@article {pmid35778611, year = {2022}, author = {Fennell, DA and Dulloo, S and Harber, J}, title = {Immunotherapy approaches for malignant pleural mesothelioma.}, journal = {Nature reviews. Clinical oncology}, volume = {}, number = {}, pages = {}, pmid = {35778611}, issn = {1759-4782}, abstract = {Over the past decade, immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. In mesothelioma, a rare cancer with a dismal prognosis generally caused by exposure to asbestos, treatment with single or dual ICIs results in robust improvements in overall survival over previous standard-of-care therapies, both in the first-line and relapsed disease settings. Predictive biological features that underpin response to ICIs remain poorly understood; however, insights into the immune microenvironment and genomic landscape of mesothelioma as well as into their association with response or acquired resistance to ICIs are emerging. Several studies of rational combinations involving ICIs with either another ICI or a different agent are ongoing, with emerging evidence of synergistic antitumour activity. Non-ICI-based immunotherapies, such as peptide-based vaccines and mesothelin-targeted chimeric antigen receptor T cells, have demonstrated promising efficacy. Moreover, results from pivotal trials of dendritic cell vaccines and viral cytokine delivery, among others, are eagerly awaited. In this Review, we comprehensively summarize the key steps in the development of immunotherapies for mesothelioma, focusing on strategies that have led to randomized clinical evaluation and emerging predictors of response. We then forecast the future treatment opportunities that could arise from ongoing research.}, }
@article {pmid35748766, year = {2022}, author = {Locher, BN and Barresi, F and Kuhn, BK and Vrugt, B and Bopp, M and Dressel, H}, title = {Occupations and geographical distribution of mesothelioma in Switzerland 1989-2018 - record linkage of an asbestos-exposed population with the Swiss National Cohort.}, journal = {Swiss medical weekly}, volume = {152}, number = {}, pages = {w30164}, doi = {10.4414/smw.2022.w30164}, pmid = {35748766}, issn = {1424-3997}, abstract = {OBJECTIVE: We investigated the possibility of linking the data of the Swiss Laboratory for Particle Analysis (Silag), a valuable but incomplete data source in the field of asbestos-related diseases, to the Swiss National Cohort (SNC). With the resulting comprehensive dataset, we intended to provide a source for further research in the field. We also conducted preliminary analyses of data focusing on occupations and regional distribution of malignant pleural mesothelioma cases.<br><br>METHODS: Data of asbestos-exposed individuals available from the Silag were anonymously linked with the SNC by means of deterministic record linkage. From this linkage, data on occupation classified according to the international standard classification of occupations (ISCO) as well as the canton of residence in Switzerland could be retrieved.<br><br>RESULTS: Of 838 eligible individuals from the Silag data, 788 (94.0%) could be linked to the SNC database, including 476 mesothelioma cases. In 340 cases of the latter, data on occupation and industries were available. Although the majority of them were blue-collar workers, a significant proportion (n = 44, 12.9%) had executive professions. The Canton of residence in 1990 was established in 430 of subjects with mesothelioma. A cluster could be identified in eastern Switzerland, especially in the canton of Glarus.<br><br>CONCLUSIONS: It was possible to link the datasets to a large extent thereby creating a data source for further research. Of note, the linkage provided data on occupation of a selection of mesothelioma cases in Switzerland.}, }
@article {pmid35743451, year = {2022}, author = {Nagamatsu, Y and Sakyo, Y and Barroga, E and Koni, R and Natori, Y and Miyashita, M}, title = {Depression and Complicated Grief, and Associated Factors, of Bereaved Family Members of Patients Who Died of Malignant Pleural Mesothelioma in Japan.}, journal = {Journal of clinical medicine}, volume = {11}, number = {12}, pages = {}, doi = {10.3390/jcm11123380}, pmid = {35743451}, issn = {2077-0383}, support = {16H05579, and 21H03241//Japan Society for the Promotion of Science/ ; 210901-01//Grants-in-Aid from the Ministry of Health, Labor and Welfare, Japan,/ ; }, abstract = {OBJECTIVES: we investigated the prevalence and associated factors of depression and complicated grief (CG) among bereaved family members of malignant pleural mesothelioma (MPM) patients in Japan.<br><br>METHODS: Bereaved family members of MPM patients (n = 72) were surveyed. The Japanese version of the Patient Health Questionnaire-9 (PHQ-9) and the Japanese version of the Brief Grief Questionnaire (BGQ) were used to assess depression and complicated grief (CG), respectively. Socio-economic factors, anger toward asbestos, care satisfaction, achievement of good death, and quality of end-of-life care were assessed in relation to depression and CG.<br><br>RESULTS: In the family members of MPM patients, the frequencies of depression and CG were 19.4% and 15.3%, respectively. The bereaved family members who were not compensated by the asbestos-related health-damage relief system (p = 0.018) and who felt the financial impacts of the patient's MPM on the family (p = 0.006) had a higher likelihood of depression. The bereaved family members who were not satisfied with the care given when the patient became critical (p = 0.034), who were not compensated by the asbestos-related health-damage relief system (p = 0.020), who felt the financial impact of the patient's MPM on the family (p = 0.016), and whose deceased relative underwent surgery (p = 0.030) had a higher likelihood of CG.<br><br>CONCLUSIONS: For bereaved family members of MPM patients, routine screening for depression and CG and the provision of grief care are suggested. In addition, for family members of MPM patients, financial support, including the promotion of the asbestos-related health-damage relief system, and improved care for patients who undergo surgery and when patients become critical, are recommended.}, }
@article {pmid35743417, year = {2022}, author = {Bellini, A and Mazzarra, S and Sterrantino, S and Argnani, D and Stella, F}, title = {Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {11}, number = {12}, pages = {}, doi = {10.3390/jcm11123340}, pmid = {35743417}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumour with poor prognosis. To date, a multimodality treatment, including chemotherapy and surgery, with or without radiotherapy, is the gold standard therapy for selected patients with epithelioid and early-stage MPM. In this setting, the goal of surgery is to achieve the macroscopic complete resection, obtained by either extrapleural pneumonectomy or pleurectomy/decortication. Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for the recurrence of MPM after the multimodal approach, and the role of surgery in this context is still controversial. By using electronic databases, studies that included recurrent MPM patients who underwent a second surgery were identified. The endpoints included were: a pattern of recurrence, post-recurrence survival (PRS), and the type of second surgery. When available, factors predicting better PRS and perioperative mortality and morbidity were collected. This systematic review offers an overview of the results that are currently obtained in patients undergoing a second surgery for relapsed MPM, with the aim to provide a comprehensive view on this subject that explores if a second surgery leads to an improvement in survival.}, }
@article {pmid35741021, year = {2022}, author = {Pellavio, G and Martinotti, S and Patrone, M and Ranzato, E and Laforenza, U}, title = {Aquaporin-6 May Increase the Resistance to Oxidative Stress of Malignant Pleural Mesothelioma Cells.}, journal = {Cells}, volume = {11}, number = {12}, pages = {}, doi = {10.3390/cells11121892}, pmid = {35741021}, issn = {2073-4409}, support = {2019//University of Piemonte Orientale, Italy under the initiative Ricerca Locale/ ; (2018-2022).//Department of Molecular Medicine of the University of Pavia, Italy under the initiative Dipartimenti di Eccellenza/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleural surface and is associated with previous asbestos exposure. The chemotherapy drug is one of the main treatments, but the median survival ranges from 8 to 14 months from diagnosis. The redox homeostasis of tumor cells should be carefully considered since elevated levels of ROS favor cancer cell progression (proliferation and migration), while a further elevation leads to ferroptosis. This study aims to analyze the functioning/role of aquaporins (AQPs) as a hydrogen peroxide (H2O2) channel in epithelial and biphasic MPM cell lines, as well as their possible involvement in chemotherapy drug resistance. Results show that AQP-3, -5, -6, -9, and -11 were expressed at mRNA and protein levels. AQP-6 was localized in the plasma membrane and intracellular structures. Compared to normal mesothelial cells, the water permeability of mesothelioma cells is not reduced by exogenous oxidative stress, but it is considerably increased by heat stress, making these cells resistant to ferroptosis. Functional experiments performed in mesothelioma cells silenced for aquaporin-6 revealed that it is responsible, at least in part, for the increase in H2O2 efflux caused by heat stress. Moreover, mesothelioma cells knocked down for AQP-6 showed a reduced proliferation compared to mock cells. Current findings suggest the major role of AQP-6 in providing mesothelioma cells with the ability to resist oxidative stress that underlies their resistance to chemotherapy drugs.}, }
@article {pmid35723508, year = {2022}, author = {Lee, JT and Mittal, DL and Warby, A and Kao, S and Dhillon, HM and Vardy, JL}, title = {Dying of mesothelioma: A qualitative exploration of caregiver experiences.}, journal = {European journal of cancer care}, volume = {}, number = {}, pages = {e13627}, doi = {10.1111/ecc.13627}, pmid = {35723508}, issn = {1365-2354}, support = {//Dust Diseases Board NSW/ ; }, abstract = {OBJECTIVE: To explore the experience of family caregivers of people with mesothelioma with focus on end-of-life issues.<br><br>METHODS: A qualitative sub-study using semi-structured interviews and thematic analysis.<br><br>RESULTS: Fourteen caregivers were interviewed; 11 were bereaved. The overarching theme was the impact of patients' diagnosis, treatment and death on caregivers and families. Three main themes were identified: (i) information provision and decision-making; (ii) grief and bereavement; and (iii) involvement and timing of palliative care. Caregivers initially had minimal knowledge of mesothelioma and wanted more information. Prognostic uncertainty caused distress. Grief and bereavement sub-themes were (i) coping and personal priorities; (ii) reflections on dying; and (iii) reflections on care. Caregivers highlighted the importance of creating meaningful events, having hope, 'doing something' and support from family and external sources. Reflections on dying contrasted regret after a 'bad', often unexpected death, with 'good' deaths. Care was made difficult by challenges navigating the health system and perceived gaps. Caregivers reported late referral to palliative care.<br><br>CONCLUSION: Lack of information caused challenges for caregivers. Grief and bereavement outcomes varied and may have been adversely impacted by lack of engagement with palliative care. Integrated care with lung cancer coordinators and improved palliative care access may reduce caregiver burden.}, }
@article {pmid35717324, year = {2022}, author = {Migliore, E and Consonni, D and Peters, S and Vermeulen, RCH and Kromhout, H and Baldassarre, A and Cavone, D and Chellini, E and Magnani, C and Mensi, C and Merler, E and Musti, M and Marinaccio, A and Mirabelli, D}, title = {Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM).}, journal = {Environmental health : a global access science source}, volume = {21}, number = {1}, pages = {60}, pmid = {35717324}, issn = {1476-069X}, mesh = {*Asbestos ; Case-Control Studies ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Diseases/epidemiology/etiology ; *Occupational Exposure/adverse effects ; Occupations ; *Pleural Neoplasms/epidemiology/etiology ; }, abstract = {BACKGROUND: The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases' exposures but cannot provide relative risk estimates.<br><br>OBJECTIVES: i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure-response relationship.<br><br>METHODS: A population-based mesothelioma case-control study was conducted in 2012-2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI).<br><br>RESULTS: Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16-1.42).<br><br>CONCLUSIONS: Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure-response relationship.}, }
@article {pmid35713639, year = {2022}, author = {Malpica, A and Euscher, ED and Marques-Piubelli, ML and Miranda, RN and Raghav, KP and Fournier, KF and Ramalingam, P}, title = {Localized Malignant Peritoneal Mesothelioma (LMPeM) in Women: A Clinicopathologic Study of 18 Cases.}, journal = {The American journal of surgical pathology}, volume = {}, number = {}, pages = {}, doi = {10.1097/PAS.0000000000001924}, pmid = {35713639}, issn = {1532-0979}, abstract = {Localized malignant peritoneal mesothelioma is a rare tumor with limited information in the literature. In this study, we present our experience with 18 cases seen in our hospital over a period of 43 years (1978 to 2021). Patients' median age was 55 years (y) (range: 33 to 79 y) and most of them were Caucasians. Patients presented with abdominal pain (11), ascites and right leg swelling (1), abdominal mass (1), and as incidental finding (1). Thirty percent of patients reported asbestos exposure, and all patients with available information had family history of tumors; a third had personal history of tumors. Seventy-seven percent had some form of abdominopelvic surgery and/or inflammatory process. Most cases had microscopic features typically seen in malignant mesothelioma; however, some cases had confounding features such as signet-ring cells, spindle cells, clear cell changes, and adenomatoid tumor-like appearance. BAP-1 by immunohistochemistry was lost in 1/3 cases. Only 1 patient underwent genetic testing and had an MSH2 germline mutation. Homozygous deletion of CDKN2A by FISH was not found in 1 tested case, although next-generation sequencing identified a CDKN2A pathogenic mutation. 16/18 (88%) had surgical treatment, and some also received adjuvant chemotherapy. The mean overall survival (OS) of our patients was 80.4 months (95% confidence interval: 54.3-106.52); the 3-year OS was 79%, while the 5-year OS was 52.6%. Fifty-three percent of patients had recurrences and 20% had tumor progression. Although the limited sample precludes definitive conclusions, small tumor size, low-grade cytology, and low mitotic index appeared to be associated with an indolent behavior.}, }
@article {pmid35703172, year = {2022}, author = {Bernstein, DM}, title = {The health effects of short fiber chrysotile and amphibole asbestos.}, journal = {Critical reviews in toxicology}, volume = {}, number = {}, pages = {1-24}, doi = {10.1080/10408444.2022.2056430}, pmid = {35703172}, issn = {1547-6898}, abstract = {The potential toxic effects of short chrysotile and amphibole asbestos fibers with lengths <5 to ∼10 µm have been debated over the years. This stems from the large database of epidemiology, toxicology, and in-vitro studies, each of which often provides different information in understanding and differentiating the effects of short fibers. The epidemiology studies in which the cancer potency estimates were based upon relatively high exposure concentrations provide a conservative assessment that shorter fibers would have little if any effect, especially under controlled exposure or environmental conditions that may occur today. The QSAR models have shown that fiber aspect ratio and Mg content are excellent predictors of cancer potency and that short fibers/particles of amphibole would have no effect. The studies of motor vehicle mechanics and in particular workers who serviced chrysotile containing brakes with the majority of the fibers being short provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma. Several inhalation toxicology studies clearly differentiated that short chrysotile and amphibole asbestos fibers did not produce a significant carcinogenic effect in the lung or pleural cavity. Because of dosing and lack of sensitivity to biosolubility, in vitro studies can be difficult to interpret; however, a number have differentiated short chrysotile and amphibole asbestos fibers from long fibers. Integral to understanding the importance of fiber length in determining possible health effects is an understanding of the biological and physiological function of the respiratory system. Short asbestos fibers, like innocuous dust, can be cleared through the tracheobronchial ciliated mucous transport, phagocytized by macrophages and cleared via the bronchial tree, and can also be removed through the lymphatic system. While the first two methods can remove them from the lung, with lymphatic transport through one-way valves, fibers are removed from the active area of the lung where the fiber-related disease has been shown to develop and can accumulate in lymphatic sumps and lymph nodes. While short asbestos fibers are present in most occupational or environmental exposures, the large body of studies strongly supports that they do not contribute to the health effects of asbestos exposure.}, }
@article {pmid35670855, year = {2022}, author = {Napoli, F and Rapa, I and Izzo, S and Rigutto, A and Libener, R and Riganti, C and Bironzo, P and Taulli, R and Papotti, M and Volante, M and Scagliotti, G and Righi, L}, title = {Correction to: Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00428-022-03355-y}, pmid = {35670855}, issn = {1432-2307}, }
@article {pmid35665561, year = {2022}, author = {Dermawan, JK and Torrence, D and Lee, CH and Villafania, L and Mullaney, KA and DiNapoli, S and Sukhadia, P and Benayed, R and Borsu, L and Agaram, NP and Nash, GM and Dickson, BC and Benhamida, J and Antonescu, CR}, title = {EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: report of 3 cases in support of an emerging entity.}, journal = {Genes, chromosomes &amp; cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/gcc.23074}, pmid = {35665561}, issn = {1098-2264}, abstract = {Mesothelioma is a rare, aggressive malignant neoplasm of mesothelial origin. A small subset of peritoneal mesothelioma is driven by recurrent gene fusions, mostly EWSR1/FUS::ATF1 fusions, with predilection for young adults. To date, only two cases of mesothelioma harboring EWSR1::YY1 fusions have been described. We present three additional cases of EWSR1::YY1-fused peritoneal mesotheliomas, two localized and one diffuse, all occurring in the peritoneum of middle-aged adults (2 females and 1 male), and discovered incidentally by imaging or during surgery performed for unrelated reasons. None presented with symptoms or had a known history of asbestos exposure. All three cases were cellular epithelioid neoplasms with heterogeneous architectural patterns comprising mostly solid nests and sheets with variably papillary and trabecular areas against collagenous stroma. Cytologically, the cells were monomorphic, polygonal, epithelioid cells with dense eosinophilic cytoplasm and centrally located nuclei. Overt mitotic activity or tumor necrosis was absent. All cases showed strong diffuse immunoreactivity for pancytokeratin, CK7, and nuclear WT1, patchy to negative calretinin, retained BAP1 expression, and were negative for Ber-EP4 and MOC31. RNA-sequencing confirmed in-frame gene fusion transcripts involving EWSR1 exon 7/8 and YY1 exon 2/3. By unsupervised clustering analysis, the methylation profiles of EWSR1::YY1-fused mesotheliomas clustered similarly with EWSR1/FUS::ATF1-fused mesotheliomas and conventional mesotheliomas, suggesting a mesothelioma epigenetic signature. All three patients underwent surgical resection or cytoreductive surgery of the masses. On follow-up imaging, no recurrence or progression of disease was identified. Our findings suggest that EWSR1::YY1-fusion defines a small subset of peritoneal epithelioid mesothelioma in middle-aged adults without history of asbestos exposure. This article is protected by copyright. All rights reserved.}, }
@article {pmid35664766, year = {2022}, author = {Usuda, K and Niida, Y and Ishikawa, M and Iwai, S and Yamagata, A and Iijima, Y and Motono, N and Yamada, S and Uramoto, H}, title = {Genomics of Tumor Origin and Characteristics for Adenocarcinoma and Malignant Pleural Mesothelioma: A Case Report.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {858094}, doi = {10.3389/fonc.2022.858094}, pmid = {35664766}, issn = {2234-943X}, abstract = {A female underwent a right middle lobectomy for a pulmonary adenocarcinoma (AD). She eventually died of a right malignant pleural mesothelioma (MPM; sarcomatoid type) 4 years and 7 months after the removal of the AD even though she did not have any history of asbestos exposure, smoking, or radiation exposure. Her chest CT revealed multiple pulmonary nodules and bilateral pleural effusion with a right pleural tumor directly invading into the abdominal cavity. The genomics of tumor origin and characteristics were examined for the AD and the MPM. As a result, 50 somatic variants were detected in the AD, and 29 somatic variants were detected in the MPM. The variants which were common in both the AD and the MPM were not present, which suggested that the AD and the MPM had occurred independently in different origins. The MPM had two driver oncogenes of TP53 and EP300, but the AD did not. Two driver oncogenes of TP53 and EP300 were hypothesized to make the MPM aggressive. The speed at which the MPM progressed without the patient having a history of asbestos exposure, smoking, or radiation exposure was alarming.}, }
@article {pmid35659582, year = {2022}, author = {Barbieri, PG and Consonni, D and Somigliana, A}, title = {Asbestos lung burden does not predicts survival in malignant pleural mesothelioma. A necropsy-based study of 185 cases.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2022.05.010}, pmid = {35659582}, issn = {1556-1380}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an asbestos-related disease with poor survival. The prognostic role of histological subtype is well established. Some studies (without a biological hypothesis) suggested that higher asbestos lung burden is associated with reduced survival.<br><br>OBJECTIVES: We performed a necropsy-based study of MPM patients to analyze the relationship between asbestos lung burden and survival.<br><br>METHODS: We selected subjects from two series of necropsies: residents in Brescia province (North-West Italy) and workers (or persons living with them) employed in the Monfalcone shipyards (North-East Italy). Asbestos fibers (AF) and bodies (AB) in lung samples were counted using a scanning electron and an optical microscope respectively. Separately in the two series, we analyzed median survival time and fitted multivariable Cox regression models (adjusted for gender, period and age at diagnosis, and morphology) to calculate hazard ratios (HR) and 95% confidence intervals (CI) for three levels of AF counts (reference: <1 million fibers per gram of dry lung tissue).<br><br>RESULTS: We analyzed 185 necropsies, 83 in Brescia and 102 in Monfalcone. Despite a much higher lung burden in Monfalcone patients, median survival was slightly shorter in Brescia (8.3 months) than in Monfalcone (10.2 months). In Brescia, for medium (1-9.9) and high (10+) fiber burden HRs were 0.91 (95% CI 0.54-1.53) and 1.23 (95% CI 0.41-3.70). In Monfalcone, the corresponding HRs were 1.18 (95% CI 0.59-2.35) and 1.63 (95% CI 0.77-3.45).<br><br>CONCLUSION: No relationship between asbestos lung burden and survival was found. Histological subtype was the strongest prognostic determinant.}, }
@article {pmid35650101, year = {2022}, author = {Tomita, R and Nishijo, N and Hayama, T and Fujioka, T}, title = {Discrimination of Malignant Pleural Mesothelioma Cell Lines Using Amino Acid Metabolomics with HPLC.}, journal = {Biological &amp; pharmaceutical bulletin}, volume = {45}, number = {6}, pages = {724-729}, doi = {10.1248/bpb.b21-00972}, pmid = {35650101}, issn = {1347-5215}, abstract = {Malignant pleural mesothelioma (MPM) is a malignancy closely associated with asbestos exposure. Although early diagnosis provides a chance of effective treatment and better prognosis, invasive biopsy and cytological procedure are required for definitive diagnosis. In this study, we developed a method to differentiate between MPM and control cell lines, named "amino acid metabolomics," consisting in the assessment of the balance of their amino acid levels in the cell culture medium. Culture media of MESO-1 (MPM cell line) and Met-5A (control) cells were used in this study to evaluate amino acid levels using HPLC, following the fluorescence derivatization method. The time-dependent changes in amino acid levels were visualized on the score plot following principal component analysis, and the results revealed differential changes in amino acid levels between the two cell culture supernatants. A discriminative model based on linear discriminant analysis could distinguish MPM and control cells.}, }
@article {pmid35649637, year = {2022}, author = {Johnson, M and Allmark, P and Tod, A}, title = {Living beyond expectations: a qualitative study into the experience of long-term survivors with pleural mesothelioma and their carers.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, doi = {10.1136/bmjresp-2022-001252}, pmid = {35649637}, issn = {2052-4439}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is characterised by poor prognosis and limited treatment options. However, a minority of patients can survive well beyond these bleak estimates. Little is known about the specific experiences and needs of long-term survivors and families.<br><br>STUDY PURPOSE: The study aimed to gain in-depth understanding of the experiences of patients diagnosed with MPM 3 or more years, along with their main carer, and to determine the care and support needs of this group.<br><br>PARTICIPANTS AND SETTING: People diagnosed with MPM 3 or more years were recruited via asbestos and mesothelioma social media and support groups. Potential participants were asked to identify someone who acted as their main carer.<br><br>METHOD: The study employed a cross-sectional qualitative interview design. A topic guide aided a conversational interview style, conducted remotely and recorded. Patient and carer pairs were interviewed jointly when possible, but were given an option for separate interviews if preferred. Fifteen patients, with 14 identifying a main carer, consented to participation.<br><br>ANALYSIS: Recorded interviews were transcribed verbatim, and then anonymised by the interviewer. Framework analysis was used to analyse the data iteratively and to develop final themes.<br><br>FINDINGS: Three themes were developed. Participants 'Living beyond expectations' remained acutely aware that MPM was incurable, but developed a range of coping strategies. Periods of disease stability were punctuated with crises of progression or treatment ending, straining coping. 'Accessing treatment' was important for patients and carers, despite the associated challenges. They were aware options were limited, and actively sought new treatments and clinical trials. 'Support needs' were met by healthcare professionals, voluntary groups and social media networks.<br><br>CONCLUSIONS: Managing patients via regional MPM multidisciplinary teams, facilitating equal access to treatment and trials, could reduce patient and carer burden. Greater awareness and support around crisis points for this group could improve care.}, }
@article {pmid35642773, year = {2022}, author = {Taeger, D and Wichert, K and Lehnert, M and Casjens, S and Pesch, B and Weber, DG and Brüning, T and Johnen, G and Behrens, T}, title = {Lung cancer and mesothelioma risks in a prospective cohort of workers with asbestos-related lung or pleural diseases.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23401}, pmid = {35642773}, issn = {1097-0274}, abstract = {BACKGROUND: Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos-related lung or pleural diseases.<br><br>METHODS: Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos-related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI).<br><br>RESULTS: We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57-23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98-1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51-19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76-1.41). The highest lung-cancer risk (SIR: 2.56; 95% CI 1.10-5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen.<br><br>CONCLUSIONS: Compared to the general population, we demonstrated an association between benign asbestos-related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung-cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.}, }
@article {pmid35637829, year = {2022}, author = {Rhazari, M and Moueqqit, O and Gartini, S and El Morabit, S and Diani, S and Aharmim, M and Thouil, A and Kouismi, H and El Bourkadi, JE}, title = {Unexplained Pleural Effusion Leads to the Revelation of a Malignant Mesothelioma: A Case Report.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e24478}, doi = {10.7759/cureus.24478}, pmid = {35637829}, issn = {2168-8184}, abstract = {Malignant mesothelioma is a rare and aggressive cancer that usually affects subjects with prior asbestos exposure, a major risk factor that has been widely known as carcinogenic, and its use is now controlled if not banned in many areas of the world. Malignant mesothelioma originates from mesothelial surface cells covering the serous cavities, and the pleura is its most common site. Malignant pleural mesothelioma (MPM) typically presents with pleural effusion and chest wall pain with wide pleural thickening at radiological investigation. Although the histological examination along with immunohistochemistry helps yield the diagnosis, clinicians and experts face many challenges in diagnosing malignant mesothelioma not only due to the rarity of the disease but also due to the similarities that the disease share with other malignancies. Here, we report a case of a 55-year-old male patient with a history of chronic asbestos work exposure for 12 years who initially presented with unexplained pleural effusion and chest wall pain and was lost to follow-up but came back later with a worsening clinical state. This case is specially presented to raise awareness against cases of unexplained pleural effusion and chest pain.}, }
@article {pmid35637530, year = {2022}, author = {Creaney, J and Patch, AM and Addala, V and Sneddon, SA and Nones, K and Dick, IM and Lee, YCG and Newell, F and Rouse, EJ and Naeini, MM and Kondrashova, O and Lakis, V and Nakas, A and Waller, D and Sharkey, A and Mukhopadhyay, P and Kazakoff, SH and Koufariotis, LT and Davidson, AL and Ramarao-Milne, P and Holmes, O and Xu, Q and Leonard, C and Wood, S and Grimmond, SM and Bueno, R and Fennell, DA and Pearson, JV and Robinson, BW and Waddell, N}, title = {Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma.}, journal = {Genome medicine}, volume = {14}, number = {1}, pages = {58}, pmid = {35637530}, issn = {1756-994X}, support = {APP1089404//National Health and Medical Research Council/ ; 1139071//National Health and Medical Research Council/ ; APP1108638//National Health and Medical Research Council/ ; na//Australian Government Research Training Program/ ; na//QIMR Berghofer Medical Research Institute/ ; na//Ian Potter Foundation/ ; na//The John Thomas Wilson Endowment/ ; na//Estate of Mr Stewart Coggins/ ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor overall survival with few treatment options. Whole genome sequencing (WGS) combined with the immune features of MPM offers the prospect of identifying changes that could inform future clinical trials.<br><br>METHODS: We analysed somatic mutations from 229 MPM samples, including previously published data and 58 samples that had undergone WGS within this study. This was combined with RNA-seq analysis to characterize the tumour immune environment.<br><br>RESULTS: The comprehensive genome analysis identified 12 driver genes, including new candidate genes. Whole genome doubling was a frequent event that correlated with shorter survival. Mutational signature analysis revealed SBS5/40 were dominant in 93% of samples, and defects in homologous recombination repair were infrequent in our cohort. The tumour immune environment contained high M2 macrophage infiltrate linked with MMP2, MMP14, TGFB1 and CCL2 expression, representing an immune suppressive environment. The expression of TGFB1 was associated with overall survival. A small subset of samples (less than 10%) had a higher proportion of CD8 T cells and a high cytolytic score, suggesting a 'hot' immune environment independent of the somatic mutations.<br><br>CONCLUSIONS: We propose accounting for genomic and immune microenvironment status may influence therapeutic planning in the future.}, }
@article {pmid35636988, year = {2022}, author = {Porcel, JM}, title = {Pleural mesothelioma.}, journal = {Medicina clinica}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.medcli.2022.03.007}, pmid = {35636988}, issn = {1578-8989}, abstract = {The diagnosis of diffuse pleural mesothelioma requires in most cases a pleural biopsy, performed either under imaging guidance (ultrasound or computed tomography) or thoracoscopy. Loss of BAP1 or MTAP expression (immunohistochemistry) and homozygous deletion of CDKN2A (fluorescence in situ hybridization) are the basic molecular markers for the diagnosis of mesothelioma. The histologic type and patient's performance status are the most important prognostic factors. Pleural effusion can be managed by the insertion of tunneled pleural catheters, either as a stand-alone measure (e.g., patients not amenable to multimodality therapy who have been diagnosed by pleural fluid cytology or image-guided biopsy) or combined with the administration of aerosolized talc during a diagnostic thoracoscopy. Immunotherapy is one of the front-line approaches in inoperable patients, particularly in biphasic or sarcomatous histologic varieties.}, }
@article {pmid35634282, year = {2022}, author = {Principe, N and Aston, WJ and Hope, DE and Tilsed, CM and Fisher, SA and Boon, L and Dick, IM and Chin, WL and McDonnell, AM and Nowak, AK and Lake, RA and Chee, J and Lesterhuis, WJ}, title = {Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive Combinations.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {872295}, doi = {10.3389/fimmu.2022.872295}, pmid = {35634282}, issn = {1664-3224}, abstract = {Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, objective responses only occur in a minority of patients. Chemotherapy is widely used in combination with immune checkpoint blockade (ICB). Although a variety of isolated immunostimulatory effects have been reported for several classes of chemotherapeutics, it is unclear which chemotherapeutics provide the most benefit when combined with ICB. We investigated 10 chemotherapies from the main canonical classes dosed at the clinically relevant maximum tolerated dose in combination with anti-CTLA-4/anti-PD-L1 ICB. We screened these chemo-immunotherapy combinations in two murine mesothelioma models from two different genetic backgrounds, and identified chemotherapies that produced additive, neutral or antagonistic effects when combined with ICB. Using flow cytometry and bulk RNAseq, we characterized the tumor immune milieu in additive chemo-immunotherapy combinations. 5-fluorouracil (5-FU) or cisplatin were additive when combined with ICB while vinorelbine and etoposide provided no additional benefit when combined with ICB. The combination of 5-FU with ICB augmented an inflammatory tumor microenvironment with markedly increased CD8+ T cell activation and upregulation of IFNγ, TNFα and IL-1β signaling. The effective anti-tumor immune response of 5-FU chemo-immunotherapy was dependent on CD8+ T cells but was unaffected when TNFα or IL-1β cytokine signaling pathways were blocked. Our study identified additive and non-additive chemotherapy/ICB combinations and suggests a possible role for increased inflammation in the tumor microenvironment as a basis for effective combination therapy.}, }
@article {pmid35602795, year = {2022}, author = {Shrestha, B and Handa, R and Poudel, B and Hingorani, R}, title = {Pericardial Mesothelioma Presenting as Constrictive Pericarditis.}, journal = {Cureus}, volume = {14}, number = {4}, pages = {e24270}, doi = {10.7759/cureus.24270}, pmid = {35602795}, issn = {2168-8184}, abstract = {This case report presents a 60-year-old gentleman with a significant smoking history and possible asbestos exposure who was referred to the emergency department for atrial fibrillation with a rapid ventricular rate and symptoms of heart failure. Labs showed normal brain natriuretic peptide and troponin I. His echocardiography finding suggested constrictive pericarditis with an ejection fraction of 60%. A computed tomography scan was concerning for a pericardial mass. Left and right heart catheterization hinted more toward constrictive physiology; however, some findings were concerning for restrictive physiology. Hence, cardiac magnetic resonance imaging was done, which established the diagnosis of constrictive pericarditis. Pericardiectomy was planned with a maze procedure for atrial fibrillation. However, a malignant neoplasm was seen on a frozen biopsy. Hence, surgery was limited to partial pericardiectomy, as the patient had advanced infiltrative neoplasm that had resulted in constrictive pericarditis. The final pathology report confirmed the diagnosis of malignant pericardial mesothelioma mixed type. Malignancy is usually diagnosed in an advanced stage, like in our case, due to nonspecific initial presentation. A literature review suggests that there is a lack of established consensus on treatment. The response to therapy also seems to be poor and results only in palliation of symptoms, with a median survival of six months from diagnosis despite optimum medical management.}, }
@article {pmid35582270, year = {2019}, author = {Williams, M and Cheng, YY and Phimmachanh, M and Winata, P and van Zandwijk, N and Reid, G}, title = {Tumour suppressor microRNAs contribute to drug resistance in malignant pleural mesothelioma by targeting anti-apoptotic pathways.}, journal = {Cancer drug resistance (Alhambra, Calif.)}, volume = {2}, number = {4}, pages = {1193-1206}, pmid = {35582270}, issn = {2578-532X}, abstract = {Aim: Aberrant microRNA expression is a common event in cancer drug resistance, however its involvement in malignant pleural mesothelioma (MPM) drug resistance is largely unexplored. We aimed to investigate the contribution of microRNAs to the resistance to drugs commonly used in the treatment of MPM. Methods: Drug resistant MPM cell lines were generated by treatment with cisplatin, gemcitabine or vinorelbine. Expression of microRNAs was quantified using RT-qPCR. Apoptosis and drug sensitivity assays were carried out following transfection with microRNA mimics or BCL2 siRNAs combined with drugs. Results: Expression of miR-15a, miR-16 and miR-34a was downregulated in MPM cells with acquired drug resistance. Transfection with miR-15a or miR-16 mimics reversed the resistance to cisplatin, gemcitabine or vinorelbine, whereas miR-34a reversed cisplatin and vinorelbine resistance only. Similarly, in parental cell lines, miR-15a or miR-16 mimics sensitised cells to all drugs, whereas miR-34a increased response to cisplatin and vinorelbine. Increased microRNA expression increased drug-induced apoptosis and caused BCL2 mRNA and protein reduction. RNAi-mediated knockdown of BCL2 partly recapitulated the increase in drug sensitivity in cisplatin and vinorelbine treated cells. Conclusion: Drug-resistant MPM cell lines exhibited reduced expression of tumour suppressor microRNAs. Increasing tumour suppressor of microRNA expression sensitised both drug resistant and parental cell lines to chemotherapeutic agents, in part through targeting of BCL2. Taken together, these data suggest that miR-15a, miR-16 and miR-34a are involved in the acquired and intrinsic drug resistance phenotype of MPM cells.}, }
@article {pmid35582652, year = {2022}, author = {Mielgo-Rubio, X and Cardeña Gutiérrez, A and Sotelo Peña, V and Sánchez Becerra, MV and González López, AM and Rosero, A and Trujillo-Reyes, JC and Couñago, F}, title = {Tsunami of immunotherapy reaches mesothelioma.}, journal = {World journal of clinical oncology}, volume = {13}, number = {4}, pages = {267-275}, doi = {10.5306/wjco.v13.i4.267}, pmid = {35582652}, issn = {2218-4333}, abstract = {Malignant pleural mesothelioma (MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase III clinical trials published results positioning immunotherapy as a promising option for the first- and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte-associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase III trials. In the CheckMate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naïve patients and patients with progressive disease after chemotherapy.}, }
@article {pmid35566667, year = {2022}, author = {Nagamatsu, Y and Sakyo, Y and Barroga, E and Koni, R and Natori, Y and Miyashita, M}, title = {Bereaved Family Members' Perspectives of Good Death and Quality of End-of-Life Care for Malignant Pleural Mesothelioma Patients: A Cross-Sectional Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {9}, pages = {}, doi = {10.3390/jcm11092541}, pmid = {35566667}, issn = {2077-0383}, support = {16H05579//the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI)/ ; 16H05579//the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI)/ ; }, abstract = {OBJECTIVE: This study investigated whether malignant pleural mesothelioma (MPM) patients achieved good deaths and good quality of end-of-life care compared with other cancer patients from the perspective of bereaved family members in Japan.<br><br>METHODS: This cross-sectional study was part of a larger study on the achievement of good deaths of MPM patients and the bereavement of their family members. Bereaved family members of MPM patients in Japan (n = 72) were surveyed. The Good Death Inventory (GDI) was used to assess the achievement of good death. The short version of the Care Evaluation Scale (CES) version 2 was used to assess the quality of end-of-life care. The GDI and CES scores of MPM patients were compared with those of a Japanese cancer population from a previous study.<br><br>RESULTS: MPM patients failed to achieve good deaths. Only 12.5% of the MPM patients were free from physical pain. The GDI scores of most of the MPM patients were significantly lower than those of the Japanese cancer population. The CES scores indicated a significantly poorer quality of end-of-life care for the MPM patients than the Japanese cancer population. The total GDI and CES scores were correlated (r = 0.55).<br><br>CONCLUSIONS: The quality of end-of-life care for MPM patients remains poor. Moreover, MPM patients do not achieve good deaths from the perspective of their bereaved family members.}, }
@article {pmid35565374, year = {2022}, author = {Holzknecht, A and Illini, O and Hochmair, MJ and Krenbek, D and Setinek, U and Huemer, F and Bitterlich, E and Kaindl, C and Getman, V and Akan, A and Weber, M and Leobacher, G and Valipour, A and Mueller, MR and Watzka, SB}, title = {Multimodal Treatment of Malignant Pleural Mesothelioma: Real-World Experience with 112 Patients.}, journal = {Cancers}, volume = {14}, number = {9}, pages = {}, doi = {10.3390/cancers14092245}, pmid = {35565374}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare pleural cancer associated with asbestos exposure. According to current evidence, the combination of chemotherapy, surgery and radiotherapy improves patients' survival. However, the optimal sequence and weighting of the respective treatment modalities is unclear. In anticipation of the upcoming results of the MARS-2 trial, we sought to determine the relative impact of the respective treatment modalities on complications and overall survival in our own consecutive institutional series of 112 patients. Fifty-seven patients (51%) underwent multimodality therapy with curative intent, while 55 patients (49%) were treated with palliative intent. The median overall survival (OS) of the entire cohort was 16.9 months (95% CI: 13.4-20.4) after diagnosis; 5-year survival was 29% for patients who underwent lung-preserving surgery. In univariate analysis, surgical treatment (p < 0.001), multimodality therapy (p < 0.001), epithelioid subtype (p < 0.001), early tumor stage (p = 0.02) and the absence of arterial hypertension (p = 0.034) were found to be prognostic factors for OS. In multivariate analysis, epithelioid subtype was associated with a survival benefit, whereas the occurrence of complications was associated with worse OS. Multimodality therapy including surgery significantly prolonged the OS of MPM patients compared with multimodal therapy without surgery.}, }
@article {pmid35559971, year = {2021}, author = {Murphy, F and Dekkers, S and Braakhuis, H and Ma-Hock, L and Johnston, H and Janer, G and di Cristo, L and Sabella, S and Jacobsen, NR and Oomen, AG and Haase, A and Fernandes, T and Stone, V}, title = {An integrated approach to testing and assessment of high aspect ratio nanomaterials and its application for grouping based on a common mesothelioma hazard.}, journal = {NanoImpact}, volume = {22}, number = {}, pages = {100314}, doi = {10.1016/j.impact.2021.100314}, pmid = {35559971}, issn = {2452-0748}, abstract = {Here we describe the development of an Integrated Approach to Testing and Assessment (IATA) to support the grouping of different types (nanoforms; NFs) of High Aspect Ratio Nanomaterials (HARNs), based on their potential to cause mesothelioma. Hazards posed by the inhalation of HARNs are of particular concern as they exhibit physical characteristics similar to pathogenic asbestos fibres. The approach for grouping HARNs presented here is part of a framework to provide guidance and tools to group similar NFs and aims to reduce the need to assess toxicity on a case-by-case basis. The approach to grouping is hypothesis-driven, in which the hypothesis is based on scientific evidence linking critical physicochemical descriptors for NFs to defined fate/toxicokinetic and hazard outcomes. The HARN IATA prompts users to address relevant questions (at decision nodes; DNs) regarding the morphology, biopersistence and inflammatory potential of the HARNs under investigation to provide the necessary evidence to accept or reject the grouping hypothesis. Each DN in the IATA is addressed in a tiered manner, using data from simple in vitro or in silico methods in the lowest tier or from in vivo approaches in the highest tier. For these proposed methods we provide justification for the critical descriptors and thresholds that allow grouping decisions to be made. Application of the IATA allows the user to selectively identify HARNs which may pose a mesothelioma hazard, as demonstrated through a literature-based case study. By promoting the use of alternative, non-rodent approaches such as in silico modelling, in vitro and cell-free tests in the initial tiers, the IATA testing strategy streamlines information gathering at all stages of innovation through to regulatory risk assessment while reducing the ethical, time and economic burden of testing.}, }
@article {pmid35558518, year = {2022}, author = {Martens, M and Kreidl, F and Ehrhart, F and Jean, D and Mei, M and Mortensen, HM and Nash, A and Nymark, P and Evelo, CT and Cerciello, F}, title = {A Community-Driven, Openly Accessible Molecular Pathway Integrating Knowledge on Malignant Pleural Mesothelioma.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {849640}, doi = {10.3389/fonc.2022.849640}, pmid = {35558518}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy mainly triggered by exposure to asbestos and characterized by complex biology. A significant body of knowledge has been generated over the decades by the research community which has improved our understanding of the disease toward prevention, diagnostic opportunities and new treatments. Omics technologies are opening for additional levels of information and hypotheses. Given the growing complexity and technological spread of biological knowledge in MPM, there is an increasing need for an integrating tool that may allow scientists to access the information and analyze data in a simple and interactive way. We envisioned that a platform to capture this widespread and fast-growing body of knowledge in a machine-readable and simple visual format together with tools for automated large-scale data analysis could be an important support for the work of the general scientist in MPM and for the community to share, critically discuss, distribute and eventually advance scientific results. Toward this goal, with the support of experts in the field and informed by existing literature, we have developed the first version of a molecular pathway model of MPM in the biological pathway database WikiPathways. This provides a visual and interactive overview of interactions and connections between the most central genes, proteins and molecular pathways known to be involved or altered in MPM. Currently, 455 unique genes and 247 interactions are included, derived after stringent manual curation of an initial 39 literature references. The pathway model provides a directly employable research tool with links to common databases and repositories for the exploration and the analysis of omics data. The resource is publicly available in the WikiPathways database (Wikipathways : WP5087) and continues to be under development and curation by the community, enabling the scientists in MPM to actively participate in the prioritization of shared biological knowledge.}, }
@article {pmid35554012, year = {2022}, author = {Costa, A and Forte, IM and Ventura, E and Pentimalli, F and Giordano, A}, title = {Pharmacological reactivation of RBL2/p130 could be an effective antitumoral strategy for malignant pleural mesothelioma.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {36 Suppl 1}, number = {}, pages = {}, doi = {10.1096/fasebj.2022.36.S1.L7720}, pmid = {35554012}, issn = {1530-6860}, abstract = {Malignant mesothelioma (MM) is an aggressive tumor developing from the mesothelium covering the body cavities. The most common MM type affects the pleura surrounding the lungs. MM is mainly associated with asbestos exposure. At present, no curative modalities are effective against MM exist. The molecular mechanisms underlying MM development seem to depend mostly on the inactivation of tumor suppressors, among which also the dysfunction of the retinoblastoma (RB) protein pathway that is a hallmark of cancers. We previously demonstrated that RBL2/p130 is a direct AKT target and its reactivation following AKT inhibition mediates apoptosis in MM. So, we hypothesize that concomitant inhibition of CDK and AKT activity, both converging on the reactivation of RBL2/p130 tumor suppressor role, synergize in counteracting MM. We first assessed, through an MTS assay, the effect of three new generation CDK inhibitors (CDKi), palbociclib, ribociclib, abemaciclib, on the cell viability of MM (NCI-H28, IST-MES TWO, NCI-H2452, MMB, MSTO-211H, NCI-H2052) and immortalized human normal mesothelial (MET-5A) cells at 72h. Then, to verify whether CDKi exerted long-term cell growth inhibition, we performed clonogenic assays upon treatment of all the MM All the MM and mesothelial cell lines. Finally, we also examined, by MTS, the possible synergistic effects of abemaciclib in combination with an AKT inhibitor (AKT1/2 VIII). Our preliminary data show that ribociclib and palbociclib only moderately reduce viability of the MPM cells, whereas abemaciclib shows cytotoxic effects at very low doses in all MM cell lines. Abemaciclib treatment induces a dose-dependent cytotoxic effect in all the MM cell lines without meaningfully affecting the normal mesothelial cells. Interestingly, abemaciclib also induced a cytotoxic effect in the most aggressive histotype, the sarcomatoid NCI-H2052 cells. To verify whether abemaciclib exerted long-term cell growth inhibition, we performed clonogenic assays upon treatment with IC50 of abemaciclib and found that the CDKi dramatically reduced colony formation in all the MM cell lines. We also examined, by MTS, the possible synergistic effects of abemaciclib in combination with a kinase AKT inhibitor (iAKT1/2 VIII), so we treated the MM cell lines for 72 h with the two agents, both alone and in combination, at five different concentrations, in a constant ratio. The cell viability data were evaluated through the Chou-Talalay method and showed a strong synergism revealing a combination index (CI) values < 1 for all cell. Although reactivating oncosoppressor genes is difficult to achieve because they are hardly 'druggable', our preliminary findings will provide the rationale for pharmacological strategies able to unleash RBL2/p130 tumor suppressor potential. The pharmacological reactivation of RBL2/p130 could be an effective strategy against MM, which can be rapidly implemented in the clinical practice.}, }
@article {pmid35552365, year = {2022}, author = {Mazurek, JM and Blackley, DJ and Weissman, DN}, title = {Malignant Mesothelioma Mortality in Women - United States, 1999-2020.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {71}, number = {19}, pages = {645-649}, doi = {10.15585/mmwr.mm7119a1}, pmid = {35552365}, issn = {1545-861X}, abstract = {Inhalation of asbestos fibers can cause malignant mesothelioma, a rapidly progressing and lethal cancer of the mesothelium, the thin layer of tissues surrounding internal organs in the chest and abdomen. Patients with malignant mesothelioma have a poor prognosis, with a median survival of 1 year from diagnosis. The estimated median interval from initial occupational asbestos exposure to death is 32 years (range = 13-70 years) (1). Occupational asbestos exposure is most often reported in men working in industries such as construction and manufacturing; however, women are also at risk for exposure to asbestos fibers, and limited data exist on longer-term trends in mesothelioma deaths among women. To characterize deaths associated with mesothelioma and temporal trends in mesothelioma mortality among women in the United States, CDC analyzed annual Multiple Cause of Death records from the National Vital Statistics System for 1999-2020, the most recent years for which complete data are available. The annual number of mesothelioma deaths among women increased significantly, from 489 in 1999 to 614 in 2020; however, the age-adjusted death rate per 1 million women declined significantly, from 4.83 in 1999 to 4.15 in 2020. The largest number of deaths was associated with the health care and social assistance industry (89; 15.7%) and homemaker occupation (129; 22.8%). Efforts to limit exposure to asbestos fibers, including among women, need to be maintained.}, }
@article {pmid35547634, year = {2022}, author = {Li, X and Wang, D and Liu, A and Hu, W and Sun, X}, title = {Epidemiological Characteristics of Occupational Cancers Reported - China, 2006-2020.}, journal = {China CDC weekly}, volume = {4}, number = {17}, pages = {370-373}, doi = {10.46234/ccdcw2022.086}, pmid = {35547634}, issn = {2096-7071}, abstract = {Introduction: Occupational cancers are a major threat to workers' health in China. The latest version of the Classification and Catalogue of the Occupational Diseases includes 11 occupational cancers. This study analyzed the epidemiological characteristics of occupational cancers in China reported to the National Occupational Disease Reporting System during 2006-2020.<br><br>Methods: Occupational cancers reported during 2016-2020 were obtained from the National Occupational Disease Reporting System. Epidemiological characteristics were analyzed by year, region, industry, gender, age at diagnosis, and exposure duration to occupational hazards.<br><br>Results: Overall, a total of 1,116 cases of occupational cancers were reported between 2006 and 2020. The main types reported were leukemia caused by benzene exposure (511, 45.79%), lung cancer caused by coke oven exhaust exposure (266, 23.84%), and lung cancer and mesothelioma caused by asbestos exposure (226, 20.25%). There were 6 provincial-level administrative divisions (PLADs) that had reported over 50 new cases in the last 15 years. Most cases (913, 81.18%) were distributed in the manufacturing industry. There were 870 (77.96%) male cases and 246 (22.04%) female cases. The average age at diagnosis of all reported cases was 51.91±15.85 years, and the median exposure duration to occupational hazards was 12 (5.29-23.25) years.<br><br>Conclusions: There is a large discrepancy between the high morbidity of occupational cancers and a low number of cases diagnosed and reported cases. Occupational cancers in China may be underestimated, and comprehensive measures should be taken to improve the diagnosis and reporting of occupational cancers.}, }
@article {pmid35533249, year = {2022}, author = {Anobile, DP and Montenovo, G and Pecoraro, C and Franczak, M and Ait Iddouch, W and Peters, GJ and Riganti, C and Giovannetti, E}, title = {Splicing deregulation, microRNA and Notch aberrations: fighting the three-headed dog to overcome drug resistance in malignant mesothelioma.}, journal = {Expert review of clinical pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17512433.2022.2074835}, pmid = {35533249}, issn = {1751-2441}, abstract = {INTRODUCTION: Malignant mesothelioma (MMe) is an aggressive rare cancer of the mesothelium, associated with asbestos exposure. MMe is currently an incurable disease at all stages mainly due to resistance to treatments. It is therefore necessary to elucidate key mechanisms underlying chemoresistance, in an effort to exploit them as novel therapeutic targets.<br><br>AREAS COVERED: Chemoresistance is frequently elicited by microRNA (miRNA) alterations and splicing deregulations. Indeed, several miRNAs, such as miR-29c, have been shown to exert oncogenic or oncosuppressive activity. Alterations in the splicing machinery might also be involved in chemoresistance. Moreover, the Notch signaling pathway, often deregulated in MMe, plays a key role in cancer stem cells formation and self-renewal, leading to drug resistance and relapses.<br><br>EXPERT OPINION: The prognosis of MMe in patients varies among different tumors and patient characteristics, and novel biomarkers and therapies are warranted. This work aims at giving an overview of MMe, with a special focus on state-of-the-art treatments and new therapeutic strategies against vulnerabilities emerging from studies on epigenetics factors. Besides, this review is also the first to discuss the interplay between miRNAs and alternative splicing as well as the role of Notch as new promising frontiers to overcome drug resistance in MMe.}, }
@article {pmid35524457, year = {2022}, author = {Almeida, GC and Santos, UP and Parente, YDM and Colares, PFB and Mizutani, RF and Bernardi, FDC and Terra, RM and Terra-Filho, M}, title = {Mesothelioma in situ with regressive malignant pleural effusion and an unexpected evolution: A case report.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23358}, pmid = {35524457}, issn = {1097-0274}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that originates from hyperplasia and metaplasia of the mesothelial cells that cover the pleural cavity. Previous exposure to asbestos is the main risk factor. Since MPM is often diagnosed at an advanced stage with rapid evolution and resistance to treatment, it is associated with an unfavorable outcome. Mesothelioma in situ (MIS) has been postulated as a preinvasive phase of MPM; however, its diagnostic criteria have been defined only recently. Diagnosis of MIS may represent an opportunity for early therapies with better results, but the optimal approach has not been defined thus far. Here, we report on a case of a 74-year-old man with right-sided pleural effusion and a previous history of occupational exposure to asbestos for 9 years who was diagnosed with MIS after a latency of 36 years. During follow-up, spontaneous disease regression was observed 5 months after the initial diagnosis; however, it recurred in the form of invasive epithelioid MPM. There is a paucity of literature on MIS and its evolution; however, our case provides relevant knowledge of this unusual behavior, which is important to define follow-up and therapeutic strategies for future cases.}, }
@article {pmid35001771, year = {2022}, author = {Korchevskiy, AA and Wylie, AG}, title = {Dimensional characteristics of the major types of amphibole mineral particles and the implications for carcinogenic risk assessment.}, journal = {Inhalation toxicology}, volume = {34}, number = {1-2}, pages = {24-38}, doi = {10.1080/08958378.2021.2024304}, pmid = {35001771}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/analysis/toxicity ; Carcinogenesis ; Carcinogens/toxicity ; Humans ; *Lung Neoplasms/chemically induced ; *Mesothelioma/chemically induced ; Minerals/toxicity ; Risk Assessment ; }, abstract = {Context: Though some significant advances have been made in recent decades to evaluate the importance of size and morphology (habit) of elongate mineral particles (EMPs), further research is needed to better understand the role of each dimensional metric in determining the levels of cancer potency.Objective: To determine dimensional parameters most relevant for predicting cancer potency of durable elongate particles, specifically amphibole and durable silicate minerals generally.Methods: A database on dimensional and other relevant characteristics of elongate amphibole mineral particles was created, containing particle-by-particle information for 128 099 particles. Integral statistical characteristics on dimensionality of various amphibole types and morphological habits of EMPs were calculated, compared, and correlated with published mesothelioma and lung cancer potency factors.Results: The highest absolute Pearson correlation (r = 0.97, r2 = 0.94, p < 0.05) was achieved between mesothelioma potency (RM) and specific surface area. The highest correlation with adjusted lung cancer potency was found with particle aspect ratio (AR) (r = 0.80, r2 = 0.64, p < 0.05). Cluster analysis demonstrates that fractions of thin fibers (width less than 0.15 and 0.25 µm) also closely relate both to lung cancer and RM. Asbestiform and non-asbestiform populations of amphiboles significantly differ by dimensionality and carcinogenic potency.Conclusions: Dimensional parameters and morphological habits of EMPs are the main drivers for the observable difference in cancer potency among amphibole populations.}, }
@article {pmid35501851, year = {2022}, author = {Malakoti, F and Targhazeh, N and Abadifard, E and Zarezadeh, R and Samemaleki, S and Asemi, Z and Younesi, S and Mohammadnejad, R and Hadi Hossini, S and Karimian, A and Alemi, F and Yousefi, B}, title = {DNA repair and damage pathways in mesothelioma development and therapy.}, journal = {Cancer cell international}, volume = {22}, number = {1}, pages = {176}, pmid = {35501851}, issn = {1475-2867}, abstract = {Malignant mesothelioma (MMe) is an aggressive neoplasm that occurs through the transformation of mesothelial cells. Asbestos exposure is the main risk factor for MMe carcinogenesis. Other important etiologies for MMe development include DNA damage, over-activation of survival signaling pathways, and failure of DNA damage response (DDR). In this review article, first, we will describe the most important signaling pathways that contribute to MMe development and their interaction with DDR. Then, the contribution of DDR failure in MMe progression will be discussed. Finally, we will review the latest MMe therapeutic strategies that target the DDR pathway.}, }
@article {pmid35497939, year = {2022}, author = {Kambara, T and Amatya, VJ and Kushitani, K and Fujii, Y and Endo, I and Takeshima, Y}, title = {Downregulation of FTL decreases proliferation of malignant mesothelioma cells by inducing G1 cell cycle arrest.}, journal = {Oncology letters}, volume = {23}, number = {6}, pages = {174}, doi = {10.3892/ol.2022.13294}, pmid = {35497939}, issn = {1792-1082}, abstract = {Pleural malignant mesothelioma is a malignant tumor with a poor prognosis that is strongly associated with asbestos exposure during its development. Because there is no adequate treatment for malignant mesothelioma, investigation of its molecular mechanism is important. The ferritin light chain (FTL) is a subunit of ferritin, and its high expression in malignant tumors, including malignant mesothelioma, has recently been reported; however, its role in malignant mesothelioma is unclear. The purpose of the present study was to clarify the function of FTL in malignant mesothelioma. The expression levels of FTL in malignant mesothelioma were examined using the Cancer Cell Line Encyclopedia database and our previous data. The short interfering (si)RNA against FTL was transfected into two mesothelioma cell lines, ACC-MESO-1 and CRL-5915, and functional analysis was performed. Expression of p21, p27, cyclin-dependent kinase 2 (CDK2) and phosphorylated retinoblastoma protein (pRb) associated with the cell cycle were examined as candidate genes associated with FTL. The expression levels of the FTL mRNA were higher in malignant mesothelioma compared with other tumors in the Cancer Cell Line Encyclopedia database, and among other genes in our previous study. Reverse transcription-quantitative PCR and western blotting demonstrated suppression of FTL expression in two cell lines transfected with FTL siRNA compared with cells transfected with negative control (NC) siRNA. In the two cell lines transfected with FTL siRNA, proliferation was significantly suppressed, and cell cycle arrest was observed in the G1 phase. The levels of p21 and p27 were increased, while those of CDK2 and pRb were decreased compared with NC. However, no significant differences in invasion and migration ability were revealed between FTL siRNA-transfected cells and NC. In conclusion, FTL may increase the proliferative capacity of malignant mesothelioma cells by affecting p21, p27, CDK2 and pRb, and promoting the cell cycle at the G1 phase.}, }
@article {pmid35489694, year = {2022}, author = {Louw, A and Panou, V and Szejniuk, WM and Meristoudis, C and Chai, SM and van Vliet, C and Lee, YCG and Dick, IM and Firth, T and Lynggaard, LA and Asghari, AB and Vyberg, M and Hansen, J and Creaney, J and Røe, OD}, title = {BAP1 loss by immunohistochemistry predicts improved survival to first line platinum/pemetrexed chemotherapy for pleural mesothelioma patients: A validation study.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2022.04.008}, pmid = {35489694}, issn = {1556-1380}, abstract = {INTRODUCTION: Pleural mesothelioma (PM) is an aggressive malignancy with no identified predictive biomarkers. We assessed whether tumour BRCA associated protein 1 (BAP1) status is a predictive biomarker for survival in patients receiving first-line combination platinum/pemetrexed therapy.introduction METHODS: PM cases (n=114) from Aalborg, Denmark were stained for BAP1 on tissue microarrays. Demographic, clinical and survival data were extracted from registries and medical records. Surgical cases were excluded. BAP1 status was associated with overall survival (OS) by Cox regression and Kaplan-Meier methods. Results were validated in an independent cohort from Perth, Australia (n=234).<br><br>RESULTS: BAP1 loss was demonstrated in 62% and 60.3% of all Danish and Australian samples respectively. BAP1 loss was an independent predictor of OS in multivariate analyses corrected for histology, performance status, age, sex and treatment (HR = 2.49, p < 0.001 and 1.48, p = 0.01, respectively). First-line platinum/pemetrexed treated patients with BAP1 loss had significantly longer median survival than those with retained BAP1 in both the Danish (20.1 vs 7.3 months, p < 0.001) and Australian cohorts (19.6 vs 11.1 months, p < 0.01). Survival in patients with BAP1 retained and treated with platinum/pemetrexed was similar as in those with best supportive care (BSC). There was a higher OS in BSC patients with BAP1 loss, but significant only in the Australian cohort (16.8 vs 8.3 months, p < 0.01).results CONCLUSION: BAP1 is a predictive biomarker for survival following first-line combination platinum/pemetrexed chemotherapy and a potential prognostic marker in PM. BAP1 in tumour is a promising clinical tool for treatment stratification.}, }
@article {pmid35472827, year = {2022}, author = {Maghin, F and Antonietti, A and Cerri, N and Lancini, LM and Maccarinelli, A and Manzoni, S and Restori, M and Rota, M and Ruffini, D and Verzeletti, A and Conti, A}, title = {Assessment protocol of mesothelioma and relevance of SEM-EDS analysis through a case studies of legal medicine of Brescia (Italy).}, journal = {Legal medicine (Tokyo, Japan)}, volume = {57}, number = {}, pages = {102076}, doi = {10.1016/j.legalmed.2022.102076}, pmid = {35472827}, issn = {1873-4162}, abstract = {INTRODUCTION: This study evaluates the assessment protocol that allows the correlation between the development of mesothelioma to a specific exposure, with particular focus on investigations with Scanning Electron Microscope with Energy Dispersion Spectroscopy.<br><br>METHODS: This retrospective study includes 80 subjects who died from mesothelioma in the period 2001-2019. A judicial autopsy was performed for each case to confirm cause of death and correlate the disease with specific asbestos exposure. In 28 cases investigations were carried out to determine the pulmonary load of the asbestos fibres and corpuscles in the lung tissue through microscopic investigations, in order to confirm the suspicion of occupational exposure.<br><br>RESULTS: Our data agree with the scientific literature reported, but it is interesting to underline how the present study uses a different systematic approach than others, which are mainly based on epidemiological and environmental studies without considering the lung content of fibres and corpuscles.<br><br>CONCLUSION: It would be desirable that the use of the microscopic analysis was introduced in the evaluation protocol: it should always be carried out if the suspicion of asbestos-related disease is raised and not only as a possible integration to the less expensive anamnestic evaluation, even more so if the work or personal history should be suggestive of exposure to asbestos fibres.}, }
@article {pmid35462085, year = {2022}, author = {Carbone, M and Pass, HI and Ak, G and Alexander, HR and Baas, P and Baumann, F and Blakely, AM and Bueno, R and Bzura, A and Cardillo, G and Churpek, JE and Dianzani, I and De Rienzo, A and Emi, M and Emri, S and Felley-Bosco, E and Fennell, DA and Flores, RM and Grosso, F and Hayward, NK and Hesdorffer, M and Hoang, CD and Johansson, PA and Kindler, HL and Kittaneh, M and Krausz, T and Mansfield, A and Metintas, M and Minaai, M and Mutti, L and Nielsen, M and O'Byrne, K and Opitz, I and Pastorino, S and Pentimalli, F and de Perrot, M and Pritchard, A and Ripley, RT and Robinson, B and Rusch, V and Taioli, E and Takinishi, Y and Tanji, M and Tsao, AS and Tuncer, AM and Walpole, S and Wolf, A and Yang, H and Yoshikawa, Y and Zolodnick, A and Schrump, DS and Hassan, R}, title = {Medical and surgical care of mesothelioma patients and their relatives carrying germline BAP1 mutations.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2022.03.014}, pmid = {35462085}, issn = {1556-1380}, abstract = {The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma; less frequently breast cancer, several types of skin carcinomas and other tumor types. Mesotheliomas in these patients are significantly less aggressive and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy. Others may grow aggressively but very often respond to therapy. Detecting BAP1 germline mutations has, therefore, significant medical, social and economic impact. Close monitoring of these patients and their relatives is expected to result in prolonged life expectancy, improved quality of life and is also cost-effective. The co-authors of this paper are those who have published the vast majority of cases of mesothelioma occurring in patients carrying inactivating germline BAP1 mutations and who have studied the families affected by the BAP1 cancer syndrome for many years. This paper reports our experience. It is intended to be a source of information for all physicians who care for patients carrying germline BAP1 mutations. We discuss the clinical presentation, diagnostic and treatment challenges and our recommendations of how to best care for these patients and their family members, as well as the potential economic and psychosocial impact.}, }
@article {pmid35461395, year = {2022}, author = {Napoli, F and Rapa, I and Izzo, S and Rigutto, A and Libener, R and Riganti, C and Bironzo, P and Taulli, R and Papotti, M and Volante, M and Scagliotti, G and Righi, L}, title = {Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {}, number = {}, pages = {}, pmid = {35461395}, issn = {1432-2307}, support = {IG 2019 - ID 23760//Associazione Italiana per la Ricerca sul Cancro/ ; GR-2011-02348356//Regione Piemonte/ ; }, abstract = {The standard front-line treatment for pleural mesothelioma (PM) is pemetrexed-based chemotherapy, whose major target is thymidylate synthase (TS). In several cancer models, miR-215 and miR-375 have been shown to target TS, while information on these miRNAs in PM are still limited although suggest their role in epithelial to mesenchymal transition. Seventy-one consecutive PM tissues (4 biphasic, 7 sarcomatoid, and 60 epithelioid types) and 16 commercial and patient-derived PM cell lines were screened for TS, miR-215, and miR-375 expression. REN and 570B cells were selected for miR-215 and miR-375 transient transfections to test TS modulation. ZEB1 protein expression in tumor samples was also tested. Moreover, genetic profile was investigated by means of BAP1 and p53 immunohistochemistry. Expression of both miR-215 and miR-375 was significantly higher in epithelioid histotype. Furthermore, inverse correlation between TS protein and both miR-215 and miR-375 expression was found. Efficiently transfected REN and 570B cell lines overexpressing miR-215 and miR-375 showed decreased TS protein levels. Epithelioid PM with a mesenchymal component highlighted by reticulin stain showed significantly higher TS and ZEB1 protein and lower miRNA expression. A better survival was recorded for BAP1 lost/TS low cases. Our data indicate that miR-215 and miR-375 are involved in TS regulation as well as in epithelial-to-mesenchymal transition in PM.}, }
@article {pmid35443624, year = {2022}, author = {Ziółkowska, B and Cybulska-Stopa, B and Papantoniou, D and Suwiński, R}, title = {Systemic treatment in patients with malignant pleural mesothelioma - real life experience.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {432}, pmid = {35443624}, issn = {1471-2407}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, aggressive malignancy of the pleural cavity linked to asbestos exposure. The combination of pemetrexed and platinum is a standard first-line therapy for malignant pleural mesothelioma. Despite some progress, almost all MPM patients experience progression after first-line therapy. The second-line treatment is still being under discussion and there are very limited data available on the second-line and subsequent treatments.<br><br>METHODS: The retrospective analysis included 57 patients (16 females and 41 males) from two Polish oncological institutions treated for advanced mesothelioma between 2013 and 2019. We analysed the efficacy of first-line and second-line therapy: progression-free survival (PFS), overall survival (OS), overall response rate (ORR).<br><br>RESULTS: In the first-line treatment, 55 patients received pemetrexed-based chemotherapy (PBC) and two cisplatin in monotherapy. Patients' characteristics at baseline: median age was 64.2 years, ECOG PS ≤ 1 (86.2%), epithelial histology (85.7%). Median PFS and OS were 7.6 months and 14 months, respectively. Patients with ECOG PS ≤ 1 vs > 1 had a longer median OS (14.8 months vs 9.7 months, p = 0.057). One-year OS and PFS were 60.9% and 32.0%, respectively. Disease control rate (DCR) was 82.5%. Response to first-line therapy: PFS ≥ 6 months and PFS ≥ 12 months had a significant impact on median OS. Twelve patients received second-line therapy (seven PBC and five other cytotoxic single agents: navelbine, gemcitabine, or adriamycin/vincristine/methotrexate triplet). Median PFS and OS were 3.7 months and 7.2 months, respectively. DCR was 83%. One-year OS and PFS were 37% and 16.7%, respectively. In the group receiving PBC, OS was prolonged by 4.5 months compared to the non-PBC group (6.0 months vs 10.5 months, p = 0.47).<br><br>CONCLUSION: Patients who benefited from first-line therapy and had prolonged PFS at first-line and achieve PFS longer than 6 months at first-line should be offered second-line treatment. Consideration of retreatment with the same cytotoxic agent could to be a viable option when no other treatment are available.}, }
@article {pmid35439870, year = {2022}, author = {Jin, MY and Jiang, ZQ}, title = {[Research progress on the role of lncRNA in the occurrence and development of malignant mesothelioma].}, 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 = {40}, number = {3}, pages = {231-235}, doi = {10.3760/cma.j.cn121094-20210413-00205}, pmid = {35439870}, issn = {1001-9391}, support = {2019RC142//Zhejiang Medical and Health Science and Technology Program/ ; 11-ZC02//Zhejiang Medical Support Discipline Labor Hygiene/ ; KYYB202113//Basic Scientific Research Projects of Hangzhou Medical College/ ; }, abstract = {Malignant mesothelioma (MM) is a long latency, poor prognosis and asbestos exposure related malignant disease. Long non-coding RNA (lncRNA) is a kind of RNA with a length of more than 200 nucleotides that does not encode protein. It plays an important role in epigenetic regulation, cell cycle regulation and cell differentiation regulation. Recent studies have shown that the abnormal expression or function of lncRNA is closely related to the diagnosis and prognosis of MM. In this paper, the lncRNA research on MM is reviewed to better understand the role of lncRNA in MM.}, }
@article {pmid35431929, year = {2022}, author = {Robinson, BWS and Redwood, AJ and Creaney, J}, title = {How Our Continuing Studies of the Pre-clinical Inbred Mouse Models of Mesothelioma Have Influenced the Development of New Therapies.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {858557}, doi = {10.3389/fphar.2022.858557}, pmid = {35431929}, issn = {1663-9812}, abstract = {Asbestos-induced preclinical mouse models of mesothelioma produce tumors that are very similar to those that develop in humans and thus represent an ideal platform to study this rare, universally fatal tumor type. Our team and a number of other research groups have established such models as a stepping stone to new treatments, including chemotherapy, immunotherapy and other approaches that have been/are being translated into clinical trials. In some cases this work has led to changes in mesothelioma treatment practice and over the last 30 years these models and studies have led to trials which have improved the response rate in mesothelioma from less than 10% to over 50%. Mouse models have had a vital role in that improvement and will continue to play a key role in the future success of mesothelioma immunotherapy. In this review we focus only on these original inbred mouse models, the large number of preclinical studies conducted using them and their contribution to current and future clinical therapy for mesothelioma.}, }
@article {pmid32520630, year = {2020}, author = {Tran, T and Egilman, D and Rigler, M}, title = {Response to Roggli et al. (2020) "Talc and mesothelioma: mineral fiber analysis of 65 cases with clinicopathological correlation".}, journal = {Ultrastructural pathology}, volume = {44}, number = {3}, pages = {314-315}, doi = {10.1080/01913123.2020.1778148}, pmid = {32520630}, issn = {1521-0758}, mesh = {Asbestos, Amphibole ; Humans ; *Mesothelioma/pathology ; *Mesothelioma, Malignant ; Mineral Fibers ; Talc ; }, }
@article {pmid35410957, year = {2022}, author = {Dawson, AG and Kutywayo, K and Mohammed, SB and Fennell, DA and Nakas, A}, title = {Cytoreductive surgery with hyperthermic intrathoracic chemotherapy for malignant pleural mesothelioma: a systematic review.}, journal = {Thorax}, volume = {}, number = {}, pages = {}, doi = {10.1136/thoraxjnl-2021-218214}, pmid = {35410957}, issn = {1468-3296}, abstract = {INTRODUCTION: Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. Delivery of hyperthermic intrathoracic chemotherapy at the time of surgery has been used to address this microscopic disease, however it's effect and place in the multimodality treatment sphere is unknown. The aim of this systematic review was to assess the effect of surgery and hyperthermic intrathoracic chemotherapy in patients with MPM on overall survival and disease-free interval.<br><br>METHODS: Ovid MEDLINE, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from database inception through to June 2021. Studies reporting overall survival and/or disease-free interval in patients with MPM undergoing cytoreductive surgery with hyperthermic intrathoracic chemotherapy were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative review was performed.<br><br>RESULTS: Fifteen studies were eligible for inclusion comprising 598 patients. Surgery with hyperthermic intrathoracic chemotherapy was associated with a median overall survival and disease-free interval ranging from 11 to 75 months and 7.2 to 57 months, respectively. These appeared to be superior to patients not receiving hyperthermic intrathoracic chemotherapy (overall survival: 5-36 months and disease-free interval: 12.1-21 months). A higher dose of hyperthermic intrathoracic chemotherapy was associated with an improvement in overall survival compared with a lower dose: 18-31 months versus 6-18 months, respectively. The most common morbidity was atrial fibrillation followed by renal complications.<br><br>CONCLUSION: Surgery with hyperthermic intrathoracic chemotherapy offers a safe and effective therapy with an improvement in disease-free interval and overall survival, particularly when hyperthermic intrathoracic chemotherapy is administered at a higher dose.<br><br>PROSPERO REGISTRATION NUMBER: CRD42019129002.}, }
@article {pmid35409711, year = {2022}, author = {Berry, TA and Belluso, E and Vigliaturo, R and Gieré, R and Emmett, EA and Testa, JR and Steinhorn, G and Wallis, SL}, title = {Asbestos and Other Hazardous Fibrous Minerals: Potential Exposure Pathways and Associated Health Risks.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {7}, pages = {}, doi = {10.3390/ijerph19074031}, pmid = {35409711}, issn = {1660-4601}, abstract = {There are six elongate mineral particles (EMPs) corresponding to specific dimensional and morphological criteria, known as asbestos. Responsible for health issues including asbestosis, and malignant mesothelioma, asbestos has been well researched. Despite this, significant exposure continues to occur throughout the world, potentially affecting 125 million people in the workplace and causing thousands of deaths annually from exposure in homes. However, there are other EMPS, such as fibrous/asbestiform erionite, that are classified as carcinogens and have been linked to cancers in areas where it has been incorporated into local building materials or released into the environment through earthmoving activities. Erionite is a more potent carcinogen than asbestos but as it is seldom used for commercial purposes, exposure pathways have been less well studied. Despite the apparent similarities between asbestos and fibrous erionite, their health risks and exposure pathways are quite different. This article examines the hazards presented by EMPs with a particular focus on fibrous erionite. It includes a discussion of the global locations of erionite and similar hazardous minerals, a comparison of the multiple exposure pathways for asbestos and fibrous erionite, a brief discussion of the confusing nomenclature associated with EMPs, and considerations of increasing global mesothelioma cases.}, }
@article {pmid35409322, year = {2022}, author = {Henzi, T and Diep, KL and Oberson, A and Salicio, V and Bochet, CG and Schwaller, B}, title = {Forchlorfenuron and Novel Analogs Cause Cytotoxic Effects in Untreated and Cisplatin-Resistant Malignant Mesothelioma-Derived Cells.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, doi = {10.3390/ijms23073963}, pmid = {35409322}, issn = {1422-0067}, abstract = {Malignant mesothelioma (MM) is a currently incurable, aggressive cancer derived from mesothelial cells, most often resulting from asbestos exposure. The current first-line treatment in unresectable MM is cisplatin/pemetrexed, which shows very little long-term effectiveness, necessitating research for novel therapeutic interventions. The existing chemotherapies often act on the cytoskeleton, including actin filaments and microtubules, but recent advances indicate the 'fourth' form consisting of the family of septins, representing a novel target. The septin inhibitor forchlorfenuron (FCF) and FCF analogs inhibit MM cell growth in vitro, but at concentrations which are too high for clinical applications. Based on the reported requirement of the chloride group in the 2-position of the pyridine ring of FCF for MM cell growth inhibition and cytotoxicity, we systematically investigated the importance (cell growth-inhibiting capacity) of the halogen atoms fluorine, chlorine, bromine and iodine in the 2- or 3-position of the pyridine ring. The MM cell lines ZL55, MSTO-211H, and SPC212, and-as a control-immortalized Met-5A mesothelial cells were used. The potency of the various halogen substitutions in FCF was mostly correlated with the atom size (covalent radius); the small fluoride analogs showed the least effect, while the largest one (iodide) most strongly decreased the MTT signals, in particular in MM cells derived from epithelioid MM. In the latter, the strongest effects in vitro were exerted by the 2-iodo and, unexpectedly, the 2-trifluoromethyl (2-CF3) FCF analogs, which were further tested in vivo in mice. However, FCF-2-I and, more strongly, FCF-2-CF3 caused rapidly occurring strong symptoms of systemic toxicity at doses lower than those previously obtained with FCF. Thus, we investigated the effectiveness of FCF (and selected analogs) in vitro in MM cells which were first exposed to cisplatin. The slowly appearing population of cisplatin-resistant cells was still susceptible to the growth-inhibiting/cytotoxic effect of FCF and its analogs, indicating that cisplatin and FCF target non-converging pathways in MM cells. Thus, a combination therapy of cisplatin and FCF (analogs) might represent a new avenue for the treatment of repopulating chemo-resistant MM cells in this currently untreatable cancer.}, }
@article {pmid35402250, year = {2022}, author = {Tilsed, CM and Casey, TH and de Jong, E and Bosco, A and Zemek, RM and Salmons, J and Wan, G and Millward, MJ and Nowak, AK and Lake, RA and Lesterhuis, WJ}, title = {Retinoic Acid Induces an IFN-Driven Inflammatory Tumour Microenvironment, Sensitizing to Immune Checkpoint Therapy.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {849793}, doi = {10.3389/fonc.2022.849793}, pmid = {35402250}, issn = {2234-943X}, abstract = {With immune checkpoint therapy (ICT) having reshaped the treatment of many cancers, the next frontier is to identify and develop novel combination therapies to improve efficacy. Previously, we and others identified beneficial immunological effects of the vitamin A derivative tretinoin on anti-tumour immunity. Although it is known that tretinoin preferentially depletes myeloid derived suppressor cells in blood, little is known about the effects of tretinoin on the tumour microenvironment, hampering the rational design of clinical trials using tretinoin in combination with ICT. Here, we aimed to identify how tretinoin changed the tumour microenvironment in mouse tumour models, using flow cytometry and RNAseq, and we sought to use that information to establish optimal dosing and scheduling of tretinoin in combination with several ICT antibodies in multiple cancer models. We found that tretinoin rapidly induced an interferon dominated inflammatory tumour microenvironment, characterised by increased CD8+ T cell infiltration. This phenotype completely overlapped with the phenotype that was induced by ICT itself, and we confirmed that the combination further amplified this inflammatory milieu. The addition of tretinoin significantly improved the efficacy of anti-CTLA4/anti-PD-L1 combination therapy, and staggered scheduling was more efficacious than concomitant scheduling, in a dose-dependent manner. The positive effects of tretinoin could be extended to ICT antibodies targeting OX40, GITR and CTLA4 monotherapy in multiple cancer models. These data show that tretinoin induces an interferon driven, CD8+ T cell tumour microenvironment that is responsive to ICT.}, }
@article {pmid35394203, year = {2022}, author = {Nakashima, K and Sakai, Y and Hoshino, H and Umeda, Y and Kawashima, H and Sekido, Y and Ishizuka, T and Kobayashi, M}, title = {Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {}, number = {}, pages = {}, pmid = {35394203}, issn = {1432-1750}, support = {21H02702//Japan Society for the Promotion of Science/ ; }, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is a malignant neoplasm of the pleura caused by asbestos exposure. For diagnosis of MPM, immunohistochemistry using multiple markers is recommended to rule out differential diagnoses, such as pulmonary adenocarcinoma. However, the specificity of currently used markers is not fully satisfactory. We previously developed a monoclonal antibody named S1, which recognizes 6-sulfo sialyl Lewis x, an L-selectin ligand expressed on high endothelial venules. During the screening process, we discovered that this antibody stained normal pleural mesothelium. This finding prompted us to hypothesize that the epitope recognized by S1 might serve as a new diagnostic marker for MPM.<br><br>METHODS: To test this hypothesis, we immunostained human MPM (n = 22) and lung adenocarcinoma (n = 25) tissues using S1 antibody.<br><br>RESULTS: 77.3% of MPM were S1 positive, and if limited to epithelioid type, the positivity rate was 100%, while that of lung adenocarcinoma was only 36.0%. Statistical analysis revealed a significant difference in the S1 positivity rate between each disease. Furthermore, immunohistochemistry using a series of anti-carbohydrate antibodies combined with glycosidase digestion revealed the structure of sulfated glycans expressed in MPM to be 6-sulfo sialyl N-acetyllactosamine attached to core 2-branched O-glycans.<br><br>CONCLUSION: We propose that the S1 glycoepitope could serve as a new diagnostic marker for MPM.}, }
@article {pmid35378379, year = {2022}, author = {Cameron, JK and Aitken, J and Reid, A and Mengersen, K and Cramb, S and Preston, P and Armstrong, B and Baade, P}, title = {Geographic distribution of malignant mesothelioma incidence and survival in Australia.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {167}, number = {}, pages = {17-24}, doi = {10.1016/j.lungcan.2022.03.017}, pmid = {35378379}, issn = {1872-8332}, abstract = {OBJECTIVES: To understand the geographic distribution of and area-level factors associated with malignant mesothelioma incidence and survival in Australia.<br><br>MATERIALS AND METHODS: Generalised linear models and Bayesian spatial models were fitted using population registry data. Area-level covariates were socioeconomic quintile, remoteness category and state or territory. The maximised excess events test was used to test for spatial heterogeneity.<br><br>RESULTS: There was strong evidence of spatial differences in standardised incidence rates for malignant mesothelioma but survival was uniformly poor. Incidence rates varied by state or territory and were lower in remote areas. Patterns in the geographic distribution of modelled incidence counts for malignant mesothelioma differed substantially from patterns of standardised incidence rates.<br><br>CONCLUSIONS: Geographic variation in the modelled incidence counts of malignant mesothelioma demonstrates varying demand for diagnostic and management services. The long latency period for this cancer coupled with migration complicates any associations with patterns of exposure, however some of the geographic distribution of diagnoses can be explained by the location of historical mines and asbestos-related industries.}, }
@article {pmid35367351, year = {2022}, author = {Laaksonen, S and Kettunen, E and Sutinen, E and Ilonen, I and Vehmas, T and Törmäkangas, T and Räsänen, J and Wolff, H and Myllärniemi, M}, title = {Pulmonary Asbestos Fiber Burden is Related to Patient Survival in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2022.03.012}, pmid = {35367351}, issn = {1556-1380}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is associated with poor prognosis and is strongly associated with occupational asbestos exposure. Given the importance of asbestos exposure in MPM pathogenesis, we retrospectively analyzed the types and concentrations of asbestos fibers within the lung tissues of patients with MPM and investigated their effects on all-cause mortality.<br><br>METHODS: We formed a national dataset of patients with MPM identified from the Finnish Cancer Registry and Statistics Finland. These data were merged with pulmonary asbestos fiber analysis results received from the Finnish Institute of Occupational Health.<br><br>RESULTS: We identified 590 patients with MPM that underwent pulmonary asbestos fiber analysis. The median asbestos concentration within dry lung tissue was 3.20 million fibers/gram (f/g) (range: 0-1700 million f/g). Crocidolite and anthophyllite were the most prevalent asbestos fiber types detected in lung tissue. The multivariable risk of death analyses, where changes over time were accounted for, revealed that total asbestos fiber concentration was associated with increased mortality. However, no difference in mortality was noted between different fiber types.<br><br>CONCLUSION: Our study revealed that pulmonary fiber concentrations correlated with the manner of asbestos usage. Anthophyllite was identified as the sole fiber in a sizable proportion of cases, supporting its independent role in the pathogenesis of MPM. Our findings suggest that asbestos fiber burden, but not fiber type, may have an impact on the prognosis of MPM.}, }
@article {pmid35360426, year = {2022}, author = {Idkedek, M and Tahayneh, KS and Abu-Akar, F and Bakri, IA}, title = {Case Report and Review of Literature: Familial Malignant Pleural Mesothelioma in a 39 Years Old Patient With an Inconclusive 18F-FDG PET/CT Result.}, journal = {Frontiers in surgery}, volume = {9}, number = {}, pages = {819596}, doi = {10.3389/fsurg.2022.819596}, pmid = {35360426}, issn = {2296-875X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare yet aggressive neoplasm that was linked only to asbestos exposure for decades, although familial clusters were diagnosed with MPM without a known history of asbestos exposure most likely due to genetic susceptibility. Here, we describe a case of familial malignant mesothelioma in a 39 years old patient with a confirmed BAP1 mutation in addition to a known family history with the same mutation. The patient presented with progressive shortness of breath and recurrent pleural effusions and diagnosis was made through biopsies taken during uniportal Video-Assisted Thoracoscopic Surgery. After the inconclusive result of 18F-FDG PET/CT scan, subxiphoid uniportal Video-Assisted Thoracoscopic Surgery left pleural and laparoscopic peritoneal biopsies were obtained for staging and evaluating contralateral lung and peritoneal cavity. Finally, two important educational values should be acquired from this case: genetic predisposition and BAP1 tumor suppressor gene mutation might affect the age of presentation and overall prognosis of the disease. Also, 18F-FDG PET/CT scan may not be the best modality for staging and confirming the diagnosis of malignant pleural mesothelioma.}, }
@article {pmid35358455, year = {2022}, author = {Kindler, HL and Novello, S and Bearz, A and Ceresoli, GL and Aerts, JGJV and Spicer, J and Taylor, P and Nackaerts, K and Greystoke, A and Jennens, R and Calabrò, L and Burgers, JA and Santoro, A and Cedrés, S and Serwatowski, P and Ponce, S and Van Meerbeeck, JP and Nowak, AK and Blumenschein, G and Siegel, JM and Kasten, L and Köchert, K and Walter, AO and Childs, BH and Elbi, C and Hassan, R and Fennell, DA}, title = {Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial.}, journal = {The Lancet. Oncology}, volume = {23}, number = {4}, pages = {540-552}, doi = {10.1016/S1470-2045(22)00061-4}, pmid = {35358455}, issn = {1474-5488}, abstract = {BACKGROUND: Few treatment options exist for second-line treatment of malignant pleural mesothelioma. We aimed to assess the antibody-drug conjugate anetumab ravtansine versus vinorelbine in patients with unresectable locally advanced or metastatic disease overexpressing mesothelin who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab.<br><br>METHODS: In this phase 2, randomised, open-label study, done at 76 hospitals in 14 countries, we enrolled adults (aged ≥18 years) with unresectable locally advanced or metastatic malignant pleural mesothelioma, an Eastern Cooperative Oncology Group performance status of 0-1, and who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. Participants were prospectively screened for mesothelin overexpression (defined as 2+ or 3+ mesothelin membrane staining intensity on at least 30% of viable tumour cells by immunohistochemistry) and were randomly assigned (2:1), using an interactive voice and web response system provided by the sponsor, to receive intravenous anetumab ravtansine (6·5 mg/kg on day 1 of each 21-day cycle) or intravenous vinorelbine (30 mg/m2 once every week) until progression, toxicity, or death. The primary endpoint was progression-free survival according to blinded central radiology review, assessed in the intention-to-treat population, with safety assessed in all participants who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02610140, and is now completed.<br><br>FINDINGS: Between Dec 3, 2015, and May 31, 2017, 589 patients were enrolled and 248 mesothelin-overexpressing patients were randomly allocated to the two treatment groups (166 patients were randomly assigned to receive anetumab ravtansine and 82 patients were randomly assigned to receive vinorelbine). 105 (63%) of 166 patients treated with anetumab ravtansine (median follow-up 4·0 months [IQR 1·4-5·5]) versus 43 (52%) of 82 patients treated with vinorelbine (3·9 months [1·4-5·4]) had disease progression or died (median progression-free survival 4·3 months [95% CI 4·1-5·2] vs 4·5 months [4·1-5·8]; hazard ratio 1·22 [0·85-1·74]; log-rank p=0·86). The most common grade 3 or worse adverse events were neutropenia (one [1%] of 163 patients for anetumab ravtansine vs 28 [39%] of 72 patients for vinorelbine), pneumonia (seven [4%] vs five [7%]), neutrophil count decrease (two [1%] vs 12 [17%]), and dyspnoea (nine [6%] vs three [4%]). Serious drug-related treatment-emergent adverse events occurred in 12 (7%) patients treated with anetumab ravtansine and 11 (15%) patients treated with vinorelbine. Ten (6%) treatment-emergent deaths occurred with anetumab ravtansine: pneumonia (three [2%]), dyspnoea (two [1%]), sepsis (two [1%]), atrial fibrillation (one [1%]), physical deterioration (one [1%]), hepatic failure (one [1%]), mesothelioma (one [1%]), and renal failure (one [1%]; one patient had 3 events). One (1%) treatment-emergent death occurred in the vinorelbine group (pneumonia).<br><br>INTERPRETATION: Anetumab ravtansine showed a manageable safety profile and was not superior to vinorelbine. Further studies are needed to define active treatments in relapsed mesothelin-expressing malignant pleural mesothelioma.<br><br>FUNDING: Bayer Healthcare Pharmaceuticals.}, }
@article {pmid35341441, year = {2022}, author = {Ierardi, AM and Best, EA and Marsh, GM}, title = {Updated Italian cohort data continues to confirm lack of mesothelioma risk in pooled cohort of international cosmetic talc miners and millers.}, journal = {Inhalation toxicology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/08958378.2022.2053251}, pmid = {35341441}, issn = {1091-7691}, abstract = {OBJECTIVES: To assess potential mesothelioma risk following inhalation of cosmetic talc, we updated previous iterations of a pooled cohort analysis, post-study statistical power analysis, and confidence interval function analysis for a pooled cohort of international cosmetic talc miners/millers given new Italian cohort data.<br><br>METHODS: Five cohorts of cosmetic talc miners/millers were pooled. Expected numbers of mesotheliomas for each cohort were reported by the original authors. We based our post-study statistical power analysis on an a priori one-sided significance level of 0.05, and exact Poisson and approximate distribution probabilities. To evaluate the confidence interval function for the observed pooled mesothelioma standardized mortality ratios (SMRs), we calculated the probability for the upper 100(1-2α)% confidence limit that equals various SMRs of interest.<br><br>RESULTS: The pooled cohorts generated a total observation time of 135,524.38 person-years. Overall, 4.14 mesotheliomas were expected (mid-value estimate), though only one case of mesothelioma has been confirmed in the pooled cohort to date. We calculated 71% and 87% post-study power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. Our complimentary confidence interval function analysis demonstrated that the probability that the true mesothelioma SMR for the pooled cohort was at or above 2.0 or at or above 3.0 was 0.00235 and 0.00005, respectively.<br><br>CONCLUSIONS: Based on the updated results of our various analyses, the current epidemiological evidence from cosmetic talc miner/miller cohort studies continues to not support the hypothesis that the inhalation of cosmetic talc is associated with an increased risk of mesothelioma.}, }
@article {pmid35339776, year = {2022}, author = {Ejegi-Memeh, S and Sherborne, V and Harrison, M and Taylor, B and Senek, M and Tod, A and Gardiner, C}, title = {Patients' and informal carers' experience of living with mesothelioma: A systematic rapid review and synthesis of the literature.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {58}, number = {}, pages = {102122}, doi = {10.1016/j.ejon.2022.102122}, pmid = {35339776}, issn = {1532-2122}, abstract = {PURPOSE: Mesothelioma is a rare and incurable cancer linked to asbestos exposure. It primarily affects the pleura. This systematic rapid review aimed to identify what is known about the experience of living with mesothelioma, from the perspective of patients and their informal carers.<br><br>METHODS: Medline, PsycInfo, Scopus and the Cumulative Index to Nursing and Allied Health Literature were searched for empirical studies published between December 2008 and October 2020. Google Scholar was searched. The inclusion criteria stated that studies were peer-reviewed, reported the experience of living with mesothelioma from the perspective of patients and carers and written in English. The Mixed-Methods Appraisal Tool was used to assess quality. The review protocol is registered on PROSPERO: CRD42020204726.<br><br>RESULTS: Twenty-five studies met the inclusion criteria. Following data extraction, a narrative synthesis identified three themes: the impact on the individual; the impact on informal carers and relationships; and interactions with professionals and systems. The physical and psychological symptom burden of mesothelioma on patients' lives was reported as high. Both the qualitative and quantitative literature highlighted that patients and carers may have different needs throughout the mesothelioma journey. Differences included psychological experiences and preferences regarding the timing of information and support provision. Patients and carers expected their health care professionals to be knowledgeable about mesothelioma or refer to those who were. Health care professionals that were compassionate, honest and supportive also positively influenced the experience of patients and carers living with mesothelioma. A lack of communication or misinformation was damaging to the patient-healthcare professional relationship. Continuity of care, coordinated care and good communication between treatment centres were widely reported as important in the literature. Fragmented care was identified as detrimental to the patient experience, increasing anxiety in patients. However, relationships with professionals were not only important in terms of co-ordinating care. There was also evidence that good relationships with healthcare professionals were beneficial to coping with the mesothelioma diagnosis.<br><br>CONCLUSION: The volume of mesothelioma experience research has grown over the past decade. This has led to our growing understanding of the complex needs and experiences of mesothelioma patients and carers. However, this review identified several evidence gaps.}, }
@article {pmid35329341, year = {2022}, author = {Saito, CA and Bussacos, MA and Salvi, L and Mensi, C and Consonni, D and Fernandes, FT and Campos, F and Cavalcante, F and Algranti, E}, title = {Sex-Specific Mortality from Asbestos-Related Diseases, Lung and Ovarian Cancer in Municipalities with High Asbestos Consumption, Brazil, 2000-2017.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, doi = {10.3390/ijerph19063656}, pmid = {35329341}, issn = {1660-4601}, support = {CODIN 45672/2014//Labor Public Prosecutor Office of Campinas/ ; BRiC 55/2019//Istituto Nazionale per l'Assicurazione Contro gli Infortuni sul Lavoro/ ; }, abstract = {The aim of this study is to compare the mortality rates for typical asbestos-related diseases (ARD-T: mesothelioma, asbestosis, and pleural plaques) and for lung and ovarian cancer in Brazilian municipalities where asbestos mines and asbestos-cement plants had been operating (areas with high asbestos consumption, H-ASB) compared with in other municipalities. The death records for adults aged 30+ years were retrieved from multiple health information systems. In the 2000-2017 time period, age-standardized mortality rates (standard: Brazil 2010) and standardized rate ratios (SRR; H-ASB vs. others) were estimated. The SRRs for ARD-T were 2.56 for men (257 deaths in H-ASB municipalities) and 1.19 for women (136 deaths). For lung cancer, the SRRs were 1.33 for men (32,604 deaths) and 1.19 for women (20,735 deaths). The SRR for ovarian cancer was 1.34 (8446 deaths). Except for ARD-T and lung cancer in women, the SRRs were higher in municipalities that began using asbestos before 1970 than in municipalities that began utilizing asbestos from 1970 onwards. In conclusion, the mortality rates for ARD-T, and lung and ovarian cancer in municipalities with a history of asbestos mining and asbestos-cement production exceed those of the whole country. Caution is needed when interpreting the results of this ecological study. Analytical studies are necessary to document the impact of asbestos exposure on health, particularly in the future given the long latency of asbestos-related cancers.}, }
@article {pmid35329152, year = {2022}, author = {Stoppa, G and Mensi, C and Fazzo, L and Minelli, G and Manno, V and Consonni, D and Biggeri, A and Catelan, D}, title = {Spatial Analysis of Shared Risk Factors between Pleural and Ovarian Cancer Mortality in Lombardy (Italy).}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, doi = {10.3390/ijerph19063467}, pmid = {35329152}, issn = {1660-4601}, support = {BRiC 55/2019//Istituto Nazionale per l'Assicurazione Contro gli Infortuni sul Lavoro/ ; }, abstract = {BACKGROUND: Asbestos exposure is a recognized risk factor for ovarian cancer and malignant mesothelioma. There are reports in the literature of geographical ecological associations between the occurrence of these two diseases. Our aim was to further explore this association by applying advanced Bayesian techniques to a large population (10 million people).<br><br>METHODS: We specified a series of Bayesian hierarchical shared models to the bivariate spatial distribution of ovarian and pleural cancer mortality by municipality in the Lombardy Region (Italy) in 2000-2018.<br><br>RESULTS: Pleural cancer showed a strongly clustered spatial distribution, while ovarian cancer showed a less structured spatial pattern. The most supported Bayesian models by predictive accuracy (widely applicable or Watanabe-Akaike information criterion, WAIC) provided evidence of a shared component between the two diseases. Among five municipalities with significant high standardized mortality ratios of ovarian cancer, three also had high pleural cancer rates. Wide uncertainty was present when addressing the risk of ovarian cancer associated with pleural cancer in areas at low background risk of ovarian cancer.<br><br>CONCLUSIONS: We found evidence of a shared risk factor between ovarian and pleural cancer at the small geographical level. The impact of the shared risk factor can be relevant and can go unnoticed when the prevalence of other risk factors for ovarian cancer is low. Bayesian modelling provides useful information to tailor epidemiological surveillance.}, }
@article {pmid35329075, year = {2022}, author = {Spinazzè, A and Consonni, D and Borghi, F and Rovelli, S and Cattaneo, A and Zellino, C and Dallari, B and Pesatori, AC and Kromhout, H and Peters, S and Riboldi, L and Cavallo, DM and Mensi, C}, title = {Asbestos Exposure in Patients with Malignant Pleural Mesothelioma included in the PRIMATE Study, Lombardy, Italy.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, doi = {10.3390/ijerph19063390}, pmid = {35329075}, issn = {1660-4601}, support = {ARL_2/2018//Fondazione Regionale per la Ricerca Biomedica/ ; BRIC55/2019//Istituto Nazionale per l'Assicurazione Contro gli Infortuni sul Lavoro/ ; }, abstract = {The PRIMATE study is an Italian translational research project, which aims to identify personalized biomarkers associated with clinical characteristics of malignant pleural mesothelioma (MPM). For this purpose, characteristics of MPM patients with different degrees of asbestos exposure will be compared to identify somatic mutations, germline polymorphism, and blood inflammatory biomarkers. In this framework, we assessed exposure to asbestos for 562 cases of MPM extracted from the Lombardy region Mesothelioma Registry (RML), for which a complete interview based on a standardized national questionnaire and histopathological specimens were available. Exposure assessment was performed: (1) through experts' evaluation (considered as the gold standard for the purpose of this study), according to the guidelines of the Italian National Mesothelioma Registry (ReNaM) and (2) using a job-exposure matrix (SYN-JEM) to obtain qualitative (ever/never) and quantitative estimates of occupational asbestos exposure (cumulative exposure expressed in fibers per mL (f/mL)). The performance of SYN-JEM was evaluated against the experts' evaluation. According to experts' evaluation, occupational asbestos exposure was recognized in 73.6% of men and 23.6% of women; furthermore, 29 men (7.8%) and 70 women (36.9%) had non-occupational exposure to asbestos. When applying SYN-JEM, 225 men (60.5%) and 25 women (13.2%) were classified as occupationally exposed, with a median cumulative exposure higher for men (1.7 f/mL-years) than for women (1.2 f/mL-years). The concordance between the two methods (Cohen's kappa) for occupational exposure assessment was 0.46 overall (0.41 in men, and 0.07 in women). Sensitivity was higher in men (0.73) than in women (0.18), while specificity was higher in women (0.88) than in men (0.74). Overall, both methods can be used to reconstruct past occupational exposure to asbestos, each with its own advantages and limitations.}, }
@article {pmid35328844, year = {2022}, author = {Anaya-Aguilar, C and Bravo, M and Magan-Fernandez, A and Del Castillo-Salmerón, R and Rodríguez-Archilla, A and Montero, J and Rosel, E and Puche, P and Anaya-Aguilar, R}, title = {Prevention of Occupational Hazards Due to Asbestos Exposure in Dentistry. A Proposal from a Panel of Experts.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, doi = {10.3390/ijerph19063153}, pmid = {35328844}, issn = {1660-4601}, abstract = {Asbestos in all its forms is a Group 1 material agent with proven carcinogenic effects in the human being since 1977. Exposure to asbestos can be considered unsafe. The use of asbestos in the field of dentistry had a common use in the manufacture of dental prostheses in the 1960s and 1970s. Taking into account the long induction period of this agent and the plausibility for being a risk factor in dentistry, the objective of this study is to propose a plan for the prevention of occupational risks due to asbestos exposure in dentistry by means of the contribution of a panel of experts. An Expert Panel (EP) approach was used in which a group of nine experts identified and documented the use of asbestos in the dental profession. EP was created and followed the protocol in accordance with the EuropeAid Assessment Guidelines. As a result of this study, EP documented the common use and sources of asbestos in dentistry in prosthetic materials, dental dressings, and in the coating of casting cylinders. EP also created a consensus document on the priority measures for the Plan for the Prevention of Risks from Asbestos in Dentistry, based on previous reports from the European Commission Senior Labour Inspectors' Committee. The document concluded that obtainment of information, receiving specific training on the subject and performing epidemiological studies, and the proper risk assessments were the priority measures to adopt.}, }
@article {pmid35327475, year = {2022}, author = {Rovers, S and Janssens, A and Raskin, J and Pauwels, P and van Meerbeeck, JP and Smits, E and Marcq, E}, title = {Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma.}, journal = {Biomedicines}, volume = {10}, number = {3}, pages = {}, doi = {10.3390/biomedicines10030673}, pmid = {35327475}, issn = {2227-9059}, support = {FFB210293//BOF research fund, University of Antwerp/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a fatal cancer type that affects the membranes lining the lungs, and is causally associated with asbestos exposure. Until recently, the first-line treatment consisted of a combination of chemotherapeutics that only had a limited impact on survival, and had not been improved in decades. With the recent approval of combined immune checkpoint inhibition for MPM, promising new immunotherapeutic strategies are now emerging for this disease. In this review, we describe the current preclinical and clinical evidence of various immune checkpoint inhibitors in MPM. We will consider the advantages of combined immune checkpoint blockade in comparison with single agent checkpoint inhibitor drugs. Furthermore, recent evidence suggests a role for T cell immunoglobulin and ITIM domain (TIGIT), an inhibitory immunoreceptor, as a novel target for immunotherapy. As this novel immune checkpoint remains largely unexplored in mesothelioma, we will discuss the potential of TIGIT blockade as an alternative therapeutic approach for MPM. This review will emphasize the necessity for new and improved treatments for MPM, while highlighting the recent advances and future perspectives of combined immune checkpoint blockade, particularly aimed at PD-L1 and TIGIT.}, }
@article {pmid35270479, year = {2022}, author = {Nishida, C and Yatera, K}, title = {The Impact of Ambient Environmental and Occupational Pollution on Respiratory Diseases.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {5}, pages = {}, doi = {10.3390/ijerph19052788}, pmid = {35270479}, issn = {1660-4601}, abstract = {Ambient pollutants and occupational pollutants may cause and exacerbate various lung and respiratory diseases. This review describes lung and respiratory diseases in relation to ambient pollutants, particularly particulate matter (PM2.5), and occupational air pollutants, excluding communicable diseases and indoor pollutants, including tobacco smoke exposure. PM2.5 produced by combustion is an important ambient pollutant. PM2.5 can cause asthma attacks and exacerbations of chronic obstructive pulmonary disease in the short term. Further, it not only carries a risk of lung cancer and death, but also hinders the development of lung function in children in the long term. It has recently been suggested that air pollution, such as PM2.5, is a risk factor for severe coronavirus disease (COVID-19). Asbestos, which causes asbestosis, lung cancer, and malignant mesothelioma, and crystalline silica, which cause silicosis, are well-known traditional occupational pollutants leading to pneumoconiosis. While work-related asthma (WRA) is the most common occupational lung disease in recent years, many different agents cause WRA, including natural and synthetic chemicals and irritant gases. Primary preventive interventions that increase awareness of pollutants and reduce the development and exacerbation of diseases caused by air pollutants are paramount to addressing ambient and occupational pollution.}, }
@article {pmid35269773, year = {2022}, author = {Serio, G and Pezzuto, F and Fortarezza, F and Marzullo, A and Delfino, MC and d'Amati, A and Romano, DE and Maniglio, S and Caporusso, C and Lettini, T and Cavone, D and Vimercati, L}, title = {Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation.}, journal = {International journal of molecular sciences}, volume = {23}, number = {5}, pages = {}, doi = {10.3390/ijms23052630}, pmid = {35269773}, issn = {1422-0067}, abstract = {There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos reaches these sites, especially through contaminated water; however, some experimental studies have shown that the inhaled fibres are mobile, so they can migrate to many organs, directly or via blood and lymph flow. We report four unusual cases of colorectal cancers in patients with a long history of asbestos exposure who also developed synchronous or metachronous mesothelioma. We evaluated the roles of BRCA associated protein-1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) in colon cancer and mesothelioma to support the hypothesis that BAP-1 and CDKN2A are tumour suppressor genes involved in disease progression, recurrence, or death in both digestive cancers and mesothelioma. Potentially, these markers may be used as predictors of worse prognosis, but we also stress the importance of clinical surveillance of exposed patients because asbestos could induce cancer in any organ.}, }
@article {pmid35264891, year = {2022}, author = {Davis, A and Ke, H and Kao, S and Pavlakis, N}, title = {An Update on Emerging Therapeutic Options for Malignant Pleural Mesothelioma.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {13}, number = {}, pages = {1-12}, doi = {10.2147/LCTT.S288535}, pmid = {35264891}, issn = {1179-2728}, abstract = {The treatment paradigm for malignant pleural mesothelioma (MPM) has changed little in the last 18 years. Radical intent treatment, consisting of surgical resection, radiotherapy and chemotherapy, has been offered to a highly select few; however, there is little randomised evidence to validate this approach. Prior to 2020 chemotherapy with platinum and an anti-folate was the only intervention with randomised evidence to demonstrate improved overall survival (OS) in MPM. No systemic therapy had been demonstrated to improve OS in the second line setting until 2020. The publication of the Checkmate 743 trial in 2021 demonstrated a survival benefit of combination immunotherapy over standard chemotherapy in newly diagnosed patients with MPM. This finding was shortly followed by the CONFIRM trial which demonstrates a modest but significant survival benefit of second line nivolumab versus placebo in patients having previously received standard chemotherapy. The results of these trials, recent biomarker directed therapy and chemotherapy adjuncts are discussed within this review. The integration of immunotherapy for the few patients in whom radical surgical therapy is intended is currently the subject of clinical trials and offers the prospect of improving outcomes in this rare but devastating disease.}, }
@article {pmid35251640, year = {2022}, author = {Rijavec, E and Biello, F and Barletta, G and Dellepiane, C and Genova, C}, title = {Novel approaches for the treatment of unresectable malignant pleural mesothelioma: A focus on immunotherapy and target therapy (Review).}, journal = {Molecular and clinical oncology}, volume = {16}, number = {4}, pages = {89}, doi = {10.3892/mco.2022.2522}, pmid = {35251640}, issn = {2049-9469}, abstract = {Malignant pleural mesothelioma (MPM) is considered a relatively uncommon disease but its incidence is increasing worldwide. Patients affected by MPM have a very severe prognosis and have been often occupationally and environmentally exposed to asbestos. In recent years, checkpoint inhibitors have dramatically revolutionized the paradigm for the treatment of several malignancies. Several efforts have also been made to improve the survival outcomes of patients with MPM and after decades, the standard-of-care systemic treatment for unresectable MPM, based on first-line combination chemotherapy with cisplatin and pemetrexed, has changed. In addition to checkpoint inhibitors, other types of treatments, such as molecularly targeted therapy have been evaluated. However, to date, the results of these investigations are not very encouraging. The aim of the present review is to provide a comprehensive overview of the most relevant data of clinical trials regarding recent treatment strategies of MPM with a particular focus on immunotherapeutic and targeted approaches.}, }
@article {pmid35236019, year = {2022}, author = {Freemantle, GG and Chetty, D and Olifant, M and Masikhwa, S}, title = {Assessment of asbestos contamination in soils at rehabilitated and abandoned mine sites, Limpopo Province, South Africa.}, journal = {Journal of hazardous materials}, volume = {429}, number = {}, pages = {127588}, doi = {10.1016/j.jhazmat.2021.127588}, pmid = {35236019}, issn = {1873-3336}, mesh = {*Asbestos ; Asbestos, Amosite ; Asbestos, Crocidolite ; Asbestos, Serpentine ; Humans ; *Mesothelioma ; Soil ; South Africa ; }, abstract = {Prior to its termination, asbestos mining in South Africa was centred on the large crocidolite fields of the present day Northern Cape, the amosite (grunerite)-crocidolite fields of Limpopo, and chrysotile fields of Mpumalanga provinces. The legacy of these activities continues to affect surrounding communities in contemporary South Africa. The asbestos fields of Limpopo host two important former mining areas at Penge and at the Bewaarkloof near Chuenespoort. A large abandoned site is located southeast of Penge at Weltevreden, where there is no evidence of any rehabilitation. Two former mines, Lagerdraai and Uitkyk, are rehabilitated sites in an extensive string of closed mines that operated in the southern Bewaarkloof. Samples from the abandoned and rehabilitated mine sites were studied using semi-quantitative X-ray powder diffraction (XRD) to determine asbestos contamination levels in soils, and to assess distribution patterns of asbestos mineral species in the surrounding soils. Only where below detection (typically 1-3 mass%) from XRD, samples were assessed optically. The Weltevreden site, with no observable rehabilitation efforts, contrasts with the rehabilitated sites at Lagerdraai and Uitkyk. The predominant asbestiform mineral species at each site were successfully identified, with underlying geological asbestos mineral distribution trends recognised in the soils at the Bewaarkloof. Trace amounts of asbestiform minerals were identified in soils downstream of the Weltevreden mine, as well as in surrounding hillsides. The results indicate that XRD is a potentially useful tool for benchmarking sites yet to be rehabilitated as well as monitoring the effectiveness of previous rehabilitation efforts. The method is also a suitable first-pass for target areas that may require more detailed, time-consuming, and costly analysis.}, }
@article {pmid35223506, year = {2022}, author = {Fortarezza, F and Pezzuto, F and Marzullo, A and Cavone, D and Romano, DE and d'Amati, A and Serio, G and Vimercati, L}, title = {Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {823839}, doi = {10.3389/fonc.2022.823839}, pmid = {35223506}, issn = {2234-943X}, abstract = {Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium and tunica vaginalis testis (<1%). The onset of pleural mesothelioma is strictly related to asbestos exposure with a long latency time. The causal link with asbestos has also been suggested for peritoneal mesothelioma, while the importance of exposure in the onset of pericardial and tunica vaginalis testis mesotheliomas is not well known. Mesothelioma remains an aggressive and fatal disease with a five-year mortality rate higher than 95%. However, new therapeutic approaches based on molecular-targeted and immunomodulatory therapies are being explored but have conflicting results. In this context, the identification of critical targets appears mandatory. Awareness of the molecular and physiological changes leading to the neoplastic degeneration of mesothelial cells and the identification of gene mutations, epigenetic alterations, gene expression profiles and altered pathways could be helpful for selecting targetable mechanisms and molecules. In this review, we aimed to report recent research in the last 20 years focusing on the molecular pathways and prognostic factors in peritoneal mesothelioma and their possible diagnostic and therapeutic implications.}, }
@article {pmid35216091, year = {2022}, author = {Štrbac, D and Dolžan, V}, title = {Novel and Future Treatment Options in Mesothelioma: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {23}, number = {4}, pages = {}, doi = {10.3390/ijms23041975}, pmid = {35216091}, issn = {1422-0067}, support = {P1-170, L3-8203, and L3-2622.//Slovenian Research Agency/ ; }, abstract = {Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been difficult in a clinical setting. The treatment is based on a trimodal approach involving surgery, chemotherapy, and radiotherapy. The introduction of chemotherapy improved the overall survival. However, the regimen of pemetrexed/cisplatin doublet has not been changed as a standard treatment since 2004. Novel combinations of ipilimumab and nivolumab have only been approved for clinical use in late 2020. The aim of this review was to systematically summarize findings on novel treatment options in mesothelioma. We searched available medical databases online, such as PubMed and Clinicaltrials.gov, to systematically review the literature on novel approaches in immunotherapy, vaccines, and Chimeric Antigen Receptor (CAR)-T cell therapy in mesothelioma. We manually screened 1127 articles on PubMed and 450 trials on ClinicalTrials.gov, and 24 papers and 12 clinical trials published in the last ten years were included in this review. Immunotherapy that was swiftly introduced to treat other thoracic malignancies was slow to reach desirable survival endpoints in mesothelioma, possibly due to limited patient numbers. Novel treatment approaches, such as CAR-T cell therapy, are being investigated. As the incidence of mesothelioma is still rising globally, novel treatment options based on a better understanding of the tumor microenvironment and the genetic drivers that modulate it are needed to support future precision-based therapies.}, }
@article {pmid35211727, year = {2022}, author = {Spinazzè, A and Consonni, D and Borghi, F and Mazzucchelli, LA and Rovelli, S and Cattaneo, A and Zellino, C and Dallari, B and Pesatori, AC and Kromhout, H and Peters, S and Riboldi, L and Mensi, C and Cavallo, DM}, title = {Development of a Crosswalk to Translate Italian Occupation Codes to ISCO-68 Codes.}, journal = {Annals of work exposures and health}, volume = {}, number = {}, pages = {}, doi = {10.1093/annweh/wxac009}, pmid = {35211727}, issn = {2398-7316}, support = {//Fondazione Regionale per la Ricerca Biomedica'/ ; //'Bando Progetto Speciale 2017 su Patologie Amianto-Correlate/ ; }, abstract = {In occupational epidemiology, job coding is an important-but time-consuming-step in assigning exposure. We implemented a tool (i.e. a crosswalk) to translate occupation codes from the Italian (ISTAT-CIP-91, n = 6319 five-digit job codes) to the International Standard Classification of Occupations (ISCO-68, n = 1881 five-digit job codes). The former is currently used in Italy for various purposes (e.g. in the National Mesothelioma Registry). The latter has been used in several studies on occupational cancers because it facilitates communication of results to the scientific community and, most importantly, because some job exposure matrices (JEMs) are based on international codes. Three authors created a table containing the crosswalk structure, providing an interpretation for each of the ISTAT-CIP-91 codes job descriptions and then manually recoding them according to ISCO-68. Two other authors independently revised it. The performance of the final version was assessed by comparison with results obtained by manual ISCO-68 coding performed in two previous case-control studies on asbestos and mesothelioma. More specifically, the automatically obtained ISCO-68 codes were merged with a JEM (DOM-JEM). The resulting individual asbestos exposure estimates (ever versus never exposed) were compared to those originally obtained (using the same DOM-JEM) from manual translation of ISTAT-CIP-91 to ISCO-68 (considered as the 'gold standard'). In the first study, among 159 peritoneal mesothelioma cases (400 job codes), Cohen's kappa was 0.91, sensitivity 0.95, and specificity 0.96. In the second study, among 716 pleural mesothelioma cases and controls (4400 job codes) kappa was 0.86, sensitivity 0.94, and specificity 0.91. Performance was better among in women. For men, performance was lower among cases than among controls (kappa 0.70, sensitivity 0.95, specificity 0.72 versus kappa 0.87, sensitivity 0.97, and specificity 0.92). In conclusion, the proposed tool allowed a rapid translation of thousands of job codes with good to excellent accuracy. The table containing ISTAT-CIP-91 codes and job descriptions and the corresponding ISCO-68 codes and job descriptions is made publicly available and can be freely used for epidemiological analyses in Italy and international collaborations.}, }
@article {pmid35207583, year = {2022}, author = {Caraballo-Arias, Y and Caffaro, P and Boffetta, P and Violante, FS}, title = {Quantitative Assessment of Asbestos Fibers in Normal and Pathological Pleural Tissue-A Scoping Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, doi = {10.3390/life12020296}, pmid = {35207583}, issn = {2075-1729}, abstract = {BACKGROUND: pleural mesothelioma is a rare cancer in the general population, but it is more common in subjects occupationally exposed to asbestos. Studies with asbestos fiber quantification in pleural tissue are scarce: for this reason, we aimed at undertaking a scoping review to summarize the evidence provided by studies in which asbestos fibers were determined by electron microscopy (SEM or TEM) in human pleural tissues, whether normal or pathologic.<br><br>MATERIALS AND METHODS: A scoping review of articles that quantified asbestos fibers in human pleural tissue (normal or pathologic) by electron microscopy (SEM or TEM), in subjects with asbestos exposure (if any) was performed.<br><br>RESULTS: The 12 studies selected comprised 137 cases, out of which 142 samples were analyzed. Asbestos fibers were detected in 111 samples (78%) and were below the detectable limit in 31 samples (22%). The concentration of asbestos fibers detected in the positive samples was distributed from as low as 0.01 mfgdt (millions of fibers per gram of dry tissue) up to 240 mfgdt. However, the minimum concentration of fibers overlaps in the three types of tissues (normal pleura, pleural plaque, mesothelioma) in terms of magnitude; therefore, it is not possible to distinguish a definite pattern which differentiates one tissue from the other.<br><br>CONCLUSIONS: The studies included were heterogeneous as to the representativeness of the samples and analytical techniques; the possibility of false negatives must be considered. It would be desirable to systematically search for asbestos fibers to fill the knowledge gap about the presence of asbestos fibers in normal or pathological pleural tissue in order to better understand the development of the different pleural diseases induced by this mineral.}, }
@article {pmid35206274, year = {2022}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, Ø}, title = {A Cohort Study on Cancer Incidence among Women Exposed to Environmental Asbestos in Childhood with a Focus on Female Cancers, including Breast Cancer.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {4}, pages = {}, doi = {10.3390/ijerph19042086}, pmid = {35206274}, issn = {1660-4601}, abstract = {OBJECTIVES: To examine the risk of cancer in former school children exposed to environmental asbestos in childhood with a focus on female cancers, including breast cancer.<br><br>METHODS: We retrieved a cohort of females (n = 6024) attending four schools located in the neighborhood of a large asbestos cement plant in Denmark. A reference cohort was frequency-matched 1:9 (n = 54,200) in sex and five-year age intervals. Using Danish registries, we linked information on historical employments, relatives' employments, cancer, and vital status. We calculated standardized incidence rates (SIRs) for all and specific cancers, comparing these rates with the reference cohort. Hazard ratios were calculated for selected cancers adjusted for occupational and familial asbestos exposure.<br><br>RESULTS: For cancer of the corpus uteri (SIR 1.29, 95% CI 1.01-1.66) and malignant mesothelioma (SIR 7.26, 95% CI 3.26-16.15), we observed significantly increased incidences. Occupationally, asbestos exposure had a significantly increased hazard ratio for cancer in the cervix, however, a significantly lower risk of ovarian cancer. The overall cancer incidence was similar to that of the reference cohort (SIR 1.02, 95% CI 0.96-1.07). The risk of cancer of the lung was increased for those exposed to occupational asbestos, those with family members occupationally exposed to asbestos and for tobacco smokers.<br><br>CONCLUSIONS: In our study, environmental asbestos exposure in childhood is associated with an increased risk of cancer of the corpus uteri and malignant mesothelioma in women.}, }
@article {pmid35205798, year = {2022}, author = {Shah, R and Klotz, LV and Glade, J}, title = {Current Management and Future Perspective in Pleural Mesothelioma.}, journal = {Cancers}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/cancers14041044}, pmid = {35205798}, issn = {2072-6694}, abstract = {Pleural mesothelioma is an aggressive malignancy arising from pleural mesothelial cell lining, predominantly associated with prior exposure to asbestos. The ban on asbestos use has led to its lower incidence in many countries, but globally the disease burden is expected to rise. Therefore, well-planned research is needed to develop more effective, tolerable and affordable drugs. The development of novel treatment has been too slow, with only two regimens of systemic therapy with robust phase 3 data approved formally to date. The treatment scenario for resectable disease remains controversial. However, recent developments in the understanding of disease and clinical trials have been encouraging, and may add better treatment options in the coming years. In this review, we discuss the current treatment options for pleural mesothelioma and shed light on some recent studies and ongoing trials.}, }
@article {pmid35204402, year = {2022}, author = {Foddis, R and Franzini, M and Bonotti, A and Marino, R and Silvestri, R and Fallahi, P and Chiappino, D and Emdin, M and Paolicchi, A and Cristaudo, A}, title = {Big and Free Fractions of Gamma-Glutamyltransferase: New Diagnostic Biomarkers for Malignant Mesothelioma?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, doi = {10.3390/diagnostics12020311}, pmid = {35204402}, issn = {2075-4418}, support = {PRA 2017//University of Pisa/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a cancer mainly caused by asbestos fiber inhalation, characterized by an extremely long latency and poor prognosis. Recently, researchers have focused on testing the diagnostic ability of several biomarkers. Gamma-Glutamyltransferase (GGT) has been demonstrated to be the sum of several GGT sub-fractions activity, classified based on their molecular weight in big-GGT, medium-GGT, small-GGT, and free-GGT. This work aims to evaluate whether specific GGT fractional enzymatic activity patterns could be helpful in MPM diagnosis. We analyzed blood samples from 175 workers previously exposed to asbestos, 157 non-exposed healthy subjects, and 37 MPM patients through a molecular exclusion chromatographic method. We found a specific profile of GGT fractions activity, significantly associated with MPM, resulting in an increase in b-, m- activity, along with an evident, yet not significant, decrease in f-activity. Receiver-operating characteristic (ROC) analysis showed that the best Area Under Curve (AUC) value resulted from the combined index b/f (0.679, 95% CI: 0.582-0.777). Combining the b-/f-GGT activity with the levels of serum mesothelin-related protein (SMRP; another promising MPM biomarker) improved the diagnostic accuracy, increasing the AUC value to 0.875 (95% CI: 0.807-0.943, p = <0.0001). Since MPM has a specific pattern of GGT enzymatic activity, we could hypothesize that GGT fractions play different specific biochemical roles. The improvement in the diagnostic power given by the combination of these two biomarkers confirms that the strategy of biomarkers combination might be a better approach for MPM diagnosis.}, }
@article {pmid35201802, year = {2022}, author = {Lond, B and Quincey, K and Apps, L and Darlison, L and Williamson, I}, title = {The experience of living with mesothelioma: A meta-ethnographic review and synthesis of the qualitative literature.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {}, number = {}, pages = {}, doi = {10.1037/hea0001166}, pmid = {35201802}, issn = {1930-7810}, abstract = {OBJECTIVE: Mesothelioma is a life limiting cancer caused by previous exposure to asbestos. Due to the continued use of asbestos products internationally, the condition presents an increasing risk to global health with case numbers peaking in industrially developed nations. With the cancer reducing patient well-being, this study aimed to synthesizes the qualitative findings of studies exploring the experiences of patients living with mesothelioma to generate new conceptual insights and guide therapeutic care.<br><br>METHOD: Thirteen databases were systematically searched: Academic Search Premier, BioMed Central, British Nursing Database, CINAHL Plus, Cochrane Library, Europe PubMed Central, MEDLINE, PsycARTICLES, PsycINFO, Science Direct, Scopus, Social Care Online, and Web of Science, between August and September 2020. Included articles were subject to quality appraisal using CASP checklists, and their respective findings analyzed using a metaethnographic form of qualitative data synthesis.<br><br>RESULTS: Twenty-two articles met the inclusion criteria, and the data synthesis produced three themes: (1) "complex trauma"; (2) "psycho-behavioral coping strategies"; and (3) "external sources of support." Combined, these themes form a novel conceptual framework and awareness of the patient experience that presents the lived trauma of disease alongside a patients coping processes and support pathways.<br><br>CONCLUSION: Robust therapeutic support is needed to address the psychosocial and existential burden shouldered by people with mesothelioma. Therapies that promote sentiments of acceptance, hope, and benefit finding are proposed alongside initiatives that foster patient empowerment and meaning, and further promote patient choice in deciding end-of-life care. Recommendations for future research are also made. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, }
@article {pmid35149582, year = {2022}, author = {van Kooten, JP and Belderbos, RA and von der Thüsen, JH and Aarts, MJ and Verhoef, C and Burgers, JA and Baas, P and Aalbers, AGJ and Maat, APWM and Aerts, JGJV and Cornelissen, R and Madsen, EVE}, title = {Incidence, treatment and survival of malignant pleural and peritoneal mesothelioma: a population-based study.}, journal = {Thorax}, volume = {}, number = {}, pages = {}, doi = {10.1136/thoraxjnl-2021-217709}, pmid = {35149582}, issn = {1468-3296}, abstract = {INTRODUCTION: Malignant mesothelioma (MM) is an aggressive cancer that primarily arises from the pleura (MPM) or peritoneum (MPeM), mostly due to asbestos exposure. This study reviewed the Dutch population-based incidence, treatment and survival since the national ban on asbestos in 1993.<br><br>MATERIALS AND METHODS: Patients with MPM or MPeM diagnosed from 1993 to 2018 were selected from the Dutch cancer registry. Annual percentage change (APC) was calculated for (age-specific and sex-specific) revised European standardised incidence rates (RESR). Treatment pattern and Kaplan-Meier overall survival analyses were performed.<br><br>RESULTS: In total, 12 168 patients were included in the study. For male patients younger than 80 years, the MM incidence significantly decreased in the last decade (APC ranging between -9.4% and -1.8%, p<0.01). Among both male and female patients aged over 80 years, the incidence significantly increased during the entire study period (APC 3.3% and 4.6%, respectively, p<0.01). From 2003 onwards, the use of systemic chemotherapy increased especially for MPM (from 9.3% to 39.4%). Overall, 62.2% of patients received no antitumour treatment. The most common reasons for not undergoing antitumour treatment were patient preference (42%) and performance status (25.6%). The median overall survival improved from 7.3 (1993-2003) to 8.9 (2004-2011) and 9.3 months from 2012 to 2018 (p<0.001).<br><br>CONCLUSION: The peak of MM incidence was reached around 2010 in the Netherlands, and currently the incidence is declining in most age groups. The use of systemic chemotherapy increased from 2003, which likely resulted in improved overall survival over time. The majority of patients do not receive treatment though and prognosis is still poor.}, }
@article {pmid35143119, year = {2022}, author = {Louw, A and van Vliet, C and Peverall, J and Colkers, S and Acott, N and Creaney, J and Lee, YCG and Chai, SM}, title = {Analysis of early pleural fluid samples in patients with mesothelioma: A case series exploration of morphology, BAP1, and CDKN2A status with implications for the concept of mesothelioma in situ in cytology.}, journal = {Cancer cytopathology}, volume = {}, number = {}, pages = {}, doi = {10.1002/cncy.22548}, pmid = {35143119}, issn = {1934-6638}, abstract = {BACKGROUND: The concept of mesothelioma in situ has been revisited and is a new World Health Organization diagnostic entity. The definition centers on ancillary techniques used in pleural mesothelioma (PM) assessment. At the authors' institution, most PM diagnoses are made on cytologic specimens. Effusion samples obtained before definitive PM diagnosis were interrogated using BRCA1-associated protein 1 gene (BAP1), cyclin-dependent kinase inhibitor 2A gene (CDKN2A) and cytologic evaluation to assess whether early or possible in situ disease could be characterized.<br><br>METHODS: All cases of PM diagnosed between January 2008 and December 2019 were identified at a tertiary referral center. Patients who had a pleural fluid sample collected 24 months before the diagnosis were selected, numbering 8 in total. The cytomorphology of each sample was reviewed; and, retrospectively, BAP1 immunohistochemistry (IHC) and CDKN2A fluorescence in situ hybridization (FISH) were performed on initial and diagnostic samples.<br><br>RESULTS: The initial samples were deemed benign in 5 cases and atypical mesothelial proliferations in 3 cases. A spectrum of apparently normal to atypical cytomorphologic changes was identified. BAP1 loss was present in 6 of 8 initial cases, whereas CDKN2A homozygous deletion was identified in 1 of 7 initial cases. Either abnormality was identified in 7 of 8 initial samples.<br><br>CONCLUSIONS: Detectable abnormalities of BAP1 IHC and CDKN2A FISH were present in pleural fluid specimens before the development of cytomorphologic features diagnostic of PM. This is the largest series to date describing cytology samples early in the course of PM development, thereby highlighting a possible cytological equivalent for mesothelioma in situ.}, }
@article {pmid35127504, year = {2021}, author = {Endo, I and Amatya, VJ and Kushitani, K and Kambara, T and Nakagiri, T and Fujii, Y and Takeshima, Y}, title = {Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Promotes Cell Proliferation of Malignant Mesothelioma Cells by Downregulating p27Kip1.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {795467}, doi = {10.3389/fonc.2021.795467}, pmid = {35127504}, issn = {2234-943X}, abstract = {Malignant mesothelioma is a tumor with a poor prognosis, mainly caused by asbestos exposure and with no adequate treatment yet. To develop future therapeutic targets, we analyzed the microarray dataset GSE 29370 of malignant mesothelioma and reactive mesothelial hyperplasia, downloaded from the Gene Expression Omnibus (GEO) database. We identified insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) as one of the significantly upregulated genes in malignant mesothelioma. IGF2BP3 functions as an oncoprotein in many human cancers; however, to our knowledge, this is the first study on the biological function of IGF2BP3 in malignant mesothelioma cells. The knockdown of IGF2BP3 in malignant mesothelioma cells resulted in the suppression of cell proliferation with an increase in the proportion of cells in the G1 phase of the cell cycle. Furthermore, knockdown of IGF2BP3 inhibited cell migration and invasion. We focused on the cell cycle assay to investigate the role of IGF2BP3 in cell proliferation in malignant mesothelioma. Among the various proteins involved in cell cycle regulation, the expression of p27 Kip1 (p27) increased significantly upon IGF2BP3 knockdown. Next, p27 siRNA was added to suppress the increased expression of p27. The results showed that p27 knockdown attenuated the effects of IGF2BP3 knockdown on cell proliferation and G1 phase arrest. In conclusion, we found that IGF2BP3 promotes cell proliferation, a critical step in tumorigenesis, by suppressing the expression of p27 in malignant mesothelioma.}, }
@article {pmid33890321, year = {2021}, author = {Zhang, F and Yuan, X and Sun, H and Yin, X and Gao, Y and Zhang, M and Jia, Z and Yu, M and Ying, S and Xia, H and Ju, L and Xiao, Y and Tao, H and Lou, J and Zhu, L}, title = {A nontoxic dose of chrysotile can malignantly transform Met-5A cells, in which microRNA-28 has inhibitory effects.}, journal = {Journal of applied toxicology : JAT}, volume = {41}, number = {11}, pages = {1879-1892}, doi = {10.1002/jat.4174}, pmid = {33890321}, issn = {1099-1263}, mesh = {Asbestos, Serpentine/*toxicity ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; MicroRNAs/*metabolism ; }, abstract = {Chrysotile, which is classified as a class I carcinogen by the International Agency for Research on Cancer (IARC), has extensive application in the industry and can lead to lung or other cancers. However, whether chrysotile causes malignant mesothelioma and its molecular mechanism remain debatable. Thus, this study aimed to demonstrate the mesothelioma-inducing potential of chrysotile at the mesothelial cellular level and the function of microRNA-28 in malignantly transformed mesothelial MeT-5A cells. MeT-5A cells malignantly transformed by a nontoxic dose of chrysotile were named Asb-T, and miR-28 expression was downregulated in Asb-T cells. Restoration of miR-28 expression inhibited the proliferation, migration and invasion of Asb-T cells. We verified that IMPDH is a putative target of miR-28. The expression of IMPDH was significantly higher in Asb-T MeT-5A cells than in control cells, whereas the opposite trend was observed with miR-28 overexpression. Additionally, inhibition of IMPDH had similar effects as miR-28 overexpression. After miR-28 was elevated or IMPDH was inhibited, Ras activation was reduced, and its downstream pathways (the Erk and Akt signalling pathways) were inhibited. Surprisingly, the content of miR-28 in the blood of mesothelioma patients was higher than that in control subjects. Overall, nontoxic doses of chrysotile can cause malignant transformation of MeT-5A cells. Moreover, miR-28 inhibits the proliferation, migration and invasion of Asb-T MeT-5A cells, negatively regulates the expression of IMPDH through the Ras signalling pathway and may be an important therapeutic target.}, }
@article {pmid35114507, year = {2022}, author = {Repo, P and Staskiewicz, A and Sutinen, E and Rönty, M and Tero T Kivelä,  and Myllärniemi, M and Turunen, JA}, title = {BAP1 germline variants in Finnish patients with malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {165}, number = {}, pages = {102-107}, doi = {10.1016/j.lungcan.2022.01.017}, pmid = {35114507}, issn = {1872-8332}, abstract = {OBJECTIVES: Although asbestos exposure is the most common cause of malignant mesothelioma (MM), an aggressive cancer of the pleura or peritoneum, up to 7% of patients harbor a genetic predisposition to MM. Pathogenic germline variants in the BRCA1-associated protein 1 (BAP1) gene cause a dominantly inherited tumor predisposition syndrome, BAP1-TPDS, in which MM is the second most common associated cancer. Other frequent cancers in BAP1-TPDS are uveal melanoma (UM), cutaneous melanoma and renal cell carcinoma. Additionally patients can exhibit benign skin lesions, BAP1-inactivated nevi (BIN). Most BINs arise sporadically, but patients with BAP1-TPDS may harbor multiple BINs before other tumors or as the only indication of the syndrome. Our objective was to establish the frequency of pathogenic germline BAP1 variants in Finnish patients with MM.<br><br>MATERIALS AND METHODS: 56 DNA samples archived in the Helsinki Biobank from Finnish patients with MM were sequenced for germline BAP1 variations. Formalin fixed paraffin embedded nevi from a pathogenic variant carrier were subjected to immunohistochemistry and exome sequencing.<br><br>RESULTS: Sanger sequencing identified one patient with Finnish founder mutation c.1780_1781insT, p.(G549Vfs*49) in BAP1. The carrier was diagnosed with MM over fifteen years before the cohorts mean onset age (mean 68, range 27 to 82) although the patient had no asbestos exposure or family history of BAP1-TPDS. However, the patient had three BINs removed prior to the MM. The c.1780_1781insT is now found from five Finnish BAP1-TPDS families with unknown common ancestor.<br><br>CONCLUSION: The frequency of pathogenic germline BAP1 variants in Finnish patients with MM is 1.8 % (95 % CI, 0.04 to 9.2), comparable to the frequency in Finnish patients with UM (1.9 %). The frequency of recurring BINs in patients with BAP1-TPDS should be studied further and genetic testing for BAP1 variants considered if the patient has ≥ 2 BAP1-TPDS core tumors, including BINs.}, }
@article {pmid34612763, year = {2021}, author = {Korchevskiy, AA and Wylie, AG}, title = {Dimensional determinants for the carcinogenic potency of elongate amphibole particles.}, journal = {Inhalation toxicology}, volume = {33}, number = {6-8}, pages = {244-259}, doi = {10.1080/08958378.2021.1971340}, pmid = {34612763}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/*adverse effects/chemistry ; Environmental Pollutants/*adverse effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; }, abstract = {CONTEXT: Carcinogenic properties of particulates depend, among other factors, on dimensional characteristics that affect their ability to reach sensitive tissue, to be removed or retained, and to interact with the cells.<br><br>OBJECTIVE: To model mesothelioma and lung cancer potency of amphibole particles based on their dimensional characteristics and mineral habit (asbestiform vs. nonasbestiform) utilizing epidemiological data and detailed size information.<br><br>METHODS: The datasets from recently created depository of dimensional information of elongate mineral particles were used to correlate mesothelioma and lung cancer potency with the fraction of particles in a specific size range and the ratio of length and width in different powers. In addition, the cancer potency factors were estimated and compared for 30 asbestiform, 15 nonasbestiform, and 10 mixed datasets.<br><br>RESULTS: For particles longer than 5 µm, the highest correlation with mesothelioma potency was achieved for width <0.22 µm, and with lung cancer <0.28 µm. The statistical power of the correlation was observed to lose significance at a maximum width of 0.6-0.7 µm. Mesothelioma potency correlated with length in the power of 1.9 divided by width in the power of 2.97, lung cancer potency with length in the power of 0.4 divided by width in the power of 1.17. The predicted cancer potencies of asbestiform, nonasbestiform, and mixed categories were significantly different.<br><br>CONCLUSION: While additional studies in this direction are warranted, this paper should serve as an additional confirmation for the role of fiber dimensions in the carcinogenicity of amphibole elongate mineral particles (EMPs).}, }
@article {pmid35102573, year = {2022}, author = {LeMasters, G and Lockey, JE and Hilbert, TJ and Burkle, JW and Rice, CH}, title = {Mortality of workers employed in refractory ceramic fiber manufacturing: An update.}, journal = {Journal of applied toxicology : JAT}, volume = {}, number = {}, pages = {}, doi = {10.1002/jat.4295}, pmid = {35102573}, issn = {1099-1263}, abstract = {This study evaluates the possible association between refractory ceramic fibers (RCF) exposure and all causes of death. Current and former employees (n=1,119) hired from 1952-1999 at manufacturing facilities in New York (NY) state and Indiana were included. Work histories and quarterly plant-wide sampling from 1987-2015 provided cumulative fiber exposure (CFE) estimates. The full cohort was evaluated as well as individuals with lower and higher exposure, <45 and >45 fiber-months/cc. The Life-Table-Analysis-System was used for all standardized mortality estimates (SMR). Person-years at risk accumulated from start of employment until 12/31/2019 or date of death. There was no significant association with all causes, all cancers, or lung cancer in any group. In the higher exposed there was a significant elevation in both malignancies of the "urinary organs" (SMR=3.59, 95% CI 1.44, 7.40), and "bladder or other urinary site" (SMR=4.04, 95% CI 1.10, 10.36) which persisted in comparison to regional mortality rates from NY state and Niagara County. However, six of the nine workers with urinary cancers were known smokers. In the lower exposed there was a significant elevation in malignancies of the lymphatic and hematopoietic system (SMR=2.54, 95% CI 1.27, 4.55) and leukemia (SMR=4.21, 95% CI 1.69, 8.67). There was one pathologically unconfirmed mesothelioma death. A second employee currently living with a pathologically confirmed mesothelioma was identified, but the SMR was non-significant when both were included in the analyses. The association of these two mesothelioma cases with RCF exposure alone is unclear because of potential past exposure to asbestos.}, }
@article {pmid35098897, year = {2022}, author = {Le, HT and Dinh, HT and Ngo, TT}, title = {Asbestos Dust Concentrations and Health Conditions of Workers at Asbestos - Cement Corrugated Sheets Production Manufacturers in Vietnam: A national-wide assessment.}, journal = {International journal of occupational safety and ergonomics : JOSE}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/10803548.2022.2035510}, pmid = {35098897}, issn = {2376-9130}, abstract = {This study examined contemporary concentrations of asbestos dust during production and health conditions of workers at Asbestos - Cement Corrugated Sheets Production Manufacturers in Vietnam. A nationwide survey was conducted on 28 factories (with 206 air samples) and 2459 workers. Asbestos fiber dust and the health status of workers were assessed. Results showed that 108/206 (52.4%) samples had asbestos fiber dust. The average concentration of asbestos fibers was 0.19±0.14 fibers/ml. The percentage of workers with thickened pleural lesions/pleural calcification nodules was low. More studies are needed to evaluate the effectiveness of biomarkers in preventing the onset of lung cancer and mesothelioma in workers.}, }
@article {pmid35098108, year = {2021}, author = {Zolondick, AA and Gaudino, G and Xue, J and Pass, HI and Carbone, M and Yang, H}, title = {Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review.}, journal = {Precision cancer medicine}, volume = {4}, number = {}, pages = {}, doi = {10.21037/pcm-21-12}, pmid = {35098108}, issn = {2617-2216}, abstract = {Objective: The aim of this review is addressing the mechanisms of asbestos carcinogenesis, including chronic inflammation and autophagy-mediated cell survival, and propose potential innovative therapeutic targets to prevent mesothelioma development or improve drug efficacy by reducing inflammation and autophagy.<br><br>Background: Diffuse malignant pleural mesothelioma is an aggressive cancer predominantly related to chronic inflammation caused by asbestos exposure. Millions of individuals have been exposed to asbestos or to other carcinogenic mineral fibers occupationally or environmentally, resulting in an increased risk of developing mesothelioma. Overall patient survival rates are notably low (about 8-14 months from the time of diagnosis) and mesothelioma is resistant to existing therapies. Additionally, individuals carrying inactivating germline mutations in the BRCA-associated protein 1 (BAP1) gene and other genes are predisposed to developing cancers, prevalently mesothelioma. Their risk of developing mesothelioma further increases upon exposure to asbestos. Recent studies have revealed the mechanisms and the role of inflammation in asbestos carcinogenesis. Biomarkers for asbestos exposure and malignant mesothelioma have also been identified. These findings are leading to the development of novel therapeutic approaches to prevent or delay the growth of mesothelioma.<br><br>Methods: Review of full length manuscripts published in English from January 1980 to February 2021 gathered from PubMed.gov from the National Center of Biotechnology Information and the National Library of Medicine were used to inform this review.<br><br>Conclusion: Key regulators of chronic inflammation mediate asbestos-driven mesothelial cell transformation and survival through autophagic pathways. Recent studies have elucidated some of the key mechanisms involved in asbestos-induced chronic inflammation, which are largely driven by extracellular high mobility group box 1 (HMGB1). Upon asbestos exposure, mesothelial cells release HMGB1 from the nucleus to the cytoplasm and extracellular space, where HMGB1 initiates an inflammatory response. HMGB1 translocation and release also activates autophagy and other pro-survival mechanisms, which promotes mesothelioma development. HMGB1 is currently being investigated as a biomarker to detect asbestos exposure and to detect mesothelioma development in its early stage when therapy is more effective. In parallel, several approaches inhibiting HMGB1 activities have been studied and have shown promising results. Moreover, additional cytokines, such as IL-1β and TNF-α are being targeted to interfere with the inflammatory process that drives mesothelioma growth. Developing early detection methods and novel therapeutic strategies is crucial to prolong overall survival of patients with mesothelioma. Novel therapies targeting regulators of asbestos-induced inflammation to reduce mesothelioma growth may lead to clinical advancements to benefit patients with mesothelioma.}, }
@article {pmid35089637, year = {2022}, author = {Yue, L and Luo, Y and Jiang, L and Sekido, Y and Toyokuni, S}, title = {PCBP2 knockdown promotes ferroptosis in malignant mesothelioma.}, journal = {Pathology international}, volume = {}, number = {}, pages = {}, doi = {10.1111/pin.13209}, pmid = {35089637}, issn = {1440-1827}, support = {19-251//Princess Takamatsu Cancer Research Fund/ ; JPMJCR19H4//Core Research for Evolutional Science and Technology/ ; JP19H05462 and JP20H05502//Japan Society for the Promotion of Science/ ; //JST CREST/ ; //JSPS Kakenhi/ ; //Research Grant of the Princess Takamatsu Cancer Research Fund/ ; }, abstract = {Malignant mesothelioma (MM) is still increasing worldwide. The pathogenesis depends on asbestos-induced iron accumulation, which eventually leads to ferroptosis-resistance of mesothelial cells via somatic mutations. Poly (rC)-binding proteins 1 and 2 (PCBP1/2) are recently recognized cytosolic Fe(II) chaperones. Here we studied the role of PCBP1/2 in rat/human mesothelial and MM cells as well as rat/human MM specimens. Normal peritoneal mesothelial cells in rats exhibited PCBP1 but not PCBP2 immunopositivity whereas primary/immortalized mesothelial cells showed PCBP1/2 immunopositivity. Rat MM specimens induced by intraperitoneal injection of chrysotile, including in situ lesion, revealed PCBP1/2 immunopositivity (90% for both) in the nucleus and cytoplasm with a tendency of higher expression in epithelioid subtype. Knockdown of PCBP2 but not PCBP1 significantly decreased both TfR1 and FTH expression in MM cells with inhibition of proliferation, indicating stagnation of intracellular iron transport. Erastin, a cysteine-deprivation type ferroptosis inducer, decreased the expression of both PCBP1/2 in MM cells. Furthermore, PCBP2 knockdown significantly increased the sensitivity of MM cells to erastin-induced ferroptosis with increased catalytic Fe(II). In conclusion, PCBP2 works for ferroptosis-resistance not only during mesothelial carcinogenesis but also in MM, which warrants further investigation as a novel therapeutic target.}, }
@article {pmid35089066, year = {2022}, author = {Kelsey, K}, title = {Epigenetics, environment and epidemiology: an interview with Karl Kelsey.}, journal = {Epigenomics}, volume = {}, number = {}, pages = {}, doi = {10.2217/epi-2022-0008}, pmid = {35089066}, issn = {1750-192X}, abstract = {In this interview, Professor Karl Kelsey speaks with Storm Johnson, Commissioning Editor for Epigenomics, on his work to date in the field of environmental epigenomics and epidemiology. Dr Karl Kelsey, MD, MOH is a Professor of Epidemiology and Pathology and Laboratory Medicine at Brown University. He is the Founding Director of the Center for Environmental Health and Technology and Head of the Environmental Health Section at the Department of Epidemiology. Dr Kelsey is interested in the application of laboratory-based biomarkers in environmental disease, with experience in chronic disease epidemiology and tumor biology. The goals of his work include a mechanistic understanding of individual susceptibility to exposure-related cancers. In addition, his laboratory is interested in tumor biology, investigating somatic alterations in tumor tissue from the patients who have developed exposure-related cancers. This work involves the use of an epidemiologic approach to characterize epigenetic and genetic alteration of genes in the causal pathway for malignancy. Active work includes several studies of individual susceptibility to cancer. Dr Kelsey's laboratory mainly investigates susceptibility to smoking-related lung cancer and studies multi-racial and ethnic populations. In addition, the laboratory is also involved with the study of inherited susceptibility to brain tumors and pancreatic cancer. Major case control studies that are ongoing in the laboratory include studies designed to understand inherited and acquired susceptibility in head and neck cancers. The laboratory is also involved in a case control study of asbestos-associated mesothelioma, arsenic exposure, cigarette smoking and bladder cancer. Considerable work is being devoted to understanding the mechanisms of action of both asbestos and arsenic including their ability to affect promoter methylation and gene silencing in carcinogenesis. Recent laboratory studies includes an interest in using newly developed DNA methylation biomarkers to probe immune profiles from archived blood. Dr Kelsey received his MD from the University of Minnesota and Masters of Occupational Health from Harvard University.}, }
@article {pmid35081587, year = {2022}, author = {Tao, XG and Curriero, FC and Chee, EM and Mahesh, M}, title = {Updated Standardized Mortality Ratio Evaluation of Disease Risks of Shipyard Workers Exposed to Low Dose Ionizing Radiation.}, journal = {Journal of occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/JOM.0000000000002491}, pmid = {35081587}, issn = {1536-5948}, abstract = {OBJECTIVE: To examine the risk of diseases among industrial workers with low and fractionated radiation exposures.<br><br>METHOD: 372,047 US male shipyard radiation and non-radiation workers were followed for 54 years and compared to US males using Standardized Mortality Ratio (SMR) method.<br><br>RESULTS: SMRs for both radiation and non-radiation workers had lower risks of death from all causes (0.74; 95% Confidence interval (CI) 0.74-0.75 and 0.77; 95% Cl 0.77-0.78, respectively) and from all cancers (0.92; 95% CI 0.91-0.93 and 0.90; 95% CI 0.89-0.91, respectively) compared to US males. Asbestos-related diseases including pleural cancers, mesothelioma, and asbestosis, but not lung cancers, were statistically higher in both radiation and non-radiation workers compared to the US males.<br><br>CONCLUSION: US shipyard male radiation and non-radiation workers did not show any elevated mortality risks that might be associated with radiation exposure.}, }
@article {pmid35078853, year = {2022}, author = {Kok, PS and Forde, PM and Hughes, B and Sun, Z and Brown, C and Ramalingam, S and Cook, A and Lesterhuis, WJ and Yip, S and O'Byrne, K and Pavlakis, N and Brahmer, J and Anagnostou, V and Ford, K and Fitzpatrick, K and Bricker, A and Cummins, MM and Stockler, M and Nowak, AK and , }, title = {Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial.}, journal = {BMJ open}, volume = {12}, number = {1}, pages = {e057663}, doi = {10.1136/bmjopen-2021-057663}, pmid = {35078853}, issn = {2044-6055}, abstract = {INTRODUCTION: There is a strong theoretical rationale for combining checkpoint blockade with cytotoxic chemotherapy in pleural mesothelioma and other cancers. Two recent single-arm, phase 2 trials [DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (PrE0505)] combining the programmed death ligand-1 (PD-L1) inhibitor durvalumab with standard first-line chemotherapy exceeded prespecified safety and activity criteria to proceed to a phase 3 confirmatory trial to assess this combination. We present the protocol of the DREAM3R trial.<br><br>METHODS AND ANALYSIS: This multicentre open-label randomised trial will recruit 480 treatment-naïve adults with advanced pleural mesothelioma, randomised (2:1) to either 3-weekly durvalumab 1500 mg plus 3-weekly doublet chemotherapy (cisplatin 75 mg/m2 or carboplatin, Area Under the Curve,AUC 5 and pemetrexed 500 mg/m2) 4-6 cycles, followed by 4-weekly durvalumab 1500 mg until disease progression, unacceptable toxicity or patient withdrawal; OR doublet chemotherapy alone for 4-6 cycles, followed by observation. The target accrual time is 27 months, with follow-up for an additional 24 months. This provides over 85% power if the true HR for overall survival (OS) is 0.70, with two-sided alpha of 0.05, assuming a median OS of 15 months in the control group. Randomisation is stratified by age (18-70 years vs >70), sex, histology (epithelioid vs non-epithelioid), platinum agent (cisplatin vs carboplatin) and region (USA vs Australia/New Zealand vs Other). The primary endpoint is OS. Secondary endpoints include progression-free survival, objective tumour response (by mRECIST V.1.1 and iRECIST), adverse events, health-related quality of life and healthcare resource use. Tertiary correlative objectives are to explore and validate potential prognostic and/or predictive biomarkers (including features identified in the DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and PrE0505 studies, PD-L1 expression, tumour mutational burden, genomic characteristics and human leukocyte antigen subtypes) in tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma.<br><br>ETHICS AND DISSEMINATION: The protocol was approved by human research ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences.<br><br>DRUG SUPPLY: AstraZeneca.<br><br>PROTOCOL VERSION: CTC 0231 / TOGA 18/001 / PrE0506 3.0, 29 July 2021.<br><br>TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04334759 ACTRN 12620001199909.}, }
@article {pmid35073065, year = {2022}, author = {Voloaca, OM and Clench, MR and Koellensperger, G and Cole, LM and Haywood-Small, SL and Theiner, S}, title = {Elemental Mapping of Human Malignant Mesothelioma Tissue Samples Using High-Speed LA-ICP-TOFMS Imaging.}, journal = {Analytical chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.analchem.1c04857}, pmid = {35073065}, issn = {1520-6882}, abstract = {This is the first report of the use of laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) to analyze human malignant pleural mesothelioma (MPM) samples at the cellular level. MPM is an aggressive, incurable cancer associated with asbestos exposure, with a long latency and poor overall survival. Following careful optimization of the laser fluence, the simultaneous ablation of soft biological tissue and hard mineral fibers was possible, allowing the spatial detection of elements such as Si, Mg, Ca, and Fe, which are also present in the glass substrate. A low-dispersion LA setup was employed, which provided the high spatial resolution necessary to identify the asbestos fibers and fiber fragments in the tissue and to characterize the metallome at the cellular level (a pixel size of 2 μm), with a high speed (at 250 Hz). The multielement LA-ICP-TOFMS imaging approach enabled (i) the detection of asbestos fibers/mineral impurities within the MPM tissue samples of patients, (ii) the visualization of the tissue structure with the endogenous elemental pattern at high spatial resolution, and (iii) obtaining insights into the metallome of MPM patients with different pathologies in a single analysis run. Asbestos and other mineral fibers were detected in the lung and pleura tissue of MPM patients, respectively, based on their multielement pattern (Si, Mg, Ca, Fe, and Sr). Interestingly, strontium was detected in asbestos fibers, suggesting a link between this potential toxic element and MPM pathogenesis. Furthermore, monitoring the metallome around the talc deposit regions (characterized by elevated levels of Al, Mg, and Si) revealed significant tissue damage and inflammation caused by talc pleurodesis. LA-ICP-TOFMS results correlated to Perls' Prussian blue and histological staining of the corresponding serial sections. Ultimately, the ultra-high-speed and high-spatial-resolution capabilities of this novel LA-ICP-TOFMS setup may become an important clinical tool for simultaneous asbestos detection, metallome monitoring, and biomarker identification.}, }
@article {pmid35058235, year = {2022}, author = {Senek, M and Robertson, S and Darlison, L and Creech, L and Tod, A}, title = {Malignant pleural mesothelioma patients' experience by gender: findings from a cross-sectional UK-national questionnaire.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, doi = {10.1136/bmjresp-2021-001050}, pmid = {35058235}, issn = {2052-4439}, abstract = {OBJECTIVES: Malignant mesothelioma is an aggressive malignancy of mesothelial surfaces, most commonly those of the pleura. The aim of this study was to understand, using a national questionnaire, the gendered care experiences of patients with malignant pleural mesothelioma (MPM).Patients were asked about their experience of the diagnostic process, about information clarity, health care professionals' knowledge, general practitioner support and overall satisfaction with care received.<br><br>SETTING: Recruitment of patients was carried out in three UK countries (England, Wales and Scotland) via mesothelioma clinical nurse specialists.<br><br>PARTICIPANTS: In total, 503 patients completed the questionnaire. 460 had MPM, the remainder had other types of mesothelioma. In accord with the study protocol, only the MPM patients were included in this study.Primary and secondary measures were: (1) time from symptom to diagnosis, (2) satisfaction with the diagnosis and treatment, and (3) quality of life and well-being.<br><br>RESULTS: There were gender differences in time from symptom to diagnosis. The time from symptom to diagnosis was significantly longer for women than men (median=152 days vs men=92 days, p=0.01). Lack of a verified source of exposure to asbestos was a hindrance to private treatment access for women (95% of those that access private treatment are men). Patients were five times more likely to be satisfied if they thought that the doctors knew enough about their condition (OR=4.4, p=0.001) and nearly three times more likely to be satisfied if information was presented in a sensitive way (OR=2.8,p=0.01).<br><br>CONCLUSIONS: This study has several implications for clinical practice. Our findings suggest that the diagnostic time in women might be reduced by reviewing diagnostic processes including occupational history taking, and by revising the occupational risk of mesothelioma categorisation.}, }
@article {pmid34673618, year = {2021}, author = {Sunitha, S and Shah, AH and Gami, A and Trivedi, P}, title = {Thigh mass in a patient with malignant pleural mesothelioma: Metastasis at an unusual site.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {4}, pages = {834-836}, doi = {10.4103/IJPM.IJPM_463_20}, pmid = {34673618}, issn = {0974-5130}, mesh = {Asbestos/adverse effects ; Humans ; Male ; Medicine, Ayurvedic ; Mesothelioma, Malignant/*pathology ; Middle Aged ; Muscle Neoplasms/*secondary ; Occupational Exposure/adverse effects ; Pleural Cavity/pathology ; Soft Tissue Neoplasms/*pathology ; Thigh/*pathology ; }, abstract = {Soft tissue tumors are a highly heterogeneous group of lesions with varied clinical presentation. The majority is primary tumors and metastatic tumors are very rare. Malignant pleural mesothelioma presenting as a soft tissue mass at a distant site is even rarer and can cause diagnostic challenges both clinically and pathologically. We report a case of malignant pleural mesothelioma presenting as a soft tissue mass in the left thigh. A 59-year-old man, non-smoker, working in a cement factory since 30 years presented with complains of difficulty in walking since 1½ months. Review of his previous medical records revealed malignant pleural mesothelioma, which was diagnosed 9 months before. He had denied chemotherapy and was on Ayurvedic medication. The lesion involved the adjacent intercostal muscles. Few enlarged lymph nodes were noted in mediastinal and cervical regions. Biopsy of left supraclavicular and right cervical lymph nodes showed metastases. Metastasis from malignant pleural mesothelioma to the thigh was confirmed by immunohistochemistry. The tumor was positive for CK5/6, CK7, Calretinin and vimentin and immunonegative for CEA, Napsin A and TTF 1.}, }
@article {pmid35042132, year = {2021}, author = {Armato, SG and Nowak, AK and Francis, RJ and Katz, SI and Kholmatov, M and Blyth, KG and Gudmundsson, E and Kidd, AC and Gill, RR}, title = {Imaging in pleural mesothelioma: A review of the 15th International Conference of the International Mesothelioma Interest Group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {164}, number = {}, pages = {76-83}, doi = {10.1016/j.lungcan.2021.12.008}, pmid = {35042132}, issn = {1872-8332}, abstract = {Imaging of mesothelioma plays a role in all aspects of patient management, including disease detection, staging, evaluation of treatment options, response assessment, pre-surgical evaluation, and surveillance. Imaging in this disease impacts a wide range of disciplines throughout the healthcare enterprise. Researchers and clinician-scientists are developing state-of-the-art techniques to extract more of the information contained within these medical images and to utilize it for more sophisticated tasks; moreover, image-acquisition technology is advancing the inherent capabilities of these images. This paper summarizes the imaging-based topics presented orally at the 2021 International Conference of the International Mesothelioma Interest Group (iMig), which was held virtually from May 7-9, 2021. These topics include an update on the mesothelioma staging system, novel molecular targets to guide therapy in mesothelioma, special considerations and potential pitfalls in imaging mesothelioma in the immunotherapy setting, tumor measurement strategies and their correlation with patient survival, tumor volume measurement in MRI and CT, CT-based texture analysis for differentiation of histologic subtype, diffusion-weighted MRI for the assessment of biphasic mesothelioma, and the prognostic significance of skeletal muscle loss with chemotherapy.}, }
@article {pmid35032816, year = {2022}, author = {Sculco, M and La Vecchia, M and Aspesi, A and Pinton, G and Clavenna, MG and Casalone, E and Allione, A and Grosso, F and Libener, R and Muzio, A and Rena, O and Baietto, G and Parini, S and Boldorini, R and Giachino, D and Papotti, M and Scagliotti, GV and Migliore, E and Mirabelli, D and Moro, L and Magnani, C and Ferrante, D and Matullo, G and Dianzani, I}, title = {Malignant pleural mesothelioma: Germline variants in DNA repair genes may steer tailored treatment.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {163}, number = {}, pages = {44-54}, doi = {10.1016/j.ejca.2021.12.023}, pmid = {35032816}, issn = {1879-0852}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a tumour associated with asbestos exposure. Approximately, 10% of patients with MPM carry a germline pathogenic variant (PV), mostly in DNA repair genes, suggesting the occurrence of inherited predispositions.<br><br>AIM: This article aimed to 1) search for new predisposing genes and assess the prevalence of PVs in DNA repair genes, by next-generation sequencing (NGS) analysis of germline DNA from 113 unselected patients with MPM and 2) evaluate whether these patients could be sensitive to tailored treatments.<br><br>METHODS: NGS was performed using a custom panel of 107 cancer-predisposing genes. To investigate the response to selected drugs in conditions of DNA repair insufficiency, we created a three-dimensional-MPM cell model that had a defect in ataxia telangiectasia mutated (ATM), the master regulator of DNA repair.<br><br>RESULTS: We identified PVs in approximately 7% of patients with MPM (8/113) and a new PV in BAP1 in a further patient with familial MPM. Most of these PVs were in genes involved or supposedly involved in DNA repair (BRCA1, BRIP1, CHEK2, SLX4, FLCN and BAP1). In vitro studies showed apoptosis induction in ATM-silenced/inhibited MPM spheroids treated with an enhancer of zeste homologue 2 inhibitor (tazemetostat).<br><br>CONCLUSIONS: Overall these data suggest that patients with MPM and DNA repair insufficiency may benefit from this treatment, which induces synthetic lethality.}, }
@article {pmid35010531, year = {2021}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, Ø}, title = {Cancer Incidence and Risk of Multiple Cancers after Environmental Asbestos Exposure in Childhood-A Long-Term Register-Based Cohort Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {1}, pages = {}, doi = {10.3390/ijerph19010268}, pmid = {35010531}, issn = {1660-4601}, abstract = {OBJECTIVES: To examine the asbestos-associated cancer incidence and the risk of multiple cancers in former school children exposed to environmental asbestos in childhood.<br><br>METHODS: A cohort of 12,111 former school children, born 1940-1970, was established using 7th grade school records from four schools located at a distance of 100-750 m in the prevailing wind direction from a large asbestos-cement plant that operated from 1928 to 1984 in Aalborg, Denmark. Using the unique Danish personal identification number, we linked information on employments, relatives' employments, date of cancer diagnosis, and type of cancer and vital status to data on cohortees extracted from the Supplementary Pension Fund Register (employment history), the Danish Cancer Registry, and the Danish Civil Registration System. We calculated standardized incidence rates (SIRs) for asbestos-associated cancers, all cancers, and multiple cancers using rates for a gender and five-year frequency-matched reference cohort.<br><br>RESULTS: The overall incidence of cancer was modestly increased for the school cohort (SIR 1.07, 95% confidence interval (CI) 1.02-1.12) compared with the reference cohort. This excess was driven primarily by a significantly increased SIR for malignant mesothelioma (SIR 8.77, 95% CI 6.38-12.05). Former school children who had combined childhood environmental and subsequent occupational exposure to asbestos had a significantly increased risk of lung cancer. Within this group, those with additional household exposure by a relative had a significantly increased SIR for cancer of the pharynx (SIR 4.24, 95% CI 1.59-11.29). We found no significant difference in the number of subjects diagnosed with multiple cancers between the two cohorts.<br><br>CONCLUSIONS: Our study confirms the strong association between environmental asbestos exposure and malignant mesothelioma and suggests that environmental asbestos exposure in childhood may increase the overall cancer risk later in life.}, }
@article {pmid35010496, year = {2021}, author = {Binazzi, A and Di Marzio, D and Verardo, M and Migliore, E and Benfatto, L and Malacarne, D and Mensi, C and Consonni, D and Eccher, S and Mazzoleni, G and Comiati, V and Negro, C and Romanelli, A and Chellini, E and Angelini, A and Grappasonni, I and Madeo, G and Romeo, E and Di Giammarco, A and Carrozza, F and Angelillo, IF and Cavone, D and Vimercati, L and Labianca, M and Tallarigo, F and Tumino, R and Melis, M and Bonafede, M and Scarselli, A and Marinaccio, A and On Behalf Of The ReNaM Working Group, }, title = {Asbestos Exposure and Malignant Mesothelioma in Construction Workers-Epidemiological Remarks by the Italian National Mesothelioma Registry (ReNaM).}, journal = {International journal of environmental research and public health}, volume = {19}, number = {1}, pages = {}, doi = {10.3390/ijerph19010235}, pmid = {35010496}, issn = {1660-4601}, abstract = {Notwithstanding the ban in 1992, asbestos exposure for workers in the construction sector in Italy remains a concern. The purpose of this study is to describe the characteristics of malignant mesothelioma (MM) cases recorded by the Italian registry (ReNaM) among construction workers. Incident mesothelioma cases with a definite asbestos exposure have been analyzed. Characteristics of cases and territorial clusters of crude rates of MM in construction workers have been described, as well as the relation between asbestos use before the ban and the historical trend of workforce in the construction sector in Italy. ReNaM has collected 31,572 incident MM cases in the period from 1993 to 2018 and asbestos exposure has been assessed for 24,864 (78.2%) cases. An occupational exposure has been reported for 17,191 MM cases (69.1% of subjects with a definite asbestos exposure). Among them, 3574 had worked in the construction sector, with an increasing trend from 15.8% in the 1993-98 period to 23.9% in 2014-2018 and a ubiquitous territorial distribution. The large use of asbestos in construction sector before the ban makes probability of exposure for workers a real concern still today, particularly for those working in maintenance and removal of old buildings. There is a clear need to assess, inform, and prevent asbestos exposure in this sector.}, }
@article {pmid35004305, year = {2021}, author = {Crovella, S and Revelant, A and Muraro, E and Moura, RR and Brandão, L and Trovò, M and Steffan, A and Zacchi, P and Zabucchi, G and Minatel, E and Borelli, V}, title = {Biological Pathways Associated With the Development of Pulmonary Toxicities in Mesothelioma Patients Treated With Radical Hemithoracic Radiation Therapy: A Preliminary Study.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {784081}, doi = {10.3389/fonc.2021.784081}, pmid = {35004305}, issn = {2234-943X}, abstract = {Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients.}, }
@article {pmid34992464, year = {2021}, author = {Tai, SY and Wu, J and Lee, LJ and Lu, TH}, title = {How Malignant Mesothelioma Was Coded in Mortality Data in Taiwan During Years When the Specific ICD Code Was Not Available?.}, journal = {Clinical epidemiology}, volume = {13}, number = {}, pages = {1135-1140}, doi = {10.2147/CLEP.S339956}, pmid = {34992464}, issn = {1179-1349}, abstract = {Purpose: Malignant mesothelioma (MM) is associated with past exposure to asbestos and the latency period ranged from 20 to 40 years. Asbestos consumption reached a peak in the 1980s in Taiwan, and the MM mortality is expected to increase since 2000s. However, no specific code for MM was available before the International Classification of Disease, Tenth Revision (ICD-10), which was launched in 2008 in Taiwan. We examined how MM was coded in mortality data in Taiwan during the years when the ICD, Ninth Revision (ICD-9) was used.<br><br>Patients and Methods: Double-coded mortality data (each death coded according to both ICD-10 and ICD-9 codes) for the period 2002-2008 were obtained for analysis. Detection rates (similar to sensitivity) and confirmation rates (similar to positive predictive value) for various potential proxy ICD-9 codes for MM were calculated.<br><br>Results: For 113 deaths, for which the underlying cause of death was ICD-10 code C45 (MM), 14 corresponding ICD-9 codes were used. Four ICD-9 codes constituted 77% (87/113) of all MM deaths. The detection rate for code 199 (malignant neoplasm [MN] without specification of site) was 37% (42/113), that for code 163 (MN of pleura) was 18% (20/113), that for code 162 (MN of trachea, bronchus, and lung) was 12% (14/113), and that for code 173 (other MN of skin) was 10% (11/113). The confirmation rates for codes 199, 163, 162, and 173 were 0.9% (42/4759), 14.3% (20/140), 0.03% (14/51,778), and 1.5% (11/717), respectively.<br><br>Conclusion: ICD-9 codes 199, 163, 162, and 173 were most commonly used for MM deaths in Taiwan during the years before the ICD-10 introduction. However, when we used only ICD-9 code 163, which was most commonly used as a surrogate measure of MM in mortality studies during the ICD-9 era, we could detect only one-fifth of MM deaths in Taiwan.}, }
@article {pmid34984327, year = {2022}, author = {Orozco Morales, ML and Rinaldi, CA and de Jong, E and Lansley, SM and Gummer, JPA and Olasz, B and Nambiar, S and Hope, DE and Casey, TH and Lee, YCG and Leslie, C and Nealon, G and Shackleford, DM and Powell, AK and Grimaldi, M and Balaguer, P and Zemek, RM and Bosco, A and Piggott, MJ and Vrielink, A and Lake, RA and Lesterhuis, WJ}, title = {PPARα and PPARγ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective.}, journal = {iScience}, volume = {25}, number = {1}, pages = {103571}, doi = {10.1016/j.isci.2021.103571}, pmid = {34984327}, issn = {2589-0042}, abstract = {Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma exposure levels sufficient for inhibition of PPARα/γ transcriptional activity did not result in significant anti-mesothelioma activity in mice. Lastly, we demonstrate that the in vitro anti-tumor effect of GW6471 is off-target. We conclude that dual PPARα/γ antagonism alone is not a viable treatment modality for mesothelioma.}, }
@article {pmid34948906, year = {2021}, author = {Lysaniuk, B and Cely-García, MF and Giraldo, M and Larrahondo, JM and Serrano-Calderón, LM and Guerrero-Bernal, JC and Briceno-Ayala, L and Cruz Rodriguez, E and Ramos-Bonilla, JP}, title = {Using GIS to Estimate Population at Risk Because of Residence Proximity to Asbestos Processing Facilities in Colombia.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {24}, pages = {}, pmid = {34948906}, issn = {1660-4601}, mesh = {*Asbestos ; Asbestos, Serpentine ; Colombia/epidemiology ; Geographic Information Systems ; Humans ; *Mesothelioma ; Risk Factors ; }, abstract = {The recent enactment of the law banning asbestos in Colombia raises a significant number of challenges. The largest factories that have historically processed asbestos include five asbestos-cement facilities located in the cities of Sibaté (Cundinamarca), Cali (Valle del Cauca), and Barranquilla (Atlántico), and Manizales (Caldas), which has two, as well as a friction products facility in Bogotá D.C. An asbestos chrysotile mine has also operated in Colombia since 1980 in Campamento (Antioquia). In the framework of developing the National Asbestos Profile for Colombia, in this study, we estimated the population residing in the vicinity of asbestos processing plants or the mine and, therefore, potentially at risk of disease. Using a geographic information system, demographic data obtained from the last two general population censuses were processed to determine the number of people living within the concentric circles surrounding the asbestos facilities and the mine. In previous studies conducted in different countries of the world, an increased risk of asbestos-related diseases has been reported for people living at different distance bands from asbestos processing facilities. Based on these studies, circles of 500, 1000, 2000, 5000, and 10,000 m radii, centered on the asbestos processing facilities and the mine that operated in Colombia, were combined with the census data to estimate the number of people living within these radii. Large numbers of people were identified. It is estimated that in 2005, at the country level, 10,489 people lived within 500 m of an asbestos processing facility or mine. In 2018, and within a distance of 10,000 m, the number of people was 6,724,677. This information can aid public health surveillance strategies.}, }
@article {pmid34965001, year = {2021}, author = {Okazaki, Y}, title = {Asbestos-induced mesothelial injury and carcinogenesis: Involvement of iron and reactive oxygen species.}, journal = {Pathology international}, volume = {}, number = {}, pages = {}, doi = {10.1111/pin.13196}, pmid = {34965001}, issn = {1440-1827}, support = {JSPS KAKENHI 21K06968//Japan Society for the Promotion of Science/ ; //JSPS KAKENHI/ ; }, abstract = {Asbestos fibers have been used as an industrial and construction material worldwide due to their high durability and low production cost. Commercial usage of asbestos is currently prohibited in Japan; however, the risk of asbestos-induced malignant mesothelioma (MM) remains. According to epidemiological data, the onset of MM is estimated to occur after a latent period of 30-40 years from initial exposure to asbestos fibers; thus, the continuous increase in MM is a concern. To explore the molecular mechanisms of MM using animal models, iron saccharate with iron chelator-induced sarcomatoid mesothelioma (SM) revealed hallmarks of homozygous deletion of Cdkn2a/2b by aCGH and microRNA-199/214 by expression microarray. Oral treatment of iron chelation by deferasirox decreased the rate of high-grade SM. Moreover, phlebotomy delayed MM development in crocidolite-induced MM in rats. In Divalent metal transporter 1 (Dmt1) transgenic mice, MM development was delayed because of low reactive oxygen species (ROS) production. These results indicate the importance of iron and ROS in mesothelial carcinogenesis. The aims of this review focus on the pathogenesis of elongated mineral particles (EMPs), including asbestos fibers and multiwalled carbon nanotubes (MWCNTs) that share similar rod-like shapes in addition to the molecular mechanisms of MM development.}, }
@article {pmid34962302, year = {2021}, author = {Kottek, M and Yuen, ML}, title = {Public health risks from asbestos cement roofing.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23321}, pmid = {34962302}, issn = {1097-0274}, support = {Regional Collaboration Programme grant//Australian Academy of Science/ ; }, abstract = {There is no identified risk-free threshold exposure to asbestos. Based on epidemiology and toxicology, asbestos fiber dimensions have been implicated in causing asbestos-related diseases. Phase-contrast microscopy provides only a limited index of exposure to fiber dimensions implicated in mesothelioma induction. Installed asbestos-containing materials (ACMs) create an ongoing risk of intense exposure during natural disasters and remodeling, along with low-level exposure arising from the continual emission of airborne asbestos into the environment arising from weathering of installed ACM. Epidemiological studies have demonstrated a risk of disease associated with proximity to asbestos cement roofing (ACR), while ongoing environmental emissions of asbestos from installed ACR have also been demonstrated. Owing to the limitations of the available data, a precautionary approach is warranted; asbestos-free roofing materials should be used in new construction and existing ACR should be removed at the earliest opportunity.}, }
@article {pmid34960727, year = {2021}, author = {Forte, IM and Indovina, P and Montagnaro, S and Costa, A and Iannuzzi, CA and Capone, F and Camerlingo, R and Malfitano, AM and Pentimalli, F and Ferrara, G and Quintiliani, M and Portella, G and Giordano, A and Ciarcia, R}, title = {The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach.}, journal = {Viruses}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/v13122458}, pmid = {34960727}, issn = {1999-4915}, support = {M4/7//Italian Ministry of Health/ ; NA//Sbarro Health Research Organization (www.shro.org)/ ; NA//the Commonwealth of Pennsylvania/ ; NA//AIL (Italian Association against Leukemia-Lymphoma and Myeloma Division "Valentina Picazio")/ ; }, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM.}, }
@article {pmid34948918, year = {2021}, author = {Klebe, S and Hocking, AJ and Soeberg, M and Leigh, J}, title = {The Significance of Short Latency in Mesothelioma for Attribution of Causation: Report of a Case with Predisposing Germline Mutations and Review of the Literature.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {24}, pages = {}, doi = {10.3390/ijerph182413310}, pmid = {34948918}, issn = {1660-4601}, abstract = {Malignant mesothelioma is a tumour of the serosal membranes, related to asbestos exposure. Median latency is in the order of 40 years in various registries, but small numbers of cases with shorter latencies have long been reported and often dismissed as unrelated to asbestos exposure. However, emerging data regarding the significance of inherited mutations leading to a predisposition to mesothelioma suggest that the causative effect of asbestos may be associated with shorter latencies in a subset of patients. Here, we describe a male patient with germline mutations in RAD51 and p53 who developed peritoneal mesothelioma 8.5 years after well-documented asbestos exposure and discuss the current literature on the subject. Mesothelioma in situ is now a WHO-accepted diagnosis, but preliminary data reveal a potential lead time of 5 or more years to invasive disease, and this is also a factor which may affect the recording of latency (and potentially survival) in the future.}, }
@article {pmid34944051, year = {2021}, author = {Abukar, A and Wipplinger, M and Hariharan, A and Sun, S and Ronner, M and Sculco, M and Okonska, A and Kresoja-Rakic, J and Rehrauer, H and Qi, W and Beusechem, VWV and Felley-Bosco, E}, title = {Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/cells10123543}, pmid = {34944051}, issn = {2073-4409}, support = {320030_182690/SNSF_/Swiss National Science Foundation/Switzerland ; }, abstract = {Mesothelioma is an aggressive cancer associated with asbestos exposure. RNA-binding motif protein 8a (RBM8A) mRNA editing increases in mouse tissues upon asbestos exposure. The aim of this study was to further characterize the role of RBM8A in mesothelioma and the consequences of its mRNA editing. RBM8A protein expression was higher in mesothelioma compared to mesothelial cells. Silencing RBM8A changed splicing patterns in mesothelial and mesothelioma cells but drastically reduced viability only in mesothelioma cells. In the tissues of asbestos-exposed mice, editing of Rbm8a mRNA was associated with increased protein immunoreactivity, with no change in mRNA levels. Increased adenosine deaminase acting on dsRNA (ADAR)-dependent editing of Alu elements in the RBM8A 3'UTR was observed in mesothelioma cells compared to mesothelial cells. Editing stabilized protein expression. The unedited RBM8A 3'UTR had a stronger interaction with Musashi (MSI) compared to the edited form. The silencing of MSI2 in mesothelioma or overexpression of Adar2 in mesothelial cells resulted in increased RBM8A protein levels. Therefore, ADAR-dependent editing contributes to maintaining elevated RBM8A protein levels in mesothelioma by counteracting MSI2-driven downregulation. A wider implication of this mechanism for the translational control of protein expression is suggested by the editing of similarly structured Alu elements in several other transcripts.}, }
@article {pmid34943522, year = {2021}, author = {Gharib, AF and Alaa Eldeen, M and Khalifa, AS and Elsawy, WH and Eed, EM and Askary, AE and Eid, RA and Soltan, MA and Raafat, N}, title = {Assessment of Glutathione Peroxidase-1 (GPX1) Gene Expression as a Specific Diagnostic and Prognostic Biomarker in Malignant Pleural Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {12}, pages = {}, doi = {10.3390/diagnostics11122285}, pmid = {34943522}, issn = {2075-4418}, support = {TURSP-2020/157//Taif University/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a malignant tumor of the mesothelial lining of the thorax. It has been related to frequent exposure to asbestos. Diagnosis of malignant pleural mesothelioma is considered a criticizing problem for clinicians. Early diagnosis and sufficient surgical excision of MPM are considered the cornerstone success factors for the management of early MPM. Glutathione peroxidase-1 (GPX1) is an intracellular protein found to be extensively distributed in all cells, and it belongs to the GPX group. In the current study, we included ninety-eight patients with MPM that underwent surgery at the Zagazig University Hospital in Egypt. We assessed GPX1 gene expression level as it was thought to be related to pathogenicity of cancer in a variety of malignant tumors. We observed a significant elevation in GPX1-mRNA levels in MPM relative to the nearby normal pleural tissues. It was found to be of important diagnostic specificity in the differentiation of MPM from normal tissues. Moreover, we studied the survival of patients in correlation to the GPX1 expression levels and we reported that median overall survival was about 16 months in patients with high GPX1 expression levels, while it was found to be about 40 months in low GPX1 levels.}, }
@article {pmid34909922, year = {2021}, author = {Hajj, GNM and Cavarson, CH and Pinto, CAL and Venturi, G and Navarro, JR and Lima, VCC}, title = {Malignant pleural mesothelioma: an update.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {47}, number = {6}, pages = {e20210129}, doi = {10.36416/1806-3756/e20210129}, pmid = {34909922}, issn = {1806-3756}, abstract = {Malignant mesotheliomas are rare types of cancers that affect the mesothelial surfaces, usually the pleura and peritoneum. They are associated with asbestos exposure, but due to a latency period of more than 30 years and difficult diagnosis, most cases are not detected until they reach advanced stages. Treatment options for this tumor type are very limited and survival ranges from 12 to 36 months. This review discusses the molecular physiopathology, current diagnosis, and latest therapeutic options for this disease.}, }
@article {pmid34907223, year = {2021}, author = {Frontini, F and Bononi, I and Torreggiani, E and Di Mauro, G and Mazzoni, E and Stendardo, M and Boschetto, P and Libener, R and Guaschino, R and Grosso, F and Guerra, G and Martini, F and Tognon, M}, title = {Circulating microRNA-197-3p as a potential biomarker for asbestos exposure.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {23955}, pmid = {34907223}, issn = {2045-2322}, support = {FAR PROJECTS 20-21//Università degli Studi di Ferrara/ ; IG 201617//Associazione Italiana per la Ricerca sul Cancro/ ; CFR 19-20//FONDAZIONE BUZZI UNICEM ONLUS/ ; }, abstract = {Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-qPCR and ddPCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n = 75) compared to HS (n = 62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p = 0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p = 0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.}, }
@article {pmid34900693, year = {2021}, author = {Johnson, BW and Takahashi, K and Cheng, YY}, title = {Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma - A Review.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {748444}, doi = {10.3389/fonc.2021.748444}, pmid = {34900693}, issn = {2234-943X}, abstract = {Malignant mesothelioma is an aggressive cancer with poor prognosis, predominantly caused by human occupational exposure to asbestos. The global incidence of mesothelioma is predicted to increase as a consequence of continued exposure to asbestos from a variety of sources, including construction material produced in the past in developed countries, as well as those currently being produced in developing countries. Mesothelioma typically develops after a long latency period and consequently it is often diagnosed in the clinic at an advanced stage, at which point standard care of treatment, such as chemo- and radio-therapy, are largely ineffective. Much of our current understanding of mesothelioma biology, particularly in relation to disease pathogenesis, diagnosis and treatment, can be attributed to decades of preclinical basic science research. Given the postulated rising incidence in mesothelioma cases and the limitations of current diagnostic and treatment options, continued preclinical research into mesothelioma is urgently needed. The ever-evolving landscape of preclinical models and laboratory technology available to researchers have made it possible to study human disease with greater precision and at an accelerated rate. In this review article we provide an overview of the various resources that can be exploited to facilitate an enhanced understanding of mesothelioma biology and their applications to research aimed to improve the diagnosis and treatment of mesothelioma. These resources include cell lines, animal models, mesothelioma-specific biobanks and modern laboratory techniques/technologies. Given that different preclinical models and laboratory technologies have varying limitations and applications, they must be selected carefully with respect to the intended objectives of the experiments. This review therefore aims to provide a comprehensive overview of the various preclinical models and technologies with respect to their advantages and limitations. Finally, we will detail about a highly valuable preclinical laboratory resource to curate high quality mesothelioma biospecimens for research; the biobank. Collectively, these resources are essential to the continued advancement of precision medicine to curtail the increasing health burden caused by malignant mesothelioma.}, }
@article {pmid34898002, year = {2021}, author = {Marazioti, A and Krontira, AC and Behrend, SJ and Giotopoulou, GA and Ntaliarda, G and Blanquart, C and Bayram, H and Iliopoulou, M and Vreka, M and Trassl, L and Pepe, MAA and Hackl, CM and Klotz, LV and Weiss, SAI and Koch, I and Lindner, M and Hatz, RA and Behr, J and Wagner, DE and Papadaki, H and Antimisiaris, SG and Jean, D and Deshayes, S and Grégoire, M and Kayalar, Ö and Mortazavi, D and Dilege, Ş and Tanju, S and Erus, S and Yavuz, Ö and Bulutay, P and Fırat, P and Psallidas, I and Spella, M and Giopanou, I and Lilis, I and Lamort, AS and Stathopoulos, GT}, title = {KRAS signaling in malignant pleural mesothelioma.}, journal = {EMBO molecular medicine}, volume = {}, number = {}, pages = {e13631}, doi = {10.15252/emmm.202013631}, pmid = {34898002}, issn = {1757-4684}, support = {NSRF 2014-2020//Greek State Scholarship Foundation/ ; LTRF 2015-1824//European Respiratory Society (ERS)/ ; ANR-16-IDEX-0007//Institut National de la Santé et de la Recherche Médicale (Inserm)/ ; GRK2338//Deutsche Forschungsgemeinschaft (DFG)/ ; //Bundesministerium für Bildung und Forschung (BMBF)/ ; //Deutsches Zentrum fuer Lungenforschung/ ; 1853a//General Secretariat for Research and Innovation and Hellenic Foundation for Research and Innovation/ ; //Pays de la Loire Region research program/ ; 260524//FP7 Ideas: European Research Council (FP7 Ideas)/ ; 679345//FP7 Ideas: European Research Council (FP7 Ideas)/ ; ANR-16-IDEX-0007//National Research Agency under the Programme d'Investissements d'Avenir/ ; ARSMESO44//INSERM, CNRS, the "Institut de Recherche en Santé Respiratoire des Pays de la Loire"/ ; //INSERM, the Ligue Contre le Cancer (Ile de France committee), and the Chancellerie des Universités de Paris (Legs POIX)/ ; NSRF 2014-2020//Greek State Scholarship Foundation Program 'Reinforcement of Postdoctoral Researchers-1st and 2nd cycles' co-financed by the European Union Social Fund and Greek national funds/ ; MIS-5033021//Greek State Scholarship Foundation Program 'Reinforcement of Postdoctoral Researchers-1st and 2nd cycles' co-financed by the European Union Social Fund and Greek national funds/ ; }, abstract = {Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.}, }
@article {pmid34874752, year = {2021}, author = {Sohn, EJ}, title = {Bioinformatic Analysis of Potential Biomarker for hsa-miR-196b-5p in Mesothelioma.}, journal = {Genetic testing and molecular biomarkers}, volume = {}, number = {}, pages = {}, doi = {10.1089/gtmb.2021.0147}, pmid = {34874752}, issn = {1945-0257}, abstract = {Purpose: Malignant pleural mesothelioma is a rare neoplasia with a poor prognosis, and the majority of patients have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Materials and Methods: To determine the cytotoxicity of geldanamycin in mesothelioma H28 cells, the MTT assay was used. To determine changes in microRNA (miRNA) expression in geldanamycin-treated H28 cells, miRNA microarray analysis was performed. To determine the function of miR-196b-5p, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of miR-196b-5p targets predicted by miRwalk. Results: Our data showed that geldanamycin treatment reduced H28 cell viability in a dose-dependent manner. MicroRNA array showed that expression of hsa-miR-196b-5p was downregulated in geldanamycin-treated H28 cells. Geldanamycin regulated miRNAs with roles in processes such as aging, angiogenesis, apoptosis, cell cycle, cell differentiation, cell proliferation, DNA repair, and secretion. Survival analysis showed that low expression of hsa-miR-196b-5p was significantly associated with a better outcome in mesothelioma patients. Expression of miR-196b-5p was also significantly associated with the developmental stages of mesothelioma. To narrow down the target genes of miR-196b-5p, we determined the overlap between the predicted target genes of miR-196b-5p and downregulated mRNAs in ovarian cancer based on the Gene Expression Omnibus dataset GSE12345. PDE1A, LAMA4, and PAPPA were identified as both miR-196b-5p targets and downregulated genes in GSE12345 and were thus considered targets of miR-196b-5p. Gene-miRNA expression correlation analysis showed that PDE1A, LAMA4, and PAPPA expression was negatively correlated with miR-196b-5p expression. Conclusions: We suggest that geldanamycin is potentially useful as an anticancer effect for the treatment of mesothelioma via regulating miR-196b-5p. Furthermore, miR-196b-5p may be a potential biomarker for mesothelioma.}, }
@article {pmid34861373, year = {2021}, author = {Popat, S and Baas, P and Faivre-Finn, C and Girard, N and Nicholson, AG and Nowak, AK and Opitz, I and Scherpereel, A and Reck, M and , }, title = {Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.annonc.2021.11.005}, pmid = {34861373}, issn = {1569-8041}, }
@article {pmid34843704, year = {2021}, author = {Chen, Z and Song, S and Yang, C and Dai, Z and Gao, Y and Li, N and Zhu, J and Mao, W and Liu, J}, title = {Lipid Profiling in Malignant Mesothelioma Reveals Promising Signatures for Diagnosis and Prognosis: A Plasma-Based LC-MS Lipidomics Study.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cca.2021.11.024}, pmid = {34843704}, issn = {1873-3492}, abstract = {BACKGROUND AND AIM: Malignant mesothelioma (MM), being a rare and aggressive carcinoma, can barely be cured. Incidence of this cancer will keep climbing up in the next few decades since its major carcinogen, asbestos, is still in use in many countries. Unfortunately, prognosis of MM is unsatisfactory principally due to poor early diagnosis as a result of its long latency period and ambiguous symptoms. Lipids are known to contribute to cellular structure, signaling, and energy storage, and are widely reported to be related with tumorigenesis. Therefore, we aim to discover novel lipid biomarkers by plasma-based lipidomics that may improve MM diagnosis.<br><br>METHODS: Plasma samples from 25 MM patients and 32 healthy controls (HCs) were collected and analysed using a high-throughput liquid chromatography-mass spectrometry (LC-MS). Univariate and multivariate analyses were subsequently performed to visualize the separation trend between two groups and to screen for differential feature ions. Ions were annotated using LipidSearch 4.2 and their enriched pathways were detected on LIPEA. Receiver operating curves (ROC) were used for analysing each annotated lipid's diagnostic value. Survival analyses were performed to investigate each lipid's prognostic value.<br><br>RESULTS: In supervised partial least squares discriminant analysis (PLS-DA), clear separation between MM and HC groups was observed. A total of 34 differential lipids were annotated, among which 5 upregulated and 29 downregulated. Levels of plasma triacylglycerols (TGs) were higher in smoking versus non-smoking patients, and lower in female versus male patients. The top six lipids possessing highest diagnostic value included two phosphatidylethanolamines (PEs), two phosphatidylcholines (PCs) and two ceramides. Moreover, elevated circulating TG levels were associated with poorer survival, whereas increased monohexosylceramide (Hex1Cer) might be beneficial.<br><br>CONCLUSIONS: Our study revealed differentially expressed lipid patterns in MM and HC. PC, PE, and ceramides showed outstanding diagnostic performance, while TG and Hex1Cer exhibited significant prognostic values. Nevertheless, more studies should verify these trends as well as further investigating underlying mechanisms.}, }
@article {pmid34841838, year = {2021}, author = {De Sario, M and Bauleo, L and Magnani, C and Ferrante, D and Marinaccio, A and Michelozzi, P and Romeo, E}, title = {L'impatto dell'esposizione occupazionale ad amianto sul tumore del polmone in Italia.}, journal = {Epidemiologia e prevenzione}, volume = {45}, number = {5}, pages = {353-367}, doi = {10.19191/EP21.5.P353.102}, pmid = {34841838}, issn = {1120-9763}, abstract = {OBJECTIVES: to perform a meta-analysis of cohort studies on lung cancer mortality in occupational sectors exposed to asbestos, particularly in the construction sector, and to use data from Italian cohorts exposed to asbestos to estimate the number of lung cancer cases attributable to asbestos in Italy.<br><br>METHODS: systematic literature review and estimation of lung cancer deaths and cases attributable to asbestos in Italian cohorts and from the Italian National Register of Malignant Mesothelioma (ReNaM).<br><br>SETTING AND PARTICIPANTS: the literature search was conducted in Medline and Embase (Ovid), including papers published from 1999 to May 2019. The following sectors were considered most exposed to asbestos: asbestos-cement, rolling-stock, shipyards, dockyards, glass workers, insulators, asphalt roll production workers, industrial ovens, miners. Moreover, the construction sector was included.<br><br>MAIN OUTCOME MEASURES: the standardized mortality ratio (SMR) was estimated from the meta-analysis of the literature review. The ratio lung cancer to mesothelioma attributable cases was estimated by occupational sector from the Italian cohorts. For the construction sector, the ratio lung cancer to mesothelioma cases was estimated within the exposed workers estimated by CAREX (1990-1993). The ratios were applied to the mesothelioma cases registered at the ReNaM for the 2010-2015 period, to obtain a national estimate of lung cancer cases attributable to occupational exposure to asbestos.<br><br>RESULTS: the meta-analytical SMR for lung cancer in men varied between 1.05 (asphalt roll) and 2.36 (insulation). The mean risk for all sectors was 1.37 in men and 1.60 in women. It increased in cohorts with latency higher than 20 years. Significant risks were observed in asbestos-cement (both genders), construction, and mining sectors. There was a mean of 1.1, 2.7, and 2.8 lung cancer deaths per mesothelioma death in the cement-asbestos, harbour, and construction sectors, respectively. The impact in terms of lung cancer cases estimated at the national level was equal to 3,814 cases between 2010 and 2015.<br><br>CONCLUSIONS: to provide an overall assessment of the impact of the occupational asbestos exposure, it is important to consider lung cancer cases, in addition to malignant mesotheliomas. This study was able to estimate the impact of asbestos on lung cancer in Italy 25 years after the ban of this occupational carcinogen, with the largest contribution in terms of attributable cases coming from the construction sector. It is urgent to implement adequate information and prevention strategies, health surveillance of workers, and the appropriate legal framework for insurance purposes.}, }
@article {pmid34840219, year = {2021}, author = {Kawamoto, Y and Kure, S and Katayama, H and Kawahara, K and Teduka, K and Kunugi, S and Onda, M and Motoda, N and Ohashi, R}, title = {Cytological assessment of desmoplastic malignant pleural mesothelioma in an autopsy case.}, journal = {Journal of Nippon Medical School = Nippon Ika Daigaku zasshi}, volume = {}, number = {}, pages = {}, doi = {10.1272/jnms.JNMS.2022_89-605}, pmid = {34840219}, issn = {1347-3409}, abstract = {INTRODUCTION: Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma type mesothelioma, comprising about 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, this may not be useful for DMPM due to its desmoplastic nature and bland cellular atypia. We hereby report a case of DMPM diagnosed through autopsy along with its cytological features that have not been described previously.<br><br>CASE PRESENTATION: A male in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. Chest computed tomography scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. In autopsy, the scrape-imprint smear and the pleural effusions cytology were performed. The scrape-imprint smear samples exhibited spindle cells with mild nuclear atypia and grooves with fibrous stroma. In the pleural effusion cytology, spindle cells having mild nuclear atypia and grooves with loose epithelial connections were observed. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in cytological samples, thus rendering the diagnosis of DMPM. Diagnosis was confirmed by fluorescence in situ hybridization.<br><br>CONCLUSION: Cytological procedures, such as pleural effusion cytology and scrape-imprinting method, may be useful as an ancillary tool in the diagnosis of rare tumors such as DMPM.}, }
@article {pmid34836499, year = {2021}, author = {Kelarji, AB and Alshutaihi, MS and Ghazal, A and Mahli, N and Agha, S}, title = {Correction to: A rare case of benign multicystic peritoneal mesothelioma misdiagnosed as hydatid cyst found in the liver parenchyma and abdomen cavity of a male with asbestos exposure.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {447}, pmid = {34836499}, issn = {1471-230X}, }
@article {pmid34834557, year = {2021}, author = {Filetti, V and Loreto, C and Falzone, L and Lombardo, C and Cannizzaro, E and Castorina, S and Ledda, C and Rapisarda, V}, title = {Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma.}, journal = {Journal of personalized medicine}, volume = {11}, number = {11}, pages = {}, doi = {10.3390/jpm11111205}, pmid = {34834557}, issn = {2075-4426}, abstract = {Fluoro-edenite (FE) is an asbestiform fiber identified in Biancavilla (Sicily, Italy). Environmental exposure to FE has been associated with a higher incidence of malignant mesothelioma (MM). The present study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched with healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR (ddPCR) to evaluate differences in the expression levels of the selected miRNAs and their MM diagnostic potential. In addition, further computational analysis has been performed to establish the correlation of these miRNAs with the available online asbestos exposure data and clinic-pathological parameters to verify the potential role of these miRNAs as prognostic tools. ddPCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. Receiver operating characteristic (ROC) analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased overall survival (OS) of MM patients.}, }
@article {pmid34830817, year = {2021}, author = {Cersosimo, F and Barbarino, M and Lonardi, S and Vermi, W and Giordano, A and Bellan, C and Giurisato, E}, title = {Mesothelioma Malignancy and the Microenvironment: Molecular Mechanisms.}, journal = {Cancers}, volume = {13}, number = {22}, pages = {}, doi = {10.3390/cancers13225664}, pmid = {34830817}, issn = {2072-6694}, abstract = {Several studies have reported that cellular and soluble components of the tumor microenvironment (TME) play a key role in cancer-initiation and progression. Considering the relevance and the complexity of TME in cancer biology, recent research has focused on the investigation of the TME content, in terms of players and informational exchange. Understanding the crosstalk between tumor and non-tumor cells is crucial to design more beneficial anti-cancer therapeutic strategies. Malignant pleural mesothelioma (MPM) is a complex and heterogenous tumor mainly caused by asbestos exposure with few treatment options and low life expectancy after standard therapy. MPM leukocyte infiltration is rich in macrophages. Given the failure of macrophages to eliminate asbestos fibers, these immune cells accumulate in pleural cavity leading to the establishment of a unique inflammatory environment and to the malignant transformation of mesothelial cells. In this inflammatory landscape, stromal and immune cells play a driven role to support tumor development and progression via a bidirectional communication with tumor cells. Characterization of the MPM microenvironment (MPM-ME) may be useful to understand the complexity of mesothelioma biology, such as to identify new molecular druggable targets, with the aim to improve the outcome of the disease. In this review, we summarize the known evidence about the MPM-ME network, including its prognostic and therapeutic relevance.}, }
@article {pmid34830097, year = {2021}, author = {Ramundo, V and Zanirato, G and Aldieri, E}, title = {The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, doi = {10.3390/ijms222212216}, pmid = {34830097}, issn = {1422-0067}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer.}, }
@article {pmid34827604, year = {2021}, author = {Javadi, J and Görgens, A and Vanky, H and Gupta, D and Hjerpe, A and El-Andaloussi, S and Hagey, D and Dobra, K}, title = {Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion.}, journal = {Biomolecules}, volume = {11}, number = {11}, pages = {}, doi = {10.3390/biom11111606}, pmid = {34827604}, issn = {2218-273X}, abstract = {Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are released by all cells into the extracellular matrix and body fluids, where they play important roles in intercellular communication and matrix remodeling in various pathological conditions. Malignant pleural mesothelioma (MPM) is a primary tumor of mesothelial origin, predominantly related to asbestos exposure. The detection of MPM at an early stage and distinguishing it from benign conditions and metastatic adenocarcinomas (AD) is sometimes challenging. Pleural effusion is often the first available biological material and an ideal source for characterizing diagnostic and prognostic factors. Specific proteins have previously been identified as diagnostic markers in effusion, but it is not currently known whether these are associated with vesicles or released in soluble form. Here, we study and characterize tumor heterogeneity and extracellular vesicle diversity in pleural effusion as diagnostic or prognostic markers for MPM. We analyzed extracellular vesicles and soluble proteins from 27 pleural effusions, which were collected and processed at the department of pathology and cytology at Karolinska University Hospital, representing three different patient groups, MPM (n = 9), benign (n = 6), and AD (n = 12). The vesicles were fractionated into apoptotic bodies, microvesicles, and exosomes by differential centrifugation and characterized by nanoparticle tracking analysis and Western blotting. Multiplex bead-based flow cytometry analysis showed that exosomal markers were expressed differently on EVs present in different fractions. Further characterization of exosomes by a multiplex immunoassay (Luminex) showed that all soluble proteins studied were also present in exosomes, though the ratio of protein concentration present in supernatant versus exosomes varied. The proportion of Angiopoietin-1 present in exosomes was generally higher in benign compared to malignant samples. The corresponding ratios of Mesothelin, Galectin-1, Osteopontin, and VEGF were higher in MPM effusions compared to those in the benign group. These findings demonstrate that relevant diagnostic markers can be recovered from exosomes.}, }
@article {pmid34823106, year = {2021}, author = {Nowak, AK and Chin, WL and Keam, S and Cook, A}, title = {Immune checkpoint inhibitor therapy for malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {162}, number = {}, pages = {162-168}, doi = {10.1016/j.lungcan.2021.11.006}, pmid = {34823106}, issn = {1872-8332}, abstract = {Mesothelioma is a rare and universally fatal cancer linked to exposure to asbestos. Until recently, standard of care treatment was chemotherapy; a treatment resulting in a minimal survival extension, and not improved upon for almost twenty years. However, the advent of cancer immunotherapy - and in particular the immune checkpoint inhibitor class of drugs - has resulted in recently approved new treatment options, with more currently under investigation. Here, we review clinical trials of both single agent and combination checkpoint inhibitors in mesothelioma, plus studies investigating their combination with chemotherapy. We also describe current advances in biomarker identification regarding prediction of patient response to checkpoint inhibitors. Finally, we assess the probable future direction of the field; including where current and developing technologies are likely to lead - in terms of both biomarker discovery and treatment options.}, }
@article {pmid34815344, year = {2021}, author = {Novelli, F and Bononi, A and Wang, Q and Bai, F and Patergnani, S and Kricek, F and Haglund, E and Suarez, JS and Tanji, M and Xu, R and Takanishi, Y and Minaai, M and Pastorino, S and Morris, P and Sakamoto, G and Pass, HI and Barbour, H and Gaudino, G and Giorgi, C and Pinton, P and Onuchic, JN and Yang, H and Carbone, M}, title = {BAP1 forms a trimer with HMGB1 and HDAC1 that modulates gene × environment interaction with asbestos.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {48}, pages = {}, doi = {10.1073/pnas.2111946118}, pmid = {34815344}, issn = {1091-6490}, abstract = {Carriers of heterozygous germline BAP1 mutations (BAP1 +/-) are affected by the "BAP1 cancer syndrome." Although they can develop almost any cancer type, they are unusually susceptible to asbestos carcinogenesis and mesothelioma. Here we investigate why among all carcinogens, BAP1 mutations cooperate with asbestos. Asbestos carcinogenesis and mesothelioma have been linked to a chronic inflammatory process promoted by the extracellular release of the high-mobility group box 1 protein (HMGB1). We report that BAP1 +/- cells secrete increased amounts of HMGB1, and that BAP1 +/- carriers have detectable serum levels of acetylated HMGB1 that further increase when they develop mesothelioma. We linked these findings to our discovery that BAP1 forms a trimeric protein complex with HMGB1 and with histone deacetylase 1 (HDAC1) that modulates HMGB1 acetylation and its release. Reduced BAP1 levels caused increased ubiquitylation and degradation of HDAC1, leading to increased acetylation of HMGB1 and its active secretion that in turn promoted mesothelial cell transformation.}, }
@article {pmid34788178, year = {2021}, author = {Dodge, DG and Engel, AM and Prueitt, RL and Peterson, MK and Goodman, JE}, title = {US EPA's TSCA risk assessment approach: a case study of asbestos in automotive brakes.}, journal = {Inhalation toxicology}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/08958378.2021.1998258}, pmid = {34788178}, issn = {1091-7691}, abstract = {The United States Environmental Protection Agency (US EPA) is currently refining its approach for risk assessments conducted under the amended Toxic Substances Control Act (TSCA), largely based on recommendations from the National Academies of Sciences, Engineering, and Medicine (NASEM). We identified several issues with the current TSCA risk assessment approach that were not addressed by NASEM in its recommendations. Here, we demonstrate these issues with a case study of the 'Risk Evaluation for Asbestos, Part 1: Chrysotile Asbestos,' which US EPA released in December 2020. In this evaluation, US EPA found that occupational and some consumer uses of automotive brakes and clutches that contain asbestos result in unreasonable risks. These risks were calculated from estimated exposures during brake work and an inhalation unit risk (IUR) developed for chrysotile asbestos. We found that US EPA overestimated risk as a result of unrealistic inputs to both the exposure and toxicity components of the risk equation, and because the Agency did not fully consider relevant epidemiology and toxicity evidence in its systematic review. Our evaluation demonstrates areas in which the TSCA risk assessment approach could be improved to result in risk evaluations that are supported by the available scientific evidence.}, }
@article {pmid34774176, year = {2021}, author = {Sidhu, C and Louw, A and Gary Lee, YC}, title = {Malignant Pleural Mesothelioma: Updates for Respiratory Physicians.}, journal = {Clinics in chest medicine}, volume = {42}, number = {4}, pages = {697-710}, doi = {10.1016/j.ccm.2021.08.006}, pmid = {34774176}, issn = {1557-8216}, }
@article {pmid34768883, year = {2021}, author = {Çakılkaya, P and Sørensen, RR and Jürgensen, HJ and Krigslund, O and Gårdsvoll, H and Nielsen, CF and Santoni-Rugiu, E and Behrendt, N and Engelholm, LH}, title = {The Collagen Receptor uPARAP in Malignant Mesothelioma: A Potential Diagnostic Marker and Therapeutic Target.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, doi = {10.3390/ijms222111452}, pmid = {34768883}, issn = {1422-0067}, support = {No 801481//European Union/ ; NNF19OC0058603//Novo Nordisk Foundation/ ; R231-A13820//Danish Cancer Society/ ; R231-A13832//Danish Cancer Society/ ; N/A//Region Hovedstadens Forskningsfond/ ; N/A//Simon Fougner Hartmanns family foundation/ ; }, abstract = {Malignant mesothelioma (MM) is a highly aggressive cancer with limited therapeutic options. We have previously shown that the endocytic collagen receptor, uPARAP, is upregulated in certain cancers and can be therapeutically targeted. Public RNA expression data display uPARAP overexpression in MM. Thus, to evaluate its potential use in diagnostics and therapy, we quantified uPARAP expression by immunohistochemical H-score in formalin-fixed paraffin-embedded bioptic/surgical human tissue samples and tissue microarrays. We detected pronounced upregulation of uPARAP in the three main MM subtypes compared to non-malignant reactive mesothelial proliferations, with higher expression in sarcomatoid and biphasic than in epithelioid MM. The upregulation appeared to be independent of patients' asbestos exposure and unaffected after chemotherapy. Using immunoblotting, we demonstrated high expression of uPARAP in MM cell lines and no expression in a non-malignant mesothelial cell line. Moreover, we showed the specific internalization of an anti-uPARAP monoclonal antibody by the MM cell lines using flow cytometry-based assays and confocal microscopy. Finally, we demonstrated the sensitivity of these cells towards sub-nanomolar concentrations of an antibody-drug conjugate formed with the uPARAP-directed antibody and a potent cytotoxin that led to efficient, uPARAP-specific eradication of the MM cells. Further studies on patient cohorts and functional preclinical models will fully reveal whether uPARAP could be exploited in diagnostics and therapeutic targeting of MM.}, }
@article {pmid34768395, year = {2021}, author = {Zupanc, C and Franko, A and Štrbac, D and Dodič Fikfak, M and Kovač, V and Dolžan, V and Goričar, K}, title = {Serum Calretinin as a Biomarker in Malignant Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {10}, number = {21}, pages = {}, doi = {10.3390/jcm10214875}, pmid = {34768395}, issn = {2077-0383}, support = {P1-0170, L3-8203, and L3-2622//Slovenian Research Agency/ ; }, abstract = {The early diagnosis of malignant mesothelioma (MM) could improve the prognosis of MM patients. To confirm an MM diagnosis, an immunohistochemical analysis of several tumor tissue markers, including calretinin, is currently required. Our aim is to evaluate serum calretinin as a potential biomarker in asbestos-related diseases, especially in MM. Our study includes 549 subjects: 164 MM patients, 117 subjects with asbestosis, 195 subjects with pleural plaques and 73 occupationally asbestos-exposed subjects without asbestos-related diseases. The serum calretinin concentration was determined with a commercially available enzyme immunoassay. Data on the soluble mesothelin-related peptides (SMRP) concentration are available from previous studies. MM patients had a significantly higher calretinin concentration than subjects without disease, subjects with pleural plaques or subjects with asbestosis (all p < 0.001). The histological type was significantly associated with serum calretinin: patients with sarcomatoid MM had lower calretinin than patients with the epithelioid type (p = 0.001). In a ROC curve analysis, the area under the curve for calretinin concentration predicting MM was 0.826 (95% CI = 0.782-0.869; p < 0.001). At the cutoff value of 0.32 ng/mL, sensitivity was 0.683, while specificity was 0.886. The combination of calretinin and SMRP had the highest predictive value. Calretinin is a useful biomarker that can distinguish MM from other asbestos-related diseases and could, therefore, contribute to an earlier non-invasive diagnosis of MM.}, }
@article {pmid34766064, year = {2021}, author = {Ke, H and Gill, AJ and McKenzie, C and Kench, JG and Chan, RCF and Pavlakis, N and Fulham, M and Koh, C and Kao, S}, title = {Malignant Peritoneal Mesothelioma With EWSR1-ATF1 Fusion: A Case Report.}, journal = {JTO clinical and research reports}, volume = {2}, number = {11}, pages = {100236}, pmid = {34766064}, issn = {2666-3643}, abstract = {Malignant mesothelioma with EWSR1-ATF1 fusion is a rare malignancy described in young adults without asbestos exposure. To the best of our knowledge, outcomes to local and systemic therapies for this subtype of malignant mesothelioma have not been described. This case report describes the clinical course of a 19-year-old man diagnosed with malignant peritoneal mesothelioma with EWSR1-ATF1 fusion localized to the abdomen. His disease followed an aggressive course and resulted in limited survival (18 mo). There was treatment resistance to several lines of conventional local and systemic treatments for peritoneal mesothelioma and biologically targeted MET inhibition with crizotinib. More research is required in this rare subtype of peritoneal mesothelioma.}, }
@article {pmid34761371, year = {2021}, author = {Rapisarda, V and Broggi, G and Caltabiano, R and Lombardo, C and Castorina, S and Trovato, A and Ledda, C and Filetti, V and Loreto, C}, title = {ATG7 immunohistochemical expression in Malignant Pleural Mesothelioma. A preliminary report.}, journal = {Histology and histopathology}, volume = {}, number = {}, pages = {18396}, doi = {10.14670/HH-18-396}, pmid = {34761371}, issn = {1699-5848}, support = {20722142130//2020/2022 PIA.CE.RI., University of Catania, DIPREME project/ ; }, abstract = {Literature evidence has demonstrated a high incidence of asbestos-related malignant pleural mesothelioma (MPM) in a Sicilian town (Biancavilla, Italy), where fluoro-edenite (FE) fibers were discovered some decades ago. As ATG7 immunohistochemical analysis has been ascribed as a prognostic tool of improved survival, we decided to investigate, in MPM patients, exposed and not exposed to FE fibers, the immunohistochemical expression of this autophagy-related protein named ATG7. We analyzed the correlation between ATG7 immunohistochemical level and clinicopathological parameters. Twenty MPM tissue samples, from patients with available clinical and follow-up data, were included in paraffin and processed for immunohistochemistry. The immunohistochemical results confirmed activation of the autophagic process in MPM. Densitometric and morphometric expressions of ATG7 were significantly increased in MPMs when compared to the control tissues. A significant association of a high level of ATG7 with increased survival was demonstrated, with a mean overall survival (OS) of 12.5 months for patients with high expression vs. a mean OS of 4.5 months for patients with low ATG7 expression. In addition, a significant correlation between ATG7 expression and the survival time of MPM patients was observed. This study represents a starting point to hypothesize the prognostic role of ATG7 which could be a reliable prognostic indicator in MPM.}, }
@article {pmid34754347, year = {2022}, author = {Touma, T and Taira, R and Makida, T and Oshiro, K and Miyara, T and Taba, Y}, title = {Marked ventilation impairment due to progression of diffuse pleural thickening after cardiac surgery.}, journal = {Radiology case reports}, volume = {17}, number = {1}, pages = {1-4}, doi = {10.1016/j.radcr.2021.09.050}, pmid = {34754347}, issn = {1930-0433}, abstract = {A 64-year-old Japanese man presented with dyspnea and shortness of breath during exertion. Chest computed tomography revealed bilateral pleural effusion. He was drowsy because of CO2 storage and died due to ventilatory impairment. His past medical history included a thymectomy and adjuvant radiotherapy with thymoma. He had undergone cardiac surgery and permanent pacemaker implantation. The autopsy examination revealed extensive bilateral pleural adhesions and diffuse visceral pleural thickening. An inspection of multiple lung sections failed to detect any asbestos body formation or mesothelioma. The patient's pleural effusion and diffuse pleural thickening may have exacerbated after cardiac surgery. In this case, the progression and pathophysiology of the pleural thickening could be traced by imaging and an autopsy, and we were able to estimate the factors that exacerbated the pleural thickening and ventilation impairment.}, }
@article {pmid34749677, year = {2021}, author = {Hemminki, K and Försti, A and Chen, T and Hemminki, A}, title = {Incidence, mortality and survival in malignant pleural mesothelioma before and after asbestos in Denmark, Finland, Norway and Sweden.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {1189}, pmid = {34749677}, issn = {1471-2407}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal cancer, which is largely caused by exposure to asbestos. Reliable information about the incidence of MPM prior the influence of asbestos is lacking. The nationwide regional incidence trends for MPM remain poorly characterized. We use nationwide MPM data for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) to assess incidence, mortality and survival trends for MPM in these countries.<br><br>METHODS: We use the NORDCAN database for the analyses: incidence data were available from 1943 in DK, 1953 in FI and NO and 1958 in SE, through 2016. Survival data were available from 1967 through 2016. World standard population was used in age standardization.<br><br>RESULTS: The lowest incidence that we recorded for MPM was 0.02/100,000 for NO women and 0.05/100,000 for FI men in 1953-57, marking the incidence before the influence of asbestos. The highest rate of 1.9/100,000 was recorded for DK in 1997. Female incidence was much lower than male incidence. In each country, the male incidence trend for MPM culminated, first in SE around 1990. The regional incidence trends matched with earlier asbestos-related industrial activity, shipbuilding in FI and SE, cement manufacturing and shipbuilding in DK and seafaring in NO. Relative 1-year survival increased from about 20 to 50% but 5-year survival remained at or below 10%.<br><br>CONCLUSION: In the Nordic countries, the male incidence trends for MPM climaxed and started to decrease, indicating that the prevention of exposure was beneficial. Survival in MPM has improved for both sexes but long-term survival remains dismal.}, }
@article {pmid34740982, year = {2021}, author = {Hessel, PA}, title = {Mesothelioma among vehicle mechanics: a controversy?.}, journal = {Thorax}, volume = {}, number = {}, pages = {}, doi = {10.1136/thoraxjnl-2021-217880}, pmid = {34740982}, issn = {1468-3296}, }
@article {pmid34738103, year = {2021}, author = {Inamasu, E and Tsuchiya, T and Yamauchi, M and Nishi, K and Matsuda, K and Sugawara, F and Sakaguchi, K and Mori, R and Matsumoto, K and Miyazaki, T and Hatachi, G and Doi, R and Watanabe, H and Tomoshige, K and Matsuda, N and Higami, Y and Shimokawa, I and Nakashima, M and Nagayasu, T}, title = {Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models.}, journal = {Journal of radiation research}, volume = {}, number = {}, pages = {}, doi = {10.1093/jrr/rrab090}, pmid = {34738103}, issn = {1349-9157}, support = {//Nagasaki University/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P = 0.0127) and the radiation treatment alone (P = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models.}, }
@article {pmid33655329, year = {2021}, author = {Yamamoto, S and Lee, S and Ariyasu, T and Endo, S and Miyata, S and Yasuda, A and Harashima, A and Ohta, T and Kumagai-Τakei, N and Ito, T and Shimizu, Y and Srinivas, B and Sada, N and Nishimura, Y and Otsuki, T}, title = {Ingredients such as trehalose and hesperidin taken as supplements or foods reverse alterations in human T cells, reducing asbestos exposure-induced antitumor immunity.}, journal = {International journal of oncology}, volume = {58}, number = {4}, pages = {}, pmid = {33655329}, issn = {1791-2423}, mesh = {Asbestos/*adverse effects ; CD4-Positive T-Lymphocytes/drug effects/*immunology/metabolism ; Cells, Cultured ; *Dietary Supplements ; Hesperidin/*pharmacology ; Humans ; Interferon-gamma/immunology ; Interleukin-17/immunology ; Male ; Mesothelioma, Malignant/chemically induced/*immunology/prevention &amp; control ; Middle Aged ; Receptors, CXCR3/immunology ; Trehalose/*pharmacology ; }, abstract = {Exposure of human immune cells to asbestos causes a reduction in antitumor immunity. The present study aimed to investigate the recovery of reduced antitumor immunity by several ingredients taken as supplements or foods, including trehalose (Treh) and glycosylated hesperidin (gHesp). Peripheral blood CD4+ cells were stimulated with IL‑2, anti‑CD3 and anti‑CD28 antibodies for 3 days, followed by further stimulation with IL‑2 for 7 days. Subsequently, cells were stimulated with IL‑2 for an additional 28 days. During the 28 days, cells were cultured in the absence or presence of 50 <em>µ</em>g/ml chrysotile asbestos fibers. In addition, cells were treated with 10 mM Treh or 10 <em>µ</em>M gHesp. Following culture for 28 days, reverse transcription‑quantitative PCR was performed to assess the expression levels of transcription factors, cytokines and specific genes, including matrix metalloproteinase‑7 (MMP‑7), nicotinamide nucleotide transhydrogenase (NNT) and C‑X‑C motif chemokine receptor 3, in unstimulated cells (fresh) and cells stimulated with PMA and ionomycin (stimuli). The results demonstrated that compared with the control group, chrysotile‑exposure induced alterations in MMP‑7, NNT and IL‑17A expression levels were not observed in the 'Treh' and 'gHesp' groups in stimulated cells. The results suggested that Treh and gHesp may reverse asbestos exposure‑induced reduced antitumor immunity in T helper cells. However, further investigation is required to confirm the efficacy of future trials involving the use of these compounds with high‑risk human populations exposed to asbestos, such as workers involved in asbestos‑handling activities.}, }
@article {pmid34725624, year = {2021}, author = {Gupta, A and Vasileva, A and Manthri, S}, title = {The Rarest of the Rare: A Case of BAP1-Mutated Primary Peritoneal Mesothelioma.}, journal = {Cureus}, volume = {13}, number = {9}, pages = {e18380}, doi = {10.7759/cureus.18380}, pmid = {34725624}, issn = {2168-8184}, abstract = {Malignant mesotheliomas (MM), as described are rare tumors that are mostly associated with occupational exposure to asbestos. They most commonly occur in the pleura. Other unfamiliar sites where they can occur are the peritoneum, pericardium, and tunica vaginalis. There is no significant correlation between the amount and duration of asbestos exposure to mesothelioma development as reported by various studies over the years. Apart from the environmental exposure, the development of malignant mesothelioma has been linked to a mutation in the BAP1 gene, which can predispose the patient to develop other malignancies associated with BAP1 mutation. We report a case of a 43-year-old man without any significant risk factors, who presented with a complaint of abdominal discomfort and was found to have malignant peritoneal mesothelioma (MPM). With a known familial history of mesothelioma and melanoma, our patient underwent genetic testing which revealed a mutation in BAP1, affirming the strong association with the development of MPM. Young patients who develop malignant mesothelioma without risk factors for MM should have germline testing for BAP1. This case report is unique and highlights a familial variant of mesothelioma, even rare with peritoneal mesothelioma in our patient.}, }
@article {pmid34698447, year = {2021}, author = {Danese, MD and Daumont, M and Nwokeji, E and Gleeson, M and Penrod, JR and Lubeck, D}, title = {Treatment patterns and outcomes in older patients with advanced malignant pleural mesothelioma: Analyses of Surveillance, Epidemiology, and End Results-Medicare data.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {}, number = {}, pages = {e1568}, doi = {10.1002/cnr2.1568}, pmid = {34698447}, issn = {2573-8348}, support = {//Bristol Myers Squibb/ ; }, abstract = {BACKGROUND: Malignant mesothelioma is a rare neoplasm associated with asbestos exposure. Characterizing treatment patterns and outcomes of older patients with advanced malignant pleural mesothelioma (MPM) is important to understand the unmet needs of this population.<br><br>AIM: To evaluate the demographic and clinical characteristics, treatment patterns, and outcomes among older patients diagnosed with advanced MPM in the United States between 2007 and 2013.<br><br>METHODS: This was a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims. We included patients who were age 66 or older at the time of their primary MPM diagnosis between 2007 and 2013 and followed them through 2014. Treated patients who received first-line chemotherapy with pemetrexed and platinum within 90 days of diagnosis, second-line, or third-line therapy were identified for evaluation of outcomes.<br><br>RESULTS: There were 666 older patients with advanced MPM, of whom 82% were male, 87% White, 78% stage IV, and 70% had no mobility limitation indicators at diagnosis. There were 262 patients who received first-line chemotherapy for advanced MPM, most of whom (80%; n = 209) received pemetrexed-platinum. Of these 209 patients, 41% (n = 86) initiated second-line therapy, and 26% (n = 22) initiated third-line therapy. Median overall survival for the cohort of 209 patients was 7.2 months. Patients with epithelioid histology had better median overall survival (12.2 months) compared with other histologies (4.4-5.6 months). Within 90 days of diagnosis of advanced MPM, 78% of patients were hospitalized, 52% visited an emergency department, and 21% had hospice care. The 2-year cost of care was over $100 000 for all patients with advanced MPM treated with first-line pemetrexed-platinum.<br><br>CONCLUSIONS: Although first-line systemic anticancer treatment was generally consistent with guidelines (e.g., pemetrexed-platinum), poor patient outcomes highlight the need for effective treatment options for older patients with advanced MPM.}, }
@article {pmid34689163, year = {2021}, author = {Shrestha, S and Adhikary, G and Naselsky, W and Xu, W and Friedberg, JS and Eckert, RL}, title = {ACTL6A suppresses p21Cip1 tumor suppressor expression to maintain an aggressive mesothelioma cancer cell phenotype.}, journal = {Oncogenesis}, volume = {10}, number = {10}, pages = {70}, pmid = {34689163}, issn = {2157-9024}, support = {R01 CA211909//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, abstract = {Mesothelioma is a poor prognosis cancer of the mesothelial lining that develops in response to exposure to various agents including asbestos. Actin-Like Protein 6A (ACTL6A, BAF53a) is a SWI/SNF regulatory complex protein that is elevated in cancer cells and has been implicated as a driver of cancer cell survival and tumor formation. In the present study, we show that ACTL6A drives mesothelioma cancer cell proliferation, spheroid formation, invasion, and migration, and that these activities are markedly attenuated by ACTL6A knockdown. ACTL6A expression reduces the levels of the p21Cip1 cyclin-dependent kinase inhibitor and tumor suppressor protein. DNA binding studies show that ACTL6A interacts with Sp1 and p53 binding DNA response elements in the p21Cip1 gene promoter and that this is associated with reduced p21Cip1 promoter activity and p21Cip1 mRNA and protein levels. Moreover, ACTL6A suppression of p21Cip1 expression is required for maintenance of the aggressive mesothelioma cancer cell phenotype suggesting that p21Cip1 is a mediator of ACTL6A action. p53, a known inducer of p21Cip1 expression, is involved ACTL6A in regulation of p21Cip1 in some but not all mesothelioma cells. In addition, ACTL6A knockout markedly reduces tumor formation and this is associated with elevated tumor levels of p21Cip1. These findings suggest that ACTL6A suppresses p21Cip1 promoter activity to reduce p21Cip1 protein as a mechanism to maintain the aggressive mesothelioma cell phenotype.}, }
@article {pmid34234080, year = {2021}, author = {Ken Takahashi, }, title = {Asbestos Diseases Research Institute - A New WHO Collaborating Center.}, journal = {Industrial health}, volume = {59}, number = {3}, pages = {143-145}, doi = {10.2486/indhealth.1-3}, pmid = {34234080}, issn = {1880-8026}, mesh = {Academies and Institutes ; *Asbestos/adverse effects ; *Asbestosis/epidemiology ; Humans ; *Mesothelioma ; *Occupational Exposure ; World Health Organization ; }, }
@article {pmid34679210, year = {2021}, author = {Hiraku, Y and Watanabe, J and Kaneko, A and Ichinose, T and Murata, M}, title = {MicroRNA expression in lung tissues of asbestos-exposed mice: Upregulation of miR-21 and downregulation of tumor suppressor genes Pdcd4 and Reck.}, journal = {Journal of occupational health}, volume = {63}, number = {1}, pages = {e12282}, doi = {10.1002/1348-9585.12282}, pmid = {34679210}, issn = {1348-9585}, support = {23659328//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; 24390153//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; 15H04784//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; 18H03038//Ministry of Education, Culture, Sports, Science and Technology, Japan/ ; //Grants-in-Aid for Scientific Research/ ; }, abstract = {OBJECTIVES: Asbestos causes lung cancer and malignant mesothelioma in humans, but the precise mechanism has not been well understood. MicroRNA (miRNA) is a short non-coding RNA that suppresses gene expression and participates in human diseases including cancer. In this study, we examined the expression levels of miRNA and potential target genes in lung tissues of asbestos-exposed mice by microarray analysis.<br><br>METHODS: We intratracheally administered asbestos (chrysotile and crocidolite, 0.05 or 0.2 mg/instillation) to 6-week-old ICR male mice four times weekly. We extracted total RNA from lung tissues and performed microarray analysis for miRNA and gene expression. We also carried out real-time polymerase chain reaction (PCR), Western blotting, and immunohistochemistry to confirm the results of microarray analysis.<br><br>RESULTS: Microarray analysis revealed that the expression levels of 14 miRNAs were significantly changed by chrysotile and/or crocidolite (>2-fold, P < .05). Especially, miR-21, an oncogenic miRNA, was significantly upregulated by both chrysotile and crocidolite. In database analysis, miR-21 was predicted to target tumor suppressor genes programmed cell death 4 (Pdcd4) and reversion-inducing-cysteine-rich protein with kazal motifs (Reck). Although real-time PCR showed that Pdcd4 was not significantly downregulated by asbestos exposure, Western blotting and immunohistochemistry revealed that PDCD4 expression was reduced especially by chrysotile. Reck was significantly downregulated by chrysotile in real-time PCR and immunohistochemistry.<br><br>CONCLUSIONS: This is the first study demonstrating that miR-21 was upregulated and corresponding tumor suppressor genes were downregulated in lung tissues of asbestos-exposed animals. These molecular events are considered to be an early response to asbestos exposure and may contribute to pulmonary toxicity and carcinogenesis.}, }
@article {pmid34676483, year = {2021}, author = {Sonobe, M and Kou, Y and Yamazaki, N and Sakaguchi, Y and Tanaka, H}, title = {Staged removal of artificial patches for thoracic empyema after extrapleural pneumonectomy for diffuse malignant pleural mesothelioma.}, journal = {General thoracic and cardiovascular surgery}, volume = {}, number = {}, pages = {}, pmid = {34676483}, issn = {1863-6713}, abstract = {A 69-year-old man with occupational exposure to asbestos was referred to our hospital with right diffuse malignant pleural mesothelioma. He underwent extrapleural pneumonectomy with reconstruction of the pericardium and diaphragm using elongated polytetrafluoroethylene patches, followed by postoperative chemotherapy and chest wall irradiation. One year later, he was hospitalized because of a right empyema caused by Escherichia coli infection. As chest drainage and systemic antibiotics did not eliminate the abscess around the artificial patches, a Clagett window was created. To avoid mediastinal and liver overshift into the right thoracic cavity, we only performed partial resection of the diaphragm patch and incision of the artificial pericardium. After 19 days of irrigation and dressing change, the artificial patches were completely removed. Two months later, the patient provided a culture-negative sample and had an improved nutritional status; we therefore performed closure of the Clagett window with thoracoplasty. He did not experience recurrence of empyema.}, }
@article {pmid34682428, year = {2021}, author = {Kim, EA}, title = {Standardized Incidence Ratio and Standardized Mortality Ratio of Malignant Mesothelioma in a Worker Cohort Using Employment Insurance Database in Korea.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {20}, pages = {}, doi = {10.3390/ijerph182010682}, pmid = {34682428}, issn = {1660-4601}, abstract = {Malignant mesothelioma is one of the appropriate indicators for assessing the carcinogenic effects of asbestos. This study compared the risk ratio of mesothelioma according to the industry in the worker cohort. A cohort was constructed using the Korean employment insurance system during 1995-2017, enrolling 13,285,895 men and 10,452,705 women. The standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were calculated using the indirect standardization method. There were 641 malignant mesotheliomas that occurred; the SIR was significantly higher than the general population (men 1.36, 95% confidence interval (CI) 1.24-1.48, women 1.44, 95% CI: 1.23-1.7). More than half (52.8%) of malignant mesothelioma cases occurred in the manufacturing (n = 240, 38.6%, SIR: men, 1.72, 95% CI: 1.37-2.15, women, 3.31, 95% CI: 1.71-5.79) and construction industries (n = 88, 14.2%, SIR: men, 1.54 95% CI: 1.33-1.78, women, 1.62 95% CI: 1.25-2.11). The accommodation and food service (men, 2.56 95% CI: 1.28-4.58, women 1.35, 95% CI: 0.65-2.48) and real estate (men 1.34, 95% CI: 0.98-1.83, women 1.95, 95% CI: 0.78-4.02) also showed a high SIR, indicating the risk of asbestos-containing materials in old buildings. The incidence of malignant mesothelioma is likely to increase in the future, given the long latency of this disease. Moreover, long-term follow-up studies will be needed.}, }
@article {pmid34681644, year = {2021}, author = {Badger, R and Park, K and Pietrofesa, RA and Christofidou-Solomidou, M and Serve, KM}, title = {Late Inflammation Induced by Asbestiform Fibers in Mice Is Ameliorated by a Small Molecule Synthetic Lignan.}, journal = {International journal of molecular sciences}, volume = {22}, number = {20}, pages = {}, doi = {10.3390/ijms222010982}, pmid = {34681644}, issn = {1422-0067}, abstract = {Exposure to Libby amphibole (LA) asbestos-like fibers is associated with increased risk of asbestosis, mesothelioma, pulmonary disease, and systemic autoimmune disease. LGM2605 is a small molecule antioxidant and free radical scavenger, with anti-inflammatory effects in various disease models. The current study aimed to determine whether the protective effects of LGM2605 persist during the late inflammatory phase post-LA exposure. Male and female C57BL/6 mice were administered daily LGM2605 (100 mg/kg) via gel cups for 3 days before and 14 days after a 200 µg LA given via intraperitoneal (i.p.) injection. Control mice were given unsupplemented gel cups and an equivalent dose of i.p. saline. On day 14 post-LA treatment, peritoneal lavage was assessed for immune cell influx, cytokine concentrations, oxidative stress biomarkers, and immunoglobulins. During the late inflammatory phase post-LA exposure, we noted an alteration in trafficking of both innate and adaptive immune cells, increased pro-inflammatory cytokine concentrations, induction of immunoglobulin isotype switching, and increased oxidized guanine species. LGM2605 countered these changes similarly among male and female mice, ameliorating late inflammation and altering immune responses in late post-LA exposure. These data support possible efficacy of LGM2605 in the prolonged treatment of LA-associated disease and other inflammatory conditions.}, }
@article {pmid34664557, year = {2021}, author = {Sánchez-Trujillo, L and Sanz-Anquela, JM and Ortega, MA}, title = {Use of the Minimum Basic Data Set as a tool for the epidemiological surveillance of mesothelioma.}, journal = {Anales del sistema sanitario de Navarra}, volume = {0}, number = {0}, pages = {}, doi = {10.23938/ASSN.0969}, pmid = {34664557}, issn = {1137-6627}, abstract = {BACKGROUND: Mesothelioma is a very aggressive tumor that appears after several decades of asbestos exposure. The Minimum Basic Data Set (MBDS) has been validated for the incidence of mesothelioma in Italy, but not in Spain. The objectives of this investigation are: to estimate the prevalence, incidence and mortality of mesothelioma in the Community of Madrid (CM); to evaluate the distribution of this risk within the territory; and to explore validity of the MBDS in the epidemiological surveillance of mesothelioma.<br><br>METHODS: Prevalence, incidence and mortality mesothelioma rates were calculated for the CM from data of the MBDS (2016 and 2017), and mortality data of the Spanish National Statistics Institute (INE) for the same period. The geographical distribution of cases and deaths, and its correlation at municipal level was studied. Statistical analysis with R and Excel tools was carried out.<br><br>RESULTS: The incidence of mesothelioma in the CM was higher than in previous years. Mortality estimated by the MBDS and calculated using INE data for 2016 were similar in the CM. The correlation between the geographical patterns of risk of mesothelioma obtained from the two sources was high (r = 0.86). The aggregation of cases continues in municipalities in the south, detecting the maximum risk in Aranjuez.<br><br>CONCLUSION: The MBDS and INE are good resources for monitoring the risk of mesothelioma. New studies that investigate the aggregation of cases in Aranjuez are required.}, }
@article {pmid34663305, year = {2021}, author = {Sato, T and Nakanishi, H and Akao, K and Okuda, M and Mukai, S and Kiyono, T and Sekido, Y}, title = {Three newly established immortalized mesothelial cell lines exhibit morphological phenotypes corresponding to malignant mesothelioma epithelioid, intermediate, and sarcomatoid types, respectively.}, journal = {Cancer cell international}, volume = {21}, number = {1}, pages = {546}, pmid = {34663305}, issn = {1475-2867}, support = {JP19H03527//japan society for the promotion of science/ ; JP18K07255//japan society for the promotion of science/ ; 20K16462//japan society for the promotion of science/ ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a very aggressive tumor that develops from mesothelial cells, mainly due to asbestos exposure. MM is categorized into three major histological subtypes: epithelioid, sarcomatoid, and biphasic, with the biphasic subtype containing both epithelioid and sarcomatoid components. Patients with sarcomatoid mesothelioma usually show a poorer prognosis than those with epithelioid mesothelioma, but it is not clear how these morphological phenotypes are determined or changed during the oncogenic transformation of mesothelial cells.<br><br>METHODS: We introduced the E6 and E7 genes of human papillomavirus type 16 and human telomerase reverse transcriptase gene in human peritoneal mesothelial cells and established three morphologically different types of immortalized mesothelial cell lines.<br><br>RESULTS: HOMC-B1 cells exhibited epithelioid morphology, HOMC-A4 cells were fibroblast-like, spindle-shaped, and HOMC-D4 cells had an intermediate morphology, indicating that these three cell lines closely mimicked the histological subtypes of MM. Gene expression profiling revealed increased expression of NOD-like receptor signaling-related genes in HOMC-A4 cells. Notably, the combination treatment of HOMC-D4 cells with TGF-β and IL-1β induced a morphological change from intermediate to sarcomatoid morphology.<br><br>CONCLUSIONS: Our established cell lines are useful for elucidating the fundamental mechanisms of mesothelial cell transformation and mesothelial-to-mesenchymal transition.}, }
@article {pmid34656224, year = {2021}, author = {Nowak, AK}, title = {CONFIRMing single-drug immune checkpoint blockade efficacy in mesothelioma.}, journal = {The Lancet. Oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S1470-2045(21)00516-7}, pmid = {34656224}, issn = {1474-5488}, }
@article {pmid34652478, year = {2021}, author = {Ebbinghaus-Mier, D and Ebbinghaus, R and Prager, HM and Schöps, W and Golka, K}, title = {[Mesothelioma of the tunica vaginalis of the testis-a histopathological finding with far-reaching consequences].}, journal = {Der Urologe. Ausg. A}, volume = {}, number = {}, pages = {}, pmid = {34652478}, issn = {1433-0563}, abstract = {Mesotheliomas are very aggressive tumors, almost exclusively caused by asbestos. Four of the 5 mesotheliomas assessed in the years 2014-2020 were recognized as occupational diseases, the 5th case was discontinued due to lack of the patient's cooperation. Surgical exposure of the testis was performed under the suspected diagnoses of hydrocele (n = 3), spermatocele (n = 1) as well as "unknown" (n = 1). This proves that a histopathological examination of removed tissue is the gold standard in scrotal interventions. Every mesothelioma must always be reported as an occupational disease.}, }
@article {pmid34651555, year = {2021}, author = {Paustenbach, D and Brew, D and Ligas, S and Heywood, J}, title = {A critical review of the 2020 EPA risk assessment for chrysotile and its many shortcomings.}, journal = {Critical reviews in toxicology}, volume = {}, number = {}, pages = {1-31}, doi = {10.1080/10408444.2021.1968337}, pmid = {34651555}, issn = {1547-6898}, abstract = {From 2018 to 2020, the United States Environmental Protection Agency (EPA) performed a risk evaluation of chrysotile asbestos to evaluate the hazards of asbestos-containing products (e.g. encapsulated products), including brakes and gaskets, allegedly currently sold in the United States. During the public review period, the EPA received more than 100 letters commenting on the proposed risk evaluation. The Science Advisory Committee on Chemicals (SACC), which peer reviewed the document, asked approximately 100 questions of the EPA that they expected to be addressed prior to publication of the final version of the risk assessment on 30 December 2020. After careful analysis, the authors of this manuscript found many significant scientific shortcomings in both the EPA's draft and final versions of the chrysotile risk evaluation. First, the EPA provided insufficient evidence regarding the current number of chrysotile-containing brakes and gaskets being sold in the United States, which influences the need for regulatory oversight. Second, the Agency did not give adequate consideration to the more than 200 air samples detailed in the published literature of auto mechanics who changed brakes in the 1970-1989 era. Third, the Agency did not consider more than 15 epidemiology studies indicating that exposures to encapsulated chrysotile asbestos in brakes and gaskets, which were generally in commerce from approximately 1950-1985, did not increase the incidence of any asbestos-related disease. Fourth, the concern about chrysotile asbestos being a mesothelioma hazard was based on populations in two facilities where mixed exposure to chrysotile and commercial amphibole asbestos (amosite and crocidolite) occurred. All 8 cases of pleural cancer and mesothelioma in the examined populations arose in facilities where amphiboles were present. It was therefore inappropriate to rely on these cohorts to predict the health risks of exposure to short fiber chrysotile, especially of those fibers filled with phenolic resins. Fifth, the suggested inhalation unit risk (IUR) for chrysotile asbestos was far too high since it was not markedly different than for amosite, despite the fact that the amphiboles are a far more potent carcinogen. Sixth, the approach to low dose modeling was not the most appropriate one in several respects, but, without question, it should have accounted for the background rate of mesothelioma in the general population. Just one month after this assessment was published, the National Academies of Science notified the EPA that the Agency's systematic review process was flawed. The result of the EPA's chrysotile asbestos risk evaluation is that society can expect dozens of years of scientifically unwarranted litigation. Due to an aging population and because some fraction of the population is naturally predisposed to mesothelioma given the presence of various genetic mutations in DNA repair mechanisms (e.g. BAP1 and others), the vast majority of mesotheliomas in the post-2035 era are expected to be spontaneous and unrelated in any way to exposure to asbestos. Due to the EPA's analysis, it is our belief that those who handled brakes and gaskets in the post-1985 era may now believe that those exposures were the cause of their mesothelioma, when a risk assessment based on the scientific weight of evidence would indicate otherwise.}, }
@article {pmid34649858, year = {2021}, author = {Magnavita, N and Congedo, MT and Di Prinzio, RR and Iuliano, A}, title = {War journalism: an occupational exposure.}, journal = {BMJ case reports}, volume = {14}, number = {10}, pages = {}, doi = {10.1136/bcr-2021-245165}, pmid = {34649858}, issn = {1757-790X}, mesh = {*Asbestos/toxicity ; Dust ; Humans ; Male ; *Mesothelioma/chemically induced ; Middle Aged ; *Occupational Diseases/etiology ; *Occupational Exposure/adverse effects ; *Pleural Neoplasms ; Silicon Dioxide ; }, abstract = {Apart from the risk of accidents, war theatres present a hazard related to numerous long-lasting toxic agents. For 10 years, a >60-year-old male journalist worked in war theatres in the Far and Near East where he was exposed to asbestos and other toxic substances (metals, silica, clays, polycyclic aromatic hydrocarbons and other organic substances) contained in dust and smoke of destroyed buildings. More than 15 years later, he developed a mucoepidermoid carcinoma of the soft palate and, subsequently, a pleural malignant mesothelioma. The safety of war journalists should focus not only on preventing the risk of being killed, but also on providing protection from toxic and carcinogenic agents. Exposure to substances released during the destruction of buildings can also pose a carcinogenic risk for survivors.}, }
@article {pmid34645127, year = {2021}, author = {Angelini, A and Chellini, E}, title = {[Inventory of occupational exposure to asbestos with particular reference to Tuscan workers].}, journal = {Epidemiologia e prevenzione}, volume = {45}, number = {}, pages = {1-120}, doi = {10.19191/EP21.5S1.073}, pmid = {34645127}, issn = {1120-9763}, abstract = {This Catalogue is a collection of information on the use of raw asbestos and asbestos-containing materials used in several industries and occupational activities, with particular attention to the situation of Tuscany, a region of Central Italy. The work was developed at the Institute for Cancer Research, Prevention and Clinical Network (ISPRO) of Florence, where epidemiologic research and surveillance activities have been developing since 1988 and where the coordination and evaluation of the regional health surveillance programme provided to past asbestos workers started in 2016 and is still ongoing. The Catalogue aims at being a working tool for all health professionals engaged in examining and classifying the occupational asbestos exposures of subjects both affected by diseases that could be associated to this carcinogen and examined within the regional health surveillance programme. It is necessary for the health personnel engaged in the above-mentioned activities to know or to have the possibility to find exact and detailed data on asbestos exposure by occupational sector. These data are briefly described in the 29 factsheets this Catalogue consists of. In each factsheet, the presence and every use of asbestos are described, with reference to a precise occupational sector. Several occupational sectors can be considered together because of analogies on asbestos exposure. Occupations are considered on the basis of existing evidence on the use of raw asbestos or asbestos-containing materials (as semi-finished or finished products or as auxiliary materials in production processes). Besides the presence and use of asbestos, a description of the possible exposures of workers is reported. Sources of information were scientific and grey literature as well as the 7,187 occupational histories of mesothelioma registered by the specific Tuscan registry. Some factsheets have been revised and enhanced by Italian experts on the asbestos exposure with a specific competence in the examined sectors. Each factsheet includes also questions to be addressed to workers in order to examine in depth their possible asbestos exposure. For those who would like to expand their knowledge on this topic, references are reported both at the end of each factsheet and at the end of the volume. In all industrialized countries, also in those which have not already banned asbestos use, a decrease in the use of this material and in the relative exposure have been observing since the end of the Seventies, few years after the general consensus within the scientific community on asbestos carcinogenicity. This decreasing trend has been becoming greater and greater since the end of the Eighties, when more restrictive regulations have been approved and applied, especially in occupational settings. Nevertheless, nowadays asbestos-related diseases are still diagnosed due to past exposures, although during next decade a decreasing incidence of malignant mesothelioma - the cancer most specifically related to this carcinogen and characterized by a very bad prognosis and the longest latency - could be observed. Particular attention will be paid to jobs regarding renovation of old buildings containing asbestos and to decontamination activities. In conclusion, this Catalogue is a working tool - although it is not exhaustive and could be upgraded with new information - for all professionals engaged in asbestos risk prevention activities as health personnel, personnel of insurance companies, employers, and employee representatives.}, }
@article {pmid34641979, year = {2021}, author = {Kuroda, A}, title = {Recent progress and perspectives on the mechanisms underlying Asbestos toxicity.}, journal = {Genes and environment : the official journal of the Japanese Environmental Mutagen Society}, volume = {43}, number = {1}, pages = {46}, pmid = {34641979}, issn = {1880-7046}, support = {JPMEERF201950001//environmental restoration and conservation agency/ ; 19H04291//japan society for the promotion of science/ ; }, abstract = {Most cases of mesothelioma are known to result from exposure to asbestos fibers in the environment or occupational ambient air. The following questions regarding asbestos toxicity remain partially unanswered: (i) why asbestos entering the alveoli during respiration exerts toxicity in the pleura; and (ii) how asbestos causes mesothelioma, even though human mesothelial cells are easily killed upon exposure to asbestos. As for the latter question, it is now thought that the frustrated phagocytosis of asbestos fibers by macrophages prolongs inflammatory responses and gives rise to a "mutagenic microenvironment" around mesothelial cells, resulting in their malignant transformation. Based on epidemiological and genetic studies, a carcinogenic model has been proposed in which BRCA1-associated protein 1 mutations are able to suppress cell death in mesothelial cells and increase genomic instability in the mutagenic microenvironment. This leads to additional mutations, such as CDKN2A [p16], NF2, TP53, LATS2, and SETD2, which are associated with mesothelioma carcinogenesis. Regarding the former question, the receptors involved in the intracellular uptake of asbestos and the mechanism of transfer of inhaled asbestos from the alveoli to the pleura are yet to be elucidated. Further studies using live-cell imaging techniques will be critical to fully understanding the mechanisms underlying asbestos toxicity.}, }
@article {pmid34641792, year = {2021}, author = {Ahmad Beshr, K and Mohammad Sami, A and Ahmad, G and Nihad, M and Agha, S}, title = {A rare case of benign multicystic peritoneal mesothelioma misdiagnosed as hydatid cyst found in the liver parenchyma and abdomen cavity of a male with asbestos exposure.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {374}, pmid = {34641792}, issn = {1471-230X}, mesh = {Abdomen ; *Asbestos ; Diagnostic Errors ; *Echinococcosis ; Humans ; Liver ; Male ; *Mesothelioma, Cystic/diagnosis/surgery ; Middle Aged ; Neoplasm Recurrence, Local ; }, abstract = {BACKGROUND: Benign Multicystic Peritoneal Mesothelioma (BMPM) is one of the rarest diseases in medicine with only more than 200 cases worldwide. This paper aims to report a case of Benign Multicystic Peritoneal Mesothelioma that strangely arose from the liver and was long treated as Hydatid cyst. The case also had many risk factors including asbestos exposure that had not yet been linked with Benign Multicystic Peritoneal Mesothelioma.<br><br>CASE PRESENTATION: We report a case of a 62 years old male with a history of a perforated peptic ulcer and a cystic mass in the liver that was misdiagnosed as hydatid cyst 7 years ago. He presented with generalized abdominal pain and bloating. Image studies showed many cystic formations filled with clear fluid. An en bloc surgery was performed and a pathologic study showed a multiloculated mass lined by flat or cuboidal epithelium leading to the diagnosis of BMPM. A follow up was scheduled after 3 months revealed total recurrence.<br><br>CONCLUSION: BMPM resembles many other cystic lesions in the abdomen and should be taken into consideration when dealing with nontypical cystic formations. Its diagnostic and treatment methods are still hazy making this disease difficult to approach.}, }
@article {pmid34639316, year = {2021}, author = {Fazzo, L and Binazzi, A and Ferrante, D and Minelli, G and Consonni, D and Bauleo, L and Bruno, C and Bugani, M and De Santis, M and Iavarone, I and Magnani, C and Romeo, E and Zona, A and Alessi, M and Comba, P and Marinaccio, A}, title = {Burden of Mortality from Asbestos-Related Diseases in Italy.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {19}, pages = {}, doi = {10.3390/ijerph181910012}, pmid = {34639316}, issn = {1660-4601}, abstract = {Asbestos is one of the major worldwide occupational carcinogens. The global burden of asbestos-related diseases (ARDs) was estimated around 231,000 cases/year. Italy was one of the main European asbestos producers until the 1992 ban. The WHO recommended national programs, including epidemiological surveillance, to eliminate ARDs. The present paper shows the estimate of the burden of mortality from ARDs in Italy, established for the first time. National standardized rates of mortality from mesothelioma and asbestosis and their temporal trends, based on the National Institute of Statistics database, were computed. Deaths from lung cancer attributable to asbestos exposure were estimated using population-based case-control studies. Asbestos-related lung and ovarian cancer deaths attributable to occupational exposure were estimated, considering the Italian occupational cohort studies. In the 2010-2016 period, 4400 deaths/year attributable to asbestos were estimated: 1515 from mesothelioma, 58 from asbestosis, 2830 from lung and 16 from ovarian cancers. The estimates based on occupational cohorts showed that each year 271 deaths from mesothelioma, 302 from lung cancer and 16 from ovarian cancer were attributable to occupational asbestos exposure in industrial sectors with high asbestos levels. The important health impact of asbestos in Italy, 10-25 years after the ban, was highlighted. These results suggest the need for appropriate interventions in terms of prevention, health care and social security at the local level and could contribute to the global estimate of ARDs.}, }
@article {pmid34639307, year = {2021}, author = {Kwon, SC and Lee, SS and Kang, MS and Huh, DA and Lee, YJ}, title = {The Epidemiologic Characteristics of Malignant Mesothelioma Cases in Korea: Findings of the Asbestos Injury Relief System from 2011-2015.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {19}, pages = {}, doi = {10.3390/ijerph181910007}, pmid = {34639307}, issn = {1660-4601}, abstract = {(1) Background: The purpose of this study was to investigate the epidemiological characteristics of malignant mesothelioma in Korea by investigating cases compensated under the asbestos injury relief system. (2) Methods: A total of 407 compensated cases between 2011 and 2015 were reviewed using medical records and resident registrations in order to investigate the dates of diagnosis and death. Asbestos exposure and patients' general characteristics were investigated through face-to-face interviews. The standardized incidence ratio was calculated as the number of observations from 2005 to 2014 per exposure region in Korea, using the mid-annual population of each region in 2009 as the standard population. (3) Results: Among the 407 cases, 65.1% were male. The pleura and peritoneum were affected in 76.9% and 23.1% of cases, respectively. For peritoneal mesothelioma, the median survival duration was longer (p = 0.005), and the proportion of affected women was higher than that in pleural mesothelioma. The standardized incidence ratio (95% CI) by province of primary exposure was Chungnam 3.33 (2.51-4.35), Ulsan 1.85 (0.97-3.21), and Seoul 1.32 (1.06-1.63). (4) Conclusions: Although the representativeness of the data is limited, it is sufficient to assume the epidemiologic characteristics of malignant mesothelioma, help improve the compensation system, and contribute to future policies.}, }
@article {pmid34638565, year = {2021}, author = {Yuen, ML and Zhuang, L and Rath, EM and Yu, T and Johnson, B and Sarun, KH and Wang, Y and Kao, S and Linton, A and Clarke, CJ and McCaughan, BC and Takahashi, K and Lee, K and Cheng, YY}, title = {The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM).}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, doi = {10.3390/ijms221910225}, pmid = {34638565}, issn = {1422-0067}, support = {2018//Regional Collaboration Program Grant/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective treatment options. Focal adhesion kinase (FAK) inhibitors have been shown to efficiently suppress MPM cell growth initially, with limited utility in the current clinical setting. In this study, we utilised a large collection of MPM cell lines and MPM tissue samples to study the role of E-cadherin (CDH1) and microRNA on the efficacy of FAK inhibitors in MPM. The immunohistochemistry (IHC) results showed that the majority of MPM FFPE samples exhibited either the absence of, or very low, E-cadherin protein expression in MPM tissue. We showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. In summary, MPM cells that did not express CDH1 mRNA were sensitive to PND-1186, and MPM cells that retained CDH1 mRNA were resistant. A cell cycle analysis showed that PND-1186 induced cell cycle disruption by inducing the G2/M arrest of MPM cells. A protein-protein interaction study showed that EGFR is linked to the FAK pathway, and a target scan of the microRNAs revealed that microRNAs (miR-17, miR221, miR-222, miR137, and miR148) interact with EGFR 3'UTR. Transfection of MPM cells with these microRNAs sensitised the CHD1-expressing FAK-inhibitor-resistant MPM cells to the FAK inhibitor.}, }
@article {pmid33851620, year = {2021}, author = {Fujishima, F and Konosu-Fukaya, S and Nabeshima, K and McNamara, KM and Sakamoto, K and Sakurada, J and Sasano, H and Nakamura, Y}, title = {Histological and immunohistochemical characteristics and p16 status studied by FISH in six incidentally detected cases of well-differentiated papillary mesothelioma of the peritoneum.}, journal = {Indian journal of pathology &amp; microbiology}, volume = {64}, number = {2}, pages = {277-281}, doi = {10.4103/IJPM.IJPM_111_20}, pmid = {33851620}, issn = {0974-5130}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Female ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization, Fluorescence ; Male ; Mesothelioma/diagnosis/*pathology/surgery ; Middle Aged ; Peritoneal Neoplasms/diagnosis/*pathology/surgery ; Peritoneum/pathology ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/metabolism ; }, abstract = {Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial neoplasm, which is generally regarded as benign or indolent in terms of its clinical behavior. However, details about WDPM have remained relatively unknown. Therefore, in this study, we examined six incidentally detected cases of WDPM of the peritoneum. All six cases were surgically excised, without any additional therapeutic measures. None of the cases showed recurrence. All six cases presented single lesions and the tumor sizes ranged from 2 to 10 mm. Histologically, all six cases exhibited papillary proliferation of cytologically bland mesothelial cells with a fibroconnective tissue core. One of the cases (Case 6) presented small invasive foci in the stalk. The tumor cells were immunohistochemically positive for mesothelial markers and negative for GLUT-1, p53, and CD146. The Ki-67 labeling index of the tumor cells was lower than 5% at the hot spots. All samples were BAP1-positive. None of the samples presented p16 homozygous deletion, as assessed by fluorescence in situ hybridization (FISH). None of the patients deceased due to WDPM. However, in Case 3, death occurred due to pancreatic cancer. The results of this study indicate the importance of analyzing immunohistochemical markers and p16 status to diagnose WDPM accurately.}, }
@article {pmid34602383, year = {2021}, author = {Gupta, N and Soni, A and Mahajan, R and Selhi, P and Tyagi, R and Garg, B and Kaur, H}, title = {Peritoneal malignant mesothelioma: Slippery like an eel to diagnose on cytology-case series of 3 cases.}, journal = {Journal of the American Society of Cytopathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jasc.2021.08.007}, pmid = {34602383}, issn = {2213-2945}, abstract = {INTRODUCTION: Peritoneal malignant mesothelioma is an extremely rare tumor and is a difficult diagnosis to be made on cytology alone. We report 3 cases where the cytologic features were misdiagnosed as carcinoma/lymphoma but histopathology and immunohistochemistry (IHC) established the diagnosis of malignant mesothelioma.<br><br>CLINICAL DETAILS: Case 1 was a 60-year-old man with multiloculated ascites and omental caking. Peritoneal fluid was reported as malignant on cytology but was misclassified as adenocarcinoma. Case 2, a 45-year-old man with ascites and peritoneal nodularity, radiologically mimicking peritoneal carcinomatosis, was also reported positive for malignancy on ascitic fluid cytology. Fine-needle aspiration (FNAC) from omental fat revealed signet ring cells, thus misleading to cytologic diagnosis of adenocarcinoma. Case 3 was a 63-year-old man with perisplenic mass with extensive omental caking and peritoneal nodularity that was also suspected to be peritoneal carcinomatosis on radiology. FNAC smears from perisplenic mass showed sheets of plasmacytoid cells. On cytology, the differential diagnoses offered were neuroendocrine tumor or non-Hodgkin lymphoma. The diagnosis of malignant mesothelioma was established only after IHC on histopathologic sections in all these cases. None of our patients had history of prior asbestos exposure.<br><br>CONCLUSION: In such clinical scenarios, with radiology suggesting peritoneal carcinomatosis, the cytologic features need corroboration by IHC/fluorescence in situ hybridization on cell block or biopsy to correctly identify malignant mesothelioma and differentiate it from metastatic carcinomatous deposits and benign mesothelial proliferation.}, }
@article {pmid34594644, year = {2020}, author = {Chen, M and Wang, H and Zhang, J and Yu, C and Liu, W and Xu, Y}, title = {Distribution of Asbestos Enterprises and Asbestosis Cases - China, 1997-2019.}, journal = {China CDC weekly}, volume = {2}, number = {18}, pages = {305-309}, doi = {10.46234/ccdcw2020.078}, pmid = {34594644}, issn = {2096-7071}, abstract = {Asbestos is classified as a Class I Carcinogen by the International Agency for Research on Cancer (IARC) because exposure causes mesothelioma and lung cancer in addition to asbestosis and plaques. So far, asbestos has been banned in 67 countries, but chrysotile, a commonly encountered form of asbestos, is still widely used in China and most developing countries. Most asbestos-caused cancers are not reported, recorded, and compensated in many countries.<br><br>What is added by this report?: Enterprises manufacturing asbestos products have been migrating from economically developed Eastern China to relatively underdeveloped central and western regions between 2010 and 2019. Asbestosis cases reported in Tianjin, Beijing, Shandong, Xinjiang, Gansu, Qinghai, and Sichuan accounted for a large proportion of the total cases in China, which was inconsistent with the distribution of asbestos-related enterprises (AREs). The reported asbestosis cases versus total pneumoconiosis cases declined from 2.81% to 0.39% from 2006-2017, and this proportion reached 0.69% in 2018.<br><br>Robust occupational and environmental health assessments and reporting are needed to define the epidemiology of asbestos-related lung diseases, and management of using asbestos and existing products containing asbestos need strengthening and follow-up. Enterprises should be encouraged to use safer substitutes and gradually ban asbestos materials in China.}, }
@article {pmid34590026, year = {2021}, author = {Nakagawa, K and Kijima, T and Okada, M and Morise, M and Kato, M and Hirano, K and Fujimoto, N and Takenoyama, M and Yokouchi, H and Ohe, Y and Hida, T and Aoe, K and Kishimoto, T and Hirokawa, M and Matsuki, H and Kaneko, Y and Yamada, T and Morimoto, C and Takeda, M}, title = {Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma.}, journal = {JTO clinical and research reports}, volume = {2}, number = {6}, pages = {100178}, doi = {10.1016/j.jtocrr.2021.100178}, pmid = {34590026}, issn = {2666-3643}, abstract = {Introduction: YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study.<br><br>Methods: The patients included were aged 20 years and older, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase 1 dose-determination part, was given in 6-weekly cycles (5 × once-weekly infusions, followed by a 1-wk rest).<br><br>Results: The study included 31 patients (median age = 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greater than or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. The best overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab-groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Common treatment-related adverse events were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths.<br><br>Conclusions: The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.}, }
@article {pmid34589956, year = {2020}, author = {Ahmadzada, T and Cooper, WA and Holmes, M and Mahar, A and Westman, H and Gill, AJ and Nordman, I and Yip, PY and Pal, A and Zielinski, R and Pavlakis, N and Nagrial, A and Daneshvar, D and Brungs, D and Karikios, D and Aleksova, V and Burn, J and Asher, R and Grau, GE and Hosseini-Beheshti, E and Reid, G and Clarke, S and Kao, S}, title = {Retrospective Evaluation of the Use of Pembrolizumab in Malignant Mesothelioma in a Real-World Australian Population.}, journal = {JTO clinical and research reports}, volume = {1}, number = {4}, pages = {100075}, doi = {10.1016/j.jtocrr.2020.100075}, pmid = {34589956}, issn = {2666-3643}, abstract = {Introduction: We investigated the efficacy and toxicity of pembrolizumab in patients with mesothelioma from a real-world Australian population. We aimed to determine clinical factors and predictive biomarkers that could help select patients who are likely to benefit from pembrolizumab.<br><br>Method: Patients with mesothelioma who were treated with pembrolizumab as part of the Insurance and Care New South Wales compensation scheme were included. Clinical information was collected retrospectively. Tumor biomarkers such as programmed death-ligand 1 (PD-L1), BAP1, and CD3-positive (CD3+) tumor-infiltrating lymphocytes (TILs) were examined using archival formalin-fixed paraffin-embedded tumor samples.<br><br>Results: A total of 98 patients were included with a median age of 70 years (range, 46-91 y); 92% were men; 76% had epithelioid subtype; 21% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Pembrolizumab was used as second-line or subsequent-line treatment in 94 patients and as first-line treatment in four patients. The overall response rate was 18%, and the disease control rate was 56%. The median progression-free survival (PFS) was 4.8 months (95% confidence interval: 3.6-6.2), and the median overall survival (OS) was 9.5 months (95% confidence interval: 6.6-13.7). Immune-related adverse events occurred in 27% of patients, of which nine (9%) were of grade 3 or higher. In the multivariable analysis, factors independently associated with longer PFS included baseline ECOG status of 0 (median PFS: 12 mo versus 4 mo, p < 0.01) and PD-L1 tumor proportion score of greater than or equal to 1% (median PFS: 6 mo versus 4 mo, p < 0.01). Baseline platelet count of less than or equal to 400 × 109/liter was independently associated with longer PFS and OS (median PFS: 6 mo versus 2 mo, p = 0.05; median OS: 10 mo versus 4 mo, p = 0.01), whereas lack of pretreatment dexamethasone was independently associated with OS but not PFS (median OS: 10 mo versus 3 mo, p = 0.01). The odds of response were higher for patients with baseline ECOG status of 0 (p = 0.02) and with greater than or equal to 5% CD3+ TILs in the tumor (p < 0.01). PD-L1 expression, BAP1 loss, and CD3+ TILs in the stroma were not significantly associated with the overall response rate.<br><br>Conclusions: Immunotherapy is a reasonable treatment option for patients with mesothelioma. Our results are comparable to other clinical trials investigating pembrolizumab in mesothelioma in terms of response. Good performance status assessment remains the most robust predictor for patient outcomes. CD3+ TILs in the tumor may help select patients that are likely to respond to pembrolizumab, whereas factors such as PD-L1 expression, baseline platelet count, and lack of pretreatment dexamethasone may help predict survival outcomes from pembrolizumab treatment.}, }
@article {pmid34575358, year = {2021}, author = {Musso, V and Diotti, C and Palleschi, A and Tosi, D and Aiolfi, A and Mendogni, P}, title = {Management of Pleural Effusion Secondary to Malignant Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {10}, number = {18}, pages = {}, doi = {10.3390/jcm10184247}, pmid = {34575358}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive pleural tumour which has been epidemiologically linked to occupational exposure to asbestos. MPM is often associated with pleural effusion, which is a common cause of morbidity and whose management remains a clinical challenge. In this review, we analysed the literature regarding the diagnosis and therapeutic options of pleural effusion secondary to mesothelioma. Our aim was to provide a comprehensive view on this subject, and a new algorithm was proposed as a practical aid to clinicians dealing with patients suffering from pleural effusion.}, }
@article {pmid34572485, year = {2021}, author = {Štrbac, D and Dolžan, V}, title = {Matrix Metalloproteinases as Biomarkers and Treatment Targets in Mesothelioma: A Systematic Review.}, journal = {Biomolecules}, volume = {11}, number = {9}, pages = {}, doi = {10.3390/biom11091272}, pmid = {34572485}, issn = {2218-273X}, support = {P1-0170, L3-8203 and L3-2622//Javna Agencija za Raziskovalno Dejavnost RS/ ; }, abstract = {Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and apoptosis in several tumors, including mesothelioma. Mesothelioma is a rare tumor arising from pleura and peritoneum and is frequently associated with asbestos exposure. We have performed a systematic search of PubMed.gov and ClinicalTrials.gov databases to retrieve and review three groups of studies: studies of MMPs expression in tumor tissue or body fluids in patients with mesothelioma, studies of MMPs genetic variability, and studies of MMPs as potential novel drug targets in mesothelioma. Several studies of MMPs in mesothelioma tissues reported a link between higher expression levels of commonly studied MMPs and clinical parameters, such as overall survival. Fewer studies have investigated genetic variability of MMP genes. Nevertheless, these studies suggested that certain genetic variants in MMP genes can have either protective or tumor-promoting effects on mesothelioma patients. MMPs have been also reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma. In conclusion, MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma.}, }
@article {pmid34566802, year = {2021}, author = {Di Basilio, D and Shigemura, J and Guglielmucci, F}, title = {Commentary: 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 = {12}, number = {}, pages = {720160}, doi = {10.3389/fpsyg.2021.720160}, pmid = {34566802}, issn = {1664-1078}, }
@article {pmid34549571, year = {2021}, author = {Barbieri, PG and Calisti, R and Calabresi, C}, title = {[Pleural malignant mesotheliomas from environmental exposures to asbestos In Italy].}, journal = {Epidemiologia e prevenzione}, volume = {45}, number = {4}, pages = {289-295}, doi = {10.19191/EP21.4.P289.085}, pmid = {34549571}, issn = {1120-9763}, abstract = {Pleural mesothelioma clusters from outdoor environmental exposure have been highlighted also in Italy and, on the basis of epidemiological surveillance coordinated by the Italian National Mesothelioma Register, their frequency has been estimated at about 4.5%. Epidemiological studies and evaluations of some regional mesothelioma registers have made it possible to highlight that the dispersion of asbestos fibers in the outdoor environment was the only ascertained cause of mesothelioma in subjects from asbestos-cement factories, from the Balangero mine (Piedmont Region), from some serpentine rock quarries with tremolite outcrops in the Southern Apennines and in Alta Val di Susa (Piedmont Region); from chrysotile and serpentine caves in Valmalenco (Lombardy Region). Furthermore, cases of pleural mesothelioma were clearly caused by environmental pollution from fluoroedenite fibers in Biancavilla (Sicily Region). On the other hand, regional mesothelioma registers have also reported other circumstances of environmental asbestos exposure, like in the case of steel industry, shipbuilding, chemical plants, railway lines, and repair/demolition of railway carriages. However, these reports have not found confirmation on the basis of ad-hoc studies and it is likely that there is a lack of homogeneity in the assessment of individual cases. Apart from the scenarios which have been the subject of ad-hoc studies, the assessment of the causal role of environmental exposure to "in place" asbestos in the onset of pleural mesothelioma is problematic without an effort to more carefully examine the circumstances of possible exposure, harmonization of the attribution criteria used in the individual regional registers, analytical assessment of the impact of such exposure on the risk of onset of mesothelioma.}, }
@article {pmid34540427, year = {2021}, author = {Khatib, S and Asad, O and Asad, H and Sabobeh, T}, title = {A Rare Case of Malignant Pleural Mesothelioma in a Young Healthy Male Without Asbestos Exposure.}, journal = {Cureus}, volume = {13}, number = {8}, pages = {e17199}, doi = {10.7759/cureus.17199}, pmid = {34540427}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive malignant tumor that arises from mesothelial cells of pleural cavity. The main risk factor for MPM is asbestos exposure with most cases discovered in elderly males after a long latency period. However, here we report a rare case of MPM diagnosed in a healthy young male patient without significant asbestos exposure. We report the case of an otherwise healthy 47-year-old male who presented with one week of exertional dyspnea and chest pain. Chest X-ray showed unilateral large pleural effusion. Chest CT scan revealed confluent right hilar mass and pleural thickening. Pleural fluid analysis showed exudative features. Cytology was negative for malignant cells. Core tissue biopsy showed features of epithelioid mesothelioma. Although most cases of MPM have been reported in elderly male patients with significant asbestos exposure, more research is needed to explain the pathogenesis of MPM in young patients without asbestos exposure.}, }
@article {pmid34526026, year = {2021}, author = {Airoldi, C and Magnani, C and Lazzarato, F and Mirabelli, D and Tunesi, S and Ferrante, D}, title = {Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case-control study.}, journal = {Environmental health : a global access science source}, volume = {20}, number = {1}, pages = {103}, pmid = {34526026}, issn = {1476-069X}, abstract = {BACKGROUND: Neighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering.<br><br>METHODS: A population-based case-control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed.<br><br>RESULTS: One hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32-22.38) and 10.48 (95%CI 4.54-24.2) for 0-5 km and 5-10 km, respectively (reference > 15 km). Finally, a significant (p < 0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors.<br><br>CONCLUSIONS: In this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.}, }
@article {pmid34519165, year = {2021}, author = {Torkki, P and Paajanen, J and Kytö, V and Laaksonen, S and Räsänen, J and Myllärniemi, M and Ilonen, I}, title = {Evidence for marked underutilization of insurance billing in malignant pleural mesothelioma in Finland.}, journal = {Thoracic cancer}, volume = {}, number = {}, pages = {}, doi = {10.1111/1759-7714.14146}, pmid = {34519165}, issn = {1759-7714}, abstract = {BACKGROUND: Substantial variation in health care costs for malignant pleural mesothelioma (MPM) has previously been identified.<br><br>MATERIALS AND METHODS: We analyzed the changes in health care costs in MPM in Finland during 2002-2012. Finland has low-threshold public health care and a mandatory Workers' Compensation scheme that covers all occupational-related disease expenses. The costs include treatment costs for inpatients, hospice care, medication costs, rehabilitation costs, and travel costs. All costs are expressed in 2012 prices, adjusted using the consumer price index.<br><br>RESULTS: A total of 907 MPM patients were included in the study. Mean duration of inpatient episodes increased 7% per year from 2002 to 2012, correlating with total costs (R2 = 0.861, p < 0.05). The annual total costs for treatment increased from 1.7 to 4.3 m€ during the study period and the cost per patient from 27 000 to 43 000 €. The overall costs increased progressively by the number of procedures performed. In patients who had been compensated for occupational cause by Workers' Compensation Center, only 36% of the overall care costs were billed from the insurance company. Billing of inpatient costs was 86% in these patients.<br><br>CONCLUSION: During the study period, we found that the costs of MPM increased more than the average health care costs. This may be because of advanced diagnostic workup or more costly treatment (e.g., pemetrexed). Moreover, only one-third of all health care costs are charged to Workers' Compensation Insurance.}, }
@article {pmid34511983, year = {2021}, author = {Xie, D and Hu, J and Wu, T and Cao, K and Luo, X}, title = {Four Immune-Related Genes (FN1, UGCG, CHPF2 and THBS2) as Potential Diagnostic and Prognostic Biomarkers for Carbon Nanotube-Induced Mesothelioma.}, journal = {International journal of general medicine}, volume = {14}, number = {}, pages = {4987-5003}, doi = {10.2147/IJGM.S324365}, pmid = {34511983}, issn = {1178-7074}, abstract = {Background: Malignant pleural mesothelioma (MPM), a highly aggressive cancer, was mainly attributed to asbestos exposure. Carbon nanotubes (CNTs) share similar negative features to asbestos, provoking concerns about their contribution to MPM. This study was used to identify genes associated with CNT-induced MPM.<br><br>Methods: Microarray datasets were available in the Gene Expression Omnibus database. The limma method was used to identify differentially expressed genes (DEGs) in CNT-exposed MeT5A cells (GSE48855) or mice (GSE51636). Weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) network construction were conducted to screen hub DEGs. The mRNA expression levels of hub DEGs were validated on MPM samples of GSE51024, GSE2549 and GSE42977 datasets, and their diagnostic efficacy was determined by receiver operating characteristic curve analysis. The prognostic values of hub DEGs were assessed using online tools based on The Cancer Genome Atlas data. Their functions were annotated by Database for Annotation, Visualization and Integrated Discovery (DAVID) enrichment and correlation with immune cells and markers.<br><br>Results: WGCNA identified that two modules were associated with disease status. Thirty-one common DEGs in the GSE48855 and GSE51636 datasets were overlapped with the genes in these two modules. Twenty of them had a high degree centrality (≥4) in the PPI network. Four DEGs (FN1, fibronectin 1; UGCG, UDP-glucose ceramide glucosyltransferase; CHPF2, chondroitin polymerizing factor 2; and THBS2, thrombospondin 2) could predict the overall survival, and they were confirmed to be upregulated in MPM samples compared with controls. Also, they could effectively predict the MPM risk, with an overall accuracy of >0.9. DAVID analysis revealed FN1, CHPF2 and THBS2 functioned in cell-ECM interactions; UGCG influenced glycosphingolipid metabolism. All genes were positively associated with infiltrating levels of immune cells (macrophages or dendritic cells) and the expression of the dendritic cell marker (NRP1, neuropilin 1).<br><br>Conclusion: These four immune-related genes represent potential biomarkers for monitoring CNT-induced MPM and predicting the prognosis.}, }
@article {pmid34491782, year = {2021}, author = {Nowak, AK and Jackson, A and Sidhu, C}, title = {Management of Advanced Pleural Mesothelioma-At the Crossroads.}, journal = {JCO oncology practice}, volume = {}, number = {}, pages = {OP2100426}, doi = {10.1200/OP.21.00426}, pmid = {34491782}, issn = {2688-1535}, abstract = {The management of pleural mesothelioma has changed with the demonstration that first-line checkpoint blockade therapy improves survival. This review covers issues of relevance to the practicing medical oncologist, with an emphasis on the palliative setting and on new information. Until recently, standard systemic therapy for mesothelioma was combination chemotherapy with platinum and pemetrexed. In 2020, combination immunotherapy with ipilimumab and nivolumab was approved as first-line systemic therapy for mesothelioma following release of the results from the CheckMate 743 trial. This trial showed improved overall survival for patients receiving ipilimumab and nivolumab over those treated with platinum and pemetrexed chemotherapy. When the survival results were examined by histologic subtype, the survival benefit was most significant in those with nonepithelioid mesothelioma, a group for which combination immunotherapy is now standard of care. The most important outstanding issue from CheckMate-743 is a better understanding, through translational studies, of which patients with epithelioid mesothelioma may benefit from combination immunotherapy. The next generation of first-line clinical trials in mesothelioma will report the results of first-line combination chemoimmunotherapy. For those patients who receive first-line dual checkpoint blockade, there is no evidence as to the efficacy of subsequent chemotherapy. However, given the known first-line efficacy of cisplatin or carboplatin and pemetrexed, combination chemotherapy is an appropriate subsequent choice for those who progress on or after dual immunotherapy. For those who previously received chemotherapy without immunotherapy, single-agent nivolumab provides benefit over best supportive care. In summary, both chemotherapy and immunotherapy should be considered for all patients during their disease course. Another topical issue is the growing appreciation that some individuals have an inherited predisposition to mesothelioma; referral to a clinical geneticist should be considered under some circumstances. The role of surgery and multimodality therapy is controversial, with results awaited from the fully recruited MARS-2 clinical trial. Patient selection, staging, and multidisciplinary review are critical to identify those who might benefit from a multimodality approach. Finally, a proactive, multidisciplinary approach to symptom management and the principles of management of pleural effusions are critical to manage the symptom burden of mesothelioma and optimize patient well-being.}, }
@article {pmid34487023, year = {2021}, author = {Dick, IM and Lee, YCG and Cheah, HM and Miranda, A and Robinson, BWS and Creaney, J}, title = {Profile of soluble factors in pleural effusions predict prognosis in mesothelioma.}, journal = {Cancer biomarkers : section A of Disease markers}, volume = {}, number = {}, pages = {}, doi = {10.3233/CBM-210280}, pmid = {34487023}, issn = {1875-8592}, abstract = {BACKGROUND: Pleural mesothelioma is a deadly asbestos induced cancer. Less than 10% of mesothelioma patients survive 5 years post diagnosis. However survival can range from a few months to a number of years. Accurate prediction of survival is important for patients to plan for their remaining life, and for clinicians to determine appropriate therapy. One unusual features of mesothelioma is that patients frequently present with tumor-associated pleural effusions early in the course of the disease.<br><br>OBJECTIVE: To study whether cells and molecules present in pleural effusions provide prognostic information for mesothelioma.<br><br>METHODS: We profiled the cellular constituents and concentrations of 40 cytokines, chemokines and cellular factors (collectively "soluble factors") involved in inflammatory and immune signalling pathways in pleural effusion samples from 50 mesothelioma patients.Associations with survival were evaluated by Cox proportional hazards regression methods. Results for the two soluble factors most significantly and independently associated with survival were validated in an independent set of samples (n= 51) using a separate assay system.<br><br>RESULTS: Survival analysis revealed thatIL8, IL2Ra (CD25) and PF4 were independent determinants of a more negative prognosis in mesothelioma patients, independent of other known prognostic factors. Lipocalin2 and IL4 were associated with better prognosis.<br><br>CONCLUSIONS: This study demonstrates that pleural effusions rich in a range of soluble factors are associated with poor prognosis. These findings will enhance our ability to prognosticate outcomes in mesothelioma patients.}, }
@article {pmid32290761, year = {2020}, author = {Laubenthal, TG}, title = {Regulated Asbestos Analysis: EPA Polarized Light Microscopy Method and the Implications for Reported Fiber Sizes.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {30}, number = {2}, pages = {83-85}, doi = {10.1177/1048291120917952}, pmid = {32290761}, issn = {1541-3772}, mesh = {*Asbestos ; Asbestos, Serpentine ; Humans ; *Mesothelioma ; Microscopy, Polarization ; }, }
@article {pmid34445720, year = {2021}, author = {Lisini, D and Lettieri, S and Nava, S and Accordino, G and Frigerio, S and Bortolotto, C and Lancia, A and Filippi, AR and Agustoni, F and Pandolfi, L and Piloni, D and Comoli, P and Corsico, AG and Stella, GM}, title = {Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach.}, journal = {International journal of molecular sciences}, volume = {22}, number = {16}, pages = {}, doi = {10.3390/ijms22169014}, pmid = {34445720}, issn = {1422-0067}, support = {#08050//IRCCS Policlinico San Mattteo/ ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.}, }
@article {pmid34444165, year = {2021}, author = {Lemen, RA and Landrigan, PJ}, title = {Sailors and the Risk of Asbestos-Related Cancer.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {16}, pages = {}, doi = {10.3390/ijerph18168417}, pmid = {34444165}, issn = {1660-4601}, abstract = {Sailors have long been known to experience high rates of injury, disease, and premature death. Many studies have shown asbestos-related diseases among shipyard workers, but few have examined the epidemiology of asbestos-related disease and death among asbestos-exposed sailors serving on ships at sea. Chrysotile and amphibole asbestos were used extensively in ship construction for insulation, joiner bulkhead systems, pipe coverings, boilers, machinery parts, bulkhead panels, and many other uses, and asbestos-containing ships are still in service. Sailors are at high risk of exposure to shipboard asbestos, because unlike shipyard workers and other occupationally exposed groups, sailors both work and live at their worksite, making asbestos standards and permissible exposure limits (PELs). based on an 8-h workday inadequate to protect their health elevated risks of mesothelioma and other asbestos-related cancers have been observed among sailors through epidemiologic studies. We review these studies here.}, }
@article {pmid34439349, year = {2021}, author = {Brims, F}, title = {Epidemiology and Clinical Aspects of Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {16}, pages = {}, doi = {10.3390/cancers13164194}, pmid = {34439349}, issn = {2072-6694}, abstract = {Mesothelioma is a cancer predominantly of the pleural cavity. There is a clear association of exposure to asbestos with a dose dependent risk of mesothelioma. The incidence of mesothelioma in different countries reflect the historical patterns of commercial asbestos utilisation in the last century and predominant occupational exposures mean that mesothelioma is mostly seen in males. Modern imaging techniques and advances in immunohistochemical staining have contributed to an improved diagnosis of mesothelioma. There have also been recent advances in immune checkpoint inhibition, however, mesothelioma remains very challenging to manage, especially considering its limited response to conventional systemic anticancer therapy and that no cure exists. Palliative interventions and support remain paramount with a median survival of 9-12 months after diagnosis. The epidemiology and diagnosis of mesothelioma has been debated over previous decades, due to a number of factors, such as the long latent period following asbestos exposure and disease occurrence, the different potencies of the various forms of asbestos used commercially, the occurrence of mesothelioma in the peritoneal cavity and its heterogeneous pathological and cytological appearances. This review will describe the contemporary knowledge on the epidemiology of mesothelioma and provide an overview of the best clinical practice including diagnostic approaches and management.}, }
@article {pmid34439164, year = {2021}, author = {Carbotti, G and Dozin, B and Martini, S and Giordano, C and Scordamaglia, F and Croce, M and Filaci, G and Ferrini, S and Fabbi, M}, title = {IL-27 Mediates PD-L1 Expression and Release by Human Mesothelioma Cells.}, journal = {Cancers}, volume = {13}, number = {16}, pages = {}, doi = {10.3390/cancers13164011}, pmid = {34439164}, issn = {2072-6694}, support = {GR-2013-02356568//Italian Ministry of Health/ ; 5 x 1000 Funds//Italian Ministry of Health/ ; Ricerca Corrente 2018-2021//Italian Ministry of Health/ ; }, abstract = {Malignant mesothelioma (MM) is a rare tumor with an unfavorable prognosis. MM genesis involves asbestos-mediated local inflammation, supported by several cytokines, including IL-6. Recent data showed that targeting PD-1/PD-L1 is an effective therapy in MM. Here, we investigated the effects of IL-6 trans-signaling and the IL-6-related cytokine IL-27 on human MM cells in vitro by Western blot analysis of STAT1/3 phosphorylation. The effects on PD-L1 expression were tested by qRT-PCR and flow-cytometry and the release of soluble (s)PD-L1 by ELISA. We also measured the concentrations of sPD-L1 and, by multiplexed immunoassay, IL-6 and IL-27 in pleural fluids obtained from 77 patients in relation to survival. IL-27 predominantly mediates STAT1 phosphorylation and increases PD-L1 gene and surface protein expression and sPD-L1 release by human MM cells in vitro. IL-6 has limited activity, whereas a sIL-6R/IL-6 chimeric protein mediates trans-signaling predominantly via STAT3 phosphorylation but has no effect on PD-L1 expression and release. IL-6, IL-27, and sPD-L1 are present in pleural fluids and show a negative correlation with overall survival, but only IL-27 shows a moderate albeit significant correlation with sPD-L1 levels. Altogether these data suggest a potential role of IL-27 in PD-L1-driven immune resistance in MM.}, }
@article {pmid34430345, year = {2021}, author = {Mathilakathu, A and Borchert, S and Wessolly, M and Mairinger, E and Beckert, H and Steinborn, J and Hager, T and Christoph, DC and Kollmeier, J and Wohlschlaeger, J and Mairinger, T and Schmid, KW and Walter, RFH and Brcic, L and Mairinger, FD}, title = {Mitogen signal-associated pathways, energy metabolism regulation, and mediation of tumor immunogenicity play essential roles in the cellular response of malignant pleural mesotheliomas to platinum-based treatment: a retrospective study.}, journal = {Translational lung cancer research}, volume = {10}, number = {7}, pages = {3030-3042}, doi = {10.21037/tlcr-21-201}, pmid = {34430345}, issn = {2218-6751}, abstract = {Background: Malignant pleural mesothelioma (MPM) is a rare malignant tumor associated with asbestos exposure, with infaust prognosis and overall survival below 20 months in treated patients. Platinum is still the backbone of the chemotherapy protocols, and the reasons for the rather poor efficacy of platinum compounds in MPM remain largely unknown. Therefore, we aimed to analyze differences in key signaling pathways and biological mechanisms in therapy-naïve samples and samples after chemotherapy in order to evaluate the effect of platinum-based chemotherapy.<br><br>Methods: The study cohort comprised 24 MPM tumor specimens, 12 from therapy-naïve and 12 from patients after platinum-based therapy. Tumor samples were screened using the NanoString nCounter platform for digital gene expression analysis with an appurtenant custom-designed panel comprising a total of 366 mRNAs covering the most important tumor signaling pathways. Significant pathway associations were identified by gene set enrichment analysis using the WEB-based GEne SeT AnaLysis Toolkit (WebGestalt).<br><br>Results: We have found reduced activity of TNF (normalized enrichment score: 2.03), IL-17 (normalized enrichment score: 1.93), MAPK (normalized enrichment score: 1.51), and relaxin signaling pathways (normalized enrichment score: 1.42) in the samples obtained after platinum-based therapy. In contrast, AMPK (normalized enrichment score: -1.58), mTOR (normalized enrichment score: -1.50), Wnt (normalized enrichment score: -1.38), and longevity regulating pathway (normalized enrichment score: -1.31) showed significantly elevated expression in the same samples.<br><br>Conclusions: We could identify deregulated signaling pathways due to a directed cellular response to platinum-induced cell stress. Our results are paving the ground for a better understanding of cellular responses and escape mechanisms, carrying a high potential for improved clinical management of patients with MPM.}, }
@article {pmid34395196, year = {2021}, author = {Tran, T and Egilman, D and Rigler, M and Emory, T}, title = {A Critique of Helsinki Criteria for Using Lung Fiber Levels to Determine Causation in Mesothelioma Cases.}, journal = {Annals of global health}, volume = {87}, number = {1}, pages = {73}, doi = {10.5334/aogh.3135}, pmid = {34395196}, issn = {2214-9996}, abstract = {Asbestos is a known human carcinogen and the chief known cause of mesothelioma. In 1997, a group of experts developed the Helsinki Criteria, which established criteria for attribution of mesothelioma to asbestos. The criteria include two methods for causation attribution: 1) a history of significant occupational, domestic, or environmental exposure and/or 2) pathologic evidence of exposure to asbestos. In 2014, the Helsinki Criteria were updated, and these attribution criteria were not changed. However, since the Helsinki Criteria were first released in 1997, some pathologists, cell biologists, and others have claimed that a history of exposure cannot establish causation unless the lung asbestos fiber burden exceeds "the background range for the laboratory in question to attribute mesothelioma cases to exposure to asbestos." This practice ignores the impact on fiber burden of clearance/translocation over time, which in part is why the Helsinki Criteria concluded that a history of exposure to asbestos was independently sufficient to attribute causation to asbestos. After reviewing the Helsinki Criteria, we conclude that their methodology is fatally flawed because a quantitative assessment of a background lung tissue fiber level cannot be established. The flaws of the Helsinki Criteria are both technical and substantive. The 1995 paper that served as the scientific basis for establishing background levels used inconsistent methods to determine exposures in controls and cases. In addition, historic controls cannot be used to establish background fiber levels for current cases because ambient exposures to asbestos have decreased over time and control cases pre-date current cases by decades. The use of scanning electron microscope (SEM) compounded the non-compatibility problem; the applied SEM cannot distinguish talc from anthophyllite because it cannot perform selected area electron diffraction, which is a crucial identifier in ATEM for distinguishing the difference between serpentine asbestos, amphibole asbestos, and talc.}, }
@article {pmid34390717, year = {2021}, author = {Ciocan, C and Pira, E and Coggiola, M and Franco, N and Godono, A and La Vecchia, C and Negri, E and Boffetta, P}, title = {Mortality in the cohort of talc miners and millers from Val Chisone, Northern Italy: 74 years of follow-up.}, journal = {Environmental research}, volume = {}, number = {}, pages = {111865}, doi = {10.1016/j.envres.2021.111865}, pmid = {34390717}, issn = {1096-0953}, abstract = {OBJECTIVE: To update the analysis of mortality of a cohort of talc miners and millers in Northern Italy.<br><br>METHODS: We analyzed overall mortality and mortality from specific causes of death during 1946-2020 of 1749 male workers in a talc mine where asbestos was not detected (1184 miners and 565 millers) employed during 1946-2002.<br><br>RESULTS: The overall standardized mortality ratio (SMR) was 1.21 (95 % confidence interval [CI] 1.14-1.28); no deaths were observed from pleural cancer. Mortality from lung cancer was not increased (SMR = 1.02 95 % CI 0.82-1.27), while mortality from pneumoconiosis was (SMR 9.55; 95 % CI 7.43-12.08), especially among miners (SMR 12.74; 95 % CI 9.79-16.31). The was a trend in risk of pneumoconiosis with increasing duration of employment in the overall cohort, and the SMR for 25+ years of employment was 15.12 (95 % CI 10.89-20.43).<br><br>CONCLUSIONS: This uniquely long-term follow up confirms the results of previous analyses, namely the lack of association between exposure to talc with no detectable level of asbestos and lung cancer and mesothelioma. Increased mortality from pneumoconiosis among miners is related to past exposure to silica.}, }
@article {pmid34389715, year = {2021}, author = {Grosso, S and Marini, A and Gyuraszova, K and Voorde, JV and Sfakianos, A and Garland, GD and Tenor, AR and Mordue, R and Chernova, T and Morone, N and Sereno, M and Smith, CP and Officer, L and Farahmand, P and Rooney, C and Sumpton, D and Das, M and Teodósio, A and Ficken, C and Martin, MG and Spriggs, RV and Sun, XM and Bushell, M and Sansom, OJ and Murphy, D and MacFarlane, M and Le Quesne, JPC and Willis, AE}, title = {The pathogenesis of mesothelioma is driven by a dysregulated translatome.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4920}, pmid = {34389715}, issn = {2041-1723}, support = {5TR00, 5TR019 and MCA/600)//RCUK | Medical Research Council (MRC)/ ; CSOBLFRG16-2 and MKMRGPG18//British Lung Foundation (BLF)/ ; A17196, A21139 and A29252//Cancer Research UK (CRUK)/ ; }, abstract = {Malignant mesothelioma (MpM) is an aggressive, invariably fatal tumour that is causally linked with asbestos exposure. The disease primarily results from loss of tumour suppressor gene function and there are no 'druggable' driver oncogenes associated with MpM. To identify opportunities for management of this disease we have carried out polysome profiling to define the MpM translatome. We show that in MpM there is a selective increase in the translation of mRNAs encoding proteins required for ribosome assembly and mitochondrial biogenesis. This results in an enhanced rate of mRNA translation, abnormal mitochondrial morphology and oxygen consumption, and a reprogramming of metabolic outputs. These alterations delimit the cellular capacity for protein biosynthesis, accelerate growth and drive disease progression. Importantly, we show that inhibition of mRNA translation, particularly through combined pharmacological targeting of mTORC1 and 2, reverses these changes and inhibits malignant cell growth in vitro and in ex-vivo tumour tissue from patients with end-stage disease. Critically, we show that these pharmacological interventions prolong survival in animal models of asbestos-induced mesothelioma, providing the basis for a targeted, viable therapeutic option for patients with this incurable disease.}, }
@article {pmid34386422, year = {2021}, author = {Zhang, C and Wu, L and de Perrot, M and Zhao, X}, title = {Carbon Nanotubes: A Summary of Beneficial and Dangerous Aspects of an Increasingly Popular Group of Nanomaterials.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {693814}, doi = {10.3389/fonc.2021.693814}, pmid = {34386422}, issn = {2234-943X}, abstract = {Carbon nanotubes (CNTs) are nanomaterials with broad applications that are produced on a large scale. Animal experiments have shown that exposure to CNTs, especially one type of multi-walled carbon nanotube, MWCNT-7, can lead to malignant transformation. CNTs have characteristics similar to asbestos (size, shape, and biopersistence) and use the same molecular mechanisms and signaling pathways as those involved in asbestos tumorigenesis. Here, a comprehensive review of the characteristics of carbon nanotubes is provided, as well as insights that may assist in the design and production of safer nanomaterials to limit the hazards of currently used CNTs.}, }
@article {pmid34379126, year = {2021}, author = {Zhai, Z and Ruan, J and Zheng, Y and Xiang, D and Li, N and Hu, J and Shen, J and Deng, Y and Yao, J and Zhao, P and Wang, S and Yang, S and Zhou, L and Wu, Y and Xu, P and Lyu, L and Lyu, J and Bergan, R and Chen, T and Dai, Z}, title = {Assessment of Global Trends in the Diagnosis of Mesothelioma From 1990 to 2017.}, journal = {JAMA network open}, volume = {4}, number = {8}, pages = {e2120360}, doi = {10.1001/jamanetworkopen.2021.20360}, pmid = {34379126}, issn = {2574-3805}, abstract = {Importance: It is difficult for policy makers and clinicians to formulate targeted management strategies for mesothelioma because data on current epidemiological patterns worldwide are lacking.<br><br>Objective: To evaluate the mesothelioma burden across the world and describe its epidemiological distribution over time and by sociodemographic index (SDI) level, geographic location, sex, and age.<br><br>Annual case data and age-standardized rates of incidence, death, and disability-adjusted life-years associated with mesothelioma among different age groups were obtained from the Global Burden of Disease 2017 database. The estimated annual percentage changes in age-standardized rates were calculated to evaluate temporal trends in incidence and mortality. The study population comprised individuals from 21 regions in 195 countries and territories who were diagnosed with mesothelioma between 1990 and 2017. Data were collected from May 23, 2019, to January 18, 2020.<br><br>Main Outcomes and Measures: Primary outcomes were incident cases, deaths, and their age-standardized rates and estimated annual percentage changes. Secondary outcomes were disability-adjusted life-years and relative temporal trends.<br><br>Results: Overall, 34 615 new cases (95% uncertainty interval [UI], 33 530-35 697 cases) of mesothelioma and 29 909 deaths (95% UI, 29 134-30 613 deaths) associated with mesothelioma were identified in 2017, and more than 70% of these cases and deaths were among male individuals. In 1990, the number of incident cases was 21 224 (95% UI, 17 503-25 450), and the number of deaths associated with mesothelioma was 17 406 (95% UI, 14 495-20 660). These numbers increased worldwide from 1990 to 2017, with more than 50% of cases recorded in regions with high SDI levels, whereas the age-standardized incidence rate (from 0.52 [95% UI, 0.43-0.62] in 1990 to 0.44 [95% UI, 0.42-0.45] in 2017) and the age-standardized death rate (from 0.44 [95% UI, 0.37-0.52] in 1990 to 0.38 [95% UI, 0.37-0.39] in 2017) decreased, with estimated annual percentage changes of -0.61 (95% CI, -0.67 to -0.54) for age-standardized incidence rate and -0.44 (95% CI, -0.52 to -0.37) for age-standardized death rate. The proportion of incident cases among those 70 years or older continued to increase (from 36.49% in 1990 to 44.67% in 2017), but the proportion of patients younger than 50 years decreased (from 16.74% in 1990 to 13.75% in 2017) over time. In addition, mesothelioma incident cases and age-standardized incidence rates began to decrease after 20 years of a complete ban on asbestos use. For example, in Italy, a complete ban on asbestos went into effect in 1992; incident cases increased from 1409 individuals (95% UI, 1013-1733 individuals) in 1990, peaked in 2015 after 23 years of the asbestos ban, then decreased from 1820 individuals (95% UI, 1699-1981 individuals) in 2015 to 1746 individuals (95% UI, 1555-1955 individuals) in 2017.<br><br>Conclusions and Relevance: This cross-sectional study found that incident cases of mesothelioma and deaths associated with mesothelioma continuously increased worldwide, especially in resource-limited regions with low SDI levels. Based on these findings, global governments and medical institutions may consider formulating optimal policies and strategies for the targeted prevention and management of mesothelioma.}, }
@article {pmid34373297, year = {2021}, author = {Ferrante, P}, title = {Hospitalisation costs of malignant mesothelioma: results from the Italian hospital discharge registry (2001-2018).}, journal = {BMJ open}, volume = {11}, number = {8}, pages = {e046456}, doi = {10.1136/bmjopen-2020-046456}, pmid = {34373297}, issn = {2044-6055}, abstract = {OBJECTIVES: This paper aims to establish hospitalisation costs of mesothelioma in Italy and to evaluate hospital-related trends associated with the 1992 asbestos ban.<br><br>DESIGN: This is a retrospective population-based study of Italian hospitalisations treating pleura, peritoneum and pericardium mesothelioma in the period 2001-2018.<br><br>SETTINGS: Public and private Italian hospitals reached by the Ministry of Health (coverage close to 100%).<br><br>PARTICIPANTS: 157 221 admissions with primary or contributing diagnosis of pleural, peritoneal or hearth cancer discharged from 2001 to 2018.Primary and secondary outcome measures: number, length and cost of hospitalisations with related percentages.<br><br>RESULTS: Each year, Italian hospitals treated a mesothelioma in 6025 admissions on average. Mean annual costs by site were €20 293 733, €3183 632 and €40 443 for pleura, peritoneum and pericardium, respectively. Pericardial mesothelioma showed the highest cost per admission (€6117), followed by peritoneal (€4549) and pleural cases (€3809). Percentage of hospitalisation costs attributable to mesothelioma was higher when it is located in pleura (53.4%) and pericardium (51.8%) with respect to peritoneum (41.2%). Overall annual hospitalisation cost, percentages of number and length of admissions showed an inverted U-shape, with maxima (of €25 850 276, 0.064% and 0.096%, respectively) reached in 2011-2013. Mean age at discharge and percentages of surgery and of urgent cases increased over time.<br><br>CONCLUSIONS: The highest impact of mesothelioma on the National Health System was recorded 20 years after the asbestos ban (2011-2013). Hospitals should expect soon fewer but more severe patients needing more cares. To study the disease prevalence could help assistance planning of next decade.}, }
@article {pmid34361048, year = {2021}, author = {Chmielewska-Kassassir, M and Wozniak, LA}, title = {Phytochemicals in Malignant Pleural Mesothelioma Treatment-Review on the Current Trends of Therapies.}, journal = {International journal of molecular sciences}, volume = {22}, number = {15}, pages = {}, doi = {10.3390/ijms22158279}, pmid = {34361048}, issn = {1422-0067}, support = {2015/19/N/NZ3/01497//Narodowym Centrum Nauki/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare but highly aggressive tumor of pleura arising in response to asbestos fibers exposure. MPM is frequently diagnosed in the advanced stage of the disease and causes poor prognostic outcomes. From the clinical perspective, MPM is resistant to conventional treatment, thus challenging the therapeutic options. There is still demand for improvement and sensitization of MPM cells to therapy in light of intensive clinical studies on chemotherapeutic drugs, including immuno-modulatory and targeted therapies. One way is looking for natural sources, whole plants, and extracts whose ingredients, especially polyphenols, have potential anticancer properties. This comprehensive review summarizes the current studies on natural compounds and plant extracts in developing new treatment strategies for MPM.}, }
@article {pmid34359365, year = {2021}, author = {Li, N and Yang, C and Zhou, S and Song, S and Jin, Y and Wang, D and Liu, J and Gao, Y and Yang, H and Mao, W and Chen, Z}, title = {Combination of Plasma-Based Metabolomics and Machine Learning Algorithm Provides a Novel Diagnostic Strategy for Malignant Mesothelioma.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, doi = {10.3390/diagnostics11071281}, pmid = {34359365}, issn = {2075-4418}, support = {81672315//National Natural Science Foundation of China/ ; 81302840//National Natural Science Foundation of China/ ; 2017C04G1360498//Key R&amp;D Program Projects in Zhejiang Province/ ; LY20H280001//Zhejiang Provincial Natural Science Fund/ ; 2017KY256//Projects of Zhejiang Province Medical and Health Science and Technology Plan/ ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive and incurable carcinoma that is primarily caused by asbestos exposure. However, the current diagnostic tool for MM is still under-developed. Therefore, the aim of this study is to explore the diagnostic significance of a strategy that combined plasma-based metabolomics with machine learning algorithms for MM.<br><br>METHODS: Plasma samples collected from 25 MM patients and 32 healthy controls (HCs) were randomly divided into train set and test set, after which analyzation was performed by liquid chromatography-mass spectrometry-based metabolomics. Differential metabolites were screened out from the samples of the train set. Subsequently, metabolite-based diagnostic models, including receiver operating characteristic (ROC) curves and Random Forest model (RF), were established, and their prediction accuracies were calculated for the test set samples.<br><br>RESULTS: Twenty differential plasma metabolites were annotated in the train set; 10 of these metabolites were validated in the test set. The seven most prevalent diagnostic metabolites were taurocholic acid), 0.7142 (uracil), 0.7142 (biliverdin), 0.8571 (histidine), 0.5000 (tauroursodeoxycholic acid), 0.8571 (pyrroline hydroxycarboxylic acid), and 0.7857 (phenylalanine). Furthermore, RF based on 20 annotated metabolites showed a prediction accuracy of 0.9286, and its optimized version achieved 1.0000 in the test set. Moreover, the comparison between the samples of peritoneal MM (n = 8) and pleural MM (n = 17) illustrated a significant increase in levels of taurocholic acid and tauroursodeoxycholic acid, as well as an evident decrease in biliverdin.<br><br>CONCLUSIONS: Our results revealed the potential diagnostic value of plasma-based metabolomics combined with machine learning for MM. Further research with large sample size is worthy conducting. Moreover, our data demonstrated dysregulated metabolism pathways in MM, which aids in better understanding of molecular mechanisms related to the initiation and development of MM.}, }
@article {pmid34354974, year = {2021}, author = {Visonà, SD and Capella, S and Bodini, S and Borrelli, P and Villani, S and Crespi, E and Colosio, C and Previderè, C and Belluso, E}, title = {Evaluation of Deposition and Clearance of Asbestos (Detected by SEM-EDS) in Lungs of Deceased Subjects Environmentally and/or Occupationally Exposed in Broni (Pavia, Northern Italy).}, journal = {Frontiers in public health}, volume = {9}, number = {}, pages = {678040}, doi = {10.3389/fpubh.2021.678040}, pmid = {34354974}, issn = {2296-2565}, abstract = {Biodurability is one of the main determinants of asbestos hazardousness for human health. Very little is known about the actual persistence of asbestos in lungs and its clearance, nor about differences in this regard between the different mineralogical types of asbestos. The aim of the present study was to evaluate the amount, the dimensional characteristics and the mineralogic kinds of asbestos in lungs (measured using SEM-EDS) of a series of 72 deceased subjects who were certainly exposed to asbestos (mainly crocidolite and chrysotile) during their life. Moreover, we investigated possible correlations between the lung burden of asbestos (in general and considering each asbestos type), as well as their dimension (length, width, and l/w ratio) and the duration of exposure, the latency- in case of malignant mesothelioma (MM), the survival and the time since the end of exposure. In 62.5% of subjects, asbestos burden in lungs was lower that the threshold considered demonstrative for occupational exposure. In 29.1% of cases no asbestos was found. Chrysotile was practically not detected. The mean length of asbestos fibers and the length to width ratio were significantly related to the duration of exposure to asbestos. No other statistically significant correlations were found between the amount and dimensional characteristics of asbestos (nor with the relative amount of each asbestos type) and the other chronological variables considered. In conclusion, it was pointed out that chrysotile can be completely removed from human lungs in <8 years and, instead, amphiboles persist much more time. The present results suggest, as well, that the finding of no asbestos in lungs cannot rule out the attribution of MM to asbestos (in particular, chrysotile) inhaled in an occupational setting. This point is of crucial importance from a legal point of view.}, }
@article {pmid34350658, year = {2021}, author = {Mensi, C and Zellino, C and Polonioli, M and Dallari, B and Pesatori, AC and Riboldi, L and Consonni, D}, title = {Pleural mesothelioma in a circus worker.}, journal = {Journal of occupational health}, volume = {63}, number = {1}, pages = {e12250}, doi = {10.1002/1348-9585.12250}, pmid = {34350658}, issn = {1348-9585}, support = {acronym: PRIMATE-code ARL_2/2018//Fondazione Regionale per la Ricerca Biomedica/ ; BRiC P55 and//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; BRiC P59//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; }, abstract = {OBJECTIVES: To describe an unusual occupational asbestos exposure in a patient with mesothelioma.<br><br>METHODS: Since 2000, the Lombardy Mesothelioma Registry (LMR) collects cases of malignant mesothelioma (MM) occurring among people residing in the Lombardy Region, North-West Italy, with a population of 10 million inhabitants. For each case, clinical records and asbestos exposure are collected. Each case is then classified in agreement with the guidelines of the National Mesothelioma Registry.<br><br>RESULTS: We identified a male (86 years old), former smoker, who had been working for 53 years as a circus truck driver and tamer of lions and tigers. The first circumstance of exposure was the use of an asbestos tape that wrapped around the hoop in the feline jumping show with a flaming hoop. The second one was the presence of insulating panels protecting the engine placed inside the trucks.<br><br>CONCLUSION: A new MM case with an occupational etiology has been found in the public entertainment, an occupational sector not usually considered at risk for the presence of asbestos.}, }
@article {pmid34349988, year = {2021}, author = {Iyoda, A and Azuma, Y and Sakai, T and Koezuka, S and Otsuka, H and Tochigi, N and Isobe, K and Sano, A}, title = {Intraoperative argon-plasma coagulation treatment for patients with malignant pleural mesothelioma.}, journal = {Molecular and clinical oncology}, volume = {15}, number = {3}, pages = {188}, doi = {10.3892/mco.2021.2350}, pmid = {34349988}, issn = {2049-9469}, abstract = {Malignant pleural mesothelioma (MPM) is often associated with asbestos exposure and carries an extremely poor prognosis. The present study assessed the effectiveness of argon plasma coagulation (APC) treatment in patients with MPM who underwent radical pleural decortication (PD). The clinical data from 11 patients who underwent radical PD treated with APC at Toho University Omori Medical Center from July 2015 to March 2020 were retrospectively analyzed. Clinical features, local recurrence, and clinical prognoses were evaluated. The median overall survival was 18.5 months, and the 1- and 2-year overall survival rates were 71.6 and 43.0%, respectively. One patient survived 5 years but had recurrent tumors. The median disease-free survival was 11.1 months. The 1- and 2-year disease-free survival rates were 49.9 and 12.5%, respectively. Three patients had no recurrences, two of whom were followed continuously (39.6 and 10.2 months). The present study revealed that APC treatment for MPM might be associated with good survival and prognosis. APC as an additional intraoperative treatment for patients with MPM may be further investigated with larger multi-center clinical trials to support its efficacy.}, }
@article {pmid34345849, year = {2021}, author = {Gualtieri, AF}, title = {Bridging the gap between toxicity and carcinogenicity of mineral fibres by connecting the fibre crystal-chemical and physical parameters to the key characteristics of cancer.}, journal = {Current research in toxicology}, volume = {2}, number = {}, pages = {42-52}, doi = {10.1016/j.crtox.2021.01.005}, pmid = {34345849}, issn = {2666-027X}, abstract = {Airborne fibres and particularly asbestos represent hazards of great concern for human health because exposure to these peculiar particulates may cause malignancies such as lung cancer and mesothelioma. Currently, many researchers worldwide are focussed on fully understanding the patho-biological mechanisms leading to carcinogenesis prompted by pathogenic fibres. Along this line, the present work introduces a novel approach to correlate how and to what extent the physical/crystal-chemical and morphological parameters (including length, chemistry, biodurability, and surface properties) of mineral fibres cause major adverse effects with an emphasis on asbestos. The model described below conceptually attempts to bridge the gap between toxicity and carcinogenicity of mineral fibres and has several implications: 1) it provides a tool to measure the toxicity and pathogenic potential of asbestos minerals, allowing a quantitative rank of the different types (e.g. chrysotile vs. crocidolite); 2) it can predict the toxicity and pathogenicity of "unregulated" or unclassified fibres; 3) it reveals the parameters of a mineral fibre that are active in stimulating key characteristics of cancer, thus offering a strategy for developing specific cancer prevention strategies and therapies. Chrysotile, crocidolite and fibrous glaucophane are described here as mineral fibres of interest.}, }
@article {pmid34339095, year = {2021}, author = {Prusak, A and van der Zwan, JM and Aarts, MJ and Arber, A and Cornelissen, R and Burgers, S and Duijts, SFA}, title = {The psychosocial impact of living with mesothelioma: Experiences and needs of patients and their carers regarding supportive care.}, journal = {European journal of cancer care}, volume = {}, number = {}, pages = {e13498}, doi = {10.1111/ecc.13498}, pmid = {34339095}, issn = {1365-2354}, abstract = {OBJECTIVE: Mesothelioma is a rare cancer with a poor prognosis caused by exposure to asbestos. Psychosocial support and care for mesothelioma patients and their carers is limited and not tailored to their specific needs. The aim of this study was to explore patients' and carers' needs and experiences regarding psychosocial support and their coping mechanisms dealing with psychosocial problems.<br><br>METHODS: A qualitative study was performed using semi-structured interviews with both mesothelioma patients and their carers. Participants were recruited through two specialised hospitals and two patient organisations. All interviews were transcribed verbatim and thematically analysed.<br><br>RESULTS: Ten patients (70% male, mean age 67.7) and five carers (20% male, mean age 65) participated in the study. The main themes identified for patients were active coping, limited needs and limited knowledge and awareness about psychosocial support. The main themes for carers were passive coping and 'it's all about the patient'.<br><br>CONCLUSION: Mesothelioma patients do not seem to have high needs for psychosocial support, whereas carers do. However, knowledge about and awareness of psychosocial support is low among mesothelioma patients. The findings from this study should be used to adjust guidelines for psychosocial support in mesothelioma patients and their carers.}, }
@article {pmid34333253, year = {2021}, author = {Onagi, H and Hayashi, T and Saito, T and Kishikawa, S and Takamochi, K and Suzuki, K}, title = {Malignant pleural mesothelioma showing rare morphology indistinguishable from myxofibrosarcoma concomitant with EGFR-mutated lung adenocarcinoma: A case report.}, journal = {International journal of surgery case reports}, volume = {85}, number = {}, pages = {106237}, doi = {10.1016/j.ijscr.2021.106237}, pmid = {34333253}, issn = {2210-2612}, abstract = {INTRODUCTION AND IMPORTANCE: Primary tumors of the pleura are rare, with malignant mesothelioma being the most common of these neoplasms. Pathological diagnosis of sarcomatoid mesothelioma can be more challenging than that of epithelioid malignant mesothelioma because of its similarities with true sarcomas and restricted or inconsistent expression of mesothelial markers in immunohistochemistry analysis.<br><br>PRESENTATION OF CASE: Here, we present an unusual case of malignant pleural mesothelioma concomitant with lung adenocarcinoma in a 72-year-old Japanese man, a smoker with no family history of cancer and asbestos exposure. Malignant pleural mesothelioma is composed of epithelial and spindle-shaped cells. Spindle-shaped cells with scant eosinophilic cytoplasm and hyperchromatic nuclei proliferated in abundant myxoid stroma containing thin-walled blood vessels, mimicking myxofibrosarcoma. The loss of BAP1 (BRCA1-associated protein 1) expression, as assessed by immunohistochemistry, and homozygous deletions of CDKN2A, detected using fluorescence in situ hybridization (FISH), were observed in both components. Targeted sequencing revealed that lung adenocarcinoma harbored EGFR mutations, whereas no mutations were detected in either component of biphasic mesothelioma.<br><br>DISCUSSION: Although alcian blue-stained mucins were detected in biphasic mesothelioma subsets, the clinicopathological significance of myxoid stroma in biphasic and sarcomatoid mesothelioma remains largely unknown.<br><br>CONCLUSION: Our case presented a unique morphology mimicking myxofibrosarcoma in a sarcomatoid component of biphasic mesothelioma; therefore, it raises a question on the clinicopathological significance of myxoid stroma in sarcomatous areas of biphasic and sarcomatoid mesothelioma.}, }
@article {pmid34322630, year = {2021}, author = {Scopa, P}, title = {Reconstruction of asbestos exposure in workers suffering from pleural neoplasms and employed in sectors not generally associated with high exposure levels: the importance of an accurate standardized assessment of occupational medicine.}, journal = {Journal of preventive medicine and hygiene}, volume = {62}, number = {1}, pages = {E148-E151}, doi = {10.15167/2421-4248/jpmh2021.62.1.1334}, pmid = {34322630}, issn = {2421-4248}, abstract = {Introduction: Malignant pleural mesothelioma onset in workers exposed to asbestos is well known with reference to multiple working sectors. In some cases, occurring among workers of sectors characterized by a presumed lower relevance of asbestos exposure, the absence of a well-defined correlation can prevent their emergence and compensation. To improve definition of these cases, this article underlines the importance of a standardized approach to occupational anamnesis.<br><br>Methods: Thorough standardized occupational health assessment method application in a case of pleural malignant neoplasm occurred in a hauler, a job generally not associated with high levels of exposure to asbestos fibres.<br><br>Results: Assessment of malignant pleural mesothelioma diagnosis and dual mode relevant occupational exposure to asbestos during both truck driving and loading and unloading operations of asbestos-containing goods.<br><br>Conclusions: Systematic occupational medicine assessment with accurate standardized approach is essential for reconstruction of asbestos exposure, in order to highlight every aspect useful to establish causal link between cases of pleural mesothelioma and possible occupational and non-occupational exposure to the mineral, even in cases where the first-level occupational history does not appear to be suggestive.}, }
@article {pmid34313510, year = {2021}, author = {Brustugun, OT and Nilssen, Y and Eide, IJZ}, title = {Epidemiology and outcome of peritoneal and pleural mesothelioma subtypes in Norway. A 20 year nation-wide study.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/0284186X.2021.1955971}, pmid = {34313510}, issn = {1651-226X}, abstract = {BACKGROUND: Mesothelioma of the pleural or peritoneal cavities is one of the deadliest cancer types. The incidence of pleural subtypes has decreased over time due to decrease in asbestos exposure, and the current treatment landscape is changing due to introduction of novel therapies. In this study we have analysed contemporary epidemiological data of mesothelioma on a national level before the advent of immunotherapy.<br><br>MATERIAL AND METHODS: Complete national data on 1509 pleural and peritoneal malignant mesothelioma from the Cancer Registry of Norway from 2000 to 2019 are presented. Age standardised incidence and median survival were calculated.<br><br>RESULTS: The age-standardised incidence of pleural mesothelioma among males has decreased from 1.7 per 100 000 in 2000-2004 to 1.1 in 2015-2019, whereas the incidence for females has been stable, lower than 0.3 per 100 000 throughout the period. Incidence of peritoneal mesotheliomas remained low, below 0.08 per 100 000. The female to male ratio among pleural mesotheliomas was 1:7 with no differences among morphological subtypes, whereas this ratio was 1:1.2 in peritoneal mesotheliomas. Median age at diagnosis for pleural mesothelioma was 73 years and 76 years for females and males respectively in the last 5-year period, and 67 years for peritoneal mesotheliomas of both sexes. Median survival among pleural mesotheliomas has been stable, with significantly worse prognosis among sarcomatoid subtype (5.4 months) compared to epithelioid subtype (15.8 months). Peritoneal mesothelioma of the epithelioid subtype, representing 38% of cases, had a median survival of 43.3 months, contrasting the non-epithelioid subtype of 5.1 months.<br><br>DISCUSSION: Mesothelioma is still a significant disease with a dismal prognosis. Improvement in treatment is warranted.}, }
@article {pmid34299971, year = {2021}, author = {Fang, YJ and Chuang, HY and Pan, CH and Chang, YY and Cheng, Y and Lee, LJ and Wang, JD}, title = {Increased Risk of Gastric Cancer in Asbestos-Exposed Workers: A Retrospective Cohort Study Based on Taiwan Cancer Registry 1980-2015.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {14}, pages = {}, doi = {10.3390/ijerph18147521}, pmid = {34299971}, issn = {1660-4601}, support = {KMU-TC109A01-1//Kaohsiung Medical University/ ; EM-108-PP-04; EM-109-PP-04//National Health Research Institutes/ ; }, abstract = {Asbestos has been recognized as a human carcinogen associated with malignant mesothelioma, cancers of lung, larynx, and ovary. However, a putative association between gastric cancer and asbestos exposure remains controversial. In this study, we aimed to explore gastric cancer risk of workers potentially exposed to asbestos in Taiwan. The asbestos occupational cohort was established from 1950 to 2015 based on the Taiwan Labor Insurance Database, and Taiwan Environmental Protection Agency regulatory datasets, followed by the Taiwan Cancer Registry for the period 1980-2015. Standardized incidence ratios (SIRs) for cancer were computed for the whole cohort using reference rates of the general population, and also reference labor population. Compared with the general population, SIR of the asbestos occupational cohort for the gastric cancer increased both in males (1.05, 95% confidence interval (CI): 1.02-1.09) and females (1.10, 95% CI: 1.01-1.18). A total of 123 worksites were identified to have cases of malignant mesothelioma, where increased risk for gastric cancer was found with a relative risk of 1.76 (95% CI: 1.63-1.90). This 35-year retrospective cohort study of asbestos-exposed workers in Taiwan may provide support for an association between occupational exposure to asbestos and gastric cancer.}, }
@article {pmid34299035, year = {2021}, author = {Yuan, L and Sun, B and Xu, L and Chen, L and Ou, W}, title = {The Updating of Biological Functions of Methyltransferase SETDB1 and Its Relevance in Lung Cancer and Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {22}, number = {14}, pages = {}, doi = {10.3390/ijms22147416}, pmid = {34299035}, issn = {1422-0067}, support = {2020Y002//the Fundamental Research Funds of Zhejiang Sci-Tech University/ ; 81728012//National Natural Science Foundation of China/ ; }, abstract = {SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 (H3K9) methyltransferase that exerts important effects on epigenetic gene regulation. SETDB1 complexes (SETDB1-KRAB-KAP1, SETDB1-DNMT3A, SETDB1-PML, SETDB1-ATF7IP-MBD1) play crucial roles in the processes of histone methylation, transcriptional suppression and chromatin remodelling. Therefore, aberrant trimethylation at H3K9 due to amplification, mutation or deletion of SETDB1 may lead to transcriptional repression of various tumour-suppressing genes and other related genes in cancer cells. Lung cancer is the most common type of cancer worldwide in which SETDB1 amplification and H3K9 hypermethylation have been indicated as potential tumourigenesis markers. In contrast, frequent inactivation mutations of SETDB1 have been revealed in mesothelioma, an asbestos-associated, locally aggressive, highly lethal, and notoriously chemotherapy-resistant cancer. Above all, the different statuses of SETDB1 indicate that it may have different biological functions and be a potential diagnostic biomarker and therapeutic target in lung cancer and mesothelioma.}, }
@article {pmid34298661, year = {2021}, author = {Pouliquen, DL and Kopecka, J}, title = {Malignant Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {14}, pages = {}, doi = {10.3390/cancers13143447}, pmid = {34298661}, issn = {2072-6694}, abstract = {Malignant mesothelioma (MM) is a rare and aggressive cancer, related to chronic inflammation and oxidative stress caused mainly by exposure to asbestos [...].}, }
@article {pmid34295692, year = {2021}, author = {Menis, J and Pasello, G and Remon, J}, title = {Immunotherapy in malignant pleural mesothelioma: a review of literature data.}, journal = {Translational lung cancer research}, volume = {10}, number = {6}, pages = {2988-3000}, pmid = {34295692}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface, associated with asbestos exposure, whose incidence is still growing in some areas of the world. MPM is still considered a rare and an orphan disease with an unchanged median overall survival (OS) ranging from 8 to 14 months and no treatment advances in the last 15 years both in local and advanced disease. In the recent years, chronic inflammation of the mesothelium together with local tumor suppression plays a major role in the malignant transformation. Also, significant heterogeneity in both tumor and the microenvironment is at the basis of MPM biology. Preclinical data have demonstrated the immunogenicity and the lack of an effective antitumor response by the immune system in MPM thus paving the way to the development of immune therapeutics in this disease. Still there is no clear evidence of any predictive biomarker so that, given the close interaction between the immune infiltrate and mesothelial cells, a number of trials are ongoing to investigate the role and prognostic value of the immune microenvironment. In this review we summarize the rationale for immune therapeutics development in MPM, as well as, the relevant literature and ongoing trials of immune checkpoint inhibitors (ICIs) and vaccines used as both first-line treatment and beyond.}, }
@article {pmid34295165, year = {2021}, author = {Gu, R and Jiang, L and Duan, T and Chen, C and Wu, S and Mu, D}, title = {A Case of Pulmonary Embolism with Sarcomatoid Malignant Pleural Mesothelioma with Long-Term Pleural Effusion.}, journal = {OncoTargets and therapy}, volume = {14}, number = {}, pages = {4231-4237}, pmid = {34295165}, issn = {1178-6930}, abstract = {Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that originates from pleural mesothelial cells. In recent years, with the development of asbestos-related industries and the increase in air pollution, its incidence has been increased. The incidence of pulmonary embolism combined with sarcomatoid MPM is very low and the prognosis is extremely poor. We here report a case of a patient with long term of pleural effusion and finally diagnosed as pulmonary embolism with sarcomatoid MPM.<br><br>Case: A 75-year-old male with a 30-year history of asbestos exposure was admitted to our hospital due to chest pain and difficulty in breathing after exercise. Radiologic examination revealed pleural effusion, computed tomography pulmonary angiography (CTPA) suggests pulmonary embolism, and we consider pleural effusion caused by pulmonary embolism. After anticoagulant therapy for pulmonary embolism and pleural puncture to reduce pleural effusion, the patient's symptoms improved. However, after that, the patient was still admitted to the hospital several times because of recurrent chest pain and dyspnea symptoms, and radiologic examination always showed unexplained pleural effusion. Finally, pathological and immunohistochemical examinations of the pleural biopsy specimens were performed, and the diagnosis was confirmed as sarcomatoid MPM.<br><br>Conclusion: In summary, sarcomatoid MPM with pulmonary embolism is relatively rare, and the prognosis is poor. Clinicians need to be alert to its occurrence. When the first diagnosis is confirmed and the effect of targeted treatment is still not good, the possibility of other diseases should be considered. In clinical practice, pleural biopsy guided by PET-CT is a good choice for patients with sarcomatoid MPM who cannot tolerate open pleural biopsies or thoracoscopy. And patients should undergo pleural morphology and immunohistochemistry as soon as possible, which are helpful for timely diagnosis.}, }
@article {pmid34291807, year = {2021}, author = {Santana, VS and Salvi, L and Cavalcante, F and Campos, F and Algranti, E}, title = {Underreporting of mesothelioma, asbestosis and pleural plaques in Brazil.}, journal = {Occupational medicine (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/occmed/kqab073}, pmid = {34291807}, issn = {1471-8405}, support = {45672/2014//Labor Prosecution Office/ ; 306708/2019-1//National Council for Scientific and Technological Development/ ; }, abstract = {BACKGROUND: Brazil has a long history of heavy asbestos consumption. However, the number of asbestos-related diseases (ARDs) falls far below the one expected compared with other asbestos consumer countries.<br><br>AIMS: To examine underreporting of ARDs, that is mesothelioma, asbestosis and pleural plaques, in Brazil's Mortality Information System (SIM).<br><br>METHODS: Health information systems (HIS) were mapped, datasets retrieved and records of ARD deaths extracted. Records were pair-matched using anonymous linkage to create a single database. ARD-reported cases missing in SIM were considered unreported. The study's period ranged from 2008 to 2014, when every HIS contributed to the ARD records pool.<br><br>RESULTS: A total of 1298 registered ARD deaths were found, 996 cases of mesothelioma (77%) and 302 (23%) of asbestosis and pleural plaques. SIM was the major single data source of ARD but 335 mesothelioma deaths were missing, an average underreporting of 33%, with no clear time trend. For asbestosis and pleural plaques, underreporting of ARD oscillated from 55% in 2010 to 25% in 2014, a declining trend. ARD underreporting was not associated with sex or age.<br><br>CONCLUSIONS: One-third of underreported ARD deaths in the universal SIM is unacceptably high and, apparently, it has not been improving substantially over time. After recoveries from multiple databases, the number of cases is still below, which could be expected based on asbestos consumption. Interoperability of multiple information systems could enhance case detection and improve the precision of mortality estimates, which are crucial for surveillance and for evaluation of remedial policies.}, }
@article {pmid34207798, year = {2021}, author = {Broggi, G and Angelico, G and Filetti, V and Ledda, C and Lombardo, C and Vitale, E and Rapisarda, V and Loreto, C and Caltabiano, R}, title = {Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Study.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {12}, pages = {}, doi = {10.3390/ijerph18126249}, pmid = {34207798}, issn = {1660-4601}, mesh = {Arginine ; Asbestos, Amphibole ; Biomarkers, Tumor/genetics ; Humans ; *Lung Neoplasms/chemically induced/genetics ; *Mesothelioma/chemically induced ; *Mesothelioma, Malignant ; RNA Splicing Factors ; Serine ; Serine-Arginine Splicing Factors/genetics ; }, abstract = {The Serine and Arginine-Rich Splicing Factor 1 (SRSF1) has a proto-oncogenic function, being associated with angiogenesis and frequently overexpressed in many human malignant neoplasms. Its immunohistochemical expression has never been investigated in malignant pleural mesothelioma (MPM). We evaluated SRSF1 immunoexpression and its possible relation to angiogenesis in a selected cohort of 10 fluoro-edenite(FE)-induced MPM cases.<br><br>METHODS: Immunohistochemical analyses with an anti-SRSF1 antibody were performed. We interpreted the cases as positive if tumor cell nuclei were stained; a semi-quantitative analysis of the cases was performed by evaluating the intensity of staining and the percentage of tumor positive cells. A microvessel density (MVD) count was also performed.<br><br>RESULTS: High and low immunoexpressions of SRSF1 were seen in six and four MPMs, respectively. A trend of shorter overall survival was found in FE-induced MPM patients with SRSF1 overexpression. In addition, a significant association between high-MVD and high SRSF1 immunoexpression (p = 0.0476) was found.<br><br>CONCLUSIONS: SRSF1 appears to be involved in MPM pathogenesis and its immunoexpression may represent a prognostic biomarker capable of identifying subgroups of patients with different prognosis. However, given the preliminary nature of the present study, further investigations on larger series, and additional in vitro studies, are required to validate our findings.}, }
@article {pmid34283067, year = {2021}, author = {Oddone, E and Bollon, J and Nava, CR and Consonni, D and Marinaccio, A and Magnani, C and Gasparrini, A and Barone-Adesi, F}, title = {Effect of Asbestos Consumption on Malignant Pleural Mesothelioma in Italy: Forecasts of Mortality up to 2040.}, journal = {Cancers}, volume = {13}, number = {13}, pages = {}, doi = {10.3390/cancers13133338}, pmid = {34283067}, issn = {2072-6694}, abstract = {Statistical models used to forecast malignant pleural mesothelioma (MPM) trends often do not take into account historical asbestos consumption, possibly resulting in less accurate predictions of the future MPM death toll. We used the distributed lag non-linear model (DLNM) approach to predict future MPM cases in Italy until 2040, based on past asbestos consumption figures. Analyses were conducted using data on male MPM deaths (1970-2014) and annual asbestos consumption using data on domestic production, importation, and exportation. According to our model, the peak of MPM deaths is expected to occur in 2021 (1122 expected cases), with a subsequent decrease in mortality (344 MPM deaths in 2039). The exposure-response curve shows that relative risk (RR) of MPM increased almost linearly for lower levels of exposure but flattened at higher levels. The lag-specific RR grew until 30 years since exposure and decreased thereafter, suggesting that the most relevant contributions to the risk come from exposures which occurred 20-40 years before death. Our results show that the Italian MPM epidemic is approaching its peak and underline that the association between temporal trends of MPM and time since exposure to asbestos is not monotonic, suggesting a lesser role of remote exposures in the development of MPM than previously assumed.}, }
@article {pmid34281119, year = {2021}, author = {Visonà, SD and Capella, S and Bodini, S and Borrelli, P and Villani, S and Crespi, E and Frontini, A and Colosio, C and Vigliaturo, R and Belluso, E}, title = {Reply to Mirabelli et al. Is Mesothelioma Unrelated to the Lung Asbestos Burden? Comment on "Visonà et al. Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples. Int. J. Environ. Res. Public Health 2021, 18, 2053".}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, doi = {10.3390/ijerph18137181}, pmid = {34281119}, issn = {1660-4601}, abstract = {We appreciate very much the interest of Mirabelli et al. [...].}, }
@article {pmid34281114, year = {2021}, author = {Mirabelli, D and Angelini, A and Barbieri, PG and Calisti, R and Capacci, F and Girardi, P and Silvestri, S and Somigliana, AB}, title = {Is Mesothelioma Unrelated to the Lung Asbestos Burden? Comment on Visonà et al. Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples. Int. J. Environ. Res. Public Health 2021, 18, 2053.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, doi = {10.3390/ijerph18137177}, pmid = {34281114}, issn = {1660-4601}, abstract = {We read with interest the report by Visonà and coworkers on the lung asbestos fiber burden in an autopsy series of decedents from mesothelioma (MM: 59 cases) and individuals who "suffered from asbestosis and died of its complications" (13 cases) [...].}, }
@article {pmid34277071, year = {2021}, author = {Freudenberger, DC and Shah, RD}, title = {A narrative review of the health disparities associated with malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {13}, number = {6}, pages = {3809-3815}, doi = {10.21037/jtd-20-3516}, pmid = {34277071}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is a cancer of the mesothelial lining of the pleura that has traditionally been associated with asbestos exposure in an industrial setting. Asbestos usage has fortunately been banned or phased out in most industrialized countries resulting in its decline in countries such as the United States. Despite this, MPM continues to place significant burden on its affected patients resulting in overall poor prognosis and survival. Questions arise as to what factors, especially what health disparities, contribute to the disease's dismal prognosis. This article will present a narrative review of recent literature that identifies the impact age, sex, race, access to medical centers, and economics have on the diagnosis, treatment, and prognosis of MPM. As will be discussed, research has shown that factors including younger age, female sex, non-white race, private insurance, Medicare, and higher income have been associated with better survival in MPM. Whereas older age, male sex, white race, lack of insurance, and lower income are associated with worse survival. The identification of these and other health disparities related to MPM may allow for future research, clinical guidelines, and policies to be implemented to decrease the burden health disparities create in the diagnosis, treatment, and prognosis of patients with MPM.}, }
@article {pmid34249695, year = {2021}, author = {Hiltbrunner, S and Mannarino, L and Kirschner, MB and Opitz, I and Rigutto, A and Laure, A and Lia, M and Nozza, P and Maconi, A and Marchini, S and D'Incalci, M and Curioni-Fontecedro, A and Grosso, F}, title = {Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {660039}, pmid = {34249695}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and fatal disease of the pleural lining. Up to 80% of the MPM cases are linked to asbestos exposure. Even though its use has been banned in the industrialized countries, the cases continue to increase. MPM is a lethal cancer, with very little survival improvements in the last years, mirroring very limited therapeutic advances. Platinum-based chemotherapy in combination with pemetrexed and surgery are the standard of care, but prognosis is still unacceptably poor with median overall survival of approximately 12 months. The genomic landscape of MPM has been widely characterized showing a low mutational burden and the impairment of tumor suppressor genes. Among them, BAP1 and BLM are present as a germline inactivation in a small subset of patients and increases predisposition to tumorigenesis. Other studies have demonstrated a high frequency of mutations in DNA repair genes. Many therapy approaches targeting these alterations have emerged and are under evaluation in the clinic. High-throughput technologies have allowed the detection of more complex molecular events, like chromotripsis and revealed different transcriptional programs for each histological subtype. Transcriptional analysis has also paved the way to the study of tumor-infiltrating cells, thus shedding lights on the crosstalk between tumor cells and the microenvironment. The tumor microenvironment of MPM is indeed crucial for the pathogenesis and outcome of this disease; it is characterized by an inflammatory response to asbestos exposure, involving a variety of chemokines and suppressive immune cells such as M2-like macrophages and regulatory T cells. Another important feature of MPM is the dysregulation of microRNA expression, being frequently linked to cancer development and drug resistance. This review will give a detailed overview of all the above mentioned features of MPM in order to improve the understanding of this disease and the development of new therapeutic strategies.}, }
@article {pmid34244457, year = {2021}, author = {Thomsen, RW and Riis, AH and Flachs, EM and Garabrant, DH and Bonde, JPE and Toft Sørensen, H}, title = {Risk of asbestosis, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study.}, journal = {Thorax}, volume = {}, number = {}, pages = {}, doi = {10.1136/thoraxjnl-2020-215041}, pmid = {34244457}, issn = {1468-3296}, abstract = {INTRODUCTION: The risk of asbestosis, malignant mesothelioma and lung cancer among motor vehicle mechanics is of concern because of potential exposure to chrysotile asbestos during brake, clutch and gasket repair and maintenance. Asbestos has also been used in insulation and exhaust systems.<br><br>METHODS: We examined the long-term risk of incident mesothelioma, lung cancer, asbestosis and other lung diseases and mortality due to mesothelioma, lung cancer, asbestosis and other lung diseases in a nationwide cohort of all men registered as motor vehicle mechanics since 1970 in Denmark. This was compared with the corresponding risk in a cohort of male workers matched 10:1 by age and calendar year, with similar socioeconomic status (instrument makers, dairymen, upholsterers, glaziers, butchers, bakers, drivers, farmers and workers in the food industry, trade or public services).<br><br>RESULTS: Our study included 138 559 motor vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)) and 1 385 590 comparison workers (median age 25 years; median follow-up 19 years (maximum 45 years)). Compared with other workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n=47 cases) (age-adjusted and calendar-year-adjusted HR=0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR=1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR=1.50 (95% CI 1.10 to 2.03)) and a chronic obstructive pulmonary disease risk close to unity (HR=1.02 (95% CI 0.99 to 1.05)). Corresponding HRs for mortality were 0.86 (95% CI 0.64 to 1.15) for mesothelioma/pleural cancer, 1.06 (95% CI 1.01 to 1.12) for lung cancer, 1.79 (95% CI 1.10 to 2.92) for asbestosis, 1.06 (95% CI 0.86 to 1.30) for other lung diseases caused by external agents and 1.00 (95% CI 0.98 to 1.01) for death due to all causes.<br><br>CONCLUSIONS: We found that the risk of asbestosis was increased among vehicle mechanics. The risk of malignant mesothelioma/pleural cancers was not increased among vehicle mechanics.}, }
@article {pmid34241641, year = {2021}, author = {Golka, K and Böthig, R and Jungmann, O and Forchert, M and Zellner, ME and Schöps, W}, title = {[Occupational cancers in urology].}, journal = {Der Urologe. Ausg. A}, volume = {}, number = {}, pages = {}, pmid = {34241641}, issn = {1433-0563}, abstract = {Cancers can be triggered by occupational causes. In the field of urology, bladder cancer is by far the most frequent occupationally induced tumor disease. Causes are particularly carcinogenic aromatic amines and carcinogenic polycyclic aromatic hydrocarbons. The frequency of this disease has shifted over the last decades from the classical hazard in the chemical industry to the users. Among a variety of hazardous occupations, hairdressers and painters are the best known. Rarely, renal cell carcinoma can be triggered by high trichloroethylene exposure and mesothelioma of the tunica vaginalis testis by asbestos. If a disease that can be caused by occupational activities has been confirmed (e.g. urinary bladder cancer), the risk factors must be recorded by a complete occupational history from the first employment on in order to be able to report a suspected occupational disease. In addition, spinal cord injury due to occupational and commuting accidents can lead to urinary bladder cancer over the long term.}, }
@article {pmid34240508, year = {2021}, author = {Hiroshima, K and Wu, D and Koh, E and Sekine, Y and Ozaki, D and Yusa, T and Nakazawa, T and Tsuji, S and Miyagi, Y and Walts, AE and Marchevsky, AM and Husain, AN and Imai, K}, title = {Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas.}, journal = {Pathology international}, volume = {}, number = {}, pages = {}, doi = {10.1111/pin.13140}, pmid = {34240508}, issn = {1440-1827}, support = {//Ministry of the Environment of Japan/ ; JP20cm0106406//Japan Agency for Medical Research and Development/ ; //Nichias Corporation, Tokyo, Japan/ ; }, abstract = {Sialylated HEG1 has been reported as a highly specific and sensitive mesothelioma marker but a comprehensive evaluation of its expression in carcinomas in different organs, various sarcomas and reactive mesothelial proliferations has not been reported. The aim of this study was to evaluate the clinical applicability of HEG1 as a marker in the diagnosis of mesothelioma. HEG1 immunoreactivity was evaluated in whole sections of 122 mesotheliomas, 75 pulmonary carcinomas, 55 other carcinomas, 16 mesenchymal tumors, and 24 reactive mesothelial proliferations and in tissue microarrays containing 70 epithelioid (EM), 36 biphasic (BM), and 2 sarcomatoid mesotheliomas (SM). In whole sections and tissue microarrays, respectively, membranous HEG1 was expressed in 93.0% and 85.5% of EM, 81.3% and 69.4% of BM, 0% and 0% of SM. HEG1 was not expressed in pulmonary adenocarcinomas. HEG1 was expressed as cytoplasmic immunoreactivity in pulmonary squamous cell carcinomas (21.7%). Membranous HEG1 staining was seen in ovarian carcinomas (66.7%), thyroid carcinomas (100%), reactive conditions (16.7%), and mesenchymal tumors (18.8%). The sensitivity of membranous HEG1 expression to distinguish EM/BM from all carcinomas was 88.8%. The specificity for the differential diagnosis between EM/BM and all carcinomas and pulmonary carcinomas was 92.3% and 98.7%, respectively.}, }
@article {pmid34235080, year = {2021}, author = {Behrouzfar, K and Burton, K and Mutsaers, SE and Morahan, G and Lake, RA and Fisher, SA}, title = {How to Better Understand the Influence of Host Genetics on Developing an Effective Immune Response to Thoracic Cancers.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {679609}, doi = {10.3389/fonc.2021.679609}, pmid = {34235080}, issn = {2234-943X}, abstract = {Thoracic cancers pose a significant global health burden. Immune checkpoint blockade therapies have improved treatment outcomes, but durable responses remain limited. Understanding how the host immune system interacts with a developing tumor is essential for the rational development of improved treatments for thoracic malignancies. Recent technical advances have improved our understanding of the mutational burden of cancer cells and changes in cancer-specific gene expression, providing a detailed understanding of the complex biology underpinning tumor-host interactions. While there has been much focus on the genetic alterations associated with cancer cells and how they may impact treatment outcomes, how host genetics affects cancer development is also critical and will greatly determine treatment response. Genome-wide association studies (GWAS) have identified genetic variants associated with cancer predisposition. This approach has successfully identified host genetic risk factors associated with common thoracic cancers like lung cancer, but is less effective for rare cancers like malignant mesothelioma. To assess how host genetics impacts rare thoracic cancers, we used the Collaborative Cross (CC); a powerful murine genetic resource designed to maximize genetic diversity and rapidly identify genes associated with any biological trait. We are using the CC in conjunction with our asbestos-induced MexTAg mouse model, to identify host genes associated with mesothelioma development. Once genes that moderate tumor development and progression are known, human homologues can be identified and human datasets interrogated to validate their association with disease outcome. Furthermore, our CC-MexTAg animal model enables in-depth study of the tumor microenvironment, allowing the correlation of immune cell infiltration and gene expression signatures with disease development. This strategy provides a detailed picture of the underlying biological pathways associated with mesothelioma susceptibility and progression; knowledge that is crucial for the rational development of new diagnostic and therapeutic strategies. Here we discuss the influence of host genetics on developing an effective immune response to thoracic cancers. We highlight current knowledge gaps, and with a focus on mesothelioma, describe the development and application of the CC-MexTAg to overcome limitations and illustrate how the knowledge gained from this unique study will inform the rational design of future treatments of mesothelioma.}, }
@article {pmid34227091, year = {2021}, author = {Pagliuca, F and Zito Marino, F and Morgillo, F and Della Corte, C and Santini, M and Vicidomini, G and Guggino, G and De Dominicis, G and Campione, S and Accardo, M and Cozzolino, I and Franco, R}, title = {Inherited predisposition to malignant mesothelioma: germline BAP1 mutations and beyond.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {12}, pages = {4236-4246}, doi = {10.26355/eurrev_202106_26129}, pmid = {34227091}, issn = {2284-0729}, abstract = {Malignant mesothelioma (MM) is a rare aggressive neoplasm arising from mesothelial lining of body cavities, most commonly pleura and peritoneum. It is characterised by a poor prognosis and limited treatment options. A universally recognised risk factor for the development of MM is exposure to asbestos. However, evidence supporting a genetic susceptibility to the development of MM has been accumulating during the last decades. Intensive research for the identification of MM susceptibility genes has led to the discovery of BAP1 and to the definition of the so-called "BAP1-related tumour predisposition syndrome". Patients carrying germline BAP1 mutations have an increased risk for the early development of tumours, including MMs, uveal melanomas, cutaneous melanocytic lesions, clear cell renal cell carcinomas and basal cell carcinomas. Furthermore, pathogenic variants in tumour suppressor genes with a role in DNA repair have been recently described in families with clustered MM cases. These genetic alterations seem to confer exaggerate sensitivity to asbestos carcinogenic effect and, arguably, increased response to specific chemotherapeutic strategies. While the translational significance of BAP1 alterations is explored in the research field, the identification of families carrying germline BAP1 mutations is mandatory to start appropriate surveillance programs and guarantee the best clinical management to these patients.}, }
@article {pmid34226685, year = {2021}, author = {Obacz, J and Yung, H and Shamseddin, M and Linnane, E and Liu, X and Azad, AA and Rassl, DM and Fairen-Jimenez, D and Rintoul, RC and Nikolić, MZ and Marciniak, SJ}, title = {Biological basis for novel mesothelioma therapies.}, journal = {British journal of cancer}, volume = {}, number = {}, pages = {}, pmid = {34226685}, issn = {1532-1827}, abstract = {Mesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology. However, recent work has revolutionised the study of mesothelioma, identifying genetic and pathophysiological vulnerabilities, including the loss of tumour suppressors, epigenetic dysregulation and susceptibility to nutrient stress. We discuss how this knowledge, combined with advances in immunotherapy, is enabling the development of novel targeted therapies.}, }
@article {pmid34211838, year = {2021}, author = {Faversani, A and Favero, C and Dioni, L and Pesatori, AC and Bollati, V and Montoli, M and Musso, V and Terrasi, A and Fusco, N and Nosotti, M and Vaira, V and Palleschi, A}, title = {An EBC/Plasma miRNA Signature Discriminates Lung Adenocarcinomas From Pleural Mesothelioma and Healthy Controls.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {643280}, pmid = {34211838}, issn = {2234-943X}, abstract = {Background: Despite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis.<br><br>Methods: We profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database.<br><br>Results: miR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways.<br><br>Conclusions: Overall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis.}, }
@article {pmid34210265, year = {2021}, author = {Saracino, L and Bortolotto, C and Tomaselli, S and Fraolini, E and Bosio, M and Accordino, G and Agustoni, F and Abbott, DM and Pozzi, E and Eleftheriou, D and Morbini, P and Rinaldi, P and Primiceri, C and Lancia, A and Comoli, P and Filippi, AR and Stella, GM}, title = {Integrating data from multidisciplinary Management of Malignant Pleural Mesothelioma: a cohort study.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {762}, pmid = {34210265}, issn = {1471-2407}, support = {Plagencell project//Fondazione Regionale per la Ricerca Biomedica/ ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural layers. MPM has a strong association with asbestos, mainly caused by exposure to its biopersistent fibers in at least 80% of cases. Individuals with a chronic exposure to asbestos might develop disease with a 20-40-year latency with few or no symptoms. Such has been the case in the Italian regions of Piedmont and Lombardy, where industrial production of materials laden with asbestos, mainly cements, has been responsible for the onset of a large epidemic. Since 2018, a multidisciplinary team at San Matteo hospital in Pavia has been collecting data on over 100 patients with MPM. The main goal of this project is to define and describe an integrated profile for each MPM case at diagnosis by using data mining and partition analysis.<br><br>METHODS: Here we bring together exhaustive epidemiologic, histologic and radiologic data of 88 MPM patients that came to our observation and draw correlations with predictive and prognostic significance.<br><br>RESULTS: The median overall survival (OS) was 15.6 months. Most patients presented with pleural effusion, irrespective of disease stage. Quite unexpectedly, no statistically significant association was demonstrated between OS and TNM disease stage at diagnosis. Although average OS is similar in male and female patients, partition analysis of data underlined a significant differential hierarchy of predictor categories based on patient gender. In females with no smoking history, full chemotherapeutic regimens are associated with better outcomes. Moreover, concerning second line treatments, vinorelbine emerged as the most advantageous choice for female patients, whereas in the male subgroup no statistically significant difference resulted between gemcitabine and vinorelbine.<br><br>CONCLUSION: A multidisciplinary approach to MPM is mandatory to define better therapeutic approaches, personalize the management and improve patient outcomes.}, }
@article {pmid34206956, year = {2021}, author = {Désage, AL and Karpathiou, G and Peoc'h, M and Froudarakis, ME}, title = {The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review.}, journal = {Cancers}, volume = {13}, number = {13}, pages = {}, doi = {10.3390/cancers13133205}, pmid = {34206956}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.}, }
@article {pmid34205400, year = {2021}, author = {Kwak, K and Cho, SI and Paek, D}, title = {Future Incidence of Malignant Mesothelioma in South Korea: Updated Projection to 2038.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {12}, pages = {}, doi = {10.3390/ijerph18126614}, pmid = {34205400}, issn = {1660-4601}, abstract = {Malignant mesothelioma (MM) is a cancer that is largely caused by exposure to asbestos. Although asbestos is no longer used in South Korea, the incidence of MM continues to increase due to its long latent period. We aimed to update the previous prediction of MM incidence until 2038. We predicted the incidence of MM over the next 20 years (2019-2038) in South Korea using Møller's age-period-cohort (APC) model and a Poisson regression model based on asbestos consumption. The APC model predicted that the crude incidence rate would increase sharply in men and slowly in women. Despite the sex discrepancy in the rate of increase, the incidence rate for both sexes is expected to continue increasing until 2038. In the Poisson model, the crude incidence rate was predicted to increase continuously until 2038, and far more cases of MM were predicted to occur compared with the results of the APC model. When compared with actual incidence data, the APC model was deemed more suitable than the Poisson model. The APC model predicted a continuous increase over the next 20 years with no peak, suggesting that the incidence of MM will continue to rise far into the future.}, }
@article {pmid34201002, year = {2021}, author = {Coccè, V and La Monica, S and Bonelli, M and Alessandri, G and Alfieri, R and Lagrasta, CA and Madeddu, D and Frati, C and Flammini, L and Lisini, D and Marcianti, A and Parati, E and Paino, F and Giannì, A and Farronato, G and Falco, A and Spaggiari, L and Petrella, F and Pessina, A}, title = {Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34201002}, issn = {2073-4409}, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM.<br><br>METHODS: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines. After large-scale production of MSCs in a bioreactor, their efficacy was also evaluated on a human MPM xenograft in mice.<br><br>RESULTS: MSCs, their lysate and secretome inhibited MPM cell proliferation in vitro with S or G0/G1 arrest of the cell cycle, respectively. MSC lysate induced cell death by apoptosis. The efficacy of MSC was confirmed in vivo by a significant inhibition of tumor growth, similar to that produced by systemic administration of paclitaxel. Interestingly, no tumor progression was observed after the last MSC treatment, while tumors started to grow again after stopping chemotherapeutic treatment.<br><br>CONCLUSIONS: These data demonstrated for the first time that MSCs, both through paracrine and cell-to-cell interaction mechanisms, induced a significant inhibition of human mesothelioma growth. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy.}, }
@article {pmid34199722, year = {2021}, author = {Terenziani, R and Zoppi, S and Fumarola, C and Alfieri, R and Bonelli, M}, title = {Immunotherapeutic Approaches in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34199722}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. The current therapeutic actions, based on cisplatin/pemetrexed treatment, are limited due to the late stage at which most patients are diagnosed and to the intrinsic chemo-resistance of the tumor. Another relevant point is the absence of approved therapies in the second line setting following progression of MPM after chemotherapy. Considering the poor prognosis of the disease and the fact that the incidence of this tumor is expected to increase in the next decade, novel therapeutic approaches are urgently needed. In the last few years, several studies have investigated the efficacy and safety of immune-checkpoint inhibitors (ICIs) in the treatment of unresectable advanced MPM, and a number of trials with immunotherapeutic agents are ongoing in both first line and second line settings. In this review, we describe the most promising emerging immunotherapy treatments for MPM (ICIs, engineered T cells to express chimeric antigen receptors (CARs), dendritic cells (DCs) vaccines), focusing on the biological and immunological features of this tumor as well as on the issues surrounding clinical trial design.}, }
@article {pmid34199544, year = {2021}, author = {Lorenzini, E and Ciarrocchi, A and Torricelli, F}, title = {Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations.}, journal = {Journal of clinical medicine}, volume = {10}, number = {11}, pages = {}, pmid = {34199544}, issn = {2077-0383}, support = {//Italian Ministry of Health though Bando per la Valorizzazione della Ricerca in ambito Oncologico 2020-Fondi 5 per Mille/ ; //Italian Ministry of Health though Bando per la Valorizzazione della Ricerca in ambito Oncologico 2019-Fondi 5 per Mille/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a clinical emergency of our time. Being strongly associated with asbestos exposure, incidence of this cancer is ramping up these days in many industrialized countries and it will soon start to increase in many developing areas where the use of this silicate derivate is still largely in use. Deficiency of reliable markers for the early identification of these tumors and the limited efficacy of the currently available therapeutic options are the basis of the impressive mortality rate of MPM. These shortcomings reflect the very poor information available about the molecular basis of this disease. Results of the recently released deep profiling studies point to the epigenome as a central element in MPM development and progression. First, MPM is characterized by a low mutational burden and a highly peculiar set of mutations that hits almost exclusively epigenetic keepers or proteins controlling chromatin organization and function. Furthermore, asbestos does not seem to be associated with a distinctive mutational signature, while the precise mapping of epigenetic changes caused by this carcinogen has been defined, suggesting that alterations in epigenetic features are the driving force in the development of this disease. Last but not least, consistent evidence also indicates that, in the setting of MPM, chromatin rewiring and epigenetic alterations of cancer cells heavily condition the microenvironment, including the immune response. In this review we aim to point to the relevance of the epigenome in MPM and to highlight the dependency of this tumor on chromatin organization and function. We also intend to discuss the opportunity of targeting these mechanisms as potential therapeutic options for MPM.}, }
@article {pmid34172838, year = {2021}, author = {Marant Micallef, C and Charvat, H and Houot, MT and Vignat, J and Straif, K and Paul, A and El Yamani, M and Pilorget, C and Soerjomataram, I}, title = {Estimated number of cancers attributable to occupational exposures in France in 2017: an update using a new method for improved estimates.}, journal = {Journal of exposure science &amp; environmental epidemiology}, volume = {}, number = {}, pages = {}, pmid = {34172838}, issn = {1559-064X}, abstract = {BACKGROUND: Over the last 50 years, occupational exposure to carcinogenic agents has been widely regulated in France.<br><br>OBJECTIVE: Report population-attributable fraction (PAF) and number of attributable cancer cases linked to occupational exposure in France based on an updated method to estimate lifetime occupational exposure prevalence.<br><br>METHODS: Population-level prevalence of lifetime exposure to ten carcinogenic agents (asbestos, benzene, chromium VI, diesel engine exhaust, formaldehyde, nickel compounds, polycyclic aromatic hydrocarbons, silica dust, trichloroethylene, wood dust) and two occupational circumstances (painters and rubber industry workers) were estimated using the French Census linked with MATGÉNÉ job-exposure matrices and French occupational surveys. PAF and number of attributable cancer cases were calculated using the estimated prevalence, relative risks from systematic review and national estimates of cancer incidence in 2017.<br><br>RESULTS: The lifetime occupational exposure prevalences were much higher in men than in women ranging from 0.2% (workers in the rubber industry) to 10.2% in men (silica), and from 0.10% (benzene, PAH and workers in the rubber industry) to 5.7% in women (formaldehyde). In total, 4,818 cancer cases (men: 4,223; women: 595) were attributable to the ten studied carcinogens and two occupational circumstances, representing 5.2% of cases among the studied cancer sites (M: 7.0%; W: 1.9%). In both sexes, mesothelioma (M: 689 cases; W: 160) and lung cancer (M: 3,032; W: 308) were the largest cancer sites impacted by the studied occupational agents and circumstances.<br><br>SIGNIFICANCE: A moderate proportion of the cancer cases in France is linked to carcinogens in occupational settings. Our method provides more precise estimates of attributable cancer taking into account evolution of exposure to occupational agents by sex, age and time. This methodology can be easily replicated using cross-sectional occupational data to aid priority making and implementation of prevention strategies in the workplace.}, }
@article {pmid34161674, year = {2021}, author = {Ke, H and Kao, S and Lee, K and Takahashi, K and Goh, HP and Linton, A}, title = {The minimum standard of care for managing malignant pleural mesothelioma in developing nations within the Asia-Pacific Region.}, journal = {Asia-Pacific journal of clinical oncology}, volume = {}, number = {}, pages = {}, doi = {10.1111/ajco.13611}, pmid = {34161674}, issn = {1743-7563}, abstract = {Malignant pleural mesothelioma (MPM) is an incurable malignancy associated with high symptom burden and poor prognosis. The relationship between asbestos exposure and MPM incidence is well-established. The incidence rate of MPM in Australia and New Zealand is among the highest globally. Matching the experience of other nations with legal restrictions on asbestos, incidence is expected to fall. In contrast, the incidence of MPM is rising in the developing nations of the Asia-Pacific as consumption and mining (albeit to a lesser extent) of asbestos continues. The incidence of MPM in these nations is currently low or unknown, reflecting insufficient latency periods since industrial use of asbestos, deficient resources for accurate diagnosis, and lack of occupational disease or cancer registries. The landscape of treatment for MPM is rapidly changing with combination immunotherapy now demonstrating improved survival in the first-line setting. Considering vast global inequity in access to anticancer treatments, establishing minimum standard of care for MPM in developing nations is of greater significance. Here, we review the evidence that form the basis of our minimum-standard recommendations for diagnosis, systemic treatment, management of recurrent pleural effusions, and symptom management. We also briefly review evidence-based treatment that may be considered for those with access.}, }
@article {pmid34155270, year = {2021}, author = {Kishimoto, T and Kojima, Y and Fujimoto, N}, title = {Significance of secretory leukocyte peptidase inhibitor in pleural fluid for the diagnosis of benign asbestos pleural effusion.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12965}, pmid = {34155270}, issn = {2045-2322}, abstract = {Secretory leukocyte peptidase inhibitor (SLPI) is a biomarker present in the respiratory tract that protects against tissue destruction and aids in wound healing. We examined whether SLPI in pleural effusion can be used to distinguish benign asbestos pleural effusion (BAPE) from early-stage malignant pleural mesothelioma (MPM) and other diseases. We measured the levels of SLPI, hyaluronic acid (HA), soluble mesothelin-related peptides (SMRP), CCL2, galectin-3, and CYFRA21-1 in 51 patients with BAPE, 37 patients with early-stage MPM, 77 patients with pleural effusions due to non-small-cell lung cancer (LCa), and 74 patients with other pleural effusions. SLPI levels in the pleural fluid of patients with BAPE were significantly lower than those in patients with MPM, LCa, and other pleural effusions (p < 0.0001). The area under the curve (AUC) for SLPI's ability to distinguish BAPE from MPM was 0.902, with a sensitivity of 82.4% and a specificity of 86.5%. This AUC was not only favourable but was better than the AUC for the ability of CYFRA21-1 to distinguish BAPE (0.853). The combination of SLPI and CYFRA21-1 achieved an AUC of 0.965 for the differentiation between BAPE and MPM. Pleural fluid SLPI as well as CYFRA21-1 and HA is useful as a biomarker to diagnose BAPE, which needs to be distinguished from early-stage MPM.}, }
@article {pmid34120777, year = {2021}, author = {Ramada Rodilla, JM and Calvo Cerrada, B and Serra Pujadas, C and Delclos, GL and Benavides, FG}, title = {Fiber burden and asbestos-related diseases: an umbrella review.}, journal = {Gaceta sanitaria}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gaceta.2021.04.001}, pmid = {34120777}, issn = {1578-1283}, abstract = {OBJECTIVE: What are the levels of asbestos exposure that cause each type of health effect? The objective of this study was to review the available scientific evidence on exposure levels for asbestos and their relationship to health effects.<br><br>METHOD: An umbrella review of English-language reviews and meta-analyses, from 1980 to March 2021 was conducted. We included reviews involving quantified asbestos exposures and health outcomes. The review has been adapted to the indications of the PRISMA declaration. Methodological quality of the selected studies was assessed using the AMSTAR instrument.<br><br>RESULTS: We retrieved 196 references. After applying the search strategy and quality analysis, 10 reviews were selected for in-depth analysis. For lung cancer, the highest risk was observed with exposure to amphiboles. Longer, thinner fibers had the greatest capacity to cause lung cancer, especially those > 10 μm in length. For mesothelioma, longer and thinner fibers were also more pathogenic; amphiboles ≥ 5 μm are especially associated with increased mesothelioma risk. No studies observed an increased risk for lung cancer or mesothelioma at asbestos exposure levels <0.1 f/ml. No reviews provided information on exposure concentrations for pulmonary fibrosis. Currently, there is limited evidence in humans to establish the causal relationship between gastrointestinal cancer and asbestos exposure.<br><br>CONCLUSIONS: Banning all asbestos exposure remains the best measure to preventing its negative health effects. The highest quality reviews and meta-analyses support that there is little risk of lung cancer or mesothelioma at daily exposure levels below 0.1 f/ml.}, }
@article {pmid34116230, year = {2021}, author = {Tsim, S and Alexander, L and Kelly, C and Shaw, A and Hinsley, S and Clark, S and Evison, M and Holme, J and Cameron, EJ and Sharma, D and Wright, A and Grundy, S and Grieve, D and Ionescu, A and Breen, DP and Paramasivam, E and Psallidas, I and Mukherjee, D and Chetty, M and Cox, G and Hart-Thomas, A and Naseer, R and Edwards, J and Daneshvar, C and Panchal, R and Munavvar, M and Ostroff, R and Alexander, L and Hall, H and Neilson, M and Miller, C and McCormick, C and Thomson, F and Chalmers, AJ and Maskell, NA and Blyth, KG}, title = {Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2021.05.018}, pmid = {34116230}, issn = {1556-1380}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory.<br><br>METHODS: A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure.<br><br>RESULTS: A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557-0.664], p = 0.0015) and 0.516 [0.443-0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume.<br><br>CONCLUSIONS: SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.}, }
@article {pmid34082107, year = {2021}, author = {Vandenhoeck, J and van Meerbeeck, JP and Fransen, E and Raskin, J and Van Camp, G and Op de Beeck, K and Lamote, K}, title = {DNA Methylation as a Diagnostic Biomarker for Malignant Mesothelioma: A Systematic Review and Meta-Analysis.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2021.05.015}, pmid = {34082107}, issn = {1556-1380}, abstract = {Malignant mesothelioma is an aggressive cancer type linked to asbestos exposure. Because of several intrinsic challenges, mesothelioma is often diagnosed in an advanced disease stage. Therefore, there is a need for diagnostic biomarkers that may contribute to early detection. Recently, the epigenome of tumors is being extensively investigated to identify biomarkers. This manuscript is a systematic review summarizing the state-of-the-art research investigating DNA methylation in mesothelioma. Four literature databases (PubMed, Scopus, Web of Science, MEDLINE) were systematically searched for studies investigating DNA methylation in mesothelioma up to October 16, 2020. A meta-analysis was performed per gene investigated in at least two independent studies. A total of 53 studies investigated DNA methylation of 97 genes in mesothelioma and are described in a qualitative overview. Furthermore, ten studies investigating 13 genes (APC, CDH1, CDKN2A, DAPK, ESR1, MGMT, miR-34b/c, PGR, RARβ, RASSF1, SFRP1, SFRP4, WIF1) were included in the quantitative meta-analysis. In this meta-analysis, the APC gene is significantly hypomethylated in mesothelioma, whereas CDH1, ESR1, miR-34b/c, PGR, RARβ, SFRP1, and WIF1 are significantly hypermethylated in mesothelioma. The three genes that are the most appropriate candidate biomarkers from this meta-analysis are APC, miR-34b/c, and WIF1. Nevertheless, both study number and study objects comprised in this meta-analysis are too low to draw final conclusions on their clinical applications. The elucidation of the genome-wide DNA methylation profile of mesothelioma is desirable in the future, using a standardized genome-wide methylation analysis approach. The most informative CpG sites from this signature could then form the basis of a panel of highly sensitive and specific biomarkers that can be used for the diagnosis of mesothelioma and even for the screening of an at high-risk population of asbestos-exposed individuals.}, }
@article {pmid34073720, year = {2021}, author = {Napoli, F and Listì, A and Zambelli, V and Witel, G and Bironzo, P and Papotti, M and Volante, M and Scagliotti, G and Righi, L}, title = {Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34073720}, issn = {2072-6694}, support = {IG 2019 - ID. 23760 project//Associazione Italiana per la Ricerca sul Cancro/ ; Ricerca Locale 2019//Università degli Studi di Torino/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13-15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients' genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.}, }
@article {pmid34071989, year = {2021}, author = {Cugliari, G and Allione, A and Russo, A and Catalano, C and Casalone, E and Guarrera, S and Grosso, F and Ferrante, D and Sculco, M and La Vecchia, M and Pirazzini, C and Libener, R and Mirabelli, D and Magnani, C and Dianzani, I and Matullo, G}, title = {New DNA Methylation Signals for Malignant Pleural Mesothelioma Risk Assessment.}, journal = {Cancers}, volume = {13}, number = {11}, pages = {}, pmid = {34071989}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive tests aimed at an MPM risk assessment tool that might improve life expectancy. Three hundred asbestos-exposed subjects (163 MPM cases and 137 cancer-free controls), from the same geographical region in Italy, were recruited. The evaluation of asbestos exposure was conducted considering the frequency, the duration and the intensity of occupational, environmental and domestic exposure. A genome-wide methylation array was performed to identify novel blood DNA methylation (DNAm) markers of MPM. Multiple regression analyses adjusting for potential confounding factors and interaction between asbestos exposure and DNAm on the MPM odds ratio were applied. Epigenome-wide analysis (EWAS) revealed 12 single-CpGs associated with the disease. Two of these showed high statistical power (99%) and effect size (>0.05) after false discovery rate (FDR) multiple comparison corrections: (i) cg03546163 in FKBP5, significantly hypomethylated in cases (Mean Difference in beta values (MD) = -0.09, 95% CI = -0.12|-0.06, p = 1.2 × 10-7), and (ii) cg06633438 in MLLT1, statistically hypermethylated in cases (MD = 0.07, 95% CI = 0.04|0.10, p = 1.0 × 10-6). Based on the interaction analysis, asbestos exposure and epigenetic profile together may improve MPM risk assessment. Above-median asbestos exposure and hypomethylation of cg03546163 in FKBP5 (OR = 20.84, 95% CI = 8.71|53.96, p = 5.5 × 10-11) and hypermethylation of cg06633438 in MLLT1 (OR = 11.71, 95% CI = 4.97|29.64, p = 5.9 × 10-8) genes compared to below-median asbestos exposure and hyper/hypomethylation of single-CpG DNAm, respectively. Receiver Operation Characteristics (ROC) for Case-Control Discrimination showed a significant increase in MPM discrimination when DNAm information was added in the model (baseline model, BM: asbestos exposure, age, gender and white blood cells); area under the curve, AUC = 0.75; BM + cg03546163 at FKBP5. AUC = 0.89, 2.1 × 10-7; BM + cg06633438 at MLLT1. AUC = 0.89, 6.3 × 10-8. Validation and replication procedures, considering independent sample size and a different DNAm analysis technique, confirmed the observed associations. Our results suggest the potential application of DNAm profiles in blood to develop noninvasive tests for MPM risk assessment in asbestos-exposed subjects.}, }
@article {pmid34070888, year = {2021}, author = {Rossi, G and Davoli, F and Poletti, V and Cavazza, A and Lococo, F}, title = {When the Diagnosis of Mesothelioma Challenges Textbooks and Guidelines.}, journal = {Journal of clinical medicine}, volume = {10}, number = {11}, pages = {}, pmid = {34070888}, issn = {2077-0383}, abstract = {The diagnosis of malignant mesothelioma (MPM) does not pose difficulties when presenting with usual clinico-radiologic features and morphology. Pathology textbooks and national/international guidelines generally describe the findings of classic MPM, underlining common clinical presentation, the gold standard of sampling techniques, usual morphologic variants, immunohistochemical results of several positive and negative primary antibodies in the differential diagnosis, and the role of novel molecular markers. Nevertheless, MPM often does not follow the golden rules in routine practice, while the literature generally does not sufficiently emphasize unusual features of its manifestation. This gap may potentially create problems for patients in sustaining a difficult diagnosis of MPM in clinical practice and during legal disputes. Indeed, the guidelines accidentally tend to favor the job of lawyers and pathologists defending asbestos-producing industries against patients suffering from MPM characterized by uncommon features. The current review is aimed at underlining the wide spectrum of clinical and radiological presentation of MPM, the possibility to consistently use cytology for diagnostic intent, the aberrant immunohistochemical expression using so-called specific negative and positive primary antibodies, and finally proposing some alternative and more unbiased approaches to the diagnosis of MPM.}, }
@article {pmid34069196, year = {2021}, author = {Lee, KM and Godderis, L and Furuya, S and Kim, YJ and Kang, D}, title = {Comparison of Asbestos Victim Relief Available Outside of Conventional Occupational Compensation Schemes.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {10}, pages = {}, pmid = {34069196}, issn = {1660-4601}, mesh = {*Asbestos ; France ; Humans ; Japan ; *Lung Neoplasms ; *Mesothelioma/chemically induced ; Netherlands ; *Occupational Diseases ; *Occupational Exposure ; Republic of Korea ; United Kingdom ; Workers' Compensation ; }, abstract = {The asbestos victim relief schemes were introduced to resolve the issue of victims of asbestos-related diseases not receiving compensation through conventional legal orders. This article seeks to derive the differences and commonalities of various asbestos victim relief schemes available outside of the conventional occupational compensation system along with a systematic understanding and to propose plans for improvement through a comparative study. After the degree of asbestos exposure, the population, and the period of implementation were corrected, the recognized claims of the total of conventional occupational compensation schemes and the asbestos victim relief schemes could be ranked in the order of South Korea (KOR) (1867, total), France (FRA) (1571), Japan (JPN) (966), KOR (847, asbestosis grade 2,3 excluded), the United Kingdom (GBR) (670), and the Netherlands (NLD) (95). The average amount of compensation per person, in the case of mesothelioma, was higher in the order of FRA (4.60 times), KOR (1.46 times), GBR (1.03 times), and NLD (0.73 times) of the median income per year. The differences between countries were largely caused by the purpose of institutional design and influenced by the level of qualification, the existence of an expiration date, type of disease, type of benefit, level of judgment criteria, the existence of a procedure for appeals, and recognition rate (GBR: 102%, FRA: 84%, NLD: 81%, JPN: 76%, KOR: 73%, and BEL: 54%). Based on this analysis, suggestions could be made regarding the expansion of disease types, benefit types, and the overall review of judgment criteria.}, }
@article {pmid34068638, year = {2021}, author = {Vimercati, L and Cavone, D and Delfino, MC and Bruni, B and De Maria, L and Caputi, A and Sponselli, S and Rossi, R and Resta, L and Fortarezza, F and Pezzuto, F and Serio, G}, title = {Primary Ovarian Mesothelioma: A Case Series with Electron Microscopy Examination and Review of the Literature.}, journal = {Cancers}, volume = {13}, number = {9}, pages = {}, pmid = {34068638}, issn = {2072-6694}, abstract = {Primary ovarian mesothelioma is a rare, aggressive neoplastic disease with a poor prognosis. At onset, the tumor is only rarely limited to the ovaries and usually already widespread in the peritoneum. The rarity of this entity and the difficulties differentiating it from either ovarian carcinoma or peritoneal mesothelioma may lead to frequent misdiagnoses and may raise some concerns about its histogenesis. Thus, reporting such rare cases is fundamental to gain greater awareness of this neoplasm and try to answer unsolved questions. Herein, we described four cases of histological diagnoses of ovarian mesothelioma extrapolated by the regional mesothelioma register of Apulia (southern Italy). In all cases, a detailed medical history was collected according to national mesothelioma register guidelines. A broad panel of antibodies was used for immunohistochemistry to confirm the diagnoses. Moreover, ovarian tissue samples were also examined by transmission and scanning electron microscopy, detecting asbestos fibers and talc crystals in two cases. Because of the few cases described, we reviewed the English literature in the Medline database, focusing on articles about ovarian mesothelioma "misclassification", "misdiagnosis", "diagnostic challenge" or "diagnostic pitfall" and on unsolved questions about its histogenesis and possible risk factors.}, }
@article {pmid34066159, year = {2021}, author = {Anobile, DP and Bironzo, P and Picca, F and Lingua, MF and Morena, D and Righi, L and Napoli, F and Papotti, MG and Pittaro, A and Di Nicolantonio, F and Gigliotti, C and Bussolino, F and Comunanza, V and Guerrera, F and Sandri, A and Leo, F and Libener, R and Aviles, P and Novello, S and Taulli, R and Scagliotti, GV and Riganti, C}, title = {Evaluation of the Preclinical Efficacy of Lurbinectedin in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {10}, pages = {}, pmid = {34066159}, issn = {2072-6694}, support = {23760//Associazione Italiana per la Ricerca sul Cancro/ ; 21408//Associazione Italiana per la Ricerca sul Cancro/ ; EX60% Funding 2019//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; TOPMESO JTC 2017//ERANet Transcan2/ ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer generally diagnosed at an advanced stage and characterized by a poor prognosis. The absence of alterations in druggable kinases, together with an immune-suppressive tumor microenvironment, limits the use of molecular targeted therapies, making the treatment of MPM particularly challenging. Here we investigated the in vitro susceptibility of MPM to lurbinectedin (PM01183), a marine-derived drug that recently received accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy.<br><br>METHODS: A panel of primary MPM cultures, resembling the three major MPM histological subtypes (epithelioid, sarcomatoid, and biphasic), was characterized in terms of BAP1 status and histological markers. Subsequently, we explored the effects of lurbinectedin at nanomolar concentration on cell cycle, cell viability, DNA damage, genotoxic stress response, and proliferation.<br><br>RESULTS: Stabilized MPM cultures exhibited high sensitivity to lurbinectedin independently from the BAP1 mutational status and histological classification. Specifically, we observed that lurbinectedin rapidly promoted a cell cycle arrest in the S-phase and the activation of the DNA damage response, two conditions that invariably resulted in an irreversible DNA fragmentation, together with strong apoptotic cell death. Moreover, the analysis of long-term treatment indicated that lurbinectedin severely impacts MPM transforming abilities in vitro.<br><br>CONCLUSION: Overall, our data provide evidence that lurbinectedin exerts a potent antitumoral activity on primary MPM cells, independently from both the histological subtype and BAP1 alteration, suggesting its potential activity in the treatment of MPM patients.}, }
@article {pmid34060417, year = {2021}, author = {Ierardi, AM and Mathis, C and Urban, A and Jacobs, N and Finley, B and Gaffney, S}, title = {Potential airborne asbestos exposures in dentistry: a comprehensive review and risk assessment.}, journal = {Critical reviews in toxicology}, volume = {51}, number = {4}, pages = {301-327}, doi = {10.1080/10408444.2021.1910624}, pmid = {34060417}, issn = {1547-6898}, abstract = {Chrysotile was formerly used in the manufacture of casting ring liner (CRL) and periodontal dressing powder (PDP). The purpose of this study was to describe the potential for airborne asbestos exposure among dental professionals who may have used these products and to assess their risk of asbestos-related disease (ARD). Task-specific exposure data associated with CRL and PDP were identified and compared to regulatory standards for asbestos and health-based benchmarks. Personal airborne fiber concentrations ranged from 0.008-3.5 f/cc by PCM (duration: 3-420 minutes) for CRL (tearing, placement), and from <0.0044-<0.297 f/cc by PCM (duration: 5-28 minutes) for PDP (mixing). Eight-hour time-weighted average (TWA) exposures were calculated using the reported task-based airborne fiber concentrations and associated sampling durations. For CRL tasks, the upper-bound calculated 8-hour TWA of 0.022 f/cc (tearing, placement) did not exceed regulatory standards for asbestos (≥0.1 f/cc). All samples collected during the mixing of PDP resulted in non-measurable fiber concentrations. The greatest estimated cumulative asbestos exposure for dental professionals using CRL (tearing, placement) of 0.33 f/cc-years is well below "best estimate", published chrysotile no-observed-adverse-effect-levels (NOAEL) for ARD (lung cancer = 89-168 f/cc-years; pleural mesothelioma = 208-415 f/cc-years). As such, the use of asbestos-containing CRL and/or PDP is not expected to pose an increased risk of ARD among dental professionals. This conclusion is consistent with the lack of an increased risk of ARD reported in epidemiological studies of these occupations.}, }
@article {pmid34059094, year = {2021}, author = {Haakensen, VD and Nowak, AK and Ellingsen, EB and Farooqi, SJ and Bjaanæs, MM and Horndalsveen, H and Mcculloch, T and Grundberg, O and Cedres, SM and Helland, Å}, title = {NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {232}, pmid = {34059094}, issn = {1479-5876}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Humans ; Ipilimumab/therapeutic use ; *Mesothelioma/drug therapy ; *Mesothelioma, Malignant ; Nivolumab/therapeutic use ; Vaccination ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour. For patients with inoperable disease, few treatment options are available after first line chemotherapy. The combination of ipilimumab and nivolumab has recently shown increased survival compared to standard chemotherapy, but most patients do not respond and improvements are called for. Telomerase is expressed in mesothelioma cells, but only sparsely in normal tissues and is therefore an attractive target for therapeutic vaccination. Vaccination against telomerase is tolerable and has shown to induce immune responses associated with increased survival in other cancer types. There is a well-founded scientific rationale for the combination of a telomerase vaccine and checkpoint inhibition to improve treatment response in MPM patients.<br><br>METHODS: NIPU is a randomized, multi-centre, open-label, phase II study comparing the efficacy and safety of nivolumab and ipilimumab with or without telomerase vaccine in patients with inoperable malignant pleural mesothelioma after first-line platinum-based chemotherapy. Participants (n = 118) are randomized 1:1 into two treatment arms. All participants receive treatment with nivolumab (240 mg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression, unacceptable toxicity or for a maximum of 2 years. Patients randomised to the experimental arm receive 8 intradermal injections of UV1 vaccine during the first three months of treatment. Tumour tissue, blood, urine, faeces and imaging will be collected for biomarker analyses and exploration of mechanisms for response and resistance to therapy.<br><br>DISCUSSION: Checkpoint inhibition is used for treatment of mesothelioma, but many patients still do not respond. Increasing therapy response to immunotherapy is an important goal. Possible approaches include combination with chemotherapy, radiotherapy, targeted therapy and other immunotherapeutic agents. Predictive biomarkers are necessary to ensure optimal treatment for each patient and to prevent unnecessary side effects. This trial seeks to improve treatment response by combining checkpoint inhibition with a telomerase vaccine and also to explore mechanisms for treatment response and resistance. Knowledge gained in the NIPU study may be transferred to the first line setting and to other cancers with limited benefit from immunotherapy.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov: NCT04300244, registered March 8th, 2020, https://clinicaltrials.gov/ct2/show/NCT04300244?term=NIPU&amp;draw=2&amp;rank=1 .}, }
@article {pmid34052509, year = {2021}, author = {Scarselli, A and Marinaccio, A and Iavicoli, S}, title = {Ophiolitic outcrops, naturally occurring asbestos exposure and mortality risk from malignant mesothelioma in Calabria (Southern Italy).}, journal = {Public health}, volume = {195}, number = {}, pages = {57-60}, doi = {10.1016/j.puhe.2021.04.008}, pmid = {34052509}, issn = {1476-5616}, abstract = {OBJECTIVES: Naturally occurring asbestos from ophiolitic outcrops can pose a health risk to the resident population. Some studies have documented this risk of exposure in many areas around the world. The aim of the study is to estimate the possible impact on health caused by asbestos outcrops present in some areas of Calabria, a region of southern Italy.<br><br>STUDY DESIGN: The design of the study is observational and uses routinely collected data on employment, compensations and mortality.<br><br>METHODS: Data from archives of mortality in the period 2005-2015 were selected. Standardized mortality ratio (SMR) for malignant mesothelioma (MM) by municipalities of residence with reference to the regional population was estimated assuming a Poisson distribution of the data. Administrative archives of companies' employment records and occupational disease compensation data were used to exclude occupational origin cases.<br><br>RESULTS: A total of 163 cases of MM were identified. Statistically significant excess risks (P-value <0.05) were observed for several municipalities, some of which were located in areas where asbestos outcrops had previously been identified. Significant SMRs vary between 44.0 and 5.2. The mean age at death in the areas at risk of ophiolitic outcrops ranges from 65.4 to 77.1 years, and the gender ratio (male/female) ranges from 0.66 to 1.3.<br><br>CONCLUSIONS: Monitoring of areas most involved in the risk of environmental contamination from ophiolitic outcrops is highly suggested. Full implementation of the local MM surveillance system is strongly encouraged. Further investigations are recommended to specifically identify the cause of exposure and confirm the hypothesis of a causal association with asbestos naturally occurring in these risk areas.}, }
@article {pmid34040906, year = {2021}, author = {Thomas, A and Karakattu, S and Cagle, J and Hoskere, G}, title = {Malignant Pleural Mesothelioma Epidemiology in the United States From 2000 to 2016.}, journal = {Cureus}, volume = {13}, number = {4}, pages = {e14605}, pmid = {34040906}, issn = {2168-8184}, abstract = {Introduction Pleural mesothelioma constitutes about 80% of all mesotheliomas. The peak incidence of malignant mesothelioma estimated using the cancer registries was in early 1990 to 2000 in the United States. The disease is primarily associated with asbestos exposure. The latency period between asbestos exposure and the development of malignant pleural mesothelioma (MPM) can range anywhere from 15 to 60 years. Asbestos exposure was peaked during the industrial revolution and World War II due to military and shipyard exposures. It is often difficult for the pathologist to distinguish different histological subtypes; due to the disease's rarity and the inadequate tissue sample obtained. There is no available data on the difference in epidemiology of different subtypes of MPM. Surveillance Epidemiology and End Results (SEER), cancer incidence data include population-based registries covering approximately 34.6% of the U.S. population. Here in our study, we analyze malignant pleural mesothelioma epidemiology in the United States, emphasizing different histological subtypes. Methods SEER data from 2000 to 2016 was used in our study. The primary site of cancer is selected as pleura, and malignant behavior only is selected as the filter. Data were analyzed using the SEER stat program. Overall epidemiology of MPM and epidemiology of epithelioid, fibrous, and biphasic histological subtypes were analyzed separately. We used annual percentage change (APC) to evaluate the trend in the epidemiology of MPM. Results summary A total of 11,857 cases of MPM were included in the primary cohort from the SEER 18 registry from 2000 to 2016. The total prevalence of MPM was highest in 2009 and was lowest in 2016. The APC in MPM incidence during this period is -2.0. After removing 5,989 cases with non-specified histology during the same period, the APC for each histological type is -0.7 for fibrous type, 1.8 for epithelioid type, and 2.9 for biphasic type. Out of 17 regional registries included in the study, the greatest statistically significant change in APC was seen in the Hawaiian registry -4.1. In contrast, the lowest statistically significant difference was seen in Seattle (Puget Sound) registry -1.7. The APC in the incidence of MPM among males during the study period was -2.4 while that of females was -0.9. The Iowa registry showed a statistically significant increase in APC of the epithelioid malignant mesothelioma with a statistically insignificant reduction in the overall MPM APC. Conclusion The overall incidence of MPM in the United States is declining, while the data showed an increase in the incidence of epithelioid and biphasic histological subtypes. The authors believe that these conflicting results can be attributed to improved histological diagnosis and improved biopsy techniques.}, }
@article {pmid34036634, year = {2021}, author = {Baur, X and Frank, AL and Soskolne, CL and Oliver, LC and Magnani, C}, title = {Malignant mesothelioma: Ongoing controversies about its etiology in females.}, journal = {American journal of industrial medicine}, volume = {64}, number = {7}, pages = {543-550}, doi = {10.1002/ajim.23257}, pmid = {34036634}, issn = {1097-0274}, abstract = {Malignant mesothelioma (MM) is one of the most aggressive cancers with the poorest of outcomes. There is no doubt that mesothelioma in males is related to asbestos exposure, but some authors suggest that most of the cases diagnosed in females are "idiopathic." In our assessment of the science, the "low risk" of mesothelioma in females is because of the nonsystematic recording of exposure histories among females. Indeed, asbestos exposure is mentioned in only some of the studies that include females. We estimate the risk of MM among females to be close to that in males. The absence of detailed exposure histories should be rectified in future studies involving ​women. As a matter of social justice, the ongoing failure to recognize asbestos as the cause of a majority of cases of MM in females does them, and their kin, a profound disservice.}, }
@article {pmid34033161, year = {2021}, author = {Louw, A and Lee, YCG and Acott, N and Creaney, J and van Vliet, C and Chai, SM}, title = {Diagnostic utility of BAP1 for malignant pleural mesothelioma in pleural fluid specimens with atypical morphology.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {}, number = {}, pages = {}, doi = {10.1111/cyt.13015}, pmid = {34033161}, issn = {1365-2303}, abstract = {OBJECTIVE: To assess the utility of BRCA1-associated protein 1 (BAP1) immunohistochemistry (IHC) for the diagnosis of malignant pleural mesothelioma (MPM) in fluid samples with atypical cytology.<br><br>METHODS: Pleural fluid samples with an atypical mesothelial proliferation (diagnostic categories: 'atypical' and 'suspicious') received between January 2015 and March 2018 at a tertiary referral centre were identified. Results of routine IHC testing were recorded for each case. BAP1 by IHC was performed and a final diagnosis sought from subsequent pathology specimens, medical records, or consensus clinical diagnosis.<br><br>RESULTS: Of 50 cases identified, 41 were reported as atypical and 9 as suspicious. Seven (14%) demonstrated loss of BAP1 staining, 40 retained BAP1 staining, 1 had heterogeneous staining, and 2 had insufficient cells for analysis. All seven cases with BAP1 loss were diagnosed with MPM on follow-up. Of those with retained BAP1, 52.5% (21) were subsequently diagnosed with MPM, while 40% (16) had non-MPM diagnoses after a median follow-up of 24 months. Three cases were not further investigated based on patient and clinician decision. The case with heterogeneous staining was diagnosed as mesothelioma by clinical consensus.<br><br>CONCLUSIONS: BAP1 IHC loss is highly specific for malignancy and has value as a rule-in test. Even in a tertiary centre with clinical interest in the cytological diagnosis of MPM this investigation was able to increase diagnostic accuracy beyond routine IHC studies. Cytological criteria remain valuable, as retained BAP1 in an atypical or suspicious mesothelial proliferation cannot exclude malignancy.}, }
@article {pmid34012597, year = {2021}, author = {Schumann, SO and Kocher, G and Minervini, F}, title = {Epidemiology, diagnosis and treatment of the malignant pleural mesothelioma, a narrative review of literature.}, journal = {Journal of thoracic disease}, volume = {13}, number = {4}, pages = {2510-2523}, pmid = {34012597}, issn = {2072-1439}, abstract = {The malignant pleural mesothelioma is a very aggressive tumor which is arising from mesothelial cells and is associated with asbestos exposure. It is a heterogeneous cancer that shows a complex pattern of molecular changes, including genetic, chromosomic, and epigenetic abnormalities. The malignant pleural mesothelioma is characterized by a silent and slow clinical progression with an average period of 20-40 years from the asbestos exposure phase to the start of the symptoms. Unfortunately, to date, the therapeutic options are very limited, especially if the tumor is detected late. This narrative review provides an extended overview of the present evidence in the literature regarding the epidemiology, diagnostic pathways and treatment approaches of the malignant pleural mesothelioma. The treatment of mesothelioma has evolved slowly over the last 20 years not only from a surgical point of view but also radiotherapy, chemotherapy and immunotherapy play nowadays a key role. Several surgical strategies are available ranging from extrapleural pneumonectomy to cytoreductive surgery but a multidisciplinary approach seems to be mandatory because a single approach has not proved to date to be resolutive. New non-surgical treatment options appear to be promising but the results have to be taken in account with caution because clear evidence with high-quality studies is still lacking.}, }
@article {pmid34008015, year = {2021}, author = {Cheung, M and Kadariya, Y and Sementino, E and Hall, MJ and Cozzi, I and Ascoli, V and Ohar, JA and Testa, JR}, title = {Novel LRRK2 mutations and other rare, non-BAP1-related candidate tumor predisposition gene variants in high-risk cancer families with mesothelioma and other tumors.}, journal = {Human molecular genetics}, volume = {}, number = {}, pages = {}, doi = {10.1093/hmg/ddab138}, pmid = {34008015}, issn = {1460-2083}, abstract = {There is irrefutable evidence that germline BAP1 mutations contribute to malignant mesothelioma (MM) susceptibility. However, BAP1 mutations are not found in all cases with evidence of familial MM or in other high-risk cancer families affected by various cancers, including MM. The goal of this study was to use whole genome sequencing (WGS) to determine the frequency and types of germline gene variants occurring in 12 MM patients selected from a series of 141 asbestos-exposed MM patients with a family history of cancer but without a germline BAP1 mutation. WGS was also performed on 2 MM cases, a proband and sibling, from a previously reported family with multiple cases of MM without inheritance of a predisposing BAP1 mutation. Altogether, germline DNA sequencing variants were identified in 20 cancer-related genes in 10 of the 13 probands. Germline indel, splice site, and missense mutations and two large deletions were identified. Among the 13 MM index cases, 6 (46%) exhibited one or more predicted pathogenic mutations. Affected genes encode proteins involved in DNA repair (ATM, ATR, BRCA2, BRIP1, CHEK2, MLH3, MUTYH, POLE, POLE4, POLQ, XRCC1), chromatin modification (ARID1B, DNMT3A, JARID2, SETD1B) or other cellular pathways: LRRK2 (2 cases) and MSH4. Notably, somatic truncating mutation or deletions of LRRK2 were occasionally found in MMs in The Cancer Genome Atlas, and expression of LRRK2 was undetectable or downregulated in a majority of primary MMs and MM cell lines we examined, implying that loss of LRRK2 expression is a newly recognized tumor suppressor alteration in MM.}, }
@article {pmid34000787, year = {2021}, author = {Wilk, E and Krówczyńska, M}, title = {Malignant mesothelioma and asbestos exposure in Europe: Evidence of spatial clustering.}, journal = {Geospatial health}, volume = {16}, number = {1}, pages = {}, doi = {10.4081/gh.2021.951}, pmid = {34000787}, issn = {1970-7096}, mesh = {Aged ; *Asbestos ; Cluster Analysis ; Europe/epidemiology ; Female ; Humans ; *Lung Neoplasms/epidemiology ; Male ; *Mesothelioma/epidemiology ; *Mesothelioma, Malignant ; Spatial Analysis ; Switzerland ; }, abstract = {Exposure to asbestos causes a wide range of diseases, such as asbestosis, malignant mesothelioma (MM) and other types of cancer. Many European countries have reduced production and use of asbestos and some have banned it altogether. Based on data derived from the World Health Organisation (WHO) Cancer Mortality Database, we investigated whether some regions in Europe could have a higher relative risk of MM incidence than others. The data were compared, including the number of MM deaths per million inhabitants and aged-standardized mortality rates. Applying Moran's I and Getis-Ord Gi statistic on the agedstandardized mortality rates of MM cases assisted the spatial analysis of the occurrence of health events leading to an assessment of the heterogeneity of distribution and cluster detection of MM. We found a statistically significant positive autocorrelation for the male population and also the general population, while there was no statistically significant positive one for the female population. Hotspots of relative risk of developing MM were found in northwestern Europe. For the general population, Great Britain and the Netherlands stood out with high levels at the 99% and 95% confidence levels, respectively. For the male population, the results were similar, but with addition of risk also in Belgium and Switzerland. However, in many European countries with high asbestos use per capita, the MM incidence was found to still be low. The reasons for this are not yet clear, but part of the problem is certainly due to incomplete data in registers and databases. The latency time can be longer than 40 years and is related to the intensity and time of exposure (occupational, para-occupational and environmental). In Europe, even though peak production occurred in the 1960s and 1970s, a significant decrease in production did not occur until 25 years later, which means that the impact will continue for as late as The mid 2030s.}, }
@article {pmid33998299, year = {2021}, author = {Tanrıverdi, Z and Meteroglu, F and Yüce, H and Şenyiğit, A and Işcan, M and Unüvar, S}, title = {The usefulness of biomarkers in diagnosis of asbestos-induced malignant pleural mesothelioma.}, journal = {Human &amp; experimental toxicology}, volume = {}, number = {}, pages = {9603271211017324}, doi = {10.1177/09603271211017324}, pmid = {33998299}, issn = {1477-0903}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a malignant tumor that is associated mostly with asbestos exposure. The present study was to evaluates the diagnostic value of neopterin, periostin, YKL-40, Tenascin-C (TNC), and Indolamine 2,3-dioxygenase (IDO) as noninvasive markers of malign pleural mesothelioma.<br><br>METHODS: Included in the study were 30 patients diagnosed with malign pleural mesothelioma, and 25 people as a control group. Biomarker levels were determined using an enzyme immunoassay . A Mann-Whitney U test and Spearman correlation methods were used for the statistical analysis.<br><br>RESULTS: All evaluated biomarkers were found to be significantly higher in the MPM group than in the control group (p < 0.05). There was no effect of such variables as gender, age or MPMsubtype on the parameters (p > 0.05) in the patient group. All biomarkers were positively correlated with each other (p < 0.001).<br><br>CONCLUSIONS: The current non-invasive biomarkers that can be used in the diagnosis of MPM yielded significant results and can make important contributions to the early diagnosis of MPM.}, }
@article {pmid33971174, year = {2021}, author = {Zhou, N and Rice, DC and Tsao, AS and Lee, PP and Haymaker, CL and Corsini, EM and Antonoff, MB and Hofstetter, WL and Rajaram, R and Roth, JA and Swisher, SG and Vaporciyan, AA and Walsh, GL and Mehran, RJ and Sepesi, B}, title = {Extrapleural Pneumonectomy versus Pleurectomy/Decortication for Malignant Pleural Mesothelioma.}, journal = {The Annals of thoracic surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.athoracsur.2021.04.078}, pmid = {33971174}, issn = {1552-6259}, abstract = {BACKGROUND: Whether extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D) is the optimal resection for malignant pleural mesothelioma (MPM) remains controversial. We therefore compared perioperative outcomes and long-term survival of patients who underwent EPP vs P/D.<br><br>METHODS: Patients with the diagnosis of MPM who underwent either EPP or P/D from 2000 to 2019 were identified from our departmental database. Propensity score matching was performed to minimize potential confounders for EPP or P/D. Survival analysis was performed by the Kaplan-Meier method and Cox multivariable analysis.<br><br>RESULTS: Of 282 patients, 187 (66%) underwent EPP and 95 (34%) P/D. Even with propensity score matching, perioperative mortality was significantly higher for EPP than for P/D (11% vs. 0%; P=0.031), when adjusted for perioperative mortality, median overall survival between EPP and P/D was 15 vs. 22 months, respectively (P=0.276). Cox multivariable analysis for the matched cohort identified epithelioid histology (hazard ratio [HR], 0.56; P=0.029), macroscopic complete resection (HR, 0.41; P=0.004), adjuvant radiation therapy (HR, 0.57; P=0.019), and more recent operative years (HR, 0.93; P=0.011)-but not P/D-to be associated with better survival. Asbestos exposure (HR, 2.35; P=0.003) and pathological nodal disease (HR, 1.61; P=0.048) were associated with worse survival.<br><br>CONCLUSIONS: In a multimodality treatment setting, P/D and EPP had comparable long-term oncological outcomes, although P/D had much lower perioperative mortality. The goal of surgical cytoreduction should be macroscopic complete resection achieved by the safest operation a patient can tolerate.}, }
@article {pmid33959504, year = {2021}, author = {Arrieta, O and Muñoz-Montaño, W and Muñiz-Hernández, S and Campos, S and Catalán, R and Soto-Molina, H and Guzmán Vázquez, S and Díaz-Álvarez, O and Martínez-Pacheco, V and Turcott, JG and Ramos-Ramírez, M and Cabrera-Miranda, L and Barrón, F and Cardona, AF}, title = {Efficacy, Safety, and Cost-Minimization Analysis of Continuous Infusion of Low-Dose Gemcitabine Plus Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {641975}, pmid = {33959504}, issn = {2234-943X}, abstract = {Background: Malignant pleural mesothelioma (MPM) is rare and aggressive neoplasia, with a poor prognosis; furthermore, the monetary cost of its treatment represents a major challenge for many patients. The economic burden this malignancy imposes is underscored by the fact that asbestos exposure, which is the most frequent risk factor, is much more prevalent in the lower socioeconomic population of developing countries. The aims of the present study were to evaluate the efficacy, safety, and cost of continuous infusion of low-dose Gemcitabine plus Cisplatin (CIGC) as a treatment strategy for patients with unresectable MPM.<br><br>Methods: We performed a prospective cohort study to determine efficacy and safety of continuous infusion gemcitabine at a dose of 250 mg/m2 in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 of a 21-day cycle in patients with unresectable MPM. We also performed a cost-minimization analysis to determine if this chemotherapy regimen is less expensive than other currently used regimens.<br><br>Results: The median number of chemotherapy cycles was six (range 1-11 cycles); objective response rate was documented in 46.2%, and disease control rate was seen in 81.2%. Median PFS was 8.05 months (CI 95% 6.97-9.13); median OS was 16.16 months (CI 95% 12.5-19.9). The cost minimization analysis revealed savings of 66.4, 61.9, and 97.7% comparing CIGC with short-infusion gemcitabine plus cisplatin (SIGC), cisplatin plus pemetrexed (CP), and cisplatin plus pemetrexed and bevacizumab (CPB), respectively. Furthermore, this chemotherapy regimen proved to be safe at the administered dosage.<br><br>Conclusion: CIGC is an effective and safe treatment option for patients with unresectable MPM; besides, this combination is a cost-saving option when compared with other frequently used chemotherapy schemes. Therefore, this treatment scheme should be strongly considered for patients with unresectable MPM and limited economic resources.}, }
@article {pmid33952230, year = {2021}, author = {Gray, SG}, title = {Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma.}, journal = {BMC pulmonary medicine}, volume = {21}, number = {1}, pages = {148}, pmid = {33952230}, issn = {1471-2466}, abstract = {BACKGROUND: The role of immunotherapy in cancer is now well-established, and therapeutic options such as checkpoint inhibitors are increasingly being approved in many cancers such as non-small cell lung cancer (NSCLC). Malignant pleural mesothelioma (MPM) is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Evidence from clinical trials of checkpoint inhibitors in this rare disease, suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer.<br><br>MAIN TEXT: While the majority of studies currently focus on the established checkpoint inhibitors (CTLA4 and PD1/PDL1), there are many other potential checkpoints that could also be targeted. In this review I provide a synopsis of current clinical trials of immunotherapies in MPM, explore potential candidate new avenues that may become future targets for immunotherapy and discuss aspects of immunotherapy that may affect the clinical outcomes of such therapies in this cancer.<br><br>CONCLUSIONS: The current situation regarding checkpoint inhibitors in the management of MPM whilst encouraging, despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Additional studies are therefore required to further delineate and improve our understanding of both checkpoint inhibitors and the immune system in MPM. Moreover, many new potential checkpoints have yet to be studied for their therapeutic potential in MPM. All these plus the existing checkpoint inhibitors will require the development of new biomarkers for patient stratification, response and also for predicting or monitoring the emergence of resistance to these agents in MPM patients. Other potential therapeutic avenues such CAR-T therapy or treatments like oncolytic viruses or agents that target the interferon pathway designed to recruit more immune cells to the tumor also hold great promise in this hard to treat cancer.}, }
@article {pmid33946118, year = {2021}, author = {Aigner, C and Brüning, T and Eberhardt, WEE and Härter, M and Kaelberlah, HP and Metzenmacher, M and Shah, R and Taube, C and Thomas, M}, title = {[The Current Therapy of Asbestos-Associated Malignant Pleural Mesothelioma - An Expert Consensus Paper].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-1404-1562}, pmid = {33946118}, issn = {1438-8790}, abstract = {Asbestos-related mesotheliomas belong to the group of the most frequent occupational diseases in Germany, reaching about 1,000 new cases per year. The disease has a dismal prognosis because most tumors remain asymptomatic for a long time and therefore are diagnosed as incidental findings at later stages.During the last decade the German Social Accident Insurance (DGUV) has made considerable efforts to prepone the diagnosis in order to detect the disease at earliest possible stages. These efforts resulted in new findings showing that, in a high-risk group, a combination of the biomarkers calretinin and mesothelin was able to advance the diagnosis up to 12 months.Ideally, the diagnosis of a mesothelioma at an early stage has to be accompanied by the best possible individualized therapy. Standard therapeutic strategies are surgery and chemotherapy, added by radiotherapy and psycho-oncology. In recent years, several new therapeutic avenues are being explored. This review comprehensively presents both old and new therapeutic options in mesothelioma, based on international Leitlinien and new studies.}, }
@article {pmid33945895, year = {2021}, author = {Ejegi-Memeh, S and Robertson, S and Taylor, B and Darlison, L and Tod, A}, title = {Gender and the experiences of living with mesothelioma: A thematic analysis.}, journal = {European journal of oncology nursing : the official journal of European Oncology Nursing Society}, volume = {52}, number = {}, pages = {101966}, doi = {10.1016/j.ejon.2021.101966}, pmid = {33945895}, issn = {1532-2122}, abstract = {PURPOSE: Mesothelioma is a terminal cancer caused by exposure to asbestos. As a cancer with a higher rate in men than women, women's experiences of living with mesothelioma are often underexplored. Furthermore, men's experiences are often taken for granted and therefore have remained underexplored. This paper considers men's and women's experiences across the mesothelioma pathway.<br><br>METHODS: This qualitative study incorporated semi-structured interviews with 13 men and 11 women living with mesothelioma. Telephone interviews took place between July and December 2019, and were audio recorded, transcribed and anonymised. Thematic analysis was used to analyse the data.<br><br>RESULTS: Three themes were developed in relation to the gendered experience of mesothelioma: familial responsibility and social perceptions; support preferences; and treatment and trials. Analysis suggests that men and women's sense of familial responsibility varied. Differences in priorities and motivations influenced approaches to seeking support, compensation and, making decisions around treatments and clinical trials.<br><br>CONCLUSIONS: The current study reports on how gender can influence the experience of living with mesothelioma. The findings indicate how the patients' role in their families and society can more broadly influence their experiences, choices and preferences. Nurses caring for mesothelioma patients need high quality research on which to base their practice. Recognition and an understanding of the underlyingfactors influencing patients' decision-making will enable nurses and other professionals to support their patients better.}, }
@article {pmid33945357, year = {2021}, author = {Davis, AP and Kao, SC and Clarke, SJ and Boyer, M and Pavlakis, N}, title = {Emerging biological therapies for the treatment of malignant pleural mesothelioma.}, journal = {Expert opinion on emerging drugs}, volume = {26}, number = {2}, pages = {179-192}, doi = {10.1080/14728214.2021.1924670}, pmid = {33945357}, issn = {1744-7623}, abstract = {Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occurred to develop immunotherapies and biomarker driven therapy to improve patient outcomes over this period.Areas covered: This review examines current standard of care systemic therapy in the first- and second line setting. The last 12 months has seen 2 significant trials (Checkmate 743 and CONFIRM) which provide evidence supporting the role of immunotherapy in the management of MPM. Further trials are underway to assess the role of combination chemoimmunotherapy and personalized therapy. Additionally, a large number of clinical trials are ongoing to assess the efficacy of oncoviral, dendritic cell, anti-mesothelin and chimeric antigen receptor T cell therapy in the treatment of MPM.Expert opinion: Recent Phase III trial results have established a role for immunotherapy in the management of MPM. The optimal sequencing and combination of chemotherapy and immunotherapy remains to be determined. Novel therapies for MPM are promising however efficacy remains to be determined and issues remain regarding access to and delivery of these therapies.}, }
@article {pmid33927865, year = {2021}, author = {Muralidhar, V}, title = {An unusual presentation of acute abdomen: infarcted peritoneal cyst-a probable asbestos-related benign cystic mesothelioma.}, journal = {Journal of surgical case reports}, volume = {2021}, number = {4}, pages = {rjab129}, pmid = {33927865}, issn = {2042-8812}, abstract = {This is a report of a rare case of an infarcted pelvic intra-abdominal cyst, having no mesenteric connection presenting as an acute abdomen. The patient had significant asbestos exposure. The cyst was treated successfully by surgical excision. Histopathology showed an infarcted cyst; the lining was destroyed, precluding marker studies. A diagnosis of benign cystic peritoneal mesothelioma (BCPM) was made by excluding other causes of solitary pelvic intra-abdominal cysts. BCPM has been classified as an asbestos-related neoplasm and is usually seen in the pelvis adjunct to the urinary bladder. One-year post-surgery, there was no recurrence. The case report shows that infarcted pelvic mesothelial cysts can present as an acute abdomen and can be treated successfully by total excision with no recurrence.}, }
@article {pmid33917061, year = {2021}, author = {Brcic, L and Mathilakathu, A and Walter, RFH and Wessolly, M and Mairinger, E and Beckert, H and Kreidt, D and Steinborn, J and Hager, T and Christoph, DC and Kollmeier, J and Mairinger, T and Wohlschlaeger, J and Schmid, KW and Borchert, S and Mairinger, FD}, title = {Digital Gene Expression Analysis of Epithelioid and Sarcomatoid Mesothelioma Reveals Differences in Immunogenicity.}, journal = {Cancers}, volume = {13}, number = {8}, pages = {}, pmid = {33917061}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with asbestos exposure. Median survival ranges from 14 to 20 months after initial diagnosis. As of November 2020, the FDA approved a combination of immune checkpoint inhibitors after promising intermediate results. Nonetheless, responses remain unsatisfying. Adequate patient stratification to improve response rates is still lacking. This retrospective study analyzed formalin fixed paraffin embedded specimens from a cohort of 22 MPM. Twelve of those samples showed sarcomatoid, ten epithelioid differentiation. Complete follow-up, including radiological assessment of response by modRECIST and time to death, was available with reported deaths of all patients. RNA of all samples was isolated and subjected to digital gene expression pattern analysis. Our study revealed a notable difference between epithelioid and sarcomatoid mesothelioma, showing differential gene expression for 304/698 expressed genes. Whereas antigen processing and presentation to resident cytotoxic T cells as well as phagocytosis is highly affected in sarcomatoid mesothelioma, cell-cell interaction via cytokines seems to be of greater importance in epithelioid cases. Our work reveals the specific role of the immune system within the different histologic subtypes of MPM, providing a more detailed background of their immunogenic potential. This is of great interest regarding therapeutic strategies including immunotherapy in mesothelioma.}, }
@article {pmid33910295, year = {2021}, author = {Li, N and Wang, D and Chen, ZJ and Mao, WM}, title = {[Asbestos-induced malignant peritoneal mesothelioma complicated with lung cancer:a case report].}, 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 = {39}, number = {4}, pages = {305-307}, doi = {10.3760/cma.j.cn121094-20200114-00029}, pmid = {33910295}, issn = {1001-9391}, support = {81672315//National Natural Science Foundation of China/ ; }, mesh = {*Asbestos/adverse effects ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Mesothelioma, Malignant ; *Occupational Exposure/adverse effects ; *Peritoneal Neoplasms ; }, abstract = {Asbestos is harmful to human, and populations with occupational and environmental exposure to respirable asbestos fibers have higher risk of cancers like malignant mesothelioma and lung cancer. At present, patient with asbestos-induced malignant peritoneal mesothelioma and lung cancer is rare. In this study, we analyzed the clinical data of a case of asbestos-induced malignant peritoneal mesothelioma complicated with lung cancer to investigate the diagnosis and treatment of this disease.}, }
@article {pmid33889258, year = {2021}, author = {Ouafki, I and Nouiakh, L and Boujarnija, R and Amarti, A and Amaadour, L and Oualla, K and Benbrahim, Z and Arifi, S and Mellas, N}, title = {[Malignant mesothelioma of the ovary: a case report].}, journal = {The Pan African medical journal}, volume = {38}, number = {}, pages = {92}, pmid = {33889258}, issn = {1937-8688}, mesh = {Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Mesothelioma, Malignant/*diagnosis/pathology/therapy ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms/*diagnosis/pathology/therapy ; Tomography, X-Ray Computed ; }, abstract = {Primary malignant mesothelioma of the ovary (PMMO) is an extremely rare tumor which can develop from mesothelial cells. This neoplasia is caused predominantly by exposure to asbestos or other cancer-causing agents. Preoperative assessment, based on computed tomography (CT) scan, magnetic resonance imaging and positron emission tomography, is essential for cancer staging. Anatomopathological diagnosis is based on immunohistochemical findings. PMMO is an exceptional disease involving a multidisciplinary therapeutic strategy including the use of chemotherapy which improves the management and prognosis of patients. This study reports the case of a female patient undergoing suboptimal surgery complemented by adjuvant chemotherapy with complete radiological response and 1-year disease-free survival.}, }
@article {pmid33874885, year = {2021}, author = {Kumagai-Takei, N and Nishimura, Y and Matsuzaki, H and Lee, S and Yoshitome, K and Ito, T and Otsuki, T}, title = {Effect of IL-15 addition on asbestos-induced suppression of human cytotoxic T lymphocyte induction.}, journal = {Environmental health and preventive medicine}, volume = {26}, number = {1}, pages = {50}, pmid = {33874885}, issn = {1347-4715}, support = {16K09114//Japan Society for the Promotion of Science/ ; 27B068//Kawasaki Medical School/ ; 28B008//Kawasaki Medical School/ ; }, mesh = {Asbestos/*adverse effects ; CD8-Positive T-Lymphocytes/cytology/drug effects/*immunology/metabolism ; Humans ; Interleukin-15/*pharmacology ; Lymphocyte Activation/*drug effects/immunology ; T-Lymphocytes, Cytotoxic/cytology/drug effects/*immunology/metabolism ; }, abstract = {BACKGROUND: Asbestos fibers possess tumorigenicity and are thought to cause mesothelioma. We have previously reported that exposure to asbestos fibers causes a reduction in antitumor immunity. Asbestos exposure in the mixed lymphocyte reaction (MLR) showed suppressed induction of cytotoxic T lymphocytes (CTLs), accompanied by a decrease in proliferation of CD8+ T cells. Recently, we reported that asbestos-induced suppression of CTL induction is not due to insufficient levels of interleukin-2 (IL-2). In this study, we continue to investigate the mechanism responsible for the effect of asbestos fibers on the differentiation of CTLs and focus on interleukin-15 (IL-15) which is known to be a regulator of T lymphocyte proliferation.<br><br>METHODS: For MLR, human peripheral blood mononuclear cells (PBMCs) were cultured with irradiated allogenic PBMCs upon exposure to chrysotile B asbestos at 5 μg/ml for 7 days. After 2 days of culture, IL-15 was added at 1 ng/ml. After 7 days of MLR, PBMCs were collected and analyzed for phenotypic and functional markers of CD8+ T cells with fluorescence-labeled anti-CD3, anti-CD8, anti-CD45RA, anti-CD45RO, anti-CD25, and anti-granzyme B antibodies using flow cytometry. To examine the effect of IL-15 on the expression level of intracellular granzyme B in proliferating and non-proliferating CD8+ lymphocytes, PBMCs were stained using carboxyfluorescein diacetate succinimidyl ester (CFSE) and then washed and used for the MLR.<br><br>RESULTS: IL-15 addition partially reversed the decrease in CD3+CD8+ cell numbers and facilitated complete recovery of granzyme B+ cell percentages. IL-15 completely reversed the asbestos-induced decrease in percentage of granzyme B+ cells in both non-proliferating CFSE-positive and proliferating CFSE-negative CD8+ cells. The asbestos-induced decrease in the percentage of CD25+ and CD45RO+ cells in CD8+ lymphocytes was not reversed by IL-15.<br><br>CONCLUSION: These findings indicate that CTLs induced upon exposure to asbestos possess dysfunctional machinery that can be partly compensated by IL-15 supplementation, and that IL-15 is more effective in the recovery of proliferation and granzyme B levels from asbestos-induced suppression of CTL induction compared with IL-2.}, }
@article {pmid33872411, year = {2021}, author = {Ezeka, G and Adhikary, G and Kandasamy, S and Friedberg, JS and Eckert, RL}, title = {Sulforaphane inhibits PRMT5 and MEP50 function to suppress the mesothelioma cancer cell phenotype.}, journal = {Molecular carcinogenesis}, volume = {60}, number = {7}, pages = {429-439}, doi = {10.1002/mc.23301}, pmid = {33872411}, issn = {1098-2744}, abstract = {Mesothelioma is a highly aggressive cancer of the mesothelial lining that is caused by exposure to asbestos. Surgical resection followed by chemotherapy is the current treatment strategy, but this is marginally successful and leads to drug-resistant disease. We are interested in factors that maintain the aggressive mesothelioma cancer phenotype as therapy targets. Protein arginine methyltransferase 5 (PRMT5) functions in concert with the methylosome protein 50 (MEP50) cofactor to catalyze symmetric dimethylation of key arginine resides in histones 3 and 4 which modifies the chromatin environment to alter tumor suppressor and oncogene expression and enhance cancer cell survival. Our studies show that PRMT5 or MEP50 loss reduces H4R3me2s formation and that this is associated with reduced cancer cell spheroid formation, invasion, and migration. Treatment with sulforaphane (SFN), a diet-derived anticancer agent, reduces PRMT5/MEP50 level and H4R3me2s formation and suppresses the cancer phenotype. We further show that SFN treatment reduces PRMT5 and MEP50 levels and that this reduction is required for SFN suppression of the cancer phenotype. SFN treatment also reduces tumor formation which is associated with reduced PRMT5/MEP50 expression and activity. These findings suggest that SFN may be a useful mesothelioma treatment agent that operates, at least in part, via suppression of PRMT5/MEP50 function.}, }
@article {pmid33834530, year = {2021}, author = {DeBono, NL and Warden, H and Logar-Henderson, C and Shakik, S and Dakouo, M and MacLeod, J and Demers, PA}, title = {Incidence of mesothelioma and asbestosis by occupation in a diverse workforce.}, journal = {American journal of industrial medicine}, volume = {64}, number = {6}, pages = {476-487}, doi = {10.1002/ajim.23245}, pmid = {33834530}, issn = {1097-0274}, abstract = {OBJECTIVE: We sought to characterize detailed patterns of mesothelioma and asbestosis incidence in the workforce as part of an occupational disease surveillance program in Ontario, Canada.<br><br>METHODS: The Occupational Disease Surveillance System (ODSS) cohort was established using workers' compensation claims data and includes 2.18 million workers employed from 1983 to 2014. Workers were followed for mesothelioma and asbestosis diagnoses in Ontario Cancer Registry, physician, hospital, and ambulatory care records through 2016. Trends in incidence rates were estimated over the study period. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).<br><br>RESULTS: A total of 854 mesothelioma and 737 asbestosis cases were diagnosed during follow-up. Compared with all other workers in the ODSS, those employed in construction trades occupations had the greatest adjusted incidence rate of both mesothelioma (223 cases; HR, 2.38; 95% CI: 2.03-2.78) and asbestosis (261 cases; HR, 3.64; 95% CI: 3.11-4.25). Rates were particularly elevated for insulators, pipefitters and plumbers, and carpenters. Workers in welding and flame cutting, boiler making, and mechanic and machinery repair occupations, as well as those in industrial chemical and primary metal manufacturing industries, had strongly elevated rates of both diseases. Rates were greater than anticipated for workers in electrical utility occupations and education and related services.<br><br>CONCLUSIONS: Results substantiate the risk of mesothelioma and asbestosis in occupation and industry groups in the Ontario workforce with known or suspected asbestos exposure. Sustained efforts to prevent the occurrence of additional cases of disease in high-risk groups are warranted.}, }
@article {pmid33816102, year = {2021}, author = {Mizuhashi, K and Okamoto, K and Kishimoto, T}, title = {A patient with epithelioid pleural mesothelioma (Myxoid variant) who survived for a long period without treatment.}, journal = {Respiratory medicine case reports}, volume = {33}, number = {}, pages = {101381}, pmid = {33816102}, issn = {2213-0071}, abstract = {Pleural mesothelioma is a disease with a very poor prognosis. Here, we report a mesothelioma patient who survived for 5 years and a half. As a result of the autopsy, the tumor was diagnosed as a myxoid variant, which is internationally proposed as a histological subtype of epithelioid mesothelioma with a relatively favorable prognosis. Since patients with this disease are expected to survive for a long period even without treatment, careful determination of the therapeutic approach is considered necessary. This report is considered to be the first of a myxoid variant epithelioid pleural mesothelioma in Japan.}, }
@article {pmid33804168, year = {2021}, author = {Barbarino, M and Giordano, A}, title = {Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System.}, journal = {Cancers}, volume = {13}, number = {6}, pages = {}, pmid = {33804168}, issn = {2072-6694}, abstract = {In 2014, the International Agency for Research on Cancer (IARC) classified the first type of carbon nanotubes (CNTs) as possibly carcinogenic to humans, while in the case of other CNTs, it was not possible to ascertain their toxicity due to lack of evidence. Moreover, the physicochemical heterogeneity of this group of substances hamper any generalization on their toxicity. Here, we review the recent relevant toxicity studies produced after the IARC meeting in 2014 on an homogeneous group of CNTs, highlighting the molecular alterations that are relevant for the onset of mesothelioma. Methods: The literature was searched on PubMed and Web of Science for the period 2015-2020, using different combinations keywords. Only data on normal cells of the respiratory system after exposure to fully characterized CNTs for their physico-chemical characteristics were included. Recent studies indicate that CNTs induce a sustained inflammatory response, oxidative stress, fibrosis and histological alterations. The development of mesothelial hyperplasia, mesothelioma, and lungs tumors have been also described in vivo. The data support a strong inflammatory potential of CNTs, similar to that of asbestos, and provide evidence that CNTs exposure led to molecular alterations known to have a key role in mesothelioma onset. These evidences call for an urgent improvement of studies on exposed human populations and adequate systems for monitoring the health of workers exposed to this putative carcinogen.}, }
@article {pmid33802313, year = {2021}, author = {Lettieri, S and Bortolotto, C and Agustoni, F and Lococo, F and Lancia, A and Comoli, P and Corsico, AG and Stella, GM}, title = {The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma.}, journal = {Journal of clinical medicine}, volume = {10}, number = {5}, pages = {}, pmid = {33802313}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. It has a strong association with exposure to biopersistent fibers, mainly asbestos (80% of cases) and-in specific geographic regions-erionite, zeolites, ophiolites, and fluoro-edenite. Individuals with a chronic exposure to asbestos generally have a long latency with no or few symptoms. Then, when patients do become symptomatic, they present with advanced disease and a worse overall survival (about 13/15 months). The fibers from industrial production not only pose a substantial risk to workers, but also to their relatives and to the surrounding community. Modern targeted therapies that have shown benefit in other human tumors have thus far failed in MPM. Overall, MPM has been listed as orphan disease by the European Union. However, molecular high-throughput profiling is currently unveiling novel biomarkers and actionable targets. We here discuss the natural evolution, mainly focusing on the novel concept of molecular epidemiology. The application of innovative endpoints, quantification of genetic damages, and definition of genetic susceptibility are reviewed, with the ultimate goal to point out new tools for screening of exposed subject and for designing more efficient diagnostic and therapeutic strategies.}, }
@article {pmid33799965, year = {2021}, author = {Schiavello, M and Gazzano, E and Bergandi, L and Silvagno, F and Libener, R and Riganti, C and Aldieri, E}, title = {Identification of Redox-Sensitive Transcription Factors as Markers of Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {5}, pages = {}, pmid = {33799965}, issn = {2072-6694}, abstract = {Although asbestos has been banned in most countries around the world, malignant pleural mesothelioma (MPM) is a current problem. MPM is an aggressive tumor with a poor prognosis, so it is crucial to identify new markers in the preventive field. Asbestos exposure induces oxidative stress and its carcinogenesis has been linked to a strong oxidative damage, event counteracted by antioxidant systems at the pulmonary level. The present study has been focused on some redox-sensitive transcription factors that regulate cellular antioxidant defense and are overexpressed in many tumors, such as Nrf2 (Nuclear factor erythroid 2-related factor 2), Ref-1 (Redox effector factor 1), and FOXM1 (Forkhead box protein M1). The research was performed in human mesothelial and MPM cells. Our results have clearly demonstrated an overexpression of Nrf2, Ref-1, and FOXM1 in mesothelioma towards mesothelium, and a consequent activation of downstream genes controlled by these factors, which in turn regulates antioxidant defense. This event is mediated by oxidative free radicals produced when mesothelial cells are exposed to asbestos fibers. We observed an increased expression of Nrf2, Ref-1, and FOXM1 towards untreated cells, confirming asbestos as the mediator of oxidative stress evoked at the mesothelium level. These factors can therefore be considered predictive biomarkers of MPM and potential pharmacological targets in the treatment of this aggressive cancer.}, }
@article {pmid33792699, year = {2021}, author = {Fujihira, H and Takakura, D and Matsuda, A and Abe, M and Miyazaki, M and Nakagawa, T and Kajino, K and Denda-Nagai, K and Noji, M and Hino, O and Irimura, T}, title = {Bisecting-GlcNAc on Asn388 is characteristic to ERC/mesothelin expressed on epithelioid mesothelioma cells.}, journal = {Journal of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1093/jb/mvab044}, pmid = {33792699}, issn = {1756-2651}, abstract = {Mesothelioma is a highly aggressive tumor associated with asbestos exposure and is histologically classified into three types: epithelioid-type, sarcomatoid-type, and biphasic-type. The prognosis of mesothelioma patients is poor and there is no effective molecular-targeting therapy as yet. ERC/mesothelin is a glycoprotein that is highly expressed on several types of cancers including epithelioid mesothelioma, but also expressed on normal mesothelial cells. This is a predicted reason why there is no clinically approved therapeutic antibody targeting ERC/mesothelin. In the present study, we focused on the differential glycosylation between ERC/mesothelin present on epithelioid mesothelioma and that on normal mesothelial cells and aimed to reveal a distinct feature of epithelioid mesothelioma cells. Lectin microarray analysis of ERC/mesothelin using cells and patient specimens showed significantly stronger binding of PHA-E4 lectin, which recognizes complex-type N-glycans having a so-called bisecting-GlcNAc structure, to ERC/mesothelin from epithelioid mesothelioma cells than that from normal mesothelial cells. Further, LC/MS analysis on ERC/mesothelin from epithelioid mesothelioma cells confirmed the presence of a bisecting-GlcNAc attached to Asn388 of ERC/mesothelin. These results suggest that this glycoproteome could serve as a potential target for the generation of a highly selective and safe therapeutic antibody for epithelioid mesothelioma.}, }
@article {pmid33781046, year = {2021}, author = {Huang, XY and Ye, Q}, title = {[Asbestos exposure and asbestos-related malignant diseases:an epidemiological review].}, 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 = {39}, number = {3}, pages = {233-236}, doi = {10.3760/cma.j.cn121094-20200226-00089}, pmid = {33781046}, issn = {1001-9391}, support = {2019-XZ-70//Consutting Research Project of Chinese Academy of Engineering/ ; Z181100001718118//Capital Clinical Character1stic Application Research/ ; }, mesh = {*Asbestos/adverse effects ; Carcinogens/toxicity ; Humans ; *Lung Neoplasms/chemically induced/epidemiology ; *Mesothelioma/chemically induced/epidemiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; }, abstract = {Asbestos has high fire resistance, electrical insulation and thermal insulation. It is an important fire prevention, insulation and insulation material. It is widely used in industrial production and daily life. In 1987, the international agency for research on cancer (IARC) has listed asbestos as a class I carcinogen; in 2012, IARC confirmed that all types of asbestos have carcinogenic effect. By 2019, asbestos has been banned in 66 countries and regions around the world. Asbestos exposure increases the risk of human malignant tumor. Lung cancer and mesothelioma are known asbestos induced tumors. Epidemiological studies also support that asbestos exposure is related to the incidence of malignant tumors in reproductive system, digestive system, urinary system, nasopharynx head and neck. We summarized the epidemiological studies of asbestos induced tumors in order to provide reference for further research.}, }
@article {pmid33778549, year = {2020}, author = {Gill, RR and Murphy, DJ and Seethamraju, RT and Mazzola, E and Bueno, R and Richards, WG}, title = {Interobserver Variability of Quantitative and Qualitative Assessment Using MRI in Malignant Pleural Mesothelioma.}, journal = {Radiology. Cardiothoracic imaging}, volume = {2}, number = {2}, pages = {e190066}, pmid = {33778549}, issn = {2638-6135}, abstract = {Purpose: To evaluate the interobserver variability associated with quantitative and qualitative MRI assessments of malignant pleural mesothelioma (MPM).<br><br>Materials and Methods: Patients with MPM who underwent uniform-protocol preoperative MRI between 2009 and 2014 were included. The MRI-derived tumor volume was estimated. Unidimensional measurements of maximal pleural thickness (P max) and average pleural thickness (P avg) on axial MR images; maximal fissural thickness (F max); maximal diaphragmatic thickness (D max); and average diaphragmatic thickness (D avg) on sagittal reconstructed images were acquired. Interobserver agreement regarding the American Joint Committee on Cancer (AJCC) tumor stage at each criterion level was assessed by using Cohen κ statistics. Agreement between quantitative measurements was assessed by using Bland-Altman plots and intraclass correlation coefficients (ICCs).<br><br>Results: The study cohort included 349 patients (median age, 68 years [age range, 30-90 years), 273 (78%) of whom were men and 203 (58%) of whom had epithelioid-subtype tumors. Qualitative assessment performed by using the AJCC staging criteria (eighth edition) was concordant in 31% of cases and yielded considerable disagreement (κ = 0.177). Inspection of the Bland-Altman plots led to decisive agreement between the two reviewers regarding MRI-derived tumor volume (ICC, 0.979). There was also a good degree of agreement between the two reviewers regarding unidimensional measurements of D max (ICC, 0.807), D avg (ICC, 0.823), P max (ICC, 0.787), P avg (ICC, 0.787), and F max (ICC, 0.659).<br><br>Conclusion: Quantitative assessment can enhance the clinical staging of MPM. Compared with qualitative assessment, quantitative assessment has low interobserver variability and could yield a tumor size criterion that is currently lacking in the AJCC clinical staging of MPM.Supplemental material is available for this article.© RSNA, 2020.}, }
@article {pmid33775406, year = {2021}, author = {Klebe, S and Nakatani, Y and Dobra, K and Butnor, KJ and Roden, AC and Nicholson, AG and Marchevsky, AM and Husain, AN and Segal, A and Walts, AE and Weynand, B and Michael, CW and Dacic, S and Godbolt, D and Attanoos, R and Santoni-Rugiu, E and Galateau-Salle, F and Hiroshima, K and Moreira, AL and Burn, J and Nabeshima, K and Gibbs, AR and Churg, A and Litzky, LA and Brcic, L and Tsao, MS and Mino-Kenudson, M and Rørvig, SB and Tazelaar, HD and Krausz, T and Zhang, YZ and Chirieac, LR and Beasley, MB and Hjerpe, A}, title = {The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis.}, journal = {Pathology}, volume = {53}, number = {4}, pages = {446-453}, doi = {10.1016/j.pathol.2020.12.005}, pmid = {33775406}, issn = {1465-3931}, abstract = {Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines. Whilst the WHO restricts the diagnosis to surgical samples, the very concept has implication for cytological diagnosis, which is already regarded as controversial in itself by some. MMIS is currently only applicable as precursor to MM with an epithelioid component, and raises the possibility for different molecular pathways for different histological MM subtypes. The clinical implications of MMIS at this stage are uncertain, but aggressive therapies are being initiated in some instances. Based on the results of the survey we here present a critical appraisal of the concept, its clinical and conceptual implications and provide practice suggestions for diagnosis. A low threshold for ancillary testing is suggested. The designations of 'malignant mesothelioma, cannot exclude MMIS' or 'atypical mesothelial proliferation with molecular indicators of malignancy, so-called MMIS' could be used on cytology samples, adding 'no evidence of invasion in sample provided' for surgical samples. Clinical and radiological correlation are integral to diagnosis and best done at multidisciplinary meetings. Finally, collaborative studies are required to improve our understanding of MMIS.}, }
@article {pmid33749247, year = {2021}, author = {Reid, G and Klebe, S and van Zandwijk, N and George, AM}, title = {Asbestos and Zeolites: from A to Z via a Common Ion.}, journal = {Chemical research in toxicology}, volume = {34}, number = {4}, pages = {936-951}, doi = {10.1021/acs.chemrestox.0c00286}, pmid = {33749247}, issn = {1520-5010}, abstract = {Asbestos and zeolites are silicate-based minerals, linked inextricably via paradoxical similarities and differences which have emanated from different geological epochs. Both have been employed in the service of humanity through millennia: asbestos, for its "inextinguishable" quality of being an insulator against heat and fire; zeolite, a "boiling stone" with its volcanic and marine sedimentary rock origins, for its propensity to adsorb water and remove metals and toxins. Serious adverse health effects observed in asbestos miners as long ago as the 1st Century AD did not halt the rising popularity of asbestos. As the miracle material of the 1900s, asbestos production and consumption exploded, culminating in its ubiquity in ships, vehicles, homes, commercial buildings, and over 3000 different industrial and household products. Through the 1940s and 1950s, epidemiological studies concluded that asbestos was a likely cause of asbestosis, lung cancer, and malignant mesothelioma, and it is now banned in many but far from all countries. The long latency between exposure to asbestos and the occurrence of cancer has obscured the deadly consequences of asbestos exposure for centuries. Even today, a considerable part of the world population is insufficiently aware of the dangers of asbestos, and millions of tons of this carcinogen continue to be mined and used worldwide. Zeolites, both natural and synthetic, are microporous aluminosilicate minerals commonly used in a myriad of processes, in the petrochemical industry, in domestic appliances and cleaning agents, as commercial adsorbents and exchangers for toxins and pollutants, and as catalysts. Zeolites are found in agriculture, veterinary science, and human health. More recently, new materials such as carbon nanotubes are being employed in materials requiring durability and thermal and electrical conductivity, yet nanotubes are now joining the ranks of more established particulates such as asbestos and silica, in causing human disease. In this review, we compare and contrast the similarities and differences of these two groups of silicate minerals and their waxing and waning use in the employ of humanity.}, }
@article {pmid33741915, year = {2021}, author = {Zhang, M and Luo, JL and Sun, Q and Harber, J and Dawson, AG and Nakas, A and Busacca, S and Sharkey, AJ and Waller, D and Sheaff, MT and Richards, C and Wells-Jordan, P and Gaba, A and Poile, C and Baitei, EY and Bzura, A and Dzialo, J and Jama, M and Le Quesne, J and Bajaj, A and Martinson, L and Shaw, JA and Pritchard, C and Kamata, T and Kuse, N and Brannan, L and De Philip Zhang, P and Yang, H and Griffiths, G and Wilson, G and Swanton, C and Dudbridge, F and Hollox, EJ and Fennell, DA}, title = {Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1751}, pmid = {33741915}, issn = {2041-1723}, support = {C61811/A24218/CRUK_/Cancer Research UK/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {*Chromosome Deletion ; Clone Cells/metabolism/pathology ; Cluster Analysis ; Cohort Studies ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; *Mutation ; Pleural Neoplasms/*genetics ; Prognosis ; Tumor Microenvironment/genetics ; Tumor Suppressor Proteins/classification/*genetics ; Whole Exome Sequencing/methods ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20-50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/-3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/-22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition.}, }
@article {pmid33718042, year = {2021}, author = {Schiopu, SRI and Käsmann, L and Schönermarck, U and Fischereder, M and Grabmaier, U and Manapov, F and Rauch, J and Orban, M}, title = {Pembrolizumab-induced myocarditis in a patient with malignant mesothelioma: plasma exchange as a successful emerging therapy-case report.}, journal = {Translational lung cancer research}, volume = {10}, number = {2}, pages = {1039-1046}, pmid = {33718042}, issn = {2218-6751}, abstract = {Malignant mesothelioma is an aggressive cancer associated with prior exposure to asbestos and dismal prognosis. Immune checkpoint inhibitor therapy is currently approved by the Food and Drug Administration for pre-treated malignant pleural mesothelioma. We describe a 75-year-old patient with disseminated, progressive malignant mesothelioma receiving 2 cycles of pembrolizumab who presented with generalized muscle weakness, shortness of breath, double vision and ptosis. There was no previous history of cardiovascular disease. The clinical picture, supported by the detection of anti-titin autoantibodies suggested myasthenia gravis (MG). Also, cardiac biomarkers were elevated. Echocardiography showed new severely reduced ejection fraction. A 12-lead resting electrocardiogram (ECG) revealed ST segment elevation in the posterior leads with polymorphic ventricular extrasystoles. Because cardiac catheterization revealed no relevant coronary lesions, immune checkpoint inhibitor-associated myocarditis and MG were suspected. Management and Outcome: The patient was started on steroids. Within a few days of presentation respiratory failure set in and the patient was intubated. Recurrent arrhythmias followed, which were treated by repeated emergency electrical cardioversion. In order to relieve myasthenic symptoms, plasma exchange was initiated and 10 cycles were carried out. This consequently also led to an improvement of myocarditis. Upon discharge, the ejection fraction recovered. The patient recovered and was alive at 1-year follow-up, without relevant limitations to his quality of life. Discussion and Conclusion: The article further discusses the use of plasma exchange for immune checkpoint inhibitor-associated myocarditis based on a review of literature. We conclude that patients showing no improvement after steroid therapy for immune checkpoint inhibitor-related myocarditis should be evaluated for plasma exchange, which appears to be an effective treatment option.}, }
@article {pmid33713739, year = {2021}, author = {Sun, S and Frontini, F and Qi, W and Hariharan, A and Ronner, M and Wipplinger, M and Blanquart, C and Rehrauer, H and Fonteneau, JF and Felley-Bosco, E}, title = {Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development.}, journal = {Cancer letters}, volume = {507}, number = {}, pages = {26-38}, doi = {10.1016/j.canlet.2021.03.004}, pmid = {33713739}, issn = {1872-7980}, abstract = {Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV ("MesoERV1-12") were identified and verified by qPCR in mouse tissues. "MesoERV1-12" expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. "MesoERV1-12" levels were significantly increased by demethylating agent 5-Aza-2'-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. "MesoERV7" promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy.}, }
@article {pmid33692175, year = {2021}, author = {Shamseddin, M and Obacz, J and Garnett, MJ and Rintoul, RC and Francies, HE and Marciniak, SJ}, title = {Use of preclinical models for malignant pleural mesothelioma.}, journal = {Thorax}, volume = {}, number = {}, pages = {}, doi = {10.1136/thoraxjnl-2020-216602}, pmid = {33692175}, issn = {1468-3296}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12-18 months, since surgery is ineffective and chemotherapy offers minimal benefit. Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are critical for the development of new treatments. The most commonly used models of MPM are two-dimensional cell lines established from primary tumours or pleural fluid. While these have provided some important insights into MPM biology, these cell models have significant limitations. In order to address some of these limitations, spheroids and microfluidic chips have more recently been used to investigate the role of the three-dimensional environment in MPM. Efforts have also been made to develop animal models of MPM, including asbestos-induced murine tumour models, MPM-prone genetically modified mice and patient-derived xenografts. Here, we discuss the available in vitro and in vivo models of MPM and highlight their strengths and limitations. We discuss how newer technologies, such as the tumour-derived organoids, might allow us to address the limitations of existing models and aid in the identification of effective treatments for this challenging-to-treat disease.}, }
@article {pmid33691361, year = {2021}, author = {Yu, M and Yu, M and Zhu, LJ and Yuan, XY and Zhang, X}, title = {[Expression and clinical significance of SETD2 in maligant pleural mesothelioma].}, 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 = {39}, number = {2}, pages = {91-98}, doi = {10.3760/cma.j.cn121094-20200831-00505}, pmid = {33691361}, issn = {1001-9391}, support = {11-ZC02//The Key Program of Zhejiang Medical Science: Occupational Health Sciences/ ; 2019D002//The Funding of Zhejiang Academy of Medical Sciences/ ; }, mesh = {*Asbestos ; Histone-Lysine N-Methyltransferase ; Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/genetics ; *Mesothelioma, Malignant ; *Pleural Neoplasms/genetics ; Protein-Serine-Threonine Kinases ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {Objective: To analyze the gene mutation profile in malignant pleural mesothelioma (MPM) and investigate the expression of high-frequency mutant genes and its relationship with clinicopathological parameters. To screen out key genes and clinicopathologic factors related to the prognosis of MPM patients. Methods: The second generation sequencing data, somatic mutation data and clinical pathological data of 86 MPM cases and gene chip expression data of 89 MPM cases were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) in March 2020. Summarize the gene mutation profile of tissue samples in the TCGA database and analyze the relationship between the expression level of high-frequency mutation genes and the clinicopathological characteristics, asbestos exposure history and prognosis of MPM patients. The genes significantly related to MPM prognosis were screened out for gene set enrichment analysis (GSEA) . Survival analysis and GSEA were performed for the selected key genes and clinicopathological features verification using the microarray expression data from the GEO database. Results: The top 10 genes with highest single nucleotide variations frequencies were BAP1, NF2, TP53, TTN, SETD2, LATS2, CCDC168, FAT4, PTCH1 and ZNF469. The high expression rates of NF2, TP53, SETD2 and CCDC168 genes in wild type were higher than those of mutated type, and the differences were statistically significant (P<0.05) . Cox multivariate analysis of TCGA data showed that MPM patients with epithelial type (HR=0.425, 95%CI: 0.235-0.767, P<0.01) and SETD2 low expression (HR=0.516, 95%CI: 0.307-0.868, P=0.011) had lower risk of death. The survival analysis of GEO data verified that patients with epithelial type MPM had longer survival time, while patients with sarcoma type MPM had shortest survival time (P<0.01) . GSEA showed that SETD2 was involved in G2M checkpoint, E2F targets, MYC signaling pathways, protein secretion, mitotic spindle, MTORC1 pathway, TGF-β pathway, androgen response and uv response. Conclusion: MPM is accompanied with higher frequency of gene mutations represented by BAP1, NF2, TP53, TTN, SETD2, LATS2 and so on. SETD2 expression level and epithelia type of MPM may be influential factors for MPM prognosis.}, }
@article {pmid33691360, year = {2021}, author = {Yu, M and Yu, M and Ying, SB and Yuan, XY and Jiang, ZQ and Lou, JL and Zhu, LJ and Zhang, X}, title = {[The impact of CD8 and CTLA-4 expression on histopathological character and survival in mesothelioma].}, 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 = {39}, number = {2}, pages = {85-90}, doi = {10.3760/cma.j.cn121094-20200831-00506}, pmid = {33691360}, issn = {1001-9391}, support = {2017183851//The Project of Zhejiang Medical &amp; Health Science/ ; 2019D002//The Funding of Zhejiang Academy of Medical Sciences/ ; 11-ZC02//The Key Program of Zhejiang Medical Science: Occupational Health Sciences/ ; }, mesh = {CD8-Positive T-Lymphocytes ; CTLA-4 Antigen ; Humans ; Ki-67 Antigen ; *Mesothelioma ; *Mesothelioma, Malignant ; Retrospective Studies ; }, abstract = {Objective: To investigate the survival and death risk factors of mesothelioma cases stratified by the expression levels of CD8 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) , providing new clue to evaluate disease progression and clinical outcome. Methods: This was a retrospective case report, which included 47 clinically and pathologically confirmed mesothelioma cases on November 2016. Their clinical and pathological information, asbestos exposure history and survival data were collected. Infiltrated lymphocyte, 5-methylcytosine (5-mC) , CTLA-4, CD8 and Ki-67 antigen were detected using hematoxylin-eosin staining and immunohistochemistry. Survival time and death risk factors of mesothelioma patients with different CD8 and CTLA-4 protein expression characteristics were analyzed. And analyze the influence of Ki-67 expression on the survival of patients with different CD8 and CTLA-4 protein and gene expression characteristics. Results: Among the 47 cases, 63.8% (30/47) had low/medium level of infiltrated lymphocyte. The immunohistochemistry scores of CTLA-4, CD8, 5-mC and Ki-67 were 92.97 (54.95, 120.65) , 72.41 (36.62, 89.82) , 11.09 (3.40, 52.89) and 5.88 (2.41, 11.48) , respectively. Patients with CD8(high) CTLA-4(high) had higher 5-mC level than those with CD8(high) CTLA-4(low) (P<0.01) . The median survival time of 27 cases was 0.83±0.29 year. The median survival times of those with CD8(high) CTLA-4(high) and CD8(high) CTLA-4(low) were 0.58±0.51 year and 0.83±0.30 year, respectively (P=0.521) . The immunohistochemistry score of Ki-67 ≥5.88 was an independent death risk factor for patients with CD8(high) CTLA-4(low) (HR=8.40, P=0.01) . Under different CD8 and CTLA-4 protein expression characteristics, in the patients with CD8(high) CTLA-4(low), the median survival times of those with high and low Ki-67 expression were 0.57±0.11 years and 2.31±0.46 years, respectively (P<0.01) . Under different CD8 and CTLA-4 mRNA expression characteristics, in the patients with CD8(high) CTLA-4(low), the median survival times of those with high and low Ki-67 mRNA expression were 1.20±0.36 years and 3.38±0.43 years, respectively (P=0.018) . Conclusion: Mesothelioma case with high CD8 but low CTLA-4 content might coexist DNA hypomethylation. In the presence of high Ki-67 expression, their survival time appears to be shortened with increased death risk.}, }
@article {pmid33691359, year = {2021}, author = {Zhang, X}, title = {[Indispensable urgency for prevention and control of asbestos-related cancer].}, 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 = {39}, number = {2}, pages = {81-84}, doi = {10.3760/cma.j.cn121094-20200831-00504}, pmid = {33691359}, issn = {1001-9391}, mesh = {*Asbestos ; *Asbestosis ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Neoplasms ; *Occupational Exposure ; }, }
@article {pmid33691040, year = {2021}, author = {García López, V}, title = {[Programs for Asbestos Abatement. Lessons from Poland].}, journal = {Archivos de prevencion de riesgos laborales}, volume = {24}, number = {1}, pages = {62-73}, doi = {10.12961/aprl.2021.24.01.06}, pmid = {33691040}, issn = {1578-2549}, mesh = {*Asbestos/adverse effects/analysis ; Europe ; Humans ; *Mesothelioma/epidemiology/etiology/prevention &amp; control ; *Occupational Exposure/prevention &amp; control ; Poland ; Spain ; }, abstract = {The commercialization of asbestos in Europe in the second half of the 20th century translated into consumption of millions of tons of this material. Occupational exposure to asbestos is controlled under the 2009 European Union Directive. Currently, through epidemiological surveillance and pathology registries (mainly mesotheliomas), it is possible to record past exposures. Despite prohibiting its use, large amounts of asbestos remain in buildings, infrastructures and vehicles, among others. The road to elimination of existing asbestos began with a 2013 European Parliament Resolution and the Opinion of the European Economic and Social Committee (2015 / C 251/03).To better understand barriers to implementing these plans, we reviewed the experience in Poland the only country that to date has implemented an action plan with great financial support, together with actions carried out in Spain generally, and Navarre specifically, given the latter's exhaustive registry of exposed workers.The enormous economic effort required to implement these plans, along with the environmental risks associated with asbestos abatement, require detailed planning, which should consider understanding why the objectives set by Poland, a benchmark country, have not been achieved to date.}, }
@article {pmid33678145, year = {2021}, author = {Carey, RN and Pfau, JC and Fritzler, MJ and Creaney, J and de Klerk, N and W Bill Musk, A and Franklin, P and Sodhi-Berry, N and Brims, F and Reid, A}, title = {Autoantibodies and cancer among asbestos-exposed cohorts in Western Australia.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {84}, number = {11}, pages = {475-483}, doi = {10.1080/15287394.2021.1889424}, pmid = {33678145}, issn = {1528-7394}, abstract = {Asbestos exposure is associated with many adverse health conditions including malignant mesothelioma and lung cancer as well as production of autoantibodies. Autoantibodies may serve as biomarkers for asbestos exposure in patients with cancer, and autoimmune dysfunction has been linked to increased rates of various cancers. The aim of this study was to examine the hypothesis that autoantibodies are more frequent in asbestos-exposed individuals with either lung cancer or mesothelioma than those without these conditions. Asbestos-exposed individuals from Western Australia who had lung cancer (n = 24), malignant mesothelioma (n = 24), or no malignancy (n = 51) were tested for antinuclear autoantibodies (ANA) using indirect immunofluorescence and specific extractable nuclear autoantibodies (ENA) employing a multiplexed addressable laser bead immunoassay. Contrary to the hypothesis, data demonstrated that individuals without malignancy were more likely to be positive for ANA compared to those with cancer. However, autoantibodies to histone and Ro-60 were found to be associated with lung cancer. These results support a possible predictive value for specific autoantibodies in the early detection of lung cancer and/or in our understanding of the role of autoimmune processes in cancer. However, further studies are needed to identify specific target antigens for the antibodies.}, }
@article {pmid33673264, year = {2021}, author = {Arachi, D and Furuya, S and David, A and Mangwiro, A and Chimed-Ochir, O and Lee, K and Tighe, P and Takala, J and Driscoll, T and Takahashi, K}, title = {Development of the "National Asbestos Profile" to Eliminate Asbestos-Related Diseases in 195 Countries.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33673264}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Income ; *Mesothelioma ; World Health Organization ; }, abstract = {Worldwide, 230,000+ people die annually from asbestos-related diseases (ARDs). The World Health Organization (WHO) recommends that countries develop a National Asbestos Profile (NAP) to eliminate ARDs. For 195 countries, we assessed the global status of NAPs (A: bona fide NAP, B: proxy NAP, C: relevant published information, D: no relevant information) by national income (HI: high, UMI: upper-middle, LMI: lower-middle, LI: low), asbestos bans (banned, no-ban) and public data availability. Fourteen (7% of 195) countries were category A (having a bona fide NAP), while 98, 51 and 32 countries were categories B, C and D, respectively. Of the 14 category-A countries, 8, 3 and 3 were LMI, UMI and HI, respectively. Development of a bona fide NAP showed no gradient by national income. The proportions of countries having a bona fide NAP were similar between asbestos-banned and no-ban countries. Public databases useful for developing NAPs contained data for most countries. Irrespective of the status of national income or asbestos ban, most countries have not developed a NAP despite having the potential. The global status of NAP is suboptimal. Country-level data on asbestos and ARDs in public databases can be better utilized to develop NAPs for globally eliminating ARDs.}, }
@article {pmid33669843, year = {2021}, author = {Visonà, SD and Capella, S and Bodini, S and Borrelli, P and Villani, S and Crespi, E and Frontini, A and Colosio, C and Belluso, E}, title = {Inorganic Fiber Lung Burden in Subjects with Occupational and/or Anthropogenic Environmental Asbestos Exposure in Broni (Pavia, Northern Italy): An SEM-EDS Study on Autoptic Samples.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33669843}, issn = {1660-4601}, mesh = {*Asbestos ; Environmental Exposure ; Humans ; Italy/epidemiology ; Lung ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Exposure/adverse effects ; Tumor Microenvironment ; }, abstract = {Increased mortality due to malignant mesothelioma has been demonstrated by several epidemiologic studies in the area around Broni (a small town in Lombardy, northern Italy), where a factory producing asbestos cement was active between 1932 and 1993. Until now, the inorganic fiber burden in lungs has not been investigated in this population. The aim of this study is to assess the lung fiber burden in 72 individuals with previous occupational and/or anthropogenic environmental exposure to asbestos during the activity of an important asbestos cement factory. Inorganic fiber lung burden was assessed in autoptic samples taken from individuals deceased from asbestos-related diseases using a scanning electron microscope equipped with an energy-dispersive spectrometer. Significant differences in the detected amount of asbestos were pointed out among the three types of exposure. In most lung samples taken from patients who died of mesothelioma, very little asbestos (or, in some cases, no fibers) was found. Such subjects showed a significantly lower median amount of asbestos as compared to asbestosis. Almost no chrysotile was detected in the examined samples. Overall, crocidolite was the most represented asbestos, followed by amosite, tremolite/actinolite asbestos, and anthophyllite asbestos. There were significant differences in the amount of crocidolite and amosite fibers according to the kind of exposure. Overall, these findings provide novel insights into the link between asbestos exposure and mesothelioma, as well as the different impacts of the various types of asbestos on human health in relation to their different biopersistences in the lung microenvironment.}, }
@article {pmid33669318, year = {2021}, author = {Gariazzo, C and Binazzi, A and Alfò, M and Massari, S and Stafoggia, M and Marinaccio, A}, title = {Predictors of Lung Cancer Risk: An Ecological Study Using Mortality and Environmental Data by Municipalities in Italy.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33669318}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Cities ; Environmental Exposure/adverse effects ; Female ; Humans ; Italy/epidemiology ; *Lung Neoplasms/epidemiology/etiology ; Male ; *Mesothelioma/epidemiology ; *Occupational Exposure ; }, abstract = {Lung cancer (LC) mortality remains a consistent part of the total deaths occurring worldwide. Its etiology is complex as it involves multifactorial components. This work aims in providing an epidemiological assessment on occupational and environmental factors associated to LC risk by means of an ecological study involving the 8092 Italian municipalities for the period 2006-2015. We consider mortality data from mesothelioma as proxy of asbestos exposure, as well as PM2.5 and radon levels as a proxy of environmental origin. The compensated cases for occupational respiratory diseases, urbanization and deprivation were included as predictors. We used a negative binomial distribution for the response, with analysis stratified by gender. We estimated that asbestos is responsible for about 1.1% (95% CI: 0.8, 1.4) and 0.5% (95% CI: 0.2, 0.8) of LC mortality in males and females, respectively. The corresponding figures are 14.0% (95% CI: 12.5, 15.7) and 16.3% (95% CI: 16.2, 16.3) for PM2.5 exposure, and 3.9% (95% CI: 3.5, 4.2) and 1.6% (95% CI: 1.4, 1.7) for radon exposure. The assessment of determinants contribution to observed LC deaths is crucial for improving awareness of its origin, leading to increase the equity of the welfare system.}, }
@article {pmid33668103, year = {2021}, author = {Wortzel, JD and Wiebe, DJ and Elahi, S and Agawu, A and Barg, FK and Emmett, EA}, title = {Ascertainment Bias in a Historic Cohort Study of Residents in an Asbestos Manufacturing Community.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {5}, pages = {}, pmid = {33668103}, issn = {1660-4601}, support = {P42 ES023720/NH/NIH HHS/United States ; P30 ES013508/NH/NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Asbestos ; Cohort Studies ; Environmental Exposure ; Female ; Humans ; *Lung Neoplasms ; *Mesothelioma ; Middle Aged ; *Occupational Exposure ; Young Adult ; }, abstract = {This paper describes follow-up for a cohort of 4530 residents living in the asbestos manufacturing community of Ambler, PA, U.S. in 1930. Using re-identified census data, cause and date of death data obtained from the genealogic website Ancestry.com, along with geospatial analysis, we explored relationships among demographic characteristics, occupational, paraoccupational and environmental asbestos exposures. We identified death data for 2430/4530 individuals. Exposure differed significantly according to race, gender, age, and recency of immigration to the U.S. Notably, there was a significant difference in the availability of year of death information for non-white vs. white individuals (odds ratio (OR) = 0.62 p-value < 0.001), females (OR = 0.53, p-value < 0.001), first-generation immigrants (OR = 0.67, p-value = 0.001), second-generation immigrants (OR = 0.31, p-value < 0.001) vs. non-immigrants, individuals aged less than 20 (OR = 0.31 p-value < 0.001) and individuals aged 20 to 59 (OR = 0.63, p-value < 0.001) vs. older individuals. Similarly, the cause of death was less often available for non-white individuals (OR = 0.42, p-value <0.001), first-generation immigrants and (OR = 0.71, p-value = 0.009), second-generation immigrants (OR = 0.49, p-value < 0.001), individuals aged less than 20 (OR = 0.028 p-value < 0.001), and individuals aged 20 to 59 (OR = 0.26, p-value < 0.001). These results identified ascertainment bias that is important to consider in analyses that investigate occupational, para-occupational and environmental asbestos exposure as risk factors for mortality in this historic cohort. While this study attempts to describe methods for assessing itemized asbestos exposure profiles for a community in 1930 using Ancestry.com and other publicly accessible databases, it also highlights how historic cohort studies likely underestimate the impact of asbestos exposure on vulnerable populations. Future work will aim to assess mortality patterns in this cohort.}, }
@article {pmid33662805, year = {2021}, author = {Kotsiou, OS and Gourgoulianis, KI and Zarogiannis, SG}, title = {The role of nitric oxide in pleural disease.}, journal = {Respiratory medicine}, volume = {179}, number = {}, pages = {106350}, doi = {10.1016/j.rmed.2021.106350}, pmid = {33662805}, issn = {1532-3064}, abstract = {Nitric oxide (NO) regulates various physiological and pathophysiological functions in the lungs. However, there is much less information about the effects of NO in the pleura. The present review aimed to explore the available evidence regarding the role of NO in pleural disease. NO, has a double-edged role in the pleural cavity. It is an essential signaling molecule mediating various physiological cell functions such as lymphatic drainage of the serous cavities, the immune response to intracellular multiplication of pathogens, and downregulation of neutrophil migration, but also induces genocytotoxic and mutagenic effects when present in excess. NO is implicated in the pathogenesis of asbestos-related or exudative pleural disease and mesothelioma. From a clinical point of view, the fraction of exhaled NO has been suggested as a potential non-invasive tool for the diagnosis of benign asbestos-related disorders. Under experimental conditions, NO-mimetics were found to attenuate hypoxia-induced therapy resistance in mesothelioma. Similarly, hybrid agents consisting of an NO donor coupled with a parent anti-inflammatory drug showed an enhancement of the anti-inflammatory activity of anti-inflammatory drugs. However, given the paucity of research work performed over the last years in this area, further research should be undertaken to establish reliable conclusions with respect to the feasibility of determining or targeting the NO signaling pathway for pleural disease diagnosis and therapeutic management.}, }
@article {pmid33660947, year = {2021}, author = {Guzmán-Casta, J and Carrasco-CaraChards, S and Guzmán-Huesca, J and Sánchez-Ríos, CP and Riera-Sala, R and Martínez-Herrera, JF and Peña-Mirabal, ES and Bonilla-Molina, D and Alatorre-Alexander, JA and Martínez-Barrera, LM and Rodríguez-Cid, JR}, title = {Prognostic factors for progression-free and overall survival in malignant pleural mesothelioma.}, journal = {Thoracic cancer}, volume = {12}, number = {7}, pages = {1014-1022}, pmid = {33660947}, issn = {1759-7714}, abstract = {BACKGROUND: Malignant pleural mesothelioma is an infrequent neoplasia with a poor prognosis and the majority of patients already have advanced disease at the time of presentation. Exposure to asbestos is the most important risk factor for malignant pleural mesothelioma. Mesothelioma is a neoplasia with a long preclinical stage that can span from 15 to 40 years.<br><br>METHODS: This was a descriptive, observational, retrospective study of 136 patients with a confirmed diagnosis of mesothelioma, which compared histological subtypes, immunohistochemical biomarkers, concomitant chronic degenerative diseases, tobacco use, age at the time of diagnosis, clinical stage and chemotherapy agents used or other treatments such as radiotherapy and surgery to identify all the factors that impact in the prognosis of overall survival (OS) and progression-free survival (PFS).<br><br>RESULTS: A total of 136 patients were included in the study. In the total study population, 84 patients were male (61.8%) and 52 were female (38.2%). Median PFS was nine months (95% confidence interval [CI]: 8.4-9.5 months) and median OS was 12 months (95% CI: 11.3-12.6). The results indicated that the most determining prognostic factors for OS and PFS were cell differentiation measured by immunohistochemical biomarkers, the treatment chosen, and that RECIST was the most significant in the evaluation of patient response to treatment.<br><br>CONCLUSIONS: Malignant pleural mesothelioma is a cancer with a poor prognosis usually diagnosed at an advanced stage of disease. Our study revealed that the prognostic factors for OS and PS were cell differentiation, the treatment chosen and RECIST.}, }
@article {pmid33652123, year = {2021}, author = {Sridharan, S and Taylor-Just, A and Bonner, JC}, title = {Osteopontin mRNA expression by rat mesothelial cells exposed to multi-walled carbon nanotubes as a potential biomarker of chronic neoplastic transformation in vitro.}, journal = {Toxicology in vitro : an international journal published in association with BIBRA}, volume = {73}, number = {}, pages = {105126}, pmid = {33652123}, issn = {1879-3177}, support = {P30 ES025128/ES/NIEHS NIH HHS/United States ; R01 ES020897/ES/NIEHS NIH HHS/United States ; }, abstract = {Mesothelioma is a cancer of the lung pleura primarily associated with inhalation of asbestos fibers. Multi-walled carbon nanotubes (MWCNTs) are engineered nanomaterials that pose a potential risk for mesothelioma due to properties that are similar to asbestos. Inhaled MWCNTs migrate to the pleura in rodents and some types cause mesothelioma. Like asbestos, there is a diversity of MWCNT types. We investigated the neoplastic potential of tangled (tMWCNT) versus rigid (rMWCNT) after chronic exposure using serial passages of rat mesothelial cells in vitro. Normal rat mesothelial (NRM2) cells were exposed to tMWCNTs or rMWCNTs for 45 weeks over 85 passages to determine if exposure resulted in transformation to a neoplastic phenotype. Rat mesothelioma (ME1) cells were used as a positive control. Osteopontin (OPN) mRNA was assayed as a biomarker of transformation by real time quantitative polymerase chain reaction (qPCR) and transformation was determined by a cell invasion assay. Exposure to rMWCNTs, but not tMWCNTs, resulted in transformation of NRM2 cells into an invasive phenotype that was similar to ME1 cells. Moreover, exposure of NRM2 cells to rMWCNTs increased OPN mRNA that correlated with cellular transformation. These data suggest that OPN is a potential biomarker that should be further investigated to screen the carcinogenicity of MWCNTs in vitro.}, }
@article {pmid33640705, year = {2021}, author = {Niu, X and Zhou, C and Hu, A and Su, L and Lin, D and Han, H and Lu, Y}, title = {Malignant mesothelioma without asbestos exposure diagnosed during EGFR-TKI treatment of lung adenocarcinoma: A case report.}, journal = {Cancer treatment and research communications}, volume = {27}, number = {}, pages = {100345}, doi = {10.1016/j.ctarc.2021.100345}, pmid = {33640705}, issn = {2468-2942}, abstract = {Synchronous malignant mesothelioma (MM) and lung carcinoma are extremely rare in patients without a history of asbestos exposure and poses tremendous difficulties in clinical management. We report a patient without asbestos exposure diagnosed with MM during EGFR-TKI treatment of lung adenocarcinoma (LUAD), who responded to first-line chemotherapy with pemetrexed plus carboplatin and failed to subsequent systemic therapy. Clinicians should be careful about the possibility of MM comorbidity in LUAD patients whose lesions respond differently to EGFR-TKI, even in those without a history of asbestos exposure.}, }
@article {pmid33635114, year = {2021}, author = {Hoton, D and Luyckx, M and Galant, C and Dano, H}, title = {Hibernoma-like Changes and TFE3 Expression in Mesothelioma Mimicking TFE3-Translocation Renal Cell Carcinoma: A Diagnostic Pitfall.}, journal = {International journal of surgical pathology}, volume = {}, number = {}, pages = {1066896921998000}, doi = {10.1177/1066896921998000}, pmid = {33635114}, issn = {1940-2465}, abstract = {The long delay between asbestos exposure and the development of mesothelioma will likely result in an increased incidence of mesothelioma in our industrialized societies. Radiation therapy is another factor known to induce these tumors. We describe a rare case of foamy looking mesothelioma in a 63-year-old patient with a long oncology history of a supposed peritoneal carcinomatosis. The pathologist was faced with a diagnostic pitfall as this peritoneal clear cell tumor expressed transcription factor binding to immunoglobulin heavy constant mu enhancer 3 (TFE3) at the nuclear level. Fortunately, the pathologist performed an extensive panel of immunomarkers, leading to a final diagnosis of epithelioid mesothelioma. Thus, we describe the first case of mesothelioma expressing TFE3. Note that there was no rearrangement of TFE3 in fluorescence in situ hybridization.}, }
@article {pmid33624546, year = {2021}, author = {Rossi, G and Caroli, G and Caruso, D and Stella, F and Davoli, F}, title = {Pseudocarcinomatous Mesothelioma: A Hitherto Unreported Presentation closely simulating primary lung cancer.}, journal = {International journal of surgical pathology}, volume = {}, number = {}, pages = {1066896921997559}, doi = {10.1177/1066896921997559}, pmid = {33624546}, issn = {1940-2465}, abstract = {Malignant mesothelioma (MM) has a wide range of clinical, radiologic, and pathologic presentations, mimicking lung cancer or interstitial lung diseases when predominantly involving the lung parenchyma. The case herein refers to a 79-year-old man, active smoker without asbestos exposure, incidentally discovered to have a pulmonary nodule in the right upper lobe (1.5 cm). The lesion was misinterpreted as primary lung adenocarcinoma at the frozen section in light of the predominant lepidic growth pattern. Definitive examination confirmed neoplastic proliferation along alveolar structures. However, the unusual globous shape of tumor cells along the alveoli abruptly merging with normal pneumocytes prompted us to perform some immunostains that surprisingly revealed a mesothelial differentiation (positive staining with calretinin, cytokeratins (CK5/6), D2-40, and negativity with BRCA-associated protein 1 (BAP1), Thyroid Transcription Factor 1 [TTF-1], claudin-4, carcinoembryonic antigen [CEA], and napsin). MM represents the pathologic counterpart of so-called pseudomesotheliomatous carcinoma, since it appears as a localized pulmonary neoplastic nodule displaying a predominant lepidic growth pattern (pseudocarcinomatous mesothelioma). The challenging diagnostic features of this unique case and a review of similar cases in the literature are discussed.}, }
@article {pmid33622366, year = {2021}, author = {Baur, X and Frank, AL}, title = {Ongoing downplaying of the carcinogenicity of chrysotile asbestos by vested interests.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {16}, number = {1}, pages = {6}, pmid = {33622366}, issn = {1745-6673}, abstract = {Industries that mine, manufacture and sell asbestos or asbestos-containing products have a long tradition of promoting the use of asbestos, while placing the burden of economic and health costs on workers and society. This has been successfully done in recent years and decades in spite of the overwhelming evidence that all asbestos types are carcinogenic and cause asbestosis. In doing so, the asbestos industry has undermined the WHO campaign to reach a worldwide ban of asbestos and to eliminate asbestos-related diseases. Even worse, in recent years they succeeded in continuing asbestos mining and consuming in the range of about 1.3 million tons annually. Nowadays, production takes place predominantly in Russia, Kazakhstan and China. Chrysotile is the only asbestos type still sold and represents 95% of asbestos traded over the last century.The asbestos industry, especially its PR agency, the International Chrysotile Association, ICA, financed by asbestos mining companies in Russia, Kazakhstan and Zimbabwe and asbestos industrialists in India and Mexico, continues to be extremely active by using slogans such as chrysotile can be used safely.Another approach of the asbestos industry and of some of its insurance agencies is to broadly defeat liability claims of asbestos victims.In doing so they systematically use inappropriate science produced by their own and/or by industry-affiliated researchers. Some of the latter were also engaged in producing defense material for other industries including the tobacco industry. Frequent examples of distributing such disinformation include questioning or denying established scientific knowledge about adverse health effects of asbestos. False evidence continues to be published in scientific journals and books.The persisting strong influence of vested asbestos-related interests in workers and public health issues including regulations and compensation necessitate ongoing alertness, corrections and appropriate reactions in scientific as well as public media and policy advisory bodies.}, }
@article {pmid33617892, year = {2021}, author = {Ierardi, AM and Urban, A and Marsh, GM}, title = {A quantitative weight of evidence assessment of Hill's guidelines for causal inference for cosmetic talc as a cause of mesothelioma.}, journal = {Toxicology and applied pharmacology}, volume = {417}, number = {}, pages = {115461}, doi = {10.1016/j.taap.2021.115461}, pmid = {33617892}, issn = {1096-0333}, mesh = {Animals ; Causality ; Humans ; Mesothelioma/*chemically induced/diagnosis/epidemiology ; Pleural Neoplasms/*chemically induced/diagnosis/epidemiology ; Probability ; Risk Assessment ; Risk Factors ; Talc/*adverse effects ; Time Factors ; Toxicity Tests ; }, abstract = {Cosmetic talc has been suggested to cause mesothelioma. To assess a potential causal relationship between cosmetic talc and mesothelioma, a quantitative weight of evidence analysis was performed in accordance with Hill's nine original guidelines for causal inference using a published empirical model to weight each respective guideline. Various epidemiological, toxicological, and exposure studies related to cosmetic talc and risk of mesothelioma were included in an evaluation of each of Hill's guidelines. Probabilities that the guidelines were true were assigned based on expert judgment. We applied a sensitivity analysis to evaluate the variability of our probability estimates. The overall probability of causality for cosmetic talc and mesothelioma was approximately 1.29% (range: 0.73%-3.96%). This low probability of causality supports the conclusion that cosmetic talc is not related to the development of mesothelioma.}, }
@article {pmid33614517, year = {2021}, author = {Cheng, YY and Yuen, ML and Jin, H}, title = {Editorial: Epigenetic Modifications in Mesothelioma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {650136}, doi = {10.3389/fonc.2021.650136}, pmid = {33614517}, issn = {2234-943X}, }
@article {pmid33614198, year = {2021}, author = {Pestak, CR and Boyce, TW and Myers, OB and Hopkins', LO and Wiggins, CL and Wissore, BR and Sood, A and Cook, LS}, title = {A Population-Based Feasibility Study of Occupation and Thoracic Malignancies in New Mexico.}, journal = {Southwest journal of pulmonary &amp; critical care}, volume = {22}, number = {1}, pages = {23-25}, pmid = {33614198}, issn = {2160-6773}, support = {KL2 RR031976/RR/NCRR NIH HHS/United States ; P30 CA118100/CA/NCI NIH HHS/United States ; UL1 TR000041/TR/NCATS NIH HHS/United States ; HHSN261201800014I/CA/NCI NIH HHS/United States ; U01 GM132175/GM/NIGMS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; HHSN261201800014C/CA/NCI NIH HHS/United States ; }, abstract = {Background: Occupational exposures in mining and oil/gas extraction are known risk factors for thoracic malignancies (TMs). Given the relatively high proportion of these industries in New Mexico (NM), we conducted a feasibility study of adult lifetime occupational history among TM cases. We hypothesized a higher proportion of occupational TM in NM relative to the estimated national average of 10-14%.<br><br>Methods: We identified incident TM cases through the population-based New Mexico Tumor Registry (NMTR), from 2017-2018. Cases completed a telephone interview. An adjudication panel reviewed case histories and classified cancers as probable, possible, or non-occupational related, taking into account the presence, duration, and latency of exposures. We characterized recruitment and describe job titles and exposures among those with occupational TMs. We also compared the distributions of industry between those with and without occupational TM.<br><br>Results: The NMTR identified 400 eligible TM cases, 290 of which were available to be recruited (n=285 lung/bronchial cancer; n=5 mesotheliomas). Of the latter, 60% refused and 18% were deceased, 9% had invalid addresses, 11% were unable to be reached by telephone, and 3% were too ill to participate. The 43 cases who completed an interview held 236 jobs. A total of 33% of cases were classified as probable occupational TM and 5% as possible occupational TM.<br><br>Conclusions: High rates of early mortality and refusals were significant barriers to study participation. Nonetheless, the proportion of probable occupational TMs greatly exceeded the estimated national average, highlighting the need for further study of occupational TM in the state.}, }
@article {pmid33577225, year = {2021}, author = {Malpica, A and Euscher, ED and Marques-Piubelli, ML and Miranda, RN and Fournier, KF and Raghav, KP and Ramalingam, P}, title = {Malignant Peritoneal Mesothelioma Associated With Endometriosis: A Clinicopathologic Study of 15 Cases.}, journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists}, volume = {}, number = {}, pages = {}, doi = {10.1097/PGP.0000000000000762}, pmid = {33577225}, issn = {1538-7151}, abstract = {Only a few cases of malignant peritoneal mesothelioma (MPeM) associated with endometriosis have been published; with chronic inflammation of the peritoneum associated with the latter being postulated as an inducing factor in the pathogenesis of this tumor. We assessed the clinicopathologic characteristics of MPeM associated with endometriosis to determine if there were other factors besides inflammation that may contribute to the pathogenesis in this patient population. Fifteen MPeM associated with endometriosis were retrieved from our files. Most presented with abdominal/pelvic pain, mass or distention; median age was 45 yr. Only 16% of patients had a history of asbestos exposure. In contrast, a third of the patients had a personal history of other neoplasms, and >80% had a family history of malignancies. Although most tumors had gross and microscopic features typical of MPeM, some had confounding features including "adhesion-like" appearance or gelatinous cysts/nodules, and signet ring cells. Tumors were epithelioid (9) and biphasic (6). MPeM was misdiagnosed as Müllerian carcinoma in 40% of cases. All patients (n=15) had cytoreductive surgery in addition to other therapies. Only 2/12 patients died of disease (17%). The 3- and 5-yr overall survival was 90%. MPeM associated with endometriosis tends to occur in patients with personal/familial history of malignancies, which may be a predisposing factor. In light of this finding, the role of endometriosis in the pathogenesis of MPeM is likely less relevant. The favorable outcome seen in these patients may be related to germline mutations or the hormonal milieu and needs further investigation.}, }
@article {pmid33574130, year = {2021}, author = {Sato, T and Mukai, S and Ikeda, H and Mishiro-Sato, E and Akao, K and Kobayashi, T and Hino, O and Shimono, W and Shibagaki, Y and Hattori, S and Sekido, Y}, title = {Silencing of SmgGDS, a Novel mTORC1 Inducer That Binds to RHEBs, Inhibits Malignant Mesothelioma Cell Proliferation.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {5}, pages = {921-931}, doi = {10.1158/1541-7786.MCR-20-0637}, pmid = {33574130}, issn = {1557-3125}, abstract = {Malignant mesothelioma (MM) is an aggressive tumor that typically develops after a long latency following asbestos exposure. Although mechanistic target of rapamycin complex 1 (mTORC1) activation enhances MM cell growth, the mTORC1 inhibitor everolimus has shown limited efficacy in clinical trials of MM patients. We explored the mechanism underlying mTORC1 activation in MM cells and its effects on cell proliferation and progression. Analysis of the expression profiles of 87 MMs from The Cancer Genome Atlas revealed that 40 samples (46%) displayed altered expression of RPTOR (mTORC1 component) and genes immediately upstream that activate mTORC1. Among them, we focused on RHEB and RHEBL1, which encode direct activators of mTORC1. Exogenous RHEBL1 expression enhanced MM cell growth, indicating that RHEB-mTORC1 signaling acts as a pro-oncogenic cascade. We investigated molecules that directly activate RHEBs, identifying SmgGDS as a novel RHEB-binding protein. SmgGDS knockdown reduced mTORC1 activation and inhibited the proliferation of MM cells with mTORC1 activation. Interestingly, SmgGDS displayed high binding affinity with inactive GDP-bound RHEBL1, and its knockdown reduced cytosolic RHEBL1 without affecting its activation. These findings suggest that SmgGDS retains GDP-bound RHEBs in the cytosol, whereas GTP-bound RHEBs are localized on intracellular membranes to promote mTORC1 activation. We revealed a novel role for SmgGDS in the RHEB-mTORC1 pathway and its potential as a therapeutic target in MM with aberrant mTORC1 activation. IMPLICATIONS: Our data showing that SmgGDS regulates RHEB localization to activate mTORC1 indicate that SmgGDS can be used as a new therapeutic target for MM exhibiting mTORC1 activation.}, }
@article {pmid33567673, year = {2021}, author = {Keller, M and Reis, K and Hjerpe, A and Dobra, K and Aspenström, P}, title = {Cytoskeletal Organization Correlates to Motility and Invasiveness of Malignant Mesothelioma Cells.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33567673}, issn = {2072-6694}, support = {CAN 2017/527//Cancerfonden/ ; CAN 2015/479//Cancerfonden/ ; Beslut 2017/160(180)//Stiftelsen Olle Engkvist Byggmästare/ ; }, abstract = {Malignant mesothelioma (MM) is a rare but highly aggressive cancer that primarily originates from the pleura, peritoneum or pericardium. There is a well-established link between asbestos exposure and progression of MM. Direct invasion of the surrounding tissues is the main feature of MM, which is dependent on dysregulated communication between the mesothelium and the microenvironment. This communication is dependent on the dynamic organization of the cytoskeleton. We have analyzed the organization and function of key cytoskeletal components in MM cell lines of increasing malignancies measured as migratory and invasive properties, and we show that highly malignant and invasive MM cells have an organization of the actin filament and vimentin systems that is distinct from the less malignant MM cell lines. In addition, the Hippo tumor suppressor pathway was inactivated in the invasive MM cells, which was seen as increased YAP nuclear localization.}, }
@article {pmid33567623, year = {2021}, author = {Lococo, F}, title = {Malignant Pleural Mesothelioma: Time Is Running Out.}, journal = {Journal of clinical medicine}, volume = {10}, number = {4}, pages = {}, pmid = {33567623}, issn = {2077-0383}, abstract = {Malignant pleural mesothelioma (MPM) is a rare but highly malignant disease of the pleura usually related to asbestos exposure [...].}, }
@article {pmid33562413, year = {2021}, author = {Emmett, EA}, title = {Asbestos in High-Risk Communities: Public Health Implications.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33562413}, issn = {1660-4601}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; }, mesh = {*Asbestos/toxicity ; Female ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma/epidemiology/etiology ; Montana ; *Occupational Exposure ; Pennsylvania ; Public Health ; Turkey ; Western Australia/epidemiology ; }, abstract = {Asbestos-related diseases (ARDs)-mesothelioma, lung cancer, and asbestosis-are well known as occupational diseases. As industrial asbestos use is eliminated, ARDs within the general community from para-occupational, environmental, and natural exposures are more prominent. ARD clusters have been studied in communities including Broni, Italy; Libby, Montana; Wittenoom, Western Australia; Karain, Turkey; Ambler, Pennsylvania; and elsewhere. Community ARDs pose specific public health issues and challenges. Community exposure results in higher proportions of mesothelioma in women and a younger age distribution than occupational exposures. Exposure amount, age at exposure, fiber type, and genetic predisposition influence ARD expression; vulnerable groups include those with social and behavioral risk, exposure to extreme events, and genetic predispositions. To address community exposure, regulations should address all carcinogenic elongated mineral fibers. Banning asbestos mining, use, and importation will not reduce risks from asbestos already in place. Residents of high-risk communities are characteristically exposed through several pathways differing among communities. Administrative responsibility for controlling environmental exposures is more diffuse than for workplaces, complicated by diverse community attitudes to risk and prevention and legal complexity. The National Mesothelioma Registries help track the identification of communities at risk. High-risk communities need enhanced services for screening, diagnosis, treatment, and social and psychological support, including for retired asbestos workers. Legal settlements could help fund community programs. A focus on prevention, public health programs, particularization to specific community needs, and participation is recommended.}, }
@article {pmid33562138, year = {2021}, author = {Vogl, M and Rosenmayr, A and Bohanes, T and Scheed, A and Brndiar, M and Stubenberger, E and Ghanim, B}, title = {Biomarkers for Malignant Pleural Mesothelioma-A Novel View on Inflammation.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, pmid = {33562138}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient's outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome.}, }
@article {pmid33555117, year = {2021}, author = {Miyagawa, C and Takaya, H and Sakai, K and Nishio, K and Konishi, M and Minamiguchi, S and Shimada, T and Matsumura, N}, title = {A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review.}, journal = {The oncologist}, volume = {26}, number = {5}, pages = {356-361}, pmid = {33555117}, issn = {1549-490X}, mesh = {Adolescent ; Anaplastic Lymphoma Kinase/genetics ; Calmodulin-Binding Proteins/genetics ; Exons/genetics ; Female ; Gene Rearrangement ; Humans ; Membrane Proteins/genetics ; *Mesothelioma, Malignant ; Nerve Tissue Proteins/genetics ; Oncogene Proteins, Fusion/genetics ; *Peritoneal Neoplasms/drug therapy/genetics ; }, abstract = {Recently, several malignant peritoneal mesotheliomas (MPMs), occurring in young women without asbestos exposure and with fusion genes such as anaplastic lymphoma kinase (ALK) and Ewing sarcoma breakpoint region 1, have been reported. In the present case, we encountered MPM with STRN-ALK fusion in a 17-year-old female adolescent. The case did not respond to chemotherapy and is currently in a clinical trial of alectinib. This is the fourth reported case of MPM with STRN-ALK fusion. Of the 45 cancer cases with STRN-ALK fusion in which the fusion partners were examined, all cases except for the current case showed fusion of exon 3 of STRN and exon 20 of ALK. This is the first case with fusion of exon 2 of STRN and exon 20 of ALK. Further advances in cancer genomic medicine may help clarify the clinical significance of this new fusion. KEY POINTS: Malignant peritoneal mesotheliomas (MPMs) can occur in young women without asbestos exposure and show fusion genes that activate anaplastic lymphoma kinase (ALK) by gene rearrangement. ALK rearrangement and the fusion partner can be detected by companion diagnostics and by next generation sequencing. Patients with MPMs with ALK rearrangement may benefit from target therapy.}, }
@article {pmid33544514, year = {2021}, author = {Franko, A and Goricar, K and Dodic Fikfak, M and Kovac, V and Dolzan, V}, title = {The role of polymorphisms in glutathione-related genes in asbestos-related diseases.}, journal = {Radiology and oncology}, volume = {55}, number = {2}, pages = {179-186}, pmid = {33544514}, issn = {1581-3207}, abstract = {BACKGROUND: The study investigated the influence of GCLC, GCLM, GSTM1, GSTT1 and GSTP1 polymorphisms, as well as the influence of interactions between polymorphism and interactions between polymorphisms and asbestos exposure, on the risk of developing pleural plaques, asbestosis and malignant mesothelioma (MM).<br><br>SUBJECTS AND METHODS: The cross sectional study included 940 asbestos-exposed subjects, among them 390 subjects with pleural plaques, 147 subjects with asbestosis, 225 subjects with MM and 178 subjects with no asbestos-related disease. GCLC rs17883901, GCLM rs41303970, GSTM1 null, GSTT1 null, GSTP1 rs1695 and GSTP1 rs1138272 genotypes were determined using PCR based methods. In statistical analysis, logistic regression was used.<br><br>RESULTS: GSTT1 null genotype was associated with the decreased risk for pleural plaques (OR = 0.63; 95% CI = 0.40-0.98; p = 0.026) and asbestosis (OR = 0.51; 95% CI = 0.28-0.93; p = 0.028), but not for MM. A positive association was found between GSTP1 rs1695 AG + GG vs. AA genotypes for MM when compared to pleural plaques (OR = 1.39; 95% CI = 1.00-1.94; p = 0.049). The interactions between different polymorphisms showed no significant influence on the risk of investigated asbestos-related diseases. The interaction between GSTT1 null polymorphism and asbestos exposure decreased the MM risk (OR = 0.17; 95% CI = 0.03-0.85; p = 0.031).<br><br>CONCLUSIONS: Our findings suggest that GSTT1 null genotype may be associated with a decreased risk for pleural plaques and asbestosis, may modify the association between asbestos exposure and MM and may consequently act protectively on MM risk. This study also revealed a protective effect of the interaction between GSTP1 rs1695 polymorphism and asbestos exposure on MM risk.}, }
@article {pmid33540554, year = {2021}, author = {De Rienzo, A and Coleman, MH and Yeap, BY and Severson, DT and Wadowski, B and Gustafson, CE and Jensen, RV and Chirieac, LR and Richards, WG and Bueno, R}, title = {Association of RERG Expression with Female Survival Advantage in Malignant Pleural Mesothelioma.}, journal = {Cancers}, volume = {13}, number = {3}, pages = {}, pmid = {33540554}, issn = {2072-6694}, support = {P30 CA006516/CA/NCI NIH HHS/United States ; RO1CA120528//National Cancer Research Institute/ ; }, abstract = {Sex differences in incidence, prognosis, and treatment response have been described for many cancers. In malignant pleural mesothelioma (MPM), a lethal disease associated with asbestos exposure, men outnumber women 4 to 1, but women consistently live longer than men following surgery-based therapy. This study investigated whether tumor expression of genes associated with estrogen signaling could potentially explain observed survival differences. Two microarray datasets of MPM tumors were analyzed to discover estrogen-related genes associated with survival. A validation cohort of MPM tumors was selected to balance the numbers of men and women and control for competing prognostic influences. The RAS like estrogen regulated growth inhibitor (RERG) gene was identified as the most differentially-expressed estrogen-related gene in these tumors and predicted prognosis in discovery datasets. In the sex-matched validation cohort, low RERG expression was significantly associated with increased risk of death among women. No association between RERG expression and survival was found among men, and no relationship between estrogen receptor protein or gene expression and survival was found for either sex. Additional investigations are needed to elucidate the molecular mechanisms underlying this association and its sex specificity.}, }
@article {pmid33538989, year = {2021}, author = {Nadal, E and Bosch-Barrera, J and Cedrés, S and Coves, J and García-Campelo, R and Guirado, M and López-Castro, R and Ortega, AL and Vicente, D and de Castro-Carpeño, J}, title = {SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020).}, journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {23}, number = {5}, pages = {980-987}, pmid = {33538989}, issn = {1699-3055}, abstract = {Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.}, }
@article {pmid33537296, year = {2020}, author = {Rossini, M and Martini, F and Torreggiani, E and Fortini, F and Aquila, G and Sega, FVD and Patergnani, S and Pinton, P and Maniscalco, P and Cavallesco, G and Rizzo, P and Tognon, M}, title = {Metformin Induces Apoptosis and Inhibits Notch1 in Malignant Pleural Mesothelioma Cells.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {534499}, pmid = {33537296}, issn = {2296-634X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related cancer arising from the mesothelial cells lining the pleural cavity. MPM is characterized by a silent clinical progression and a highly resistance to conventional chemo/radio-therapies. MPM patients die in a few months/years from diagnosis. Notch signaling is a well-conserved cell communication system, which regulates many biological processes. In humans, the dysregulation of Notch pathway potentially contributes to cancer onset/progression, including MPM. Metformin is the first-line drug used to treat type 2 diabetes mellitus. Metformin is proven to be an effective antitumor drug in preclinical models of different types of cancer. To date, clinical efficacy is being studied in many clinical trials. In this study, the anti-proliferative effect of metformin on MPM cells and the putative involvement of Notch1 as a mediator of metformin activities, were investigated. MPM cells showed high levels of Notch1 activation compared to normal pleural mesothelial cells. Furthermore, metformin treatment hampered MPM cell proliferation and enhanced the apoptotic process, accompanied by decreased Notch1 activation.}, }
@article {pmid33533198, year = {2021}, author = {Fukui, T and Okubo, T and Tanimoto, N and Okuma, H and Shiina, Y and Kohama, M and Yamada, J and Funada, Y and Ikura, Y}, title = {Malignant pleural mesothelioma in a patient with pneumothorax: A cumbersome subtype both clinically and pathologically.}, journal = {Thoracic cancer}, volume = {12}, number = {6}, pages = {974-977}, pmid = {33533198}, issn = {1759-7714}, abstract = {Here, we report a case of malignant pleural mesothelioma (MPM) that was very difficult to diagnose. A 62-year-old woman with a surgical history of recurrent bilateral pneumothorax was admitted to our hospital with severe dysphagia. Computed tomography (CT) detected stenosis in the lower esophagus. Immunohistochemical examination of a biopsy sample from the stenotic region was suggestive of MPM. Chemotherapy was initiated, but the patient soon weakened and died. Autopsy revealed atypical cells, identical to those seen in the biopsy sample which had spread into the stenotic esophagus and entire thoracic cavity. Although neither pleural thickening/nodules nor asbestos bodies were observed, we finally diagnosed the tumor as a biphasic-type MPM. We re-examined previous surgical specimens of pneumothorax and acknowledged foci of bland mesothelial cell proliferation which had the same pathological findings as tumor cells at autopsy. The lack of asbestos exposure and pleural thickening, an initial manifestation of pneumothorax, and faint cytological atypia prevented an early diagnosis. In cases of recurrent pneumothorax in elderly patients, MPM should be included in the differential diagnosis.}, }
@article {pmid33533181, year = {2021}, author = {Piro, R and Fontana, M and Livrieri, F and Menzella, F and Casalini, E and Taddei, S and De Giorgi, F and Facciolongo, N}, title = {Pleural mesothelioma: When echo-endoscopy (EUS-B-FNA) leads to diagnosis in a minimally invasive way.}, journal = {Thoracic cancer}, volume = {12}, number = {6}, pages = {981-984}, pmid = {33533181}, issn = {1759-7714}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related and locally invasive tumor with poor prognosis. The acquisition of histological material is mandatory in order to establish a diagnosis. In this situation, the sampling of tissue is generally performed via a thoracoscopic pleural biopsy, either medically or surgically. The use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or transesophageal fine needle aspiration with an EBUS scope (EUS-B-FNA) of pleural lesions have only rarely been reported due to the theoretical limitations of tissue acquisition in such cases. We herein report a rare case of MPM successfully diagnosed via EUS-B-FNA in a 49-year-old woman with an unusual presentation characterized by solid thickening in the right mediastinal pleura.}, }
@article {pmid33533080, year = {2021}, author = {Dell, LD and Gallagher, AE and Yost, LJ and Mundt, KA}, title = {Integration of Evidence on Community Cancer Risks from Elongate Mineral Particles in Silver Bay, Minnesota.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {}, number = {}, pages = {}, doi = {10.1111/risa.13673}, pmid = {33533080}, issn = {1539-6924}, abstract = {The potential for cancer-related risks to community members from ambient exposure to elongate mineral particles (EMPs) in taconite processing has not been formally evaluated. We evaluated 926 ambient air samples including 12,928 EMPs (particle structures with length-to-width ratio ≥3:1) collected over 26 years near a taconite processing facility in Silver Bay, Minnesota. Eighty-two percent of EMPs were ≤3 μm in length and 97% of EMPs had an average aspect ratio <20:1. A total of 935 (7.3%) EMPs had length >5 μm and AR ≥3:1. Average ambient concentration of NIOSH countable amphibole EMPs over all years was 0.000387 EMPs per cubic centimeter (EMP/cm3). Of 12,765 nonchrysotile EMPs, the number of amphiboles with length and width dimensions that correlate best with asbestos-related carcinogenicity ranged from four (0.03%) to 13 (0.1%) and the associated ambient amphibole air concentrations ranged from 0.000003 to 0.000007 EMP/cm3 . After 65 years of taconite processing in Silver Bay, evidence of an increased risk of mesothelioma and lung cancer in community members who did not work in the taconite industry is lacking. The absence of an increased risk of asbestos-related cancer in the Silver Bay community is coherent with supporting evidence from epidemiological and toxicological studies, as well as ambient exposure data and lake sediment data collected in Minnesota Iron Range communities. Collectively, the data provide consistent evidence that nonasbestiform amphibole minerals lack the carcinogenic potential exhibited by amphibole asbestos.}, }
@article {pmid33515502, year = {2021}, author = {Nowak, AK}, title = {New and old treatments for malignant mesothelioma: not just immunotherapy.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {6}, pages = {547-549}, doi = {10.1016/S2213-2600(20)30516-6}, pmid = {33515502}, issn = {2213-2619}, mesh = {Deoxycytidine/analogs &amp; derivatives ; Humans ; Immunotherapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/drug therapy ; }, }
@article {pmid33509005, year = {2021}, author = {Cook, AM and McDonnell, A and Millward, MJ and Creaney, J and Hasani, A and McMullen, M and Meniawy, T and Robinson, BWS and Lake, RA and Nowak, AK}, title = {A phase 1b clinical trial optimizing regulatory T cell depletion in combination with platinum-based chemotherapy in thoracic cancers.}, journal = {Expert review of anticancer therapy}, volume = {21}, number = {5}, pages = {465-474}, doi = {10.1080/14737140.2021.1882308}, pmid = {33509005}, issn = {1744-8328}, abstract = {Background: Single-agent cyclophosphamide can deplete regulatory T-cells (Treg). We aimed to determine optimal dosing and scheduling of oral cyclophosphamide, alongside pemetrexed-based chemotherapy, to deplete Treg in mesothelioma or non-small-cell lung cancer patients.Methods: 31 Patients received pemetrexed ± cisplatin or carboplatin on day 1 of a 21-day cycle (maximum 6 cycles). From cycle two, patients received cyclophosphamide, 50 mg/day, with intrapatient escalation to maximum 100/150 mg/day alternately. Immunological changes were examined by flow cytometry. Primary endpoint was Treg proportion of CD4+ T-cells, with doses tailored to target Treg nadir <4%.Results: Reduction in Treg proportion was observed on day 8 of all cycles, and was not augmented by cyclophosphamide. Few patients achieved the <4% Treg target. Treg proliferation reached nadir one week after chemotherapy, and peaked on day 1 of the subsequent cycle. Efficacy parameters were similar to chemotherapy alone. Seventeen percent of patients ceased cyclophosphamide due to toxicity.Conclusions: Specific Treg depletion to the degree seen with single-agent cyclophosphamide was not observed during pemetrexed-based chemotherapy. This study highlights the poor evidence basis for use of cyclophosphamide as an immunotherapeutic in combination with chemotherapy, and the importance of detailed flow cytometry studies.Trial registration: Clinical trial registration: www.anzctr.org.au identifier is ACTRN12609000260224.}, }
@article {pmid33506658, year = {2020}, author = {Barone Adesi, F and Bruno, C and Calisti, R and Chellini, E and Comba, P and Consonni, D and Fazzo, L and Fedeli, U and Forastiere, F and Magnani, C and Marinaccio, A and Merler, E and Mirabelli, D and Ricci, P and Terracini, B}, title = {[Effects of Asbestos on Human Health. Document of the Italian Epidemiological Association (AIE)].}, journal = {Epidemiologia e prevenzione}, volume = {44}, number = {5-6}, pages = {In press}, doi = {10.19191/EP20.5-6.A001.064}, pmid = {33506658}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; *Asbestosis/epidemiology/etiology ; Carcinogens/toxicity ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Occupational Exposure/statistics &amp; numerical data ; }, abstract = {OBJECTIVES: the Italian Epidemiological Association (AIE) intends to formulate assessments and recommendations on the most relevant and critical aspects in the preparation, conduct, and interpretation of epidemiological investigations on the health effects of exposure to asbestos and asbestos-like fibres.<br><br>the document was prepared by a working group of AIE associates, with a broad curriculum of epidemiological investigations, starting from the evaluation of scientific evidence, and was subsequently evaluated by the AIE governing body.<br><br>RESULTS: the topics covered included: • consumption and presence of asbestos; • association between asbestos exposure and disease; • epidemiological surveillance of asbestos related diseases in Italy; • risk function for asbestos related diseases; • increased risk and anticipation of the disease; • interaction between asbestos and other carcinogens; • diagnosis in epidemiological studies; • assessment of exposure to asbestos; • epidemiological evidence on asbestos related diseases.<br><br>CONCLUSIONS: the document ends with a summary of the conclusions of scientific research shared by AIE, with reflection on the methodology to be followed for the application at individual level of the results of epidemiological studies, and the proposal of themes on which to direct research.}, }
@article {pmid33502280, year = {2021}, author = {Ringgaard Petersen, T and Panou, V and Meristoudis, C and Weinreich, UM and Røe, OD}, title = {Clinical prognostic factors in pleural mesothelioma: best supportive care and anti-tumor treatments in a real-life setting.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {60}, number = {4}, pages = {521-527}, doi = {10.1080/0284186X.2021.1876246}, pmid = {33502280}, issn = {1651-226X}, abstract = {BACKGROUND: This study aims to investigate patient- and disease characteristics associated with survival in malignant pleural mesothelioma (MPM) patients with anti-tumor treatment or with best supportive care (BSC).<br><br>MATERIALS AND METHODS: Consecutive MPM cases diagnosed in North Denmark Region from 1972 to 2015 were reevaluated and verified by two pathologists using modern immunohistochemical techniques. Danish registries and hospital records were used to gather patient-, asbestos exposure-, and disease information.<br><br>RESULTS: Of the 279 patients, anti-tumor treatment was administered to 184 patients (66.0%). All of those received chemotherapy alone or as part of a multimodal treatment, where pemetrexed was given to 126 (68.5%) patients. Asbestos exposure was documented in 92.5% of all patients. In the treated group, mean age was lower (66 years versus 74 years, p < 0.01), rate of occupational asbestos exposure was higher (74.5 versus 54.7%, p < 0.01), more patients had better performance score (98.4 versus 60%, p < 0.01) and stage was lower (81 versus 63.2%, p < 0.01) compared to the BSC group. Multivariate analysis showed that epithelioid subtype was the only common prognostic factor for OS in both groups. In BSC patients, good PS and female gender was associated with improved OS. Median overall survival (OS) was 17 versus 4 months (p < 0.01), and independently of the histopathological subtype, the median and 2-year survival was higher in the treated versus the BSC group (p < 0.02).<br><br>CONCLUSIONS: This retrospective study showed that epithelioid subtype is the only independent positive prognostic factor of survival in treated patients with MPM. For BSC patients, the epithelioid subtype, good PS, and female gender were positive prognostic factors, while age and comorbidities were not significant. This study with long-term follow-up of treated and BSC MPM patients can contribute to the clinical stratification of patients. Further validation is appropriate to verify these findings.}, }
@article {pmid33498425, year = {2021}, author = {Kwak, K and Zoh, KE and Paek, D}, title = {Incidence of Cancer and Asbestos-Related Diseases among Residents Living near Abandoned Asbestos Mines in South Korea: A Retrospective Cohort Study Using National Health Insurance Database.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {3}, pages = {}, pmid = {33498425}, issn = {1660-4601}, mesh = {*Asbestos/toxicity ; Humans ; Incidence ; Male ; *Mesothelioma ; National Health Programs ; *Occupational Exposure ; Republic of Korea/epidemiology ; Retrospective Studies ; }, abstract = {The use of asbestos has been banned since 2009 in South Korea. However, there is still a risk of exposure to environmental asbestos originating from abandoned asbestos mines. We constructed a retrospective dynamic cohort using the National Health Insurance Database of South Korea. We determined the risk of developing asbestos-related diseases (ARDs) among residents living near asbestos mines compared with those living in the control area and the general population. The risks of asbestosis (adjusted hazards ratio [HR] 65.40, 95% CI = 35.02-122.12) and pleural plaques (adjusted HR 3.55, 95% CI = 1.96-6.41) were significantly increased among residents living near the asbestos mines compared with the control area. The risk of malignant mesothelioma was increased near asbestos mines compared with the control area; however, it was not significant (adjusted HR 1.83, 95% CI = 0.61-5.47). When a separate analysis according to sex was conducted, the risk of mesothelioma among male residents was statistically significant (adjusted HR 8.30, 95% CI = 1.04-66.63), and the standardized incidence ratio (SIR) was significantly increased (SIR 3.48, 95% CI = 1.50-6.85). The risk of ARDs was increased due to environmental asbestos exposure near abandoned asbestos mines in South Korea.}, }
@article {pmid33472960, year = {2021}, author = {Asciak, R and George, V and Rahman, NM}, title = {Update on biology and management of mesothelioma.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {30}, number = {159}, pages = {}, doi = {10.1183/16000617.0226-2020}, pmid = {33472960}, issn = {1600-0617}, abstract = {Malignant pleural mesothelioma is an aggressive, incurable cancer that is usually caused by asbestos exposure several decades before symptoms arise. Despite widespread prohibition of asbestos production and supply, its incidence continues to increase. It is heterogeneous in its presentation and behaviour, and diagnosis can be notoriously difficult. Identification of actionable gene mutations has proven challenging and current treatment options are largely ineffective, with a median survival of 10-12 months.However, the past few years have witnessed major advances in our understanding of the biology and pathogenesis of mesothelioma. This has also revealed the limitations of existing diagnostic algorithms and identified new treatment targets.Recent clinical trials have re-examined the role of surgery, provided new options for the management of associated pleural effusions and heralded the addition of targeted therapies. The increasing complexity of mesothelioma management, along with a desperate need for further research, means that a multidisciplinary team framework is essential for the delivery of contemporary mesothelioma care.This review provides a synthesised overview of the current state of knowledge and an update on the latest research in the field.}, }
@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 = {}, 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 = {}, pmid = {33466544}, issn = {1660-4601}, mesh = {Aged ; Aged, 80 and over ; *Agriculture ; *Asbestos/toxicity ; Female ; Humans ; Italy/epidemiology ; Male ; *Mesothelioma/chemically induced/epidemiology ; Middle Aged ; *Occupational Exposure ; }, 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 = {129}, number = {7}, pages = {506-516}, 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 &amp; 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 {pmid33422732, year = {2021}, 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}, mesh = {Adaptation, Psychological ; Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Family/psychology ; Female ; Humans ; Life Change Events ; Male ; Mesothelioma/nursing/*psychology ; Middle Aged ; Military Personnel/psychology ; Qualitative Research ; Self-Help Groups ; United Kingdom ; Veterans/*psychology ; }, 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 = {}, 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}, 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 "invisible killer" 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 = {}, 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}, 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 = {45}, number = {5}, pages = {653-661}, doi = {10.1097/PAS.0000000000001656}, pmid = {33399341}, issn = {1532-0979}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA140146/CA/NCI NIH HHS/United States ; P50 CA217694/CA/NCI NIH HHS/United States ; }, mesh = {Abdominal Neoplasms/enzymology/*genetics/pathology ; Adolescent ; Anaplastic Lymphoma Kinase/*genetics ; Biomarkers, Tumor/analysis/*genetics ; Child ; Female ; *Gene Fusion ; *Gene Rearrangement ; Genetic Predisposition to Disease ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/enzymology/*genetics/pathology ; Molecular Diagnostic Techniques ; Testicular Neoplasms/enzymology/*genetics/pathology ; }, 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 "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 = {87-89}, 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 "the regional distribution of controls is different from that of person-time observed". 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 = {2021}, 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 = {16}, number = {6}, pages = {697-708}, pmid = {33380218}, issn = {1746-045X}, support = {ZIA BC011657/ImNIH/Intramural NIH HHS/United States ; }, 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 = {}, pmid = {33379304}, issn = {1660-4601}, mesh = {Aged ; Aged, 80 and over ; Female ; Forecasting ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*mortality ; Middle Aged ; Peritoneal Neoplasms/*mortality ; }, 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 = {2021}, 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 = {49}, number = {6}, pages = {E234-E237}, 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 "peritoneal inclusion cyst (PCM)" instead of "benign cystic mesothelioma" 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 = {2021}, 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 = {67}, number = {2}, pages = {363-373}, 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 = {2021}, 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 = {12}, number = {4}, pages = {491-503}, 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}, pmid = {33318203}, issn = {1091-6490}, support = {P20 GM103466/GM/NIGMS NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; R01 ES030948/ES/NIEHS NIH HHS/United States ; Z01 BC010816/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; Asbestos, Crocidolite ; Asbestosis/*genetics ; Family ; Female ; *Genetic Predisposition to Disease ; Genomic Instability ; Germ-Line Mutation/*genetics ; Heterozygote ; Humans ; Incidence ; Inflammation/pathology ; Male ; Mesothelioma/*genetics ; Mice ; Middle Aged ; RecQ Helicases/*genetics ; }, 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 = {2021}, 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 = {39}, number = {3}, pages = {644-657}, 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 "drug repositioning" 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}, mesh = {Aged ; Antineoplastic Agents, Immunological/*therapeutic use ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Male ; Mesothelioma, Malignant/diagnostic imaging/*drug therapy ; Nivolumab/*therapeutic use ; Peritoneal Neoplasms/diagnostic imaging/*drug therapy ; Radiography, Abdominal ; Tomography, X-Ray Computed ; }, 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 = {2021}, 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 = {21}, number = {4}, pages = {413-424}, 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}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/*genetics/metabolism ; Extracellular Matrix Proteins/*genetics/metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; HMGB1 Protein/*genetics/metabolism ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/chemically induced/diagnosis/*genetics/mortality ; Male ; Mesothelioma, Malignant/chemically induced/diagnosis/*genetics/mortality ; Microarray Analysis ; Middle Aged ; Prognosis ; Proportional Hazards Models ; }, 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 = {2021}, 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}, mesh = {Biomarkers ; Biomarkers, Tumor ; Chromatography, Liquid ; Humans ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms ; ROC Curve ; Tandem Mass Spectrometry ; }, 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}, mesh = {Air Pollutants, Occupational/adverse effects ; Animals ; Asbestos/*adverse effects ; Asbestos, Amphibole/adverse effects ; Autoimmune Diseases/chemically induced/metabolism ; Bodily Secretions/*drug effects ; Cells, Cultured ; Cytokines/*metabolism ; Lung Neoplasms/chemically induced/metabolism ; Macrophages, Alveolar/*drug effects/metabolism ; Mesothelioma, Malignant/chemically induced/metabolism ; Mice ; Mice, Inbred C57BL ; Mineral Fibers/adverse effects ; Minerals/*adverse effects ; Occupational Exposure/adverse effects ; Particle Size ; Particulate Matter/adverse effects ; Transcription, Genetic/*drug effects ; }, 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}, mesh = {Female ; Humans ; *Lupus Erythematosus, Systemic/complications/diagnosis/drug therapy ; *Mesothelioma/diagnosis/drug therapy ; *Mesothelioma, Malignant ; *Pleural Effusion/etiology ; *Pleural Neoplasms/diagnosis/drug therapy ; }, 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}, mesh = {Calcitriol/*pharmacology/therapeutic use ; Cell Cycle Checkpoints/drug effects/physiology ; Cell Line, Tumor ; Cell Proliferation/*drug effects/physiology ; Cell Survival/*drug effects/physiology ; Humans ; Mesothelioma, Malignant/drug therapy/*pathology ; Tumor Cells, Cultured ; Vitamins/*pharmacology/therapeutic use ; }, 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}, mesh = {B7-H1 Antigen ; Humans ; *Lung Neoplasms ; Lymphocytes, Tumor-Infiltrating ; *Mesothelioma, Malignant ; Prognosis ; Tumor Microenvironment ; }, 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 = {2021}, 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 = {60}, number = {5}, pages = {663-665}, pmid = {33055488}, issn = {1349-7235}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms/radiotherapy ; *Mesothelioma/radiotherapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/radiotherapy ; }, }
@article {pmid33055477, year = {2021}, 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 = {60}, number = {5}, pages = {771-775}, pmid = {33055477}, issn = {1349-7235}, mesh = {*Asbestos ; Europe ; Female ; *Hodgkin Disease/radiotherapy ; Humans ; Japan/epidemiology ; *Mesothelioma/diagnosis/etiology ; *Mesothelioma, Malignant ; Middle Aged ; *Pleural Neoplasms/etiology/radiotherapy ; }, 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}, mesh = {Air Pollutants/*toxicity ; Animals ; Asbestos, Crocidolite ; Carcinogenicity Tests ; Inhalation Exposure ; Lung ; Lung Neoplasms ; Mesothelioma ; Nanotubes, Carbon/*toxicity ; Rats ; Trachea/drug effects ; }, 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}, mesh = {Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Chemotherapy, Adjuvant/methods ; Child ; Child, Preschool ; Cisplatin/therapeutic use ; Cytoreduction Surgical Procedures/methods ; Europe ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Mesothelioma, Malignant/*drug therapy ; Neoadjuvant Therapy/methods ; Peritoneal Neoplasms/drug therapy ; Retrospective Studies ; Young Adult ; }, 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}, 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}, 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 "best fit" 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}, mesh = {Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/genetics/metabolism ; Computational Biology/*methods ; Databases, Genetic ; Down-Regulation ; Drug Discovery/*methods ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Genes, Neoplasm ; Humans ; Mesothelioma, Malignant/*drug therapy/*genetics ; Microarray Analysis ; Molecular Targeted Therapy/methods ; Peroxisome Proliferator-Activated Receptors/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Prognosis ; Protein Interaction Maps/genetics ; Up-Regulation ; }, 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}, mesh = {Adenoviridae/genetics ; Apoptosis/drug effects ; Asbestos/toxicity ; Cell Cycle Proteins/*antagonists &amp; inhibitors/genetics/pharmacology ; Cell Line, Tumor ; Cell Survival/*drug effects ; DNA Damage/drug effects ; Humans ; Mesothelioma, Malignant/chemically induced/*drug therapy/genetics/virology ; Oncolytic Virotherapy ; Oncolytic Viruses/genetics ; Phosphorylation/drug effects ; Protein Kinase Inhibitors ; Protein-Tyrosine Kinases/*antagonists &amp; inhibitors/genetics ; Pyrazoles/*pharmacology ; Pyrimidinones/*pharmacology ; }, 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}, mesh = {Humans ; Mesothelioma, Malignant/*surgery ; Pleura/*surgery ; Pleural Neoplasms/surgery ; Thoracic Surgical Procedures/*methods ; Treatment Outcome ; }, 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}, mesh = {Asbestos/adverse effects ; *Biomarkers, Tumor/analysis/blood/genetics/metabolism ; Calbindin 2/analysis/blood/genetics/metabolism ; Extracellular Matrix Proteins/analysis/blood/genetics/metabolism ; HMGB1 Protein/analysis/blood/genetics/metabolism ; Humans ; Mesothelioma, Malignant/*blood/chemistry/genetics/metabolism ; Multidrug Resistance-Associated Proteins/analysis/*blood/genetics/metabolism ; Pleural Neoplasms/blood/chemistry/genetics/metabolism ; Prognosis ; Proteomics ; }, 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}, pmid = {33012428}, issn = {1558-5069}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Asbestos/adverse effects ; Computational Biology/methods ; Epigenesis, Genetic ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Mesothelioma, Malignant/etiology/*genetics ; Pleural Neoplasms/etiology/genetics ; Transcriptome ; }, 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}, 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 "locus minoris resistentiae" 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}, mesh = {Asbestos/*toxicity ; CD8-Positive T-Lymphocytes/*immunology/pathology ; Humans ; *Immunity, Cellular ; Mesothelioma, Malignant/chemically induced/*immunology/pathology ; T-Lymphocytes, Regulatory/*immunology/pathology ; }, 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}, mesh = {*Asbestos ; Cities ; Colombia ; Environmental Exposure ; *Occupational Exposure ; Waste Disposal Facilities ; }, 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 = {2021}, 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 = {36}, number = {1}, pages = {15-26}, doi = {10.1515/reveh-2020-0061}, pmid = {32966235}, issn = {2191-0308}, mesh = {Animals ; Asbestos/*toxicity ; Gastrointestinal Neoplasms/chemically induced/*epidemiology/pathology ; Humans ; Mesothelioma/chemically induced/epidemiology/pathology ; }, 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 {pmid32959879, year = {2021}, author = {Giles Murphy, T and Bornstein, S and Oudyk, J and Demers, PA}, title = {A Quantitative Retrospective Exposure Assessment for Former Chrysotile Asbestos Miners and Millers from Baie Verte, NL, Canada.}, journal = {Annals of work exposures and health}, volume = {65}, number = {1}, pages = {113-126}, pmid = {32959879}, issn = {2398-7316}, support = {//CIHR/Canada ; }, mesh = {*Asbestos/adverse effects ; Asbestos, Serpentine ; Canada ; Humans ; Italy ; *Mesothelioma/chemically induced/epidemiology ; *Occupational Diseases/chemically induced/epidemiology ; *Occupational Exposure ; Quebec ; Retrospective Studies ; }, abstract = {Despite numerous studies of asbestos workers in the epidemiologic literature, there are very few cohort studies of chrysotile asbestos miners/millers that include high-quality retrospective exposure assessments. As part of the creation of the Baie Verte Miners' Registry in 2008, a two-dimensional job exposure matrix (JEM) was developed for estimating asbestos exposures for former chrysotile asbestos miners/millers. Industrial hygiene data collected between 1963 and 1994 were analysed to assess validity for use in a retrospective exposure assessment and epidemiologic study. Registered former employees were divided into 52 exposure groups (EGs) based on job title and department and mean asbestos concentrations were calculated for each EG. The resulting exposure estimates were linked to individual registrants' work histories allowing for the calculation of cumulative asbestos exposure for each registrant. The distribution of exposure for most EGs (82.6%) could be described as fitting a log-normal distribution, although variability within some EGs (55%) exceeded a geometric standard deviation (GSD) of 2.5. Overall, the data used to create EGs in the development of the JEM were deemed to be of adequate quality for estimating cumulative asbestos exposures for the former employees of the Baie Verte asbestos mine/mill. The variability between workers in the same job was often high and is an important factor to be considered when using estimates of cumulative asbestos exposure to adjudicate compensation claims. The exposures experienced in this cohort were comparable to those of other chrysotile asbestos miners/millers cohorts, specifically Italian and Québec cohorts.}, }
@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/ ; }, mesh = {Animals ; *Asbestos/toxicity ; Disease Models, Animal ; *Mesothelioma/chemically induced/therapy ; *Mesothelioma, Malignant ; Mice ; *Occupational Exposure ; }, 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}, pmid = {32929059}, issn = {2041-4889}, mesh = {B7-H1 Antigen/*genetics/*metabolism ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Down-Regulation ; HEK293 Cells ; Humans ; Mesothelioma, Malignant/genetics/*metabolism/pathology ; MicroRNAs/genetics/*metabolism ; Transfection ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, 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 ; }, mesh = {Animals ; CCAAT-Enhancer-Binding Proteins/genetics ; Cell Line, Tumor ; Cell Proliferation ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; *Lung Neoplasms/genetics ; *Mesothelioma/drug therapy/genetics ; *Mesothelioma, Malignant ; Mice ; *Pleural Neoplasms/drug therapy/genetics ; Ubiquitin-Protein Ligases ; }, 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}, mesh = {Animals ; Eflornithine ; Heterografts ; *Lung Neoplasms/drug therapy ; *Mesothelioma, Malignant ; Mice ; Mice, Nude ; Polyamines ; }, 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 "extended adjuvant DFMO treatment" 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 "DFMO treatment" 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}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Female ; GATA3 Transcription Factor/*analysis ; Humans ; *Immunohistochemistry ; Ki-67 Antigen/analysis ; Male ; Mesothelioma, Malignant/*chemistry/mortality/pathology/therapy ; Middle Aged ; Pleural Neoplasms/*chemistry/mortality/pathology/therapy ; Predictive Value of Tests ; Prognosis ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, 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 = {G0601840/MRC_/Medical Research Council/United Kingdom ; G1002610/MRC_/Medical Research Council/United Kingdom ; MR/R009120/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Basigin/metabolism ; Humans ; *Mesothelioma, Malignant ; Monocarboxylic Acid Transporters ; Muscle Proteins/metabolism ; Prognosis ; *Symporters ; }, 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}, mesh = {Animals ; Biomarkers, Tumor/genetics/*metabolism ; Genomics/*methods ; Humans ; Mesothelioma, Malignant/genetics/metabolism/*pathology ; Phenomics/*methods ; Pleural Neoplasms/genetics/metabolism/*pathology ; }, 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}, mesh = {*Asbestos/toxicity ; Belgium/epidemiology ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology ; *Mesothelioma, Malignant ; *Occupational Exposure ; Spatial Analysis ; }, 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}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/*adverse effects ; Clinical Trials as Topic ; Humans ; Mesothelioma, Malignant/chemically induced/*therapy ; Neoplasm Staging ; Pleural Neoplasms/chemically induced/*therapy ; Radiotherapy, Adjuvant ; }, 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}, mesh = {Animals ; *Asbestos ; Epithelium ; *Ferroptosis ; Ferrous Compounds ; Hydrogen Peroxide ; Macrophages ; *Mesothelioma ; Mutagens ; Rats ; beta Catenin/genetics ; }, 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 = {2021}, 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 = {45}, number = {2}, pages = {255-262}, doi = {10.1097/PAS.0000000000001574}, pmid = {32826527}, issn = {1532-0979}, mesh = {Adolescent ; Adult ; Catheters, Indwelling/*adverse effects ; Female ; Humans ; Male ; Mesothelioma, Malignant/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/*etiology/pathology ; Portasystemic Shunt, Surgical/*adverse effects ; Ventriculoperitoneal Shunt/*adverse effects ; Young Adult ; }, 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}, mesh = {Adolescent ; Adult ; Asbestos/*adverse effects ; Carcinogens/*toxicity ; Child ; Child, Preschool ; Female ; Geography ; Humans ; Infant ; Infant, Newborn ; Male ; Mesothelioma/epidemiology/etiology/*mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Peru/epidemiology ; Prognosis ; Survival Rate ; Young Adult ; }, 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 = {2021}, author = {Johnson, NF}, title = {Inhalation Toxicity of Talc.}, journal = {Journal of aerosol medicine and pulmonary drug delivery}, volume = {34}, number = {2}, pages = {79-107}, 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}, doi = {10.1097/COC.0000000000000745}, 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 = {2021}, author = {Barbieri, PG and Mirabelli, D}, title = {Diagnosis of lung cancer: a necropsy-based study of 128 cases (1997-2016).}, journal = {Tumori}, volume = {107}, number = {3}, pages = {226-230}, doi = {10.1177/0300891620949665}, pmid = {32811344}, issn = {2038-2529}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Asbestosis/diagnosis ; Autopsy/methods ; Female ; Humans ; Lung Neoplasms/chemically induced/*diagnosis ; Male ; Mesothelioma/chemically induced/diagnosis ; Mesothelioma, Malignant/chemically induced/diagnosis ; Middle Aged ; Pleural Diseases/chemically induced/diagnosis ; Pleural Neoplasms/chemically induced/diagnosis ; Prevalence ; }, 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 {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 {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}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Male ; Mesothelioma, Malignant/mortality/*pathology/therapy ; Middle Aged ; Peritoneal Neoplasms/mortality/*pathology/therapy ; Young Adult ; }, 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}, mesh = {Aged ; Biomarkers, Tumor ; Diagnosis, Differential ; Fatal Outcome ; Humans ; Immunohistochemistry ; Male ; Mesothelioma/diagnosis/*pathology ; Mesothelioma, Malignant ; Orchiectomy ; Testicular Hydrocele/diagnosis ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Testis/*pathology/surgery ; }, 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 ; }, mesh = {Adenocarcinoma/diagnosis/*pathology ; Biomarkers, Tumor/analysis ; Humans ; Lung Neoplasms/diagnosis/*pathology ; Mesothelioma, Malignant/diagnosis/*pathology ; Pleural Effusion/diagnosis/*pathology ; Prognosis ; }, 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/ ; }, mesh = {Calbindin 2 ; Cross-Sectional Studies ; Humans ; *Mesothelioma/diagnosis ; *Mesothelioma, Malignant ; *Pleural Neoplasms/diagnosis ; }, 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/ ; }, mesh = {Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cyclin-Dependent Kinase 4/*antagonists &amp; inhibitors ; Cyclin-Dependent Kinase 6/*antagonists &amp; inhibitors ; Energy Metabolism/*drug effects ; Glycolysis/drug effects ; Humans ; Mesothelioma, Malignant/drug therapy/*metabolism ; Mitochondria/drug effects/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Piperazines/pharmacology ; Pleural Neoplasms/drug therapy/*metabolism ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/antagonists &amp; inhibitors/metabolism ; Pyridines/pharmacology ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/*antagonists &amp; inhibitors/metabolism ; }, 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}, support = {U01 CA214195/CA/NCI NIH HHS/United States ; }, 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 "breath testing" 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, "NCI Early Detection Research Network: Making Cancer Detection Possible."}, }
@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}, support = {81802995//National Natural Science Foundation of China/ ; 2018RC020, 2018KY024//Medical Science and Technology Project of Zhejiang Province/ ; }, 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}, mesh = {Humans ; *Lung Neoplasms/diagnosis/epidemiology/therapy ; *Mesothelioma/diagnosis/epidemiology/therapy ; *Mesothelioma, Malignant ; *Pleural Neoplasms/epidemiology/therapy ; Spain/epidemiology ; }, 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}, mesh = {Asbestos ; Asbestosis/*epidemiology ; Cohort Studies ; Construction Materials ; Female ; Humans ; Male ; Mesothelioma/epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; Occupational Exposure/*statistics &amp; numerical data ; Sicily/epidemiology ; }, 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}, 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, "[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." By contrast, Marinaccio et al (1) stated, "[t]he economic sectors more frequently associated with asbestos exposure were construction, steel mills, metal-working industry, textile industry and agriculture." The possibility of exposure in the "agriculture economic sector" 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}, mesh = {Adult ; Diagnosis, Differential ; Giant Cell Arteritis/diagnosis ; Glucocorticoids/therapeutic use ; Humans ; Male ; Mesothelioma, Malignant/*complications ; Paraneoplastic Syndromes/*complications/*diagnosis ; Peritoneal Neoplasms/*complications ; Polymyalgia Rheumatica/diagnosis ; }, 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}, mesh = {Aged ; Biomarkers, Tumor/genetics/*metabolism ; CD8-Positive T-Lymphocytes/immunology/metabolism/pathology ; Cytokines/metabolism ; Female ; Follow-Up Studies ; Humans ; Interleukins/genetics/*metabolism ; Macrophage Colony-Stimulating Factor/genetics/*metabolism ; Macrophages/immunology/metabolism/pathology ; Male ; Mesothelioma, Malignant/genetics/immunology/metabolism/*pathology ; Monocytes/immunology/metabolism/pathology ; Pleural Effusion/immunology/metabolism/*pathology ; Pleural Neoplasms/genetics/immunology/metabolism/*pathology ; Prognosis ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics/*metabolism ; Survival Rate ; T-Lymphocytes, Cytotoxic/immunology ; Tumor Microenvironment/immunology ; }, 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}, mesh = {Cohort Studies ; Cosmetics ; Europe/epidemiology ; Extraction and Processing Industry ; Humans ; Mesothelioma/*epidemiology ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; Pleural Neoplasms/*epidemiology ; Risk Factors ; *Talc ; Vermont/epidemiology ; }, 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}, mesh = {Alleles ; Animals ; DNA Repair ; *Genetic Association Studies ; *Genetic Predisposition to Disease ; Genetic Variation ; *Germ-Line Mutation ; Humans ; Mesothelioma, Malignant/*genetics ; Pedigree ; *Polymorphism, Single Nucleotide ; }, 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}, mesh = {*Asbestos/toxicity ; *Asbestosis/diagnostic imaging/epidemiology ; Humans ; *Lung Neoplasms/epidemiology/etiology ; *Mesothelioma/epidemiology/etiology/therapy ; Pleura ; }, 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 "safe" 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}, 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}, mesh = {Confidence Intervals ; Cosmetics ; Data Interpretation, Statistical ; Humans ; Mesothelioma/*epidemiology ; Mining ; Occupational Diseases/*epidemiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology ; Risk ; Talc/*adverse effects ; }, 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}, mesh = {*Breast Neoplasms ; Female ; Humans ; *Lung Neoplasms/diagnostic imaging ; Male ; *Mesothelioma/diagnostic imaging ; *Mesothelioma, Malignant ; Middle Aged ; *Pleural Neoplasms/diagnostic imaging ; }, 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}, mesh = {Asbestos/toxicity ; Humans ; Male ; Mesothelioma, Malignant/*diagnosis/pathology ; Middle Aged ; Occupational Exposure/adverse effects ; Sarcoma/*diagnosis/pathology ; Testicular Neoplasms/*diagnosis/pathology ; WT1 Proteins/analysis ; }, 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 "application actuality" 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}, mesh = {Carcinogenesis ; Cohort Studies ; Female ; *Genes, Tumor Suppressor ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma, Malignant/*genetics ; Middle Aged ; *Mutation ; *Oncogenes ; Paraffin Embedding ; }, 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}, 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 "Although a valuable method in occupational epidemiology, job-exposure matrices are no magic fix" 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 "average" 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 ; }, mesh = {Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/epidemiology/pathology/*therapy ; Middle Aged ; Pleural Neoplasms/epidemiology/pathology/*therapy ; Pneumonectomy/*mortality ; Prognosis ; Radiotherapy/*mortality ; Registries/*statistics &amp; numerical data ; Survival Rate ; Young Adult ; }, 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}, 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 "certainly occupational exposed" 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}, mesh = {*Asbestos/adverse effects ; Asbestos, Serpentine ; *Asbestosis ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; *Occupational Exposure/adverse effects ; }, 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}, 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}, pmid = {32253443}, issn = {1795-990X}, mesh = {Adolescent ; Adult ; Aged ; *Asbestos ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Italy/epidemiology ; Male ; Mesothelioma, Malignant/*epidemiology ; Middle Aged ; Occupational Diseases/*epidemiology ; *Occupational Exposure ; Pericardium/*pathology ; Registries ; Testicular Neoplasms/*epidemiology ; Young Adult ; }, 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}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab/administration &amp; dosage ; Cisplatin/administration &amp; dosage ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase III as Topic ; *Eligibility Determination ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma, Malignant/*drug therapy/pathology ; Middle Aged ; *Patient Selection ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Survival Rate ; }, 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}, mesh = {Academies and Institutes ; Asbestos/analysis/*toxicity ; Colombia/epidemiology ; Conservation of Natural Resources/*legislation &amp; jurisprudence ; Construction Materials ; Environmental Exposure ; *Epidemiologic Studies ; Female ; Humans ; Intersectoral Collaboration ; Male ; *Manufacturing and Industrial Facilities ; Mesothelioma/epidemiology/etiology/*prevention &amp; control ; Occupational Exposure ; Pleural Neoplasms/epidemiology/etiology/*prevention &amp; control ; Soil Pollutants/analysis ; Universities ; Urban Health ; Waste Disposal Facilities ; }, 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}, mesh = {Animals ; Asbestos/*toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Serpentine/toxicity ; Humans ; Lung Neoplasms/epidemiology/etiology ; Mesothelioma/epidemiology/etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/*adverse effects ; }, 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 = {}, pmid = {32213537}, issn = {2052-4439}, mesh = {Absorptiometry, Photon ; Appetite Stimulants/adverse effects/*therapeutic use ; Australia ; Body Composition/drug effects ; Cachexia/*complications/*drug therapy/etiology/physiopathology ; Clinical Trials, Phase II as Topic ; Cross-Over Studies ; Double-Blind Method ; Humans ; Hydrazines/adverse effects/*therapeutic use ; Linear Models ; Mesothelioma, Malignant/*complications ; Muscle Strength/drug effects ; Oligopeptides/adverse effects/*therapeutic use ; Pilot Projects ; Quality of Life ; Randomized Controlled Trials as Topic ; Weight Gain/drug effects ; }, 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}, 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}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects/analysis ; Female ; Humans ; Male ; Mesothelioma, Malignant/*chemistry ; Middle Aged ; Mineral Fibers/adverse effects/*analysis ; Peritoneal Neoplasms/*chemistry ; Pleural Neoplasms/*chemistry ; Talc/adverse effects/*analysis ; }, 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}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects/analysis ; Asbestos, Amphibole/adverse effects/analysis ; Barbering ; Beauty Culture ; Female ; Humans ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma, Malignant/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects/analysis ; Pleural Neoplasms/epidemiology/etiology ; Talc/*adverse effects/analysis ; Time Factors ; }, 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 = {e000669}, 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}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cell Line, Tumor ; Female ; *Genetic Heterogeneity ; Humans ; Kaplan-Meier Estimate ; Male ; Mesothelioma, Malignant/epidemiology/*genetics/pathology ; Middle Aged ; Mutation/genetics ; Pleural Neoplasms/epidemiology/*genetics/pathology ; Survival Analysis ; Young Adult ; }, 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}, mesh = {*Asbestos/adverse effects ; Autopsy ; Female ; Humans ; Lung ; *Mesothelioma/etiology ; Occupational Exposure ; *Pleural Neoplasms/etiology ; }, 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)