosis of MPE included in our prospective medical thoracoscopy database. The clinical characteristics and imaging features of patients with primary MPE were compared with those of patients with secondary MPE.<br><br>RESULTS: Male sex (82 vs. 59%, p = 0.02), asbestos exposure (58 vs. 10%, p < 0.001), and mediastinal (68 vs. 33%, p = 0.04), diaphragmatic (75 vs. 31%, p = 0.001) and circumferential pleural thickening (55 vs. 19% p = 0.001) were significantly more frequent in MPM patients. In a multivariate linear regression model, only asbestos exposure (OR 11.2; 95% CI 3.4-36.9) and circumferential pleural thickening (OR 4.7; 95% CI 1.6-13.9) were significantly associated with a diagnosis of MPM.<br><br>CONCLUSION: In situations where it is impossible to obtain adequate pleural samples to differentiate MPM from a secondary pleural malignancy, the combination of circumferential pleural thickening and a history of asbestos exposure may be sufficient to make a clinical diagnosis.}, }
@article {pmid31648983, year = {2019}, author = {Alcala, N and Mangiante, L and Le-Stang, N and Gustafson, CE and Boyault, S and Damiola, F and Alcala, K and Brevet, M and Thivolet-Bejui, F and Blanc-Fournier, C and Le Rochais, JP and Planchard, G and Rousseau, N and Damotte, D and Pairon, JC and Copin, MC and Scherpereel, A and Wasielewski, E and Wicquart, L and Lacomme, S and Vignaud, JM and Ancelin, G and Girard, C and Sagan, C and Bonnetaud, C and Hofman, V and Hofman, P and Mouroux, J and Thomas de Montpreville, V and Clermont-Taranchon, E and Mazieres, J and Rouquette, I and Begueret, H and Blay, JY and Lantuejoul, S and Bueno, R and Caux, C and Girard, N and McKay, JD and Foll, M and Galateau-Salle, F and Fernandez-Cuesta, L}, title = {Redefining malignant pleural mesothelioma types as a continuum uncovers immune-vascular interactions.}, journal = {EBioMedicine}, volume = {48}, number = {}, pages = {191-202}, pmid = {31648983}, issn = {2352-3964}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor ; *Disease Susceptibility ; Female ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/*etiology/pathology ; Male ; Mesothelioma/*diagnosis/*etiology/pathology ; Mesothelioma, Malignant ; Neovascularization, Pathologic/*immunology ; Pleural Neoplasms/*diagnosis/*etiology/pathology ; Transcriptome ; Tumor Microenvironment/*immunology ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options.<br><br>METHODS: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples.<br><br>FINDINGS: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a &quot;hot&quot; bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a &quot;cold&quot; bad-prognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a &quot;VEGFR2+/VISTA+&quot; better-prognosis profile, with high expression of immune checkpoint VISTA and pro-angiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series.<br><br>INTERPRETATION: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response.}, }
@article {pmid31632972, year = {2019}, author = {Johnson, TG and Schelch, K and Mehta, S and Burgess, A and Reid, G}, title = {Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {221}, pmid = {31632972}, issn = {2296-634X}, abstract = {Lung cancers and malignant pleural mesothelioma (MPM) have some of the worst 5-year survival rates of all cancer types, primarily due to a lack of effective treatment options for most patients. Targeted therapies have shown some promise in thoracic cancers, although efficacy is limited only to patients harboring specific mutations or target expression. Although a number of actionable mutations have now been identified, a large population of thoracic cancer patients have no therapeutic options outside of first-line chemotherapy. It is therefore crucial to identify alternative targets that might lead to the development of new ways of treating patients diagnosed with these diseases. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) could serve as one such target. Recent studies also link this protein to many inherent behaviors of thoracic cancer cells such as proliferation, invasion, metastasis and involvement in cancer stem-like cells. Here, we review the regulation of YB-1 at the transcriptional, translational, post-translational and sub-cellular levels in thoracic cancer and discuss its potential use as a biomarker and therapeutic target.}, }
@article {pmid31624358, year = {2019}, author = {Nowak, AK and Forde, PM}, title = {Immunotherapy trials in mesothelioma - promising results, but don't stop here.}, journal = {Nature reviews. Clinical oncology}, volume = {16}, number = {12}, pages = {726-728}, doi = {10.1038/s41571-019-0291-4}, pmid = {31624358}, issn = {1759-4782}, mesh = {Humans ; Immunotherapy ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid31619883, year = {2019}, author = {Munot, MN and Utpat, KV and Desai, UD and Joshi, JM}, title = {Malignant Mesothelioma - Report of Two Cases with Different Presentations.}, journal = {Indian journal of occupational and environmental medicine}, volume = {23}, number = {2}, pages = {93-96}, pmid = {31619883}, issn = {0973-2284}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm that stems from the mesothelial cells lining the visceral cavities, namely, the pleura, peritoneum, pericardium, and tunica vaginalis of the testes. MPM is the most common variant of these and constitutes up to 80% of all malignant mesotheliomas. It is usually associated with asbestos exposure and is a locally invasive neoplasm that spreads along pleura and can involve lungs with locoregional metastasis. Diagnosis remains challenging due to the latency between asbestos exposure and clinical presentation and the variable clinicoradiological manifestations. Meticulous history taking, high index of, suspicion and multimodality approach toward diagnosis are the keys to better prognosis. We hereby present two interesting cases of MPM with different presentations.}, }
@article {pmid31610664, year = {2019}, author = {Levý, M and Boublíková, L and Büchler, T and Šimša, J}, title = {Treatment of Malignant Peritoneal Mesothelioma.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {32}, number = {5}, pages = {333-337}, doi = {10.14735/amko2019333}, pmid = {31610664}, issn = {1802-5307}, mesh = {Combined Modality Therapy ; *Cytoreduction Surgical Procedures ; Humans ; *Hyperthermia, Induced ; Mesothelioma/diagnosis/epidemiology/*therapy ; Peritoneal Neoplasms/diagnosis/epidemiology/*therapy ; }, abstract = {Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.}, }
@article {pmid31609780, year = {2020}, author = {Moline, J and Bevilacqua, K and Alexandri, M and Gordon, RE}, title = {Mesothelioma Associated With the Use of Cosmetic Talc.}, journal = {Journal of occupational and environmental medicine}, volume = {62}, number = {1}, pages = {11-17}, doi = {10.1097/JOM.0000000000001723}, pmid = {31609780}, issn = {1536-5948}, abstract = {OBJECTIVE: To describe 33 cases of malignant mesothelioma among individuals with no known asbestos exposure other than cosmetic talcum powder.<br><br>METHODS: Cases were referred for medico-legal evaluation, and tissue digestions were performed in some cases. Tissue digestion for the six cases described was done according to standard methodology.<br><br>RESULTS: Asbestos of the type found in talcum powder was found in all six cases evaluated. Talcum powder usage was the only source of asbestos for all 33 cases.<br><br>CONCLUSIONS: Exposure to asbestos-contaminated talcum powders can cause mesothelioma. Clinicians should elicit a history of talcum powder usage in all patients presenting with mesothelioma.}, }
@article {pmid31596154, year = {2019}, author = {Ceresoli, GL and Rossi, A}, title = {Approved and emerging treatments of malignant pleural mesothelioma in elderly patients.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {12}, pages = {1179-1188}, doi = {10.1080/17476348.2019.1678386}, pmid = {31596154}, issn = {1747-6356}, mesh = {Aged ; Combined Modality Therapy ; Humans ; *Immunotherapy ; Lung Neoplasms/*drug therapy/therapy ; Mesothelioma/*drug therapy/therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/*drug therapy/therapy ; Treatment Outcome ; }, abstract = {Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with asbestos exposure as the dominant etiologic agent. Owing to the long latent period following exposure, MPM is often diagnosed late in life. Despite this, elderly patients are under-represented in clinical trials. To date, data regarding the tolerability and efficacy of anticancer treatments for elderly patients affected by MPM are still lacking.Areas covered: The current state-of-the-art of approved treatments employed in the treatment of MPM elderly patients is reviewed and discussed, with a look to emerging therapies. A structured search of bibliographic databases for peer-reviewed research literature and of main meeting abstracts using a focused review question was undertaken.Expert opinion: Even though the median age of MPM patients enrolled in the most recent experimental trials is increasing, no specific analysis has been reported so far in the elderly. Moreover, no data are available for the 'oldest of the elderly' (>75 years). Treatment of elderly patients with MPM is one of the major challenges to the clinician. There is a clear need of large, well-conducted retrospective studies and above all of prospective investigations in this patient population, both in the first-and in the second-line setting.}, }
@article {pmid31594840, year = {2019}, author = {Kwak, K and Paek, D and Zoh, KE}, title = {Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {11}, pages = {861-871}, doi = {10.1136/oemed-2019-105735}, pmid = {31594840}, issn = {1470-7926}, mesh = {Asbestos/*toxicity ; Cohort Studies ; Colorectal Neoplasms/*epidemiology/*mortality ; Female ; Hazardous Substances/*toxicity ; Humans ; Lung Neoplasms/epidemiology ; Male ; Occupational Exposure/*statistics &amp; numerical data ; Risk Factors ; }, abstract = {Asbestos exposure is associated with mesothelioma and cancer of the lung, larynx and ovary. However, the association between asbestos exposure and colorectal cancer is controversial despite several systematic reviews of the literature, including a number of meta-analyses. We performed a systematic review and meta-analysis to evaluate quantitatively the association between exposure to asbestos and colorectal cancer. We searched for articles on occupational asbestos exposure and colorectal cancer in PubMed, EMBASE and Web of Science published before April 2018. In total, 44 articles were selected and 46 cohort studies were analysed. The overall pooled risk estimates and corresponding 95% CIs of the association between occupational asbestos exposure and colorectal cancer were calculated using a random-effects model. Subgroup analyses and sensitivity tests were also performed. There was a significantly increased risk of colorectal cancer mortality among workers exposed to asbestos occupationally, with an overall pooled SMR of 1.16 (95% CI: 1.05 to 1.29). The pooled SMR for colorectal cancer was elevated in studies in which the asbestos-associated risk of lung cancer was also elevated (1.43; 95% CI: 1.30 to 1.56). This implies that the risk of colorectal cancer mortality increases as the level of asbestos exposure rises. A sensitivity analysis showed robust results and there was no publication bias. Although the effect size was small and the heterogeneity among studies was large, our findings indicate that occupational exposure to asbestos is a risk factor for colorectal cancer.}, }
@article {pmid31564247, year = {2019}, author = {Vimercati, L and Cavone, D and Caputi, A and Delfino, MC and De Maria, L and Ferri, GM and Serio, G}, title = {Malignant mesothelioma in construction workers: the Apulia regional mesothelioma register, Southern Italy.}, journal = {BMC research notes}, volume = {12}, number = {1}, pages = {636}, pmid = {31564247}, issn = {1756-0500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Construction Industry/instrumentation ; Environmental Exposure/*adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Lung/drug effects/pathology ; Lung Neoplasms/chemically induced/diagnosis/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/diagnosis/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; *Registries ; }, abstract = {OBJECTIVE: Asbestos was widely used in construction in both a friable and a compact form until the 1990s, before its use was banned. Today, many of these materials are still in situ and represent a source of risk for construction workers. The objective of the study was to analyse the cases of mesothelioma arising among construction workers registered in the Apulia regional register of mesothelioma.<br><br>RESULTS: For the period 1993-2018, there were 178 male cases, and 10.2% of the cases were present in the regional register. The average age at diagnosis was 64.7 years. The site was pleural in 96.06% of cases, with a diagnosis of certainty in 86.5% of the total cases and 61.8% of cases with epithelial histology. The average latency is 43.9 years. In 75.2% of cases, the exposure began between 1941 and 1970, with an average duration of 24.3 years. The age at the start of exposure in 68.5% of cases is between 8 and 20 years. The ORs were 2.5 (C.I. 95% 1.01-6.17) for the epithelioid histotype and the high duration of exposure. The data underline the need for prevention and information on all activities involving construction workers in which asbestos-containing materials are still used.}, }
@article {pmid31557561, year = {2019}, author = {Takeda, M and Ohe, Y and Horinouchi, H and Hida, T and Shimizu, J and Seto, T and Nosaki, K and Kishimoto, T and Miyashita, I and Yamada, M and Kaneko, Y and Morimoto, C and Nakagawa, K}, title = {Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {137}, number = {}, pages = {64-70}, doi = {10.1016/j.lungcan.2019.09.010}, pmid = {31557561}, issn = {1872-8332}, mesh = {Adult ; Aged ; Antibodies, Monoclonal/pharmacokinetics/*therapeutic use ; Cohort Studies ; Dipeptidyl Peptidase 4/immunology ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*drug therapy/immunology/pathology ; Male ; Maximum Tolerated Dose ; Mesothelioma/*drug therapy/immunology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*drug therapy/immunology/pathology ; Prognosis ; Response Evaluation Criteria in Solid Tumors ; Tissue Distribution ; Young Adult ; }, abstract = {OBJECTIVES: CD26 is a transmembrane glycoprotein with dipeptidyl peptidase IV activity that is overexpressed in malignant pleural mesothelioma (MPM). We performed a phase I study to determine the maximum tolerated dose, pharmacokinetics, and antitumor activity of YS110, a monoclonal antibody to CD26, in Japanese patients with MPM intolerant of or refractory to prior standard therapies.<br><br>MATERIAL AND METHODS: The study was designed as an open-label, 3 + 3 dose-escalation, phase I trial. Patients were sequentially assigned to three dosing cohorts (2, 4, or 6 mg/kg). Each 6-week treatment cycle consisted of YS110 administration weekly for 5 weeks followed by a 1-week rest period. Treatment was continued until disease progression, death, or intolerable toxicity. Corticosteroid, antihistamine, and acetaminophen administration before each infusion was adopted to limit infusion-related reactions (IRRs).<br><br>RESULTS: Nine Japanese patients (seven men and two women, mean age of 62.2 years), three in each dosing cohort, were enrolled in the study. No patient developed a dose-limiting toxicity. Adverse events of grade 3 or 4 developed in seven patients, with the most common such event being a decreased lymphocyte count. Two patients had mild or moderate IRRs. The serum concentration of YS110 increased in a dose-dependent manner. Among seven patients evaluable for tumor response, four showed stable disease and one achieved a partial response.<br><br>CONCLUSIONS: YS110 showed promising antitumor efficacy and was generally well tolerated in Japanese patients with advanced MPM at doses of up to 6 mg/kg. YS110 will be tested at 6 mg/kg in a subsequent phase II study.}, }
@article {pmid31546009, year = {2020}, author = {Hinz, TK and Heasley, LE}, title = {Translating mesothelioma molecular genomics and dependencies into precision oncology-based therapies.}, journal = {Seminars in cancer biology}, volume = {61}, number = {}, pages = {11-22}, doi = {10.1016/j.semcancer.2019.09.014}, pmid = {31546009}, issn = {1096-3650}, mesh = {Animals ; Biomarkers, Tumor ; Combined Modality Therapy ; Gene Expression Profiling/methods ; Genetic Association Studies ; Genetic Predisposition to Disease ; *Genomics/methods ; Humans ; Loss of Function Mutation ; Mesothelioma/diagnosis/*etiology/*therapy ; Mesothelioma, Malignant/diagnosis/etiology/therapy ; Mutation ; *Precision Medicine/methods ; Receptor, Fibroblast Growth Factor, Type 1/genetics ; *Translational Medical Research/methods ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, yet lethal asbestos-induced cancer and despite marked efforts to reduce occupational exposure, the incidence has not yet significantly declined. Since 2003, combined treatment with a platinum-based agent and pemetrexed has been the first-line therapy and no effective or approved second-line treatments have emerged. The seemingly slow advance in developing new MPM treatments does not appear to be related to a low level of clinical and pre-clinical research activity. Rather, we suggest that a key hurdle in successfully translating basic discovery into novel MPM therapeutics is the underlying assumption that as a rare cancer, it will also be molecularly and genetically homogeneous. In fact, lung adenocarcinoma and melanoma only benefitted from precision oncology upon full appreciation of the high degree of molecular heterogeneity inherent in these cancers, especially regarding the diversity of oncogenic drivers. Herein, we consider the recent explosion of molecular and genetic information that has become available regarding MPM and suggest ways in which the unfolding landscape may guide identification of novel therapeutic vulnerabilities within subsets of MPM that can be targeted in a manner consistent with the tenets of precision oncology.}, }
@article {pmid31538797, year = {2019}, author = {Geyer, SJ}, title = {Malignant Mesothelioma and Its Nonasbestos Causes: Talcum Powder Does Not Create Occult Asbestos Exposure.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {143}, number = {12}, pages = {1439}, doi = {10.5858/arpa.2019-0388-LE}, pmid = {31538797}, issn = {1543-2165}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Talc ; }, }
@article {pmid31534051, year = {2019}, author = {Hamaidia, M and Gazon, H and Hoyos, C and Hoffmann, GB and Louis, R and Duysinx, B and Willems, L}, title = {Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1-dependent mechanism.}, journal = {JCI insight}, volume = {4}, number = {18}, pages = {}, pmid = {31534051}, issn = {2379-3708}, mesh = {Animals ; Antineoplastic Agents, Immunological/pharmacology/therapeutic use ; Cell Communication/*immunology ; Cell Culture Techniques ; Cell Line, Tumor/transplantation ; Coculture Techniques ; Disease Models, Animal ; Enhancer of Zeste Homolog 2 Protein/antagonists &amp; inhibitors/genetics/immunology/*metabolism ; Humans ; Immunogenic Cell Death/drug effects/genetics ; Lung Neoplasms/*immunology/therapy ; Macrophages/*immunology/metabolism/transplantation ; Male ; Mesothelioma/*immunology/therapy ; Mesothelioma, Malignant ; Mice ; Peroxynitrous Acid/metabolism ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/*immunology ; RAW 264.7 Cells/transplantation ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {The roles of macrophages in orchestrating innate immunity through phagocytosis and T lymphocyte activation have been extensively investigated. Much less understood is the unexpected role of macrophages in direct tumor regression. Tumoricidal macrophages can indeed manifest cancer immunoediting activity in the absence of adaptive immunity. We investigated direct macrophage cytotoxicity in malignant pleural mesothelioma, a lethal cancer that develops from mesothelial cells of the pleural cavity after occupational asbestos exposure. In particular, we analyzed the cytotoxic activity of mouse RAW264.7 macrophages upon cell-cell contact with autologous AB1/AB12 mesothelioma cells. We show that macrophages killed mesothelioma cells by oxeiptosis via a mechanism involving enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27-specific (H3K27-specific) methyltransferase of the polycomb repressive complex 2 (PRC2). A selective inhibitor of EZH2 indeed impaired RAW264.7-directed cytotoxicity and concomitantly stimulated the PD-1 immune checkpoint. In the immunocompetent BALB/c model, RAW264.7 macrophages pretreated with the EZH2 inhibitor failed to control tumor growth of AB1 and AB12 mesothelioma cells. Blockade of PD-1 engagement restored macrophage-dependent antitumor activity. We conclude that macrophages can be directly cytotoxic for mesothelioma cells independent of phagocytosis. Inhibition of the PRC2 EZH2 methyltransferase reduces this activity because of PD-1 overexpression. Combination of PD-1 blockade and EZH2 inhibition restores macrophage cytotoxicity.}, }
@article {pmid31525810, year = {2019}, author = {Kim, RY and Sterman, DH and Haas, AR}, title = {Malignant Mesothelioma: Has Anything Changed?.}, journal = {Seminars in respiratory and critical care medicine}, volume = {40}, number = {3}, pages = {347-360}, doi = {10.1055/s-0039-1693406}, pmid = {31525810}, issn = {1098-9048}, mesh = {Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; Biomarkers, Tumor ; Biopsy ; CTLA-4 Antigen/antagonists &amp; inhibitors ; Catheters, Indwelling ; Combined Modality Therapy ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnosis/pathology/*therapy ; Mesothelioma/diagnosis/pathology/*therapy ; Mesothelioma, Malignant ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/pathology/*therapy ; Pneumonectomy/methods ; Prognosis ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; Radiotherapy, Adjuvant ; Thoracoscopy ; }, abstract = {Malignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma.}, }
@article {pmid31511437, year = {2020}, author = {Huang, Q and Lan, YJ}, title = {Colorectal cancer and asbestos exposure-an overview.}, journal = {Industrial health}, volume = {58}, number = {3}, pages = {200-211}, pmid = {31511437}, issn = {1880-8026}, abstract = {The relationship between colorectal cancer and asbestos exposure has not been fully clarified. This study aimed to determine the associations between asbestos exposure and colorectal cancer. We performed a meta-analysis to quantitatively evaluate this association. A fixed effects model was used to summarize the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. We analyzed the dose-effect relationship using lung cancer standardized mortality ratio (SMR) and the risk of mesothelioma as a percent (%) as exposure surrogates. A total of 47 cohort studies were included. We identified 28 incidence cohort studies from 17 separate papers and extracted colorectal cancer standardized incidence ratio (SIR). Cancer mortality data were extracted from 19 separate cohorts among 13 papers. The overall colorectal cancer SMR for synthesis cohort was 1.07 (95% CI 1.02-1.12). Statistically significant excesses were observed in exposure to mixed asbestos (SMR/SIR=1.07), exposure to production (SMR/SIR=1.11), among asbestos cement workers (SMR/SIR=1.18) and asbestos textile workers (SMR/SIR=1.11). Additionally, we determined that the SMR for lung cancer increased with increased exposure to asbestos, as did the risk for colorectal cancer. This study confirms that colorectal cancer has a positive weak associations with asbestos exposure.}, }
@article {pmid31477126, year = {2019}, author = {Abdelgied, M and El-Gazzar, AM and Alexander, WT and Numano, T and Iigou, M and Naiki-Ito, A and Takase, H and Hirose, A and Taquahashi, Y and Kanno, J and Abdelhamid, M and Abdou, KA and Takahashi, S and Alexander, DB and Tsuda, H}, title = {Carcinogenic effect of potassium octatitanate (POT) fibers in the lung and pleura of male Fischer 344 rats after intrapulmonary administration.}, journal = {Particle and fibre toxicology}, volume = {16}, number = {1}, pages = {34}, pmid = {31477126}, issn = {1743-8977}, mesh = {Animals ; Carcinogens/chemistry/pharmacokinetics/*toxicity ; Inhalation Exposure ; Lung/*drug effects/pathology ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mesothelioma, Malignant ; Mineral Fibers ; Pleura/*drug effects/pathology ; Rats, Inbred F344 ; Surface Properties ; Tissue Distribution ; Titanium/chemistry/pharmacokinetics/*toxicity ; }, abstract = {BACKGROUND: Potassium octatitanate fibers (K2O•8TiO2, POT fibers) are used as an asbestos substitute. Their physical characteristics suggest that respirable POT fibers are likely to be carcinogenic in the lung and pleura. However, previous 2-year inhalation studies reported that respired POT fibers had little or no carcinogenic potential. In the present study ten-week old male F344 rats were left untreated or were administered vehicle, 0.25 or 0.5 mg rutile-type nano TiO2 (r-nTiO2), 0.25 or 0.5 mg POT fibers, or 0.5 mg MWCNT-7 by intra-tracheal intra-pulmonary spraying (TIPS), and then observed for 2 years.<br><br>RESULTS: There were no differences between the r-nTiO2 and control groups. The incidence of bronchiolo-alveolar cell hyperplasia was significantly increased in the groups treated with 0.50 mg POT and 0.50 mg MWCNT-7. The overall incidence of lung tumors, however, was not increased in either the POT or MWCNT-7 treated groups. Notably, the carcinomas that developed in the POT and MWCNT-7 treated rats were accompanied by proliferative fibrous connective tissue while the carcinomas that developed in the untreated rats and the r-nTiO2 treated rats were not (carcinomas did not develop in the vehicle control rats). In addition, the carcinoma that developed in the rat treated with 0.25 mg POT was a squamous cell carcinoma, a tumor that develops spontaneously in about 1 per 1700 rats. The incidence of mesothelial cell hyperplasia was 4/17, 7/16, and 10/14 and the incidence of malignant mesothelioma was 3/17, 1/16, and 2/14 in the 0.25 mg POT, 0.5 mg POT, and MWCNT-7 treated groups, respectively. Neither mesothelial cell hyperplasia nor mesothelioma developed in control rats or the rats treated with r-nTiO2. Since the incidence of spontaneously occurring malignant mesothelioma in rats is extremely low, approximately 1 per 1000 animals (Japan Bioassay Research Center [JBRC] historical control data), the development of multiple malignant mesotheliomas in the POT and MWCNT-7 treated groups was biologically significant.<br><br>CONCLUSION: The incidence of pleural mesotheliomas in male F344 rats administered POT fibers and MWCNT-7 was significantly higher than the JBRC historical control data, indicating that the incidence of pleural mesothelioma in the groups administered POT fibers and MWCNT-7 fibers via the airway using TIPS was biologically significant. The incidence of type II epithelial cell hyperplasia and the histology of the carcinomas that developed in the POT treated rats also indicates that respirable POT fibers are highly likely to be carcinogenic in the lungs of male F344 rats.}, }
@article {pmid31475103, year = {2019}, author = {Cavallari, I and Urso, L and Sharova, E and Pasello, G and Ciminale, V}, title = {Liquid Biopsy in Malignant Pleural Mesothelioma: State of the Art, Pitfalls, and Perspectives.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {740}, pmid = {31475103}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to asbestos exposure. Although the risk factors for MPM are well-known, the majority of MPM patients are diagnosed at an advanced stage and have a very poor prognosis. Circulating biomarkers for early diagnosis remain to be identified, and the current standard for MPM diagnosis relies on pleural biopsies. Robust non-invasive tests for the screening of asbestos-exposed subjects are therefore an important unmet clinical need. This review provides a critical summary of recent liquid biopsy-based studies aimed at discovering novel blood-based circulating biomarkers for the early diagnosis and prognostic stratification of MPM patients.}, }
@article {pmid31470859, year = {2019}, author = {Vimercati, L and Cavone, D and Delfino, MC and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (southern Italy) mesothelioma register.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {78}, pmid = {31470859}, issn = {1476-069X}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Mesothelioma, Malignant ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure/*adverse effects ; Registries/*statistics &amp; numerical data ; Testicular Neoplasms/chemically induced/*epidemiology ; }, abstract = {BACKGROUND: Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare disease with a poor prognosis. The diagnosis and management of these lesions are often difficult for pathologists, surgeons, oncologists and occupational physicians. A preoperative diagnosis of malignancy is rarely made, and there is no established effective therapy except orchidectomy.<br><br>METHODS: A systematic literature review was conducted among the articles published in the English literature on primary MMTVT. Moreover four cases from the Apulia mesothelioma register are reported here.<br><br>RESULTS: Two hundred eighty-nine cases of MMTVT have been reported from 1943 to 2018. Overall asbestos exposure has been investigated only for 58% of all cases reported in this review, while in 41.8% this data are not available. Noteworthy is the fact that in many reports there is not an anamnestic reconstruction of any asbestos exposure. A history of direct occupational, environmental or familial asbestos exposure is found in 27.6% of the cases. The four cases from the Apulia mesothelioma register are all with ascertained occupational exposure to asbestos.<br><br>CONCLUSIONS: The true incidence of asbestos exposure in MMTVT is underestimated because of insufficient information reported in older literature. To establish a broad consensus on the causal relationship between asbestos and MMTVT in the scientific community its necessary to analyze the same variables in the epidemiological studies. In general it should be recommended that a positive history of exposure to asbestos or to asbestos-containing materials are at risk for the development of a MMTVT and should be monitored.}, }
@article {pmid31467759, year = {2019}, author = {Hassan, D and Ligato, S}, title = {Localized Biphasic Malignant Peritoneal Mesothelioma with Rhabdoid Features Involving the Liver: Case Report and Review of the Literature.}, journal = {Case reports in pathology}, volume = {2019}, number = {}, pages = {2732674}, pmid = {31467759}, issn = {2090-6781}, abstract = {Introduction: Localized malignant mesotheliomas, defined as sharply circumscribed tumors of the serosal membrane with the microscopic appearance of diffuse malignant mesothelioma, are rare tumors; their behavior and prognosis are uncertain. Intrahepatic mesotheliomas are postulated to arise from mesothelial cells of Glisson's capsule.<br><br>Case Presentation: A 69-year-old female with no history of asbestos exposure presented with a one-month history of increasing abdominal pain associated with constitutional symptoms. Computerized Tomography (CT) scan of the abdomen and pelvis revealed a sizable soft tissue mass within the right paracolic gutter, abutting the inferior hepatic margin, the lateral abdominal wall, and descending colon. Ultrasound-guided biopsy of the mass suggested a poorly differentiated hepatocellular carcinoma. There was no disease elsewhere on PET scan. Surgical resection of the mass was performed. Pathological assessment suggested the tumor to be arising from the liver with invasion of the liver, abdominal wall musculature, and the adventitial surface of the ascending colon. A final diagnosis of localized biphasic malignant peritoneal mesothelioma with rhabdoid features was rendered based on morphology and the result of immunohistochemical studies. The abdominal wall margin was positive. The patient progressed over the course of 6 months despite receiving adjuvant chemotherapy and immunotherapy with metastases and a decline in performance status and was transitioned to hospice.<br><br>Conclusion: Localized malignant peritoneal mesotheliomas are rare tumors that may present clinically as a liver mass and simulate primary hepatic or secondary tumors. Definitive diagnosis is obtained by surgical resection in most cases. The clinical outcome is variable with most cases having a poor outcome.}, }
@article {pmid31442913, year = {2019}, author = {Li, Z and Jiang, L and Chew, SH and Hirayama, T and Sekido, Y and Toyokuni, S}, title = {Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia.}, journal = {Redox biology}, volume = {26}, number = {}, pages = {101297}, pmid = {31442913}, issn = {2213-2317}, mesh = {Antigens, Neoplasm/*genetics/*metabolism ; Apoptosis/*genetics ; Biomarkers ; Carbonic Anhydrase IX/*genetics/*metabolism ; Cell Line, Tumor ; Ferroptosis/*genetics ; Humans ; Hypoxia/*metabolism ; Lung Neoplasms/*genetics/*metabolism ; Mesothelioma/*genetics/*metabolism ; Mesothelioma, Malignant ; Mitochondria/genetics/metabolism ; Models, Biological ; Reactive Oxygen Species/metabolism ; }, abstract = {Hypoxia and acidity provide microenvironment for selection under evolutionary pressure and proliferation in cancer cells. Carbonic anhydrases (CAs) are a superfamily of metalloenzymes present in all life kingdoms, equilibrating the reactions among CO2, bicarbonate and H+. CA9, a membrane-associated α-CA, has been a drug target for various cancers. Whereas iron is essential not only for cancer cells but also for all the lives on earth, little is known on the association among hypoxia, iron metabolism, extracellular acidity and redox regulation. Malignant mesothelioma (MM), an aggressive tumor with poor prognosis, is an intriguing model in that asbestos-associated pathogenesis includes excess iron environment during carcinogenesis. Re-analysis of rat asbestos-induced MM model revealed an inverse association between high CA9 expression and survival. Here we used human MMs to identify the molecular events surrounding CA9 from the viewpoint of iron metabolism. CA9 expression was significantly higher in MM cells than in MeT-5A mesothelial cells, which was further amplified under hypoxia (1%O2) with increased catalytic Fe(II). CA9 suppression by inhibitors (S4 and U104) decreased viability and migration of MM cells, accompanied by overexpression of TFRC, IREB1/2 and FPN1(SLC40A1) and by downregulation of FTH/FTL. This expressional pattern was similar to that of erastin-induced ferroptosis in the same cells. Furthermore, we observed mitochondrial fission and enhanced autophagy with increased catalytic Fe(II) in both mitochondria and lysosomes after CA9 inhibition, accompanied by increased peroxides, mitochondrial O2- and lipid peroxidation. The eventual cell death was significantly inhibited by deferoxamine, ferrostatin-1 and Z-VAD-FMK, suggesting a mixed cell death of ferroptosis and apoptosis. Therefore, CA9 plays a role in equilibrating among hypoxia, iron metabolism and redox regulation in MM cells.}, }
@article {pmid31428834, year = {2019}, author = {Keshava, HB and Tang, A and Siddiqui, HU and Raja, S and Raymond, DP and Bribriesco, A and Stevenson, J and Murthy, SC and Ahmad, U}, title = {Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA.}, journal = {World journal of surgery}, volume = {43}, number = {12}, pages = {3239-3247}, pmid = {31428834}, issn = {1432-2323}, support = {U01 HL088955/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology/mortality ; United States/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Projections based on regulations curtailing asbestos use in the USA suggest that peak incidence of pleural mesothelioma would occur between 2000 and 2005 and then decline. We analyzed the National Cancer Database (NCDB) to assess current trends in disease incidence, patient demographics, cancer treatment, and survival.<br><br>METHODS: The NCDB was queried to identify patients diagnosed with pleural mesothelioma from 2004 through 2014. Clinical and pathologic characteristics, treatments, and survival were analyzed. Risk factors for death were identified by multivariable Cox regression.<br><br>RESULTS: A total of 20,988 patients with pleural mesothelioma were reported to the NCDB. The number of cases per year increased from 1783 to 1961, accounting for roughly 0.3% of all reported cancers each year. The proportion of elderly patients increased from 75 to 80%, but distribution by sex remained constant (20% female). The proportion of patients undergoing treatment increased from 34 to 54%. One-year survival increased from 37 to 47% and 3-year survival from 9 to 15% (p < 0.001). Factors associated with improved survival included younger age, female sex, epithelioid histology, treatment in an academic center, health insurance, higher income, and multimodality therapy.<br><br>CONCLUSIONS: The annual incidence of mesothelioma has not declined this century and remains stable. Reporting of histologic and clinical staging has improved. National trends suggest that survival is slowly increasing despite an aging cohort. Multimodal therapy and treatment at academic centers are modifiable risk factors associated with improved survival.}, }
@article {pmid31428586, year = {2019}, author = {Hoffmann, PR and Hoffmann, FW and Premeaux, TA and Fujita, T and Soprana, E and Panigada, M and Chew, GM and Richard, G and Hindocha, P and Menor, M and Khadka, VS and Deng, Y and Moise, L and Ndhlovu, LC and Siccardi, A and Weinberg, AD and De Groot, AS and Bertino, P}, title = {Multi-antigen Vaccination With Simultaneous Engagement of the OX40 Receptor Delays Malignant Mesothelioma Growth and Increases Survival in Animal Models.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {720}, pmid = {31428586}, issn = {2234-943X}, support = {G12 MD007601/MD/NIMHD NIH HHS/United States ; R01 AI089999/AI/NIAID NIH HHS/United States ; P20 GM103466/GM/NIGMS NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; R13 CA150300/CA/NCI NIH HHS/United States ; P30 GM114737/GM/NIGMS NIH HHS/United States ; U54 MD007584/MD/NIMHD NIH HHS/United States ; P30 GM103341/GM/NIGMS NIH HHS/United States ; G12 RR003061/RR/NCRR NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; }, abstract = {Malignant Mesothelioma (MM) is a rare and highly aggressive cancer that develops from mesothelial cells lining the pleura and other internal cavities, and is often associated with asbestos exposure. To date, no effective treatments have been made available for this pathology. Herein, we propose a novel immunotherapeutic approach based on a unique vaccine targeting a series of antigens that we found expressed in different MM tumors, but largely undetectable in normal tissues. This vaccine, that we term p-Tvax, is comprised of a series of immunogenic peptides presented by both MHC-I and -II to generate robust immune responses. The peptides were designed using in silico algorithms that discriminate between highly immunogenic T cell epitopes and other harmful epitopes, such as suppressive regulatory T cell epitopes and autoimmune epitopes. Vaccination of mice with p-Tvax led to antigen-specific immune responses that involved both CD8+ and CD4+ T cells, which exhibited cytolytic activity against MM cells in vitro. In mice carrying MM tumors, p-Tvax increased tumor infiltration of CD4+ T cells. Moreover, combining p-Tvax with an OX40 agonist led to decreased tumor growth and increased survival. Mice treated with this combination immunotherapy displayed higher numbers of tumor-infiltrating CD8+ and CD4+ T cells and reduced T regulatory cells in tumors. Collectively, these data suggest that the combination of p-Tvax with an OX40 agonist could be an effective strategy for MM treatment.}, }
@article {pmid31420427, year = {2019}, author = {Bousema, JE and van de Luijtgaarden, KM and Wilhelmus, S and Poelman, MM}, title = {Acute severe abdominal pain in a young woman caused by a well-differentiated papillary mesothelioma of the peritoneum.}, journal = {BMJ case reports}, volume = {12}, number = {8}, pages = {}, doi = {10.1136/bcr-2019-229769}, pmid = {31420427}, issn = {1757-790X}, mesh = {Abdominal Pain/*diagnosis/etiology ; Acute Pain/*diagnosis/etiology ; Adult ; Female ; Humans ; Mesothelioma/complications/*diagnosis ; Peritoneal Neoplasms/complications/*diagnosis ; }, abstract = {Acute abdominal pain is a common symptom in young women. We describe a patient with acute illness and severe lower abdominal pain. Laboratory tests were normal except for mildly deranged inflammatory markers. No abnormalities were reported on abdominal ultrasonography and MRI, whereas diagnostic laparoscopy revealed a tumour located dorsally from the uterus. We resected the tumour and pathology results showed a well-differentiated papillary mesothelioma of the peritoneum (WDPMP). Microscopy showed evidence of acute ischaemia in the resected lesion, which was likely the cause of the acute abdominal pain. WDPMP is a rare disease that arises from the serous membranes which does not seem to have a relation to asbestos exposure. Generally, WDPMP has a mild clinical course and good long-term prognosis.}, }
@article {pmid31419715, year = {2019}, author = {Consonni, D and Migliore, E and Barone-Adesi, F and Dallari, B and De Matteis, S and Oddone, E and Pesatori, AC and Riboldi, L and Mirabelli, D and Mensi, C}, title = {Gender differences in pleural mesothelioma occurrence in Lombardy and Piedmont, Italy.}, journal = {Environmental research}, volume = {177}, number = {}, pages = {108636}, doi = {10.1016/j.envres.2019.108636}, pmid = {31419715}, issn = {1096-0953}, mesh = {*Asbestos ; Female ; Humans ; Incidence ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Exposure/*statistics &amp; numerical data ; Pleural Neoplasms/*epidemiology ; Registries ; Sex Factors ; }, abstract = {BACKGROUND: Higher mesothelioma rates in men (vs women) reflect more frequent and more intense asbestos exposure. We assessed the impact of exposure difference between genders on age-specific rates of pleural mesothelioma (PM) occurrence using data from two Italian regions.<br><br>METHODS: We used data from the Lombardy and Piedmont mesothelioma registries (period 2000-2016, age 45-74 years) to compare rates of PM in men and women and to estimate the rate advancement period (RAP).<br><br>RESULTS: Based on 3384 cases (2405 men, 979 women) in Lombardy and 2042 (1389 men, 653 women) in Piedmont, the rate ratio was 2.81 (90% confidence interval: 2.61-3.03) in Lombardy and 2.39 (2.17-2.62) in Piedmont. In both regions RAP ranged from 7 to 10 years (at age 45 and 63 in men, respectively).<br><br>CONCLUSION: Men showed more than twofold increased PM rates and reached the same incidence as women 7-10 years earlier. RAP can be a useful measure of exposure impact on premature disease occurrence.}, }
@article {pmid31416570, year = {2019}, author = {Betti, M and Aspesi, A and Sculco, M and Matullo, G and Magnani, C and Dianzani, I}, title = {Genetic predisposition for malignant mesothelioma: A concise review.}, journal = {Mutation research}, volume = {781}, number = {}, pages = {1-10}, doi = {10.1016/j.mrrev.2019.03.001}, pmid = {31416570}, issn = {1873-135X}, mesh = {Animals ; Asbestos/toxicity ; DNA Repair/drug effects/genetics ; Environmental Exposure/adverse effects ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/drug effects/genetics ; Humans ; Lung Neoplasms/chemically induced/*etiology ; Mesothelioma/chemically induced/*etiology ; Mesothelioma, Malignant ; Risk Factors ; }, abstract = {Malignant mesothelioma (MM) is an aggressive cancer associated with asbestos exposure. Studies of familial malignant pleural mesothelioma (MPM) have suggested the existence of a genetic predisposition. Information on the role of genetic risk factors in the development of MM has been growing in the last years, and both low- and high-risk genetic factors have been identified, but genetic factors alone (without any exposure to asbestos or other mineral fibers) have never been shown to induce MM. Low-risk genetic factors have been identified in studies that systematically analyzed the whole genome. When considered alone these low-risk genetic factors carry a relative risk of MPM that is 10- to 15-fold lower than that carried by asbestos exposure; however, a large number of these factors in combination may increase the impact of asbestos exposure. High-risk genetic factors include truncating variants in the tumor suppressor BAP1 and in other tumor suppressor genes belonging to DNA repair pathways. Heterozygous germline variants in these genes may favor carcinogenesis if a second somatic variant occurs that impairs the wild-type allele. This impairment can cause genetic instability due to the suppression of a specific DNA repair pathway, and transformation. This genetic predisposition may have translational consequences, as it may predict patient response to drugs that induce tumor-specific synthetic lethality.}, }
@article {pmid31413184, year = {2019}, author = {Barone-Adesi, F and Ferrante, D and Chellini, E and Merler, E and Pavone, V and Silvestri, S and Miligi, L and Gorini, G and Bressan, V and Girardi, P and Ancona, L and Romeo, E and Luberto, F and Sala, O and Scarnato, C and Menegozzo, S and Oddone, E and Tunesi, S and Perticaroli, P and Pettinari, A and Cuccaro, F and Curti, S and Baldassarre, A and Cena, T and Angelini, A and Marinaccio, A and Mirabelli, D and Musti, M and Pirastu, R and Ranucci, A and Magnani, C and , }, title = {Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {9}, pages = {611-616}, doi = {10.1136/oemed-2019-105779}, pmid = {31413184}, issn = {1470-7926}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Models, Theoretical ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis.<br><br>METHODS: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time.<br><br>RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer.<br><br>CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.}, }
@article {pmid31411568, year = {2019}, author = {Gudmundsson, G and Tomasson, K}, title = {[Asbestos and its effects on health of Icelanders - review].}, journal = {Laeknabladid}, volume = {105}, number = {7}, pages = {327-334}, doi = {10.17992/lbl.2019.0708.241}, pmid = {31411568}, issn = {1670-4959}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/diagnostic imaging/*epidemiology/pathology ; Construction Materials/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Iceland/epidemiology ; Incidence ; Lung Neoplasms/diagnostic imaging/*epidemiology/pathology ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Risk Assessment ; Risk Factors ; Sex Distribution ; Time Factors ; }, abstract = {Asbestos are crystallized silicate minerals that form fibers with different structures and characteristics. Asbestos fibers are very durable and can tolerate very high temperatures. Therefore it was common to use asbestos as a fire retardants, heat insulation and where high temperature is used. Asbestos has been banned in Iceland from 1983 but can still be found in large amounts in buildings, ships and hot water pipes. Large amounts of asbestos were imported in the years before the ban but diminished soon to almost nothing today. Needle or filamentous shaped dust is released when working with asbestos. It is this dust that is dangerous for health. The latent time from exposure to disease can be up to forty years. Asbestos reaches the lungs via inhalation and can cause asbestosis that is a form of lung fibrosis with slow progression. Asbestos can also cause benign pleural effusions, pleural plaques and diffuse pleural thickening. Asbestos is a carcinogen. Lung cancer is most common but asbestos is also a risk factor for cancers of other organs. Mesothelioma is most common in the pleura but can be seen in other membranes. The incidence of these tumors is high in Iceland and is still increasing among males. Of all the European countries mortality is highest in Iceland. It is important for physicians to include asbestos exposure in the differential diagnosis of lung diseases and when lung cancer is diagnosed.}, }
@article {pmid31411522, year = {2019}, author = {Jiang, Y and Mei, Z and Cao, H and Li, S and Xu, H and Qiu, H and Liu, Y}, title = {Meningeal metastasis of a malignant peritoneal mesothelioma: A case report and literature review.}, journal = {Cancer biology &amp; therapy}, volume = {20}, number = {12}, pages = {1409-1415}, pmid = {31411522}, issn = {1555-8576}, mesh = {Asbestos/adverse effects ; Biomarkers, Tumor ; Biopsy ; Disease Progression ; Fatal Outcome ; Female ; Genetic Testing ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnostic imaging/etiology/*pathology ; Meningeal Neoplasms/*diagnosis/*secondary/therapy ; Mesothelioma/diagnostic imaging/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Multimodal Imaging/methods ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/diagnostic imaging/etiology/*pathology ; Radiotherapy, Intensity-Modulated ; }, abstract = {Malignant peritoneal mesothelioma is a very rare tumor originating from the peritoneal serous mesothelium. Meningeal metastasis of malignant peritoneal is even more rare. Here, we reported a case of a 60-year-old female patient with a history of exposure to asbestos for 10 years who presented with massive peritoneal effusion followed by disorder of consciousness and symptoms of cranial nerve injury. The patient was diagnosed as peritoneal mesothelioma with meningeal metastasis through neurological symptoms, cytological finding of cerebrospinal fluid combined with cranial magnetic resonance imaging (MRI). The patient received systemic chemotherapy and total craniospinal irradiation. The follow up visits showed that the survival time of patient after diagnosis of meningeal metastasis from peritoneal mesothelioma was 5 months. To our knowledge, this is the first case of menigeal metastasis of peritoneal mesothelioma. We hope this particular case may be helpful in providing some experience to the treatment of peritoneal mesothelioma with meningeal metastasis.}, }
@article {pmid31406977, year = {2019}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {11}, pages = {1844}, doi = {10.1093/annonc/mdz217}, pmid = {31406977}, issn = {1569-8041}, }
@article {pmid31406207, year = {2019}, author = {Munson, PB and Hall, EM and Farina, NH and Pass, HI and Shukla, A}, title = {Exosomal miR-16-5p as a target for malignant mesothelioma.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {11688}, doi = {10.1038/s41598-019-48133-0}, pmid = {31406207}, issn = {2045-2322}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; R21 ES028857/ES/NIEHS NIH HHS/United States ; S10 OD025030/OD/NIH HHS/United States ; }, mesh = {Aniline Compounds/pharmacology ; Antineoplastic Agents/*pharmacology ; Benzylidene Compounds/pharmacology ; Cell Death ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclin D1/*genetics/metabolism ; Exosomes/*chemistry/metabolism ; *Gene Expression Regulation, Neoplastic ; Humans ; Indoles/pharmacology ; Lung Neoplasms/genetics/metabolism/pathology ; Maleimides/pharmacology ; Mesothelioma/genetics/metabolism/pathology ; Mesothelioma, Malignant ; MicroRNAs/*genetics/metabolism ; Molecular Targeted Therapy/methods ; Ornithine/analogs &amp; derivatives/pharmacology ; Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism ; Signal Transduction ; Small Molecule Libraries/pharmacology ; Transfection ; }, abstract = {Malignant mesothelioma (MM) is an asbestos-induced cancer arising on the mesothelial surface of organ cavities. MM is essentially incurable without a means of early diagnosis and no successful standard of care. These facts indicate a deep chasm of knowledge that needs to be filled. Our group recently delved into MM tumor biology from the perspective of exosome-contained microRNAs (miRNAs). We discovered that the most abundant miRNAs in MM cancer exosomes were tumor suppressors, particularly miR-16-5p. This observation lead us to hypothesize that MM cells preferentially secreted tumor-suppressor miRNAs via exosomes. Through separate avenues of potential therapeutic advance, we embarked on an innovative strategy to kill MM tumor cells. We employed small molecule inhibitors to block exosome secretion, thereby reducing miR-16-5p exosome loss and replenishing cellular miR-16-5p leading to reduced tumorigenic capacity and miR-16-5p target oncoproteins CCND1 and BCL2. Additionally, we force-fed MM tumor exosomes back to MM tumor cells, which led to cell death, and a reduction in the same oncoproteins. We recapitulated these results with direct transfection of miR-16-5p, confirmed that this is a cancer-cell specific effect, and elucidated a part of the miR-16-5p mechanism of exosome loading.}, }
@article {pmid31391078, year = {2019}, author = {Luberto, F and Ferrante, D and Silvestri, S and Angelini, A and Cuccaro, F and Nannavecchia, AM and Oddone, E and Vicentini, M and Barone-Adesi, F and Cena, T and Mirabelli, D and Mangone, L and Roncaglia, F and Sala, O and Menegozzo, S and Pirastu, R and Azzolina, D and Tunesi, S and Chellini, E and Miligi, L and Perticaroli, P and Pettinari, A and Bressan, V and Merler, E and Girardi, P and Bisceglia, L and Marinaccio, A and Massari, S and Magnani, C and , }, title = {Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {71}, pmid = {31391078}, issn = {1476-069X}, support = {Current research 2012: asbestos project. Operative Unit 2//Istituto Superiore Sanità/International ; Piano Ricerca 2016-2018, &quot;Programma Speciale Amianto&quot;, Ricerca BRIC id 55//INAIL/International ; Piano Ricerca 2016-2018, &quot;Programma Speciale Amianto&quot;, Ricerca BRIC id 59//INAIL/International ; }, mesh = {Adult ; Asbestos/*adverse effects ; Asbestosis/*epidemiology/etiology ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Neoplasms/chemically induced/*epidemiology ; Occupational Exposure/*adverse effects ; Sex Factors ; Time Factors ; Young Adult ; }, abstract = {BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos.<br><br>METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution.<br><br>RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%.<br><br>CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.}, }
@article {pmid31388672, year = {2020}, author = {Corti, A and Bonetti, J and Dominici, S and Piaggi, S and Fierabracci, V and Foddis, R and Pompella, A}, title = {Induction of Gamma-Glutamyltransferase Activity and Consequent Pro-oxidant Reactions in Human Macrophages Exposed to Crocidolite Asbestos.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {177}, number = {2}, pages = {476-482}, doi = {10.1093/toxsci/kfz175}, pmid = {31388672}, issn = {1096-0929}, abstract = {Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact react with macrophage-derived hydrogen peroxide in the so called Fenton reaction, giving rise to highly reactive and mutagenic hydroxyl radical. On the other hand, hydroxyl radical can as well originate after thiol-dependent reduction of iron, a process capable of starting its redox cycling. Previous studies showed that glutathione (GSH) is one such thiol, and that cellular gamma-glutamyltransferase (GGT) can efficiently potentiate GSH-dependent iron redox cycling and consequent oxidative stress. As GGT is expressed in macrophages and is released upon their activation, the present study was aimed at verifying the hypothesis that GSH/GGT-dependent redox reactions may participate in the oxidative stress following the activation of macrophages induced by crocidolite asbestos. Experiments in acellular systems confirmed that GGT-mediated metabolism of GSH can potentiate crocidolite-dependent production of superoxide anion, through the production of highly reactive dipeptide thiol cysteinyl-glycine. Cultured THP-1 macrophagic cells, as well as isolated monocytes obtained from healthy donors and differentiated to macrophages in vitro, were investigated as to their expression of GGT and the effects of exposure to crocidolite. The results show that crocidolite asbestos at subtoxic concentrations (50-250 ng/1000 cells) can upregulate GGT expression, which raises the possibility that macrophage-initiated, GSH/GGT-dependent pro-oxidant reactions may participate in the pathogenesis of tissue damage and inflammation consequent to crocidolite intoxication.}, }
@article {pmid31383968, year = {2020}, author = {Wronkiewicz, SK and Roggli, VL and Hinrichs, BH and Kendler, A and Butler, RA and Christensen, BC and Marsit, CJ and Nelson, HH and McClean, MD and Kelsey, KT and Langevin, SM}, title = {Chrysotile fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {2}, pages = {228-234}, pmid = {31383968}, issn = {1530-0285}, support = {R21 DE027227/DE/NIDCR NIH HHS/United States ; P30 ES006096/ES/NIEHS NIH HHS/United States ; R01 CA100679/CA/NCI NIH HHS/United States ; }, abstract = {Asbestos describes a group of naturally occurring fibrous silicate mineral compounds that have been associated with a number of respiratory maladies, including mesothelioma and lung cancer. In addition, based primarily on epidemiologic studies, asbestos has been implicated as a risk factor for laryngeal and pharyngeal squamous cell carcinoma (SCC). The main objective of this work was to strengthen existing evidence via empirical demonstration of persistent asbestos fibers embedded in the tissue surrounding laryngeal and pharyngeal SCC, thus providing a more definitive biological link between exposure and disease. Six human papillomavirus (HPV)-negative laryngeal (n = 4) and pharyngeal (n = 2) SCC cases with a history working in an asbestos-exposed occupation were selected from a large population-based case-control study of head and neck cancer. A laryngeal SCC case with no history of occupational asbestos exposure was included as a control. Tissue cores were obtained from adjacent nonneoplastic tissue in tumor blocks from the initial primary tumor resection, and mineral fiber analysis was performed using a scanning electron microscope equipped with an energy dispersive X-ray analyzer (EDXA). Chrysotile asbestos fiber bundles were identified in 3/6 of evaluated cases with a history of occupational asbestos exposure. All three cases had tumors originating in the larynx. In addition, a wollastonite fiber of unclear significance was identified one of the HPV-negative pharyngeal SCC cases. No mineral fibers were identified in adjacent tissue of the case without occupational exposure. The presence of asbestos fibers in the epithelial tissue surrounding laryngeal SCC in cases with a history of occupational asbestos exposure adds a key line of physical evidence implicating asbestos as an etiologic factor.}, }
@article {pmid31380709, year = {2019}, author = {Jacobs, NFB and Towle, KM and Finley, BL and Gaffney, SH}, title = {An updated evaluation of potential health hazards associated with exposures to asbestos-containing drywall accessory products.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {5}, pages = {430-444}, doi = {10.1080/10408444.2019.1639612}, pmid = {31380709}, issn = {1547-6898}, mesh = {*Asbestos ; Asbestos, Amphibole ; Asbestos, Serpentine ; *Construction Materials ; Environmental Exposure/*analysis/standards/statistics &amp; numerical data ; Humans ; Lung Neoplasms/epidemiology ; No-Observed-Adverse-Effect Level ; Risk Assessment ; }, abstract = {Following a previously published (2012) evaluation of the potential health hazards related to the use of asbestos-containing drywall accessory products, additional information regarding asbestos exposures during the use of accessory products, as well as studies of chrysotile asbestos risk as a function of exposure, have been published in the peer-reviewed literature. The purpose of this analysis is to update the original evaluation with this new information. It was previously estimated that a professional drywaller performing joint compound-associated tasks could have a lifetime cumulative chrysotile exposure of 12-26 f/cc-year. Using conservative assumptions regarding airborne asbestos levels during different drywalling tasks, task duration, and job tenure, we found that a range of 4.3-36.3 f/cc-year is a plausible estimate of a career drywaller's cumulative asbestos exposure from historical joint compound use. The estimated range for bystander exposures would be below (sometimes significantly below) this range depending on the frequency and duration of work near drywallers. Further, the estimated drywaller and bystander total fiber exposures were well below a recently published &quot;no-observed adverse effect level, best estimate&quot; for predominately chrysotile exposures of 89-168 f/cc-year for lung cancer and 208-415 f/cc-year for mesothelioma. We also determined that, even if the chrysotile or possibly talc ingredients in the drywall products had contained asbestiform tremolite, the cumulative tremolite exposures would have been well below a recently published tremolite no-effect level of 0.5-2.6 f/cc-year. Based on our calculations, typical drywall work using asbestos-containing drywall accessory products is not expected to increase the risk of asbestos-related lung cancer or mesothelioma. These conclusions are consistent with the lack of epidemiological evidence that drywall work resulted in an increased incidence of asbestos-related disease in the drywall trades.}, }
@article {pmid31380702, year = {2019}, author = {Marsh, GM and Ierardi, AM and Benson, SM and Finley, BL}, title = {Occupational exposures to cosmetic talc and risk of mesothelioma: an updated pooled cohort and statistical power analysis with consideration of latency period.}, journal = {Inhalation toxicology}, volume = {31}, number = {6}, pages = {213-223}, doi = {10.1080/08958378.2019.1645768}, pmid = {31380702}, issn = {1091-7691}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Cohort Studies ; Europe/epidemiology ; Humans ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; Talc/*adverse effects ; Young Adult ; }, abstract = {Objectives: We previously published a pooled statistical power analysis of mesothelioma incidence in the Italian, Norwegian, Austrian, and French cosmetic talc miner and miller cohorts. Soon thereafter, updates to the Italian and Norwegian cohorts were published, providing an additional 14,322 person-years of observation. In this study, we provide an updated power analysis using the newly available information. Methods: We pooled the current results regarding pleural cancer/mesothelioma mortality or incidence in four cosmetic talc miner and miller cohorts in Italy, Norway, Austria, and France. We used the expected numbers of cases as reported by the authors and the power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities. Results: There was a pooled total of 113,344 person-years in the cohorts. Although 3.0 pleural cancers/mesotheliomas were expected, there were no reported pleural cancer or mesothelioma cases in any cohort. Our pooled analysis was associated with 79 and 62% power to detect a 3.0-fold and 2.5-fold or greater increase in pleural cancer/mesothelioma, respectively. These favorable power characteristics were effectively maintained when restricting the pooled cohort to workers with a latency period of 30 or more years (observation time from first employment). Conclusions: The epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that exposure to cosmetic talc is associated with the development of pleural cancer/mesothelioma.}, }
@article {pmid31376434, year = {2019}, author = {Butnor, KJ and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Mesothelioma of the tunica vaginalis testis.}, journal = {Human pathology}, volume = {92}, number = {}, pages = {48-58}, doi = {10.1016/j.humpath.2019.07.009}, pmid = {31376434}, issn = {1532-8392}, mesh = {Adult ; Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/*pathology/surgery ; Male ; Mesothelioma/*pathology/surgery ; Mesothelioma, Malignant ; Middle Aged ; Orchiectomy ; Retrospective Studies ; Testicular Neoplasms/*pathology/surgery ; Testis/*pathology/surgery ; Treatment Outcome ; }, abstract = {Malignant mesothelioma (MM) arising from the serosal membranes of the tunica vaginalis testis (TVT) is rare. Most examples in the published medical literature are individual case reports. This study presents the clinicopathological findings of mesothelioma of the TVT in one of the largest series to date. Individuals with mesothelioma of the TVT were identified from a database of more than 4000 mesothelioma cases, and their clinicopathological features were recorded. Eighteen men with MM and 2 with well-differentiated papillary mesothelioma of the TVT were identified, which represented 0.6% of males with mesothelioma in study population. The median age at diagnosis was 72 years (range, 32-85 years). A neoplasm was not suspected preoperatively in 12 of the 17 (71%) men whose clinical presentation was known, 7 of whom presented with hydrocele and 5 with inguinal hernia. The other 5 had a clinically recognized mass. Seven of the men underwent herniorrhaphy; 7, radical orchiectomy; 3, hydrocelectomy; and 3, paratesticular mass biopsy or excision as the initial diagnostic procedure. Twelve of the MM cases were epithelioid and 6 were biphasic. Among the 6 men with MM who had ≥6 months of follow-up, 1 was alive with no evidence of disease at 6 months, and 5 were known to have died of disease 8-74 months (median = 31.5 months) following diagnosis. Three men with MM had received either chemotherapy or radiation therapy. Of the 2 men initially diagnosed with well-differentiated papillary mesothelioma, 1 was alive without evidence of disease 5 years after diagnosis, while the other had findings more compatible with MM with peritoneal involvement 2 years following initial diagnosis. In 15 of the 18 cases of MM (83%), there was documented occupational or paraoccupational exposure to asbestos, the average duration of which was 33 years (range, 2-46 years). Information regarding the presence or absence of pleural plaques was available in 5 of the MM cases, and pleural plaques had been found in 4. Lung tissue was not available for fiber analysis in any of the cases. One additional case originally diagnosed at another institution as MM of the TVT was reclassified as adenocarcinoma following performance of additional immunohistochemical testing. TVT is a rare site of MM, the diagnosis of which is often unsuspected preoperatively. Like its counterparts at other serosal sites, MM of the TVT is an aggressive tumor with a poor prognosis that evidence would suggest is etiologically associated with asbestos in at least some cases.}, }
@article {pmid31375830, year = {2019}, author = {Sorahan, TM}, title = {Cancer incidence in UK electricity generation and transmission workers, 1973-2015.}, journal = {Occupational medicine (Oxford, England)}, volume = {69}, number = {5}, pages = {342-351}, pmid = {31375830}, issn = {1471-8405}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Incidence ; Male ; Mesothelioma/epidemiology/etiology ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology ; Occupational Exposure/adverse effects/statistics &amp; numerical data ; *Power Plants ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Long-term health outcomes in cohorts of workers from the electricity supply industry have been studied.<br><br>AIMS: The aim of the study was to examine updated cancer incidence findings among a cohort of UK electricity generation and transmission workers.<br><br>METHODS: Cancer morbidity experienced by 81 616 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-2015. All employees had worked for at least 6 months with some employment between 1973 and 1982. Standardized registration ratios (SRRs) were calculated based on national rates.<br><br>RESULTS: Overall cancer morbidity was slightly below expectation in males. Significant excesses were found in male workers for mesothelioma (observed [Obs] 763, SRR 326), skin cancer (non-melanoma) (Obs 5616, SRR 106), and prostate cancer (Obs 4298, SRR 106), and in female workers for cancer of the small intestine (Obs 13, SRR 220), nasal cancer (Obs 11, SRR 407), and breast cancer (Obs 758, SRR 110). More detailed analyses showed important contrasts, particularly for mesothelioma, lung cancer, skin cancer, prostate cancer and breast cancer.<br><br>CONCLUSIONS: A clear occupational excess of mesothelioma was not matched by a corresponding excess of asbestos-induced lung cancer. Confident interpretation of the excesses of cancers of the nasal cavities and small intestine is not possible, although occupational exposures received in this industry may well not be involved. An excess of skin cancer in transmission workers may be associated with outdoor working.}, }
@article {pmid31375770, year = {2020}, author = {Churg, A and Galateau-Salle, F and Roden, AC and Attanoos, R and von der Thusen, JH and Tsao, MS and Chang, N and De Perrot, M and Dacic, S}, title = {Malignant mesothelioma in situ: morphologic features and clinical outcome.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {33}, number = {2}, pages = {297-302}, pmid = {31375770}, issn = {1530-0285}, abstract = {The existence of an in situ phase of malignant mesothelioma has long been postulated but until recently has been impossible to prove. Here we describe ten patients with mesothelioma in situ, defined by a single layer of surface mesothelial cells showing loss of BAP1 nuclear immunostaining, no evidence of tumor by imaging and/or by direct examination of the pleura/peritoneum, and no invasive mesothelioma developing for at least 1 year. Nine cases were pleural and one peritoneal. Most patients were biopsied for repeated effusions of unknown etiology; in two patients mesothelioma in situ was found incidentally in lung cancer resections. In addition to surface mesothelium with BAP1 loss, one case had a surface papillary proliferation with BAP1 loss, and two cases had a small (few millimeter) nodule with BAP1 loss. CDKN2A was deleted by FISH in one of eight cases. Methylthioadenosine phosphorylase showed partial loss in the surface mesothelium by immunohistochemistry in three cases. Invasive malignant mesothelioma developed in seven patients with time between biopsy and invasive disease from 12 to 92 (median 60) months. Invasive mesothelioma has not developed in the other three patients at 12, 57, and 120 months, but the latter patient, who has pleural plaques, still has repeated pleural effusions, probably representing a so-called &quot;benign asbestos effusion.&quot; We conclude that mesothelioma in situ, as diagnosed using the criteria outlined above, is associated with a high risk of developing invasive mesothelioma, but typically over a relatively protracted time, so that curable interventions maybe possible.}, }
@article {pmid31372931, year = {2020}, author = {Itano, H and Takeda, T and Yamada, T and Koide, M and Kobayashi, T}, title = {Heterologous sarcomatoid pleural mesothelioma with osteosarcomatous differentiation: a report of autopsy case that accomplished trimodality therapy and review of the literature.}, journal = {General thoracic and cardiovascular surgery}, volume = {68}, number = {8}, pages = {871-879}, doi = {10.1007/s11748-019-01182-8}, pmid = {31372931}, issn = {1863-6713}, mesh = {Aged ; Asbestos/adverse effects ; Autopsy ; Biopsy ; Cell Differentiation ; Fatal Outcome ; Humans ; Lung/pathology ; Male ; Mesothelioma/chemically induced/diagnostic imaging/*surgery ; Mesothelioma, Malignant/*surgery ; Neoplasm Recurrence, Local/mortality/*surgery ; Osteosarcoma/*surgery ; Pericardium/surgery ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/diagnostic imaging/*surgery ; Pneumonectomy ; Thoracic Wall/pathology ; }, abstract = {Heterologous mesothelioma is a very rare subtype of sarcomatoid mesothelioma characterized by the presence of malignant heterologous elements. A 69-year-old man with a strong history of asbestos exposure presented with a 5-cm mass in his chest wall, destroying the right 5th rib and spreading along the parietal pleura, on a CT. Biopsy revealed heterologous mesothelioma with osteosarcomatous elements, following which left extrapleural pneumonectomy was performed with combined resection of pericardium, hemidiaphragm, and 4th, 5th, and 6th costal segments. A small cytokeratin-positive epithelioid component in the resected tumor definitively confirmed the diagnosis. Post-operative chemotherapy and intensity-modulated radiotherapy were undertaken. After 12-month disease-free period post treatment, rapid intraperitoneal recurrence resulted in death. Autopsy revealed no tumors in the left thorax. We present here a case of heterologous osteosarcomatous pleural mesothelioma that followed a unique clinical course after trimodality therapy. In addition, literature of 54 cases of the similar heterologous mesothelioma was reviewed.}, }
@article {pmid31366157, year = {2019}, author = {Gogou, E and Hatzoglou, C and Zarogiannis, SG and Malli, F and Jagirdar, RM and Gourgoulianis, KI}, title = {Mesothelioma Mortality Rates in Greece for the Period 2005-2015 Is Increased Compared to Previous Decades.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {55}, number = {8}, pages = {}, pmid = {31366157}, issn = {1648-9144}, mesh = {Aged ; Aged, 80 and over ; Cause of Death/*trends ; Female ; Geographic Mapping ; Greece/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology/*mortality ; Middle Aged ; Occupational Diseases/epidemiology/mortality ; }, abstract = {Background and Objective: To present summary statistics regarding malignant mesothelioma (MM) mortality in Greece during the period 2005-2015 and compare it with previous decades, along with gender, age and geographical area analysis. Materials and Methods: The Hellenic Statistical Authority provided the data, which included all deaths for the period 1983 to 2015 that mentioned MM as the death cause in the corresponding death certificate. MM mortality rates have been calculated with respect to gender, age, and geographical location in Greece. Furthermore, a comparison analysis was made among three eleven consecutive year periods, in order to assess potential changes in the mortality rates. Results: The MM mortality rate has significantly increased during the period 2005-2015 both in males and females compared to earlier decades. The maximum number of MM deaths has shifted to an older age group of 70-80 years during the 2005-2015 period as compared to that of 1983-2004 in both genders. Additionally, MM mortality rates have significantly increased in all geographical areas except for the Epirus Prefecture. Conclusions: Our results demonstrate an increased MM mortality rate in Greece for the decade 2005-2015 as compared to the two previous decades. This increase is possibly due to the fact that the peak in asbestos production and use in Greece was in mid 1990s, while the asbestos ban came in effect in 2005. Based on these findings the MM epidemic in Greece has not yet peaked, therefore it is important to implement screening strategies for early MM detection.}, }
@article {pmid31364588, year = {2019}, author = {The Lancet Oncology, }, title = {Asbestos exposure: the dust cloud lingers.}, journal = {The Lancet. Oncology}, volume = {20}, number = {8}, pages = {1035}, doi = {10.1016/S1470-2045(19)30462-0}, pmid = {31364588}, issn = {1474-5488}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/adverse effects ; Humans ; Lung Neoplasms/*etiology ; Mesothelioma/*etiology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; }, }
@article {pmid31360386, year = {2019}, author = {Borrelli, E and Babcock, Z and Kogut, S}, title = {Costs of medical care for mesothelioma.}, journal = {Rare tumors}, volume = {11}, number = {}, pages = {2036361319863498}, pmid = {31360386}, issn = {2036-3605}, abstract = {Malignant mesothelioma is a rare and devastating form of cancer with an increasing economic burden. We sought to describe the direct cost burden of mesothelioma to the US health system. A systematic literature review was performed to locate published estimates of the medical cost of mesothelioma. In addition, we performed an analysis of hospital discharge data from the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. We also reviewed publicly available legal settlements. We found that published estimates of the cost of medical care for mesothelioma are sparse, and differ with respect to nation, timeframe, and types of cost included. For the year 2014 in the United States, we estimated a mean cost per mesothelioma hospitalization of US$24,124 (95% confidence interval: US$20,819-US$28,983) and a total cost for hospital care of US$44,214,835. In conclusion, we found that reports describing the direct medical cost of care for mesothelioma in the United States are lacking, yet the per-patient cost of care is substantial, as evidenced by analyses of inpatient care and legal settlements.}, }
@article {pmid31355511, year = {2019}, author = {Lee, MJ and Kuehne, N and Hueniken, K and Liang, S and Rai, S and Sorotsky, H and Herman, M and Shepshelovich, D and Bruce, J and Liang, M and Patel, D and Cheng, D and Chen, Z and Eng, L and Brown, MC and Cho, J and Leighl, NB and de Perrot, M and Reisman, D and Xu, W and Bradbury, PA and Liu, G}, title = {Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis.}, journal = {Molecular carcinogenesis}, volume = {58}, number = {11}, pages = {1960-1973}, doi = {10.1002/mc.23088}, pmid = {31355511}, issn = {1098-2744}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*genetics/pathology ; Polymorphism, Single Nucleotide/genetics ; Prognosis ; Promoter Regions, Genetic ; Risk Factors ; Smoking/*adverse effects/genetics ; Transcription Factors/*genetics ; }, abstract = {Brahma (BRM), of the SWI/SNF complex, has two 6 to 7 bp insertion promoter polymorphisms (BRM-741/BRM-1321) that cause epigenetic BRM suppression, and are associated with risk of multiple cancers. BRM polymorphisms were genotyped in malignant pleural mesothelioma (MPM) cases and asbestos-exposed controls. Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between BRM-741/BRM-1321 and risk in patients with MPM, a differential effect by smoking status was observed (P-interaction < .001), where homozygous variants were protective (aOR of 0.18-0.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7-4.4). While there was no association between BRM polymorphisms and OS in ever-smokers, the aHR of carrying homozygous-variants of BRM-741, BRM-1321 or both were 4.0 to 8.6 in never-smokers when compared to wild-type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA-affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never-smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever-smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.}, }
@article {pmid31355131, year = {2019}, author = {Di Somma, S and Iannuzzi, CA and Passaro, C and Forte, IM and Iannone, R and Gigantino, V and Indovina, P and Botti, G and Giordano, A and Formisano, P and Portella, G and Malfitano, AM and Pentimalli, F}, title = {The Oncolytic Virus dl922-947 Triggers Immunogenic Cell Death in Mesothelioma and Reduces Xenograft Growth.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {564}, pmid = {31355131}, issn = {2234-943X}, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure that urgently requires effective therapeutic strategies. Current treatments are unable to increase significantly patient survival, which is often limited to <1 year from diagnosis. Virotherapy, based on the use of oncolytic viruses that exert anti-cancer effects by direct cell lysis and through the induction of anti-tumor immune response, represents an alternative therapeutic option for rare tumors with limited life expectancy. In this study, we propose the use of the adenovirus dl922-947, engineered to allow selective replication in cancer cells, to counteract MPM. Methods: We performed a thorough preclinical assessment of dl922-947 effects in a set of MPM cell lines and xenografts. Cytotoxicity of dl922-947 alone and in combination assays was evaluated by sulforhodamine B assay. Cell cycle, calreticulin expression, and high mobility group box protein 1 (HMGB1) secretion were determined by flow cytometry, whereas ATP content was determined by a luminescence-based bioassay. The modulation of angiogenic factors in MPM-infected cells was evaluated through ELISA. Results: We found that dl922-947 infection exhibits cytotoxic effects in MPM cell lines, affecting cell viability, cell cycle progression, and regulating main hallmarks of immunogenic cell death inducing calreticulin surface exposure, HMGB1 and ATP release. Our results also suggest that dl922-947 may affect angiogenic signals by regulation of VEGF-A and IL-8 secretion. Furthermore, dl922-947 shows anti-tumor efficacy in murine xenograft models reducing tumor growth and enhancing survival. Finally, the combination with cisplatin potentiated the cytotoxic effect of dl922-947. Conclusions: Overall our data identify virotherapy, based on the use of dl922-947, as a new possible therapeutic strategy against MPM, which could be used alone, in combination with standard chemotherapy drugs, as shown here, or other approaches also aimed at enhancing the antitumoral immune response elicited by the virus.}, }
@article {pmid31336692, year = {2019}, author = {Krówczyńska, M and Wilk, E}, title = {Environmental and Occupational Exposure to Asbestos as a Result of Consumption and Use in Poland.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {14}, pages = {}, pmid = {31336692}, issn = {1660-4601}, mesh = {Asbestos/*analysis ; Construction Materials ; Environmental Exposure/*analysis ; Female ; Humans ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Poland/epidemiology ; }, abstract = {Asbestos is harmful to human health; exposure to asbestos causes a wide range of asbestos-related diseases.<br><br>AIM: Malignant mesothelioma (MM) is unique to occupational and environmental asbestos exposure.<br><br>METHODS: Environmental asbestos exposure was examined in relation to asbestos use and manufacturing, the quantity of the asbestos-containing products still in use, the concentrations of asbestos fibres in the air and the number of MM cases diagnosed each year per county.<br><br>RESULTS: The correlation coefficient of the measurements of the asbestos fibre concentrations in the air and the quantity of asbestos-cement products in use is high and amounts to 0.68. Meanwhile, the correlation coefficient of the measurements of asbestos fibre concentrations in air and MM morbidity rate resulting from environmental exposure calculated for particular counties in provinces is low and amounts to 0.37. The highest MM morbidity rate was observed for Małopolskie and Śląskie, a typical industrial area of Poland.<br><br>CONCLUSIONS: There are MM cases which are still attributable to occupational asbestos exposure, although MM cases resulting from environmental exposure to asbestos have an increased MM risk. Poland is among those countries with a low MM incidence rate, which seems to be an underestimation of environmental asbestos exposure. As long as asbestos-cement products are used in the environment, actions should be undertaken to protect public health.}, }
@article {pmid31328588, year = {2019}, author = {Korchevskiy, A and Rasmuson, JO and Rasmuson, EJ}, title = {Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality.}, journal = {Inhalation toxicology}, volume = {31}, number = {5}, pages = {180-191}, doi = {10.1080/08958378.2019.1640320}, pmid = {31328588}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Mesothelioma, Malignant ; Mineral Fibers/*toxicity ; *Models, Biological ; }, abstract = {Context: The potency of various mineral fiber types to produce mesothelioma was previously evaluated for numerous cohorts, but the differences in potencies for distinct fiber types have yet to be explained. Objective: To develop an empirical model that would reconstruct mesothelioma potency factors for various types of fiber based on their chemical composition and dimensionality. Methods: Typical chemical composition and dimensionality metrics (aspect ratios) were obtained and combined with mesothelioma potency factors estimated by Hodgson and Darnton method for Quebec chrysotile, South Africa amosite, South Africa and Australian crocidolite, Russian anthophyllite, Libby amphiboles, and Turkey erionite. The forward stepwise log-log regression method was utilized to determine the best combination of input parameters. Results: Mesothelioma potency factors (RM) for selected cohorts were effectively reconstructed utilizing the median aspect ratio of fibers and equivalent fractions of SiO2, total Fe oxides or total equivalent Fe3+ as Fe2O3, and MgO. Modeled potency factors increase as the aspect ratio, SiO2, and total Fe oxide (or Fe2O3) content grow, and as the MgO content diminishes. Correlation coefficients up to 0.999, p < 0.01, were achieved. The models also yield reasonable estimates of mesothelioma potencies for other fiber types, including Bolivian crocidolite, Russian chrysotile, fluoro-edenite, and others. Conclusion: In spite of the empirical approach, the proposed models provide a starting point for targeted studies of mesothelioma mechanisms by elucidating significant contributing physicochemical factors. The models have an exploratory and preliminary character but can potentially be useful to introduce quantitative structure-activity relationship approaches for the toxicology of fibrous minerals.}, }
@article {pmid31314677, year = {2020}, author = {Henley, SJ and Peipins, LA and Rim, SH and Larson, TC and Miller, JW}, title = {Geographic Co-Occurrence of Mesothelioma and Ovarian Cancer Incidence.}, journal = {Journal of women's health (2002)}, volume = {29}, number = {1}, pages = {111-118}, pmid = {31314677}, issn = {1931-843X}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Carcinoma, Ovarian Epithelial/*epidemiology ; Female ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Ovarian Neoplasms/*epidemiology ; Registries ; United States/epidemiology ; }, abstract = {Background: Asbestos is an established cause of several cancers, including mesothelioma and ovarian cancer. Incidence of mesothelioma, the sentinel asbestos-associated cancer, varies by state, likely reflecting different levels of asbestos exposure. We hypothesized that states with high mesothelioma incidence may also have high ovarian cancer incidence. Materials and Methods: Using data from the Centers for Disease Control and Prevention National Program for Cancer Registries and the National Cancer Institute Surveillance, Epidemiology, and End Results Program, we examined the geographic co-occurrence of mesothelioma and ovarian cancer incidence rates by U.S. state for 2003-2015. Results: By state, mesothelioma incidence ranged from 0.5 to 1.3 cases per 100,000 persons and ovarian cancer incidence ranged from 9 to 12 cases per 100,000 females. When states were grouped by quartile of mesothelioma incidence, the average ovarian cancer incidence rate was 10% higher in states with the highest mesothelioma incidence than in states with the lowest mesothelioma incidence. Ovarian cancer incidence tended to be higher in states with high mesothelioma incidence (Pearson correlation r = 0.54; p < 0.0001). Conclusions: Data from state cancer registries show ovarian cancer incidence was positively correlated with mesothelioma incidence, suggesting asbestos may be a common exposure. The potential for asbestos exposure has declined since the 1970s because fewer products contain asbestos; however, some products, materials, and buildings may still release asbestos and thousands of workers may be exposed. Ensuring that people are protected from exposure to asbestos in their workplaces, homes, schools, and communities may reduce the risk of several cancers.}, }
@article {pmid31295974, year = {2019}, author = {Zona, A and Iavarone, I and Buzzoni, C and Conti, S and Santoro, M and Fazzo, L and Pasetto, R and Pirastu, R and Bruno, C and Ancona, C and Bianchi, F and Forastiere, F and Manno, V and Minelli, G and Minerba, A and Minichilli, F and Stoppa, G and Pierini, A and Ricci, P and Scondotto, S and Bisceglia, L and Cernigliaro, A and Ranzi, A and Comba, P and ,  and ,  and , }, title = {[SENTIERI: Epidemiological Study of Residents in National Priority Contaminated Sites. Fifth Report].}, journal = {Epidemiologia e prevenzione}, volume = {43}, number = {2-3 Suppl 1}, pages = {1-208}, doi = {10.19191/EP19.2-3.S1.032}, pmid = {31295974}, issn = {1120-9763}, mesh = {Adolescent ; Adult ; Aged ; Cause of Death ; Child ; Child, Preschool ; Congenital Abnormalities/epidemiology/etiology ; Endocrine Disruptors/toxicity ; Environmental Exposure/adverse effects ; Environmental Pollution/*adverse effects ; Environmental Restoration and Remediation ; Female ; Humans ; Incidence ; Industrial Waste/adverse effects ; Infant ; Infant, Newborn ; Italy/epidemiology ; Male ; Middle Aged ; Neoplasms/epidemiology/etiology ; Pregnancy ; Young Adult ; }, abstract = {INTRODUCTION AND OBJECTIVES: This volume provides an update of the health status of the populations living in the National Priority Contaminated Sites (NPCSs) included in the SENTIERI Project. This update is part of an epidemiological surveillance programme carried out in NPCSs, promoted by the Italian Ministry of Health as a further step of a project started in 2006, when the health status of residents in contaminated sites was first addressed within the National Strategic Program &quot;Environment and Health&quot;. The Report focuses on five health outcomes: mortality, cancer incidence, hospital discharges, congenital anomalies, and children, adolescents and young adults' health. A key element of SENTIERI project is the a priori evaluation of the epidemiological evidence of a causal association between the considered cause of disease and the exposure. When an a priori evidence is identified, it is given a greater importance in the comment of the study findings.<br><br>METHODS: The present update of the SENTIERI Project concerns 45 NPCSs including in all 319 Italian Municipalities (out of over 8,000 Municipalities), with an overall population of 5,900,000 inhabitants at the 2011 Italian Census. Standardized Mortality Ratios (SMRs) and Standardized Hospitalization Ratios (SHRs), referring to a time window of 2006-2013, were computed for all the 45 NPCSs, using as a reference the corresponding mortality and hospitalization rates of the Regions where each NCPS is located. Standardized Incidence Ratios (SIRs) were computed by the Italian Association of Cancer Registries (AIRTUM) for the 22 NPCSs served by a Cancer Registry. AIRTUM covers about 56% of Italy, with partly different time-windows. SIRs have been estimated using as reference population the 4 macroareas in which Italy is divided (North-West, North-East, Centre, South). Prevalence of congenital anomalies was computed for 15 NPCSs.<br><br>RESULTS: An all-cause excess of 5,267 and 6,725 deaths was observed, respectively, in men and women; the cancer death excess was of 3,375 in men and 1,910 in women. It was estimated an excess of cancer incidence of 1,220 case in men and 1,425 in women over a five-year time window. With regard to the diseases with an a priori environmental aetiological validity, an excess for malignant mesothelioma, lung, colon, and gastric cancer, and for non-malignant respiratory diseases was observed. Cancer excess mainly affected NPCSs with presence of chemical and petrochemical plants, oil refineries, and dumping hazardous wastes. An excess of non-malignant respiratory disease was also detected in NPCSs in which steel industries and thermoelectric plants were present. An excess of mesothelioma was observed in NPCSs characterized by presence of asbestos and fluoro-edenite; it was also observed where the presence of asbestos was not reported in the legislative national decrees which define the NPCS areas. It is worth noting that, even if the presence of asbestos is not reported in many NPCSs legislative decrees, petrochemical plants and steel industries, for instance, are often characterized by the presence of a large amount of this mineral that, in the past, was extensively used as an insulating material. For the first time, the present Report includes a focus on the health status of children and adolescents (1,160,000 subjects, aged 0-19 years), and young adults (660,000 subjects, aged 20-29 years). Among infants (0-1 year), an excess of 7,000 hospitalizations was observed, 2,000 of which due to conditions of perinatal origin. In the age class 0-14, an excess of 22,000 hospitalizations for all causes was observed; 4,000 of them were due to acute respiratory diseases, and 2,000 to asthma. Data on cancer incidence for subjects aged 0-24 years were derived from general population cancer registries for twenty NPCSs, and from children cancer registries (age group: 0-19 years) for six NPCSs; 666 cases where diagnosed in the age group 0-24 years, corresponding to an excess of 9%. The main contributions to this excess are from soft tissue sarcomas in children (aged 0-14 years), acute myeloid leukaemia in children (aged 0-14 years) and in the age group 0-29 years, non-Hodgkin lymphoma and testicular cancer in young adults (aged 20-29 years). In seven out of 15 NPCSs, an excess prevalence rate of overall congenital anomalies at birth was observed. Congenital anomalies excesses included the following sites: genital organs, heart, limbs, nervous system, digestive system, and urinary system.<br><br>CONCLUSIONS: The main findings of SENTIERI Project have been the detection of excesses for the diseases which showed an a priori epidemiological evidence of a causal association with the environmental exposures specific for each considered NPCS. These observations are valuable within public health, because they contribute to priority health promotion activities. Looking ahead, the health benefits of an improved environmental quality might be appreciated in terms of reduction of the occurrence of adverse health effects attributable to each Site major pollutant agents. Due to the methodological approach of the present study, it was not possible to adjust for several confounding factors reported to be risk factors for the studied diseases (e.g., smoking, alcohol consumption, obesity). Even if excesses of mortality, hospitalization, cancer incidence, and prevalence of congenital anomalies were found in several NPCSs, the study design and the multifactorial aetiology of the considered diseases do not permit, for all of them, to draw conclusions in terms of causal links with environmental contamination. Moreover, it must be taken into consideration that economic factors and the availability of health services may also play a relevant role in a diseases outcome. A few observations regarding some methodological limitations of SENTIERI Project should be made. There is not a uniform environmental characterisation of the studied NPCSs in term of quality and detection of the pollutants, because this information is present in different databases which at present are not adequately connected. Moreover, the recognition of a contaminated site as a National Priority Site is based on soil and groundwater pollution, and the available information on air quality is currently sparse and not homogenous. Another limitation, in term of statistical power, is the small population size of many NPCSs and the low frequency of several health outcomes. A special caution must be paid in data interpretation when considering the correspondence between the contaminated areas and the municipality boundaries, as they do not always coincide perfectly: in some cases, a small municipality with a large industrial site, while in other settings only a part of the municipality is exposed to the sources of pollution. Furthermore, all available health information systems are currently accessible at municipality level. The real breakthrough is essentially comprised of the development and fostering of a networking system involving all local health authorities and regional environmental protection agencies operating in the areas under study. The possibility to integrate the geographic approach of SENTIERI Project with a set of ad hoc analytic epidemiological investigations, such as residential cohort studies, case control studies, children health surveys, biomonitoring surveys, and with socioepidemiological studies, might greatly contribute to the identification of health priorities for environmental remediation activities. Finally, as discussed in the last section of the report, there is a need to adopt, in each NPCS, a two-way oriented communication plan involving public health authorities, scientific community, and resident population, taking into account that the history, the cultural frame and the network of relationships specific of each local context play a major role in the risk perception perspective.}, }
@article {pmid31290725, year = {2019}, author = {Mumma, MT and Sirko, JL and Boice, JD and Blot, WJ}, title = {Mesothelioma mortality within two radiation monitored occupational cohorts.}, journal = {International journal of radiation biology}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/09553002.2019.1642540}, pmid = {31290725}, issn = {1362-3095}, abstract = {Purpose: The risk of mesothelioma, including cancers of the pleura and peritoneum, was examined within two large cohorts of workers monitored for exposure to ionizing radiation. Methods and materials: Mortality was assessed among 253,632 workers routinely monitored for external radiation, including 30,724 industrial radiographers (IR) at shipyards, 142,583 workers at nuclear power plants (NPP), and 83,441 IR who had not worked at an NPP or shipyard. Follow-up was from 1969 through 2011. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were computed; observed numbers of deaths from mesothelioma (including cancers of the pleura and peritoneum) and asbestosis were compared with numbers expected based on age-, sex-, and calendar year-specific national mortality rates. Job history and quantitative asbestos exposure data were unavailable, but work at a shipyard was taken as a surrogate for the likelihood of exposure. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mesothelioma in relation to estimated cumulative radiation exposure to the lung. Results: The mean duration of follow-up was 25.3 years (max 42 years). The mean cumulative lung dose was 28.6 mGy (7.3% > 250 mGy). Nearly 20% of the workers had died by 2011. A total of 421 mesothelioma deaths were found (75% occurring after 1999) with increased SMRs among workers monitored in shipyards (SMR 9.97; 95% CI 8.50-11.63) and for NPP workers (SMR 5.55; 95% CI 4.88-6.29), but not for IR who had not worked in shipyards (SMR 1.15; 95% CI 0.53-2.19). Likewise, deaths from asbestosis (n = 189) were also increased for shipyard and NPP workers (SMR = 18.1 and 9.2, respectively), but not among workers who never worked at a shipyard or NPP (SMR = 0.70; n = 1). Radiation dose to the lung was not associated with a statistically meaningful dose-response trend for mesothelioma in the combined cohorts (HR at 100 mGy = 1.10; 95% CI 0.96-1.27; p = .18), nor was mesothelioma risk associated with radiation exposure among IR who had not worked in a shipyard and assumed minimally exposed to asbestos. Conclusions: An elevated rate of death from mesothelioma was observed in two radiation-exposed occupational groups with potential for asbestos exposure. The increased risk of death from asbestosis, combined with little evidence of a rising trend in mesothelioma mortality with increasing radiation exposure, suggests that the mesothelioma (and asbestosis) excess in these workers was due to asbestos exposure in shipyards and power plants and not to occupational low-dose radiation.}, }
@article {pmid31289611, year = {2019}, author = {Williams, M and Cheng, YY and Kirschner, MB and Sarun, KH and Schelch, K and Winata, P and McCaughan, B and Kao, S and Van Zandwijk, N and Reid, G}, title = {Transcriptional suppression of the miR-15/16 family by c-Myc in malignant pleural mesothelioma.}, journal = {Oncotarget}, volume = {10}, number = {41}, pages = {4125-4138}, pmid = {31289611}, issn = {1949-2553}, abstract = {MicroRNA downregulation is frequent in malignant pleural mesothelioma (MPM), but the mechanisms responsible for loss of miR-15/16 and miR-193a are yet to be elucidated and were investigated in this study. Copy Number Variation (CNV) of microRNA-coding genes was analyzed in MPM cells by digital droplet PCR (ddPCR) and revealed heterozygous loss of miR-193a and miR-15a/16-1, but no change in miR-15b/16-2. Epigenetic control of microRNA expression was inferred following decitabine and Trichostatin A (TSA) treatment which did not substantially affect microRNA expression. Knockdown of c-Myc expression led to upregulation of SMC4, miR-15b and 16, and to a lesser extent DLEU2 and miR-15a, whereas c-Myc overexpression repressed microRNA expression. Chromatin immunoprecipitation (ChIP) assays confirmed the interaction of c-Myc with the DLEU2 and SMC4 promoters. Tumor microRNA expression was determined in samples from MPM patients, with samples of pleura from cardiac surgery patients used as controls. In tumor samples, a strong correlation was observed between the expression of miR-15b and 16 (R2=0.793), but not miR-15a and 16. Our data suggest that in MPM, the downregulation of miR-15/16 is due to transcriptional repression by c-Myc, primarily via control of the miR-15b/16-2 locus, while miR-193a-3p loss is due to genomic deletion.}, }
@article {pmid31289169, year = {2019}, author = {Taylor, L and Cooper, D and Aujayeb, A}, title = {Malignant deciduoid mesothelioma: a rare variant of epithelioid mesothelioma.}, journal = {BMJ case reports}, volume = {12}, number = {7}, pages = {}, doi = {10.1136/bcr-2019-229945}, pmid = {31289169}, issn = {1757-790X}, mesh = {Aged ; Asbestos/*adverse effects ; Deciduoma/*pathology ; Environmental Exposure ; Humans ; Lung Neoplasms/diagnostic imaging/metabolism/*pathology ; Male ; Mesothelioma/diagnostic imaging/metabolism/*pathology ; Mesothelioma, Malignant ; Palliative Care/methods ; Pleural Neoplasms/diagnostic imaging/pathology ; Prognosis ; Thoracoscopy/methods ; Tomography, X-Ray Computed/methods ; }, abstract = {We describe a case of a deciduoid mesothelioma, a rare variant of epithelioid mesothelioma, which is associated with a very poor prognosis. A review of the relevant literature is also included. The patient was a man with probable asbestos exposure and presented with classic features of pleural malignancy. Diagnosis was reached with close correlation between clinical, radiological and pathological findings.}, }
@article {pmid31285358, year = {2019}, author = {Consonni, D and Calvi, C and De Matteis, S and Mirabelli, D and Landi, MT and Caporaso, NE and Peters, S and Vermeulen, R and Kromhout, H and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Peritoneal mesothelioma and asbestos exposure: a population-based case-control study in Lombardy, Italy.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {8}, pages = {545-553}, pmid = {31285358}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/*epidemiology/etiology ; }, abstract = {OBJECTIVES: Asbestos is the main risk factor for peritoneal mesothelioma (PeM). However, due to its rarity, PeM has rarely been investigated in community-based studies. We examined the association between asbestos exposure and PeM risk in a general population in Lombardy, Italy.<br><br>METHODS: From the regional mesothelioma registry, we selected PeM cases diagnosed in 2000-2015. Population controls (matched by area, gender and age) came from two case-control studies in Lombardy on lung cancer (2002-2004) and pleural mesothelioma (2014). Assessment of exposure to asbestos was performed through a quantitative job-exposure matrix (SYN-JEM) and expert evaluation based on a standardised questionnaire. We calculated period-specific and gender-specific OR and 90% CI using conditional logistic regression adjusted for age, province of residence and education.<br><br>RESULTS: We selected 68 cases and 2116 controls (2000-2007) and 159 cases and 205 controls (2008-2015). The ORs for ever asbestos exposure (expert-based, 2008-2015 only) were 5.78 (90% CI 3.03 to 11.0) in men and 8.00 (2.56 to 25.0) in women; the ORs for definite occupational exposure were 12.3 (5.62 to 26.7) in men and 14.3 (3.16 to 65.0) in women. The ORs for ever versus never occupational asbestos exposure based on SYN-JEM (both periods) were 2.05 (90% CI 1.39 to 3.01) in men and 1.62 (0.79 to 3.27) in women. In men, clear positive associations were found for duration, cumulative exposure (OR 1.33 (1.19 to 1.48) per fibres/mL-years) and latency.<br><br>CONCLUSIONS: Using two different methods of exposure assessment we provided evidence of a clear association between asbestos exposure and PeM risk in the general population.}, }
@article {pmid31283845, year = {2019}, author = {Carbone, M and Adusumilli, PS and Alexander, HR and Baas, P and Bardelli, F and Bononi, A and Bueno, R and Felley-Bosco, E and Galateau-Salle, F and Jablons, D and Mansfield, AS and Minaai, M and de Perrot, M and Pesavento, P and Rusch, V and Severson, DT and Taioli, E and Tsao, A and Woodard, G and Yang, H and Zauderer, MG and Pass, HI}, title = {Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.}, journal = {CA: a cancer journal for clinicians}, volume = {69}, number = {5}, pages = {402-429}, doi = {10.3322/caac.21572}, pmid = {31283845}, issn = {1542-4863}, support = {U01 CA214195/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents, Immunological/*therapeutic use ; Asbestos/adverse effects ; Australia/epidemiology ; Biomarkers, Tumor/*analysis/genetics/metabolism ; Carcinogenesis/chemically induced/genetics/pathology ; Combined Modality Therapy/methods ; Diagnostic Errors ; Europe/epidemiology ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Global Burden of Disease ; Humans ; Incidence ; Inhalation Exposure/adverse effects ; International Cooperation ; Mesothelioma/diagnosis/epidemiology/etiology/*therapy ; Molecular Targeted Therapy/methods ; Occupational Exposure/adverse effects ; Pleura/drug effects/pathology/surgery ; Pleural Neoplasms/diagnosis/epidemiology/etiology/*therapy ; Pneumonectomy/*methods ; Prognosis ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; United States/epidemiology ; }, abstract = {Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.}, }
@article {pmid31280996, year = {2019}, author = {Tsao, A and Nakano, T and Nowak, AK and Popat, S and Scagliotti, GV and Heymach, J}, title = {Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma.}, journal = {Seminars in oncology}, volume = {46}, number = {2}, pages = {145-154}, doi = {10.1053/j.seminoncol.2019.06.001}, pmid = {31280996}, issn = {1532-8708}, mesh = {Asbestos/toxicity ; Bevacizumab/therapeutic use ; Carcinogenesis/*drug effects/genetics ; Humans ; Indoles/therapeutic use ; Lung Neoplasms/*drug therapy/genetics/pathology ; Mesothelioma/*drug therapy/genetics/pathology ; Mesothelioma, Malignant ; Neovascularization, Pathologic/*drug therapy/genetics/pathology ; Pleural Neoplasms/*drug therapy/genetics/pathology ; Quinazolines/therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a global health issue, the principal cause of which is exposure to asbestos. The prevalence is anticipated to rise over the next 2 decades, particularly in developing countries, due to the 30-50-year latency period between exposure to asbestos and carcinogenic development. Unresectable MPM has a poor prognosis and limited treatment options and, as such, there is a broad range of therapeutic targets of interest, including angiogenesis, immune checkpoints, mesothelin, as well as chemotherapeutic agents. Recently, the results of several randomized trials in the first-line setting combining antiangiogenic agents with chemotherapy have been reported. This review examines the scientific rationale for targeting angiogenesis in the treatment of unresectable MPM and analyzes recent clinical results with antiangiogenic agents in development (bevacizumab, nintedanib, and cediranib) for the management of MPM.}, }
@article {pmid31273181, year = {2019}, author = {Terakawa, H and Gabata, R and Haba, Y and Takada, S and Sakamoto, K and Sasaki, M}, title = {[A Case of Peritoneal Mesothelioma Diagnosed by Ileus].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {6}, pages = {1081-1083}, pmid = {31273181}, issn = {0385-0684}, mesh = {Aged ; *Asbestos ; Humans ; *Ileus/etiology ; Male ; *Mesothelioma/complications ; *Peritoneal Neoplasms/complications ; }, abstract = {The present case involved a man aged about 70 years. He visited our hospital with the main complaint of abdominal pain. We diagnosed him with intestinal obstruction, and we decided to perform surgery. White knot sections were spread inside the abdominal cavity, and the small intestine appeared as a single block. This block was resected and examined for peritoneal mesothelioma. Peritoneal mesothelioma is thought to have incubation period of 20-25 years after exposure to asbestos, and the number of affected patients will increase in the future. In some cases, peritoneal mesothelioma occurs only in the peritoneum; therefore, diagnosis often becomes difficult. Once intestinal obstruction occurs, administering chemotherapy is difficult. Therefore, early diagnosis is thought to be very important.}, }
@article {pmid31269586, year = {2019}, author = {Liu, XH and Wu, H and Huang, YF and Zhang, GY and Xu, MH}, title = {[Clinical characteristics of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis: a report of 6 cases].}, journal = {Zhonghua yi xue za zhi}, volume = {99}, number = {24}, pages = {1893-1897}, doi = {10.3760/cma.j.issn.0376-2491.2019.24.011}, pmid = {31269586}, issn = {0376-2491}, mesh = {Adult ; Aged ; Humans ; Male ; *Mesothelioma ; Middle Aged ; *Peritoneal Neoplasms ; *Peritonitis, Tuberculous ; Retrospective Studies ; }, abstract = {Objective: To reduce the misdiagnosis rate of ascites and improve the diagnosis rate of malignant peritoneal mesothelioma. Methods: From May 2008 to May 2018, in Xiangya Hospital of Central South University,the clinical data of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis were retrospectively analyzed. Results: (1) Among the 6 patients, they were male; the age of onset was 42-70 (52±9.57) years old, and there was no history of asbestos exposure. (2) All cases with abdominal pain or abdominal distension were there and the course of disease was more than 1 month to more than 2 years. (3) In all patients,the nature of ascites was exudate; ADA was higher than normal value and below 45 U/L; LDH value in ascites was higher than 200 U/L (83.3%); mesothelioma was considered in ascites cytology in 1 case. (4) Laparoscopic biopsy was performed in 2 cases and B-ultrasound guided biopsy in 4 cases; Among them, malignant peritoneal mesothelioma diagnosed by pathology. (5) In Immunohistochemical positive markers, MC was the most sensitive (100%), followed by CR (67%), CK-Pan (67%), Ki-67 (67%) and EMA (67%). (6) Two patients received treatment with operation, abdominal hyperthermic perfusion and postoperative systemic chemotherapy. Conclusions: (1) Malignant peritoneal mesothelioma should be considered in middle-aged and aged male patients with unexplained ascites and early laparoscopy or laparotomy for diagnosis. (2) ADA and LDH level in ascites are significant in differentiating tuberculous peritonitis from malignant peritoneal mesothelioma. (3) Immunohistochemical positive marker MC may be a potential specific marker for malignant mesothelioma. (4) The survival time of patients is improved by comprehensive treatment such as operation and chemotherapy.}, }
@article {pmid31267149, year = {2019}, author = {Jiménez-Ramírez, C and Casjens, S and Juárez-Pérez, CA and Raiko, I and Del Razo, LM and Taeger, D and Calderón-Aranda, ES and Rihs, HP and Acosta-Saavedra, LC and Weber, DG and Cabello-López, A and Pesch, B and Ochoa-Vázquez, MD and Burek, K and Torre-Bouscoulet, L and Pérez-Padilla, JR and García-Bazan, EM and Brüning, T and Johnen, G and Aguilar-Madrid, G}, title = {Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {197}, number = {5}, pages = {641-649}, pmid = {31267149}, issn = {1432-1750}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Calbindin 2/*blood ; Enzyme-Linked Immunosorbent Assay ; Female ; GPI-Linked Proteins/*blood ; Humans ; Incidence ; Lung Neoplasms/*blood/diagnosis/epidemiology ; Male ; Mesothelioma/*blood/diagnosis/epidemiology ; Mesothelioma, Malignant ; Mexico/epidemiology ; Middle Aged ; Pleural Neoplasms/*blood/diagnosis/epidemiology ; Predictive Value of Tests ; Prognosis ; Risk Assessment ; Risk Factors ; Sex Factors ; }, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM.<br><br>METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016.<br><br>RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively.<br><br>CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.}, }
@article {pmid31265162, year = {2019}, author = {Numano, T and Higuchi, H and Alexander, DB and Alexander, WT and Abdelgied, M and El-Gazzar, AM and Saleh, D and Takase, H and Hirose, A and Naiki-Ito, A and Suzuki, S and Takahashi, S and Tsuda, H}, title = {MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats.}, journal = {Cancer science}, volume = {110}, number = {8}, pages = {2485-2492}, pmid = {31265162}, issn = {1349-7006}, support = {//5th Term Long-Range Research Initiative (2017) by Japan Chemical Industry Association/ ; H22-kagaku-ippan-005//Ministry of Health, Labour and Welfare/ ; H22-kagaku-shitei-004//Ministry of Health, Labour and Welfare/ ; H25-kagaku-ippan-004//Ministry of Health, Labour and Welfare/ ; H27-kagaku-shitei-004//Ministry of Health, Labour and Welfare/ ; H28-kagaku-ippan-004//Ministry of Health, Labour and Welfare/ ; //Egyptian Cultural Affairs and Missions Sector/ ; }, mesh = {Animals ; Asbestos, Crocidolite/adverse effects ; Injections, Intraperitoneal/methods ; Lung/*drug effects ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Mesothelioma, Malignant ; Nanotubes, Carbon/*adverse effects ; Pleural Neoplasms/*chemically induced/pathology ; Rats ; Rats, Inbred F344 ; Trachea/drug effects/pathology ; }, abstract = {Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 μg/mL MWCNT-7 or 0.250 μg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.}, }
@article {pmid31262194, year = {2019}, author = {Guazzelli, A and Meysami, P and Bakker, E and Bonanni, E and Demonacos, C and Krstic-Demonacos, M and Mutti, L}, title = {What can independent research for mesothelioma achieve to treat this orphan disease?.}, journal = {Expert opinion on investigational drugs}, volume = {28}, number = {8}, pages = {719-732}, doi = {10.1080/13543784.2019.1638363}, pmid = {31262194}, issn = {1744-7658}, mesh = {Animals ; Antineoplastic Agents/*administration &amp; dosage/pharmacology ; Drug Repositioning ; Humans ; Immunotherapy/methods ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Molecular Docking Simulation ; Molecular Targeted Therapy ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Rare Diseases/drug therapy/pathology ; Survival Rate ; }, abstract = {Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival. Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy. Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment.}, }
@article {pmid31260913, year = {2019}, author = {Pyana Kitenge, J and Kapinga Kayembe, D and Tshibangu Muamba, M and Kachil Rubing, H and De Vos, B and Van Bouwel, J and Nemery, B}, title = {Malignant mesothelioma in Sub-Saharan Africa: A case report from Lubumbashi, DR Congo.}, journal = {Environmental research}, volume = {176}, number = {}, pages = {108556}, doi = {10.1016/j.envres.2019.108556}, pmid = {31260913}, issn = {1096-0953}, mesh = {Adult ; *Asbestos ; Congo ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; South Africa ; }, abstract = {Although asbestos has been used throughout Africa in the past decades, no reports of asbestos-related malignant mesothelioma are available from sub-Saharan Africa, except from South Africa and Zimbabwe. We present a case of a 39-year-old man who died from a histologically proven malignant mesothelioma of the peritoneum in Lubumbashi, DR Congo. No occupational exposure to asbestos could be found in his history. In view of his young age, we speculated that he had been exposed to asbestos as a child, which was highly plausible because he had grown up in one of the numerous mining estates of the region. The houses of these estates were often built with asbestos-containing materials, notably roofs made of corrugated asbestos-cement. The possibility of past domestic or environmental exposure to asbestos was substantiated by the identification of chrysotile and crocidolite fibres in samples of asbestos-cement collected from the home where the patient had lived as a child. To our knowledge, this is the first report of malignant mesothelioma from a country in the Central African region. We expect that heightened awareness and improved diagnosis will lead to the detection of more asbestos-related diseases in Africa.}, }
@article {pmid31260832, year = {2019}, author = {Tsao, MS and Carbone, M and Galateau-Salle, F and Moreira, AL and Nicholson, AG and Roden, AC and Adjei, AA and Aubry, MC and Fennell, DA and Gomez, D and Harpole, D and Hesdorffer, M and Hirsch, FR and Liu, G and Malik, S and Nowak, A and Peikert, T and Salgia, R and Szlosarek, P and Taioli, E and Yang, H and Tsao, A and Mansfield, AS}, title = {Pathologic Considerations and Standardization in Mesothelioma Clinical Trials.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {10}, pages = {1704-1717}, doi = {10.1016/j.jtho.2019.06.020}, pmid = {31260832}, issn = {1556-1380}, mesh = {Biological Specimen Banks ; Biomarkers, Tumor/*genetics ; Clinical Trials as Topic/*standards ; Diagnosis, Differential ; Humans ; Mesothelioma/*classification/genetics/*pathology ; Pleural Neoplasms/*classification/genetics/*pathology ; }, abstract = {The accurate diagnosis of mesothelioma is critical for the appropriate clinical management of this cancer. Many issues complicate making the diagnosis of mesothelioma including the presence of reactive mesothelial cells in benign pleural effusions, the heterogeneity of mesothelioma histopathology, the relatively high incidence of other epithelial malignancies that metastasize to the pleura, and primary sarcomas that arise within the pleura. Given the rapidly evolving field of molecular profiling and the need for translational correlates in mesothelioma clinical trials, the National Cancer Institute (NCI)-International Association for the Study of Lung Cancer-Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting was convened in March 2017 to develop a consensus on standard pathology guidelines for future NCI-sponsored clinical trials in mesothelioma. This consensus statement covers recommendations for specimen handling, pathologic classification and diagnosis, biobanking, and tissue correlative studies.}, }
@article {pmid31239765, year = {2019}, author = {Ospina, D and Villegas, VE and Rodríguez-Leguizamón, G and Rondón-Lagos, M}, title = {Analyzing biological and molecular characteristics and genomic damage induced by exposure to asbestos.}, journal = {Cancer management and research}, volume = {11}, number = {}, pages = {4997-5012}, pmid = {31239765}, issn = {1179-1322}, abstract = {Asbestos is one of the most important occupational carcinogens. Currently, about 125 million people worldwide are exposed to asbestos in the workplace. According to global estimates, at least 107,000 people die each year from lung cancer, mesothelioma, and asbestosis as a result of occupational exposure to asbestos. The high pathogenicity of this material is currently known, being associated with the development of pulmonary diseases, of which lung cancer is the main cause of death due to exposure to this mineral. Pulmonary diseases related to asbestos are a common clinical problem and a major health concern worldwide. Extensive research has identified many important pathogenic mechanisms; however, the precise molecular mechanisms involved, and the generated genomic damage that lead to the development of these diseases, are not completely understood. The modes of action that underlie this type of disease seem to differ depending on the type of fiber, lung clearance, and genetics. This evidences the need to increase our knowledge about these effects on human health. This review focuses on the characteristics of asbestos and the cellular and genomic damage generated in humans via exposure.}, }
@article {pmid31237454, year = {2019}, author = {Ledda, C and Caltabiano, R and Vella, F and Matera, S and Marconi, A and Loreto, C and Rapisarda, V}, title = {Fibulin-3 as biomarker of malignant mesothelioma.}, journal = {Biomarkers in medicine}, volume = {13}, number = {10}, pages = {875-886}, doi = {10.2217/bmm-2018-0285}, pmid = {31237454}, issn = {1752-0371}, mesh = {Asbestos/toxicity ; Biomarkers, Tumor/blood/*metabolism ; Databases, Factual ; ErbB Receptors/metabolism ; Extracellular Matrix Proteins/blood/*metabolism ; Humans ; Lung Neoplasms/chemically induced/mortality/*pathology ; Mesothelioma/chemically induced/mortality/*pathology ; Mesothelioma, Malignant ; Survival Rate ; }, abstract = {Many malignant diseases are associated with past asbestos exposure; the most lethal and strictly related to previous fiber exposure being malignant mesothelioma (MM). Effective preventive protocols may include sensitive and specific biomarkers. The role of Fb-3 has been recently investigated for MM early detection, but its role is still under debate. After an independent search for scientific literature, nine studies were included for a systematic review. Human Fb-3 levels seem to be able to separate healthy people with previous exposure to asbestiform fibers from MM patients. Fb-3 blood levels can distinguish MM effusions from other malignant and benign effusions. Furthers investigations on more significant groups of patients are desirable to validate and assess the validity of combining Fb-3 with other biomarkers.}, }
@article {pmid31229775, year = {2019}, author = {Ramos-Bonilla, JP and Cely-García, MF and Giraldo, M and Comba, P and Terracini, B and Pasetto, R and Marsili, D and Ascoli, V and Lysaniuk, B and Rodríguez, MC and Mazzeo, A and Panqueva, RDPL and Baldión, M and Cañón, D and García-Herreros, LG and Pinzón, B and Hernández, LJ and Silva, YA}, title = {An asbestos contaminated town in the vicinity of an asbestos-cement facility: The case study of Sibaté, Colombia.}, journal = {Environmental research}, volume = {176}, number = {}, pages = {108464}, doi = {10.1016/j.envres.2019.04.031}, pmid = {31229775}, issn = {1096-0953}, mesh = {Adult ; *Asbestos/toxicity ; Cities ; Colombia ; Environmental Exposure ; Female ; Humans ; Incidence ; Male ; *Mesothelioma/epidemiology ; Middle Aged ; *Occupational Exposure ; }, abstract = {INTRODUCTION: The asbestos industry began operations in Colombia in 1942, with an asbestos-cement facility located in the municipality of Sibaté. In recent years residents from Sibaté have been complaining about what they consider is an unusually large number of people diagnosed with asbestos-related diseases in the town. A study to analyze the situation of Sibaté started in 2015, to verify if the number of asbestos related diseases being diagnosed were higher than expected, and to identify potential asbestos exposure sources in the town.<br><br>METHODS: A health and socioeconomic survey was implemented door-to-door to identify potential asbestos-related diseases. Several self-reported mesothelioma cases were identified, and for confirmation purposes, copies of the medical record with the histopathology report were obtained. A panel of six physicians analyzed the medical records. Information of validated cases was used to estimate the male and female age-adjusted incidence rate for Sibaté. Based on reports of the existence of potential asbestos-contaminated landfills, topographic maps, a digital elevation model, and current satellite images were crossed using a geographic information system to identify potential landfilled areas, and soils samples were collected in some of these areas.<br><br>RESULTS: A total of 355 surveys were completed, and 29 self-reported mesothelioma cases were identified. Twenty-five of these cases have been persons who had lived at some moment of their lives in Sibaté. It was possible to obtain copies of the medical diagnosis for 17 cases. Of these, the panel of physicians classified 15 cases as certain pleural mesothelioma, one as probable, and one as not mesothelioma. Based on this information, the estimated age-adjusted incidence rate of mesothelioma in Sibaté was 3.1 × 105 persons-year for males and 1.6 × 105 persons-year for females. These rates are high in comparison to those reported in other cities, regions, and countries of the world. Using geographic information systems, landfilled zones in the urban area of Sibaté were identified, on top of which a school and different sports facilities were built. The analysis of four soil samples collected in landfilled zones, confirmed the existence of an underground layer of friable and non-friable asbestos.<br><br>CONCLUSION: The collected evidence suggests the presence of a malignant pleural mesothelioma cluster in Sibaté.}, }
@article {pmid31225962, year = {2019}, author = {Marsili, D and Canepa, A and Mossone, N and Comba, P}, title = {Environmental Health Education for Asbestos-Contaminated Communities in Italy: The Casale Monferrato Case Study.}, journal = {Annals of global health}, volume = {85}, number = {1}, pages = {}, pmid = {31225962}, issn = {2214-9996}, mesh = {Adolescent ; Adult ; Asbestos/*toxicity ; Construction Materials/*toxicity ; Curriculum ; Environmental Exposure/adverse effects ; Environmental Health/*education ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology ; Male ; Mesothelioma/epidemiology ; Mesothelioma, Malignant ; Occupational Exposure/adverse effects ; Peer Group ; Pleural Neoplasms/epidemiology ; *Schools ; }, abstract = {BACKGROUND: Environmental health education contributes towards increasing awareness of communities to prevent exposure to hazardous substances. Casale Monferrato, the operating site for the Eternit asbestos-cement factory from 1907 to 1986, is a prioritized asbestos-contaminated site for remediation in Italy. The area is prone to severe asbestos-related diseases. About 50 cases of mesothelioma are diagnosed in Casale Monferrato annually; mesothelioma has been shown to be caused by occupational, environmental and domestic asbestos exposure.<br><br>OBJECTIVES: The goal of this paper is to analyze the Casale Monferrato case study in terms of youth engagement in environmental health education initiatives on asbestos risk and health impact. The paper aims at underlining the lessons learned in order to share the success of this initiative with other communities living in asbestos-contaminated sites in different countries.<br><br>METHODS: Peer education methodology has been used through the Asbestos Classroom to involve teachers, students and other local stakeholders in training activities, in selection of the contents for educational materials and interactive tools, as well as in choosing the presentation process for the aforementioned knowledge sharing instruments.<br><br>FINDINGS: From November 2014 to June 2018, 185 high school students and teachers were trained through the Asbestos Classroom. Through December 2018, they trained 3,241 classroom visitors. The Classroom relies on an inclusive participative process in which young people play a key role in the network of relationships within their community.<br><br>CONCLUSIONS: The paper corroborates the importance of engaging the educational system in communication efforts aimed at fostering collective awareness on environmental risk and health-related impacts for communities living in industrially contaminated sites. Considering the global dimension of the asbestos contamination and disease burden, this experience might be of relevance both in countries that banned asbestos and in those where asbestos is not yet prohibited.}, }
@article {pmid31211722, year = {2019}, author = {Metintas, M and Ak, G and Metintas, S and Yildirim, H and Dündar, E and Rahman, N}, title = {Prospective Study of the Utility of Computed Tomography Triage of Pleural Biopsy Strategies in Patients With Pleural Diseases.}, journal = {Journal of bronchology &amp; interventional pulmonology}, volume = {26}, number = {3}, pages = {210-218}, doi = {10.1097/LBR.0000000000000559}, pmid = {31211722}, issn = {1948-8270}, support = {MCCC-RP-14-A17178/MCCC_/Marie Curie/United Kingdom ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Algorithms ; Female ; Humans ; *Image-Guided Biopsy/adverse effects/methods ; Male ; Mesothelioma/complications/*diagnostic imaging/pathology ; Middle Aged ; Patient Selection ; Pleura/diagnostic imaging/pathology ; Pleural Effusion/*diagnostic imaging/etiology ; Pleural Neoplasms/complications/*diagnostic imaging/pathology/secondary ; Predictive Value of Tests ; Prospective Studies ; Thoracoscopy ; *Tomography, X-Ray Computed ; Triage ; Tuberculosis, Pleural/complications/*diagnostic imaging/pathology ; Young Adult ; }, abstract = {BACKGROUND: This study aimed to prospectively evaluate the efficacy and reliability of a diagnostic workup, triaging pleural biopsy method according to baseline computerized tomography (CT) findings in the diagnosis of pleural diseases.<br><br>METHODS: Patients with pleural pathology were divided into 3 arms according to findings on CT scan images. Arm A: patients with pleural thickening/lesion in addition to pleural effusion. These patients underwent CT scan-guided Abrams' needle pleural biopsy. Arm B: patients with pleural effusion alone or suspected benign asbestos pleurisy. This group underwent medical thoracoscopy (MT). Arm C: patients with only pleural thickening. This group underwent ultrasonography-guided cutting needle pleural biopsy. MT was planned in patients who did not have a specific diagnosis in the CT scan-guided Abrams' needle pleural biopsy group. When patients with a histopathologic diagnosis of fibrinous pleuritis after MT were assessed in terms of the risk factors for malignant pleural diseases, we offered a further invasive procedure.<br><br>RESULTS: A total of 164 patients were enrolled in the study. Diagnostic sensitivity after the initial procedure was 90.2% in Arm A, 93.3% in Arm B, 95.2% in Arm C, and 92.4% in the entire workup. The negative predictive value of the entire workup was 90.4% for malignant pleural mesothelioma, 97.1% for metastatic malignant pleural diseases, and 100% for tuberculous pleurisy. Five cases who had a diagnosis of fibrinous pleuritis after MT were detected to have risk factors, 4 of which (80%) indicated malignant disease. Complication rates were low and acceptable.<br><br>CONCLUSION: Use of CT scans to triage an appropriate pleural biopsy method is associated with high diagnostic success. We recommend that the proposed diagnostic workup in this study may be used as a diagnostic algorithm for pleural diseases that require a histopathologic analysis. Determination of risk factors predicting malignant disease in patients where fibrinous pleuritis is reported after MT would be useful for clinical practice.}, }
@article {pmid31207975, year = {2019}, author = {Catino, A and de Gennaro, G and Di Gilio, A and Facchini, L and Galetta, D and Palmisani, J and Porcelli, F and Varesano, N}, title = {Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma.}, journal = {Cancers}, volume = {11}, number = {6}, pages = {}, pmid = {31207975}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm related to asbestos exposure and with high mortality rate. The management of patients with MPM is complex and controversial, particularly with regard to early diagnosis. In the last few years, breath analysis has been greatly implemented with this aim. In this review the strengths of breath analysis and preliminary results in searching breath biomarkers of MPM are highlighted and discussed, respectively. Through a systematic electronic literature search, collecting papers published from 2000 until December 2018, fifteen relevant scientific papers were selected. All papers considered were prospective, comparative, observational case-control studies although every single one pilot and based on a relatively small number of samples. The identification of diagnostic VOCs pattern, through breath sample characterization and the statistical data treatment, allows to obtain a strategic information for clinical diagnostics. To date the collected data provide just preliminary information and, despite the promising results and diagnostic accuracy, conclusions cannot be generalized due to the limited number of individuals included in each cohort study. Furthermore none of studies was externally validated, although validation process is a necessary step towards clinical implementation. Breathomics-based biomarker approach should be further explored to confirm and validate preliminary findings and to evaluate its potential role in monitoring the therapeutic response.}, }
@article {pmid31205069, year = {2020}, author = {Alchami, FS and Attanoos, RL and Gibbs, A and Morgan, F and Jasani, B}, title = {Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {28}, number = {6}, pages = {444-447}, doi = {10.1097/PAI.0000000000000779}, pmid = {31205069}, issn = {1533-4058}, abstract = {BACKGROUND: Simian virus 40 (SV40)-contaminated polio vaccine was accidentally administered to about one-third of the UK population receiving polio vaccines between 1956 and 1962. SV40 was subsequently demonstrated to be a carcinogenic virus in experimental and animal models. Since then, the SV40 oncogenic protein large T antigen (SV40 Tag) has been shown to cause malignant transformation of asbestos-treated human pleural mesothelial cells and malignant pleural mesotheliomas in asbestos-exposed SV40 Tag transgenic mice. The present study was designed to investigate the possible association of SV40 Tag with human malignant pleural mesothelioma samples from birth cohorts of the UK population exposed to combined peak levels of asbestos and SV40-contaminated polio vaccines.<br><br>MATERIALS AND METHODS: Tumor and background lung tissue microarrays prepared from archival surgical specimens of 139 pleural mesothelioma cases, collected over a period of 8 years (1998 to 2005), were analyzed. These represented birth cohorts overlapping with the period 1950 to 1960, exposed to a high level of both asbestos and SV40-contaminated live polio vaccines. SV40 Tag mRNA expression was investigated using a highly sensitive and specific SV40 Tag RNA in situ hybridization detection method on the basis of the novel RNAscope technology.<br><br>RESULTS: SV40 Tag RNA was not detected in any of the 127 evaluable tumor cases, despite appropriate results obtained for the external positive and negative controls included.<br><br>CONCLUSION: The complete absence of SV40 Tag mRNA in this large series of cases contradicts experimental evidence suggestive of SV40 link with asbestos-exposed malignant pleural mesotheliomas in the UK population. Alternative explanations of the negative findings are discussed to exclude possible confounding factors.}, }
@article {pmid31200818, year = {2019}, author = {Tsim, S and Paterson, S and Cartwright, D and Fong, CJ and Alexander, L and Kelly, C and Holme, J and Evison, M and Blyth, KG}, title = {Baseline predictors of negative and incomplete pleural cytology in patients with suspected pleural malignancy - Data supporting 'Direct to LAT' in selected groups.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {133}, number = {}, pages = {123-129}, doi = {10.1016/j.lungcan.2019.05.017}, pmid = {31200818}, issn = {1872-8332}, support = {ETM/285/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Pleura/*pathology ; Pleural Effusion, Malignant/*diagnosis/pathology ; Pleural Neoplasms/*diagnosis/pathology ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVES: Negative effusion cytology is more common in certain forms of Malignant Pleural Effusion (MPE) and results in pathway delay. Local Anaesthetic Thoracoscopy (LAT) is extremely sensitive and safe but cannot be offered to all. A stratified pathway, including 'Direct to LAT' in selected cases could enhance patient experience but requires reliable baseline predictors of unhelpful cytology, including both negative (no malignant cells) and incomplete results (malignant cells identified but predictive markers failed), since pleural biopsies will be required in the latter for optimal management. This retrospective analysis of a prospective multi-centre study, sought to identify baseline features for pathway rationalization.<br><br>MATERIALS AND METHODS: 363/638 (57%) of patients recruited to the DIAPHRAGM study (ISRCTN10079972) were included. Prospective data, including final diagnoses, asbestos exposure and fluid cytology results were supplemented by retrospective Computed Tomography (CT) and predictive marker reports. Independent predictors of negative and incomplete cytology were determined by multivariable logistic regression. Contingency tables were used to assess diagnostic value of cytology in associated phenotypes.<br><br>RESULTS: 238/363 (66%) patients were diagnosed with MPE (18 tumour types). Fluid cytology was negative in 151/238 (63%) and independently associated with asbestos-exposure (Odds Ratio (OR) 5.34) and a malignant CT (OR 2.25). When both features were recorded the sensitivity and negative predictive value of fluid cytology were 19% (95% CI 11-30%) and 9% (95% CI 4-20%)), respectively. Cytology was incomplete in 34/238 (14%), i.e. 47% of positive cytology cases) but was not associated with any baseline feature. ORs for incomplete cytology in Ovarian, Breast, Renal and Lung Cancer were 83, 22, 21 and 9, respectively.<br><br>CONCLUSION: Negative cytology is extremely likely in patients with asbestos exposure and a malignant CT report. A 'Direct-to-LAT' approach may be appropriate in this setting. No baseline predictors of incomplete cytology were identified.}, }
@article {pmid31192957, year = {2019}, author = {Zan, X and Wang, Y and Shi, J and Zhao, L and Zhao, Y and Liu, R and Zhou, Y and Wan, Y and , }, title = {Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy.}, journal = {Medicine}, volume = {98}, number = {24}, pages = {e16028}, pmid = {31192957}, issn = {1536-5964}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; *Meta-Analysis as Topic ; Pleural Neoplasms/*metabolism ; *Systematic Reviews as Topic ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM.<br><br>METHODS: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers.<br><br>RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication.<br><br>CONCLUSION: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM.<br><br>ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews.<br><br>PROSPERO REGISTRATION NUMBER: CRD42019125880.}, }
@article {pmid31179006, year = {2019}, author = {Taylor, BH and Warnock, C and Tod, A}, title = {Communication of a mesothelioma diagnosis: developing recommendations to improve the patient experience.}, journal = {BMJ open respiratory research}, volume = {6}, number = {1}, pages = {e000413}, pmid = {31179006}, issn = {2052-4439}, mesh = {Asbestos/adverse effects ; Caregivers/*psychology ; *Communication ; Female ; Health Personnel/*psychology ; Humans ; Lung Neoplasms/*diagnosis/etiology/mortality/psychology ; Male ; Mesothelioma/*diagnosis/etiology/mortality/psychology ; Mesothelioma, Malignant ; *Professional-Patient Relations ; Prognosis ; Qualitative Research ; }, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer linked to asbestos exposure and inhalation. As with other cancers, receiving a diagnosis of MPM is challenging and distressing. Particular challenges are associated with communicating a diagnosis of MPM, including explaining the disease and its prognosis, treatment options and legal and financial implications. Receiving A Diagnosis Of Mesothelioma (RADIO Meso) aimed to understand the experience of communicating a diagnosis of MPM from the perspective of patients, family carers and health professionals.<br><br>Methods: This qualitative study comprised 31 individual interviews with patients, family carers and health professionals. This was followed by two group interviews (n=42) and an electronic consultation exercise (n=39).<br><br>Results: This study provides unique insight into the mesothelioma diagnostic experience of patients, family carers and health professionals. Key findings include the importance of regarding diagnosis as a process, and provision of continuity and consistency. The clinical nurse specialist and effective multidisciplinary team working provided vital contributions to successful mesothelioma diagnostic communication. Facilitators to diagnostic communication included honesty and timeliness in communication, partnership working and maintaining a patient-centred approach. Challenges to enhancing mesothelioma diagnosis communication included accessing ongoing training, ensuring a suitable clinical environment and being able to allocate appropriate time.<br><br>Conclusion: The RADIO Meso study highlights factors that influence the communication of a diagnosis of MPM from the perspectives of individual patients and family carers. These findings provide the basis for a set of recommendations that can be used by health professionals to improve the MPM diagnostic experience.}, }
@article {pmid31171576, year = {2019}, author = {Takada, K and Fujimoto, N and Ozeki, T and Nishimura, J and Miyamoto, Y and Asano, M and Fuchimoto, Y and Wada, S and Ozaki, S and Igawa, T and Sonobe, H and Kishimoto, T}, title = {Small intestinal intussusception in an adult.}, journal = {Journal of clinical pathology}, volume = {72}, number = {7}, pages = {510}, doi = {10.1136/jclinpath-2017-204973}, pmid = {31171576}, issn = {1472-4146}, mesh = {Aged ; Autopsy ; Cell Proliferation ; Fatal Outcome ; Humans ; Intestine, Small/diagnostic imaging/pathology ; Intussusception/*diagnostic imaging/pathology ; Male ; Mesothelioma/*diagnostic imaging/pathology ; }, }
@article {pmid31169558, year = {2019}, author = {Louw, A and Badiei, A and Creaney, J and Chai, MS and Lee, YCG}, title = {Advances in pathological diagnosis of mesothelioma: what pulmonologists should know.}, journal = {Current opinion in pulmonary medicine}, volume = {25}, number = {4}, pages = {354-361}, doi = {10.1097/MCP.0000000000000578}, pmid = {31169558}, issn = {1531-6971}, mesh = {Cyclin-Dependent Kinase Inhibitor p16/analysis ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; *Lung Neoplasms/diagnosis/pathology ; *Mesothelioma/diagnosis/pathology ; Mesothelioma, Malignant ; Pleural Effusion/*diagnosis/metabolism ; *Pleural Neoplasms/diagnosis/pathology ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {PURPOSE OF REVIEW: Malignant pleural mesothelioma (MPM) is a universally fatal illness with a rising incidence, particularly in developing countries. The diagnosis can be challenging and require repeated investigations with implications for the patient and healthcare system.<br><br>RECENT FINDINGS: Distinguishing between benign/reactive and malignant mesothelial proliferations can be challenging. Cytological diagnosis of MPM from pleural fluid is as reliable as histological analysis of tissue biopsies in epithelioid MPM - an approach endorsed by the International Academy of Cytology. Identification of BRCA1-associated protein 1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations in MPM have led to the development of new ancillary tests that can streamline the diagnostic pathway. The prognostic values of these molecules are being investigated. Clinicians should be aware of the recently described BAP1 tumor predisposition syndrome and offer genetic investigations in potential patients. Routine use of prophylactic radiotherapy in MPM patients after pleural interventions has been disproved in a randomized trial.<br><br>SUMMARY: Diagnosis of epithelioid MPM can be established on pleural fluid analysis in most patients. The use of BAP1 immunostaining and CDKN2A/p16 fluorescence in-situ hybridization are particularly useful in distinguishing benign from malignant mesothelial proliferations. Clinicians should ensure these investigations are available in the pathological assessment of cases to minimize invasive investigations and the associated risks.}, }
@article {pmid31166112, year = {2019}, author = {Santos Seoane, SM and Yano Escudero, R and Arenas García, V}, title = {An unexpected cause of dysphagia: pleural mesothelioma.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {111}, number = {6}, pages = {494-495}, doi = {10.17235/reed.2019.6024/2018}, pmid = {31166112}, issn = {1130-0108}, mesh = {Aged ; Deglutition Disorders/*etiology ; Humans ; Male ; Mesothelioma/*complications ; Pleural Neoplasms/*complications ; }, abstract = {Malignant mesothelioma usually originates from the pleura or peritoneum, and has a poor prognosis. The incidence of this type of tumor is increasing worldwide, which is probably a result of occupational or environmental exposure to asbestos. In 90% dyspnea, chest pain or a combination of both are usually the initial symptoms. Dysphagia only occurs in 1.4% and is very rare as the initial symptom. We present the case of a middle-aged patient, in whom the initial symptom was dysphagia, so an endoscopy was performed. This showed extrinsic compression of the esophagus that was demonstrated when performing the chest X-ray, in which it was revealed a posterior mediastinal mass surrounding the esophagus concentrically without mucosal invasion.}, }
@article {pmid31158563, year = {2019}, author = {Konen, T and Johnson, JE and Lindgren, P and Williams, A}, title = {Cancer incidence and mortality associated with non-occupational and low dose exposure to Libby vermiculite in Minnesota.}, journal = {Environmental research}, volume = {175}, number = {}, pages = {449-456}, doi = {10.1016/j.envres.2019.04.004}, pmid = {31158563}, issn = {1096-0953}, mesh = {*Aluminum Silicates ; *Asbestos ; Asbestos, Amphibole ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Minnesota/epidemiology ; Montana ; Occupational Exposure/*statistics &amp; numerical data ; }, abstract = {BACKGROUND: A vermiculite processing plant in a Minneapolis, Minnesota neighborhood utilized asbestos-containing ore from Libby, Montana from the late 1930's until 1989. Multiple pathways of exposure to Libby asbestos were characterized in a cohort of over 6000 plant workers and residents living near the plant.<br><br>OBJECTIVE: We conducted a cohort linkage study to assess the impact of cumulative low dose exposure and the role of occupational history on asbestos-related mortality and cancer morbidity among cohort members residing near a vermiculite plant.<br><br>METHODS: Cohort members alive in 1988 (n = 5848) were linked to the Minnesota Cancer Surveillance System to identify incident cases of mesothelioma, lung cancer, and all-cancer diagnosed from 1988 to 2010. Proportional incidence ratios (PIRs) were calculated for mesothelioma and lung cancer. Vital status and cause of death were ascertained from Minnesota vital records and the National Death Index (1988-2011). Mortality rates of the cohort (2001-2011) for asbestos-related outcomes were compared to the Minnesota population to estimate standardized mortality ratios (SMRs) and stratified by gender, exposure, and occupational history categories.<br><br>RESULTS: We identified seven cases of mesothelioma, with elevated incidence only in females (PIR = 11.76, 95% CI: 3.17, 30.12). Lung cancer was elevated in both genders: PIR = 1.54 (95% CI: 1.19, 2.0) in males and 1.62 (95% CI: 1.21, 2.12) in females. We found elevated mortality from COPD, lung cancer, and mesothelioma among females (SMR for mesothelioma in females = 18.97, CI: 3.91, 55.45), among the 546 deaths identified. All four deaths from mesothelioma occurred in the >75th percentile of exposure (>0.0156 fiber/cc x months). The SMR for lung cancer and all respiratory cancer was elevated even after controlling for occupation.<br><br>CONCLUSIONS: Community exposure to Libby amphibole asbestos from a vermiculite processing plant is associated with increased risk of COPD, lung cancer and mesothelioma incidence and mortality, most notably among females, and is likely to remain a public health issue for years to come.}, }
@article {pmid31138176, year = {2019}, author = {Kettunen, E and Savukoski, S and Salmenkivi, K and Böhling, T and Vanhala, E and Kuosma, E and Anttila, S and Wolff, H}, title = {CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {507}, pmid = {31138176}, issn = {1471-2407}, support = {115372//Terveyden Tutkimuksen Toimikunta/ ; 109003//Työsuojelurahasto/ ; }, mesh = {Aged ; Asbestos/*adverse effects ; Chromosomes, Human/genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/*metabolism ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/chemically induced/genetics/*metabolism ; Male ; Mesothelioma/chemically induced/genetics/*metabolism ; Mesothelioma, Malignant ; Middle Aged ; Stromal Cells/metabolism ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Deletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protein, p16, in relation to MPM patient's asbestos exposure is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier been shown to accumulate in lung cancer in relation to asbestos exposure but their status in MPM is unclear.<br><br>METHODS: We studied DNA copy numbers for CDKN2A using fluorescence in situ hybridization (FISH) and p16 expression by immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 and 19p13 by FISH.<br><br>RESULTS: We were unable to detect an association between p16 expression and pulmonary asbestos fiber count in MPM tumor cells. However, significantly more MPM patients with high pulmonary asbestos fiber count (> 1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure (≤ 0.5 million f/g) (51.4% vs 16.7%; p = 0.035, Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells associated with a high pulmonary asbestos fiber count (p = 0.044, Fisher's Exact test, two-tailed). In contrast to our earlier findings in asbestos associated lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in MPM although single cases with variable copy numbers on those regions were seen.<br><br>CONCLUSIONS: We found two instances where the gene locus CDKN2A or its corresponding protein expression, is associated with high asbestos exposure levels. This suggests that there may be biological differences between the mesotheliomas with high pulmonary asbestos fiber count and those with low fiber count.}, }
@article {pmid31132706, year = {2019}, author = {Colombino, E and Capella, S and Casalinuovo, F and Racco, R and Pruiti, F and Volante, M and Di Marco Lo Presti, V and Belluso, E and Capucchio, MT}, title = {Malignant peritoneal mesothelioma in a boar who lived in Calabria (Italy): Wild animal as sentinel system of human health.}, journal = {The Science of the total environment}, volume = {683}, number = {}, pages = {267-274}, doi = {10.1016/j.scitotenv.2019.05.254}, pmid = {31132706}, issn = {1879-1026}, mesh = {Animals ; Asbestos/analysis ; Asbestosis/epidemiology/veterinary ; Environmental Exposure/*statistics &amp; numerical data ; Environmental Monitoring/*methods ; Environmental Pollutants/analysis ; Humans ; Italy ; Lung Neoplasms/epidemiology/*veterinary ; Mesothelioma/epidemiology/*veterinary ; Mesothelioma, Malignant ; Swine ; }, abstract = {Mesothelioma is a tumor of the serosal membranes described both in human and veterinary medicine. While in humans the relationship between mesothelioma and exposure to asbestos and some other asbestiform minerals is well known, in animals it is still difficult to establish. In this paper a case of malignant peritoneal mesothelioma probably related to asbestos exposure in a wild boar is described. At post-mortem evaluation the peritoneum, diaphragm and serosal surface of liver and kidneys showed isolated to coalescent multiple nodular lesions. Samples from diaphragm, liver and lung were collected to perform microbiological and histological investigations. To assess the presence of asbestos and/or other asbestiform minerals, SEM-EDS investigations were performed on organs and soil samples collected from the area where the wild boar lived. Microbiological investigations were negative for Mycobacterium species. Gross and histological examination were compatible with a biphasic mesothelioma, with nodules composed of epithelioid and sarcomatoid elements with high pleomorphism. Immunohistochemistry revealed only multifocal scattered positivity for WT-1 and D2-40. Asbestos fibres were detected in all samples (organs and soil) by SEM-EDS, demonstrating a potential relationship between the neoplasia and the exposure to naturally occurring asbestos (NOA). In conclusion, the results of the present study are further confirmation that wild animals, such as the boar, are suitable sentinels to indicate the risk of environmental exposure to asbestos for human populations.}, }
@article {pmid31120531, year = {2019}, author = {Chen, T and Sun, XM and Wu, L}, title = {High Time for Complete Ban on Asbestos Use in Developing Countries.}, journal = {JAMA oncology}, volume = {5}, number = {6}, pages = {779-780}, doi = {10.1001/jamaoncol.2019.0446}, pmid = {31120531}, issn = {2374-2445}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; China ; Developing Countries ; Humans ; Mesothelioma/etiology/*prevention &amp; control ; Occupational Diseases/etiology/*prevention &amp; control ; Occupational Exposure/adverse effects/*prevention &amp; control ; Pleural Neoplasms/etiology/*prevention &amp; control ; }, }
@article {pmid31120100, year = {2019}, author = {Kamiya, H and Peters, S and Sodhi-Berry, N and Reid, A and Gordon, L and de Klerk, N and Brims, F and Musk, AW and Franklin, P}, title = {Validation of an Asbestos Job-Exposure Matrix (AsbJEM) in Australia: Exposure-Response Relationships for Malignant Mesothelioma.}, journal = {Annals of work exposures and health}, volume = {63}, number = {7}, pages = {719-728}, doi = {10.1093/annweh/wxz038}, pmid = {31120100}, issn = {2398-7316}, mesh = {Adult ; Asbestos/*adverse effects ; Australia/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*analysis ; Occupations/statistics &amp; numerical data ; Proportional Hazards Models ; Young Adult ; }, abstract = {OBJECTIVES: An asbestos job-exposure matrix (AsbJEM) has been developed to systematically and cost-effectively evaluate occupational exposures in population-based studies. The primary aim of this study was to examine the accuracy of the AsbJEM in determining exposure-response relationships between asbestos exposure estimates and malignant mesothelioma (MM) incidence (indirect validation). The secondary aim was to investigate whether the assumptions used in the development of the original AsbJEM provided accurate asbestos exposure estimates.<br><br>METHODS: The study population consisted of participants in an annual health surveillance program, who had at least 3-month occupational asbestos exposure. Calculated asbestos exposure indices included cumulative asbestos exposure and the average exposure intensity, estimated using the AsbJEM and duration of employment. Asbestos and MM exposure-response relationships were compared between the original AsbJEM and its variations based on manipulations of the intensity, duration and frequency of exposure. Twenty-four exposure estimates were calculated for both cumulative asbestos exposure and the average exposure intensity using three exposure intensities (50th, 75th and 90th percentile of the range of mode exposure), four peak durations (15, 30, 60 and 120 min) and two patterns of peak frequency (original and doubled). Cox proportional hazards models were used to describe the associations between MM incidence and each of the cumulative and average intensity estimates.<br><br>RESULTS: Data were collected from 1602 male participants. Of these, 40 developed MM during the study period. There were significant associations between MM incidence and both cumulative and average exposure intensity for all estimates. The strongest association, based on the regression-coefficient from the models, was found for the 50th percentile of mode exposure, 15-min peak duration and the doubled frequency of peak exposure. Using these assumptions, the hazard ratios for mesothelioma were 1 (reference), 1.91, 3.24 and 5.37 for the quartiles of cumulative asbestos exposure and 1 (reference), 1.84, 2.31 and 4.40 for the quartiles of the average exposure intensity, respectively.<br><br>CONCLUSION: The well-known positive exposure-response relationship between MM incidence and both estimated cumulative asbestos exposure and average exposure intensity was confirmed. The strongest relationship was found when the frequency of peak exposure in the AsbJEM was doubled from the originally published estimates.}, }
@article {pmid31119375, year = {2019}, author = {Galani, V and Varouktsi, A and Papadatos, SS and Mitselou, A and Sainis, I and Constantopoulos, S and Dalavanga, Y}, title = {The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment.}, journal = {Cancer chemotherapy and pharmacology}, volume = {84}, number = {2}, pages = {241-253}, doi = {10.1007/s00280-019-03878-3}, pmid = {31119375}, issn = {1432-0843}, mesh = {Apoptosis/*immunology ; Humans ; Lung Neoplasms/pathology/*therapy ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Prognosis ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive tumor that is strongly related to asbestos fiber exposure. The tumorigenesis procedure in MM is complex, and many pathogenetic mechanisms including chronic inflammation, deregulation of cell death, and the genomic copy-number losses and gains may contribute to carcinogenesis. MM cells are resistant to TRAIL-mediated apoptosis due to defects in extrinsic apoptotic pathway. CAPS, a regulator of cell cycle and death, may contribute to the MM development as well. BAP1 is the most frequently inactivated gene in MPM; BAP1 deficiency triggers malignant transformation via disruption of DNA repair, transcription regulation, cell metabolism, apoptosis, and ferroptosis. In addition, bcl-2 family proteins as well as abnormal activation of PI3 K/Akt/mTOR pathway and deregulation of the Wnt signaling pathway may result in MM tumorigenesis. Finally, the Hippo pathway plays a critical role in MPM development. Mutations of NF2 and LATS lead to YAP activation in MPM. Thus, inhibition of YAP activity by YAP inhibitors could be a potentially promising treatment option for MM. In conclusion, extensive genetic alterations exist in mesotheliomas associated with the signaling of apoptotic HM cells death. The comprehension of these pathways may contribute to enhancing survival via developing new effective therapeutic strategies.}, }
@article {pmid31110054, year = {2019}, author = {Waqar, AB and Menzies, D and Casey, M and Doran, M}, title = {Paraneoplastic phenomenon in mesothelioma.}, journal = {Thorax}, volume = {74}, number = {7}, pages = {719-720}, doi = {10.1136/thoraxjnl-2019-213176}, pmid = {31110054}, issn = {1468-3296}, mesh = {Aged ; Biopsy ; Humans ; Lung Neoplasms/*complications/diagnostic imaging/pathology ; Male ; Mesothelioma/*complications/diagnostic imaging/pathology ; Mesothelioma, Malignant ; Ophthalmoplegia/*etiology ; Paraneoplastic Syndromes, Ocular/*etiology ; Pleural Effusion, Malignant/etiology ; Tomography, X-Ray Computed ; }, abstract = {A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy.}, }
@article {pmid31107974, year = {2020}, author = {Milosevic, V and Kopecka, J and Salaroglio, IC and Libener, R and Napoli, F and Izzo, S and Orecchia, S and Ananthanarayanan, P and Bironzo, P and Grosso, F and Tabbò, F and Comunanza, V and Alexa-Stratulat, T and Bussolino, F and Righi, L and Novello, S and Scagliotti, GV and Riganti, C}, title = {Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.}, journal = {International journal of cancer}, volume = {146}, number = {1}, pages = {192-207}, doi = {10.1002/ijc.32419}, pmid = {31107974}, issn = {1097-0215}, mesh = {ATP Binding Cassette Transporter, Subfamily B/*genetics ; Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*genetics ; Female ; Humans ; Interleukin-1beta/*metabolism ; Interleukin-8/*metabolism ; Mesothelioma/*drug therapy/metabolism/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Pleural Neoplasms/*drug therapy/metabolism/pathology ; *Wnt Signaling Pathway ; }, abstract = {Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM-initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness-related pathways determine chemoresistance. Moreover, there are no predictive markers of IC-associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness-related pathways. We generated MPM IC from primary MPM samples and compared the gene expression and chemo-sensitivity profile of IC and differentiated/adherent cells (AC) of the same patient. Compared to AC, IC had upregulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed. ABCB5-knocked-out (KO) IC clones were resensitized to the drugs in vitro and in patient-derived xenografts. ABCB5 was transcriptionally activated by the Wnt/GSK3β/β-catenin/c-myc axis that also increased IL-8 and IL-1β production. IL-8 and IL-1β-KO IC clones reduced the c-myc-driven transcription of ABCB5 and reacquired chemosensitivity. ABCB5-KO clones had lower IL-8 and IL-1β secretion, and c-myc transcriptional activity, suggesting that either Wnt/GSK3β/β-catenin and IL-8/IL-1β signaling drive c-myc-mediated transcription of ABCB5. ABCB5 correlated with lower time-to-progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first-line chemotherapy in MPM patients.}, }
@article {pmid31103412, year = {2019}, author = {Scagliotti, GV and Gaafar, R and Nowak, AK and Nakano, T and van Meerbeeck, J and Popat, S and Vogelzang, NJ and Grosso, F and Aboelhassan, R and Jakopovic, M and Ceresoli, GL and Taylor, P and Orlandi, F and Fennell, DA and Novello, S and Scherpereel, A and Kuribayashi, K and Cedres, S and Sørensen, JB and Pavlakis, N and Reck, M and Velema, D and von Wangenheim, U and Kim, M and Barrueco, J and Tsao, AS}, title = {Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial.}, journal = {The Lancet. Respiratory medicine}, volume = {7}, number = {7}, pages = {569-580}, doi = {10.1016/S2213-2600(19)30139-0}, pmid = {31103412}, issn = {2213-2619}, mesh = {Aged ; Antineoplastic Agents/*administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols ; Cisplatin/*administration &amp; dosage ; Double-Blind Method ; Female ; Humans ; Indoles/*administration &amp; dosage ; Lung Neoplasms/*drug therapy/mortality/pathology ; Male ; Mesothelioma/*drug therapy/mortality/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/*administration &amp; dosage ; Pleural Neoplasms/*drug therapy/mortality/pathology ; Progression-Free Survival ; }, abstract = {BACKGROUND: Nintedanib targets VEGF receptors 1-3, PDGF receptors α and β, FGF receptors 1-3, and Src and Abl kinases, which are all implicated in malignant pleural mesothelioma pathogenesis. Here, we report the final results of the phase 3 part of the LUME-Meso trial, which aimed to investigate the efficacy and safety of pemetrexed plus cisplatin combined with nintedanib or placebo in unresectable malignant pleural mesothelioma.<br><br>METHODS: This double-blind, randomised, placebo-controlled phase 3 trial was done at 120 academic medical centres and community clinics in 27 countries across the world. Chemotherapy-naive adults (aged ≥18 years) with unresectable epithelioid malignant pleural mesothelioma and ECOG performance status 0-1 were randomly assigned 1:1 via an independently verified random number-generating system to receive up to six 21-day cycles of pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on day 1, then nintedanib (200 mg twice daily) or matched placebo on days 2-21. Patients without disease progression after six cycles received nintedanib or placebo maintenance on days 1-21 of each cycle. The primary endpoint was progression-free survival (investigator-assessed according to mRECIST) in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of their assigned study drug. This study is registered with ClinicalTrials.gov, number NCT01907100.<br><br>FINDINGS: Between April 14, 2016, and Jan 5, 2018, 541 patients were screened and 458 were randomly assigned to either the nintedanib group (n=229) or the placebo group (n=229). Median treatment duration was 5·3 months (IQR 2·8-7·3) in the nintedanib group and 5·1 months (2·7-7·8) in the placebo group. After 250 events, progression-free survival was not different between the nintedanib group (median 6·8 months [95% CI 6·1-7·0]) and the placebo group (7·0 months [6·7-7·2]; HR 1·01 [95% CI 0·79-1·30], p=0·91). The most frequently reported grade 3 or worse adverse event in both treatment groups was neutropenia (73 [32%] in the nintedanib group vs 54 [24%] in the placebo group). Serious adverse events were reported in 99 (44%) patients in the nintedanib group and 89 (39%) patients in the placebo group. The only serious adverse event occurring in at least 5% of patients in either group was pulmonary embolism (13 [6%] vs seven [3%]).<br><br>INTERPRETATION: The primary progression-free survival endpoint of the phase 3 part of LUME-Meso was not met and phase 2 findings were not confirmed. No unexpected safety findings were reported.<br><br>FUNDING: Boehringer Ingelheim.}, }
@article {pmid31097089, year = {2019}, author = {MacRae, RM and Ashton, M and Lauk, O and Wilson, W and O'Rourke, N and Simone, CB and Rimner, A}, title = {The role of radiation treatment in pleural mesothelioma: Highlights of the 14th International Conference of the International mesothelioma interest group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {132}, number = {}, pages = {24-27}, doi = {10.1016/j.lungcan.2019.03.023}, pmid = {31097089}, issn = {1872-8332}, mesh = {Animals ; Combined Modality Therapy ; Congresses as Topic ; Humans ; International Cooperation ; Mesothelioma/*radiotherapy ; Pleural Neoplasms/*radiotherapy ; Public Opinion ; Radiation Oncology/*trends ; Radiotherapy/*methods ; }, abstract = {Radiation remains an important component of mesothelioma treatment in 2018. Its use as a treatment modality continues to evolve as the technology for planning and delivery continues to improve. Use of radiation to improve local control in the involved hemithorax has been a common adjuvant treatment post extrapleural pneumonectomy for many years. Modern treatment options with advanced planning techniques including protons and intensity modulated radiation therapy lead to new potential options for treatment post lung-sparing surgery or in the unresectable setting. Presentations and discussions on the implementation of these strategies for palliation, treatment of oligometastatic recurrence or unresectable disease were the focus of a session dedicated to the role of radiation therapy at the 14th International Conference of the International Mesothelioma Interest Group and are reviewed in this article. Preclinical data to better understand how to integrate radiation and the delivery of novel systemic therapy approached like check point inhibitors are also presented.}, }
@article {pmid31095409, year = {2019}, author = {Rosner, D and Markowitz, G and Chowkwanyun, M}, title = {&quot;Nondetected&quot;: The Politics of Measurement of Asbestos in Talc, 1971-1976.}, journal = {American journal of public health}, volume = {109}, number = {7}, pages = {969-974}, pmid = {31095409}, issn = {1541-0048}, mesh = {Asbestos/*toxicity ; Carcinogens, Environmental/*adverse effects ; Cosmetics/*toxicity ; Humans ; Mesothelioma/chemically induced ; Mineral Fibers/adverse effects ; Particulate Matter/analysis ; Talc/*toxicity ; }, abstract = {The recent lawsuits against Johnson &amp; Johnson have raised the issue of what and when talcum powder manufacturers knew about the presence of asbestos in their products and what they did or did not do to protect the public. Low-level exposure to asbestos in talc is said to result in either mesothelioma or ovarian cancer. Johnson &amp; Johnson has claimed that there was &quot;no detectable asbestos&quot; in their products and that any possible incidental presence was too small to act as a carcinogen. But what exactly does &quot;nondetected&quot; mean? Here, we examine the historical development of the argument that asbestos in talcum powder was &quot;nondetected.&quot; We use a unique set of historical documents from the early 1970s, when low-level pollution of talc with asbestos consumed the cosmetics industry. We trace the debate over the Food and Drug Administration's efforts to guarantee that talc was up to 99.99% free of chrysotile and 99.9% free of amphibole asbestos. Cosmetic talc powder manufacturers, through their trade association, pressed for a less stringent methodology and adopted the term &quot;nondetected&quot; rather than &quot;asbestos-free&quot; as a term of art.}, }
@article {pmid31092657, year = {2019}, author = {de Boer, NL and van Kooten, JP and Burger, JWA and Verhoef, C and Aerts, JGJV and Madsen, EVE}, title = {Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial.}, journal = {BMJ open}, volume = {9}, number = {5}, pages = {e026779}, pmid = {31092657}, issn = {2044-6055}, mesh = {Adjuvants, Immunologic/*therapeutic use ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; Cancer Vaccines/*administration &amp; dosage/*therapeutic use ; *Clinical Trials, Phase II as Topic ; *Cytoreduction Surgical Procedures ; Dendritic Cells/*immunology ; Feasibility Studies ; Female ; Humans ; *Hyperthermia, Induced ; Immunotherapy ; Lung Neoplasms/pathology/*therapy ; Male ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/pathology/*therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.<br><br>METHODS AND ANALYSIS: The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma.<br><br>INTERVENTION: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.<br><br>ETHICS AND DISSEMINATION: Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.<br><br>TRIAL REGISTRATION NUMBER: NTR7060. EudraCT: 2017-000897-12; Pre-Results.}, }
@article {pmid31087402, year = {2019}, author = {Loomis, D and Richardson, DB and Elliott, L}, title = {Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality.}, journal = {American journal of industrial medicine}, volume = {62}, number = {6}, pages = {471-477}, pmid = {31087402}, issn = {1097-0274}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R01-OH007803/OH/NIOSH CDC HHS/United States ; }, mesh = {Adult ; Age Factors ; Asbestos, Serpentine/*adverse effects/analysis ; Cohort Studies ; Confidence Intervals ; Environmental Monitoring/methods ; Evaluation Studies as Topic ; Female ; Humans ; Lung Neoplasms/*chemically induced/*mortality/physiopathology ; Male ; Maximum Allowable Concentration ; Mesothelioma/*chemically induced/*mortality/physiopathology ; Mesothelioma, Malignant ; Middle Aged ; North Carolina/epidemiology ; Occupational Diseases/etiology/mortality ; Occupational Exposure/*adverse effects/analysis ; Pleural Neoplasms/*chemically induced/*mortality/physiopathology ; Retrospective Studies ; Risk Assessment ; Sex Factors ; Survival Analysis ; Textile Industry ; }, abstract = {BACKGROUND: While asbestos has long been known to cause mesothelioma, quantitative exposure-response data on the relation of mesothelioma risk and exposure to chrysotile asbestos are sparse.<br><br>METHODS: Quantitative relationships of mortality from mesothelioma and pleural cancer were investigated in an established cohort of 5397 asbestos textile manufacturing workers in North Carolina, USA. Eligible workers were those employed between 1950 and 1973 with mortality follow-up through 2003. Individual exposure to chrysotile fibres was estimated on the basis of 3420 air samples covering the entire study period linked to work history records. Exposure coefficients adjusted for age, race, and time-related covariates were estimated by Poisson regression.<br><br>RESULTS: Positive, statistically significant associations were observed between mortality from all pleural cancer (including mesothelioma) and time since first exposure (TSFE) to asbestos (rate ratio [RR], 1.19; 95% confidence interval [CI], 1.06-1.34 per year), duration of exposure, and cumulative asbestos fibre exposure (RR, 1.15; 95% CI, 1.04-1.28 per 100 f-years/mL; 10-year lag). Analyses of the shape of exposure-response functions suggested a linear relationship with TSFE and a less-than-linear relationship with cumulative exposure. Restricting the analysis to years when mesothelioma was coded as a unique cause of death yielded stronger but less precise associations.<br><br>CONCLUSIONS: These observations support with quantitative data the conclusion that chrysotile causes mesothelioma and encourage exposure-response analyses of mesothelioma in other cohorts exposed to chrysotile.}, }
@article {pmid31078776, year = {2019}, author = {Salaroglio, IC and Kopecka, J and Napoli, F and Pradotto, M and Maletta, F and Costardi, L and Gagliasso, M and Milosevic, V and Ananthanarayanan, P and Bironzo, P and Tabbò, F and Cartia, CF and Passone, E and Comunanza, V and Ardissone, F and Ruffini, E and Bussolino, F and Righi, L and Novello, S and Di Maio, M and Papotti, M and Scagliotti, GV and Riganti, C}, title = {Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {8}, pages = {1458-1471}, doi = {10.1016/j.jtho.2019.03.029}, pmid = {31078776}, issn = {1556-1380}, mesh = {Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Mesothelioma, Malignant ; Prognosis ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified.<br><br>METHODS: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome.<br><br>RESULTS: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4+) programmed death 1-positive (PD-1+) (>5.2%) and CD8+PD-1+ (6.4%) cells, CD4+ lymphocyte activating 3-positive (LAG-3+) (>2.8%) and CD8+LAG-3+ (>2.8%) cells, CD4+ T cell immunoglobulin and mucin domain 3-positive (TIM-3+) (>2.5%), and CD8+TIM-3+ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1+/LAG-3+/TIM-3+ CD4+ tumor-infiltrating lymphocytes correlated with overall survival.<br><br>CONCLUSIONS: A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome.}, }
@article {pmid31078166, year = {2019}, author = {Labrèche, F and Kim, J and Song, C and Pahwa, M and Ge, CB and Arrandale, VH and McLeod, CB and Peters, CE and Lavoué, J and Davies, HW and Nicol, AM and Demers, PA}, title = {The current burden of cancer attributable to occupational exposures in Canada.}, journal = {Preventive medicine}, volume = {122}, number = {}, pages = {128-139}, doi = {10.1016/j.ypmed.2019.03.016}, pmid = {31078166}, issn = {1096-0260}, support = {//CIHR/Canada ; }, mesh = {Adolescent ; Adult ; Asbestos/toxicity ; Breast Neoplasms ; Canada/epidemiology ; Carcinogens/*toxicity ; Censuses ; Female ; Humans ; Lung Neoplasms ; Male ; Middle Aged ; Neoplasms/*epidemiology/etiology/prevention &amp; control ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics &amp; numerical data ; Prevalence ; Silicon Dioxide/toxicity ; Skin Neoplasms ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Exposure to occupational carcinogens is often overlooked as a contributor to the burden of cancer. To estimate the proportion of cancer cases attributable to occupational exposure in Canada in 2011, exposure prevalence and levels of 44 carcinogens were informed by data from the Canadian carcinogen exposure surveillance project (CAREX Canada). These were used with Canadian Census (between 1961 and 2011) and Labour Force Survey (annual surveys between 1976 and 2013) data to estimate the number of workers ever exposed to occupational carcinogens. Risk estimates of the association between each carcinogen and cancer site were selected mainly from published literature reviews. Population attributable risks were estimated using Levin's equation and applied to the 2011 cancer statistics from the Canadian Cancer Registry. It is estimated that 15.5 million Canadians alive in 2011 were exposed, during at least one year between 1961 and 2001, to at least one carcinogen in the workplace. Overall, we estimated that in 2011, between 3.9% (95% CI: 3.1%-8.1%) and 4.2% (95% CI: 3.3%-8.7%) of all incident cases of cancer were due to occupational exposure, corresponding to lower and upper numbers of 7700-21,800 cases. Five of the cancer sites - mesothelioma, non-melanoma skin cancer, lung, female breast, and urinary bladder - account for a total of 7600 to 21,200 cancers attributable to occupational exposures such as solar radiation, asbestos, diesel engine exhaust, crystalline silica, and night shift work. Our study highlights cancer sites and occupational exposures that need recognition and efforts by all stakeholders to avoid preventable cancers in the future.}, }
@article {pmid31068670, year = {2019}, author = {Fitzgerald, RC and Rhodes, JM}, title = {Ingested asbestos in filtered beer, in addition to occupational exposure, as a causative factor in oesophageal adenocarcinoma.}, journal = {British journal of cancer}, volume = {120}, number = {12}, pages = {1099-1104}, doi = {10.1038/s41416-019-0467-9}, pmid = {31068670}, issn = {1532-1827}, mesh = {Adenocarcinoma/*epidemiology/etiology ; Alcohol Drinking/*epidemiology ; Asbestos/*poisoning ; *Beer ; Esophageal Neoplasms/*epidemiology/etiology ; Food Contamination ; Humans ; Incidence ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/statistics &amp; numerical data ; }, abstract = {Oesophageal adenocarcinoma has become much more common over the past 50 years, particularly in Britain, with an unexplained male to female ratio of > 4:1. Given the use of asbestos filtration in commercial brewing and reports of its unregulated use in British public houses in the 1970's to clear draught beer &quot;slops&quot;, we have assessed the hypothesis that ingested asbestos could be a causative factor for this increased incidence. Importantly, occupational asbestos exposure increases the risk of adenocarcinoma but not squamous cell carcinoma of the oesophagus. The presence of asbestos fibres was consistently reported in filtered beverages including beers in the 1970s and asbestos bodies have been found in gastrointestinal tissue, particularly oesophageal tissue, at autopsy. There is no reported association between the intake of alcohol and oesophageal adenocarcinoma but studies would mostly have missed exposure from draught beer before 1980. Oesophageal adenocarcinoma has some molecular similarities to pleural mesothelioma, a condition that is largely due to inhalation of asbestos fibres, including predominant loss of tumour suppressor genes rather than an increase of classical oncogenic drivers. Trends in incidence of oesophageal adenocarcinoma and mesothelioma are similar, rising rapidly over the past 50 years but now plateauing. Asbestos ingestion, either from beer consumed before around 1980, or from occupational exposure, seems a plausible causative factor for oesophageal adenocarcinoma. If this is indeed the case, its incidence should fall back to a low baseline by around 2050.}, }
@article {pmid31057996, year = {2019}, author = {Barsky, AR and Cengel, KA and Katz, SI and Sterman, DH and Simone, CB}, title = {First-ever Abscopal Effect after Palliative Radiotherapy and Immuno-gene Therapy for Malignant Pleural Mesothelioma.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4102}, pmid = {31057996}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive disease, with few, if any, curative interventions. While there is growing interest in using immunotherapy and immuno-gene therapy to treat MPM, very limited data currently exist for combining these modalities with radiotherapy. Preclinical data suggest that radiotherapy may be combined with immunotherapy to produce disease regression, with abscopal effects in mice with MPM. We report the first-ever case of abscopal effect in a patient with MPM, following radiotherapy and immuno-gene therapy. The patient was a 67-year-old male with prior asbestos exposure who presented with progressive dyspnea and thoracic pain. He underwent partial right pleurectomy, pleural biopsy, and talc pleurodesis, with pathology revealing epithelioid MPM. A subsequent chest computed tomography (CT) scan and fluoro-deoxyglucose positron-emission tomography (FDG-PET) CT scan showed extensive, right-sided, fluoro-deoxyglucose (FDG) avid mass-like pleural thickening encasing the right lung, with likely mediastinal extension, nodal metastases, and vascular compression. He enrolled in a clinical trial in which he received intrapleural interferon-alpha gene therapy but needed to discontinue therapy due to supraventricular tachycardia and superior vena cava syndrome induced from tumor burden. He was emergently treated with palliative radiotherapy to 30 Gy in 10 fractions. He was then started on pemetrexed and cisplatin chemotherapy. His subsequent chest CT scan two months after radiotherapy completion showed a dramatic treatment response within, as well as outside of, the irradiated field. After completion of radiotherapy, he did experience radiation esophagitis requiring nasogastric tube placement. Herein, we highlight the feasibility and efficacy of combining immuno-gene therapy with palliative radiotherapy to produce a substantial treatment response and an abscopal effect in a patient with unresectable MPM.}, }
@article {pmid31055741, year = {2019}, author = {Cui, Y and Zha, Y and Li, T and Bai, J and Tang, L and Deng, J and He, R and Dong, F and Zhang, Q}, title = {Oxidative effects of lungs in Wistar rats caused by long-term exposure to four kinds of China representative chrysotile.}, journal = {Environmental science and pollution research international}, volume = {26}, number = {18}, pages = {18708-18718}, doi = {10.1007/s11356-019-04978-6}, pmid = {31055741}, issn = {1614-7499}, support = {No. 41472046//National Natural Fund Project of China/ ; No. 41602033//National Natural Youth Fund Project of China/ ; No. YF17-Y12//the Fund Project of Sichuan Medical Law Research Center/ ; No. 2017LZXNYD-J24//Collaborative Fund of Luzhou Government and Southwest Medical University/ ; }, mesh = {Animals ; Asbestos, Serpentine/chemistry/*toxicity ; China ; Heme Oxygenase-1/metabolism ; Lipid Peroxidation/drug effects ; Lung/*drug effects/metabolism ; Lung Injury/*chemically induced/metabolism ; Male ; Oxidative Stress/*drug effects ; Particle Size ; Rats ; Rats, Wistar ; }, abstract = {Chrysotile accounts for some 90% to 95% of all the asbestos used worldwide. Scientific evidences have shown that asbestos (including chrysotile) exposure is associated with increased rates of lung cancer, asbestosis, and mesothelioma. However, molecular mechanisms underlying the toxicity effects of chrysotile are not clear. This study evaluated the oxidative stress in chronic lung toxicity caused by the intratracheal instillation (IT) of four kinds China representative chrysotile once a month for 12 months in Wistar rats. These results indicated that chrysotile exposure led to an obvious increase in lung mass and slowed the growth of body mass. Inflammation and fibrosis were observed by hematoxylin-eosin (HE) staining. Exposure to chrysotile significantly increased the accumulation of reactive oxygen species (ROS) and the level of lipid peroxidation and decreased antioxidant capacity in lung tissues. Furthermore, 1-6-month chrysotile exposure activated heme oxygenase-1 (HO-1) and heat shock protein 70 (HSP70) expression, whereas 12-month exposure caused significant decreases of two-factor expression levels in XK and MN groups when compared to negative control group. Therefore, our results suggested that chronic chrysotile pulmonary injury in Wistar rats is triggered by oxidative damage. Meanwhile, the oxidative damage of MN and XK was stronger than that of SSX and AKS, and the difference of oxidative damage in four chrysotile could have been brought by its properties, morphology, chemical composition, and particle size. With all the above mentioned in view, we hope that the revealed data in the experiment could contribute to the progress of further researches on the toxicity and mechanism of chrysotile.}, }
@article {pmid31046484, year = {2019}, author = {Nowak, AK and McDonnell, A and Cook, A}, title = {Immune checkpoint inhibition for the treatment of mesothelioma.}, journal = {Expert opinion on biological therapy}, volume = {19}, number = {7}, pages = {697-706}, doi = {10.1080/14712598.2019.1606209}, pmid = {31046484}, issn = {1744-7682}, mesh = {Antibodies, Monoclonal/*therapeutic use ; B7-H1 Antigen/immunology/metabolism ; Biomarkers, Tumor/metabolism ; CTLA-4 Antigen/immunology/metabolism ; Drug Therapy, Combination ; Humans ; Immunotherapy ; Mesothelioma/*drug therapy/pathology ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: Combination chemotherapy is currently standard care for advanced mesothelioma. Checkpoint blockade is a promising new treatment.<br><br>AREAS COVERED: This review covers clinical use and biomarkers of checkpoint blockade. Medline search used keywords 'mesothelioma' combined with 'checkpoint blockade' OR 'PD-L1' OR 'PD1' OR 'anti-CTLA4'; the search terms AND 'clinical trial' or AND 'biomarker*' were added. Handsearching covered abstracts from relevant meetings from 2016 to 2018 and reference lists. Data informed a narrative review.<br><br>EXPERT OPINION: Single agent anti-CTLA4 blockade is inactive in mesothelioma. Single agent PD-1 blockade as second or subsequent treatment gives 20-29% partial responses; no randomized comparisons against placebo or chemotherapy are available. Biomarkers of response have been difficult to identify. There is no consensus as to whether tumor PD-L1 expression predicts outcomes. Combination checkpoint inhibitors (CTLA4 and PD1 blockade) provide a small incremental increase in response rates and progression-free survival. Chemoimmunotherapy is the next frontier.}, }
@article {pmid31046142, year = {2019}, author = {Macedo, RF and Cerqueira, EMFP and Algranti, E and Silva, D and De Capitani, EM}, title = {High frequency and severity of pleural changes in former workers exposed to anthophyllite associated with other contaminating amphibole asbestos in Brazil.}, journal = {American journal of industrial medicine}, volume = {62}, number = {6}, pages = {503-510}, doi = {10.1002/ajim.22977}, pmid = {31046142}, issn = {1097-0274}, mesh = {Aged ; Asbestos, Amphibole/*adverse effects/analysis ; Asbestosis/*epidemiology/etiology ; Brazil/epidemiology ; Cohort Studies ; Databases, Factual ; Environmental Monitoring/methods ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*diagnosis/epidemiology ; Male ; Maximum Allowable Concentration ; Mesothelioma/chemically induced/*diagnosis/epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Mining ; Occupational Exposure/*adverse effects ; Occupational Health ; Pleural Neoplasms/chemically induced/*epidemiology/physiopathology ; Retrospective Studies ; Risk Assessment ; Spirometry/methods ; Time Factors ; Vital Capacity ; }, abstract = {OBJECTIVE: To evaluate the frequency and severity of pleuropulmonary alterations in anthophyllite-exposed former workers in Itapira, São Paulo, Brazil. The amphibole anthophyllite, a magnesium-iron silicate, had its mining, marketing, and use forbidden in Brazil in 1995.<br><br>METHODS: Former workers were followed from 1999 to 2011. All completed chest X-ray interpreted using the International Labour Office (ILO) classification. High-resolution computed tomography was used at the final evaluation. Spirometry assessed forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC throughout the follow-up period. Samples from the mined ore were analyzed by X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS).<br><br>RESULTS: XRD and SEM-EDS confirmed the presence in ore of anthophyllite at a concentration of 75%, in addition to tremolite and other amphiboles in lower concentrations. Twenty-eight subjects were evaluated. Median time of exposure was 3 years (minimum = 1; maximum = 18; interquartile interval = 1-4). Twenty cases of pleural abnormalities were diagnosed in 26 evaluated (77%). The average latency time was 25.6 ± 7.4 years. Two individuals (7.7%) showed progressive worsening of diffuse pleural thickening (DPT) and exhibited an annual FVC decrease of 85 mL and 150 mL, respectively.<br><br>CONCLUSION: This small sample showed a very high index of nonmalignant pleural abnormalities in anthophyllite-exposed workers compared with workers exposed to other kinds of fibers. Rapidly progressive DPT, defined by the severity of pleural compromise, was possibly secondary to the presence of other amphibole types in the inhaled dust. No significant loss of FVC was found in the studied group as a whole. No cases of asbestosis, lung carcinoma, and mesothelioma were diagnosed in this cohort.}, }
@article {pmid31038674, year = {2019}, author = {Oey, H and Daniels, M and Relan, V and Chee, TM and Davidson, MR and Yang, IA and Ellis, JJ and Fong, KM and Krause, L and Bowman, RV}, title = {Whole-genome sequencing of human malignant mesothelioma tumours and cell lines.}, journal = {Carcinogenesis}, volume = {40}, number = {6}, pages = {724-734}, doi = {10.1093/carcin/bgz066}, pmid = {31038674}, issn = {1460-2180}, mesh = {Cell Line, Tumor ; Humans ; Mesothelioma/*genetics/pathology ; Mutation ; Pleural Neoplasms/*genetics/pathology ; *Whole Genome Sequencing ; }, abstract = {Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes.}, }
@article {pmid31033031, year = {2019}, author = {Shih, AR and Kradin, RL}, title = {Malignant mesothelioma in Lynch syndrome: A report of two cases and a review of the literature.}, journal = {American journal of industrial medicine}, volume = {62}, number = {5}, pages = {448-452}, doi = {10.1002/ajim.22968}, pmid = {31033031}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*adverse effects ; Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics ; Female ; *Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*chemically induced/*genetics ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/*adverse effects ; Risk Factors ; }, abstract = {Malignant mesothelioma is a rare and aggressive cancer most typically associated with prior asbestos exposure. The nature of the relationship between asbestos exposure and hereditary familial syndromes predisposing to malignancy has not been determined. We report two Lynch syndrome patients with paraoccupational asbestos exposure who developed diffuse malignant mesothelioma of the pleura or peritoneum. Interestingly, one showed a separate focus of pleural well-differentiated papillary mesothelioma. It is likely that Lynch syndrome patients are at increased risk for the development of mesothelioma in the setting of exposure to asbestos, even at what is generally considered to be low levels. In the presence of a documented history of low-level asbestos exposure, patients with genetic predisposition disorders (including Lynch syndrome) should be considered to have an independent risk factor modifying the effects of asbestos exposure.}, }
@article {pmid31032152, year = {2019}, author = {Rakhra, A and Munir, A and Chilukuri, RS and Nahas, J}, title = {A Rare Case of Malignant Mesothelioma Presenting with Systemic Lupus Erythematosus Seropositivity: A Case Report and Review of Literature.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4092}, pmid = {31032152}, issn = {2168-8184}, abstract = {While malignant mesothelioma may initially present in a variety of ways, it is uncommon to present with systemic lupus erythematosus (SLE) seropositivity and thus obscuring its diagnosis. Our case involves a 75-year-old Caucasian male with a past medical history of essential hypertension, remote prostate cancer status post prostatectomy, and lifetime nontobacco use presenting with progressive shortness of breath over one month. After a negative cardiac assessment, a postcardiac catheterization chest X-ray (CXR) revealed a right-sided moderate-to-large pleural effusion that, on further workup, was found to be exudative. Effusion studies were negative for malignancy and bacterial growth. Recurrent accumulation of fluid after a thoracentesis one week prior prompted an autoimmune work up. Positive markers included antinuclear antibodies, anti-double stranded DNA antibodies, and anti-histone antibodies, while anti-Smith antibodies were negative. Although SLE was initially suspected based on serologies, no clinical signs or symptoms were present to fulfill the diagnosis criteria. A trial of oral prednisone resulted in decreased pleural effusion size with no further recurrence. Additional studies included a CT scan of the chest that showed pleural masses confirmed with biopsy to be epithelioid mesothelioma. Given the patient's age and new diagnosis of malignant mesothelioma, we hypothesized that the presence of autoantibodies was likely false positives due to acquired autoantibodies with age, hyperactivity of the immune system from malignancy, and possible prior asbestos exposure.}, }
@article {pmid31030080, year = {2019}, author = {Zona, A and Fazzo, L and Minelli, G and De Santis, M and Bruno, C and Conti, S and Comba, P}, title = {Peritoneal mesothelioma mortality in Italy: Spatial analysis and search for asbestos exposure sources.}, journal = {Cancer epidemiology}, volume = {60}, number = {}, pages = {162-167}, doi = {10.1016/j.canep.2019.04.001}, pmid = {31030080}, issn = {1877-783X}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Female ; Humans ; Italy ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality ; Spatial Analysis ; }, abstract = {BACKGROUND: This study is part of a national plan of epidemiological surveillance of malignant mesothelioma (MM) mortality in Italy. The paper shows the results of malignant peritoneal mesothelioma (MPeM) mortality study in Italian Regions and municipalities.<br><br>METHODS: National Bureau of Statistics data for MPeM municipal mortality (ICD-10, Code C45.1) were analyzed in the time-window 2003-2014: mortality standardized rates (reference Italian population, census 2011), temporal trends of the annual national rates, Standardized Mortality Ratios and a municipal clustering analysis were performed.<br><br>RESULTS: 747 deaths for MPeM were recorded (0.10/100,000): 464 in men (0.14/100,000) and in 283 women (0.07/100,000). No significant MPeM mortality temporal trend was found. Seventeen municipalities showed excesses of mortality for MPeM in at least one gender and/or overall population. Four clusters in male population, and one in women were identified.<br><br>CONCLUSIONS: The study identifies some areas where remediation activities and/or health care actions may be warranted.}, }
@article {pmid31023248, year = {2019}, author = {Nagamatsu, Y and Oze, I and Aoe, K and Hotta, K and Kato, K and Nakagawa, J and Hara, K and Kishimoto, T and Fujimoto, N}, title = {Physician requests by patients with malignant pleural mesothelioma in Japan.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {383}, pmid = {31023248}, issn = {1471-2407}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Environmental Exposure ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care ; Physicians ; Pleural Neoplasms/chemically induced/*epidemiology/pathology ; Quality of Life ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed.<br><br>METHODS: This cross-sectional survey was part of a larger study (N = 133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content.<br><br>RESULTS: Responses (N = 217) from MPM patients (N = 73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients.<br><br>CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.}, }
@article {pmid31022494, year = {2019}, author = {Christofidou-Solomidou, M and Pietrofesa, RA and Park, K and Albelda, SM and Serve, KM and Keil, DE and Pfau, JC}, title = {Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice.}, journal = {Toxicology and applied pharmacology}, volume = {375}, number = {}, pages = {81-93}, pmid = {31022494}, issn = {1096-0333}, support = {R21 CA178654/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Butylene Glycols/*pharmacology ; Female ; Glucosides/*pharmacology ; Inflammation/*chemically induced/*prevention &amp; control ; Male ; Mice ; Mice, Inbred C57BL ; Organ Size ; Peritoneum/drug effects/pathology ; Spleen/drug effects/pathology ; }, abstract = {BACKGROUND: Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice.<br><br>METHODS: Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry.<br><br>RESULTS: LA exposure induced a significant increase (p < 0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p < 0.0001) elevated post LA exposure, and were significantly (p < 0.0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells.<br><br>CONCLUSIONS: LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases.<br><br>SUMMARY: Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.}, }
@article {pmid30993422, year = {2019}, author = {Boffetta, P and Donato, F and Pira, E and Luu, HN and La Vecchia, C}, title = {Risk of mesothelioma after cessation of asbestos exposure: a systematic review and meta-regression.}, journal = {International archives of occupational and environmental health}, volume = {92}, number = {7}, pages = {949-957}, pmid = {30993422}, issn = {1432-1246}, mesh = {Asbestos/*toxicity ; Carcinogens, Environmental/adverse effects ; Female ; Humans ; Lung Neoplasms/epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Occupational Exposure/*adverse effects ; Peritoneal Neoplasms/epidemiology/mortality ; Pleural Neoplasms/epidemiology/mortality ; Risk Factors ; *Time Factors ; }, abstract = {PURPOSE: A 'risk reversal' has been observed for several human carcinogens following cessation of exposure, but it is unclear whether it also exists for asbestos-related mesothelioma.<br><br>METHODS: We conducted a systematic review of the literature and identified nine studies that reported information on risk of mesothelioma after cessation of asbestos exposure, and performed a meta-regression based on random effects models. As comparison we analyzed results on lung cancer risk from four of these studies.<br><br>RESULTS: A total of six risk estimates from five studies were included in the meta-analysis. The summary relative risk (RR) of mesothelioma for 10-year interval since cessation of exposure was 1.02 [95% confidence interval (CI) 0.87-1.19; p-heterogeneity 0.01]. The corresponding RR of lung cancer was 0.91 (95% CI 0.84-0.98).<br><br>CONCLUSIONS: This analysis provides evidence that the risk of mesothelioma does not decrease after cessation of asbestos exposure, while lung cancer risk does.}, }
@article {pmid30968843, year = {2019}, author = {Fedrigotti, A and Riccadonna, A and Riccadonna, D}, title = {&quot;Candido's List&quot;: the workers of Collotta Cis &amp; Figli at Molina di Ledro in Trento Province, Italy. A tale of magnesia, asbestos and work.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {90-93}, doi = {10.4415/ANN_19_01_16}, pmid = {30968843}, issn = {2384-8553}, mesh = {Asbestos, Amosite/*adverse effects/history ; Environmental Restoration and Remediation ; Female ; History, 19th Century ; Humans ; Italy ; Magnesium/adverse effects ; Magnesium Oxide/adverse effects ; Male ; Mesothelioma/*epidemiology/etiology/history ; Occupational Diseases/etiology/history ; Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology/history ; }, abstract = {The study entitled &quot;Candido's List&quot; (La Lista di Candido) is not the work of the three authors alone. A good part of the community is entitled to feel itself coauthor, each for his/her own part, of a research project that has succeeded in blending a variety of different ingredients: history, entrepreneurship, the industrialization of the Trento Province with all its high and low points, personal life stories, medicine, genius, work, women's emancipation, the past but also the present and future. The research comprises an eloquent collection of memories and a variety of iconographic materials; it has now become a book and a travelling exhibition containing the accounts of the people who worked at the Collotta-Cis factory in Molina di Ledro. It starts with the brilliance of Pier Antonio Cassoni, who in 1816 deposited the first patent in the world for the extraction of magnesium carbonate, and closes with the decontamination of the factory site in the late 1980s. A needful section has been set aside for the painful facts relating to the processing of asbestos fibre; a final space, midway between an artistic reading and an interpretation for the future, has seen the involvement of the Circolo Fotoamatori di Ledro, with a photographic itinerary enabling the reader to &quot;virtually' enter the remaining worksites and listen to these spaces &quot;tell&quot; their stories after years of silence. A story in black and white, where the two tones are also messages for reading a complex story, one that it is important to remember.}, }
@article {pmid30968842, year = {2019}, author = {Parolari, G}, title = {An outbreak of cancer and asbestosis among former amosite-exposed subjects in Ledro Valley, Italy. From discovery to environmental cleanup.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {80-89}, doi = {10.4415/ANN_19_01_15}, pmid = {30968842}, issn = {2384-8553}, mesh = {Adolescent ; Adult ; Aged ; Asbestos ; Asbestos, Amosite/*adverse effects ; Asbestosis/*epidemiology/mortality ; Child ; Disease Outbreaks ; Environmental Restoration and Remediation/*methods ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology/mortality ; Male ; Mesothelioma/epidemiology/etiology/mortality ; Middle Aged ; Neoplasms/chemically induced/*epidemiology/mortality ; Occupational Exposure/statistics &amp; numerical data ; Young Adult ; }, abstract = {Here are reviewed the studies conducted on asbestos-amosite pollution and its effects on the health of workers exposed from 1928 to 1973 at the Collotta-Cis factory of Ledro, Italy. The methods adopted to conduct the initial research, involving the population itself and the local administrations are described. The data summarized include: epidemiological studies of mortality carried out in 1977-85 and updated in 2009; results of the investigations carried out throughout the 1980s on the health consequences on workers, their families and residents near the factory; process of environmental cleanup from asbestos of the industrial area, completed in 1989, and the pollution risk assessment in the whole Ledro Valley. Although this was a small community of about 400 workers, these studies show that exposure to asbestos is responsible for the death of 81 people (22 mesotheliomas, 21 asbestosis, 38 malignant tumors of the lung, digestive system, ovary), for 1400 years of life lost, and for about 100 invalidity pensions, as recognized to former workers by INAIL.}, }
@article {pmid30968841, year = {2019}, author = {Marsili, D and Magnani, C and Canepa, A and Bruno, C and Luberto, F and Caputo, A and Fazzo, L and Zona, A and Comba, P}, title = {Communication and health education in communities experiencing asbestos risk and health impacts in Italy.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {70-79}, doi = {10.4415/ANN_19_01_14}, pmid = {30968841}, issn = {2384-8553}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/prevention &amp; control ; Communication ; Environmental Exposure ; Health Education/*statistics &amp; numerical data ; Humans ; Incidence ; Italy/epidemiology ; Neoplasms/epidemiology/etiology ; Occupational Exposure ; Public Health Surveillance ; }, abstract = {INTRODUCTION: Numerous municipalities in Italy currently experience asbestos health impact, in particular excesses of pleural mesothelioma incidence and mortality. This paper presents an integrated analysis of epidemiological studies and communication actions in affected municipalities to highlight how communication has been implemented depending on health impact evidence and involvement of local stakeholders.<br><br>METHODOLOGY: Four case studies are identified concerning industrial and natural sources of asbestos exposure having different diseases burden. This integrated analysis benefited from multidisciplinary skills.<br><br>DISCUSSION: Evidence of different stakeholders engagement is presented to emphasize their role in the communication process. Similarities and differences among case studies allowed us to identify lessons-learned to be transferred in other asbestos contaminated sites.<br><br>CONCLUSIONS: The adoption of communication strategies and practices, since the very early evidence of asbestos health impact, represents a relevant contribution for epidemiological and health surveillance, particularly for those communities where asbestos health impact has only been recently reported.}, }
@article {pmid30946862, year = {2019}, author = {Finkelstein, MM}, title = {A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.}, journal = {Toxicology and applied pharmacology}, volume = {371}, number = {}, pages = {1-2}, doi = {10.1016/j.taap.2019.03.023}, pmid = {30946862}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*adverse effects ; Animals ; Asbestos/*adverse effects ; Mesothelioma/*chemically induced/diagnosis/epidemiology ; Mineral Fibers/adverse effects ; Occupational Exposure/*adverse effects ; Risk Assessment ; Risk Factors ; }, abstract = {Dr. Garabrant presented a paper concerning a comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans at the Elongate Mineral Particles Conference in Charlottesville, Virginia in 2017. I was a participant at the Conference. Following Dr. Garabrant's talk, I rose in question period to point out that he had not considered information about the occurrence of mesothelioma in several cohorts that was published after the studies that he cited. These additional data were still not addressed in the paper published in your Journal. I believe that your readers would be interested in these, so this letter is written to draw the additional data to their attention.}, }
@article {pmid30944991, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {A survey of patient and caregiver experience with malignant pleural mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {12}, pages = {4675-4686}, pmid = {30944991}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Caregivers/*psychology ; Decision Making ; Female ; Grief ; Health Personnel/*psychology ; Humans ; Lung Neoplasms/*psychology/*therapy ; Male ; Mesothelioma/*psychology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care/methods ; Physician-Patient Relations ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with poor prognosis. As there is little information on the lived experience of MPM, our aim was to document the experience of MPM patients and their caregivers.<br><br>METHODS: Surveys for MPM patients and caregivers were developed from previous interviews with patients, caregivers, and health professionals, about treatments and decision-making. Participants were recruited from two hospitals, government compensation body, and support groups.<br><br>RESULTS: Survey responses were received from 78 MPM patients and 106 caregivers from January to September 2014.<br><br>PATIENTS: 85% male, median age 69 years, median time since diagnosis 15 months. Caregivers: median age 68, 91% female, 90% spouse of MPM patient, 95% bereaved. Most participants felt informed about treatment options but only 69% thought all treatment options were discussed. Chemotherapy was discussed most frequently (92-95%); ~80% had sufficient information for decision-making. Decision regarding chemotherapy was made by patient considering doctor's opinion (24%), doctor and patient equally (18%), and doctor (17%). Participants 'agreed'/'strongly agreed' that they made the right decision about chemotherapy (patients 81%, caregivers 60%), but 5% and 16%, respectively, regretted the decision. Most participants received 'sufficient' support (71%). A quarter reported seeing cancer nurse specialists. Palliative care referral: 31% patients, 85% caregivers. Caregivers would have liked to talk to someone by themselves (41%), more time with doctors (30%), psychological support (29%), and clearer information (31%). Bereaved caregivers requested grief counselling (39%) and post-death consultation with specialists (23-25%).<br><br>CONCLUSIONS: Satisfaction with treatment was high, but participants identified need for improved communication and quality information, discussion about all treatments, end-of-life assistance, and caregiver support after the patient's death.}, }
@article {pmid30941506, year = {2019}, author = {Lococo, F and Di Stefano, T and Rapicetta, C and Piro, R and Gelli, MC and Muratore, F and Ricchetti, T and Taddei, S and Zizzo, M and Cesario, A and Facciolongo, N and Paci, M}, title = {Thoracic Hyper-IgG4-Related Disease Mimicking Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {197}, number = {3}, pages = {387-390}, pmid = {30941506}, issn = {1432-1750}, mesh = {Aged ; Bronchoscopy ; Diagnosis, Differential ; Endosonography ; Glucocorticoids/therapeutic use ; Humans ; Immunoglobulin G4-Related Disease/complications/*diagnosis/drug therapy/pathology ; Lung Neoplasms/*diagnosis ; Lymphadenopathy/diagnosis/etiology/pathology ; Male ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Pleural Diseases/complications/*diagnosis/drug therapy/pathology ; Pleural Effusion/etiology ; Pleural Neoplasms/*diagnosis ; Positron Emission Tomography Computed Tomography ; Prednisone/therapeutic use ; }, abstract = {We report a rare case of a IgG4-related disease presenting with recurrent pleural effusion, pleural thickness and multiple mediastinal lymphadenopathies and no involvement of other extrathoracic organs. A 65-year-old man with a previous asbestos exposure presented with cough and pain discomfort. A large right pleural effusion was detected and evacuated (siero-haematic liquid). With the suspicious of a pleural mesothelioma, a CT-scan before and a 18F-FDG PET/CT-scan later were performed revealing multiple pleural thickenings and multiple mediastinal lymphadenopathies with radiotracer uptake. EBUS-TBNA EBUS-TBNA did not result in a formal pathological diagnosis; thus, multiple pleural biopsy were performed via right thoracoscopy. At pathology the pleura was markedly thickened by a chronic fibroinflammatory process with scattered lymphoid follicles and a large number of mature plasma cells. Immunohistochemistry shows a mixed B (CD20+) and T (CD3+) population of lymphocytes, without light chain restriction and an increased number of IgG4-positive plasma cells. A presumptive diagnosis of IgG4-related disease was formulated. Total body CT-scan excluded other organ involvement. Blood test showed elevated serum IgG4 concentrations (253 mg/dL) and mild elevation of acute-phase reactants (C-reactive protein 10.7 mg/L). Autoimmune profile was negative. A diagnosis of definite IgG4-related disease was made, and treatment with prednisone 50 mg/day was started.}, }
@article {pmid30937282, year = {2019}, author = {Haygarth, M and Zaw, KK and Yachmenikova, V and Pokorny, AMJ and Kwong, KK and Heraganahally, SS}, title = {Bilateral diffuse pulmonary infiltrates secondary to malignant peritoneal mesothelioma - A rare clinical presentation.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {326-327}, pmid = {30937282}, issn = {2213-0071}, abstract = {Diffuse pulmonary metastasis secondary to primary peritoneal malignant mesothelioma is rarely reported in the literature. In this report we describe a 59-year-old Caucasian women with no known previous asbestos exposure presenting with bilateral diffuse pulmonary opacities in association with primary malignant peritoneal mesothelioma. The diagnosis was confirmed by ultrasound guided abdominal and bronchoscopy, trans-bronchial lung biopsy. The biopsy demonstrated positive staining with AE1/3, CK7, CK5/6, WT1, calretinin and D2 40. The cells were negative for BerEP4, PAX8, CA125, ER, CD34, ERG, P63, P40, Melan A, Gata3 and mammaglobin. The morphology and immunohistochemical profile supported a diagnosis of epithelioid malignant mesothelioma.}, }
@article {pmid30936339, year = {2019}, author = {Muralidhar, V and Raghav, P and Das, P and Goel, A}, title = {A case from India of pleural malignant mesothelioma probably due to domestic and environmental asbestos exposure: a posthumous report.}, journal = {BMJ case reports}, volume = {12}, number = {3}, pages = {}, doi = {10.1136/bcr-2018-227882}, pmid = {30936339}, issn = {1757-790X}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Compensation and Redress/legislation &amp; jurisprudence ; Environmental Exposure/*adverse effects/legislation &amp; jurisprudence ; Fatal Outcome ; Humans ; India ; Lung Neoplasms/chemically induced/*diagnosis/mortality ; Male ; Mesothelioma/chemically induced/*diagnosis/mortality ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects/legislation &amp; jurisprudence ; Pleural Neoplasms/chemically induced/*diagnosis/mortality ; Workers' Compensation/legislation &amp; jurisprudence ; }, abstract = {India is the largest consumer of asbestos in the world. There is no report from India of mesothelioma related to asbestos. The case is a 42-year-old man who died of pleural mesothelioma. He was exposed to asbestos domestically and from the environment since birth. Two of his close family members worked in a factory that used asbestos. The living quarter of the family was within the premises of the factory. Asbestos waste was strewn on the grounds surrounding the quarters. After decades of legal battles by workers and families exposed to asbestos, Indian courts have ordered remedial measures and compensation to people, who are exposed to asbestos at work and the environment. Mesothelioma, currently in epidemic proportions in the west where asbestos production was banned in the 1990s, could rise to alarming levels in the next decades in India if the legal remedial measures are not implemented soon.}, }
@article {pmid30928905, year = {2019}, author = {Reid, A and Franklin, P and Berry, G and Peters, S and Sodhi-Berry, N and Brims, F and Musk, AW and de Klerk, NH}, title = {Response to letter by Farioli et al.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {5}, pages = {356}, doi = {10.1136/oemed-2019-105740}, pmid = {30928905}, issn = {1470-7926}, mesh = {Adult ; Asbestos, Crocidolite ; Child ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30927363, year = {2019}, author = {Koutros, S and Lubin, JH and Graubard, BI and Blair, A and Stewart, PA and Beane Freeman, LE and Silverman, DT}, title = {Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile.}, journal = {American journal of epidemiology}, volume = {188}, number = {8}, pages = {1484-1492}, pmid = {30927363}, issn = {1476-6256}, support = {Z01 CP010120/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Acrylonitrile/*toxicity ; Aged ; Aged, 80 and over ; Cause of Death ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Mortality/*trends ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; United States/epidemiology ; }, abstract = {We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.}, }
@article {pmid30927189, year = {2019}, author = {Kennedy, JM}, title = {The forensic significance of pseudomesotheliomatous adenocarcinoma of the lung.}, journal = {Forensic science, medicine, and pathology}, volume = {15}, number = {3}, pages = {458-462}, pmid = {30927189}, issn = {1556-2891}, mesh = {Adenocarcinoma/metabolism/*pathology ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lung/*pathology ; Lung Neoplasms/metabolism/*pathology ; Mesothelioma ; Mesothelioma, Malignant ; }, abstract = {Pseudomesotheliomatous carcinomas (PMC) are rare tumors that clinically, macroscopically, and sometimes histologically resemble malignant pleural mesotheliomas. We report a case of a 91 year woman who was found to have diffuse nodular pleural thickening and a lung mass during a workup for persistent cough. She declined rapidly and died before a histologic diagnosis could be made. Postmortem examination revealed a tumor that diffusely involved the pleural surface with local extension into the chest wall, pericardium, and diaphragm along with a concurrent lung mass. Histologic examination showed poorly-differentiated cells predominantly arranged in sheets, cords, and nests with focal glandular differentiation. An immunohistochemical panel of calretinin, WT1, BEREP4, MOC31, and TTF1 confirmed the diagnosis of primary lung adenocarcinoma. The macroscopic, histologic, and immunohistochemical features used to distinguish metastatic and primary lung adenocarcinoma from epithelioid malignant mesothelioma are discussed. The distinction of malignant mesothelioma from pseudomesotheliomatous carcinoma is important for medicolegal reasons regarding asbestos related compensation claims.}, }
@article {pmid30924615, year = {2019}, author = {Algranti, E and Ramos-Bonilla, JP and Terracini, B and Santana, VS and Comba, P and Pasetto, R and Mazzeo, A and Cavariani, F and Trotta, A and Marsili, D}, title = {Prevention of Asbestos Exposure in Latin America within a Global Public Health Perspective.}, journal = {Annals of global health}, volume = {85}, number = {1}, pages = {}, pmid = {30924615}, issn = {2214-9996}, mesh = {Asbestos, Serpentine/*economics/*toxicity ; Carcinogenesis ; Environmental Exposure/adverse effects/analysis/prevention &amp; control ; Humans ; Latin America/epidemiology ; Lung Neoplasms/*epidemiology/*etiology ; Mesothelioma/*epidemiology ; Mining ; Occupational Exposure/adverse effects/analysis/*prevention &amp; control ; Public Health ; }, abstract = {BACKGROUND: Asbestos consumption in Latin America (LA) amounts to 10% of yearly global production. Little is known about the impact of asbestos exposure in the region.<br><br>OBJECTIVE: To discuss scientific and socio-economic issues and conflicts of interest and to summarize epidemiological data of asbestos health effects in LA.<br><br>DISCUSSION: Recent data on chrysotile strengthened the evidence of its carcinogenicity and showed an excessive risk of lung cancer at cumulative exposure levels as low as 1.5 fibre-years/ml. Technology for substitution is available for all asbestos-containing products and ceasing asbestos production and manufacturing will not result in unemployment and loss of income, except for the mining industry. The flawed arguments used by the industry to maintain its market, both to the public and in courtrooms, strongly relies on the lack of local evidence of the ill effects and on the invisibility of asbestos-related diseases in LA, due to the limited number of studies and the exposed workers' difficulty accessing health services. The few epidemiological studies available show clear evidence of clusters of mesothelioma in municipalities with a history of asbestos consumption and a forecasted rise in its incidence in Argentina and Brazil for the next decade. In Brazil, non-governmental organizations of asbestos workers were pivotal to counterbalance misinformation and inequities, ending recently in a Supreme Court decision backing an asbestos ban. In parallel, continuous efforts should be made to stimulate the growth of competent and ethical researchers to convey adequate information to the scientific community and to the general public.}, }
@article {pmid30917938, year = {2019}, author = {Linton, A and Blinman, P and Kao, S and van Zandwijk, N}, title = {Patterns of care and survival of older patients with malignant pleural mesothelioma.}, journal = {Journal of geriatric oncology}, volume = {10}, number = {4}, pages = {573-576}, doi = {10.1016/j.jgo.2019.02.013}, pmid = {30917938}, issn = {1879-4076}, mesh = {Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/mortality/*therapy ; Male ; Mesothelioma/mortality/*therapy ; Mesothelioma, Malignant ; New South Wales ; Palliative Care/*statistics &amp; numerical data ; Pleural Neoplasms/mortality/*therapy ; Pneumonectomy/*statistics &amp; numerical data ; Radiotherapy/*statistics &amp; numerical data ; Radiotherapy, Adjuvant ; Survival Rate ; Thoracic Surgical Procedures/statistics &amp; numerical data ; }, abstract = {OBJECTIVE: Malignant pleural mesothelioma (MPM) is a cancer that primarily affects older adults. However this patient population is frequently under-represented in clinical studies. Therefore, we studied the impact of advancing age on treatment utilisation and clinical outcomes in an extensive series of minimally selected MPM patients.<br><br>MATERIALS AND METHODS: Patients with MPM receiving compensation from the New South Wales (NSW) Dust Diseases Authority (2002-2009) were assessed. They were categorised by age (<70 years, 70-80 years or > 80 years) and chi-square testing was used to assess the relationship between clinical and demographic variables, age, treatment and overall survival (OS).<br><br>RESULTS: We identified 910 patients; 41% were aged <70 years, 40% were aged 70-80 years, and 19% were aged >80 years old. Median OS decreased with increasing age: 13.5 months in <70 years, 9.5 months in 70-80 years and 7.1 months in >80 years as did chemotherapy use (66%, 35% and 8% respectively). Radical surgical intervention, adjuvant, and palliative radiotherapy were less frequently used with advanced age. A Kaplan Meier analysis revealed that there was a significant survival advantage (p < .001) for patients <70 and 70-80 years receiving chemotherapy (16.8 vs 7.0 months; 13.9 vs 5.8 months respectively), but not for patients >80 years.<br><br>CONCLUSION: Advancing age group of NSW patients with MPM was associated with reduced treatment utilisation and a decline in OS. Prospective studies are warranted to verify if current treatment guidelines are relevant for the older adults with MPM.}, }
@article {pmid30915902, year = {2019}, author = {Grosso, F and Croce, A and Libener, R and Mariani, N and Pastormerlo, M and Maconi, A and Rinaudo, C}, title = {Asbestos fiber identification in liver from cholangiocarcinoma patients living in an asbestos polluted area: a preliminary study.}, journal = {Tumori}, volume = {105}, number = {5}, pages = {404-410}, doi = {10.1177/0300891619839305}, pmid = {30915902}, issn = {2038-2529}, mesh = {Asbestos/isolation &amp; purification/*toxicity ; Bile Duct Neoplasms/chemically induced/*diagnostic imaging/pathology ; Cholangiocarcinoma/chemically induced/*diagnostic imaging/pathology ; Environmental Pollutants/isolation &amp; purification/toxicity ; Female ; Humans ; Italy ; Liver/*diagnostic imaging/drug effects/pathology ; Male ; Mesothelioma/chemically induced ; Microscopy, Electron, Scanning ; Occupational Exposure ; }, abstract = {PURPOSE: To assess whether asbestos fibers may be observed in liver tissue of patients with cholangiocarcinoma (CC) with environmental or working asbestos exposure.<br><br>METHODS: Detection of fibers was performed directly on histologic sections of liver from 7 patients with CC using optical microscope and variable pressure scanning electron microscopy equipped with energy-dispersive spectroscopy (VP-SEM/EDS). All patients were from Casale Monferrato, Italy, a highly asbestos-polluted town. Due to ethical constraints, observers were blinded to patients' clinical features.<br><br>RESULTS: Fibers/bundles of fibers of chrysotile were detected in 5 out of 7 patients (71%). The boundary between healthy and neoplastic tissue or the fibrocollagen tissue produced by the neoplasia were identified as areas of fiber incorporation.<br><br>CONCLUSIONS: This study is the first report about the detection of chrysotile asbestos fibers in the liver of patients with CC. Further studies on larger cohorts are needed to corroborate our preliminary findings.}, }
@article {pmid30915265, year = {2019}, author = {Robalino Gonzaga, ES and Guzman Rojas, P and Vanar, V}, title = {Malignant Peritoneal Mesothelioma Mimicking Recurrent Diverticulitis.}, journal = {Cureus}, volume = {11}, number = {1}, pages = {e3906}, pmid = {30915265}, issn = {2168-8184}, abstract = {Mesothelioma is an uncommon type of cancer arising from the mesothelial cells that form the lining of several cavities in the body. Exposure to asbestos is the leading known cause of mesothelioma. We present a 73-year-old male with a significant asbestos exposure and a recent history of recurrent diverticulitis who reported persistent left lower quadrant (LLQ) pain despite several courses of empiric antibiotic therapy. A recent computed tomography (CT) performed due to nonresolving symptoms showed possible nodularity of the mesentery and subsequent positron emission tomography (PET) scan demonstrated multiple hypermetabolic mesenteric lesions, notably in the left paracolic gutter. A colonoscopy was subsequently performed which demonstrated severe diverticulosis, but no obvious luminal lesions. The patient underwent an exploratory laparoscopy showing extensive peritoneal carcinomatosis involving all mesenteric surfaces and partial involvement of the right diaphragm. Final pathology revealed malignant epithelial mesothelioma with peritoneal seeding. The patient was referred to oncology and was started on hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS). Our case highlights a challenging presentation of malignant peritoneal mesothelioma (MPM), which is often initially misdiagnosed due to vague symptoms. Physicians should consider further diagnostic workup for unrelenting LLQ abdominal pain after diverticulitis has been treated.}, }
@article {pmid30900641, year = {2019}, author = {Punatar, CB and Jadhav, KK and Kumar, V and Sagade, SN}, title = {Malignant mesothelioma of tunica vaginalis without any risk factors: An uncommon case.}, journal = {Journal of cancer research and therapeutics}, volume = {15}, number = {Supplement}, pages = {S167-S169}, doi = {10.4103/jcrt.JCRT_1403_16}, pmid = {30900641}, issn = {1998-4138}, mesh = {Adult ; Humans ; Lung Neoplasms/*diagnosis/pathology/surgery ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Mesothelioma, Malignant ; Orchiectomy ; Positron Emission Tomography Computed Tomography ; Scrotum/diagnostic imaging/*pathology/surgery ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Testis/diagnostic imaging/*pathology/surgery ; Treatment Outcome ; Ultrasonography ; }, abstract = {Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare tumor. It is seen in elderly patients, with painless scrotal swelling being the most common presentation. The exact etiology is unknown; a few risk factors have been suggested. Here, we present an uncommon case of MM of TV without any known predisposing factors. We also discuss the possible risk factors, clinical presentation, pathological features and the difficulties in diagnosis, and management of this rare malignancy.}, }
@article {pmid30893058, year = {2019}, author = {Levpuscek, K and Goricar, K and Kovac, V and Dolzan, V and Franko, A}, title = {The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma.}, journal = {Radiology and oncology}, volume = {53}, number = {2}, pages = {206-212}, pmid = {30893058}, issn = {1581-3207}, mesh = {Aged ; Asbestos/toxicity ; Carcinogens/toxicity ; Case-Control Studies ; *DNA Repair ; DNA-Binding Proteins/*genetics ; Endonucleases/*genetics ; Female ; *Genetic Variation ; Humans ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Mesothelioma, Malignant ; Middle Aged ; *Polymorphism, Genetic ; Retrospective Studies ; Risk ; X-ray Repair Cross Complementing Protein 1/*genetics ; }, abstract = {Background Malignant mesothelioma (MM) is a rare aggressive tumour of mesothelium caused by asbestos exposure. It has been suggested that the genetic variability of proteins involved in DNA repair mechanisms affects the risk of MM. This study investigated the influence of functional polymorphisms in ERCC1 and XRCC1 genes, the interactions between these polymorphisms as well as the interactions between these polymorphisms and asbestos exposure on MM risk. Patients and methods In total, 237 cases with MM and 193 controls with no asbestos-related disease were genotyped for ERCC1 and XRCC1 polymorphisms. Results ERCC1 rs3212986 polymorphism was significantly associated with a decreased risk of MM (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.41-0.91; p = 0.014). No associations were observed between other genetic polymorphisms and MM risk. Interactions between polymorphisms did not significantly influence MM risk. Interaction between ERCC1 rs11615 and asbestos exposure significantly influenced MM risk (OR = 3.61; 95% CI = 1.12-11.66; p = 0.032). Carriers of polymorphic ERCC1 rs11615 allele who were exposed to low level of asbestos had a decreased risk of MM (OR = 0.40; 95% CI = 0.19-0.84; p = 0.016). Interactions between other polymorphisms and asbestos exposure did not significantly influence MM risk. Conclusions Our findings suggest that the genetic variability of DNA repair mechanisms could contribute to the risk of developing MM.}, }
@article {pmid30892588, year = {2019}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Corrigendum: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {492}, doi = {10.1093/carcin/bgz037}, pmid = {30892588}, issn = {1460-2180}, }
@article {pmid30891101, year = {2019}, author = {Wang, Y and Jiang, Z and Yan, J and Ying, S}, title = {HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma.}, journal = {Disease markers}, volume = {2019}, number = {}, pages = {4183157}, pmid = {30891101}, issn = {1875-8630}, mesh = {Animals ; Biomarkers, Tumor/*genetics/metabolism ; Gene Expression Regulation, Neoplastic ; HMGB1 Protein/*genetics/metabolism ; Humans ; Lung Neoplasms/drug therapy/*genetics/metabolism/pathology ; Mesothelioma/drug therapy/*genetics/metabolism/pathology ; Mesothelioma, Malignant ; }, abstract = {Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is substantially induced by exposure to asbestos fibers. High-mobility group box 1 (HMGB1) is an intriguing proinflammatory molecule involved in MM. In this review, we describe the possible crucial roles of HMGB1 in carcinogenic mechanisms based on in vivo and in vitro experimental evidence and outline the clinical findings of epidemiological investigations regarding the possible roles of HMGB1 as a biomarker for MM. We conclude that novel strategies targeting HMGB1 may suppress MM cells and interfere with asbestos-induced inflammation.}, }
@article {pmid30888083, year = {2019}, author = {Hino, O and Abe, M and Han, B and Yan, Y}, title = {In commemoration of the 2018 Mataro Nagayo Prize: A road to early diagnosis and monitoring of asbestos-related mesothelioma.}, journal = {Cancer science}, volume = {110}, number = {5}, pages = {1518-1524}, pmid = {30888083}, issn = {1349-7006}, support = {S1311011//Foundation of Strategic Research Projects in Private Universities of the NEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan)/ ; S1511008L//Foundation of Strategic Research Projects in Private Universities of the NEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan)/ ; //Institute for Environmental and Gender-Specific Medicine of Juntendo University Urayasu Hospital/ ; //Shizuoka Medical Research Center for Disaster of Juntendo University Shizuoka Hospital/ ; 221S0001//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Animals ; Asbestos/*adverse effects ; Awards and Prizes ; Biomarkers, Tumor/blood ; Disease Management ; Early Detection of Cancer/*methods ; Humans ; Japan ; Lung Neoplasms/blood/chemically induced/*diagnosis/*surgery ; Mesothelioma/blood/chemically induced/*diagnosis/*surgery ; Mesothelioma, Malignant ; Occupational Diseases/chemically induced/diagnosis/surgery ; Oncogene Proteins/*blood ; }, abstract = {Primarily caused by exposure to asbestos, mesothelioma is a typical occupational disease. The latency of mesothelioma is as long as 20-40 years, and the cancer initially progresses mainly along the surfaces of pleura or peritoneum without forming masses. As symptoms do not develop until late stages, it has been challenging to diagnose this disease in its early stages and to carry out complete surgical removal. In responding to Japan's asbestos crisis in the mid-2000s, we have developed and improved ERC/MSLN-based serum and radiological markers and pioneered the use of an N-ERC ELISA kit for screening populations at risk for asbestos exposure. In the present article, we review our research toward early diagnosis of asbestos-related mesothelioma before symptoms develop and share our clinical experience of screening, diagnosing and monitoring of this disease. This paper is dedicated to the author (Dr Okio Hino) to commemorate the honor bestowed upon him as the recipient of the Mataro Nagayo Prize in 2018.}, }
@article {pmid30886321, year = {2019}, author = {Jeffery, E and Lee, YCG and Newton, RU and Lyons-Wall, P and McVeigh, J and Nowak, AK and Cheah, HM and Nguyen, B and Fitzgerald, DB and Creaney, J and Straker, L and Peddle-McIntyre, CJ}, title = {Body composition and nutritional status in malignant pleural mesothelioma: implications for activity levels and quality of life.}, journal = {European journal of clinical nutrition}, volume = {73}, number = {10}, pages = {1412-1421}, doi = {10.1038/s41430-019-0418-9}, pmid = {30886321}, issn = {1476-5640}, mesh = {Aged ; Australia/epidemiology ; *Body Composition ; Cross-Sectional Studies ; Diet ; Exercise/*physiology ; Female ; Humans ; Lung Neoplasms/*physiopathology ; Male ; Malnutrition/epidemiology ; Mesothelioma/*physiopathology ; Mesothelioma, Malignant ; Middle Aged ; *Nutritional Status ; Pleural Neoplasms/*physiopathology ; Prospective Studies ; *Quality of Life ; Sarcopenia/epidemiology ; }, abstract = {BACKGROUND/OBJECTIVES: Malignant pleural mesothelioma (MPM) is an incurable cancer and optimizing daily physical activity and quality of life are key goals of patient management. Little is known about the prevalence of pre-sarcopenia and malnutrition in MPM or their associations with patient outcomes. This study aimed to determine the prevalence of pre-sarcopenia and malnutrition in MPM and investigate if activity levels and quality of life differed according to body composition and nutritional status.<br><br>SUBJECTS/METHODS: Patients with a diagnosis of MPM were recruited. Pre-sarcopenia was defined as low appendicular skeletal muscle mass (≤ 7.26 kg/m2 for men and ≤ 5.45 kg/m2 for women), measured by dual energy X-ray absorptiometry. Malnutrition was defined as a rating of B or C on the Patient-Generated Subjective Global Assessment. Outcome measures included objective activity levels (Actigraph GT3X) and health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy General).<br><br>RESULTS: Sixty-one people participated (79% male, median age 69 [IQR 62-74] years and median BMI 25.8 [IQR 24.3-28.4] kg/m2). Fifty-four percent were pre-sarcopenic and 38% were malnourished. Percent of time spent in light activity/day was lower in participants with pre-sarcopenia compared with non-sarcopenic participants (median 25.4 [IQR 19.8-32.1]% vs. 32.3 [27.1-35.6]%; p = 0.008). Participants with malnutrition had poorer HRQoL than well-nourished participants (mean 69.0 (16.3) vs. 84.4 (13.3); p < 0.001).<br><br>CONCLUSION: Participants with MPM had high rates of pre-sarcopenia and malnutrition. Pre-sarcopenia was associated with poorer activity levels, whilst malnutrition was associated with poorer quality of life. Interventions that aim to address reduced muscle mass and weight loss, should be tested in MPM to assess their impact on patient outcomes.}, }
@article {pmid30885349, year = {2019}, author = {Ahmadzada, T and Lee, K and Clarke, C and Cooper, WA and Linton, A and McCaughan, B and Asher, R and Clarke, S and Reid, G and Kao, S}, title = {High BIN1 expression has a favorable prognosis in malignant pleural mesothelioma and is associated with tumor infiltrating lymphocytes.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {130}, number = {}, pages = {35-41}, doi = {10.1016/j.lungcan.2019.02.005}, pmid = {30885349}, issn = {1872-8332}, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism ; Lung Neoplasms/*genetics/immunology/mortality ; Lymphocytes, Tumor-Infiltrating/*immunology ; Male ; Mesothelioma/*genetics/immunology/mortality ; Mesothelioma, Malignant ; Middle Aged ; Nuclear Proteins/genetics/*metabolism ; Pleural Neoplasms/*genetics/immunology/mortality ; Prognosis ; Survival Analysis ; Tumor Suppressor Proteins/genetics/*metabolism ; Up-Regulation ; }, abstract = {OBJECTIVES: A number of key immune regulators show prognostic value in malignant pleural mesothelioma (MPM), but the association between Bridging integrator 1 (BIN1), indoleamine 2,3 dioxygenase 1 (IDO1) and patient outcome has not been investigated. We aimed to determine the expression of BIN1 and IDO1, their association with other markers and impact on overall survival (OS) in MPM.<br><br>MATERIALS AND METHODS: The expression of BIN1, IDO1, CD3, CD20 and CD68 were evaluated by immunohistochemistry in 67 patients who underwent pleurectomy/decortication. Survival analyses were performed using the Kaplan Meier method and significant biomarkers were entered into a Cox Regression multivariate model, accounting for known prognostic factors such as age, gender, histological subtype, PD-L1 expression and neutrophil-to-lymphocyte ratio.<br><br>RESULTS: Immune markers were variably expressed in tumor cells, ranging from 0% to 100% for BIN1 (median: 89%), and 0% to 77.5% for IDO1 (median: 0%). Expression of markers of tumor-infiltrating lymphocytes (TILs) and macrophages ranged from 0% to more than 50%. BIN1 expression was high in 35 patients (51%) and was associated with increased OS (median: 12 vs 6 months for high and low BIN1 respectively,p = 0.03). Multivariate analysis showed BIN1 remained an independent prognostic indicator (HR 0.39; 95% CI: 0.18-0.82, p = 0.01). The majority of patients had immune inflamed tumors (77%) and there was a significant association between TILs and BIN1 (p = 0 < 0.01), PD-L1 (p=0.04) and CD68+ macrophages in the tumor (p < 0.01). There were no significant associations between PD-L1 and BIN1 or IDO1.<br><br>CONCLUSION: High BIN1 expression is a favorable prognostic biomarker and is associated with TILs in MPM.}, }
@article {pmid30882147, year = {2019}, author = {Nakai, T and Matsumoto, Y and Sasada, S and Tanaka, M and Tsuchida, T and Ohe, Y and Motoi, N}, title = {Cryobiopsy during flex-rigid pleuroscopy: an emerging alternative biopsy method in malignant pleural mesothelioma. A comparative study of pathology.}, journal = {Japanese journal of clinical oncology}, volume = {49}, number = {6}, pages = {559-566}, doi = {10.1093/jjco/hyz032}, pmid = {30882147}, issn = {1465-3621}, mesh = {Aged ; Biopsy/instrumentation/methods ; Female ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*diagnosis ; Thoracoscopy/*instrumentation/*methods ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is rarely an asbestos-related cancer with a poor prognosis that is difficult to distinguish from some benign conditions by using conventional biopsy techniques. The purpose of this study was to evaluate the utility of a novel biopsy technique using a cryoprobe during flex-rigid pleuroscopy for diagnosing MPM.<br><br>METHODS: Consecutive patients who underwent pleural cryobiopsy during flex-rigid pleuroscopy from June through November 2017 to diagnose the cause of pleural effusion were collected. From these, cases ultimately diagnosed as MPM were selected. Pleural biopsies were performed by using conventional instruments followed by a cryoprobe. The obtained samples were histologically examined and compared with regard to the quality (sample size, tissue depth, and crush rate), immunohistochemical (IHC) staining, and p16 by fluorescence in situ hybridization (FISH).<br><br>RESULTS: In total, five patients ultimately diagnosed as MPM were enrolled. The sample collected was significantly larger for cryobiopsy than conventional biopsy (18.9 mm2 vs. 6.7 mm2, P < 0.001). Full-thickness biopsies were achieved in four cases by using cryobiopsy compared with one case by conventional biopsy. Moreover, the crush rate was significantly less for cryobiopsy than conventional biopsy (9% vs. 35%, P < 0.001). The results of IHC staining and p16 by FISH were similar between biopsy techniques. Cryobiopsy successfully led to accurate diagnosis of MPM in all cases, whereas conventional biopsy was diagnostic in one case. No severe complications developed after either biopsy technique.<br><br>CONCLUSION: Cryobiopsy during flex-rigid pleuroscopy is a feasible and convenient biopsy technique that supports precise diagnosis of MPM.}, }
@article {pmid30879467, year = {2019}, author = {Miyata, T and Fujiwara, Y and Nishijima, K and Futagami, F and Nakamura, T and Takamura, H}, title = {Localized multiple malignant epithelioid peritoneal mesotheliomas arising from the hepatoduodenal ligament and diaphragm: a case report.}, journal = {Journal of medical case reports}, volume = {13}, number = {1}, pages = {66}, pmid = {30879467}, issn = {1752-1947}, mesh = {Female ; Humans ; Liver Neoplasms/diagnostic imaging/*pathology/secondary/surgery ; Lung Neoplasms/diagnostic imaging/*pathology/surgery ; Mesothelioma/diagnostic imaging/*pathology/surgery ; Mesothelioma, Malignant ; Middle Aged ; Muscle Neoplasms/*pathology ; Neoplasm Invasiveness ; Peritoneal Neoplasms/diagnostic imaging/*pathology/secondary/surgery ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma is a rare aggressive tumor of the peritoneum. We report a rare case of resection of multiple localized malignant peritoneal mesotheliomas.<br><br>CASE PRESENTATION: A 55-year-old Japanese woman was admitted to our hospital because liver tumors were detected by abdominal ultrasonography during a screening examination. Blood examination findings, including tumor makers, were within normal ranges. She had no evidence of exposure to asbestos. Computed tomography showed four hypervascular, round liver tumors, one in the lateral liver segment adjacent to the hepatic hilus, and the other three on the liver surface. Computed tomography angiography revealed that the tumor in the lateral segment had strong enhancement and was fed from the left gastric artery. In contrast, the other tumors showed no enhancement, and were fed from the right inferior phrenic artery. Abnormal accumulation was identified in the four tumors only with 18F-fluorodeoxyglucose positron emission tomography. It was very difficult to obtain a definitive preoperative diagnosis, but surgical resection was performed because we considered potential malignancy. Laparotomy revealed the principal site of the tumor in the lateral segment was on the hepatoduodenal ligament, and all other tumors were on the diaphragm. A left lobectomy and partial diaphragmatic resection were performed. The final pathological diagnosis was multiple malignant epithelioid mesotheliomas. Our patient has had no recurrence for 20 months postoperatively.<br><br>CONCLUSIONS: In general, malignant peritoneal mesotheliomas are classified as diffuse tumors, which are often unresectable and have a poor prognosis. However, early diagnosis and treatment, particularly with the localized type, as in our patient, could lead to long-term survival of the patient. We recommend that multiple malignant epithelioid mesotheliomas be included in the differential diagnosis for patients with subcapsular hepatic tumors.}, }
@article {pmid30874891, year = {2019}, author = {Hutter, HP and Waldhoer, T and Müller, K and Hackl, M and Weitensfelder, L and Heinzl, H}, title = {Cancer incidence in an Austrian alpine valley 1983-2012 : A descriptive study.}, journal = {Wiener klinische Wochenschrift}, volume = {131}, number = {9-10}, pages = {200-204}, pmid = {30874891}, issn = {1613-7671}, mesh = {Asbestos/adverse effects ; Austria/epidemiology ; Hexachlorobenzene/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Neoplasms/*epidemiology ; }, abstract = {After one of Austria's largest environmental scandals in 2014, which involved the release of hexachlorobenzene (HCB) in the Carinthian valley Görtschitztal, concerns about increased cancer rates have arísen in the affected local population. A descriptive study was conducted to examine the cancer incidence rates between 1983 and 2012. Data from the affected area (Görtschitztal, district St. Veit) were compared to data from the neighboring area within the same district and Carinthia excluding St. Veit, considering incidence rates of liver, lung, kidney, thyroid cancer and mesothelioma. Prostate cancer and carcinoma in situ were both included and excluded from overall cancer incidents in order to prevent potential bias due to screening programs. Considering the observed variability at an overall level, no conspicuous differences in cancer incidences could be found (Carinthia: 495, St. Veit West: 408, St. Veit East: 572 cases per 100,000 person-years in 2012). For some cancer types, e. g. liver, thyroid cancer and mesothelioma, the affected region showed a higher increase in rates than the neighboring area or Carinthia overall; however, these increased rates date back to a time prior to the HCB exposure, suggesting other carcinogenic influences, such as asbestos exposure from antecedent years.}, }
@article {pmid30873891, year = {2019}, author = {Poland, CA and Duffin, R}, title = {The toxicology of chrysotile-containing brake debris: implications for mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {1}, pages = {11-35}, doi = {10.1080/10408444.2019.1568385}, pmid = {30873891}, issn = {1547-6898}, mesh = {Asbestos, Serpentine/*toxicity ; *Automobiles ; *Environmental Exposure ; Humans ; Mesothelioma/chemically induced/*epidemiology ; }, abstract = {The global use of &quot;asbestos&quot; in various commercial products has led to a wide range and pervasive legacy of disease. One such use of chrysotile asbestos was brake pads and was utilized commonly in automobiles and heavy vehicles. The result of incorporation of chrysotile into brake pads is associated with the exposure of mechanics fitting and servicing vehicles to liberated chrysotile fibers. Despite the proven exposure, the relative risk of malignant mesothelioma (MM) in this occupational population is broadly seen as low. The toxicity of particulates, including fibers such as chrysotile, is driven by a combination of dose and physicochemical properties. As such, it is plausible that chrysotile released from brake pads may have undergone modification, thereby altering the pathogenicity profile. The impact of high sheer stress causing shortening of long fibers, heat modification, binding of resin matrix to the fiber surface on the relative toxicity of brake debris with regards to MM is considered. It is apparent that released chrysotile can undergo significant modification, reducing the long fiber dose although not all modifications may lead to reduced toxicity.}, }
@article {pmid30873867, year = {2019}, author = {Baqui, AA and Boire, NA and Baqui, TT and Etwaru, DJ}, title = {Malignant Mesothelioma of the Tunica Vaginalis Testis-A Malignancy Associated With Asbestos Exposure and Trauma: A Case Report and Literature Review.}, journal = {Journal of investigative medicine high impact case reports}, volume = {7}, number = {}, pages = {2324709619827335}, pmid = {30873867}, issn = {2324-7096}, mesh = {Asbestos/*adverse effects ; Humans ; Immunohistochemistry ; Lung Neoplasms/etiology/*pathology ; Male ; Mesothelioma/etiology/*pathology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Orchiectomy ; Testicular Hydrocele/etiology/*pathology ; Testicular Neoplasms/etiology/*pathology ; Testis/*injuries/*pathology ; }, abstract = {In this article, we report an unusual case of a malignant mesothelioma of the testis, presenting as hydrocele. The patient has a known medical history of trauma and occupational exposure to asbestos. The clinical features of this injury are discussed together with its immunohistochemistry. Surgical intervention is discussed due to the nature of this pathology.}, }
@article {pmid30870398, year = {2019}, author = {Cuccaro, F and Nannavecchia, AM and Silvestri, S and Angelini, A and Coviello, V and Bisceglia, L and Magnani, C}, title = {Mortality for Mesothelioma and Lung Cancer in a Cohort of Asbestos Cement Workers in BARI (Italy): Time Related Aspects of Exposure.}, journal = {Journal of occupational and environmental medicine}, volume = {61}, number = {5}, pages = {410-416}, doi = {10.1097/JOM.0000000000001580}, pmid = {30870398}, issn = {1536-5948}, mesh = {Asbestos/*adverse effects ; *Construction Industry ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Mesothelioma/*mortality ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; Time Factors ; }, abstract = {OBJECTIVE: In this cohort mortality study we used an exposure index to evaluate individual cumulative exposure as proxy of asbestos dose and we evaluated change in cancer mortality pattern after long time since the end of exposure.<br><br>METHODS: We calculated standardized mortality ratios (SMRs) for several causes of death stratified by latency, cumulative exposure, and time since last exposure (TSLE).<br><br>RESULTS: Latency: we observed a peak and then a decrease in SMR for lung, pleural, and peritoneal cancer. Cumulative Exposure: We observed a peak and then a decrease in SMR for lung and pleural cancer, not for peritoneal cancer. TSLE: Pleural cancer SMR peaked at 20 to 29 years, then decreased, peritoneal cancer SMR reached a plateau after 20 years and lung cancer mortality was in excess in each class.<br><br>CONCLUSIONS: We found different patterns in mortality in the main asbestos-related tumors.}, }
@article {pmid30863440, year = {2019}, author = {Liang, Y and Zheng, G and Yin, W and Song, H and Li, C and Tian, L and Yang, D}, title = {Significance of EGFR and PTEN Expression and PLR and NLR for Predicting the Prognosis of Epithelioid Malignant Peritoneal Mesothelioma.}, journal = {Gastroenterology research and practice}, volume = {2019}, number = {}, pages = {7103915}, pmid = {30863440}, issn = {1687-6121}, abstract = {Objective: The aim of our study was to investigate the expression of EGFR and PTEN in tissues and measure the serum platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) to evaluate the prognostic factors of patients with epithelioid malignant peritoneal mesothelioma (MPeM).<br><br>Methods: 33 patients of pathologically diagnosed epithelioid MPeM tissues were analyzed using immunohistochemistry to detect EGFR and PTEN; the PLR and NLR were determined by using a routine blood test. We analyzed the relationships of these markers to age, sex, asbestos exposure, elevated platelet count, ascites, and clinical stage.<br><br>Results: EGFR and PTEN expressions were positive in 22 (66.67%) and 7 (21.21%) epithelioid MPeM patients, respectively. However, these two markers as well as PLR and NLR were not significantly associated with age, sex, asbestos exposure, elevated platelet counts, ascites, and clinical stage (P > 0.05). The correlation between EGFR and PTEN was negative (r = -0.577, P < 0.001), but the correlation between NLR and PLR was positive (r = 0.456, P = 0.008). The median survival of all patients was 6 months. In univariate analysis, PTEN (P < 0.001), PLR (P = 0.014), and NLR (P = 0.015) affected the overall survival. Multivariate analysis revealed that PTEN and PLR were validated as predictive for overall survival of epithelioid MPeM (HR = 0.070, P = 0.001, and HR = 3.379, P = 0.007, respectively).<br><br>Conclusion: On the basis of these results, it is suggested that PTEN and PLR are risk factors for the prognosis of epithelioid MPeM, which may be targets for selective therapies and improve the outcomes of patients with epithelioid MPeM.}, }
@article {pmid30863365, year = {2019}, author = {Baird, AM and Easty, D and Jarzabek, M and Shiels, L and Soltermann, A and Klebe, S and Raeppel, S and MacDonagh, L and Wu, C and Griggs, K and Kirschner, MB and Stanfill, B and Nonaka, D and Goparaju, CM and Murer, B and Fennell, DA and O'Donnell, DM and Barr, MP and Mutti, L and Reid, G and Finn, S and Cuffe, S and Pass, HI and Opitz, I and Byrne, AT and O'Byrne, KJ and Gray, SG}, title = {When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {89}, pmid = {30863365}, issn = {1664-2392}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer with a poor survival rate. Treatment options are limited at best and drug resistance is common. Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times. MST1R (RON) is a trans-membrane receptor tyrosine kinase (RTK), which is part of the c-MET proto-oncogene family. The only ligand recognized to bind MST1R (RON) is Macrophage Stimulating 1 (MST1), also known as Macrophage Stimulating Protein (MSP) or Hepatocyte Growth Factor-Like Protein (HGFL). In this study, we demonstrate that the MST1-MST1R (RON) signaling axis is active in MPM. Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. Cell cycle progression was also affected. Recombinant MST1 treatment was unable to overcome the effect of LCRF-0004 in terms of either proliferation or apoptosis. Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. In a cohort of MPM patient samples, high positivity for total MST1R by IHC was an independent predictor of favorable prognosis. Additionally, elevated expression levels of MST1 also correlated with better survival. This study also determined the efficacy of LCRF-0004 and BMS-777607 in xenograft MPM models. Both LCRF-0004 and BMS-777607 demonstrated significant anti-tumor efficacy in vitro, however BMS-777607 was far superior to LCRF-0004. The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone.}, }
@article {pmid30859065, year = {2019}, author = {Wallen, T and Jagan, N and Krishnan, M and Depew, Z}, title = {A 75 year old male with recurrent unilateral pleural effusion and positive ANA.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {301-303}, pmid = {30859065}, issn = {2213-0071}, abstract = {This case report describes the clinical course and diagnostic challenges arising in a 75 year old man who initially presented with progressive shortness of breath. Imaging revealed a pleural effusion, which was recurrent following thoracentesis. While his initial workup suggested an autoimmune etiology, further diagnostic testing revealed a diagnosis of malignant pleural mesothelioma. Curiously, the patient had no known asbestos exposure, which is classically associated with acquired mesothelioma. There are a small number of similar cases with a possible overlap between positive autoimmune serologies and mesothelioma; however, the underlying pathophysiology remains elusive. It is the authors' goal to contribute this case to the few cases describing such overlap syndromes.}, }
@article {pmid30851279, year = {2019}, author = {Mandel, JH and Odo, NU and Alexander, BH}, title = {Potential Problems with Determining Elongate Mineral Particle (EMP) Potency (Comments on article entitled, &quot;A Comparison of Asbestos Fiber Potency and Elongate Mineral Particle (EMP) Potency for Mesothelioma in Humans&quot;).}, journal = {Toxicology and applied pharmacology}, volume = {370}, number = {}, pages = {131-132}, doi = {10.1016/j.taap.2019.03.002}, pmid = {30851279}, issn = {1096-0333}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30840592, year = {2019}, author = {Senk, B and Goricar, K and Kovac, V and Dolzan, V and Franko, A}, title = {Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment.}, journal = {Radiology and oncology}, volume = {53}, number = {1}, pages = {96-104}, pmid = {30840592}, issn = {1581-3207}, mesh = {Age Factors ; Aged ; Alopecia/chemically induced ; Anemia/chemically induced ; Antineoplastic Agents/adverse effects/*therapeutic use ; Aquaporin 1/*genetics ; Case-Control Studies ; Cisplatin/adverse effects/*therapeutic use ; Female ; Humans ; Leukopenia/chemically induced ; Logistic Models ; Lung Neoplasms/*drug therapy/*genetics/mortality ; Male ; Mesothelioma/*drug therapy/*genetics/mortality ; Mesothelioma, Malignant ; Middle Aged ; *Polymorphism, Single Nucleotide ; Risk Assessment ; Sex Factors ; Thrombocytopenia/chemically induced ; }, abstract = {Background Malignant mesothelioma (MM) is an asbestos related aggressive tumor with poor prognosis. The aim of this study was to investigate if aquaporin 1 (AQP1) genetic polymorphisms influence the risk of MM and the response to cisplatin based MM treatment. Patients and methods The case-control study included 231 patients with MM and a control group of 316 healthy blood donors. All subjects were genotyped for three AQP1polymorphisms (rs1049305, rs1476597 and rs28362731). Logistic and Cox regression were used in statistical analysis. Results AQP1 rs1049305 polymorphism was significantly associated with MM risk in dominant model adjusted for gender and age (OR = 0.60, 95% CI = 0.37-0.96, Padj = 0.033). This polymorphism was also significantly associated with cisplatin based treatment related anaemia (unadjusted: OR = 0.49, 95% CI = 0.27-0.90, P = 0.021; adjusted: for CRP: OR = 0.52, 95% CI = 0.27-0.99, P = 0.046), with leukopenia (OR = 2.09, 95% CI = 1.00-4.35, P = 0.049) in dominant model and with thrombocytopenia (OR = 3.06, 95% CI = 1.01-9.28, P = 0.048) and alopecia (OR = 2.92, 95% CI = 1.00-8.46, P = 0.049) in additive model. AQP1 rs28362731 was significantly associated with thrombocytopenia (unadjusted: OR = 3.73, 95% CI = 1.00-13.84, P = 0.049; adjusted for pain: OR = 4.63, 95% CI = 1.13-19.05, P = 0.034) in additive model. Conclusions AQP1 may play a role in the risk of MM. Furthermore, AQP1 genotype information could improve the prediction of MM patients at increased risk for cisplatin toxicity.}, }
@article {pmid30834036, year = {2019}, author = {Abbas, H and Rodriguez, JC and Tariq, H and Niazi, M and Alemam, A and Nayudu, SK}, title = {Malignant Peritoneal Mesothelioma Without Asbestos Exposure.}, journal = {Gastroenterology research}, volume = {12}, number = {1}, pages = {48-51}, pmid = {30834036}, issn = {1918-2805}, abstract = {Malignant mesothelioma is a rare neoplasm of the serosal linings. Mesothelioma has been linked to asbestos exposure, with prior asbestos exposure linked to 33-50% of malignant peritoneal mesotheliomas. We describe a case of malignant peritoneal mesothelioma (MPM) without any prior exposure to asbestos in a 40-year-old Hispanic female who presented to the emergency department with worsening abdominal pain and distension. She had a history of beta thalassemia trait and iron deficiency anemia. Examination revealed a distended abdomen with protruding umbilicus and positive shifting dullness. Laboratory tests showed anemia. Computed tomography (CT) of the abdomen revealed massive complex ascites suspicious of a malignant process. Ascitic fluid analysis showed serum ascites albumin gradient (SAAG) of 1.1 g/dL with a total protein of 5.2 g/dL. She underwent laparoscopic peritoneal biopsy which yielded epithelioid type malignant mesothelioma. She was started on chemotherapy with cisplatin and pemetrexed. The last follow-up was 27 months after the diagnosis. MPM is a rare and life-threatening malignancy. Frequently, the symptoms are non-specific. This poses a diagnostic challenge for physicians and probably the reason why the diagnosis is often delayed, especially in the absence of risk factors.}, }
@article {pmid30815702, year = {2019}, author = {Pasetto, R and Zona, A and Fazzo, L and Binazzi, A and Bruno, C and Pirastu, R and Comba, P and Marinaccio, A}, title = {Proportion of mesothelioma attributable to living in industrially contaminated areas in Italy.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {45}, number = {5}, pages = {444-449}, doi = {10.5271/sjweh.3809}, pmid = {30815702}, issn = {1795-990X}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Environmental Exposure/*statistics &amp; numerical data ; Female ; Humans ; Industry/*statistics &amp; numerical data ; Infant ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Risk Factors ; Sex Factors ; Spatial Analysis ; Young Adult ; }, abstract = {Objectives The aim of this study was to estimate the attributable proportion (AP) of mesothelioma resulting from living in or close to major Italian industrially contaminated areas. Methods For populations living close to 39 sites of &quot;national priority for remediation&quot;, incident mesothelioma cases were extracted from the Italian National Mesothelioma Registry (ReNaM) in the period 2000‒2011. Each site was classified in one of seven asbestos risk groups (RG) on the basis of the type of industrial plants. RG were ranked by the a priori evidence on asbestos risk. The AP for each RG was calculated as the meta-analytic estimate of AP of sites of the same group by gender and age class (0-64, 65-74, ≥75 years). The sex ratio (men/women) was computed for each RG. Results Among men, the AP by age class had the same gradient in each RG, with the highest values in the age class 0-64 years and the lowest in the ≥75 class; in the age class 0-64 years, the AP was positive in each RG, >90% in the presence of asbestos cement factories and harbors with shipyards. Among women, the overall AP decreased by RG, with negative values in the last two ranked RG; the AP by age class was variable without a definite gradient. The sex ratio was close to one only in the RG &quot;only asbestos-cement factories&quot;; the highest value (9.6) was observed in the age class 0-64 years in the RG &quot;harbors with shipyard&quot;. Conclusions The integration of a geographic- and case-based approach provides valuable insights into occupational and environmental determinants of mesothelioma risk in industrially contaminated sites.}, }
@article {pmid30809599, year = {2018}, author = {Biersack, B}, title = {Relations between approved platinum drugs and non-coding RNAs in mesothelioma.}, journal = {Non-coding RNA research}, volume = {3}, number = {4}, pages = {161-173}, pmid = {30809599}, issn = {2468-0540}, abstract = {Malignant mesothelioma diseases feature an increasing risk due to their severe forms and their association with asbestos exposure. Platinum(II) complexes such as cisplatin and carboplatin are clinically approved for the therapy of mesothelioma often in combination with antimetabolites such as pemetrexed or gemcitabine. It was observed that pathogenic properties of mesothelioma cells and the response of mesothelioma tumors towards platinum-based drugs are strongly influenced by non-coding RNAs, in particular, by small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These non-coding RNAs controlled drug sensitivity and the development of tumor resistance towards platinum drugs. An overview of the interactions between platinum drugs and non-coding RNAs is given and the influence of non-coding RNAs on platinum drug efficacy in mesothelioma is discussed. Suitable non-coding RNA-modulating agents with potentially beneficial effects on cisplatin treatment of mesothelioma diseases are mentioned. The understanding of mesothelioma diseases concerning the interactions of non-coding RNAs and platinum drugs will optimize existing therapy schemes and pave the way to new treatment options in future.}, }
@article {pmid30804167, year = {2019}, author = {Farioli, A and Boffetta, P and Curti, S and Garzaro, G and La Vecchia, C and Mattioli, S and Spatari, G and Violante, FS}, title = {Response to: 'Are children more vulnerable to mesothelioma than adults? A comparison of mesothelioma risk among children and adults exposed non-occupationally to blue asbestos at Wittenoom' by Reid et al.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {5}, pages = {355}, doi = {10.1136/oemed-2018-105637}, pmid = {30804167}, issn = {1470-7926}, mesh = {Adult ; Asbestos, Crocidolite ; Child ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30804166, year = {2019}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, Ø}, title = {Environmental asbestos exposure in childhood and risk of mesothelioma later in life: a long-term follow-up register-based cohort study.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {6}, pages = {407-413}, doi = {10.1136/oemed-2018-105392}, pmid = {30804166}, issn = {1470-7926}, mesh = {Aged ; Asbestos/*adverse effects ; Cohort Studies ; Denmark/epidemiology ; Environmental Exposure/adverse effects/statistics &amp; numerical data ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/epidemiology/*etiology ; Metallurgy/statistics &amp; numerical data ; Middle Aged ; Registries/statistics &amp; numerical data ; Risk Assessment/*methods ; }, abstract = {OBJECTIVE: To examine the risk of malignant mesothelioma (MM) in former pupils who attended primary school near an asbestos cement plant.<br><br>METHODS: A cohort of 12 111 former pupils, born 1940-1970, was established from individual historical records from four primary schools located at a distance of 100-750 m in the prevailing wind direction from an asbestos cement plant operating from 1928 to 1984 in Aalborg, Denmark. The school cohort and a comparison cohort consisting of 108 987 gender and 5-year frequency-matched subjects were followed up (2015) for MM in the Danish Cancer Registry. Using Cox regression, HRs were estimated for the incidence of MM. Adjustments for occupational and familial asbestos exposure were made with a job exposure matrix. An SIR analysis including latency periods testing the cancer incidence rate was performed with the comparison cohort as the reference rate.<br><br>RESULTS: The median person-years of follow-up were 62.5 years in the school cohort and 62.2 years in the comparison cohort. There were 32 males and 6 females of the former pupils who developed MM during the follow-up: HRmale 7.01 (95% CI 4.24 to 11.57), HRfemale 7.43 (95% CI 2.50 to 22.13). Those who attended school 250 m north of the plant had the highest HR for MM, 10.65 (95% Cl 5.82 to 19.48). No significant trend between school distance and risk of MM was established (p=0.35).<br><br>CONCLUSION: Our results suggest that boys and girls who attended schools and lived in the neighbourhood of an asbestos cement plant later in life have a significantly increased risk of MM.}, }
@article {pmid30804152, year = {2019}, author = {Kim, M and Kim, HS}, title = {Clinicopathological Characteristics of Well-differentiated Papillary Mesothelioma of The Peritoneum: A Single-institutional Experience of 12 Cases.}, journal = {In vivo (Athens, Greece)}, volume = {33}, number = {2}, pages = {633-642}, pmid = {30804152}, issn = {1791-7549}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*pathology ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*pathology ; Patient Selection ; Peritoneal Neoplasms/epidemiology/*pathology ; Peritoneum/pathology ; Pleural Neoplasms/epidemiology/*pathology ; }, abstract = {BACKGROUND/AIM: Well-differentiated papillary mesothelioma (WDPM) is histologically characterized by papillary architecture with fibrovascular cores, lined by bland mesothelial cells. We recently experienced a case of WDPM associated with multiple peritoneal inclusion cysts, which prompted us to initiate a comprehensive review of previously diagnosed WDPM cases.<br><br>MATERIALS AND METHODS: The clinicopathological characteristics and immunophenotype of 12 cases of peritoneal WDPM were investigated using a review of electronic medical records, pathological examination, and immunostaining.<br><br>RESULTS: The patients' ages ranged from 23 to 75 years. No patient had endometriosis or a previous history of asbestos exposure. Ten tumors were detected incidentally during surgery for other causes. Most tumors appeared as a small, single nodule on the peritoneal surface, but in three cases, WDPM presented as multiple lesions. All but one patient had no symptoms. All the patients examined are still well without postoperative recurrence. Histologically, all cases demonstrated typical papillary architecture with fibrovascular cores. The mesothelial cells lining the papillae consisted mostly of single row of cells, although areas of proliferation to multiple layers were observed in a few cases. Their nuclei appeared bland, but two cases exhibited mild nuclear atypia and prominent nucleoli. Immunostaining revealed that the mesothelial cells were positive for D2-40, cytokeratin 5/6, cytokeratin 7, and Wilms' tumor 1.<br><br>CONCLUSION: We herein demonstrated the clinicopathological characteristics of peritoneal WDPMs. WDPM has distinct pathological features. Although all cases we examined were uneventful after surgery, further surveillance is recommended since the biological behavior of WDPM is still uncertain.}, }
@article {pmid30776941, year = {2019}, author = {Wang, F and Chen, Y and Wang, Y and Yin, Y and Qu, G and Song, M and Wang, H}, title = {Ultra-long silver nanowires induced mitotic abnormalities and cytokinetic failure in A549 cells.}, journal = {Nanotoxicology}, volume = {13}, number = {4}, pages = {543-557}, doi = {10.1080/17435390.2019.1571645}, pmid = {30776941}, issn = {1743-5404}, mesh = {A549 Cells ; Cell Culture Techniques ; Cell Proliferation/*drug effects ; Cell Survival/drug effects ; Cytokinesis/*drug effects ; Epithelial Cells/*drug effects/pathology ; Humans ; Mitosis/*drug effects ; Nanowires/chemistry/*toxicity ; Particle Size ; Silver/chemistry/*toxicity ; Surface Properties ; }, abstract = {Asbestos fiber has been associated with mesothelioma and lung cancer. However, the carcinogenic risks of other fiber nanomaterials with morphological similarities to asbestos have not been fully studied. Ultra-long silver nanowires (AgNWs) are increasingly used fiber-shaped nanomaterials with a high aspect ratio, but very few studies have investigated their health risks. Here, proliferation abnormalities of lung epithelial cells induced by ultra-long AgNWs were investigated. Ultra-long AgNW treatment induced dose- and diameter-dependent increase in the ratio of multinucleated cells. Further, proteins involved in mitosis and cytokinesis, including Aurora A, p-Histone 3 (ser10), RhoA, p-MLC, and myosin IIb, were significantly upregulated after an ultra-long AgNW treatment, leading to mitotic abnormalities and cytokinetic failure. Meanwhile, exposure to ultra-long AgNWs induced cell cycle arrest. Interestingly, a series of experiments demonstrated that ROS generation and Ag+ release were not responsible for the multinucleation induced by ultra-long AgNWs, but ultra-long AgNWs in the intercellular bridge might obstruct the contractile ring and inhibit abscission of the cytokinetic furrow by direct physical contact. Altogether, our findings indicate that ultra-long AgNWs can induce chromosomal instability, which has important consequences for the safety of ultra-long AgNWs to human health.}, }
@article {pmid30774332, year = {2019}, author = {Cova, E and Pandolfi, L and Colombo, M and Frangipane, V and Inghilleri, S and Morosini, M and Mrakic-Sposta, S and Moretti, S and Monti, M and Pignochino, Y and Benvenuti, S and Prosperi, D and Stella, G and Morbini, P and Meloni, F}, title = {Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study.}, journal = {International journal of nanomedicine}, volume = {14}, number = {}, pages = {773-785}, pmid = {30774332}, issn = {1178-2013}, mesh = {Apoptosis/drug effects ; Biopsy ; CD146 Antigen/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Endocytosis/drug effects ; Gold/chemistry ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Mesothelioma, Malignant ; Metal Nanoparticles/*chemistry ; Pemetrexed/pharmacology/*therapeutic use ; Pleural Neoplasms/*drug therapy/pathology ; Reactive Oxygen Species/metabolism ; }, abstract = {Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.<br><br>Methods: MPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).<br><br>Results: GNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.<br><br>Conclusion: GNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.}, }
@article {pmid30773744, year = {2019}, author = {Yoshida, GJ}, title = {Beyond Stanton and Pott hypothesis; carbon nanotubes-induced malignant mesothelioma as a disease of gene loss.}, journal = {Journal of occupational health}, volume = {61}, number = {2}, pages = {203-205}, pmid = {30773744}, issn = {1348-9585}, mesh = {Animals ; Asbestos/adverse effects ; Genes, p16 ; Humans ; Lung Neoplasms/*chemically induced/*genetics ; Mesothelioma/*chemically induced/*genetics ; Mesothelioma, Malignant ; Mice ; Nanotubes, Carbon/*adverse effects ; Occupational Exposure/adverse effects ; }, }
@article {pmid30770142, year = {2019}, author = {Douglas, T and Van den Borre, L}, title = {Asbestos neglect: Why asbestos exposure deserves greater policy attention.}, journal = {Health policy (Amsterdam, Netherlands)}, volume = {123}, number = {5}, pages = {516-519}, doi = {10.1016/j.healthpol.2019.02.001}, pmid = {30770142}, issn = {1872-6054}, mesh = {*Asbestos ; *Carcinogens, Environmental ; Developing Countries ; Environmental Exposure/*adverse effects ; Health Policy ; Humans ; Lung Neoplasms/chemically induced/prevention &amp; control ; Mesothelioma/chemically induced/prevention &amp; control ; Occupational Exposure/adverse effects ; }, abstract = {While many public health threats are now widely appreciated by the public, the risks from asbestos exposure remain poorly understood, even in high-risk groups. This article makes the case that asbestos exposure is an important, ongoing global health threat, and argues for greater policy efforts to raise awareness of this threat. It also proposes the extension of asbestos bans to developing countries and increased public subsidies for asbestos testing and abatement.}, }
@article {pmid30759891, year = {2019}, author = {Bertrand, P and Blanquart, C and Héroguez, V}, title = {The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy.}, journal = {Biomolecules}, volume = {9}, number = {2}, pages = {}, pmid = {30759891}, issn = {2218-273X}, mesh = {Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Cell Proliferation/drug effects ; Drug Carriers/chemistry ; Drug Delivery Systems ; Histone Deacetylase Inhibitors/chemistry/*pharmacology ; Humans ; Hydrogen-Ion Concentration ; Nanoparticles/*chemistry ; Neoplasms/*drug therapy/pathology ; Polymerization ; }, abstract = {Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.}, }
@article {pmid30754975, year = {2018}, author = {Pelclová, D}, title = {Diagnostics and acknowledgement of occupational diseases - topics and challenges in the Czech Republic.}, journal = {Casopis lekaru ceskych}, volume = {157}, number = {8}, pages = {396-399}, pmid = {30754975}, issn = {0008-7335}, mesh = {*Asbestos/adverse effects ; *Asthma/diagnosis/etiology ; Czech Republic ; Humans ; *Mesothelioma/diagnosis/etiology ; *Occupational Diseases/diagnosis/therapy ; }, abstract = {The causes of occupational diseases are changing, thats why a regular update of Czech List of Occupational Diseases is needed. New compensable occupational diseases, such as cancer of the larynx and ovarian cancer due to asbestos, and chronic obstructive pulmonary diseases due to black coal dust were included in the last two updates of the Czech List. The need of an early examination at the Centers of Occupational Diseases is stressed in this article, especially before a surgery or other treatment of epicondylitis and carpal tunnel syndrome. These treatments may suppress the diagnostic hallmarks requested for acknowledgements of these disorders. Extrinsic allergic alveolitis, allergic rhinitis and bronchial asthma are underdiagnosed, and isocyanates belong among the key factors. Only about 10 % patients with mesotheliomas due to asbestos are compensated. The latency in cancers due to asbestos may reach more than 50 years.}, }
@article {pmid30744695, year = {2019}, author = {Weber, DG and Brik, A and Casjens, S and Burek, K and Lehnert, M and Pesch, B and Taeger, D and Brüning, T and Johnen, G and , }, title = {Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study.}, journal = {BMC research notes}, volume = {12}, number = {1}, pages = {77}, pmid = {30744695}, issn = {1756-0500}, mesh = {Adult ; Asbestosis/blood ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Circulating MicroRNA/*blood ; Early Detection of Cancer/*standards ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelioma/blood/*diagnosis ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Middle Aged ; Prodromal Symptoms ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case-control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease.<br><br>RESULTS: Using prediagnostic plasma samples collected in median 8.9 months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.}, }
@article {pmid30741658, year = {2019}, author = {García-Ibáñez, J and Cayuelas-Rubio, C and Durán-Rivera, A and Mitjana-Biosca, S and Monzó-Cataluña, A and Sánchez Ballester, F and Ramos de Campos, M and Ramos de Campos, M and López-Alcina, E}, title = {[Report of two cases of malignant mesothelioma of the tunica vaginalis.].}, journal = {Archivos espanoles de urologia}, volume = {72}, number = {1}, pages = {85-88}, pmid = {30741658}, issn = {0004-0614}, mesh = {Aged ; Humans ; *Lung Neoplasms ; Male ; *Mesothelioma/diagnosis ; *Testicular Hydrocele ; *Testicular Neoplasms/diagnosis ; }, abstract = {OBJECTIVE: Paratesticular mesothelioma isan infrequent tumor and only 250 cases have been published.It originates in the scrotal tunica vaginalis. It represents0.3-1.4% of mesotheliomas and it predominates inpatients with history of asbestos exposure and old age. Itsdiagnosis is usually casual. Our objective is to present thecases that occurred in our service with malignant paratesticularmesothelioma and to carry out a review of the currentliterature on this pathology.<br><br>METHODS: We report two cases diagnosed with malignantparatesticular mesothelioma that happened in the lasttwo years.<br><br>RESULT: The first case was a 73-year-old male with asymptomatichydrocele. The second was a 57-year-oldmale who had testicular pain and hydrocele. Both werediagnosed of mesothelioma after hydrocelectomy. The firsttreatment was radical orchiectomy in both cases. The firstpatient did not need more treatments. The second patientpresented pulmonary nodules, lymphadenopathy and localrelapse, which was treated with chemotherapy and localresection.<br><br>CONCLUSION: Paratesticular mesothelioma is an infrequenttumor. Scrotal mass associated with hydrocele is thetypical form of presentation. Surgical treatment consists ofradical orchiectomy. They have poor prognosis because inmost cases there is rapid local and dissemination.}, }
@article {pmid30719319, year = {2019}, author = {Guo, X and Watanabe, J and Takahashi, K and Hayashi, T and Kurose, N and Sasaguri, Y and Uramoto, H and Iwagaki, H and Nabeshima, K and Yamada, S}, title = {Localized malignant pleural mesothelioma arising in the interlobar fissure: a unique surgical case masquerading clinicopathologically as primary lung adenocarcinoma.}, journal = {SAGE open medical case reports}, volume = {7}, number = {}, pages = {2050313X18824802}, pmid = {30719319}, issn = {2050-313X}, abstract = {An 80-year-old male with previous workplace exposure to asbestos presented with a history of an increase in the pulmonary-to-hilar mass, measuring more than 50 mm in diameter, likely in the right lower lobe. We first interpreted it as suspicious of primary lung adenocarcinoma with direct invasion to the right hilar lymph node. A right middle and lower lobectomy with partial resection of upper lobe was performed, and gross examination showed a hilar tumor lesion, involving the middle/lower lobe to hilar lymph node and looking whitish to yellow-grayish, partly adjacent to the right pulmonary artery. On microscopic examination, the tumor was located on the extrapulmonary, interlobar pleural fissure, predominantly composed of a proliferation of atypical epithelioid cells, often arranged in an irregular and fused tubular growth pattern with an involvement of pulmonary artery. Immunohistochemically, these atypical cells are positive for several mesothelial markers, including calretinin, cytokeratin 5/6, and WT-1, whereas negative for thyroid transcription factor 1. Furthermore, p16 deletions were specifically detected by fluorescence in situ hybridization, and electron microscopy showed numerous, significantly elongated microvilli. Taken together, we finally made a diagnosis of localized malignant pleural mesothelioma, epithelioid-type, arising in the right interlobar fissure between lower and middle lobes. We should be aware that, owing to its characteristic features, clinicians and pathologists might be able to raise interlobar fissure localized malignant pleural mesothelioma as one of the differential diagnoses, based on careful clinicopathological examinations.}, }
@article {pmid30711965, year = {2019}, author = {Salo, SAS and Ilonen, I and Laaksonen, S and Myllärniemi, M and Salo, JA and Rantanen, T}, title = {Malignant Peritoneal Mesothelioma: Treatment Options and Survival.}, journal = {Anticancer research}, volume = {39}, number = {2}, pages = {839-845}, doi = {10.21873/anticanres.13183}, pmid = {30711965}, issn = {1791-7530}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; Cytoreduction Surgical Procedures/mortality ; Female ; Finland ; Humans ; Hyperthermia, Induced ; Lung Neoplasms/*drug therapy/mortality/*surgery ; Male ; Mesothelioma/*drug therapy/mortality/*surgery ; Mesothelioma, Malignant ; Middle Aged ; Peritoneal Neoplasms/*drug therapy/mortality/*surgery ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland.<br><br>MATERIALS AND METHODS: The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure.<br><br>RESULTS: Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009).<br><br>CONCLUSION: Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.}, }
@article {pmid30706690, year = {2019}, author = {Rojas, L and Cardona, AF and Trejo-Rosales, R and Zatarain-Barrón, ZL and Ramírez-Tirado, LA and Ruiz-Patiño, A and Campos Gómez, S and Corrales, L and Oblitas, G and Bacon, L and Martín, C and de Lima, VCC and Freitas, HC and Mas, L and Vargas, C and Carranza, H and Otero, J and Pérez, MA and González, L and Chirinos, L and Granados, ST and Rodriguez, J and Báez, R and Remolina Bonilla, YA and Núñez Cerrillo, G and Archila, P and Cuello, M and Karachaliou, N and Rosell, R and Arrieta, O and , }, title = {Characteristics and long-term outcomes of advanced pleural mesothelioma in Latin America (MeSO-CLICaP).}, journal = {Thoracic cancer}, volume = {10}, number = {3}, pages = {508-518}, pmid = {30706690}, issn = {1759-7714}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cisplatin/therapeutic use ; Female ; Humans ; Latin America/epidemiology ; Lung Neoplasms/drug therapy/*epidemiology/pathology/surgery ; Male ; Mesothelioma/drug therapy/*epidemiology/pathology/surgery ; Mesothelioma, Malignant ; Middle Aged ; Pemetrexed/therapeutic use ; Platinum/*therapeutic use ; Pleural Neoplasms/drug therapy/*epidemiology/pathology/surgery ; Progression-Free Survival ; Thoracic Surgical Procedures/methods ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor, associated with poor prognosis. There is a lack of information about the clinical and pathological features related with survival in the Latin American population.<br><br>METHODS: The MeSO-CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first-line chemotherapy among Latin American patients.<br><br>RESULTS: The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first-line platinum-based chemotherapy. The overall response rate to first-line chemotherapy was 40.4%, progression-free survival to first-line treatment was 5.7 months (95% CI 4.9-6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0-20.5), and multivariate analysis found that stage (P = 0.013), and pleurodesis (P = 0.048), were independent prognostic factors for first-line overall survival. The model to predict response to first-line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non-responders.<br><br>CONCLUSION: This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes.}, }
@article {pmid30706505, year = {2019}, author = {Sun, H}, title = {North-south gradient of mesothelioma and asbestos consumption-production in the United States-Progresses since the 1st asbestos partial ban in 1973.}, journal = {American journal of industrial medicine}, volume = {62}, number = {4}, pages = {337-346}, doi = {10.1002/ajim.22955}, pmid = {30706505}, issn = {1097-0274}, mesh = {*Asbestos ; Asbestos, Amphibole ; Asbestos, Serpentine ; Female ; Geography ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Mining/*statistics &amp; numerical data ; United States/epidemiology ; }, abstract = {BACKGROUND: Temporal trends and broad geographical distributions of asbestos use and the incidence of malignant mesothelioma (MM) in the US still need to be studied.<br><br>METHODS: Data on asbestos consumption and production between 1900 and 2015 and MM mortality and incidence rates between 1975 and 2015 in the US were examined. Spatial distributions of MM mortality and incidence rates and their association with climate zone were analyzed.<br><br>RESULTS: Decline of MM incidence and mortality rates in the US occurred about 20 years after the peak of asbestos consumption-production in 1973. There are apparent north-south (N-S) gradients in MM mortality and incidence rates in the US.<br><br>CONCLUSION: Recent decline of MM incidence and mortality rates in the US may be associated with reduced US asbestos consumption. N-S MM gradients between 1999 and 2015 were likely related to larger asbestos requirements in building materials in the northern states.}, }
@article {pmid30702033, year = {2020}, author = {Germine, M and Puffer, JH}, title = {Analytical transmission electron microscopy of amosite asbestos from South Africa.}, journal = {Archives of environmental &amp; occupational health}, volume = {75}, number = {1}, pages = {36-44}, doi = {10.1080/19338244.2018.1556201}, pmid = {30702033}, issn = {2154-4700}, mesh = {Asbestos, Amosite/*chemistry ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Molecular Structure ; South Africa ; }, abstract = {Using the recognized amosite standard, we have performed transmission electron microscopy (TEM), scanning electron microscopy (SEM), and chemical analyses. We use high-resolution transmission electron microscopy (HRTEM) and zone-axis selected area electron diffraction (SAED) to describe the molecular structure of the fibers. We find that both microscopic observational evidence and statistical dimensional characteristics indicate that the amosite fibers are formed by longitudinal splitting, with surfaces produced by fine twinning and lateral boundaries formed by parting parallel to the planes of double and triple sheets of amphibole chain structures. Our findings indicate that amosite would not be regulated under current asbestos regulations, which define amphibole asbestos as whole crystals that are not split and that form fibril bundles, not found in our standard. However, it is fully documented that amosite causes mesothelioma, lung cancer, and asbestosis.}, }
@article {pmid30687679, year = {2018}, author = {Visonà, SD and Villani, S and Manzoni, F and Chen, Y and Ardissino, G and Russo, F and Moretti, M and Javan, GT and Osculati, A}, title = {Impact of asbestos on public health: a retrospective study on a series of subjects with occupational and non-occupational exposure to asbestos during the activity of Fibronit plant (Broni, Italy).}, journal = {Journal of public health research}, volume = {7}, number = {3}, pages = {1519}, pmid = {30687679}, issn = {2279-9028}, abstract = {The goal of this study is to understand more about the role of asbestos in causing human diseases, first of all mesothelioma, by investigating a large series of deaths due to asbestos-related diseases (ARDs). The main aim is to clarify if even very low amounts of asbestos can cause mesothelioma and other ARDs, as well as to find out if a different individual vulnerability can be important. This retrospective study included 188 subjects who died from asbestos related diseases in 2000-2017 in the area around Broni, Italy, where an important asbestos cement factory had been active from 1932 until 1993. In each case, a forensic autopsy has been performed. In order to perform the present study, the records were retrieved, including the clinical files, the autopsy, and the histological report. The statistical analysis performed showed that there was a significant relation between the cause of death (mesothelioma, lung cancer or asbestosis) and the kind of exposure (occupational, neighborhood or household), showing that all the subjects not exposed occupationally (and, therefore, exposed to lower amounts of asbestos) died from mesothelioma, whereas the individuals who used to work at the plant died also from other caused (asbestosis, lung cancer). Significant differences were highlighted examining the distribution of the causes of death according to the smoking habits. Moreover, among the mesothelioma patients, the survival time was shorter in the subjects with a neighborhood or household exposure than in the occupationally exposed individuals. The study provided meaningful data about the role of asbestos in causing human pathologies. In particular, the present data appear to support the hypothesis that even an exposure to a very little amount of asbestos can cause mesothelioma in hypersusceptible subjects (probably, on a genetic basis).}, }
@article {pmid30687504, year = {2019}, author = {Matthews, C and Freeman, C and Sharples, LD and Fox-Rushby, J and Tod, A and Maskell, NA and Edwards, JG and Coonar, AS and Sivasothy, P and Hughes, V and Rahman, NM and Waller, DA and Rintoul, RC}, title = {MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial.}, journal = {BMJ open respiratory research}, volume = {6}, number = {1}, pages = {e000368}, pmid = {30687504}, issn = {2052-4439}, support = {G0600475/MRC_/Medical Research Council/United Kingdom ; PB-PG-1014-35050/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Catheters, Indwelling ; Clinical Trials, Phase III as Topic ; England/epidemiology ; Feasibility Studies ; Female ; Humans ; Lung Neoplasms/complications/mortality/*surgery ; Male ; Mesothelioma/complications/mortality/*surgery ; Mesothelioma, Malignant ; Multicenter Studies as Topic ; Observational Studies as Topic ; Pilot Projects ; Pleural Effusion, Malignant/etiology/mortality/*surgery ; Pleural Neoplasms/complications/mortality/*surgery ; Pleurodesis/adverse effects/instrumentation/*methods ; Randomized Controlled Trials as Topic ; Sample Size ; Survival Analysis ; Thoracic Surgery, Video-Assisted/adverse effects/instrumentation/*methods ; Treatment Outcome ; }, abstract = {Introduction: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand.<br><br>Methods and analysis: MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months.<br><br>Ethics and dissemination: This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy.<br><br>Trial registration: NCT03412357.}, }
@article {pmid30686559, year = {2019}, author = {Neviere, Z and Berthet, P and Polycarpe, F and Dubos-Arvis, C and Dô, P and Gervais, R}, title = {[Malignant mesothelioma and constitutional BAP1 gene mutations].}, journal = {Revue des maladies respiratoires}, volume = {36}, number = {2}, pages = {241-248}, doi = {10.1016/j.rmr.2017.11.014}, pmid = {30686559}, issn = {1776-2588}, mesh = {Aftercare/methods ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*genetics/*therapy ; Medical Oncology/methods ; Mesothelioma/diagnosis/epidemiology/*genetics/*therapy ; Mesothelioma, Malignant ; *Mutation ; Referral and Consultation ; Tumor Suppressor Proteins/*genetics/physiology ; Ubiquitin Thiolesterase/*genetics/physiology ; }, abstract = {Malignant mesothelioma is a rare tumour, usually the result of asbestos exposure. Several cases of familial aggregation have been reported and recently shown to be associated with constitutional mutations of the BAP1 gene. BAP1 is a deubiquitinating enzyme implicated in several different cellular mechanisms such as the repair or differentiation of DNA. About a half of malignant mesotheliomas present a somatic, bi-allelic inactivation of BAP1, demonstrated by nuclear extinction on histochemistry. Constitutional alterations of BAP1 are extremely rare. Present in the heterozygous state they are transmitted as an autosomal dominant. They are associated with a risk of developing other tumours such as uveal and cutaneous melanomas, benign melanocytic tumours (melanocytic BAP1-mutated atypical intradermal tumour or MBAITS) and clear cell renal carcinomas. The causal link between mesothelioma and germinal mutations of BAP1 has still not been clearly identified. At present there is, in France, no consensus on recommendations for the management of patients with these mutations. This article is a synthesis of the literature on the functions of the BAP1 gene, the tumour risks related to its alteration and the follow up of patients bearing a constitutional mutation.}, }
@article {pmid30685089, year = {2019}, author = {Abayasiriwardana, KS and Wood, MK and Prêle, CM and Birnie, KA and Robinson, BW and Laurent, GJ and McAnulty, RJ and Mutsaers, SE}, title = {Inhibition of collagen production delays malignant mesothelioma tumor growth in a murine model.}, journal = {Biochemical and biophysical research communications}, volume = {510}, number = {2}, pages = {198-204}, doi = {10.1016/j.bbrc.2019.01.057}, pmid = {30685089}, issn = {1090-2104}, support = {/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Collagen/antagonists &amp; inhibitors/*biosynthesis ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Female ; Humans ; Inflammation ; Lung Neoplasms/*metabolism/pathology ; Mesothelioma/*metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred CBA ; Pleural Neoplasms/*metabolism/pathology ; Thiazolidines/pharmacology ; Transforming Growth Factor beta/metabolism ; }, abstract = {Malignant mesothelioma is an aggressive fibrous tumor, predominantly of the pleura, with a very poor prognosis. Cell-matrix interactions are recognized important determinants of tumor growth and invasiveness but the role of the extracellular matrix in mesothelioma is unknown. Mesothelioma cells synthesize collagen as well as transforming growth factor-beta (TGF-β), a key regulator of collagen production. This study examined the effect of inhibiting collagen production on mesothelioma cell proliferation in vitro and tumor growth in vivo. Collagen production by mesothelioma cells was inhibited by incubating cells in vitro with the proline analogue thiaproline (thiazolidine-4-carboxylic acid) or by oral administration of thiaproline in a murine tumor model. Cell cytotoxicity was measured using neutral red uptake and lactate dehydrogenase assays. Proliferation was measured by tritiated thymidine incorporation, and inflammatory cell influx, proliferation, apoptosis and angiogenesis in tumors examined by immunohistochemical labelling. Tumor size was determined by tumor weight and collagen production was measured by HPLC. Thiaproline at non-toxic doses significantly reduced basal and TGF-β-induced collagen production by over 50% and cell proliferation by over 65%. In vivo thiaproline administration inhibited tumor growth at 10 days, decreasing the median tumor weight by 80%. The mean concentration of collagen was 50% lower in the thiaproline-treated tumors compared with the controls. There were no significant differences in vasculature or inflammatory cell infiltration but apoptosis was increased in thiaproline treated tumors at day 10. In conclusion, these observations strongly support a role for collagen in mesothelioma growth and establish the potential for inhibitors of collagen synthesis in mesothelioma treatment.}, }
@article {pmid30684047, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {Managing malignant pleural mesothelioma: experience and perceptions of health care professionals caring for people with mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {9}, pages = {3509-3519}, pmid = {30684047}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, mesh = {Adult ; Aged ; *Attitude of Health Personnel ; Caregivers/*psychology ; Communication ; Female ; Humans ; Lung Neoplasms/pathology/*therapy ; Male ; Medical Oncology ; Mesothelioma/pathology/*therapy ; Mesothelioma, Malignant ; Middle Aged ; Palliative Care/methods ; Pleural Neoplasms/pathology/*therapy ; Practice Patterns, Physicians'/*statistics &amp; numerical data ; Referral and Consultation ; Refusal to Treat/*statistics &amp; numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor prognosis and heavy symptom burden. Here, we investigate health professionals' attitudes to management and decision-making in people with MPM.<br><br>METHODS: Survey questions were based on previous interviews with health professionals, MPM patients, and caregivers. Surveys were sent to specialist doctors and nurses who treat MPM.<br><br>RESULTS: Surveys were completed by 107 doctors and 19 nurses from January-September 2014. Most doctors were respiratory physicians (50%) or medical oncologists (35%). Overall, 90% of doctors estimated > 10% of eligible MPM patients did not receive chemotherapy; 43% estimated the rate was > 20%. Doctors believed clinical barriers to chemotherapy were clinician nihilism (70%); non-referral to medical oncology (49%); and lack of specialists in rural/regional areas (44%). Nurses perceived barriers as follows: delayed diagnosis (74%); non-referral to medical oncology (63%); lack of clinician knowledge (58%). Patient-related barriers were negative perception of chemotherapy (83%) and belief survival benefit not worthwhile (63%). Doctors' preference in decision-making was for the patient to make the decision while strongly considering the doctor's opinion (33%); equally with the doctor (29%); and using knowledge gained (23%). Nurses described their roles as providing patient support (100%); information (95%); intermediary (74%); and link to palliative care (74%). Overall, 95% believed they enabled better resource allocation and provided patients with holistic care (95%); clearer communication (89%); more time (89%); additional information (89%); timely referrals (89%).<br><br>CONCLUSIONS: Caring for patients with MPM is challenging and complex. Health care professionals believe under-utilisation of chemotherapy is occurring, primarily due to clinician nihilism and lack of medical oncology referral.}, }
@article {pmid30663400, year = {2018}, author = {Wang, QQ and Zheng, GQ and Yang, DL and Liang, YF and Yin, WJ and Su, SS}, title = {Pretreatment Controlling Nutritional Status Score and Lactate Dehydrogenase as Predictive Markers of Survival in Patients with Malignant Peritoneal Mesothelioma.}, journal = {Nutrition and cancer}, volume = {70}, number = {8}, pages = {1264-1274}, doi = {10.1080/01635581.2018.1560481}, pmid = {30663400}, issn = {1532-7914}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/therapeutic use ; Asbestos/toxicity ; Biomarkers, Tumor/blood ; Female ; Humans ; L-Lactate Dehydrogenase/*blood ; Male ; Mesothelioma/drug therapy/*mortality/surgery ; Middle Aged ; Nutritional Status/*physiology ; Peritoneal Neoplasms/drug therapy/*mortality/surgery ; Prognosis ; ROC Curve ; }, abstract = {OBJECTIVE: To investigate the relationships between the Controlling Nutritional Status (CONUT) score and ascites fluid lactate dehydrogenase (LDH) level, and prognosis in patients with malignant peritoneal mesothelioma (MPeM).<br><br>METHODS: A total of 125 patients with MPeM were selected for the study using a pathological screening method. Once the diagnosis is established, before the treatment their clinical characteristics and nutritional evaluations were recorded including CONUT score and ascites LDH level. The associations between CONUT, ascites LDH, and other clinicopathological features including body mass index, asbestos exposure, pathological type, and treatment method were analyzed. Prognostic parameters predicting overall survival (OS) were analyzed by Cox regression.<br><br>RESULTS: High CONUT score, high ascites LDH level were positively associated with poor prognosis in patients with MPeM according to univariate analyses (P < 0.001, P < 0.001, respectively), and CONUT score and ascites LDH were independent predictors of a poor prognosis according to multivariate analysis. When the CONUT score is greater than 3 and the ascites LHD is greater than 474 IU/l, it indicates a poor prognosis.<br><br>CONCLUSIONS: CONUT score and ascites LDH are important factors influencing the prognosis of MPeM patients and should thus be considered in clinical applications.}, }
@article {pmid30659154, year = {2019}, author = {Villanova, T and Gesmundo, I and Audrito, V and Vitale, N and Silvagno, F and Musuraca, C and Righi, L and Libener, R and Riganti, C and Bironzo, P and Deaglio, S and Papotti, M and Cai, R and Sha, W and Ghigo, E and Schally, AV and Granata, R}, title = {Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {6}, pages = {2226-2231}, pmid = {30659154}, issn = {1091-6490}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Disease Models, Animal ; Gene Expression ; Growth Hormone-Releasing Hormone/*antagonists &amp; inhibitors/genetics/metabolism ; Humans ; Lung Neoplasms/drug therapy/*metabolism/*pathology ; Mesothelioma/drug therapy/*metabolism/*pathology ; Mesothelioma, Malignant ; Mice ; Mitochondria/drug effects/metabolism ; Pleural Neoplasms/drug therapy/*metabolism/*pathology ; Receptors, Neuropeptide/genetics/metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with exposure to asbestos, with poor prognosis and no effective therapies. The strong inhibitory activities of growth hormone-releasing hormone (GHRH) antagonists have been demonstrated in different experimental human cancers, including lung cancer; however, their role in MPM remains unknown. We assessed the effects of the GHRH antagonists MIA-602 and MIA-690 in vitro in MPM cell lines and in primary MPM cells, and in vivo in MPM xenografts. GHRH, GHRH receptor, and its main splice variant SV1 were found in all the MPM cell types examined. In vitro, MIA-602 and MIA-690 reduced survival and proliferation in both MPM cell lines and primary cells and showed synergistic inhibitory activity with the chemotherapy drug pemetrexed. In MPM cells, GHRH antagonists also regulated activity and expression of apoptotic molecules, inhibited cell migration, and reduced the expression of matrix metalloproteinases. These effects were accompanied by impairment of mitochondrial activity and increased production of reactive oxygen species. In vivo, s.c. administration of MIA-602 and MIA-690 at the dose of 5 μg/d for 4 wk strongly inhibited the growth of MPM xenografts in mice, along with reduction of tumor insulin-like growth factor-I and vascular endothelial growth factor. Overall, these results suggest that treatment with GHRH antagonists, alone or in association with chemotherapy, may offer an approach for the treatment of MPM.}, }
@article {pmid30651596, year = {2019}, author = {Sépult, C and Bellefroid, M and Rocks, N and Donati, K and Gérard, C and Gilles, C and Ludwig, A and Duysinx, B and Noël, A and Cataldo, D}, title = {ADAM10 mediates malignant pleural mesothelioma invasiveness.}, journal = {Oncogene}, volume = {38}, number = {18}, pages = {3521-3534}, pmid = {30651596}, issn = {1476-5594}, mesh = {ADAM10 Protein/*genetics ; Amyloid Precursor Protein Secretases/*genetics ; Animals ; Cadherins/genetics ; Cell Line, Tumor ; Cell Movement/*genetics ; Disease Progression ; Down-Regulation/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Lung Neoplasms/*genetics/*pathology ; Male ; Membrane Proteins/*genetics ; Mesothelioma/*genetics/*pathology ; Mesothelioma, Malignant ; Mice ; Mice, Inbred BALB C ; Pleural Neoplasms/*genetics/*pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options and treatment efficiency. Even if the latency period between asbestos exposure, the main risk factor, and mesothelioma development is very long, the local invasion of mesothelioma is very rapid leading to a mean survival of one year after diagnosis. ADAM10 (A Disintegrin And Metalloprotease) sheddase targets membrane-bound substrates and its overexpression is associated with progression in several cancers. However, nothing is known about ADAM10 implication in MPM. In this study, we demonstrated higher ADAM10 expression levels in human MPM as compared to control pleural samples and in human MPM cell line. This ADAM10 overexpression was also observed in murine MPM samples. Two mouse mesothelioma cell lines were used in this study including one primary cell line obtained by repeated asbestos fibre injections. We show, in vitro, that ADAM10 targeting through shRNA and pharmacological (GI254023X) approaches reduced drastically mesothelioma cell migration and invasion, as well as for human mesothelioma cells treated with siRNA targeting ADAM10. Moreover, ADAM10 downregulation in murine mesothelioma cells significantly impairs MPM progression in vivo after intrapleural cell injection. We also demonstrate that ADAM10 sheddase downregulation decreases the production of a soluble N-cadherin fragment through membrane N-cadherin, which stimulated mesothelioma cell migration. Taken together, we demonstrate that ADAM10 is overexpressed in MPM and takes part to MPM progression through the generation of N-cadherin fragment that stimulates mesothelioma cell migration. ADAM10 inhibition is worth considering as a therapeutic perspective in mesothelioma context.}, }
@article {pmid30648431, year = {2019}, author = {Harris, EJA and Musk, A and de Klerk, N and Reid, A and Franklin, P and Brims, FJH}, title = {Diagnosis of asbestos-related lung diseases.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {3}, pages = {241-249}, doi = {10.1080/17476348.2019.1568875}, pmid = {30648431}, issn = {1747-6356}, mesh = {Asbestos/*toxicity ; Asbestosis/diagnosis/diagnostic imaging ; Humans ; Lung Diseases/chemically induced/*diagnosis/diagnostic imaging ; Lung Neoplasms/chemically induced/diagnosis/diagnostic imaging ; Occupational Exposure ; Risk Assessment ; }, abstract = {INTRODUCTION: The diagnosis of lung disease in asbestos-exposed individuals is a process that not only requires a detailed occupational and tobacco smoking history, but the correlation with physical signs, appropriate imaging, detailed lung function assessment and histology/cytology when required. Worldwide, the total quantity of asbestos mined is static, having decreased dramatically in developed countries but increased in countries where there is no restriction on mining: for example, Russia, China, Brazil, and Kazakhstan. The predominant diagnostic challenge in most cases of possible asbestos-related disease is the significant interval between exposure and development of the disease. Also challenging is the estimation of an individual's risk of disease, not least because asbestos-induced malignancy can be rapidly fatal, and, in the case of lung cancer, early detection can lead to treatment with curative intent. Areas covered: Discussion of quantitative asbestos exposure estimation and risk assessment, selection of the most appropriate imaging modality and frequency of imaging. Expert commentary: Consideration of the future for asbestos-related lung disease includes screening those at highest risk particularly in relation to ongoing mining operations and the management of in-situ asbestos. In the future, screening programs designed with estimation of risk of malignancy, based on quantitative estimates of asbestos exposure, and smoking history are indicated.}, }
@article {pmid30642542, year = {2019}, author = {Wu, L and Dell'Anno, I and Lapidot, M and Sekido, Y and Chan, ML and Kohno, M and Serre-Beinier, V and Felley-Bosco, E and de Perrot, M}, title = {Progress of malignant mesothelioma research in basic science: A review of the 14th international conference of the international mesothelioma interest group (iMig2018).}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {127}, number = {}, pages = {138-145}, doi = {10.1016/j.lungcan.2018.11.034}, pmid = {30642542}, issn = {1872-8332}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Congresses as Topic ; Humans ; *International Cooperation ; Lung Neoplasms/*metabolism/pathology/therapy ; Mesothelioma/*metabolism/pathology/therapy ; Mesothelioma, Malignant ; Molecular Targeted Therapy ; Pleural Neoplasms/*metabolism/pathology/therapy ; Public Opinion ; *Research ; Tumor Microenvironment ; }, abstract = {Here we summarize the most recent update of mesothelioma research in basic science presented at the 14th iMig2018 international conference. The symposium of basic science track mainly focused on the drivers of mesothelioma initiation and progression, molecular pathogenesis, and perspectives on potential therapeutic approaches. This review covers several promising fields including strategies efficiently inhibiting YAP/TAZ functions or their critical downstream targets, heparanase inhibitors, RAN depletion, and MIF/CD74 inhibitors that may be developed as novel therapeutic approaches. In addition, targeting mesothelioma stem cells by depleting M2-polarized macrophages in tumor microenvironment or blocking Tnfsf18 (GITRL)-GITR signalling might be translated into therapeutic modalities in mesothelioma treatment.}, }
@article {pmid30629589, year = {2019}, author = {Chicco, D and Rovelli, C}, title = {Computational prediction of diagnosis and feature selection on mesothelioma patient health records.}, journal = {PloS one}, volume = {14}, number = {1}, pages = {e0208737}, pmid = {30629589}, issn = {1932-6203}, mesh = {Computational Biology/methods ; Female ; Health Records, Personal ; Humans ; *Machine Learning ; Male ; Mesothelioma/*diagnosis ; Regression Analysis ; }, abstract = {BACKGROUND: Mesothelioma is a lung cancer that kills thousands of people worldwide annually, especially those with exposure to asbestos. Diagnosis of mesothelioma in patients often requires time-consuming imaging techniques and biopsies. Machine learning can provide for a more effective, cheaper, and faster patient diagnosis and feature selection from clinical data in patient records.<br><br>METHODS AND FINDINGS: We analyzed a dataset of health records of 324 patients having mesothelioma symptoms from Turkey. The patients had prior asbestos exposure and displayed symptoms consistent with mesothelioma. We compared probabilistic neural network, perceptron-based neural network, random forest, one rule, and decision tree classifiers to predict diagnosis of the patient records. We measured classifiers' performance through standard confusion matrix scores such as Matthews correlation coefficient (MCC). Random forest outperformed all models tried, obtaining MCC = +0.37 on the complete imbalanced dataset and MCC = +0.64 on the under-sampled balanced dataset. We then employed random forest feature selection to identify the two most relevant dataset traits associated with mesothelioma: lung side and platelet count. These two risk factors resulted so predictive, that decision tree focusing on them achieved the second top accuracy on the complete dataset diagnosis prediction (MCC = +0.28), outperforming all other methods and even decision tree itself applied to all features.<br><br>CONCLUSIONS: Our results show that machine learning can predict diagnoses of patients having mesothelioma symptoms with high accuracy, sensitivity, and specificity, in few minutes. Additionally, random forest can efficiently select the most important features of this clinical dataset (lung side and platelet count) in few seconds. The importance of pleural plaques in lung sides and blood platelets in mesothelioma diagnosis indicates that physicians should focus on these two features when reading records of patients with mesothelioma symptoms. Moreover, doctors can exploit our machinery to predict patient diagnosis when only lung side and platelet data are available.}, }
@article {pmid30623323, year = {2019}, author = {Taghizadeh, F and Jafari, AJ and Gholami, M and Kermani, M and Arfaeinia, H and Mohammadi, S and Dowlati, M and Shahsavani, A}, title = {Monitoring of airborne asbestos fibers in an urban ambient air of Shahryar City, Iran: levels, spatial distribution, seasonal variations, and health risk assessment.}, journal = {Environmental science and pollution research international}, volume = {26}, number = {7}, pages = {6450-6459}, pmid = {30623323}, issn = {1614-7499}, support = {31563//Environmental and occupational health center/ ; }, mesh = {Air Pollutants/*analysis ; Air Pollution/statistics &amp; numerical data ; Asbestos/*analysis ; Cities ; Environmental Exposure/*statistics &amp; numerical data ; Environmental Monitoring ; Humans ; Iran/epidemiology ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Mesothelioma, Malignant ; Microscopy, Phase-Contrast ; Risk Assessment ; Seasons ; }, abstract = {Asbestos, as with other pollutants in the air, has adverse effects on the health of human beings and animals. Today, the relationship between presence of asbestos fibers in the air breathed by humans and developing serious diseases such as lung cancer (asbestosis) and mesothelioma has been proven. This study was designed and conducted within the time period of August 2017 and June 2018 to determine the concentration of asbestos fiber in the ambient air of Shahryar City and to evaluate their health effects for the general population of the city. For this purpose, samples were taken from four points, and overall 32 air samples were taken along the year. The samples were then analyzed by the phase contrast microscopy (PCM) method. Also, to investigate the type of asbestos and for more accurate counting of fibers, SEM analysis was utilized. Finally, based on the EPA IRIS method, the health effects resulting from asbestos risks were also evaluated. The results of this study indicated that the mean annual concentration of asbestos fiber in the ambient air of Shahryar City was obtained as 0.0019 f/ml PCM and 0.0072 f/ml SEM. Furthermore, the most polluted point was S1 point (0.0119 -0.0026 f/ml, PCM), while the lowest concentration was related to S4 point (0.001 f/ml PCM-0.0021 f/ml SEM). The mean annual risk resulting from airborne asbestos fiber in the ambient air of Shahryar City for all samples was obtained as 1.72 × 10-6 to 2.2 × 10-4, which was higher than the recommended risk range in some points.}, }
@article {pmid30622932, year = {2018}, author = {Lo Russo, G and Tessari, A and Capece, M and Galli, G and de Braud, F and Garassino, MC and Palmieri, D}, title = {MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {650}, pmid = {30622932}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a variable incidence among different countries. Occupational asbestos exposure is the most important etiological factor and a very long latency period is widely reported. In the early phase of the disease, clinical signs are absent or not specific. For this reason, the diagnosis is frequently achieved only in the advanced stages. The histopathological diagnosis per se is also very complex, and no known factor can predict the prognosis with certainty. Nonetheless, current survival rates remain very low, despite the use of standard treatments, which include surgery, chemotherapy and radiotherapy. The identification of new prognostic and/or diagnostic biomarkers, and the discovery of therapeutic targets is a priority and could lead to a real significant impact on the management of malignant pleural mesothelioma. In this scenario, the role of microRNAs is becoming increasingly relevant, with the promise of a quick translation in the current clinical practice. Despite the relative novelty of this field, the number of works and candidate microRNAs that are present in literature is striking. Unfortunately, to date the microRNAs with the most clinical relevance for MPM are still matter of debate, probably due to the variety of approaches, techniques, and collected samples. Although specific microRNAs (e.g., let-7, miR-15 and miR-16, miR-21, miR-34a, and the miR-200 family) have been reported several times from different groups, the heterogeneity of published data reinforces the need of more comprehensive and unified studies on this topic. In this review we collect and discuss the studies focused on the involvement of microRNAs in different aspects of MPM, from their biological role in tumorigenesis and progression, to their possible application as diagnostic, prognostic and predictive biomarkers. Lastly, we examine their potential value as for the design of therapeutic approaches that could benefit MPM patients.}, }
@article {pmid30618090, year = {2019}, author = {Zha, L and Kitamura, Y and Kitamura, T and Liu, R and Shima, M and Kurumatani, N and Nakaya, T and Goji, J and Sobue, T}, title = {Population-based cohort study on health effects of asbestos exposure in Japan.}, journal = {Cancer science}, volume = {110}, number = {3}, pages = {1076-1084}, pmid = {30618090}, issn = {1349-7006}, support = {15H04774//Japan Society for the Promotion of Science KAKENHI/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Cohort Studies ; Humans ; Japan/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Mesothelioma, Malignant ; Middle Aged ; Occupational Diseases/*epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/epidemiology/etiology ; }, abstract = {Occupational asbestos exposure occurs in many workplaces and is a well-known cause of mesothelioma and lung cancer. However, the association between nonoccupational asbestos exposure and those diseases is not clearly described. The aim of this study was to investigate cause-specific mortality among the residents of Amagasaki, a city in Japan with many asbestos factories, and evaluate the potential excess mortality due to established and suspected asbestos-related diseases. The study population consisted of 143 929 residents in Amagasaki City before 1975 until 2002, aged 40 years or older on January 1, 2002. Follow-up was carried out from 2002 to 2015. Standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated by sex, using the mortality rate of the Japanese population as reference. A total of 38 546 deaths (including 303 from mesothelioma and 2683 from lung cancer) were observed. The SMRs in the long-term residents' cohort were as follows: death due to all causes, 1.12 (95% CI, 1.10-1.13) in men and 1.07 (95% CI, 1.06-1.09) in women; lung cancer, 1.28 (95% CI, 1.23-1.34) in men and 1.23 (95% CI, 1.14-1.32) in women; and mesothelioma, 6.75 (95% CI, 5.83-7.78) in men and 14.99 (95% CI, 12.34-18.06) in women. These SMRs were significantly higher than expected. The increased SMR of mesothelioma suggests the impact of occupational asbestos exposure among men and nonoccupational asbestos exposure among women in the long-term residents' cohort. In addition, the high level of excess mortality from mesothelioma has persisted, despite the mixture of crocidolite and chrysotile no longer being used for three or four decades.}, }
@article {pmid30609805, year = {2019}, author = {Turini, S and Bergandi, L and Gazzano, E and Prato, M and Aldieri, E}, title = {Epithelial to Mesenchymal Transition in Human Mesothelial Cells Exposed to Asbestos Fibers: Role of TGF-β as Mediator of Malignant Mesothelioma Development or Metastasis via EMT Event.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, pmid = {30609805}, issn = {1422-0067}, mesh = {Antibodies/immunology ; Asbestos, Serpentine/*toxicity ; Cadherins/genetics/metabolism ; Cell Line ; Down-Regulation/drug effects ; Epithelial Cells/cytology/drug effects/metabolism ; Epithelial-Mesenchymal Transition/*drug effects ; Fibronectins/genetics/metabolism ; Humans ; Lung Neoplasms/chemically induced/pathology ; Matrix Metalloproteinase 2/genetics/metabolism ; Mesothelioma/chemically induced/pathology ; Mesothelioma, Malignant ; Smad Proteins/genetics/metabolism ; Snail Family Transcription Factors/genetics/metabolism ; Transforming Growth Factor beta/immunology/*metabolism ; Up-Regulation/drug effects ; Vimentin/genetics/metabolism ; Zinc Finger E-box-Binding Homeobox 1/genetics/metabolism ; beta Catenin/genetics/metabolism ; }, abstract = {Asbestos exposure increases the risk of asbestosis and malignant mesothelioma (MM). Both fibrosis and cancer have been correlated with the Epithelial to Mesenchymal Transition (EMT)-an event involved in fibrotic development and cancer progression. During EMT, epithelial cells acquire a mesenchymal phenotype by modulating some proteins. Different factors can induce EMT, but Transforming Growth Factor β (TGF-β) plays a crucial role in promoting EMT. In this work, we verified if EMT could be associated with MM development. We explored EMT in human mesothelial cells (MeT-5A) exposed to chrysotile asbestos: we demonstrated that asbestos induces EMT in MeT-5A cells by downregulating epithelial markers E-cadherin, β-catenin, and occludin, and contemporarily, by upregulating mesenchymal markers fibronectin, α-SMA, and vimentin, thus promoting EMT. In these cells, this mechanism is mediated by increased TGF-β secretion, which in turn downregulates E-cadherin and increases fibronectin. These events are reverted in the presence of TGF-β antibody, via a Small Mother Against Decapentaplegic (SMAD)-dependent pathway and its downstream effectors, such as Zinc finger protein SNAI1 (SNAIL-1), Twist-related protein (Twist), and Zinc Finger E-Box Binding Homeobox 1 (ZEB-1), which downregulate the E-cadherin gene. Since SNAIL-1, Twist, and ZEB-1 have been shown to be overexpressed in MM, these genes could be considered possible predictive or diagnostic markers of MM development.}, }
@article {pmid30603603, year = {2019}, author = {Shehata, M and Zaid, F and Ottaviano, P and Shweihat, Y and Munn, N}, title = {Case report: Steroid responsive mesothelioma-related pleural effusion.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {131-135}, pmid = {30603603}, issn = {2213-0071}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related tumor arising in the pleural cavity. Symptoms reflect extension of disease and include shortness of breath and chest pain. Unexplained pleural effusion and pleural pain in patients exposed to asbestos should raise the suspicion of MPM. The most common radiologic presentation is ipsilateral pleural effusion with or without pleural thickening or a mass. Thoracoscopic biopsy remains the most appropriate procedure for definitive diagnosis of mesothelioma. Despite advancement in diagnostic procedures and biomolecular research, this tumor nevertheless has poor prognosis. Mesothelioma remains a diagnostic and therapeutic challenge and is likely to remain one in the years to come. Here we present the first reported case of steroid treatment responsive pleural effusion in a 72 year-old-male that initially was misdiagnosed as rheumatoid related effusion. However, Pleuroscopy with biopsy revealed mesothelioma.}, }
@article {pmid30596292, year = {2019}, author = {Ye, L and Ma, S and Robinson, BW and Creaney, J}, title = {Immunotherapy strategies for mesothelioma - the role of tumor specific neoantigens in a new era of precision medicine.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {2}, pages = {181-192}, doi = {10.1080/17476348.2019.1563488}, pmid = {30596292}, issn = {1747-6356}, mesh = {*Cancer Vaccines ; Humans ; Immunologic Factors/*therapeutic use ; Immunotherapy/*methods ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Mesothelioma, Malignant ; Precision Medicine/methods ; }, abstract = {INTRODUCTION: Immunotherapy has long been considered a potential therapy for malignant mesothelioma and is currently being pursued as such. Some of the early phase clinical trials involving immunomodulators have demonstrated encouraging results and numerous clinical trials are underway to further investigate this treatment approach in various treatment settings and larger patient cohorts. Areas covered: This review summarizes the current and emerging clinical evidence for checkpoint blockade and other immunotherapeutic strategies in mesothelioma. The mesothelioma tumor immune microenvironment and mutational landscape are also discussed, including their impact on treatment strategies. We also provide an evaluation of the current evidence for neoantigen targeted personalized immunotherapy. Expert opinion: Immune checkpoint inhibitors work by unleashing the host immune response against probable neoantigens. Despite impressive activity in a small subset of patients and the potential for prolonged responses, most patients experience treatment failure. Neoantigen vaccines provide a potential complementary therapeutic strategy by increasing the immunogenic antigen load, which can lead to an increased tumor specific immune response. Further research is needed explore this treatment option in mesothelioma and technological advances are required to translate this concept into clinical practice.}, }
@article {pmid32704189, year = {2019}, author = {Berry, D and Januch, J and Woodbury, L and Kent, D}, title = {Detection of Erionite and Other Zeolite Fibers in Soil by the Fluidized Bed Preparation Methodology.}, journal = {Microscope (Carshalton Beeches (Surrey))}, volume = {67}, number = {4}, pages = {147-158}, pmid = {32704189}, issn = {0026-282X}, support = {EPA999999/ImEPA/Intramural EPA/United States ; }, abstract = {Erionite is a zeolite mineral that can occur as fibrous particles in soil. Inhalation exposure to erionite fibers may result in increased risk of diseases, such as mesothelioma. Low level detection of mineral fibers in soils has traditionally been accomplished using polarized light microscopy (PLM) methods to analyze bulk samples providing detection limits of around 0.25% by weight. This detection level may not be sufficiently low enough for protection of human health and is subject to large variability between laboratories. The fluidized bed asbestos segregator (FBAS) soil preparation method uses air elutriation to separate mineral fibers, such as erionite, from soil particles with higher aerodynamic diameter and deposits those mineral fibers onto filters that can be quantitatively analyzed by microscopic techniques, such as transmission electron microscopy (TEM). In this study, performance evaluation (PE) standards of erionite in soil with nominal concentrations ranging from 0.1% to 0.0001% by weight were prepared using the FBAS soil preparation method and the resulting filters were analyzed by TEM. The analytical results of this study illustrate a linear relationship between the nominal concentration of erionite (as % by weight) in the PE standard and the concentration estimated by TEM analysis expressed as erionite structures per gram of test material (s/g). A method detection limit of 0.003% by weight was achieved, which is approximately 100 times lower than typical detection limits for soils by PLM. The FBAS soil preparation method was also used to evaluate authentic field soil samples to better estimate the concentrations of erionite in soils on a weight percent basis. This study demonstrates the FBAS preparation method, which has already been shown to reliably detect low levels of asbestos in soil, can also be used to quantify low levels of erionite in soil.}, }
@article {pmid32464005, year = {2019}, author = {Bolognesi, C and Bruzzone, M and Fontana, V and Ugolini, D and Compalati, A and Stagnaro, L and Ceppi, M}, title = {The Role of Micronucleus Assay to Detect Genetic Instability in Respiratory Cancer Patients.}, journal = {Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer}, volume = {38}, number = {4}, pages = {345-352}, doi = {10.1615/JEnvironPatholToxicolOncol.2019030907}, pmid = {32464005}, issn = {2162-6537}, mesh = {Adult ; Biomarkers, Tumor/metabolism ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/genetics ; Mesothelioma, Malignant ; *Micronucleus Tests ; Middle Aged ; }, abstract = {Asbestos represents the main risk factor for malignant pleural mesothelioma (PM) even if only a minority of exposed people develop this tumor, suggesting a significant role for genetic susceptibility. This study aims to evaluate micronuclei (MN) frequency as a biomarker of genome instability in peripheral blood lymphocytes of PM and lung cancer (LC) patients when compared with healthy controls (HCs) and patients with nonneoplastic respiratory diseases (RDs). Lymphocyte cytokinesis-block MN assay was carried out on 317 subjects. Mutagen sensitivity, measured by quantifying MN frequency after an in vitro challenge with ionizing radiation, was evaluated in 252 subjects. A significant increase in MN frequency was observed in cancer patients compared to HCs, with a mean ratio (MR) of 1.35 and 1.36 at baseline and 1.43 and 1.38 after irradiation in PM and LC patients, respectively. A positive (synergistic) interaction between asbestos exposure and disease status was observed for MN frequency after irradiation in PM patients with possible exposure to asbestos (MR = 1.62). The evidence of increased genetic damage in cancer cases confirms lymphocyte cytokinesis-block MN assay as a sensitive predictor of the role of genetic instability in carcinogenic processes.}, }
@article {pmid30594459, year = {2019}, author = {McGehee, E and Gerber, DE and Reisch, J and Dowell, JE}, title = {Treatment and Outcomes of Primary Pericardial Mesothelioma: A Contemporary Review of 103 Published Cases.}, journal = {Clinical lung cancer}, volume = {20}, number = {2}, pages = {e152-e157}, doi = {10.1016/j.cllc.2018.11.008}, pmid = {30594459}, issn = {1938-0690}, support = {K24 CA201543/CA/NCI NIH HHS/United States ; UL1 TR001105/TR/NCATS NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Heart Neoplasms/mortality/*therapy ; Humans ; Neoplasms, Mesothelial/mortality/*therapy ; Pemetrexed/*therapeutic use ; Pericardium ; Platinum/*therapeutic use ; Risk Factors ; Survival Analysis ; Treatment Outcome ; }, abstract = {Primary pericardial mesothelioma (PPM) is a rare cancer for which there is no consensus on treatment. We evaluated and summarized a large contemporary population of published PPM cases to characterize risk factors, treatment patterns, and clinical outcomes. Using Ovid and PubMed, literature published from 2000 through 2016 was searched using the terms &quot;primary pericardial mesothelioma,&quot; &quot;pericardial mesothelioma,&quot; and &quot;malignant pericardial mesothelioma.&quot; We identified 6 case series and 84 case reports for a total of 103 PPM cases published from 2000 through 2016. The median age at diagnosis was 55 years, and the median overall survival was 6 months. In univariate analyses of clinical characteristics including gender, asbestos exposure, tobacco use, prior radiation exposure, histologic subtype, and metastasis and/or mediastinal spread, only the presence of metastasis and/or mediastinal spread was a significant predictor of decreased survival (P = .015). Surgery did not provide a statistically significant survival benefit (P = .12). A survival benefit was noted in those who received chemotherapy (median survival, 13 months vs. 0.5 months, P = .002), specifically chemotherapy with a platinum agent with or without pemetrexed. In multivariate analysis, only the receipt of chemotherapy was associated with improved survival. PPM remains a rare and poorly understood malignancy with unclear etiology and a poor prognosis. In this retrospective systematic review, a survival benefit was seen in patients who received chemotherapy.}, }
@article {pmid30594195, year = {2018}, author = {Merlo, DF and Bruzzone, M and Bruzzi, P and Garrone, E and Puntoni, R and Maiorana, L and Ceppi, M}, title = {Mortality among workers exposed to asbestos at the shipyard of Genoa, Italy: a 55 years follow-up.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {94}, pmid = {30594195}, issn = {1476-069X}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Respiratory Tract Diseases/*mortality ; *Ships ; Young Adult ; }, abstract = {BACKGROUND: Exposure to asbestos remains a global issue due to its massive use in the twentieth century and its long environmental persistence. Exposure to asbestos still occurs during dismantling of ships and vessels, buildings renovation, mining operations, and is reported in developing countries. Current estimate report exposure of hundreds of million people in occupational settings in countries where its use remains unregulated.<br><br>METHODS: We conducted a historical prospective cohort mortality study aimed at estimating mortality from specific causes, the temporal changes of pleural and lung cancer mortality, and the attributable fraction (AF) of lung cancer deaths following asbestos exposure. The study included 3984 shipyard workers employed at the shipyard of Genoa, Italy, between 1960 and 1981 and followed up to December 2014. Standardized Mortality Ratios (SMR) and their 95% confidence intervals (95%CI) were computed.<br><br>RESULTS: Overall deaths recorded were 3331 (83.6%). Excess mortality was observed for all cancers (SMR = 127, 95%CI:120-134), pleural mesothelioma (575, 469-697), cancers of the larynx (183, 134-244) and of the lung (154, 139-170), and for respiratory tract diseases (127, 114-141), including asbestosis (2277, 1525-3270). Ninety out of 399 deaths (22.6%) from lung cancer were attributed to asbestos exposure. The estimated lung cancer AF was 49.3% in workers with the highest SMR for pleural cancer. Median latency times for pleural and lung cancer were 42.8 years (minimum latency: 9.3 years) and 38.7 years (minimum latency: 6 years). The peak of mesothelioma incidence, expected in Italy in the period 2015-2024, was confirmed.<br><br>CONCLUSIONS: The long follow-up period of our study allowed the detection of a substantial disease burden following asbestos exposure. These findings support the urgent need for the prevention of asbestos related diseases through the implementation of asbestos ban worldwide, including those countries where asbestos is still mined, manufactured and used.}, }
@article {pmid30567579, year = {2018}, author = {Xu, R and Barg, FK and Emmett, EA and Wiebe, DJ and Hwang, WT}, title = {Association between mesothelioma and non-occupational asbestos exposure: systematic review and meta-analysis.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {90}, pmid = {30567579}, issn = {1476-069X}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42ES023720/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Cohort Studies ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/*epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: The risk of mesothelioma has been shown to be associated with exposure to asbestos fibers. Most of the existing literature focuses on occupational exposure; however, non-occupational asbestos exposure has also been identified as an important risk factor.<br><br>OBJECTIVE: To estimate the association between mesothelioma and non-occupational asbestos exposure, and evaluate control recruitment and exposure measurement methods.<br><br>METHODS: A systematic literature review was conducted to identify case-control (CC) and cohort studies that examined the association between mesothelioma and non-occupational exposure to asbestos, including neighborhood, domestic, and household exposure. Meta-analysis was performed to estimate a summary relative risk estimate (SRRE) and 95% confidence interval using random-effects models. Subgroup analyses were also conducted by exposure type, gender, region, and fiber type.<br><br>RESULTS: Twenty CC and 7 cohort studies were selected. Controls in CC studies were selected from the general population (55%), hospital records (18%), cancer registry (23%) and a combination of population and hospital records (5%). Multiple methods were used to measure neighborhood exposure (e.g., linear distance and direction of residence from an asbestos factory), domestic (e.g., whether living with an asbestos worker) and household exposure (e.g., whether involved in asbestos-containing home improvement projects). Primary meta-analyses suggested a SRRE of mesothelioma of 5.33 (95%CI: 2.53, 11.23) from neighborhood exposure, 4.31 (95%CI, 2.58, 7.20) from domestic exposure, and 2.41 (95%CI, 1.30, 4.48) from household exposure with large I2 statistics ranging from 83-99%.<br><br>CONCLUSIONS: Non-occupational asbestos exposure is significantly associated with an elevated risk of mesothelioma. Funnel plots indicated a potential of publication bias. Some SRREs should be interpreted with cautions because of high between-studies heterogeneity.}, }
@article {pmid30563645, year = {2018}, author = {Rogers, AJ}, title = {Exposures estimates of the Wittenoom mining workforce and town residents - Implications associated with risk estimation for persons exposed to asbestiform riebeckite.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {168-170}, doi = {10.1016/j.taap.2018.06.032}, pmid = {30563645}, issn = {1096-0333}, mesh = {Adult ; Asbestos/analysis ; Asbestos, Crocidolite/analysis/*toxicity ; Australia/epidemiology ; Child ; Dust/analysis ; Environmental Exposure/*statistics &amp; numerical data ; Female ; Humans ; Industry ; Inhalation Exposure/*analysis ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; *Mining ; Occupational Exposure/*statistics &amp; numerical data ; Risk Assessment ; Workforce ; }, abstract = {The mining of crocidolite at Wittenoom from 1943 to 1966 is infamous due to the adverse health outcomes in the mining and milling workforce and the non-mining residents and families. Proportional latency risk analysis provided estimates that 6% of the mine workforce along with 1.9% of women and 1.1% of children residents who were environmentally exposed, have or will die from mesothelioma. The absence of environmental exposure data relevant to the period restricts the extrapolation of these historical risk outcomes being applied to the low level exposures from natural contaminant crocidolite and other amphibole fibres experienced in contemporary mining practices in the Pilbara region.}, }
@article {pmid30561515, year = {2019}, author = {Oddone, E and Terracini, B and Mirabelli, D and Mensi, C and Consonni, D and Barone-Adesi, F}, title = {Comment on: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {488-489}, doi = {10.1093/carcin/bgy179}, pmid = {30561515}, issn = {1460-2180}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30558734, year = {2019}, author = {Kai, Y and Tsutani, Y and Ito, M and Mimura, T and Miyata, Y and Okada, M}, title = {Metachronous Lung Cancer After Pleurectomy/Decortication.}, journal = {The Annals of thoracic surgery}, volume = {107}, number = {1}, pages = {e1-e3}, doi = {10.1016/j.athoracsur.2018.05.087}, pmid = {30558734}, issn = {1552-6259}, abstract = {Pleurectomy/decortication is a surgical procedure for malignant pleural mesothelioma (MPM) and has been proposed as an alternative to extrapleural pneumonectomy. We report a second primary lung cancer developing after pleurectomy/decortication for MPM. A 59-year-old man was diagnosed with MPM on the right side and underwent pleurectomy/decortication. Follow-up computed tomography detected a nodule in the right upper lobe that was diagnosed as adenocarcinoma by wedge resection. Lung cancer and MPM are associated with asbestos exposure. However, predicting lung cancer after treatment for MPM is difficult. Careful follow-up of the spared lung is necessary for detecting second primary lung cancer or MPM recurrence.}, }
@article {pmid30557225, year = {2019}, author = {Schnatter, AR and Wojcik, NC and Jorgensen, G}, title = {Mortality Update of a Cohort of Canadian Petroleum Workers.}, journal = {Journal of occupational and environmental medicine}, volume = {61}, number = {3}, pages = {225-238}, pmid = {30557225}, issn = {1536-5948}, mesh = {Adult ; Canada/epidemiology ; Cause of Death ; *Extraction and Processing Industry ; Female ; Humans ; Lung Neoplasms/*epidemiology/*mortality ; Male ; Mesothelioma/*epidemiology/*mortality ; Mesothelioma, Malignant ; Occupational Diseases/*epidemiology/*mortality ; *Occupational Exposure ; *Petroleum ; }, abstract = {OBJECTIVE: This study updates the mortality experience of over 25,000 workers in a large Canadian petroleum company through December 31, 2006.<br><br>METHODS: Standardized mortality ratios were generated for all-cause and specific cause mortality.<br><br>RESULTS: All cause and all cancer mortality were favorable compared with the general Canadian population. Cancers of previous interest were largely consistent with expectation. There is a continuing excess of mesothelioma, which is of similar magnitude as the previous update, although based on larger numbers. This excess is mostly attributable to men who died in their 50s and 60s and who worked in the refining sector.<br><br>CONCLUSION: Most causes of death show mortality rates lower than the Canadian general population. Given the excess of mesothelioma observed, this study supports ongoing vigilance in asbestos exposure control programs, as refineries continue to remove asbestos from their facilities.}, }
@article {pmid30545133, year = {2018}, author = {Wörthmüller, J and Oberson, A and Salicio, V and Blum, W and Schwaller, B}, title = {Calretinin Functions in Malignant Mesothelioma Cells Cannot Be Replaced by the Closely Related Ca2+-Binding Proteins Calbindin-D28k and Parvalbumin.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, pmid = {30545133}, issn = {1422-0067}, support = {130680, 139226, 147697/1//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {Calbindin 1/*metabolism ; Calbindin 2/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Clone Cells ; Down-Regulation ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Focal Adhesions/metabolism ; Green Fluorescent Proteins/metabolism ; Humans ; Lentivirus/metabolism ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Mesothelioma, Malignant ; Parvalbumins/*metabolism ; Phenotype ; }, abstract = {Calretinin (CR; CALB2) belonging to the family of EF-hand Ca2+-binding proteins (CaBP) is widely used as a positive marker for the identification of human malignant mesothelioma (MM) and functionally was suggested to play a critical role during carcinogenesis of this highly aggressive asbestos-associated neoplasm. Increasing evidence suggests that CR not only acts as a prototypical Ca2+ buffer protein, i.e., limiting the amplitude of Ca2+ signals but also as a Ca2+ sensor. No studies have yet investigated whether other closely related CaBPs might serve as substitutes for CR's functions(s) in MM cells. Genetically modified MM cell lines with medium (MSTO-211H and ZL5) or low (SPC111) endogenous CR expression levels were generated that overexpress either CR's closest homologue calbindin-D28k (CB) or parvalbumin (PV), the latter considered as a &quot;pure&quot; Ca2+ buffer protein. After lentiviral shCALB2-mediated CR downregulation, in both MSTO-211H and ZL5 cells expressing CB or PV, the CR deficiency-mediated increase in cell death was not prevented by CB or PV. With respect to proliferation and cell morphology of SPC111 cells, CB was able to substitute for CR, but not for CR's other functions to promote cell migration or invasion. In conclusion, CR has a likely unique role in MM that cannot be substituted by &quot;similar&quot; CaBPs.}, }
@article {pmid30534997, year = {2019}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Reply to letters to the editor by Brentisci et al. and Consonni and Mensi.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {2}, pages = {341}, doi = {10.1093/annonc/mdy523}, pmid = {30534997}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30533375, year = {2019}, author = {Yamazoe, M and Tomioka, H and Kamada, T and Kaneko, M and Katsuyama, E}, title = {Simultaneous presence of lung adenocarcinoma and malignant pleural mesothelioma: A case report.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {45-49}, pmid = {30533375}, issn = {2213-0071}, abstract = {The co-presence of malignant pleural mesothelioma (MPM) and lung cancer is rare. We report a 70-year-old male with exposure to asbestos. Chest computed tomography revealed a right mediastinal mass combined with an enlarged ipsilateral lymph node and left pleural effusion. Transbronchial lung biopsy revealed lung adenocarcinoma. Thoracoscopic examination revealed multiple left pleural nodules, leading to the diagnosis of MPM. Despite aggressive anticancer drug therapy, he expired due to disease progression 2.5 years after diagnosis. Autopsy confirmed an epithelioid MPM in the left pleura. MPM comorbidity in patients diagnosed with lung cancer should be considered, especially in those exposed to asbestos.}, }
@article {pmid30530573, year = {2018}, author = {Lee, LJ and Lin, CK and Pan, CH and Cheng, Y and Chang, YY and Liou, SH and Wang, JD}, title = {Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.}, journal = {BMJ open}, volume = {8}, number = {12}, pages = {e021063}, pmid = {30530573}, issn = {2044-6055}, mesh = {Asbestos/*adverse effects ; Cluster Analysis ; Cohort Studies ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Manufacturing and Industrial Facilities/*statistics &amp; numerical data ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; Risk ; Taiwan ; }, abstract = {OBJECTIVE: Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency.<br><br>METHODS: We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed for each factory where any case of MPM was diagnosed by assuming Poisson distribution with a minimal latency of 20 years.<br><br>RESULTS: A total of 18 MPM (17 males, 1 female) in eight factories were found. The incidence rate of MPM for the eight factories was 18.0 per million, ranging from 6.2 per million (military factory) to 268.2 per million (asbestos cement). We observed significantly increased risks for MPM in asbestos cement, thermal insulation and shipbuilding industries, with eRR (genders combined) of 113.6, 87.5 and 15.8, respectively. The sensitivity analyses considering latency showed similar findings in latency ≥30 years, and the shipbuilding industry presented a significant eRR given a latency ≥40 years. The gender-specific eRR showed similar results in men, but high eRR of 729.6 was observed in an asbestos cement factory where a female MPM was diagnosed.<br><br>CONCLUSIONS: This nationwide study in Taiwan comprehensively shows that different asbestos manufacturing processes, including asbestos cement, thermal insulation and shipbuilding industries, were at significantly increased risks for MPM. We recommend to establish a medical screening programme for workers previously exposed to asbestos to identify MPM and other asbestos-related diseases at an earlier stage.}, }
@article {pmid30527173, year = {2018}, author = {Serio, G and Vimercati, L and Pennella, A and Gentile, M and Cavone, D and Buonadonna, AL and Scattone, A and Fortarezza, F and De Palma, A and Marzullo, A}, title = {Genomic changes of chromosomes 8p23.1 and 1q21: Novel mutations in malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {126}, number = {}, pages = {106-111}, doi = {10.1016/j.lungcan.2018.10.012}, pmid = {30527173}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 8/*genetics ; Comparative Genomic Hybridization ; Female ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; *Mutation ; Ubiquitin-Conjugating Enzymes/genetics ; }, abstract = {INTRODUCTION: Malignant mesothelioma is an aggressive malignancy of the thoracic cavity caused by prior asbestos exposure. In the peritoneum the mesothelioma is an extremely rare condition. In the present preliminary study, high-resolution array-comparative genomic hybridization (a-CGH) was performed to identify genetic imbalances in a series of malignant peritoneal mesothelioma cases.<br><br>MATERIALS AND METHODS: Between 1990 and 2008, among the cases recorded in the Apulia Mesothelioma Register, we found 22 peritoneal mesothelioma cases. CGH-array was performed on samples from all patients.<br><br>RESULTS: The CGH-array analysis revealed multiple chromosomal imbalances. Interestingly, deletion at 8p23.1 was observed in 12 cases. Furthermore, another novel deletion at 1q21 was present in 11. Often, 1q21 and 8p23.1 losses were present in the same patient (7 cases). Losses of BAP1 and CDKN2A loci were not detected.<br><br>DISCUSSION: The region at 8p23.1 contains the beta-defensin gene cluster (DEF) and 1q21 contains ubiquitin conjugating enzyme E2 (UBE2Q1). We hypotesized that the loss of function of ubiquitination, as well as of the defensins, could play an important role in the initial development and subsequent progression of mesothelioma.}, }
@article {pmid30518402, year = {2018}, author = {Chee, J and Watson, MW and Chopra, A and Nguyen, B and Cook, AM and Creaney, J and Lesterhuis, WJ and Robinson, BW and Lee, YCG and Nowak, AK and Lake, RA and McDonnell, AM}, title = {Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {864}, pmid = {30518402}, issn = {1756-0500}, support = {CA150787//U.S. Department of Defense/ ; }, mesh = {Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/blood/*immunology ; Mesothelioma/blood/*immunology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Effusion/blood/*immunology ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Cell Surface/*metabolism ; T-Lymphocytes/*immunology ; }, abstract = {OBJECTIVE: Pleural effusion (PE) is a common feature of malignant pleural mesothelioma. These effusions typically contain lymphocytes and malignant cells. We postulated that the PE would be a source of lymphocytes for analysis of tumor immune milieu. The aim of this study was to compare the phenotype and T cell receptor usage of pleural effusion T cells with paired concurrently drawn peripheral blood lymphocytes. We used multi-parameter flow cytometry and high-throughput T cell receptor sequencing to analyse peripheral blood and pleural effusion mononuclear cells.<br><br>RESULTS: Both CD8+ and CD4+ T cells from effusion showed increased expression of T cell inhibitory receptors PD-1, LAG-3 and Tim-3 compared to blood. Comprehensive T cell receptor sequencing on one of the patients showed a discordant distribution of clonotypes in the antigen-experienced (PD-1+) compartment between effusion and blood, suggesting an enrichment of antigen specific clonotypes in the effusion, with potential as an immunological response biomarker.}, }
@article {pmid30506035, year = {2018}, author = {Okita, R and Nojima, Y and Saisho, S and Shimizu, K and Shirai, R and Kanomata, N and Oka, M and Nakata, M}, title = {Deciduoid type malignant pleural mesothelioma: a case report.}, journal = {AME case reports}, volume = {2}, number = {}, pages = {43}, pmid = {30506035}, issn = {2523-1995}, abstract = {Here, we report a patient with deciduoid type malignant pleural mesothelioma (MPM), which rapidly progressed. A 55-year-old man who might have been exposed to asbestos a few decades ago had severe back pain. The chest X-ray scanning and computed tomography (CT) revealed pleural thickness on his right thoracic space, without the presence of a lung mass. A pleural biopsy was performed and the patient was histologically diagnosed with deciduoid type MPM. Although he received two cycles of chemotherapy, his disease rapidly progressed and he died within two months of the diagnosis of deciduoid type MPM.}, }
@article {pmid30501113, year = {2018}, author = {Izquierdo-Sánchez, V and Muñiz-Hernández, S and Vázquez-Becerra, H and Pacheco-Yepez, J and Romero-Piña, ME and Arrieta, O and Medina, LA}, title = {Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft.}, journal = {Molecules (Basel, Switzerland)}, volume = {23}, number = {12}, pages = {}, pmid = {30501113}, issn = {1420-3049}, support = {PAPIIT IN-225014, IN209916//Universidad Nacional Autónoma de México/ ; 154557//Consejo Nacional de Ciencia y Tecnología/ ; (017/027/IBI)(CEI/1147/17)//Instituto Nacional de Cancerología/ ; }, mesh = {Animals ; Antibodies, Monoclonal, Humanized/*pharmacokinetics ; Cell Line, Tumor ; Fluorodeoxyglucose F18/chemistry ; Gallium Radioisotopes/*pharmacokinetics ; Humans ; Imaging, Three-Dimensional ; Liver/metabolism ; Lung Neoplasms/diagnostic imaging/*metabolism ; Male ; Mesothelioma/diagnostic imaging/*metabolism ; Mesothelioma, Malignant ; Mice, Nude ; Pleural Neoplasms/diagnostic imaging/*metabolism ; Positron Emission Tomography Computed Tomography ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.}, }
@article {pmid30513236, year = {2018}, author = {Till, JE and Beck, HL and Boice, JD and Mohler, HJ and Mumma, MT and Aanenson, JW and Grogan, HA}, title = {Asbestos Exposure and Mesothelioma Mortality among Atomic Veterans.}, journal = {International journal of radiation biology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/09553002.2018.1551641}, pmid = {30513236}, issn = {1362-3095}, abstract = {BACKGROUND: During the Cold War the United States (U.S.) conducted 230 above-ground atmospheric nuclear weapons tests between 1945 and 1962 at the Nevada Test Site and the Pacific Proving Grounds. These tests involved over 250,000 military personnel. Asbestos was used on the naval vessels for insulation in the boiler room, engine room, and other areas. This is the first quantitative assessment of asbestos-related mesothelioma, including cancers of the pleura and peritoneum, among military personnel who participated in above-ground nuclear weapons testing.<br><br>METHODS: Approximately 114,000 atomic veterans were selected for an epidemiological study because they were in one of eight series of weapons tests that were associated with somewhat higher personnel exposures than the other tests and because they have been previously studied. We were able to categorize specific jobs into potential for asbestos exposure based on a detailed database of the military activities of the atomic veterans, developed using historical records provided by the Defense Threat Reduction Agency. Standardized mortality ratios (SMR) were calculated by service, rank(officer/enlisted) and ratings (occupation code and work location aboard ship) after 65 years of follow-up… Results: Mesothelioma deaths were significantly increased overall (SMR 1.56; 95% CI 1.32-1.82; n= 153). This increase was seen only among those serving in the Pacific Proving Ground (SMR 1.97; 95% CI 1.65-2.34; n= 134), enlisted men (SMR 1.81; 95% CI 1.53-2.13; n= 145) and the 70,309 navy personnel (SMR 2.15; 95% CI 1.80-2.56; n= 130). No increased mortality rates were seen among the other services: army (SMR 0.45), air force (SMR 0.85) or marines (SMR 0.75). Job categories with the highest potential for asbestos exposure (machinist's mates, boiler technicians, water tender, pipe fitters, and fireman) had an of SMR 6.47. Job categories with lower potential (SMR =1.35) or no potential (SMR =1.28) for asbestos exposure had non-significantly elevated mesothelioma mortality.<br><br>CONCLUSIONS: Although jobs with high potential for exposure to asbestos products were held by only 20% of the enlisted naval population, sailors with these jobs (machinist's mate, pipe fitter, boiler technician, water tender and fireman) experienced 55% of mesothelioma deaths. The significantly higher mortality rate overall was explained by asbestos exposure among enlisted naval personnel in this low-dose radiation exposed cohort.}, }
@article {pmid30500290, year = {2019}, author = {Regragui, M and Guebessi, NB}, title = {Primary Malignant Deciduoid Mesothelioma: A Challenging Diagnosis.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {143}, number = {4}, pages = {531-533}, doi = {10.5858/arpa.2017-0461-RS}, pmid = {30500290}, issn = {1543-2165}, mesh = {Decidua/*pathology ; Female ; Humans ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/*pathology ; }, abstract = {Primary malignant deciduoid mesothelioma is a rare subtype of epithelioid mesothelioma that was first described in the peritoneum in young women without a history of asbestos exposure. It was thought to be a distinct clinicopathologic entity with ominous prognosis; recent studies have better characterized this entity. On morphology, primary malignant deciduoid mesothelioma is characterized by cytomorphologic features resembling decidualized tissue. Pleomorphism is variable. The immunoprofile is similar to other epithelioid mesotheliomas. The prognosis is the same as other epithelioid mesotheliomas and seems to depend on histological grade.}, }
@article {pmid30489434, year = {2019}, author = {Dournes, G and Dubois, A and Benlala, I and Lacourt, A and Paris, C and Gislard, A and Clin, B and Pairon, JC and Baldacci, F and Laurent, F}, title = {3-Dimensional Quantification of Composite Pleural Plaque Volume in Patients Exposed to Asbestos Using High-resolution Computed Tomography: A Validation Study.}, journal = {Journal of thoracic imaging}, volume = {34}, number = {5}, pages = {320-325}, doi = {10.1097/RTI.0000000000000377}, pmid = {30489434}, issn = {1536-0237}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Imaging, Three-Dimensional/*methods ; Male ; Plaque, Atherosclerotic/*diagnostic imaging ; Pleural Diseases/*chemically induced/*diagnostic imaging ; Reproducibility of Results ; Retrospective Studies ; Tomography, X-Ray Computed/*methods ; }, abstract = {RATIONALE: As pleural plaque has been reported as a risk factor in the occurrence of lung cancer and mesothelioma, a reproducible and precise method of measurement of pleural plaque volume (PPV) is needed to further describe these relationships. The aim of the study was to assess the reproducibility of a 3-dimensional computed tomography (3D-CT) volumetric analysis of PPV in patients with occupational exposure to asbestos.<br><br>MATERIAL AND METHODS: A total of 28 patients were retrospectively randomly selected from the multicenter APEXS (Asbestos Post Exposure Survey) study, which was held between 2003 and 2005. All patients underwent a 3D-CT scan. Two readers specialized in chest radiology completed the 3D semiautomated quantification of lung volume using dedicated software. They also had to categorize the visual extent of pleural plaque in terms of thickness and circumference. Reproducibility of the continuous PPV variable was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Reproducibility of categorical variables was assessed using the κ test.<br><br>RESULTS: Intraobserver reproducibility of PPV was almost perfect (ICC=0.98 [95% interval: 0.97-0.99]), and interobserver reproducibility was very good (ICC=0.93 [0.88-0.97]). At Bland-Altman analysis, the mean differences were 0.1 (limit of agreement: -11.0 to 11.2) and 3.7 cc (-17.8 to 25.2), respectively. Visual analysis of both plaque in terms of thickness and circumference were fair to moderate, with κ values ranging from 0.30 to 0.60.<br><br>CONCLUSIONS: 3D semiautomatic quantification of PPV is feasible and reproducible using CT in patients with occupational exposure to asbestos. PPV measurement may be useful to correlate with other asbestos-related disease outcomes and prognosis.}, }
@article {pmid30479777, year = {2018}, author = {Park, S and Park, J and Lee, E and Eom, H and Shin, MY and Kim, J and Kang, D and Lee, S}, title = {Ovarian cancer in a former asbestos textile factory worker: a case report.}, journal = {Annals of occupational and environmental medicine}, volume = {30}, number = {}, pages = {65}, pmid = {30479777}, issn = {2052-4374}, abstract = {Background: The International Agency for Research on Cancer (IARC) defined that asbestos is a group 1 substance that causes lung cancer, mesothelioma (pleura and peritoneum), laryngeal cancer, and ovarian cancer in humans. Many studies on lung cancer, and mesothelioma caused by asbestos exposure have been conducted, but there was no case report of ovarian cancer due to asbestos exposure in Korea. We describe a case of ovarian cancer caused by asbestos exposure in a worker who worked at an asbestos textile factory for 3 years and 7 months in the late 1970s.<br><br>Case presentation: A 57-year-old woman visited the hospital because she had difficulty urinating. Ovarian cancer was suspected in radiologic examination, and exploratory laparotomy was performed. She was diagnosed with epithelial ovarian cancer. The patient did not undergo postoperative chemotherapy and recovered. She joined the asbestos factory in March 1976 and engaged in asbestos textile twisting and spinning for 1 year, 2 years and 7 months respectively. In addition, she lived near the asbestos factory for more than 20 years. There was no other specificity or family history.<br><br>Conclusion: Considering the patient's occupational and environmental history, it is estimated that she had been exposed to asbestos significantly, so we determined that ovarian cancer in the patient is highly correlated with the occupational exposure of asbestos and environmental exposure is a possible cause as well. Social devices are needed to prevent further exposure to asbestos. It is also necessary to recognize that ovarian cancer can occur in workers who have previously been exposed to asbestos, and the education and social compensation for those workers are needed.}, }
@article {pmid30479770, year = {2019}, author = {Tlotleng, N and Sidwell Wilson, K and Naicker, N and Koegelenberg, CF and Rees, D and Phillips, JI}, title = {The significance of non-occupational asbestos exposure in women with mesothelioma.}, journal = {Respirology case reports}, volume = {7}, number = {1}, pages = {e00386}, pmid = {30479770}, issn = {2051-3380}, abstract = {Malignant mesothelioma is a rare and aggressive pleural or peritoneal tumour almost always caused by exposure to asbestos fibres. Exposure to asbestos can cause malignant mesothelioma 30-40 years after exposure. A description of sources of exposure is important for prevention and possible financial compensation. Three women with cases of histologically confirmed malignant mesothelioma diagnosed from non-occupational asbestos exposure are described. Patients were contacted for an interview to assess their exposure history to asbestos. All three cases had mixed exposure histories related to secondary, environmental contamination, and domestic exposure. This case series highlight how ubiquitous asbestos is in the environment and how diverse the exposures may be. It is anticipated that a significant number of cases of non-occupational mesothelioma will be seen in many countries for several decades given the extent of asbestos containing materials.}, }
@article {pmid30475941, year = {2019}, author = {Consonni, D and Mensi, C}, title = {Comment on the paper 'Boffetta et al. Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy. Ann Oncol 2018; 29(2): 484-489'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {2}, pages = {340-341}, doi = {10.1093/annonc/mdy521}, pmid = {30475941}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30451473, year = {2018}, author = {Krówczyńska, M and Wilk, E and Pabjanek, P and Olędzka, G}, title = {Pleural mesothelioma in Poland: Spatial analysis of malignant mesothelioma prevalence in the period 1999-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.667}, pmid = {30451473}, issn = {1970-7096}, mesh = {Air Pollutants/analysis ; Asbestos/*analysis ; Female ; Humans ; Incidence ; Inhalation Exposure/analysis ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Mesothelioma, Malignant ; Pleural Neoplasms/*chemically induced/*epidemiology ; Poland/epidemiology ; Prevalence ; Spatial Analysis ; }, abstract = {Malignant mesothelioma (MM), a rare and very deadly tumour, can be due to asbestos exposure. To better understand the cause of incidence of MM, spatial autocorrelation analysis with reference to the quantity of asbestos-cement products in use and the localisation of former asbestos manufacturing plants was applied. Geostatistical analysis shows that strong spatial clustering of MM incidence (referring to the general population as well as females and males separately) during the period 1999-2013 in the administrative units of Poland (provinces and counties). Incidence hotspots were found to be concentrated primarily in southern Poland but also seen in the county of Szczecin, which stands out in local autocorrelation analysis in north-western Poland. High incidence rates were discovered, in particular with reference to counties around former plants manufacturing asbestos-containing products, mainly asbestos-cement manufacturers. The highest frequency of MM incidence rate was found in within a 55 km radius of plants in or near the towns Trzebinia, Ogrodzieniec and Szczucin in the South, where asbestos-cement products had been manufactured for close to 40 years. Areas with significantly high incidence rates were also discovered in the provinces of Śląskie, Małopolskie and Świętokrzyskie in southern Poland.}, }
@article {pmid30451463, year = {2018}, author = {Krówczyńska, M and Wilk, E}, title = {Spatial analysis of asbestos exposure and occupational health care in Poland during the period 2004-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.689}, pmid = {30451463}, issn = {1970-7096}, mesh = {Air Pollutants, Occupational/adverse effects/*analysis ; Asbestos/*adverse effects/analysis ; Asbestosis/epidemiology ; Humans ; Inhalation Exposure/adverse effects/*analysis ; Lung Neoplasms/chemically induced/epidemiology ; Manufacturing Industry ; Mesothelioma/chemically induced/epidemiology ; Mineral Fibers ; Occupational Exposure/adverse effects/*analysis ; Occupational Health/*statistics &amp; numerical data ; Poland/epidemiology ; Smoking/epidemiology ; *Spatial Analysis ; Time Factors ; }, abstract = {Asbestos is carcinogenic to humans and exposure to this substance can cause a wide range of diseases. In Poland 1997, a statutory ban was introduced on the production, use and marketing of products containing asbestos. The National Programme for Asbestos Abatement for 2009-2032 includes scheduled activities considering asbestos exposure assessment and health protection. As there are several data sources for asbestos exposure in Poland, which are not linked, the aim of this study was to gather and order them developing a PostgreSQL database, an open-source, objectrelational system. The data gathered combines the following information: the quantity of asbestos-cement products in use, details of asbestos manufacturing plants, the results of the measurements of asbestos fibre concentrations in the air and cases of asbestos-related diseases. The relational database was then used to develop a spatial analysis of asbestos monitoring and exposure in Poland to demonstrate the current state of realisation of the National Asbestos Abatement Programme in the country for 2009-2032 with the use of geoinformation techniques. The use of a database on health aspects of occupational and environmental asbestos exposure was also proposed in Asbestos, Asbestosis, and Cancer: Helsinki Criteria update 2014.}, }
@article {pmid30450291, year = {2018}, author = {Broeckx, G and Pauwels, P}, title = {Malignant peritoneal mesothelioma: a review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {537-542}, pmid = {30450291}, issn = {2218-6751}, abstract = {Malignant peritoneal mesothelioma (MPM) is a very rare malignancy of the peritoneum and has a poor prognosis. Of all mesotheliomas, pleural mesothelioma is more common than MPM. In comparison to pleural mesothelioma, the link with asbestos exposure is weaker (33-50% vs. >80%), but it is still the best-defined risk factor. MPM spreads predominantly expansive rather than infiltrative and symptoms are related to tumor spread within the abdominal cavity. Often, MPM is encountered incidentally by diagnostic imaging or by surgery. Computed tomography scan is widely accepted as a first line modality in diagnostic imaging. In diagnostic histopathology, MPM presents some challenges. Firstly, adequate clinical information is of utmost importance to consider the possibility of the diagnosis of MPM. Furthermore, a few morphological subtypes and variants exist. The most sensitive immunohistochemical markers are calretinin (100%), WT1 (94%) and CK5/6 (89%). The malignant character of immunohistochemically demonstrated mesothelial cells is not always obvious. This paradigm somewhat changed with the advent of immunohistochemical demonstration of BAP1 (BRCA-1 associated protein 1). Loss of BAP1 expression supports a diagnosis of malignancy. The gold standard in treatment remains cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Targetable molecular pathways in MPM are being identified. An exciting finding was the demonstration of ALK rearrangements in a small subset of patients with MPM and it is hoped for that at least this small subgroup of patients could benefit from treatment with ALK inhibitors. First-generation tyrosine kinase inhibitors against epidermal growth factor receptor (EGFR) did not show any significant activity in MPM. In contrast, nintedanib, an angiokinase inhibitor, improved progression-free survival and bevacizumab, a humanized anti-VEGF antibody increased overall survival in patients with MPM, when administered in combination with cisplatin and pemetrexed. Ongoing immunotherapy trials will offer a possible new treatment.}, }
@article {pmid30450290, year = {2018}, author = {Brusselmans, L and Arnouts, L and Millevert, C and Vandersnickt, J and van Meerbeeck, JP and Lamote, K}, title = {Breath analysis as a diagnostic and screening tool for malignant pleural mesothelioma: a systematic review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {520-536}, pmid = {30450290}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a tumour related to a historical exposure to asbestos fibres. Currently, the definite diagnosis is made only by the histological examination of a biopsy obtained through an invasive thoracoscopy. However, diagnosis is made too late for curative treatment because of non-specific symptoms mainly appearing at advanced stage disease. Hence, due to its biologic aggressiveness and the late diagnosis, survival rate is low and the patients' outcome poor. In addition, radiological imaging, like computed tomographic scans, and blood biomarkers are found not to be sensitive enough to be used as an early diagnostic tool. Detection in an early stage is assumed to improve the patients' outcome but is hampered due to non-specific and late symptomology. Hence, there is a need for a new screening and diagnostic test which could improve the patients' outcome. Despite extensive research has focused on blood biomarkers, not a single has been shown clinically useful, and therefore research recently shifted to &quot;breathomics&quot; techniques to recognize specific volatile organic compounds (VOCs) in the breath of the patient as potential non-invasive biomarkers for disease. In this review, we summarize the acquired knowledge about using breath analysis for diagnosing and monitoring MPM and asbestos-related disorders (ARD). Gas chromatography-mass spectrometry (GC-MS), the gold standard of breath analysis, appears to be the method with the highest accuracy (97%) to differentiate MPM patients from at risk asbestos-exposed subjects. There have already been found some interesting biomarkers that are significantly elevated in asbestosis (NO, 8-isoprostane, leukotriene B4, α-Pinene…) and MPM (cyclohexane) patients. Regrettably, the different techniques and the plethora of studies suffer some limitations. Most studies are pilot studies with the inclusion of a limited number of patients. Nevertheless, given the promising results and easy sampling methods, we can conclude that breath analysis may become a useful tool in the future to screen for MPM, but further research is warranted.}, }
@article {pmid30450289, year = {2018}, author = {Nuyts, V and Nawrot, T and Nemery, B and Nackaerts, K}, title = {Hotspots of malignant pleural mesothelioma in Western Europe.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {516-519}, pmid = {30450289}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma, a highly invasive tumour, has been epidemiologically linked to an occupational or environmental exposure to asbestos. Although asbestos has been widely used in diverse industrial applications and in construction, some industrial sectors have been affected much more than others. The objective of this review was to describe the existence of clusters of malignant pleural mesothelioma in Western European countries, based on epidemiological studies published between 2000 and 2015. MEDLINE (PubMed) and Embase were searched for relevant studies on spatial clustering of mesothelioma in Western European countries. Eventually, 16 different studies published between 2000 and 2015 were selected for a comprehensive analysis. Relevant studies on spatial clustering of mesothelioma were found for Belgium, the Netherlands, the United Kingdom, Germany, France, Spain, Italy and Denmark. Clustering of pleural mesothelioma was found mainly around shipyards (16 studies) and asbestos cement industries (10 studies). Although malignant pleural mesothelioma may be found throughout Western Europe, the present study indicates specific areas with higher past and also probable future incidence.}, }
@article {pmid30446780, year = {2018}, author = {Feder, IS and Jülich, M and Tannapfel, A and Tischoff, I}, title = {[The German Mesothelioma Register : Current pathological diagnostics and services].}, journal = {Der Pathologe}, volume = {39}, number = {Suppl 2}, pages = {241-246}, pmid = {30446780}, issn = {1432-1963}, mesh = {*Asbestos ; Germany ; Humans ; Lung ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Exposure ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {BACKGROUND: In Germany, asbestos-related diseases (asbestosis, lung cancer, mesothelioma) are recognised and compensated occupational diseases. The histologic diagnosis of mesothelioma is sometimes a challenge; additional immunohistochemical and molecular methods are needed. With lung dust analysis, the current asbestos fibre burden of the lung is measured (biomonitoring). Identification of grade I asbestosis (minimal asbestosis) requires directed histological examinations with up to 400-fold magnification, additional iron staining and possibly in connection with a lung dust analysis.<br><br>OBJECTIVES: Demonstration of current pathologic diagnostics in association with mesothelioma and lung dust analysis.<br><br>MATERIALS AND METHODS: Analysis of routine data from the German Mesothelioma Register.<br><br>RESULTS: Contrary to reactive mesothelial hyperplasia, malignant mesotheliomas have a nuclear BAP1 loss-of-expression in up to 66% of cases. For differential diagnosis between reactive versus malignant, a p16-FISH test may be helpful. BAP1 loss-of-expression and p16-deletion are independent markers. Evaluation of the dataset of the German Mesothelioma Register of patients with repeated tissue sampling proves the detection of asbestos fibres at the same level even after 40 years. The asbestos fibre burden in the human lung remains stable over this long period of time. In the electron microscopic analysis, white asbestos was predominantly found.<br><br>CONCLUSIONS: The well-known and industrially appreciated characteristics of asbestos fibres (in ancient ἄσβεστος asbestos &quot;imperishable&quot;) as biopersistent have also been experimentally confirmed in human lungs.}, }
@article {pmid30426024, year = {2018}, author = {Kumagai-Takei, N and Nishimura, Y and Matsuzaki, H and Lee, S and Yoshitome, K and Otsuki, T}, title = {Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8+ T Cell Line following Long-Term Exposure to Asbestos Fibers.}, journal = {Journal of immunology research}, volume = {2018}, number = {}, pages = {4391731}, pmid = {30426024}, issn = {2314-7156}, mesh = {Asbestos/adverse effects ; Asbestos, Serpentine/adverse effects ; CD8-Positive T-Lymphocytes/*immunology ; Cell Degranulation ; Cell Line ; Environmental Exposure/adverse effects ; Granzymes/metabolism ; Humans ; Interferon-gamma/*metabolism ; Lung Neoplasms/immunology/*metabolism ; Lymphocyte Activation ; Mesothelioma/immunology/*metabolism ; Mesothelioma, Malignant ; Perforin/*metabolism ; }, abstract = {Although the tumorigenicity of asbestos, which is thought to cause mesothelioma, has been clarified, its effect on antitumor immunity requires further investigation. We previously reported a decrease in the percentage of perforin+ cells of stimulated CD8+ lymphocytes derived from patients with malignant mesothelioma. Therefore, we examined the effects of long-term exposure to asbestos on CD8+ T cell functions by comparing long-term cultures of the human CD8+ T cell line EBT-8 with and without exposure to chrysotile (CH) asbestos as an in vitro model. Exposure to CH asbestos at 5 μg/ml or 30 μg/ml did not result in a decrease in intracellular granzyme B in EBT-8 cells. In contrast, the percentage of perforin+ cells decreased at both doses of CH exposure. CH exposure at 30 μg/ml did not suppress degranulation following stimulation with antibodies to CD3. Secreted production of IFN-γ stimulated via CD3 decreased by CH exposure at 30 μg/ml, although the percentage of IFN-γ+ cells induced by PMA/ionomycin did not decrease. These results indicate that long-term exposure to asbestos can potentially suppress perforin levels and the production of IFN-γ in human CD8+ T cells.}, }
@article {pmid30417819, year = {2018}, author = {Røe, OD}, title = {[Asbestos and mesothelioma in Denmark 2017: status of a man-made cancer epidemic].}, journal = {Ugeskrift for laeger}, volume = {180}, number = {46}, pages = {}, pmid = {30417819}, issn = {1603-6824}, mesh = {*Asbestos/adverse effects ; Denmark/epidemiology ; Humans ; *Lung Neoplasms ; *Mesothelioma/epidemiology ; *Pleural Neoplasms/epidemiology ; Risk Factors ; }, abstract = {Asbestos-induced cancer is an increasing problem in Denmark, and 32 years after the closure of the Danish Eternit Factory in Aalborg there are > 140 new mesothelioma cases diagnosed yearly, numbers rapidly increasing. Asbestos-induced lung cancer may be six times this number. The non-occupational exposure and even neighborhood exposure as a risk factor suggests, that compensation for mesothelioma should be universal. At the Aalborg University Hospital a multidisciplinary research team has been formed to do epidemiological, translational and clinical studies through national and international collaborations. Transformative research on asbestos cancer should be stimulated.}, }
@article {pmid30410726, year = {2018}, author = {Berzenji, L and Van Schil, P}, title = {Multimodality treatment of malignant pleural mesothelioma.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {}, pmid = {30410726}, issn = {2046-1402}, mesh = {Animals ; Combined Modality Therapy/*methods/standards/trends ; Humans ; Lung Neoplasms/mortality/*therapy ; Mesothelioma/mortality/*therapy ; Mesothelioma, Malignant ; Pleura/pathology ; Rare Diseases/therapy ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which the lung is removed en bloc, and pleurectomy/decortication, in which the lung stays in situ. Chemotherapy usually consists of a platinum-based chemotherapy, such as cisplatin, often combined with a folate antimetabolite, such as pemetrexed. More recently, immunotherapy has emerged as a possible therapeutic strategy for MPM. Evidence suggests that single-modality treatments are not an effective therapeutic approach for MPM. Therefore, researchers have started to explore different multimodality treatment approaches, in which often combinations of surgery, chemotherapy, immunotherapy, and RT are investigated. There is still no definitive answer to the question of which multimodality treatment combinations are most effective in improving the poor prognosis of MPM. Research into the effects of trimodality treatment approaches have found that radical approaches such as EPP and hemithoracic RT post-EPP are less effective than was previously assumed. In general, there are still a great number of unanswered questions and unknown factors regarding the ideal treatment approach for MPM. Hopefully, more research into multimodality therapy will provide insight into which combination of treatment modalities is most effective.}, }
@article {pmid30408567, year = {2019}, author = {Guarrera, S and Viberti, C and Cugliari, G and Allione, A and Casalone, E and Betti, M and Ferrante, D and Aspesi, A and Casadio, C and Grosso, F and Libener, R and Piccolini, E and Mirabelli, D and Dianzani, I and Magnani, C and Matullo, G}, title = {Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {3}, pages = {527-539}, doi = {10.1016/j.jtho.2018.10.163}, pmid = {30408567}, issn = {1556-1380}, mesh = {Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/blood/*genetics ; Carcinogens/toxicity ; Case-Control Studies ; DNA/*blood/chemistry/genetics ; *DNA Methylation ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/blood/*diagnosis/etiology/pathology ; Male ; Mesothelioma/blood/*diagnosis/etiology/pathology ; Mesothelioma, Malignant ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/blood/*diagnosis/etiology/pathology ; Prognosis ; ROC Curve ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive tumor strongly associated with asbestos exposure. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive early diagnostic tests to monitor asbestos-exposed people.<br><br>METHODS: We used a genome-wide methylation array to identify, in asbestos-exposed subjects, novel blood DNA methylation markers of MPM in 163 MPM cases and 137 cancer-free controls (82 MPM cases and 68 controls, training set; replication in 81 MPM cases and 69 controls, test set) sampled from the same areas.<br><br>RESULTS: Evidence of differential methylation between MPM cases and controls was found (more than 800 cytosine-guanine dinucleotide sites, false discovery rate p value (pfdr) < 0.05), mainly in immune system-related genes. Considering the top differentially methylated signals, seven single- cytosine-guanine dinucleotides and five genomic regions of coordinated methylation replicated with similar effect size in the test set (pfdr < 0.05). The top hypomethylated single-CpG (cases versus controls effect size less than -0.15, pfdr < 0.05 in both the training and test sets) was detected in FOXK1 (Forkhead-box K1) gene, an interactor of BAP1 which was found mutated in MPM tissue and as germline mutation in familial MPM. In the test set, comparison of receiver operating characteristic curves and the area under the curve (AUC) of two models, including or excluding methylation, showed a significant increase in case/control discrimination when considering DNA methylation together with asbestos exposure (AUC = 0.81 versus AUC = 0.89, DeLong's test p = 0.0013).<br><br>CONCLUSIONS: We identified signatures of differential methylation in DNA from whole blood between asbestos exposed MPM cases and controls. Our results provide the rationale to further investigate, in prospective studies, the potential use of blood DNA methylation profiles for the identification of early changes related to the MPM carcinogenic process.}, }
@article {pmid30401981, year = {2019}, author = {Matsushita, A and Sato, T and Mukai, S and Fujishita, T and Mishiro-Sato, E and Okuda, M and Aoki, M and Hasegawa, Y and Sekido, Y}, title = {TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation.}, journal = {Oncogene}, volume = {38}, number = {11}, pages = {1966-1978}, pmid = {30401981}, issn = {1476-5594}, support = {25090053//Japan Society for the Promotion of Science (JSPS)/International ; 16H04706//Japan Society for the Promotion of Science (JSPS)/International ; 17K19628//Japan Society for the Promotion of Science (JSPS)/International ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*genetics ; Cytokines/*genetics/metabolism ; Epithelium/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics/metabolism ; Lung Neoplasms/*genetics/metabolism/pathology ; Mesothelioma/*genetics/metabolism/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; Protein-Serine-Threonine Kinases/*genetics/metabolism ; Signal Transduction/genetics ; Trans-Activators ; Transcription Factors/*genetics/metabolism ; Transcriptional Activation ; }, abstract = {Malignant mesothelioma (MM) constitutes a very aggressive tumor that is caused by asbestos exposure after long latency. The NF2 tumor suppressor gene is mutated in 40-50% of MM; moreover, one of its downstream signaling cascades, the Hippo signaling pathway, is also frequently inactivated in MM cells. Although the YAP transcriptional coactivator, which is regulated by the Hippo pathway, can function as a pro-oncogenic protein, the role of TAZ, a paralog of YAP, in MM cells has not yet been clarified. Here, we show that TAZ is expressed and underphosphorylated (activated) in the majority of MM cells compared to immortalized mesothelial cells. ShRNA-mediated TAZ knockdown highly suppressed cell proliferation, anchorage-independent growth, cell motility, and invasion in MM cells harboring activated TAZ. Conversely, transduction of an activated form of TAZ in immortalized mesothelial cells enhanced these in vitro phenotypes and conferred tumorigenicity in vivo. Microarray analysis determined that activated TAZ most significantly enhanced the transcription of genes related to &quot;cytokine-cytokine receptor interaction.&quot; Among selected cytokines, we found that IL-1 signaling activation plays a major role in proliferation in TAZ-activated MM cells. Both IL1B knockdown and an IL-1 receptor antagonist significantly suppressed malignant phenotypes of immortalized mesothelial cells and MM cells with activated TAZ. Overall, these results indicate an oncogenic role for TAZ in MMs via transcriptional induction of distinct pro-oncogenic genes including cytokines. Among these, IL-1 signaling appears as one of the most important cascades, thus potentially serving as a target pathway in MM cells harboring Hippo pathway inactivation.}, }
@article {pmid30376426, year = {2018}, author = {Pastorino, S and Yoshikawa, Y and Pass, HI and Emi, M and Nasu, M and Pagano, I and Takinishi, Y and Yamamoto, R and Minaai, M and Hashimoto-Tamaoki, T and Ohmuraya, M and Goto, K and Goparaju, C and Sarin, KY and Tanji, M and Bononi, A and Napolitano, A and Gaudino, G and Hesdorffer, M and Yang, H and Carbone, M}, title = {A Subset of Mesotheliomas With Improved Survival Occurring in Carriers of BAP1 and Other Germline Mutations.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {}, number = {}, pages = {JCO2018790352}, pmid = {30376426}, issn = {1527-7755}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA111295/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: We hypothesized that four criteria could help identify malignant mesotheliomas (MMs) most likely linked to germline mutations of BAP1 or of other genes: family history of MM, BAP1-associated cancers, or multiple malignancies; or age younger than 50 years.<br><br>PATIENTS AND METHODS: Over the course of 7 years, 79 patients with MM met the four criteria; 22 of the 79 (28%) reported possible asbestos exposure. They were screened for germline BAP1 mutations by Sanger sequencing and by targeted next-generation sequencing (tNGS) for germline mutations in 55 additional cancer-linked genes. Deleterious mutations detected by tNGS were validated by Sanger sequencing.<br><br>RESULTS: Of the 79 patients, 43 (16 probands and 27 relatives) had deleterious germline BAP1 mutations. The median age at diagnosis was 54 years and median survival was 5 years. Among the remaining 36 patients with no BAP1 mutation, median age at diagnosis was 45 years, median survival was 9 years, and 12 had deleterious mutations of additional genes linked to cancer. When compared with patients with MMs in the SEER cohort, median age at diagnosis (72 years), median survival for all MM stages (8 months), and stage I (11 months) were significantly different from the 79 patients with MM in the current study (P < .0001).<br><br>CONCLUSION: We provide criteria that help identify a subset of patients with MM who had significantly improved survival. Most of these patients were not aware of asbestos exposure and carried either pathogenic germline mutations of BAP1 or of additional genes linked to cancer, some of which may have targeted-therapy options. These patients and their relatives are susceptible to development of additional cancers; therefore, genetic counseling and cancer screening should be considered.}, }
@article {pmid30375909, year = {2019}, author = {Laaksonen, S and Ilonen, I and Kuosma, E and Sutinen, E and Wolff, H and Vehmas, T and Husgafvel-Pursiainen, K and Salo, JA and Koli, K and Räsänen, J and Myllärniemi, M}, title = {Malignant pleural mesothelioma in Finland: regional and gender variation.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {58}, number = {1}, pages = {38-44}, doi = {10.1080/0284186X.2018.1532599}, pmid = {30375909}, issn = {1651-226X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Finland/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Registries ; Sex Distribution ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare occupational cancer with a poor prognosis. Even with a multimodality treatment approach, the treatment outcomes remain unsatisfactory. The use of asbestos has been banned in most developed countries, but MPM continues to be a significant occupational disease also in these countries. Aim of this study is to identify modern epidemiology and assess equality in care.<br><br>METHODS: Our study cohort consists of 1010 patients diagnosed with MPM in Finland during 2000-2012. The data were collected from the Finnish Cancer Registry, the National Workers' Compensation Center Registry and the National Registry of Causes of Death, Statistics Finland.<br><br>RESULTS: Women were diagnosed a mean of 4.5 years later than males (p = .001), but survival did not differ (overall median survival 9.7 months). A workers' compensation claim was more common in males (OR 11.0 [95% CI 7.5-16.2]) and in regions with a major asbestos industry (OR 1.7 [95% CI 1.3-2.2]). One-year and three-year survivals did not differ regionally. Patients without chemotherapy treatment had an inferior survival (RR 1.8 [95% CI 1.5-2.0]). The initial survival benefit gained with pemetrexed was diluted at 51 months.<br><br>CONCLUSIONS: MPM is a disease with a poor prognosis, although chemotherapy appears to improve survival time. Significant gender and regional variation exists among patients, with notable differences in diagnostic and treatment practices. Long-term outcomes with pemetrexed remain indeterminate.<br><br>IMPACT: Emphasize centralized consult services for the diagnosis, treatment and support that patients receive for MPM, facilitating equal outcomes and compensation.}, }
@article {pmid30370748, year = {2018}, author = {Algranti, E and Giannasi, F and Sousa Santana, V}, title = {[The fight for the asbestos ban in Brazil and the 2nd International seminar &quot;Brazil without asbestos&quot;].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {5-6}, pages = {388-390}, doi = {10.19191/EP18.5-6.P388.115}, pmid = {30370748}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; Asbestosis/*prevention &amp; control ; Brazil ; Congresses as Topic ; Construction Materials/standards/statistics &amp; numerical data ; Environmental Policy/*legislation &amp; jurisprudence ; *Environmental Pollutants/toxicity ; Environmental Pollution/legislation &amp; jurisprudence/*prevention &amp; control ; Flame Retardants/toxicity ; Humans ; Mesothelioma/etiology/prevention &amp; control ; Occupational Health/legislation &amp; jurisprudence ; Pleural Neoplasms/etiology/prevention &amp; control ; }, }
@article {pmid30370160, year = {2018}, author = {Plato, N and Martinsen, JI and Kjaerheim, K and Kyyronen, P and Sparen, P and Weiderpass, E}, title = {Mesothelioma in Sweden: Dose-Response Analysis for Exposure to 29 Potential Occupational Carcinogenic Agents.}, journal = {Safety and health at work}, volume = {9}, number = {3}, pages = {290-295}, pmid = {30370160}, issn = {2093-7911}, abstract = {Background: There is little information on the dose-response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma.<br><br>Methods: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961-2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratios and 95% confidence intervals.<br><br>Results: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25-2.0 fb/ml but also a clear dose-response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix.<br><br>Conclusion: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.}, }
@article {pmid30366103, year = {2019}, author = {Harris, EJA and Kao, S and McCaughan, B and Nakano, T and Kondo, N and Hyland, R and Nowak, AK and de Klerk, NH and Brims, FJH}, title = {Prediction modelling using routine clinical parameters to stratify survival in Malignant Pleural Mesothelioma patients undergoing cytoreductive surgery.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {288-293}, doi = {10.1016/j.jtho.2018.10.005}, pmid = {30366103}, issn = {1556-1380}, mesh = {Aged ; Anemia/blood ; Chest Pain/etiology ; Cytoreduction Surgical Procedures ; Dyspnea/etiology ; Female ; Health Status Indicators ; Hemoglobins/metabolism ; Humans ; Male ; Mesothelioma/blood/complications/pathology/*surgery ; Middle Aged ; *Models, Statistical ; Pleural Neoplasms/blood/complications/pathology/*surgery ; Risk Assessment/methods ; Risk Factors ; Serum Albumin/metabolism ; Survival Rate ; Weight Loss ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.<br><br>METHODS: Data were collected from subjects undergoing cytoreductive surgery for MPM from specialist centers in Hyõgo, Japan, and Sydney, Australia, between 1991 and 2016. The CART model was applied using the combination of clinical variables to stratify subjects into risk groups (1 through 4); survival characteristics were then compared.<br><br>RESULTS: Two hundred eighty-nine cases were included (205 from Australia, 84 from Japan). Overall median survival was 34.6 (interquartile range: 17.5-56.1) months; median age was 63.0 (interquartile range: 57.0-67.8) years, and 83.0% (n = 240) were male. There were no clinically meaningful differences between the two cohorts. Survival across the four risk groups was significantly different (p < 0.0001); the model stratified survival well with a Harrell's concordance statistic of 0.62 (95% confidence interval: 0.57-0.66) at 36 months. The group with the longest survival (median, 82.5 months) had: no weight loss, hemoglobin > 153 g/L and serum albumin > 43 g/L at time of referral to the surgical center.<br><br>CONCLUSIONS: Using routinely available clinical variables, the CART model was able to stratify surgical patients into risk groups with statistically different survival characteristics with fair to good performance. Presence of weight loss, anemia, and low albumin should confer caution when considering surgical therapy for MPM.}, }
@article {pmid30362690, year = {2018}, author = {Trenti, E and Palermo, SM and D'Elia, C and Comploj, E and Pycha, A and Carella, R and Pycha, A}, title = {Malignant mesothelioma of tunica vaginalis testis: Report of a very rare case with review of the literature.}, journal = {Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica}, volume = {90}, number = {3}, pages = {212-214}, doi = {10.4081/aiua.2018.3.212}, pmid = {30362690}, issn = {1124-3562}, mesh = {Adult ; Follow-Up Studies ; Frozen Sections ; Humans ; Lung Neoplasms/*diagnosis/pathology/surgery ; Lymph Node Excision ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Mesothelioma, Malignant ; Prognosis ; Testicular Hydrocele/*surgery ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: Mesothelioma of the tunica vaginalis testis is a extremely rare tumor and represents 0.3 to 0.5% of all malignant mesotheliomas. Exposure to asbestos often precedes illness. Because of its low incidence and nonspecific clinical presentation, it is mostly diagnosed accidentally during surgery for other reasons and the prognosis is usually poor. We present a case of a patient with a mesothelioma of tunica vaginalis testis, diagnosed secondarily during hydrocele surgery, with long-term survival after radical surgery.<br><br>MATERIALS AND METHODS: a 40 years old patient was admitted to our department for routine surgery of a left hydrocele. During the operation a frozen section analysis was requested because of the unusual nodular thickening of the tunica vaginalis: the examination revealed a diffuse malignant mesothelioma with epithelioid structure and tubular-papillary proliferation. Therefore a left hemi-scrotectomy with left inguinal lymph node dissection was performed.<br><br>RESULTS: The definitive histology confirmed the previous report of diffuse malignant mesothelioma with angio-invasion but normal testicle findings and negative lymph nodes. No metastases were found on the CT-scan. For the first 2 years a CT was repeated every 4 months, for other 3 years every 6 months and then yearly. Six years after surgery the patient is classified as no evidence of disease.<br><br>CONCLUSIONS: malignant mesothelioma of the tunica vaginalis testis is a rare entity, often initially thought to be a hydrocele or an epididymal cyst. An aggressive approach with hemiscrotectomy with or without inguinal and retroperitoneal lymphadenectomy can reduce the risk of recurrence.}, }
@article {pmid30362153, year = {2019}, author = {Matboli, M and Shafei, AE and Ali, MA and Gaber, AI and Galal, A and Tarek, O and Marei, M and Khairy, E and El-Khazragy, N and Anber, N and Abdel-Rahman, O}, title = {Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma.}, journal = {Journal of cellular biochemistry}, volume = {120}, number = {3}, pages = {3203-3211}, doi = {10.1002/jcb.27586}, pmid = {30362153}, issn = {1097-4644}, mesh = {Cerebroside-Sulfatase/*blood ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Linear Models ; Lung Neoplasms/*blood ; Male ; Membrane Proteins/*blood ; Mesothelioma/*blood ; Mesothelioma, Malignant ; MicroRNAs/*blood ; Pleural Neoplasms/*blood ; RNA, Long Noncoding/*blood ; Real-Time Polymerase Chain Reaction ; }, abstract = {AIM AND BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM.<br><br>METHODS: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A (ARSA) gene expression with their epigenetic regulators microRNA (miR-2053) and long noncoding RNA (lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed.<br><br>RESULTS: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM.<br><br>CONCLUSION: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.}, }
@article {pmid30357666, year = {2018}, author = {Pascotto, E and Gianoncelli, A and Calligaro, C and Marcuzzo, T and Melato, M and Rizzardi, C and Pascolo, L}, title = {Ferruginous bodies resolved by synchrotron XRF in a dog with peritoneal malignant mesothelioma.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {35}, pages = {35707-35714}, pmid = {30357666}, issn = {1614-7499}, mesh = {Animals ; Asbestos/toxicity ; Dogs ; Environmental Exposure/*adverse effects ; Immunohistochemistry ; Iron/analysis ; Lung/pathology ; Lung Neoplasms/diagnostic imaging/*pathology ; Male ; Mesothelioma/diagnostic imaging/*pathology ; Mesothelioma, Malignant ; Peritoneal Neoplasms/diagnostic imaging/*pathology ; Silicon/analysis ; Spectrometry, X-Ray Emission ; Synchrotrons ; }, abstract = {Mesothelioma is a malignant tumor mainly correlated to occupational asbestos exposure. Rare reports describe its occurrence also in animals, mainly linked to asbestos in the environment. Asbestos exposure is demonstrated by the appearance of characteristic histological hallmarks: asbestos containing ferruginous bodies that are iron-based structures forming around fibers and also other dust particles. Here we present a clinical case of a suspect of mesothelioma in the peritoneum of a dog with parallel histological observation of ferruginous bodies. To possibly correlate the dog tumor to environmental exposure, we performed X-ray fluorescence (XRF) analyses at two different synchrotrons to resolve the ferruginous bodies' composition. While the histological examination diagnoses a tubulo-papillary mesothelioma, the XRF analyses show that ferruginous bodies contain Si particles, resembling formations of exogenous origin; however, the morphology is unlikely that of asbestos fibers. We speculate that the peritoneal mesothelioma of this dog could be related to environmental exposure to non-asbestos material.}, }
@article {pmid30357324, year = {2019}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Response to comments on 'Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure' by Farioli et al. and Oddone et al.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {490-491}, doi = {10.1093/carcin/bgy145}, pmid = {30357324}, issn = {1460-2180}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30349836, year = {2018}, author = {Ibrahim, AM and Al-Akchar, M and Obaidi, Z and Al-Johany, H}, title = {Malignant Peritoneal Mesothelioma: A Rare Cause of Ascites.}, journal = {Journal of investigative medicine high impact case reports}, volume = {6}, number = {}, pages = {2324709618807506}, pmid = {30349836}, issn = {2324-7096}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare diagnosis that presents with difficulties in diagnosis and management. This article reports a case of an 88-year-old male who presented with a 2-week history of abdominal distention and bloating. He worked at an insulation production factory between the ages of 23 and 25 years with presumed asbestos exposure. On the computed tomography scan of the abdomen/pelvis, the patient was found to have diffuse omental, peritoneal, and mesenteric nodularity with moderate to large ascites. Omental biopsy revealed MPM. The overall prognosis of MPM remains poor, with a median survival time of 12 months at the time of diagnosis. Treatment modalities offered in the United States include chemotherapy alone, cytoreductive surgery alone, or cytoreductive surgery/chemotherapy combination.}, }
@article {pmid30349716, year = {2018}, author = {Grosso, F and Roveta, A and Gallizzi, G and Belletti, M}, title = {Management of recurrent pleural mesothelioma: Successful rechallenge with nintedanib in combination with chemotherapy.}, journal = {Clinical case reports}, volume = {6}, number = {10}, pages = {2000-2004}, pmid = {30349716}, issn = {2050-0904}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm, generally caused by asbestos exposure. This case details how a patient treated with nintedanib during the LUME-Meso study was rechallenged with nintedanib. The findings highlight the benefit of nintedanib rechallenge and the potential use of continuous anti-angiogenic therapy in MPM treatment.}, }
@article {pmid30349644, year = {2018}, author = {Adhikary, G and Grun, D and Alexander, HR and Friedberg, JS and Xu, W and Keillor, JW and Kandasamy, S and Eckert, RL}, title = {Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation.}, journal = {Oncotarget}, volume = {9}, number = {77}, pages = {34495-34505}, pmid = {30349644}, issn = {1949-2553}, support = {R01 CA184027/CA/NCI NIH HHS/United States ; R01 CA211909/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, abstract = {Mesothelioma is a rare cancer of the mesothelial cell layer of the pleura, peritoneum, pericardium and tunica vaginalis. It is typically caused by asbestos, notoriously resistant to chemotherapy and generally considered incurable with a poor life expectancy. Transglutaminase 2 (TG2), a GTP binding regulatory protein, is an important cancer stem cell survival and therapy resistance factor. We show that TG2 is highly expressed in human mesothelioma tumors and in mesothelioma cancer stem cells (MCS cells). TG2 knockdown or TG2 inhibitor treatment reduces MCS cell spheroid formation, matrigel invasion, migration and tumor formation. Time to tumor first appearance is doubled in TG2 knockout cells as compared to wild-type. In addition, TG2 loss is associated with reduced expression of stemness, and epithelial mesenchymal transition markers, and enhanced apoptosis. These studies indicate that TG2 is an important MCS cell survival protein and suggest that TG2 may serve as a mesothelioma cancer stem cell therapy target.}, }
@article {pmid30338612, year = {2018}, author = {Betti, M and Aspesi, A and Ferrante, D and Sculco, M and Righi, L and Mirabelli, D and Napoli, F and Rondón-Lagos, M and Casalone, E and Vignolo Lutati, F and Ogliara, P and Bironzo, P and Gironi, CL and Savoia, P and Maffè, A and Ungari, S and Grosso, F and Libener, R and Boldorini, R and Valiante, M and Pasini, B and Matullo, G and Scagliotti, G and Magnani, C and Dianzani, I}, title = {Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes.}, journal = {Genes, chromosomes &amp; cancer}, volume = {57}, number = {11}, pages = {573-583}, doi = {10.1002/gcc.22670}, pmid = {30338612}, issn = {1098-2264}, support = {IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; 2015 IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; //Istituto Superiore di Sanità (Progetto Amianto)/International ; //Italian Institute for Genomic Medicine/International ; //Ministry of Health - Italy/International ; //Regione Piemonte/International ; GR-2011-02348356//Young Researcher/International ; 2011-02348356//Young Researcher/International ; //INAIL Bric program 2016-2018/International ; }, mesh = {Adult ; Asbestos/*adverse effects ; Cohort Studies ; DNA Repair/genetics ; Environmental Exposure/*analysis ; Female ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/*genetics ; Humans ; Italy ; Male ; Mesothelioma/epidemiology/*genetics ; Middle Aged ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1-TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1-TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5-year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer-predisposing genes. We report here a new pathogenic germline variant in BAP1: c.783 + 2 T > C. The prevalence of pathogenic germline variants in BAP1 was 7.7% among patients with familial MPM (3/39). Patients with pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes showed lower cumulative asbestos exposure than patients without germline variants in 94 cancer-predisposing genes (P = .00002). This suggests an interaction between genetic risk factors and asbestos in the development of mesothelioma.}, }
@article {pmid30321262, year = {2018}, author = {Brentisci, C and Gangemi, M and Migliore, E and Mirabelli, D and Stura, A}, title = {Comment on 'Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {29}, number = {12}, pages = {2395-2396}, doi = {10.1093/annonc/mdy463}, pmid = {30321262}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30319235, year = {2018}, author = {Jargin, SV}, title = {Asbestos and Mesothelioma: A Comment.}, journal = {Indian journal of occupational and environmental medicine}, volume = {22}, number = {2}, pages = {113-114}, pmid = {30319235}, issn = {0973-2284}, }
@article {pmid30317900, year = {2018}, author = {Duke, KS and Thompson, EA and Ihrie, MD and Taylor-Just, AJ and Ash, EA and Shipkowski, KA and Hall, JR and Tokarz, DA and Cesta, MF and Hubbs, AF and Porter, DW and Sargent, LM and Bonner, JC}, title = {Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes.}, journal = {Nanotoxicology}, volume = {12}, number = {9}, pages = {975-991}, pmid = {30317900}, issn = {1743-5404}, support = {CC999999//Intramural CDC HHS/United States ; P30 ES025128/ES/NIEHS NIH HHS/United States ; R01 ES020897/ES/NIEHS NIH HHS/United States ; T32 ES007046/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Dose-Response Relationship, Drug ; Granuloma, Respiratory Tract/*chemically induced/genetics/immunology ; Inhalation Exposure ; Lung/*drug effects/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nanotubes, Carbon/*chemistry/*toxicity ; Surface Properties ; Tertiary Lymphoid Structures/*chemically induced/genetics/immunology ; Tumor Suppressor Protein p53/genetics/*physiology ; }, abstract = {The fiber-like shape of multi-walled carbon nanotubes (MWCNTs) is reminiscent of asbestos, suggesting they pose similar health hazards when inhaled, including pulmonary fibrosis and mesothelioma. Mice deficient in the tumor suppressor p53 are susceptible to carcinogenesis. However, the chronic pathologic effect of MWCNTs delivered to the lungs of p53 heterozygous (p53+/-) mice has not been investigated. We hypothesized that p53+/- mice would be susceptible to lung tumor development after exposure to either tangled (t-) or rod-like (r-) MWCNTs. Wild-type (p53+/+) or p53+/- mice were exposed to MWCNTs (1 mg/kg) via oropharyngeal aspiration weekly over four consecutive weeks and evaluated for cellular and pathologic outcomes 11-months post-initial exposure. No lung or pleural tumors were observed in p53+/+ or p53+/- mice exposed to either t- or rMWCNTs. In comparison to tMWCNTs, the rMWCNTs induced the formation of larger granulomas, a greater number of lymphoid aggregates and greater epithelial cell hyperplasia in terminal bronchioles in both p53+/- and p53+/+ mice. A constitutively larger area of CD45R+/CD3+ lymphoid tissue was observed in p53+/- mice compared to p53+/+ mice. Importantly, p53+/- mice had larger granulomas induced by rMWCNTs as compared to p53+/+ mice. These findings indicate that a combination of p53 deficiency and physicochemical characteristics including nanotube geometry are factors in susceptibility to MWCNT-induced lymphoid infiltration and granuloma formation.}, }
@article {pmid30316650, year = {2018}, author = {Fournel, L and Janet-Vendroux, A and Canny-Hamelin, E and Mansuet-Lupo, A and Guinet, C and Bobbio, A and Damotte, D and Alifano, M}, title = {[Malignant pleural mesothelioma: The role of surgery].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {5}, pages = {351-358}, doi = {10.1016/j.pneumo.2018.09.006}, pmid = {30316650}, issn = {1776-2561}, mesh = {Chemotherapy, Adjuvant ; Combined Modality Therapy ; Humans ; Lung Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Mesothelioma/diagnosis/drug therapy/radiotherapy/*surgery ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Pneumonectomy ; Radiotherapy, Adjuvant ; Thoracic Surgical Procedures/*methods ; Thoracoscopy ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease, whose incidence is increasing. Asbestos is the primary causal agent.<br><br>STATE OF KNOWLEDGE: Knowledge about MPM has evolved. Thoracoscopy is essential for diagnosis of MPM. It allows performing pleural biopsies, to study the extent of the disease and to relieve dyspnea. The pathological diagnosis is also better codified with immunohistochemistry and with analysis by expert of Mesopath group. Curative surgical treatments are pleurectomy decortication and extended pneumonectomy in combination with chemotherapy and/or radiotherapy. Those heavy treatments improve survival in highly selected patients. For the other patients, supportive measures will be considered to reduce pain and dyspnea.<br><br>PROSPECT: Radical surgical treatment is only offered in therapeutic trials or multimodal treatment. Its place is not formally established. New therapies associated to surgical treatment are being studied.<br><br>CONCLUSIONS: Surgical management of MPM has to be operated in specialized teams where the survival benefit and quality of life is discussed case by case.}, }
@article {pmid30316012, year = {2019}, author = {Mansfield, AS and Peikert, T and Smadbeck, JB and Udell, JBM and Garcia-Rivera, E and Elsbernd, L and Erskine, CL and Van Keulen, VP and Kosari, F and Murphy, SJ and Ren, H and Serla, VV and Schaefer Klein, JL and Karagouga, G and Harris, FR and Sosa, C and Johnson, SH and Nevala, W and Markovic, SN and Bungum, AO and Edell, ES and Dong, H and Cheville, JC and Aubry, MC and Jen, J and Vasmatzis, G}, title = {Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {276-287}, pmid = {30316012}, issn = {1556-1380}, support = {K12 CA090628/CA/NCI NIH HHS/United States ; }, mesh = {Antigens/*genetics ; *Chromothripsis ; Clonal Selection, Antigen-Mediated ; Computer Simulation ; DNA, Neoplasm/analysis ; Gene Dosage ; Gene Rearrangement ; Genomics ; HLA-A Antigens/genetics ; HLA-B Antigens/genetics ; Humans ; Lymphocytes, Tumor-Infiltrating ; Mesothelioma/*genetics/pathology ; Peptides/genetics/immunology ; Pleural Neoplasms/*genetics/pathology ; Receptors, Antigen, T-Cell/genetics ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA ; Survival Rate ; T-Lymphocytes/immunology ; Transcriptome/*genetics ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy.<br><br>METHODS: We used mate-pair (n = 22), RNA (n = 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome.<br><br>RESULTS: We observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival.<br><br>CONCLUSIONS: Our findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies.}, }
@article {pmid30312759, year = {2019}, author = {Toyokuni, S}, title = {Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention.}, journal = {Free radical biology &amp; medicine}, volume = {133}, number = {}, pages = {206-215}, doi = {10.1016/j.freeradbiomed.2018.10.401}, pmid = {30312759}, issn = {1873-4596}, mesh = {Animals ; Asbestos/toxicity ; Carcinogenesis/chemically induced/*genetics/pathology ; Ferroptosis/*genetics ; Humans ; Iron/*metabolism ; Iron Overload/chemically induced/genetics/metabolism/pathology ; Lung Neoplasms/chemically induced/*metabolism/pathology ; Mesothelioma/chemically induced/*metabolism/pathology ; Mesothelioma, Malignant ; Nanotubes, Carbon/toxicity ; Rats ; Transferrin/metabolism ; }, abstract = {Cancer is the primary cause of human mortality in most countries. This tendency has increased as various medical therapeutics have advanced, which suggests that we cannot escape carcinogenesis, although the final outcome may be modified by exposomes and statistics. Cancer is classified by its cellular differentiation. Mesothelial cells are distinct in that they line somatic cavities, facilitating the smooth movement of organs, but are not exposed to the external environment. Malignant mesothelioma, or simply mesothelioma, develops either in the pleural, peritoneal or pericardial cavities, or in the tunica vaginalis testes. Mesothelioma has been a relatively rare cancer but is socially important due to its association with asbestos exposure, caused by modern industrial development. The major pathogenic mechanisms include oxidative stress either via catalytic reactions against the asbestos surface or frustrated phagocytosis of macrophages, and specific adsorption of hemoglobin and histones by asbestos fibers in the presence of phagocytic activity of mesothelial cells. Multiwall carbon nanotubes of ~50 nm-diameter, additionally adsorbing transferrin, are similarly carcinogenic to mesothelial cells in rodents and were thus classified as Group 2B carcinogens. Genetic alterations found in human and rat mesothelioma notably contain changes found in other excess iron-induced carcinogenesis models. Phlebotomy and iron chelation therapies have been successful in the prevention of mesothelioma in rats. Alternatively, loading of oxidative stress by non-thermal plasma to mesothelioma cells causes ferroptosis. Therefore, carcinogenesis by foreign fibrous inorganic materials may overlap the uncovered molecular mechanisms of birth of life and its evolution.}, }
@article {pmid30309369, year = {2018}, author = {Smeele, P and d'Almeida, SM and Meiller, C and Chéné, AL and Liddell, C and Cellerin, L and Montagne, F and Deshayes, S and Benziane, S and Copin, MC and Hofman, P and Le Pimpec-Barthes, F and Porte, H and Scherpereel, A and Grégoire, M and Jean, D and Blanquart, C}, title = {Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis.}, journal = {Molecular cancer}, volume = {17}, number = {1}, pages = {148}, pmid = {30309369}, issn = {1476-4598}, mesh = {Biomarkers, Tumor ; Brain-Derived Neurotrophic Factor/*blood/genetics ; Gene Expression ; Humans ; Lung Neoplasms/*blood/genetics/mortality/*pathology ; Mesothelioma/*blood/genetics/mortality/*pathology ; Mesothelioma, Malignant ; Neovascularization, Pathologic/*blood ; Pleural Effusion, Malignant/genetics/metabolism ; Pleural Neoplasms/*blood/genetics/mortality/*pathology ; Prognosis ; RNA, Messenger/genetics ; ROC Curve ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.}, }
@article {pmid30309285, year = {2018}, author = {Funahashi, S and Okazaki, Y and Nishiyama, T and Ohyoshi, H and Yasui, H and Nishida, K and Matsui, S and Toyokuni, S}, title = {Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice.}, journal = {Free radical research}, volume = {52}, number = {9}, pages = {1030-1039}, doi = {10.1080/10715762.2018.1514604}, pmid = {30309285}, issn = {1029-2470}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Carcinogenesis/drug effects/*genetics ; Cation Transport Proteins/*genetics ; Epithelial Cells ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Iron ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mesothelioma, Malignant ; Mice ; Mice, Transgenic ; }, abstract = {Exposure to asbestos fiber is central to mesothelial carcinogenesis, for which iron overload in or near mesothelial cells is a key pathogenic mechanism. Alternatively, iron chelation therapy with deferasirox or regular phlebotomy was significantly preventive against crocidolite-induced mesothelial carcinogenesis in rats. However, the role of iron transporters during asbestos-induced carcinogenesis remains elusive. Here, we studied the role of divalent metal transporter 1 (DMT1; Slc11a2), which is a Fe(II) transporter, that is present not only on the apical plasma membrane of duodenal cells but also on the lysosomal membrane of every cell, in crocidolite-induced mesothelial carcinogenesis using DMT1 transgenic (DMT1Tg) mice. DMT1Tg mice show mucosal block of iron absorption without cancer susceptibility under normal diet. We unexpectedly found that superoxide production was significantly decreased upon stimulation with crocidolite both in neutrophils and macrophages of DMT1Tg mice, and the macrophage surface revealed higher iron content 1 h after contact with crocidolite. Intraperitoneal injection of 3 mg crocidolite ultimately induced malignant mesothelioma in ∼50% of both wild-type and DMT1Tg mice (23/47 and 14/28, respectively); this effect was marginally (p = 0.069) delayed in DMT1Tg mice, promoting survival. The promotional effect of nitrilotriacetic acid was limited, and the liver showed significantly higher iron content both in DMT1Tg mice and after crocidolite exposure. The results indicate that global DMT1 overexpression causes decreased superoxide generation upon stimulation in inflammatory cells, which presumably delayed the promotional stage of crocidolite-induced mesothelial carcinogenesis. DMT1Tg mice with low-stamina inflammatory cells may be helpful to evaluate the involvement of inflammation in various pathologies.}, }
@article {pmid30301262, year = {2018}, author = {Sarun, KH and Lee, K and Williams, M and Wright, CM and Clarke, CJ and Cheng, NC and Takahashi, K and Cheng, YY}, title = {Genomic Deletion of BAP1 and CDKN2A Are Useful Markers for Quality Control of Malignant Pleural Mesothelioma (MPM) Primary Cultures.}, journal = {International journal of molecular sciences}, volume = {19}, number = {10}, pages = {}, pmid = {30301262}, issn = {1422-0067}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*standards ; Cell Line, Tumor ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/*genetics ; Gene Deletion ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Mesothelioma, Malignant ; Middle Aged ; Primary Cell Culture/methods/*standards ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a deadly cancer that is caused by asbestos exposure and that has limited treatment options. The current standard of MPM diagnosis requires the testing of multiple immunohistochemical (IHC) markers on formalin-fixed paraffin-embedded tissue to differentiate MPM from other lung malignancies. To date, no single biomarker exists for definitive diagnosis of MPM due to the lack of specificity and sensitivity; therefore, there is ongoing research and development in order to identify alternative biomarkers for this purpose. In this study, we utilized primary MPM cell lines and tested the expression of clinically used biomarker panels, including CK8/18, Calretinin, CK 5/6, CD141, HBME-1, WT-1, D2-40, EMA, CEA, TAG72, BG8, CD15, TTF-1, BAP1, and Ber-Ep4. The genomic alteration of CDNK2A and BAP1 is common in MPM and has potential diagnostic value. Changes in CDKN2A and BAP1 genomic expression were confirmed in MPM samples in the current study using Fluorescence In situ Hybridization (FISH) analysis or copy number variation (CNV) analysis with digital droplet PCR (ddPCR). To determine whether MPM tissue and cell lines were comparable in terms of molecular alterations, IHC marker expression was analyzed in both sample types. The percentage of MPM biomarker levels showed variation between original tissue and matched cells established in culture. Genomic deletions of BAP1 and CDKN2A, however, showed consistent levels between the two. The data from this study suggest that genomic deletion analysis may provide more accurate biomarker options for MPM diagnosis.}, }
@article {pmid30300743, year = {2019}, author = {White, R and Pulford, E and Elliot, DJ and Thurgood, LA and Klebe, S}, title = {Quantitative mass spectrometry to identify protein markers for diagnosis of malignant pleural mesothelioma.}, journal = {Journal of proteomics}, volume = {192}, number = {}, pages = {374-382}, doi = {10.1016/j.jprot.2018.09.018}, pmid = {30300743}, issn = {1876-7737}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Disease-Free Survival ; Female ; Humans ; Male ; Mass Spectrometry ; *Mesothelioma/metabolism/mortality ; Middle Aged ; Neoplasm Proteins/*metabolism ; *Pleural Effusion, Malignant/metabolism/mortality ; Survival Rate ; Vascular Endothelial Growth Factor A/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is a devastating malignancy with a prognosis of <12 months. Even with bans on the use of asbestos in most Western countries, the incidence is still increasing due to the long latency periods between exposure and development of the disease. Diagnosis is often delayed due to invasive biopsies and lack of distinguishable markers. Patients frequently present with pleural effusions months to years before a radiologically detectable mass appears. This study aimed to investigate the proteome of pleural effusions taken from patients with MPM, adenocarcinoma and benign conditions in an attempt to identify a biomarker for early diagnosis. We identified several proteins that may be possible targets and warrant further investigation. Due to the predominance of up regulated proteins involved in VEGF signalling in MPM, we analysed VEGFA levels in effusions and found a strong correlation between VEGFA levels and survival in MPM.}, }
@article {pmid30296019, year = {2018}, author = {Behrens, MA}, title = {Asbestos Trust Transparency.}, journal = {Fordham law review}, volume = {87}, number = {1}, pages = {107-124}, pmid = {30296019}, issn = {0015-704X}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Asbestosis/etiology ; Bankruptcy ; Humans ; Liability, Legal/*economics ; Mesothelioma/etiology ; Occupational Exposure/*legislation &amp; jurisprudence ; *Truth Disclosure ; United States ; }, }
@article {pmid30293912, year = {2018}, author = {Mlika, M and Lamzirbi, O and Limam, M and Mejri, N and Ben Saad, S and Chaouch, N and Ben Miled, K and Marghli, A and Mezni, F}, title = {[Clinical and pathological profile of the pleural malignant mesothelioma: A retrospective study about 30 cases].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {6}, pages = {427-435}, doi = {10.1016/j.pneumo.2018.06.004}, pmid = {30293912}, issn = {1776-2561}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/diagnosis/*epidemiology/pathology ; Male ; Mesothelioma/diagnosis/*epidemiology/pathology ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/diagnosis/*epidemiology/pathology ; Retrospective Studies ; Tunisia/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: The malignant pleural mesothelioma (MPM) is a rare tumour usually associated to asbestos exposure. The delay between the exposure and the occurrence of the cancer can reach 40 years. This caused the pick of incidence described in many countries including Tunisia. The diagnosis is suspected based on clinical features but positive diagnosis is microscopic. Our aim was to describe the clinical and microscopic features of MPM through a single institution experience.<br><br>PATIENTS AND METHODS: We conducted a retrospective study about 30 MPM diagnosed over a 20-year-period (1995-2015). We included only patients with complete records including clinical, radiologic and microscopic features. All the microscopic diagnoses were reviewed by 2 pathologists. A mean of 12 slides per case was reviewed. The diagnosis was based on the 2015 WHO classification.<br><br>RESULTS: The mean age of the patients was 61 years, average 22 to 80 years. The sex ratio was 6,5. An asbetose exposition was reported in 21 cases. The most frequent symptoms was chest pain reported in 25 cases. Physical exam was normal in 9 cases. It revealed pleural syndorm in most patients (60 %). Imaging findings consisted mainly in diffuse pleural thickening in 17 cases. Twelve tumours were classified as stage I, 3 stage II, 14 stage III et 1 stage IV. Pleural biopsy was performed using needle in 18 cases, through thoracoscopy in 16 cases, thoracotomy in 3 cases and allowed the diagnosis in respectively 7 cases/18, 16 cases/16 and 3 cases/3. A lymph node biopsy was performed through mediastinoscopy in one case and yelded the diagnosis. The diagnosis was performed on surgical specimen in 2 patients: one bullectomy and one right upper lobectomy. The microscopic exam concluded to an EM in 17 cases, sarcomatoid mesothelioma (SM) in 4 cases and biphasic mesothelioma (BM) in 9 cases. Pan-cytokeratin antibody was used in all cases in association with 2 antibodies with positive diagnostic value and 2 antibodies with negative diagnostic value. It was repeated in 15 cases and the most used antibodies were the anti-calretinin and the TTF1. This was due to the lack of fixation in one case and in order to reach a quality criteria in the other cases. Surgical resection was possible in 2 patients. 15 patients were lost of view after a mean follow-up period of 3 months. Thirteen patients died before or during the follow-up.<br><br>CONCLUSION: This work was about a Tunisian experience in the diagnosis and management of MPM. The major limits faced were the incomplete databases, the small number of patients included. Microsocpic positive diagnosis necessitates a degree of expertise and every laboratory has to determine the most valuable antibodies through its experience in order to optimize the diagnosis and to reduce the delay of diagnosis.}, }
@article {pmid30293239, year = {2018}, author = {van Gerwen, M and Wolf, A and Liu, B and Flores, R and Taioli, E}, title = {Short-term outcomes of pleurectomy decortication and extrapleural pneumonectomy in mesothelioma.}, journal = {Journal of surgical oncology}, volume = {118}, number = {7}, pages = {1178-1187}, doi = {10.1002/jso.25260}, pmid = {30293239}, issn = {1096-9098}, support = {NCI CCSG P30 CA196521//National Cancer Institute/ ; }, mesh = {Aged ; Arrhythmias, Cardiac/epidemiology ; Databases, Factual ; Female ; *Hospital Mortality ; Humans ; Male ; Mesothelioma/mortality/*surgery ; Middle Aged ; New York/epidemiology ; Pleura/*surgery ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/*adverse effects ; Postoperative Complications ; Propensity Score ; }, abstract = {BACKGROUND/OBJECTIVES: We evaluated postoperative mortality and complications after extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) to better understand their effectiveness in malignant pleural mesothelioma (MPM).<br><br>METHODS: A meta-analysis was done to evaluate 30-day mortality and postoperative complications. In addition, in-patients data of 500 eligible patients with MPM who underwent EPP or P/D was extracted from the New York Statewide Planning and Research Cooperative System (SPARCS). Multivariate analyses and propensity matching were used to compare in-hospital mortality and postoperative complications in EPP vs P/D.<br><br>RESULTS: The meta-analysis showed a statistically significant difference in 30-day mortality (5% [95% CI: 4-6] vs P/D 2% [95% CI: 1-3]), proportion of complications (46% [95% CI: 36-56] vs 24% [95% CI: 15-34]) and postoperative arrhythmias (20% [95% CI: 12-31] vs 5% [95% CI: 2-8]) for EPP vs P/D. In-hospital mortality (OR adj : 2.6; 95% CI: 0.86-7.75) and postoperative complications (OR adj : 1.1; 95% CI: 0.68-1.86) were not different in EPP compared with P/D while supraventricular arrhythmia was significantly more frequent after EPP vs P/D (OR adj : 5.2; 95% CI: 2.34-11.33).<br><br>CONCLUSIONS: Postoperative mortality, postoperative complications, and particularly supraventricular arrhythmia are less frequent after P/D vs EPP. P/D, a less invasive surgery, may provide a better option when technically feasible for patients with MPM.}, }
@article {pmid30288361, year = {2018}, author = {Fear, VS and Tilsed, C and Chee, J and Forbes, CA and Casey, T and Solin, JN and Lansley, SM and Lesterhuis, WJ and Dick, IM and Nowak, AK and Robinson, BW and Lake, RA and Fisher, SA}, title = {Combination immune checkpoint blockade as an effective therapy for mesothelioma.}, journal = {Oncoimmunology}, volume = {7}, number = {10}, pages = {e1494111}, pmid = {30288361}, issn = {2162-4011}, abstract = {Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma and is now being applied to other cancers, including mesothelioma. However, the efficacy of ICPB and which immune checkpoint combinations constitute the best therapeutic option for mesothelioma have yet to be fully elucidated. Here, we used our well characterised mesothelioma tumour model to investigate the efficacy of different ICBP treatments to generate effective therapy for mesothelioma. We show that tumour resident regulatory T cell co-express high levels of CTLA-4, OX40 and GITR relative to T effector subsets and that these receptors are co-expressed on a large proportion of cells. Targeting any of CTLA-4, OX40 or GITR individually generated effective responses against mesothelioma. Furthermore, the combination of αCTLA-4 and αOX40 was synergistic, with an increase in complete tumour regressions from 20% to 80%. Other combinations did not synergise to enhance treatment outcomes. Finally, an early pattern in T cell response was predictive of response, with activation status and ICP receptor