@article {pmid31120100, year = {2019}, author = {Kamiya, H and Peters, S and Sodhi-Berry, N and Reid, A and Gordon, L and de Klerk, N and Brims, F and Musk, AW and Franklin, P}, title = {Validation of an Asbestos Job-Exposure Matrix (AsbJEM) in Australia: Exposure-Response Relationships for Malignant Mesothelioma.}, journal = {Annals of work exposures and health}, volume = {}, number = {}, pages = {}, doi = {10.1093/annweh/wxz038}, pmid = {31120100}, issn = {2398-7316}, abstract = {OBJECTIVES: An asbestos job-exposure matrix (AsbJEM) has been developed to systematically and cost-effectively evaluate occupational exposures in population-based studies. The primary aim of this study was to examine the accuracy of the AsbJEM in determining exposure-response relationships between asbestos exposure estimates and malignant mesothelioma (MM) incidence (indirect validation). The secondary aim was to investigate whether the assumptions used in the development of the original AsbJEM provided accurate asbestos exposure estimates.

METHODS: The study population consisted of participants in an annual health surveillance program, who had at least 3-month occupational asbestos exposure. Calculated asbestos exposure indices included cumulative asbestos exposure and the average exposure intensity, estimated using the AsbJEM and duration of employment. Asbestos and MM exposure-response relationships were compared between the original AsbJEM and its variations based on manipulations of the intensity, duration and frequency of exposure. Twenty-four exposure estimates were calculated for both cumulative asbestos exposure and the average exposure intensity using three exposure intensities (50th, 75th and 90th percentile of the range of mode exposure), four peak durations (15, 30, 60 and 120 min) and two patterns of peak frequency (original and doubled). Cox proportional hazards models were used to describe the associations between MM incidence and each of the cumulative and average intensity estimates.

RESULTS: Data were collected from 1602 male participants. Of these, 40 developed MM during the study period. There were significant associations between MM incidence and both cumulative and average exposure intensity for all estimates. The strongest association, based on the regression-coefficient from the models, was found for the 50th percentile of mode exposure, 15-min peak duration and the doubled frequency of peak exposure. Using these assumptions, the hazard ratios for mesothelioma were 1 (reference), 1.91, 3.24 and 5.37 for the quartiles of cumulative asbestos exposure and 1 (reference), 1.84, 2.31 and 4.40 for the quartiles of the average exposure intensity, respectively.

CONCLUSION: The well-known positive exposure-response relationship between MM incidence and both estimated cumulative asbestos exposure and average exposure intensity was confirmed. The strongest relationship was found when the frequency of peak exposure in the AsbJEM was doubled from the originally published estimates.}, } @article {pmid31119375, year = {2019}, author = {Galani, V and Varouktsi, A and Papadatos, SS and Mitselou, A and Sainis, I and Constantopoulos, S and Dalavanga, Y}, title = {The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment.}, journal = {Cancer chemotherapy and pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00280-019-03878-3}, pmid = {31119375}, issn = {1432-0843}, abstract = {Malignant mesothelioma (MM) is a highly aggressive tumor that is strongly related to asbestos fiber exposure. The tumorigenesis procedure in MM is complex, and many pathogenetic mechanisms including chronic inflammation, deregulation of cell death, and the genomic copy-number losses and gains may contribute to carcinogenesis. MM cells are resistant to TRAIL-mediated apoptosis due to defects in extrinsic apoptotic pathway. CAPS, a regulator of cell cycle and death, may contribute to the MM development as well. BAP1 is the most frequently inactivated gene in MPM; BAP1 deficiency triggers malignant transformation via disruption of DNA repair, transcription regulation, cell metabolism, apoptosis, and ferroptosis. In addition, bcl-2 family proteins as well as abnormal activation of PI3 K/Akt/mTOR pathway and deregulation of the Wnt signaling pathway may result in MM tumorigenesis. Finally, the Hippo pathway plays a critical role in MPM development. Mutations of NF2 and LATS lead to YAP activation in MPM. Thus, inhibition of YAP activity by YAP inhibitors could be a potentially promising treatment option for MM. In conclusion, extensive genetic alterations exist in mesotheliomas associated with the signaling of apoptotic HM cells death. The comprehension of these pathways may contribute to enhancing survival via developing new effective therapeutic strategies.}, } @article {pmid31110054, year = {2019}, author = {Waqar, AB and Menzies, D and Casey, M and Doran, M}, title = {Paraneoplastic phenomenon in mesothelioma.}, journal = {Thorax}, volume = {}, number = {}, pages = {}, doi = {10.1136/thoraxjnl-2019-213176}, pmid = {31110054}, issn = {1468-3296}, abstract = {A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy.}, } @article {pmid31107974, year = {2019}, author = {Milosevic, V and Kopecka, J and Salaroglio, IC and Libener, R and Napoli, F and Izzo, S and Orecchia, S and Ananthanarayanan, P and Bironzo, P and Grosso, F and Tabbò, F and Comunanza, V and Alexa-Stratulat, T and Bussolino, F and Righi, L and Novello, S and Scagliotti, GV and Riganti, C}, title = {Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.32419}, pmid = {31107974}, issn = {1097-0215}, abstract = {Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM-initiating cells (IC) are known to be drug resistant, but it is unknown if and how stemness-related pathways determine chemoresistance. Moreover, there are no predictive markers of IC-associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness-related pathways. We generated MPM IC s from primary MPM samples and compared the gene expression and chemo-sensitivity profile of IC and differentiated/adherent cells (AC) of the same patient. Compared to AC, IC had up-regulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed. ABCB5-knocked-out (KO) IC clones were re-sensitized to the drugs in vitro and in patient-derived xenografts. ABCB5 was transcriptionally activated by the Wnt/GSK3β/β-catenin/c-myc axis, that also increased IL-8 and IL-1β production. IL-8 and IL-1β-KO IC clones reduced the c-myc-driven transcription of ABCB5 and re-acquired chemosensitivity. ABCB5-KO clones had lower IL-8 and IL-1β secretion, and c-myc transcriptional activity, suggesting that either Wnt/GSK3β/β-catenin and IL-8/IL-1β signaling drive c-myc-mediated transcription of ABCB5. ABCB5 correlated with lower time-to-progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first-line chemotherapy in MPM patients. This article is protected by copyright. All rights reserved.}, } @article {pmid31103412, year = {2019}, author = {Scagliotti, GV and Gaafar, R and Nowak, AK and Nakano, T and van Meerbeeck, J and Popat, S and Vogelzang, NJ and Grosso, F and Aboelhassan, R and Jakopovic, M and Ceresoli, GL and Taylor, P and Orlandi, F and Fennell, DA and Novello, S and Scherpereel, A and Kuribayashi, K and Cedres, S and Sørensen, JB and Pavlakis, N and Reck, M and Velema, D and von Wangenheim, U and Kim, M and Barrueco, J and Tsao, AS}, title = {Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial.}, journal = {The Lancet. Respiratory medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2213-2600(19)30139-0}, pmid = {31103412}, issn = {2213-2619}, abstract = {BACKGROUND: Nintedanib targets VEGF receptors 1-3, PDGF receptors α and β, FGF receptors 1-3, and Src and Abl kinases, which are all implicated in malignant pleural mesothelioma pathogenesis. Here, we report the final results of the phase 3 part of the LUME-Meso trial, which aimed to investigate the efficacy and safety of pemetrexed plus cisplatin combined with nintedanib or placebo in unresectable malignant pleural mesothelioma.

METHODS: This double-blind, randomised, placebo-controlled phase 3 trial was done at 120 academic medical centres and community clinics in 27 countries across the world. Chemotherapy-naive adults (aged ≥18 years) with unresectable epithelioid malignant pleural mesothelioma and ECOG performance status 0-1 were randomly assigned 1:1 via an independently verified random number-generating system to receive up to six 21-day cycles of pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on day 1, then nintedanib (200 mg twice daily) or matched placebo on days 2-21. Patients without disease progression after six cycles received nintedanib or placebo maintenance on days 1-21 of each cycle. The primary endpoint was progression-free survival (investigator-assessed according to mRECIST) in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of their assigned study drug. This study is registered with ClinicalTrials.gov, number NCT01907100.

FINDINGS: Between April 14, 2016, and Jan 5, 2018, 541 patients were screened and 458 were randomly assigned to either the nintedanib group (n=229) or the placebo group (n=229). Median treatment duration was 5·3 months (IQR 2·8-7·3) in the nintedanib group and 5·1 months (2·7-7·8) in the placebo group. After 250 events, progression-free survival was not different between the nintedanib group (median 6·8 months [95% CI 6·1-7·0]) and the placebo group (7·0 months [6·7-7·2]; HR 1·01 [95% CI 0·79-1·30], p=0·91). The most frequently reported grade 3 or worse adverse event in both treatment groups was neutropenia (73 [32%] in the nintedanib group vs 54 [24%] in the placebo group). Serious adverse events were reported in 99 (44%) patients in the nintedanib group and 89 (39%) patients in the placebo group. The only serious adverse event occurring in at least 5% of patients in either group was pulmonary embolism (13 [6%] vs seven [3%]).

INTERPRETATION: The primary progression-free survival endpoint of the phase 3 part of LUME-Meso was not met and phase 2 findings were not confirmed. No unexpected safety findings were reported.

FUNDING: Boehringer Ingelheim.}, } @article {pmid31097089, year = {2019}, author = {MacRae, RM and Ashton, M and Lauk, O and Wilson, W and O'Rourke, N and Simone, CB and Rimner, A}, title = {The role of radiation treatment in pleural mesothelioma: Highlights of the 14th International Conference of the International mesothelioma interest group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {132}, number = {}, pages = {24-27}, doi = {10.1016/j.lungcan.2019.03.023}, pmid = {31097089}, issn = {1872-8332}, abstract = {Radiation remains an important component of mesothelioma treatment in 2018. Its use as a treatment modality continues to evolve as the technology for planning and delivery continues to improve. Use of radiation to improve local control in the involved hemithorax has been a common adjuvant treatment post extrapleural pneumonectomy for many years. Modern treatment options with advanced planning techniques including protons and intensity modulated radiation therapy lead to new potential options for treatment post lung-sparing surgery or in the unresectable setting. Presentations and discussions on the implementation of these strategies for palliation, treatment of oligometastatic recurrence or unresectable disease were the focus of a session dedicated to the role of radiation therapy at the 14th International Conference of the International Mesothelioma Interest Group and are reviewed in this article. Preclinical data to better understand how to integrate radiation and the delivery of novel systemic therapy approached like check point inhibitors are also presented.}, } @article {pmid31095409, year = {2019}, author = {Rosner, D and Markowitz, G and Chowkwanyun, M}, title = {"Nondetected": The Politics of Measurement of Asbestos in Talc, 1971-1976.}, journal = {American journal of public health}, volume = {}, number = {}, pages = {e1-e6}, doi = {10.2105/AJPH.2019.305085}, pmid = {31095409}, issn = {1541-0048}, abstract = {The recent lawsuits against Johnson & Johnson have raised the issue of what and when talcum powder manufacturers knew about the presence of asbestos in their products and what they did or did not do to protect the public. Low-level exposure to asbestos in talc is said to result in either mesothelioma or ovarian cancer. Johnson & Johnson has claimed that there was "no detectable asbestos" in their products and that any possible incidental presence was too small to act as a carcinogen. But what exactly does "nondetected" mean? Here, we examine the historical development of the argument that asbestos in talcum powder was "nondetected." We use a unique set of historical documents from the early 1970s, when low-level pollution of talc with asbestos consumed the cosmetics industry. We trace the debate over the Food and Drug Administration's efforts to guarantee that talc was up to 99.99% free of chrysotile and 99.9% free of amphibole asbestos. Cosmetic talc powder manufacturers, through their trade association, pressed for a less stringent methodology and adopted the term "nondetected" rather than "asbestos-free" as a term of art. Am J Public Health. Published online ahead of print May 16, 2019; e1-e6. doi: 10.2105/AJPH.2019.305085).}, } @article {pmid31092657, year = {2019}, author = {de Boer, NL and van Kooten, JP and Burger, JWA and Verhoef, C and Aerts, JGJV and Madsen, EVE}, title = {Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial.}, journal = {BMJ open}, volume = {9}, number = {5}, pages = {e026779}, doi = {10.1136/bmjopen-2018-026779}, pmid = {31092657}, issn = {2044-6055}, abstract = {INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.

METHODS AND ANALYSIS: The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma.

INTERVENTION: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.

ETHICS AND DISSEMINATION: Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.

TRIAL REGISTRATION NUMBER: NTR7060. EudraCT: 2017-000897-12; Pre-Results.}, } @article {pmid31087402, year = {2019}, author = {Loomis, D and Richardson, DB and Elliott, L}, title = {Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.22985}, pmid = {31087402}, issn = {1097-0274}, support = {R01-OH007803//National Institute for Occupational Safety and Health/ ; }, abstract = {BACKGROUND: While asbestos has long been known to cause mesothelioma, quantitative exposure-response data on the relation of mesothelioma risk and exposure to chrysotile asbestos are sparse.

METHODS: Quantitative relationships of mortality from mesothelioma and pleural cancer were investigated in an established cohort of 5397 asbestos textile manufacturing workers in North Carolina, USA. Eligible workers were those employed between 1950 and 1973 with mortality follow-up through 2003. Individual exposure to chrysotile fibres was estimated on the basis of 3420 air samples covering the entire study period linked to work history records. Exposure coefficients adjusted for age, race, and time-related covariates were estimated by Poisson regression.

RESULTS: Positive, statistically significant associations were observed between mortality from all pleural cancer (including mesothelioma) and time since first exposure (TSFE) to asbestos (rate ratio [RR], 1.19; 95% confidence interval [CI], 1.06-1.34 per year), duration of exposure, and cumulative asbestos fibre exposure (RR, 1.15; 95% CI, 1.04-1.28 per 100 f-years/mL; 10-year lag). Analyses of the shape of exposure-response functions suggested a linear relationship with TSFE and a less-than-linear relationship with cumulative exposure. Restricting the analysis to years when mesothelioma was coded as a unique cause of death yielded stronger but less precise associations.

CONCLUSIONS: These observations support with quantitative data the conclusion that chrysotile causes mesothelioma and encourage exposure-response analyses of mesothelioma in other cohorts exposed to chrysotile.}, } @article {pmid29572002, year = {2018}, author = {Tsim, S and Humphreys, CA and Cowell, GW and Stobo, DB and Noble, C and Woodward, R and Kelly, CA and Alexander, L and Foster, JE and Dick, C and Blyth, KG}, title = {Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of pleural malignancy.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {118}, number = {}, pages = {48-56}, pmid = {29572002}, issn = {1872-8332}, support = {ETM/285//Chief Scientist Office/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor ; Contrast Media ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Magnetic Resonance Imaging/*methods ; Male ; Mesothelioma/*diagnosis/pathology ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/*diagnosis/pathology ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: Pleural Malignancy (PM) is often occult on subjective radiological assessment. We sought to define a novel, semi-objective Magnetic Resonance Imaging (MRI) biomarker of PM, targeted to increased tumour microvessel density (MVD) and applicable to minimal pleural thickening.

MATERIALS AND METHODS: 60 consecutive patients with suspected PM underwent contrast-enhanced 3-T MRI then pleural biopsy. In 58/60, parietal pleura signal intensity (SI) was measured in multiple regions of interest (ROI) at multiple time-points, generating ROI SI/time curves and Mean SI gradient (MSIG: SI increment/time). The diagnostic performance of Early Contrast Enhancement (ECE; which was defined as a SI peak in at least one ROI at or before 4.5 min) was compared with subjective MRI and Computed Tomography (CT) morphology results. MSIG was correlated against tumour MVD (based on Factor VIII immunostain) in 31 patients with Mesothelioma.

RESULTS: 71% (41/58) patients had PM. Pleural thickening was <10 mm in 49/58 (84%). ECE sensitivity was 83% (95% CI 61-94%), specificity 83% (95% CI 68-91%), positive predictive value 68% (95% CI 47-84%), negative predictive value 92% (78-97%). ECE performance was similar or superior to subjective CT and MRI. MSIG correlated with MVD (r = 0.4258, p = .02).

DISCUSSION: ECE is a semi-objective, perfusion-based biomarker of PM, measurable in minimal pleural thickening. Further studies are warranted.}, } @article {pmid31078776, year = {2019}, author = {Salaroglio, IC and Kopecka, J and Napoli, F and Pradotto, M and Maletta, F and Costardi, L and Gagliasso, M and Milosevic, V and Ananthanarayanan, P and Bironzo, P and Tabbò, F and Cartia, CF and Passone, E and Comunanza, V and Ardissone, F and Ruffini, E and Bussolino, F and Righi, L and Novello, S and Di Maio, M and Papotti, M and Scagliotti, G and Riganti, C}, title = {Potential diagnostic and prognostic role of micro-environment 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.2019.03.029}, pmid = {31078776}, issn = {1556-1380}, abstract = {INTRODUCTION: A comprehensive analysis of the immune-cell infiltrate collected from pleural fluid and from biopsies of malignant pleural mesothelioma (MPM) may contribute to understand the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Till now such approach has not routinely been verified.

METHODS: We enrolled in 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsies used for the pathological diagnosis and the immune-phenotype analyses were blindly investigated by multi-parametric flow cytometry. The results were analyzed by Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune-phenotype data with patients' outcome.

RESULTS: The cut-offs of intra-tumor T-regulatory (Treg; >1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4+PD1+ (>5.2%) and CD8+PD1+ (6.4%) cells, CD4+LAG-3+ (>2.8%) and CD8+LAG-3+ (>2.8%) cells, CD4+TIM-3+ (>2.5%) and CD8+TIM-3+ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intra-tumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes (TILs). The immune-phenotype of pleural fluid cells had no prognostic significance. By contrast, the intra-tumor Treg and MDSC levels significantly correlated with progression-free and overall survival, the PD-1+/LAG-3+/TIM-3+ CD4+TILs correlated with overall survival.

CONCLUSIONS: A clear immune-signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome.}, } @article {pmid31078166, year = {2019}, author = {Labrèche, F and Kim, J and Song, C and Pahwa, M and Ge, CB and Arrandale, VH and McLeod, CB and Peters, CE and Lavoué, J and Davies, HW and Nicol, AM and Demers, PA}, title = {The current burden of cancer attributable to occupational exposures in Canada.}, journal = {Preventive medicine}, volume = {122}, number = {}, pages = {128-139}, doi = {10.1016/j.ypmed.2019.03.016}, pmid = {31078166}, issn = {1096-0260}, abstract = {Exposure to occupational carcinogens is often overlooked as a contributor to the burden of cancer. To estimate the proportion of cancer cases attributable to occupational exposure in Canada in 2011, exposure prevalence and levels of 44 carcinogens were informed by data from the Canadian carcinogen exposure surveillance project (CAREX Canada). These were used with Canadian Census (between 1961 and 2011) and Labour Force Survey (annual surveys between 1976 and 2013) data to estimate the number of workers ever exposed to occupational carcinogens. Risk estimates of the association between each carcinogen and cancer site were selected mainly from published literature reviews. Population attributable risks were estimated using Levin's equation and applied to the 2011 cancer statistics from the Canadian Cancer Registry. It is estimated that 15.5 million Canadians alive in 2011 were exposed, during at least one year between 1961 and 2001, to at least one carcinogen in the workplace. Overall, we estimated that in 2011, between 3.9% (95% CI: 3.1%-8.1%) and 4.2% (95% CI: 3.3%-8.7%) of all incident cases of cancer were due to occupational exposure, corresponding to lower and upper numbers of 7700-21,800 cases. Five of the cancer sites - mesothelioma, non-melanoma skin cancer, lung, female breast, and urinary bladder - account for a total of 7600 to 21,200 cancers attributable to occupational exposures such as solar radiation, asbestos, diesel engine exhaust, crystalline silica, and night shift work. Our study highlights cancer sites and occupational exposures that need recognition and efforts by all stakeholders to avoid preventable cancers in the future.}, } @article {pmid30563645, year = {2018}, author = {Rogers, AJ}, title = {Exposures estimates of the Wittenoom mining workforce and town residents - Implications associated with risk estimation for persons exposed to asbestiform riebeckite.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {168-170}, doi = {10.1016/j.taap.2018.06.032}, pmid = {30563645}, issn = {1096-0333}, mesh = {Adult ; Asbestos/analysis ; Asbestos, Crocidolite/analysis/*toxicity ; Australia/epidemiology ; Child ; Dust/analysis ; Environmental Exposure/*statistics & numerical data ; Female ; Humans ; Industry ; Inhalation Exposure/*analysis ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; *Mining ; Occupational Exposure/*statistics & numerical data ; Risk Assessment ; Workforce ; }, abstract = {The mining of crocidolite at Wittenoom from 1943 to 1966 is infamous due to the adverse health outcomes in the mining and milling workforce and the non-mining residents and families. Proportional latency risk analysis provided estimates that 6% of the mine workforce along with 1.9% of women and 1.1% of children residents who were environmentally exposed, have or will die from mesothelioma. The absence of environmental exposure data relevant to the period restricts the extrapolation of these historical risk outcomes being applied to the low level exposures from natural contaminant crocidolite and other amphibole fibres experienced in contemporary mining practices in the Pilbara region.}, } @article {pmid30240694, year = {2018}, author = {Boffetta, P and Mundt, KA and Thompson, WJ}, title = {The epidemiologic evidence for elongate mineral particle (EMP)-related human cancer risk.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {100-106}, doi = {10.1016/j.taap.2018.09.021}, pmid = {30240694}, issn = {1096-0333}, mesh = {Air Pollutants, Occupational/*toxicity ; Asbestos/toxicity ; Carcinogens/toxicity ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Minerals/*toxicity ; Neoplasms/*chemically induced/*epidemiology ; Occupational Exposure ; Particulate Matter/*toxicity ; Risk Assessment ; }, abstract = {Epidemiologic research on the role of fibers and other elongate mineral particles (EMP) and human diseases including cancers has generated a large body of literature over the last decades: nevertheless, there remain some questions for which the scientific community appears unable to reach consensus. Reasons for genuine differences in opinion include (i) ways in which exposures have been classified; (ii) methodological limitations of the available studies, (iii) criteria for the interpretation of study results, including potential underlying biological mechanisms, and (iv) methodology for integrating the evidence. Various approaches have been proposed in recent years to address these issues, which will be illustrated using examples from asbestos, talc, taconite, synthetic mineral fibers and silicon carbide, with emphasis on potential carcinogenic effects. Potential solutions include improved exposure and outcome assessment - including use of biomarkers and other molecular approaches, consideration of potential confounding and other sources of bias, implementation of guidelines for study quality assessment and evidence evaluation and integration.}, } @article {pmid31068670, year = {2019}, author = {Fitzgerald, RC and Rhodes, JM}, title = {Ingested asbestos in filtered beer, in addition to occupational exposure, as a causative factor in oesophageal adenocarcinoma.}, journal = {British journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41416-019-0467-9}, pmid = {31068670}, issn = {1532-1827}, abstract = {Oesophageal adenocarcinoma has become much more common over the past 50 years, particularly in Britain, with an unexplained male to female ratio of > 4:1. Given the use of asbestos filtration in commercial brewing and reports of its unregulated use in British public houses in the 1970's to clear draught beer "slops", we have assessed the hypothesis that ingested asbestos could be a causative factor for this increased incidence. Importantly, occupational asbestos exposure increases the risk of adenocarcinoma but not squamous cell carcinoma of the oesophagus. The presence of asbestos fibres was consistently reported in filtered beverages including beers in the 1970s and asbestos bodies have been found in gastrointestinal tissue, particularly oesophageal tissue, at autopsy. There is no reported association between the intake of alcohol and oesophageal adenocarcinoma but studies would mostly have missed exposure from draught beer before 1980. Oesophageal adenocarcinoma has some molecular similarities to pleural mesothelioma, a condition that is largely due to inhalation of asbestos fibres, including predominant loss of tumour suppressor genes rather than an increase of classical oncogenic drivers. Trends in incidence of oesophageal adenocarcinoma and mesothelioma are similar, rising rapidly over the past 50 years but now plateauing. Asbestos ingestion, either from beer consumed before around 1980, or from occupational exposure, seems a plausible causative factor for oesophageal adenocarcinoma. If this is indeed the case, its incidence should fall back to a low baseline by around 2050.}, } @article {pmid31057996, year = {2019}, author = {Barsky, AR and Cengel, KA and Katz, SI and Sterman, DH and Simone, CB}, title = {First-ever Abscopal Effect after Palliative Radiotherapy and Immuno-gene Therapy for Malignant Pleural Mesothelioma.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4102}, doi = {10.7759/cureus.4102}, pmid = {31057996}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive disease, with few, if any, curative interventions. While there is growing interest in using immunotherapy and immuno-gene therapy to treat MPM, very limited data currently exist for combining these modalities with radiotherapy. Preclinical data suggest that radiotherapy may be combined with immunotherapy to produce disease regression, with abscopal effects in mice with MPM. We report the first-ever case of abscopal effect in a patient with MPM, following radiotherapy and immuno-gene therapy. The patient was a 67-year-old male with prior asbestos exposure who presented with progressive dyspnea and thoracic pain. He underwent partial right pleurectomy, pleural biopsy, and talc pleurodesis, with pathology revealing epithelioid MPM. A subsequent chest computed tomography (CT) scan and fluoro-deoxyglucose positron-emission tomography (FDG-PET) CT scan showed extensive, right-sided, fluoro-deoxyglucose (FDG) avid mass-like pleural thickening encasing the right lung, with likely mediastinal extension, nodal metastases, and vascular compression. He enrolled in a clinical trial in which he received intrapleural interferon-alpha gene therapy but needed to discontinue therapy due to supraventricular tachycardia and superior vena cava syndrome induced from tumor burden. He was emergently treated with palliative radiotherapy to 30 Gy in 10 fractions. He was then started on pemetrexed and cisplatin chemotherapy. His subsequent chest CT scan two months after radiotherapy completion showed a dramatic treatment response within, as well as outside of, the irradiated field. After completion of radiotherapy, he did experience radiation esophagitis requiring nasogastric tube placement. Herein, we highlight the feasibility and efficacy of combining immuno-gene therapy with palliative radiotherapy to produce a substantial treatment response and an abscopal effect in a patient with unresectable MPM.}, } @article {pmid31055741, year = {2019}, author = {Cui, Y and Zha, Y and Li, T and Bai, J and Tang, L and Deng, J and He, R and Dong, F and Zhang, Q}, title = {Oxidative effects of lungs in Wistar rats caused by long-term exposure to four kinds of China representative chrysotile.}, journal = {Environmental science and pollution research international}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11356-019-04978-6}, pmid = {31055741}, issn = {1614-7499}, support = {No. 41472046//National Natural Fund Project of China/ ; No. 41602033//National Natural Youth Fund Project of China/ ; No. YF17-Y12//the Fund Project of Sichuan Medical Law Research Center/ ; No. 2017LZXNYD-J24//Collaborative Fund of Luzhou Government and Southwest Medical University/ ; }, abstract = {Chrysotile accounts for some 90% to 95% of all the asbestos used worldwide. Scientific evidences have shown that asbestos (including chrysotile) exposure is associated with increased rates of lung cancer, asbestosis, and mesothelioma. However, molecular mechanisms underlying the toxicity effects of chrysotile are not clear. This study evaluated the oxidative stress in chronic lung toxicity caused by the intratracheal instillation (IT) of four kinds China representative chrysotile once a month for 12 months in Wistar rats. These results indicated that chrysotile exposure led to an obvious increase in lung mass and slowed the growth of body mass. Inflammation and fibrosis were observed by hematoxylin-eosin (HE) staining. Exposure to chrysotile significantly increased the accumulation of reactive oxygen species (ROS) and the level of lipid peroxidation and decreased antioxidant capacity in lung tissues. Furthermore, 1-6-month chrysotile exposure activated heme oxygenase-1 (HO-1) and heat shock protein 70 (HSP70) expression, whereas 12-month exposure caused significant decreases of two-factor expression levels in XK and MN groups when compared to negative control group. Therefore, our results suggested that chronic chrysotile pulmonary injury in Wistar rats is triggered by oxidative damage. Meanwhile, the oxidative damage of MN and XK was stronger than that of SSX and AKS, and the difference of oxidative damage in four chrysotile could have been brought by its properties, morphology, chemical composition, and particle size. With all the above mentioned in view, we hope that the revealed data in the experiment could contribute to the progress of further researches on the toxicity and mechanism of chrysotile.}, } @article {pmid31046484, year = {2019}, author = {Nowak, AK and McDonnell, A and Cook, A}, title = {Immune checkpoint inhibition for the treatment of mesothelioma.}, journal = {Expert opinion on biological therapy}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/14712598.2019.1606209}, pmid = {31046484}, issn = {1744-7682}, abstract = {INTRODUCTION: Combination chemotherapy is currently standard care for advanced mesothelioma. Checkpoint blockade is a promising new treatment. Areas covered: This review covers clinical use and biomarkers of checkpoint blockade. Medline search used keywords 'mesothelioma' combined with 'checkpoint blockade' OR 'PD-L1' OR 'PD1' OR 'anti-CTLA4'; the search terms AND 'clinical trial' or AND 'biomarker*' were added. Handsearching covered abstracts from relevant meetings from 2016 to 2018 and reference lists. Data informed a narrative review. Expert Opinion: Single agent anti-CTLA4 blockade is inactive in mesothelioma. Single agent PD-1 blockade as second or subsequent treatment gives 20-29% partial responses; no randomized comparisons against placebo or chemotherapy are available. Biomarkers of response have been difficult to identify. There is no consensus as to whether tumor PD-L1 expression predicts outcomes. Combination checkpoint inhibitors (CTLA4 and PD1 blockade) provide a small incremental increase in response rates and progression-free survival. Chemoimmunotherapy is the next frontier.}, } @article {pmid31046142, year = {2019}, author = {Macedo, RF and Cerqueira, EMFP and Algranti, E and Silva, D and De Capitani, EM}, title = {High frequency and severity of pleural changes in former workers exposed to anthophyllite associated with other contaminating amphibole asbestos in Brazil.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.22977}, pmid = {31046142}, issn = {1097-0274}, abstract = {OBJECTIVE: To evaluate the frequency and severity of pleuropulmonary alterations in anthophyllite-exposed former workers in Itapira, São Paulo, Brazil. The amphibole anthophyllite, a magnesium-iron silicate, had its mining, marketing, and use forbidden in Brazil in 1995.

METHODS: Former workers were followed from 1999 to 2011. All completed chest X-ray interpreted using the International Labour Office (ILO) classification. High-resolution computed tomography was used at the final evaluation. Spirometry assessed forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC throughout the follow-up period. Samples from the mined ore were analyzed by X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS).

RESULTS: XRD and SEM-EDS confirmed the presence in ore of anthophyllite at a concentration of 75%, in addition to tremolite and other amphiboles in lower concentrations. Twenty-eight subjects were evaluated. Median time of exposure was 3 years (minimum = 1; maximum = 18; interquartile interval = 1-4). Twenty cases of pleural abnormalities were diagnosed in 26 evaluated (77%). The average latency time was 25.6 ± 7.4 years. Two individuals (7.7%) showed progressive worsening of diffuse pleural thickening (DPT) and exhibited an annual FVC decrease of 85 mL and 150 mL, respectively.

CONCLUSION: This small sample showed a very high index of nonmalignant pleural abnormalities in anthophyllite-exposed workers compared with workers exposed to other kinds of fibers. Rapidly progressive DPT, defined by the severity of pleural compromise, was possibly secondary to the presence of other amphibole types in the inhaled dust. No significant loss of FVC was found in the studied group as a whole. No cases of asbestosis, lung carcinoma, and mesothelioma were diagnosed in this cohort.}, } @article {pmid31038674, year = {2019}, author = {Oey, H and Daniels, M and Relan, V and Chee, TM and Davidson, MR and Yang, IA and Ellis, JJ and Fong, KM and Krause, L and Bowman, RV}, title = {Whole-genome sequencing of human malignant mesothelioma tumours and cell lines.}, journal = {Carcinogenesis}, volume = {}, number = {}, pages = {}, doi = {10.1093/carcin/bgz066}, pmid = {31038674}, issn = {1460-2180}, abstract = {Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes.}, } @article {pmid31033031, year = {2019}, author = {Shih, AR and Kradin, RL}, title = {Malignant mesothelioma in Lynch syndrome: A report of two cases and a review of the literature.}, journal = {American journal of industrial medicine}, volume = {62}, number = {5}, pages = {448-452}, doi = {10.1002/ajim.22968}, pmid = {31033031}, issn = {1097-0274}, abstract = {Malignant mesothelioma is a rare and aggressive cancer most typically associated with prior asbestos exposure. The nature of the relationship between asbestos exposure and hereditary familial syndromes predisposing to malignancy has not been determined. We report two Lynch syndrome patients with paraoccupational asbestos exposure who developed diffuse malignant mesothelioma of the pleura or peritoneum. Interestingly, one showed a separate focus of pleural well-differentiated papillary mesothelioma. It is likely that Lynch syndrome patients are at increased risk for the development of mesothelioma in the setting of exposure to asbestos, even at what is generally considered to be low levels. In the presence of a documented history of low-level asbestos exposure, patients with genetic predisposition disorders (including Lynch syndrome) should be considered to have an independent risk factor modifying the effects of asbestos exposure.}, } @article {pmid31032152, year = {2019}, author = {Rakhra, A and Munir, A and Chilukuri, RS and Nahas, J}, title = {A Rare Case of Malignant Mesothelioma Presenting with Systemic Lupus Erythematosus Seropositivity: A Case Report and Review of Literature.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4092}, doi = {10.7759/cureus.4092}, pmid = {31032152}, issn = {2168-8184}, abstract = {While malignant mesothelioma may initially present in a variety of ways, it is uncommon to present with systemic lupus erythematosus (SLE) seropositivity and thus obscuring its diagnosis. Our case involves a 75-year-old Caucasian male with a past medical history of essential hypertension, remote prostate cancer status post prostatectomy, and lifetime nontobacco use presenting with progressive shortness of breath over one month. After a negative cardiac assessment, a postcardiac catheterization chest X-ray (CXR) revealed a right-sided moderate-to-large pleural effusion that, on further workup, was found to be exudative. Effusion studies were negative for malignancy and bacterial growth. Recurrent accumulation of fluid after a thoracentesis one week prior prompted an autoimmune work up. Positive markers included antinuclear antibodies, anti-double stranded DNA antibodies, and anti-histone antibodies, while anti-Smith antibodies were negative. Although SLE was initially suspected based on serologies, no clinical signs or symptoms were present to fulfill the diagnosis criteria. A trial of oral prednisone resulted in decreased pleural effusion size with no further recurrence. Additional studies included a CT scan of the chest that showed pleural masses confirmed with biopsy to be epithelioid mesothelioma. Given the patient's age and new diagnosis of malignant mesothelioma, we hypothesized that the presence of autoantibodies was likely false positives due to acquired autoantibodies with age, hyperactivity of the immune system from malignancy, and possible prior asbestos exposure.}, } @article {pmid31030080, year = {2019}, author = {Zona, A and Fazzo, L and Minelli, G and De Santis, M and Bruno, C and Conti, S and Comba, P}, title = {Peritoneal mesothelioma mortality in Italy: Spatial analysis and search for asbestos exposure sources.}, journal = {Cancer epidemiology}, volume = {60}, number = {}, pages = {162-167}, doi = {10.1016/j.canep.2019.04.001}, pmid = {31030080}, issn = {1877-783X}, abstract = {BACKGROUND: This study is part of a national plan of epidemiological surveillance of malignant mesothelioma (MM) mortality in Italy. The paper shows the results of malignant peritoneal mesothelioma (MPeM) mortality study in Italian Regions and municipalities.

METHODS: National Bureau of Statistics data for MPeM municipal mortality (ICD-10, Code C45.1) were analyzed in the time-window 2003-2014: mortality standardized rates (reference Italian population, census 2011), temporal trends of the annual national rates, Standardized Mortality Ratios and a municipal clustering analysis were performed.

RESULTS: 747 deaths for MPeM were recorded (0.10/100,000): 464 in men (0.14/100,000) and in 283 women (0.07/100,000). No significant MPeM mortality temporal trend was found. Seventeen municipalities showed excesses of mortality for MPeM in at least one gender and/or overall population. Four clusters in male population, and one in women were identified.

CONCLUSIONS: The study identifies some areas where remediation activities and/or health care actions may be warranted.}, } @article {pmid31023248, year = {2019}, author = {Nagamatsu, Y and Oze, I and Aoe, K and Hotta, K and Kato, K and Nakagawa, J and Hara, K and Kishimoto, T and Fujimoto, N}, title = {Physician requests by patients with malignant pleural mesothelioma in Japan.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {383}, doi = {10.1186/s12885-019-5591-7}, pmid = {31023248}, issn = {1471-2407}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed.

METHODS: This cross-sectional survey was part of a larger study (N = 133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content.

RESULTS: Responses (N = 217) from MPM patients (N = 73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients.

CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.}, } @article {pmid31022494, year = {2019}, author = {Christofidou-Solomidou, M and Pietrofesa, RA and Park, K and Albelda, SM and Serve, KM and Keil, DE and Pfau, JC}, title = {Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice.}, journal = {Toxicology and applied pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.taap.2019.04.018}, pmid = {31022494}, issn = {1096-0333}, abstract = {BACKGROUND: Exposure to the Libby Amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice.

METHODS: Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry.

RESULTS: LA exposure induced a significant increase (p < 0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p < .0001) elevated post-LA exposure, and were significantly (p < .0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells.

CONCLUSIONS: LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases.

SUMMARY: Following acute exposure to Libby Amphibole (LA) asbestos-like fibers, synthetic secoisolariciresinol diglucoside (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.}, } @article {pmid30993422, year = {2019}, author = {Boffetta, P and Donato, F and Pira, E and Luu, HN and La Vecchia, C}, title = {Risk of mesothelioma after cessation of asbestos exposure: a systematic review and meta-regression.}, journal = {International archives of occupational and environmental health}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00420-019-01433-4}, pmid = {30993422}, issn = {1432-1246}, abstract = {PURPOSE: A 'risk reversal' has been observed for several human carcinogens following cessation of exposure, but it is unclear whether it also exists for asbestos-related mesothelioma.

METHODS: We conducted a systematic review of the literature and identified nine studies that reported information on risk of mesothelioma after cessation of asbestos exposure, and performed a meta-regression based on random effects models. As comparison we analyzed results on lung cancer risk from four of these studies.

RESULTS: A total of six risk estimates from five studies were included in the meta-analysis. The summary relative risk (RR) of mesothelioma for 10-year interval since cessation of exposure was 1.02 [95% confidence interval (CI) 0.87-1.19; p-heterogeneity 0.01]. The corresponding RR of lung cancer was 0.91 (95% CI 0.84-0.98).

CONCLUSIONS: This analysis provides evidence that the risk of mesothelioma does not decrease after cessation of asbestos exposure, while lung cancer risk does.}, } @article {pmid30968841, year = {2019}, author = {Marsili, D and Magnani, C and Canepa, A and Bruno, C and Luberto, F and Caputo, A and Fazzo, L and Zona, A and Comba, P}, title = {Communication and health education in communities experiencing asbestos risk and health impacts in Italy.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {70-79}, doi = {10.4415/ANN_19_01_14}, pmid = {30968841}, issn = {2384-8553}, abstract = {INTRODUCTION: Numerous municipalities in Italy currently experience asbestos health impact, in particular excesses of pleural mesothelioma incidence and mortality. This paper presents an integrated analysis of epidemiological studies and communication actions in affected municipalities to highlight how communication has been implemented depending on health impact evidence and involvement of local stakeholders.

METHODOLOGY: Four case studies are identified concerning industrial and natural sources of asbestos exposure having different diseases burden. This integrated analysis benefited from multidisciplinary skills.

DISCUSSION: Evidence of different stakeholders engagement is presented to emphasize their role in the communication process. Similarities and differences among case studies allowed us to identify lessons-learned to be transferred in other asbestos contaminated sites.

CONCLUSIONS: The adoption of communication strategies and practices, since the very early evidence of asbestos health impact, represents a relevant contribution for epidemiological and health surveillance, particularly for those communities where asbestos health impact has only been recently reported.}, } @article {pmid30451463, year = {2018}, author = {Krówczyńska, M and Wilk, E}, title = {Spatial analysis of asbestos exposure and occupational health care in Poland during the period 2004-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.689}, pmid = {30451463}, issn = {1970-7096}, mesh = {Air Pollutants, Occupational/adverse effects/*analysis ; Asbestos/*adverse effects/analysis ; Asbestosis/epidemiology ; Humans ; Inhalation Exposure/adverse effects/*analysis ; Lung Neoplasms/chemically induced/epidemiology ; Manufacturing Industry ; Mesothelioma/chemically induced/epidemiology ; Mineral Fibers ; Occupational Exposure/adverse effects/*analysis ; Occupational Health/*statistics & numerical data ; Poland/epidemiology ; Smoking/epidemiology ; *Spatial Analysis ; Time Factors ; }, abstract = {Asbestos is carcinogenic to humans and exposure to this substance can cause a wide range of diseases. In Poland 1997, a statutory ban was introduced on the production, use and marketing of products containing asbestos. The National Programme for Asbestos Abatement for 2009-2032 includes scheduled activities considering asbestos exposure assessment and health protection. As there are several data sources for asbestos exposure in Poland, which are not linked, the aim of this study was to gather and order them developing a PostgreSQL database, an open-source, objectrelational system. The data gathered combines the following information: the quantity of asbestos-cement products in use, details of asbestos manufacturing plants, the results of the measurements of asbestos fibre concentrations in the air and cases of asbestos-related diseases. The relational database was then used to develop a spatial analysis of asbestos monitoring and exposure in Poland to demonstrate the current state of realisation of the National Asbestos Abatement Programme in the country for 2009-2032 with the use of geoinformation techniques. The use of a database on health aspects of occupational and environmental asbestos exposure was also proposed in Asbestos, Asbestosis, and Cancer: Helsinki Criteria update 2014.}, } @article {pmid30946862, year = {2019}, author = {Finkelstein, MM}, title = {A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.}, journal = {Toxicology and applied pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.taap.2019.03.023}, pmid = {30946862}, issn = {1096-0333}, abstract = {Dr. Garabrant presented a paper concerning a comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans at the Elongate Mineral Particles Conference in Charlottesville, Virginia in 2017. I was a participant at the Conference. Following Dr. Garabrant's talk, I rose in question period to point out that he had not considered information about the occurrence of mesothelioma in several cohorts that was published after the studies that he cited. These additional data were still not addressed in the paper published in your Journal. I believe that your readers would be interested in these, so this letter is written to draw the additional data to their attention.}, } @article {pmid30944991, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {A survey of patient and caregiver experience with malignant pleural mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00520-019-04760-x}, pmid = {30944991}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with poor prognosis. As there is little information on the lived experience of MPM, our aim was to document the experience of MPM patients and their caregivers.

METHODS: Surveys for MPM patients and caregivers were developed from previous interviews with patients, caregivers, and health professionals, about treatments and decision-making. Participants were recruited from two hospitals, government compensation body, and support groups.

RESULTS: Survey responses were received from 78 MPM patients and 106 caregivers from January to September 2014.

PATIENTS: 85% male, median age 69 years, median time since diagnosis 15 months. Caregivers: median age 68, 91% female, 90% spouse of MPM patient, 95% bereaved. Most participants felt informed about treatment options but only 69% thought all treatment options were discussed. Chemotherapy was discussed most frequently (92-95%); ~80% had sufficient information for decision-making. Decision regarding chemotherapy was made by patient considering doctor's opinion (24%), doctor and patient equally (18%), and doctor (17%). Participants 'agreed'/'strongly agreed' that they made the right decision about chemotherapy (patients 81%, caregivers 60%), but 5% and 16%, respectively, regretted the decision. Most participants received 'sufficient' support (71%). A quarter reported seeing cancer nurse specialists. Palliative care referral: 31% patients, 85% caregivers. Caregivers would have liked to talk to someone by themselves (41%), more time with doctors (30%), psychological support (29%), and clearer information (31%). Bereaved caregivers requested grief counselling (39%) and post-death consultation with specialists (23-25%).

CONCLUSIONS: Satisfaction with treatment was high, but participants identified need for improved communication and quality information, discussion about all treatments, end-of-life assistance, and caregiver support after the patient's death.}, } @article {pmid30941506, year = {2019}, author = {Lococo, F and Di Stefano, T and Rapicetta, C and Piro, R and Gelli, MC and Muratore, F and Ricchetti, T and Taddei, S and Zizzo, M and Cesario, A and Facciolongo, N and Paci, M}, title = {Thoracic Hyper-IgG4-Related Disease Mimicking Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00408-019-00224-5}, pmid = {30941506}, issn = {1432-1750}, abstract = {We report a rare case of a IgG4-related disease presenting with recurrent pleural effusion, pleural thickness and multiple mediastinal lymphadenopathies and no involvement of other extrathoracic organs. A 65-year-old man with a previous asbestos exposure presented with cough and pain discomfort. A large right pleural effusion was detected and evacuated (siero-haematic liquid). With the suspicious of a pleural mesothelioma, a CT-scan before and a 18F-FDG PET/CT-scan later were performed revealing multiple pleural thickenings and multiple mediastinal lymphadenopathies with radiotracer uptake. EBUS-TBNA EBUS-TBNA did not result in a formal pathological diagnosis; thus, multiple pleural biopsy were performed via right thoracoscopy. At pathology the pleura was markedly thickened by a chronic fibroinflammatory process with scattered lymphoid follicles and a large number of mature plasma cells. Immunohistochemistry shows a mixed B (CD20+) and T (CD3+) population of lymphocytes, without light chain restriction and an increased number of IgG4-positive plasma cells. A presumptive diagnosis of IgG4-related disease was formulated. Total body CT-scan excluded other organ involvement. Blood test showed elevated serum IgG4 concentrations (253 mg/dL) and mild elevation of acute-phase reactants (C-reactive protein 10.7 mg/L). Autoimmune profile was negative. A diagnosis of definite IgG4-related disease was made, and treatment with prednisone 50 mg/day was started.}, } @article {pmid30937282, year = {2019}, author = {Haygarth, M and Zaw, KK and Yachmenikova, V and Pokorny, AMJ and Kwong, KK and Heraganahally, SS}, title = {Bilateral diffuse pulmonary infiltrates secondary to malignant peritoneal mesothelioma - A rare clinical presentation.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {326-327}, doi = {10.1016/j.rmcr.2019.03.003}, pmid = {30937282}, issn = {2213-0071}, abstract = {Diffuse pulmonary metastasis secondary to primary peritoneal malignant mesothelioma is rarely reported in the literature. In this report we describe a 59-year-old Caucasian women with no known previous asbestos exposure presenting with bilateral diffuse pulmonary opacities in association with primary malignant peritoneal mesothelioma. The diagnosis was confirmed by ultrasound guided abdominal and bronchoscopy, trans-bronchial lung biopsy. The biopsy demonstrated positive staining with AE1/3, CK7, CK5/6, WT1, calretinin and D2 40. The cells were negative for BerEP4, PAX8, CA125, ER, CD34, ERG, P63, P40, Melan A, Gata3 and mammaglobin. The morphology and immunohistochemical profile supported a diagnosis of epithelioid malignant mesothelioma.}, } @article {pmid30936339, year = {2019}, author = {Muralidhar, V and Raghav, P and Das, P and Goel, A}, title = {A case from India of pleural malignant mesothelioma probably due to domestic and environmental asbestos exposure: a posthumous report.}, journal = {BMJ case reports}, volume = {12}, number = {3}, pages = {}, doi = {10.1136/bcr-2018-227882}, pmid = {30936339}, issn = {1757-790X}, abstract = {India is the largest consumer of asbestos in the world. There is no report from India of mesothelioma related to asbestos. The case is a 42-year-old man who died of pleural mesothelioma. He was exposed to asbestos domestically and from the environment since birth. Two of his close family members worked in a factory that used asbestos. The living quarter of the family was within the premises of the factory. Asbestos waste was strewn on the grounds surrounding the quarters. After decades of legal battles by workers and families exposed to asbestos, Indian courts have ordered remedial measures and compensation to people, who are exposed to asbestos at work and the environment. Mesothelioma, currently in epidemic proportions in the west where asbestos production was banned in the 1990s, could rise to alarming levels in the next decades in India if the legal remedial measures are not implemented soon.}, } @article {pmid30928905, year = {2019}, author = {Reid, A and Franklin, P and Berry, G and Peters, S and Sodhi-Berry, N and Brims, F and Musk, AW and de Klerk, NH}, title = {Response to letter by Farioli et al.}, journal = {Occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1136/oemed-2019-105740}, pmid = {30928905}, issn = {1470-7926}, } @article {pmid30927363, year = {2019}, author = {Koutros, S and Lubin, JH and Graubard, BI and Blair, A and Stewart, PA and Beane Freeman, LE and Silverman, DT}, title = {Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile.}, journal = {American journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/aje/kwz086}, pmid = {30927363}, issn = {1476-6256}, abstract = {We extended the mortality follow-up of a cohort of 25,460 workers employed at eight acrylonitrile (AN)-producing facilities in the United States by 21 years. Based on 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and mortality. Standardized mortality ratios (SMR) based on deaths through December 31, 2011 were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios (HR) were estimated by Cox proportional hazards regression. All-cause mortality and mortality from total cancer were less than expected compared with the U.S. population. We observed an excess of death due to mesothelioma (SMR=2.24,95%CI:1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (N=808 deaths), with an HR>12.1 ppm-year vs Unexposed=1.43 (95%CI:1.13-1.81, p-trend=0.05), lagged 10-yrs, that was robust in sensitivity analyses adjusting for smoking and co-exposures including asbestos. Mortality from bladder cancer (HR, lagged 10 years>2.56 ppm vs Unexposed=2.96 (95%CI:1.38-6.34,p-trend=0.02) and pneumonitis (HR>3.12 ppm-year vs Unexposed=4.73 (95%CI:1.42-15.76,p-trend=0.007) was also associated with AN exposure. This study provides additional evidence of an association between AN exposure and lung cancer, as well as possible increased mortality from bladder cancer and pneumonitis.}, } @article {pmid30927189, year = {2019}, author = {Kennedy, JM}, title = {The forensic significance of pseudomesotheliomatous adenocarcinoma of the lung.}, journal = {Forensic science, medicine, and pathology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12024-019-00110-9}, pmid = {30927189}, issn = {1556-2891}, abstract = {Pseudomesotheliomatous carcinomas (PMC) are rare tumors that clinically, macroscopically, and sometimes histologically resemble malignant pleural mesotheliomas. We report a case of a 91 year woman who was found to have diffuse nodular pleural thickening and a lung mass during a workup for persistent cough. She declined rapidly and died before a histologic diagnosis could be made. Postmortem examination revealed a tumor that diffusely involved the pleural surface with local extension into the chest wall, pericardium, and diaphragm along with a concurrent lung mass. Histologic examination showed poorly-differentiated cells predominantly arranged in sheets, cords, and nests with focal glandular differentiation. An immunohistochemical panel of calretinin, WT1, BEREP4, MOC31, and TTF1 confirmed the diagnosis of primary lung adenocarcinoma. The macroscopic, histologic, and immunohistochemical features used to distinguish metastatic and primary lung adenocarcinoma from epithelioid malignant mesothelioma are discussed. The distinction of malignant mesothelioma from pseudomesotheliomatous carcinoma is important for medicolegal reasons regarding asbestos related compensation claims.}, } @article {pmid30924615, year = {2019}, author = {Algranti, E and Ramos-Bonilla, JP and Terracini, B and Santana, VS and Comba, P and Pasetto, R and Mazzeo, A and Cavariani, F and Trotta, A and Marsili, D}, title = {Prevention of Asbestos Exposure in Latin America within a Global Public Health Perspective.}, journal = {Annals of global health}, volume = {85}, number = {1}, pages = {}, doi = {10.5334/aogh.2341}, pmid = {30924615}, issn = {2214-9996}, abstract = {BACKGROUND: Asbestos consumption in Latin America (LA) amounts to 10% of yearly global production. Little is known about the impact of asbestos exposure in the region.

OBJECTIVE: To discuss scientific and socio-economic issues and conflicts of interest and to summarize epidemiological data of asbestos health effects in LA.

DISCUSSION: Recent data on chrysotile strengthened the evidence of its carcinogenicity and showed an excessive risk of lung cancer at cumulative exposure levels as low as 1.5 fibre-years/ml. Technology for substitution is available for all asbestos-containing products and ceasing asbestos production and manufacturing will not result in unemployment and loss of income, except for the mining industry. The flawed arguments used by the industry to maintain its market, both to the public and in courtrooms, strongly relies on the lack of local evidence of the ill effects and on the invisibility of asbestos-related diseases in LA, due to the limited number of studies and the exposed workers' difficulty accessing health services. The few epidemiological studies available show clear evidence of clusters of mesothelioma in municipalities with a history of asbestos consumption and a forecasted rise in its incidence in Argentina and Brazil for the next decade. In Brazil, non-governmental organizations of asbestos workers were pivotal to counterbalance misinformation and inequities, ending recently in a Supreme Court decision backing an asbestos ban. In parallel, continuous efforts should be made to stimulate the growth of competent and ethical researchers to convey adequate information to the scientific community and to the general public.}, } @article {pmid30917938, year = {2019}, author = {Linton, A and Blinman, P and Kao, S and van Zandwijk, N}, title = {Patterns of care and survival of older patients with malignant pleural mesothelioma.}, journal = {Journal of geriatric oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgo.2019.02.013}, pmid = {30917938}, issn = {1879-4076}, abstract = {OBJECTIVE: Malignant pleural mesothelioma (MPM) is a cancer that primarily affects older adults. However this patient population is frequently under-represented in clinical studies. Therefore, we studied the impact of advancing age on treatment utilisation and clinical outcomes in an extensive series of minimally selected MPM patients.

MATERIALS AND METHODS: Patients with MPM receiving compensation from the New South Wales (NSW) Dust Diseases Authority (2002-2009) were assessed. They were categorised by age (<70 years, 70-80 years or > 80 years) and chi-square testing was used to assess the relationship between clinical and demographic variables, age, treatment and overall survival (OS).

RESULTS: We identified 910 patients; 41% were aged <70 years, 40% were aged 70-80 years, and 19% were aged >80 years old. Median OS decreased with increasing age: 13.5 months in <70 years, 9.5 months in 70-80 years and 7.1 months in >80 years as did chemotherapy use (66%, 35% and 8% respectively). Radical surgical intervention, adjuvant, and palliative radiotherapy were less frequently used with advanced age. A Kaplan Meier analysis revealed that there was a significant survival advantage (p < .001) for patients <70 and 70-80 years receiving chemotherapy (16.8 vs 7.0 months; 13.9 vs 5.8 months respectively), but not for patients >80 years.

CONCLUSION: Advancing age group of NSW patients with MPM was associated with reduced treatment utilisation and a decline in OS. Prospective studies are warranted to verify if current treatment guidelines are relevant for the older adults with MPM.}, } @article {pmid30357324, year = {2018}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Response to comments on ‘Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure’ by Farioli et al. and Oddone et al.}, journal = {Carcinogenesis}, volume = {}, number = {}, pages = {}, doi = {10.1093/carcin/bgy145}, pmid = {30357324}, issn = {1460-2180}, } @article {pmid30915902, year = {2019}, author = {Grosso, F and Croce, A and Libener, R and Mariani, N and Pastormerlo, M and Maconi, A and Rinaudo, C}, title = {Asbestos fiber identification in liver from cholangiocarcinoma patients living in an asbestos polluted area: a preliminary study.}, journal = {Tumori}, volume = {}, number = {}, pages = {300891619839305}, doi = {10.1177/0300891619839305}, pmid = {30915902}, issn = {2038-2529}, abstract = {PURPOSE:: To assess whether asbestos fibers may be observed in liver tissue of patients with cholangiocarcinoma (CC) with environmental or working asbestos exposure.

METHODS:: Detection of fibers was performed directly on histologic sections of liver from 7 patients with CC using optical microscope and variable pressure scanning electron microscopy equipped with energy-dispersive spectroscopy (VP-SEM/EDS). All patients were from Casale Monferrato, Italy, a highly asbestos-polluted town. Due to ethical constraints, observers were blinded to patients' clinical features.

RESULTS:: Fibers/bundles of fibers of chrysotile were detected in 5 out of 7 patients (71%). The boundary between healthy and neoplastic tissue or the fibrocollagen tissue produced by the neoplasia were identified as areas of fiber incorporation.

CONCLUSIONS:: This study is the first report about the detection of chrysotile asbestos fibers in the liver of patients with CC. Further studies on larger cohorts are needed to corroborate our preliminary findings.}, } @article {pmid30915265, year = {2019}, author = {Robalino Gonzaga, ES and Guzman Rojas, P and Vanar, V}, title = {Malignant Peritoneal Mesothelioma Mimicking Recurrent Diverticulitis.}, journal = {Cureus}, volume = {11}, number = {1}, pages = {e3906}, doi = {10.7759/cureus.3906}, pmid = {30915265}, issn = {2168-8184}, abstract = {Mesothelioma is an uncommon type of cancer arising from the mesothelial cells that form the lining of several cavities in the body. Exposure to asbestos is the leading known cause of mesothelioma. We present a 73-year-old male with a significant asbestos exposure and a recent history of recurrent diverticulitis who reported persistent left lower quadrant (LLQ) pain despite several courses of empiric antibiotic therapy. A recent computed tomography (CT) performed due to nonresolving symptoms showed possible nodularity of the mesentery and subsequent positron emission tomography (PET) scan demonstrated multiple hypermetabolic mesenteric lesions, notably in the left paracolic gutter. A colonoscopy was subsequently performed which demonstrated severe diverticulosis, but no obvious luminal lesions. The patient underwent an exploratory laparoscopy showing extensive peritoneal carcinomatosis involving all mesenteric surfaces and partial involvement of the right diaphragm. Final pathology revealed malignant epithelial mesothelioma with peritoneal seeding. The patient was referred to oncology and was started on hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS). Our case highlights a challenging presentation of malignant peritoneal mesothelioma (MPM), which is often initially misdiagnosed due to vague symptoms. Physicians should consider further diagnostic workup for unrelenting LLQ abdominal pain after diverticulitis has been treated.}, } @article {pmid30900641, year = {2019}, author = {Punatar, CB and Jadhav, KK and Kumar, V and Sagade, SN}, title = {Malignant mesothelioma of tunica vaginalis without any risk factors: An uncommon case.}, journal = {Journal of cancer research and therapeutics}, volume = {15}, number = {Supplement}, pages = {S167-S169}, doi = {10.4103/jcrt.JCRT_1403_16}, pmid = {30900641}, issn = {1998-4138}, abstract = {Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare tumor. It is seen in elderly patients, with painless scrotal swelling being the most common presentation. The exact etiology is unknown; a few risk factors have been suggested. Here, we present an uncommon case of MM of TV without any known predisposing factors. We also discuss the possible risk factors, clinical presentation, pathological features and the difficulties in diagnosis, and management of this rare malignancy.}, } @article {pmid30893058, year = {2019}, author = {Levpuscek, K and Goricar, K and Kovac, V and Dolzan, V and Franko, A}, title = {The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma.}, journal = {Radiology and oncology}, volume = {}, number = {}, pages = {}, doi = {10.2478/raon-2019-0016}, pmid = {30893058}, issn = {1581-3207}, abstract = {Background Malignant mesothelioma (MM) is a rare aggressive tumour of mesothelium caused by asbestos exposure. It has been suggested that the genetic variability of proteins involved in DNA repair mechanisms affects the risk of MM. This study investigated the influence of functional polymorphisms in ERCC1 and XRCC1 genes, the interactions between these polymorphisms as well as the interactions between these polymorphisms and asbestos exposure on MM risk. Patients and methods In total, 237 cases with MM and 193 controls with no asbestos-related disease were genotyped for ERCC1 and XRCC1 polymorphisms. Results ERCC1 rs3212986 polymorphism was significantly associated with a decreased risk of MM (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.41-0.91; p = 0.014). No associations were observed between other genetic polymorphisms and MM risk. Interactions between polymorphisms did not significantly influence MM risk. Interaction between ERCC1 rs11615 and asbestos exposure significantly influenced MM risk (OR = 3.61; 95% CI = 1.12-11.66; p = 0.032). Carriers of polymorphic ERCC1 rs11615 allele who were exposed to low level of asbestos had a decreased risk of MM (OR = 0.40; 95% CI = 0.19-0.84; p = 0.016). Interactions between other polymorphisms and asbestos exposure did not significantly influence MM risk. Conclusions Our findings suggest that the genetic variability of DNA repair mechanisms could contribute to the risk of developing MM.}, } @article {pmid30892588, year = {2019}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {}, number = {}, pages = {}, doi = {10.1093/carcin/bgz037}, pmid = {30892588}, issn = {1460-2180}, } @article {pmid30891101, year = {2019}, author = {Wang, Y and Jiang, Z and Yan, J and Ying, S}, title = {HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma.}, journal = {Disease markers}, volume = {2019}, number = {}, pages = {4183157}, doi = {10.1155/2019/4183157}, pmid = {30891101}, issn = {1875-8630}, abstract = {Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is substantially induced by exposure to asbestos fibers. High-mobility group box 1 (HMGB1) is an intriguing proinflammatory molecule involved in MM. In this review, we describe the possible crucial roles of HMGB1 in carcinogenic mechanisms based on in vivo and in vitro experimental evidence and outline the clinical findings of epidemiological investigations regarding the possible roles of HMGB1 as a biomarker for MM. We conclude that novel strategies targeting HMGB1 may suppress MM cells and interfere with asbestos-induced inflammation.}, } @article {pmid29774715, year = {2018}, author = {Chellini, E and Battisti, F and Pellegri, M and Baldacci, M and Sallese, D and Cristaudo, A and Sartorelli, P and Arcangeli, G and Paoli, M and Fani, S and Festa, G and Calà, P}, title = {[Health surveillance programme for workers with past asbestos exposure in Tuscany Region (Central Italy)].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {2}, pages = {171-177}, doi = {10.19191/EP18.2.P171.047}, pmid = {29774715}, issn = {1120-9763}, mesh = {Aged ; Aged, 80 and over ; Air Pollutants, Occupational/*toxicity ; Asbestos/*toxicity ; Asbestosis/complications/diagnosis/*epidemiology ; Diagnostic Screening Programs ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/diagnosis/*epidemiology/etiology ; Middle Aged ; Occupational Exposure ; Pleural Neoplasms/diagnosis/*epidemiology/etiology ; *Population Surveillance ; Program Evaluation ; Stakeholder Participation ; }, abstract = {Asbestos-related diseases are characterized by a long latency time since exposure. This accounts for a health surveillance programme addressed to asbestos workers to be performed for decades after the cessation of occupational exposure. We describe the health surveillance programme for former asbestos-exposed workers in Tuscany Region (Central Italy), with particular attention to organization and related critical issues. The Deliberation of the Regional Administration of Tuscany (No. 396/2016) supports the programme, defined by a regional group of experts, and defines the public health services where the programme has to be implemented. The programme activities are classified in two levels: a first level for a basic health evaluation and a second level for in-depth analyses. The former asbestos workers, aged less than 80 years and with cessation of occupational asbestos exposure in the last 30 years, that might be included free of charge in the programme are about 5.600. The funds assigned to develop the programme from 2016 to 2024 were 2,044,808 euros. The Regional Administration of Tuscany decided to offer and guarantee a homogeneous programme in the whole region. The identification of a specific public health programme and the cooperation of social stakeholders, defined with specific regional agreements, might facilitate to overcome the problems which are still open, such as a broaden invitation to adhere to the programme, an extended knowledge on the service, and the application of a similar health programme for still-working former asbestos workers.}, } @article {pmid30888083, year = {2019}, author = {Hino, O and Abe, M and Han, B and Yan, Y}, title = {In Commemoration of the 2018 Mataro Nagayo Prize - A road to early diagnosis and monitoring of asbestos-related mesothelioma.}, journal = {Cancer science}, volume = {}, number = {}, pages = {}, doi = {10.1111/cas.14001}, pmid = {30888083}, issn = {1349-7006}, abstract = {Primarily caused by exposure to asbestos, mesothelioma is a typical occupational disease. The latency of mesothelioma is as long as 20-40 years, and the cancer initially progresses mainly along the surfaces of pleura or peritoneum without forming masses. Since the symptoms won't develop until late stages, it has been challenging to diagnose this disease in its early stages and to perform complete surgical removal. In responding to Japan's asbestos crisis in the mid-2000s, we've developed and improved ERC/MSLN-based serum and radiological markers and pioneered the use of an N-ERC ELISA kit for screening populations at risk for asbestos exposures. In this paper, we'll review our research toward early diagnosis of asbestos-related mesothelioma before symptoms develop and share our clinical experience of screening, diagnosing and monitoring of this disease. This paper is dedicated to the author (Dr. Okio Hino) to commemorate the honor bestowed upon him as the recipient of the Mataro Nagayo Prize in 2018. This article is protected by copyright. All rights reserved.}, } @article {pmid30886321, year = {2019}, author = {Jeffery, E and Lee, YCG and Newton, RU and Lyons-Wall, P and McVeigh, J and Nowak, AK and Cheah, HM and Nguyen, B and Fitzgerald, DB and Creaney, J and Straker, L and Peddle-McIntyre, CJ}, title = {Body composition and nutritional status in malignant pleural mesothelioma: implications for activity levels and quality of life.}, journal = {European journal of clinical nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41430-019-0418-9}, pmid = {30886321}, issn = {1476-5640}, abstract = {BACKGROUND/OBJECTIVES: Malignant pleural mesothelioma (MPM) is an incurable cancer and optimizing daily physical activity and quality of life are key goals of patient management. Little is known about the prevalence of pre-sarcopenia and malnutrition in MPM or their associations with patient outcomes. This study aimed to determine the prevalence of pre-sarcopenia and malnutrition in MPM and investigate if activity levels and quality of life differed according to body composition and nutritional status.

SUBJECTS/METHODS: Patients with a diagnosis of MPM were recruited. Pre-sarcopenia was defined as low appendicular skeletal muscle mass (≤ 7.26 kg/m2 for men and ≤ 5.45 kg/m2 for women), measured by dual energy X-ray absorptiometry. Malnutrition was defined as a rating of B or C on the Patient-Generated Subjective Global Assessment. Outcome measures included objective activity levels (Actigraph GT3X) and health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy General).

RESULTS: Sixty-one people participated (79% male, median age 69 [IQR 62-74] years and median BMI 25.8 [IQR 24.3-28.4] kg/m2). Fifty-four percent were pre-sarcopenic and 38% were malnourished. Percent of time spent in light activity/day was lower in participants with pre-sarcopenia compared with non-sarcopenic participants (median 25.4 [IQR 19.8-32.1]% vs. 32.3 [27.1-35.6]%; p = 0.008). Participants with malnutrition had poorer HRQoL than well-nourished participants (mean 69.0 (16.3) vs. 84.4 (13.3); p < 0.001).

CONCLUSION: Participants with MPM had high rates of pre-sarcopenia and malnutrition. Pre-sarcopenia was associated with poorer activity levels, whilst malnutrition was associated with poorer quality of life. Interventions that aim to address reduced muscle mass and weight loss, should be tested in MPM to assess their impact on patient outcomes.}, } @article {pmid30885349, year = {2019}, author = {Ahmadzada, T and Lee, K and Clarke, C and Cooper, WA and Linton, A and McCaughan, B and Asher, R and Clarke, S and Reid, G and Kao, S}, title = {High BIN1 expression has a favorable prognosis in malignant pleural mesothelioma and is associated with tumor infiltrating lymphocytes.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {130}, number = {}, pages = {35-41}, doi = {10.1016/j.lungcan.2019.02.005}, pmid = {30885349}, issn = {1872-8332}, abstract = {OBJECTIVES: A number of key immune regulators show prognostic value in malignant pleural mesothelioma (MPM), but the association between Bridging integrator 1 (BIN1), indoleamine 2,3 dioxygenase 1 (IDO1) and patient outcome has not been investigated. We aimed to determine the expression of BIN1 and IDO1, their association with other markers and impact on overall survival (OS) in MPM.

MATERIALS AND METHODS: The expression of BIN1, IDO1, CD3, CD20 and CD68 were evaluated by immunohistochemistry in 67 patients who underwent pleurectomy/decortication. Survival analyses were performed using the Kaplan Meier method and significant biomarkers were entered into a Cox Regression multivariate model, accounting for known prognostic factors such as age, gender, histological subtype, PD-L1 expression and neutrophil-to-lymphocyte ratio.

RESULTS: Immune markers were variably expressed in tumor cells, ranging from 0% to 100% for BIN1 (median: 89%), and 0% to 77.5% for IDO1 (median: 0%). Expression of markers of tumor-infiltrating lymphocytes (TILs) and macrophages ranged from 0% to more than 50%. BIN1 expression was high in 35 patients (51%) and was associated with increased OS (median: 12 vs 6 months for high and low BIN1 respectively,p = 0.03). Multivariate analysis showed BIN1 remained an independent prognostic indicator (HR 0.39; 95% CI: 0.18-0.82, p = 0.01). The majority of patients had immune inflamed tumors (77%) and there was a significant association between TILs and BIN1 (p = 0 < 0.01), PD-L1 (p=0.04) and CD68+ macrophages in the tumor (p < 0.01). There were no significant associations between PD-L1 and BIN1 or IDO1.

CONCLUSION: High BIN1 expression is a favorable prognostic biomarker and is associated with TILs in MPM.}, } @article {pmid30882147, year = {2019}, author = {Nakai, T and Matsumoto, Y and Sasada, S and Tanaka, M and Tsuchida, T and Ohe, Y and Motoi, N}, title = {Cryobiopsy during flex-rigid pleuroscopy: an emerging alternative biopsy method in malignant pleural mesothelioma. A comparative study of pathology.}, journal = {Japanese journal of clinical oncology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jjco/hyz032}, pmid = {30882147}, issn = {1465-3621}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is rarely an asbestos-related cancer with a poor prognosis that is difficult to distinguish from some benign conditions by using conventional biopsy techniques. The purpose of this study was to evaluate the utility of a novel biopsy technique using a cryoprobe during flex-rigid pleuroscopy for diagnosing MPM.

METHODS: Consecutive patients who underwent pleural cryobiopsy during flex-rigid pleuroscopy from June through November 2017 to diagnose the cause of pleural effusion were collected. From these, cases ultimately diagnosed as MPM were selected. Pleural biopsies were performed by using conventional instruments followed by a cryoprobe. The obtained samples were histologically examined and compared with regard to the quality (sample size, tissue depth, and crush rate), immunohistochemical (IHC) staining, and p16 by fluorescence in situ hybridization (FISH).

RESULTS: In total, five patients ultimately diagnosed as MPM were enrolled. The sample collected was significantly larger for cryobiopsy than conventional biopsy (18.9 mm2 vs. 6.7 mm2, P < 0.001). Full-thickness biopsies were achieved in four cases by using cryobiopsy compared with one case by conventional biopsy. Moreover, the crush rate was significantly less for cryobiopsy than conventional biopsy (9% vs. 35%, P < 0.001). The results of IHC staining and p16 by FISH were similar between biopsy techniques. Cryobiopsy successfully led to accurate diagnosis of MPM in all cases, whereas conventional biopsy was diagnostic in one case. No severe complications developed after either biopsy technique.

CONCLUSION: Cryobiopsy during flex-rigid pleuroscopy is a feasible and convenient biopsy technique that supports precise diagnosis of MPM.}, } @article {pmid30879467, year = {2019}, author = {Miyata, T and Fujiwara, Y and Nishijima, K and Futagami, F and Nakamura, T and Takamura, H}, title = {Localized multiple malignant epithelioid peritoneal mesotheliomas arising from the hepatoduodenal ligament and diaphragm: a case report.}, journal = {Journal of medical case reports}, volume = {13}, number = {1}, pages = {66}, doi = {10.1186/s13256-019-2008-9}, pmid = {30879467}, issn = {1752-1947}, abstract = {BACKGROUND: Malignant peritoneal mesothelioma is a rare aggressive tumor of the peritoneum. We report a rare case of resection of multiple localized malignant peritoneal mesotheliomas.

CASE PRESENTATION: A 55-year-old Japanese woman was admitted to our hospital because liver tumors were detected by abdominal ultrasonography during a screening examination. Blood examination findings, including tumor makers, were within normal ranges. She had no evidence of exposure to asbestos. Computed tomography showed four hypervascular, round liver tumors, one in the lateral liver segment adjacent to the hepatic hilus, and the other three on the liver surface. Computed tomography angiography revealed that the tumor in the lateral segment had strong enhancement and was fed from the left gastric artery. In contrast, the other tumors showed no enhancement, and were fed from the right inferior phrenic artery. Abnormal accumulation was identified in the four tumors only with 18F-fluorodeoxyglucose positron emission tomography. It was very difficult to obtain a definitive preoperative diagnosis, but surgical resection was performed because we considered potential malignancy. Laparotomy revealed the principal site of the tumor in the lateral segment was on the hepatoduodenal ligament, and all other tumors were on the diaphragm. A left lobectomy and partial diaphragmatic resection were performed. The final pathological diagnosis was multiple malignant epithelioid mesotheliomas. Our patient has had no recurrence for 20 months postoperatively.

CONCLUSIONS: In general, malignant peritoneal mesotheliomas are classified as diffuse tumors, which are often unresectable and have a poor prognosis. However, early diagnosis and treatment, particularly with the localized type, as in our patient, could lead to long-term survival of the patient. We recommend that multiple malignant epithelioid mesotheliomas be included in the differential diagnosis for patients with subcapsular hepatic tumors.}, } @article {pmid30874891, year = {2019}, author = {Hutter, HP and Waldhoer, T and Müller, K and Hackl, M and Weitensfelder, L and Heinzl, H}, title = {Cancer incidence in an Austrian alpine valley 1983-2012 : A descriptive study.}, journal = {Wiener klinische Wochenschrift}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00508-019-1476-7}, pmid = {30874891}, issn = {1613-7671}, abstract = {After one of Austria's largest environmental scandals in 2014, which involved the release of hexachlorobenzene (HCB) in the Carinthian valley Görtschitztal, concerns about increased cancer rates have arísen in the affected local population. A descriptive study was conducted to examine the cancer incidence rates between 1983 and 2012. Data from the affected area (Görtschitztal, district St. Veit) were compared to data from the neighboring area within the same district and Carinthia excluding St. Veit, considering incidence rates of liver, lung, kidney, thyroid cancer and mesothelioma. Prostate cancer and carcinoma in situ were both included and excluded from overall cancer incidents in order to prevent potential bias due to screening programs. Considering the observed variability at an overall level, no conspicuous differences in cancer incidences could be found (Carinthia: 495, St. Veit West: 408, St. Veit East: 572 cases per 100,000 person-years in 2012). For some cancer types, e. g. liver, thyroid cancer and mesothelioma, the affected region showed a higher increase in rates than the neighboring area or Carinthia overall; however, these increased rates date back to a time prior to the HCB exposure, suggesting other carcinogenic influences, such as asbestos exposure from antecedent years.}, } @article {pmid30873891, year = {2019}, author = {Poland, CA and Duffin, R}, title = {The toxicology of chrysotile-containing brake debris: implications for mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {}, number = {}, pages = {1-25}, doi = {10.1080/10408444.2019.1568385}, pmid = {30873891}, issn = {1547-6898}, abstract = {The global use of "asbestos" in various commercial products has led to a wide range and pervasive legacy of disease. One such use of chrysotile asbestos was brake pads and was utilized commonly in automobiles and heavy vehicles. The result of incorporation of chrysotile into brake pads is associated with the exposure of mechanics fitting and servicing vehicles to liberated chrysotile fibers. Despite the proven exposure, the relative risk of malignant mesothelioma (MM) in this occupational population is broadly seen as low. The toxicity of particulates, including fibers such as chrysotile, is driven by a combination of dose and physicochemical properties. As such, it is plausible that chrysotile released from brake pads may have undergone modification, thereby altering the pathogenicity profile. The impact of high sheer stress causing shortening of long fibers, heat modification, binding of resin matrix to the fiber surface on the relative toxicity of brake debris with regards to MM is considered. It is apparent that released chrysotile can undergo significant modification, reducing the long fiber dose although not all modifications may lead to reduced toxicity.}, } @article {pmid30873867, year = {2019}, author = {Baqui, AA and Boire, NA and Baqui, TT and Etwaru, DJ}, title = {Malignant Mesothelioma of the Tunica Vaginalis Testis-A Malignancy Associated With Asbestos Exposure and Trauma: A Case Report and Literature Review.}, journal = {Journal of investigative medicine high impact case reports}, volume = {7}, number = {}, pages = {2324709619827335}, doi = {10.1177/2324709619827335}, pmid = {30873867}, issn = {2324-7096}, abstract = {In this article, we report an unusual case of a malignant mesothelioma of the testis, presenting as hydrocele. The patient has a known medical history of trauma and occupational exposure to asbestos. The clinical features of this injury are discussed together with its immunohistochemistry. Surgical intervention is discussed due to the nature of this pathology.}, } @article {pmid30870398, year = {2019}, author = {Cuccaro, F and Nannavecchia, AM and Silvestri, S and Angelini, A and Coviello, V and Bisceglia, L and Magnani, C}, title = {Mortality for Mesothelioma and Lung Cancer in a Cohort of Asbestos Cement Workers in BARI (Italy): Time Related Aspects of Exposure.}, journal = {Journal of occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/JOM.0000000000001580}, pmid = {30870398}, issn = {1536-5948}, abstract = {OBJECTIVE: In this cohort mortality study we used an exposure index to evaluate individual cumulative exposure as proxy of asbestos dose and we evaluated change in cancer mortality pattern after long time since the end of exposure.

METHODS: We calculated SMRs for several causes of death stratified by latency, cumulative exposure and time since last exposure (TSLE).

RESULTS: Latency: we observed a peak and then a decrease in SMR for lung, pleural and peritoneal cancer. CUMULATIVE EXPOSURE:: we observed a peak and then a decrease in SMR for lung and pleural cancer, not for peritoneal cancer. TSLE:: pleural cancer SMR peaked at 20-29 years, then decreased, peritoneal cancer SMR reached a plateau after 20 years and lung cancer mortality was in excess in each class.

CONCLUSIONS: We found different patterns in mortality in the main asbestos-related tumours.}, } @article {pmid30863440, year = {2019}, author = {Liang, Y and Zheng, G and Yin, W and Song, H and Li, C and Tian, L and Yang, D}, title = {Significance of EGFR and PTEN Expression and PLR and NLR for Predicting the Prognosis of Epithelioid Malignant Peritoneal Mesothelioma.}, journal = {Gastroenterology research and practice}, volume = {2019}, number = {}, pages = {7103915}, doi = {10.1155/2019/7103915}, pmid = {30863440}, issn = {1687-6121}, abstract = {Objective: The aim of our study was to investigate the expression of EGFR and PTEN in tissues and measure the serum platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) to evaluate the prognostic factors of patients with epithelioid malignant peritoneal mesothelioma (MPeM).

Methods: 33 patients of pathologically diagnosed epithelioid MPeM tissues were analyzed using immunohistochemistry to detect EGFR and PTEN; the PLR and NLR were determined by using a routine blood test. We analyzed the relationships of these markers to age, sex, asbestos exposure, elevated platelet count, ascites, and clinical stage.

Results: EGFR and PTEN expressions were positive in 22 (66.67%) and 7 (21.21%) epithelioid MPeM patients, respectively. However, these two markers as well as PLR and NLR were not significantly associated with age, sex, asbestos exposure, elevated platelet counts, ascites, and clinical stage (P > 0.05). The correlation between EGFR and PTEN was negative (r = -0.577, P < 0.001), but the correlation between NLR and PLR was positive (r = 0.456, P = 0.008). The median survival of all patients was 6 months. In univariate analysis, PTEN (P < 0.001), PLR (P = 0.014), and NLR (P = 0.015) affected the overall survival. Multivariate analysis revealed that PTEN and PLR were validated as predictive for overall survival of epithelioid MPeM (HR = 0.070, P = 0.001, and HR = 3.379, P = 0.007, respectively).

Conclusion: On the basis of these results, it is suggested that PTEN and PLR are risk factors for the prognosis of epithelioid MPeM, which may be targets for selective therapies and improve the outcomes of patients with epithelioid MPeM.}, } @article {pmid30863365, year = {2019}, author = {Baird, AM and Easty, D and Jarzabek, M and Shiels, L and Soltermann, A and Klebe, S and Raeppel, S and MacDonagh, L and Wu, C and Griggs, K and Kirschner, MB and Stanfill, B and Nonaka, D and Goparaju, CM and Murer, B and Fennell, DA and O'Donnell, DM and Barr, MP and Mutti, L and Reid, G and Finn, S and Cuffe, S and Pass, HI and Opitz, I and Byrne, AT and O'Byrne, KJ and Gray, SG}, title = {When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {89}, doi = {10.3389/fendo.2019.00089}, pmid = {30863365}, issn = {1664-2392}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer with a poor survival rate. Treatment options are limited at best and drug resistance is common. Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times. MST1R (RON) is a trans-membrane receptor tyrosine kinase (RTK), which is part of the c-MET proto-oncogene family. The only ligand recognized to bind MST1R (RON) is Macrophage Stimulating 1 (MST1), also known as Macrophage Stimulating Protein (MSP) or Hepatocyte Growth Factor-Like Protein (HGFL). In this study, we demonstrate that the MST1-MST1R (RON) signaling axis is active in MPM. Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. Cell cycle progression was also affected. Recombinant MST1 treatment was unable to overcome the effect of LCRF-0004 in terms of either proliferation or apoptosis. Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. In a cohort of MPM patient samples, high positivity for total MST1R by IHC was an independent predictor of favorable prognosis. Additionally, elevated expression levels of MST1 also correlated with better survival. This study also determined the efficacy of LCRF-0004 and BMS-777607 in xenograft MPM models. Both LCRF-0004 and BMS-777607 demonstrated significant anti-tumor efficacy in vitro, however BMS-777607 was far superior to LCRF-0004. The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone.}, } @article {pmid30859065, year = {2019}, author = {Wallen, T and Jagan, N and Krishnan, M and Depew, Z}, title = {A 75 year old male with recurrent unilateral pleural effusion and positive ANA.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {301-303}, doi = {10.1016/j.rmcr.2019.02.019}, pmid = {30859065}, issn = {2213-0071}, abstract = {This case report describes the clinical course and diagnostic challenges arising in a 75 year old man who initially presented with progressive shortness of breath. Imaging revealed a pleural effusion, which was recurrent following thoracentesis. While his initial workup suggested an autoimmune etiology, further diagnostic testing revealed a diagnosis of malignant pleural mesothelioma. Curiously, the patient had no known asbestos exposure, which is classically associated with acquired mesothelioma. There are a small number of similar cases with a possible overlap between positive autoimmune serologies and mesothelioma; however, the underlying pathophysiology remains elusive. It is the authors' goal to contribute this case to the few cases describing such overlap syndromes.}, } @article {pmid30851279, year = {2019}, author = {Mandel, JH and Odo, NU and Alexander, BH}, title = {Potential Problems with Determining Elongate Mineral Particle (EMP) Potency (Comments on article entitled, "A Comparison of Asbestos Fiber Potency and Elongate Mineral Particle (EMP) Potency for Mesothelioma in Humans").}, journal = {Toxicology and applied pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.taap.2019.03.002}, pmid = {30851279}, issn = {1096-0333}, } @article {pmid30840592, year = {2019}, author = {Senk, B and Goricar, K and Kovac, V and Dolzan, V and Franko, A}, title = {Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment.}, journal = {Radiology and oncology}, volume = {53}, number = {1}, pages = {96-104}, doi = {10.2478/raon-2019-0009}, pmid = {30840592}, issn = {1581-3207}, abstract = {Background Malignant mesothelioma (MM) is an asbestos related aggressive tumor with poor prognosis. The aim of this study was to investigate if aquaporin 1 (AQP1) genetic polymorphisms influence the risk of MM and the response to cisplatin based MM treatment. Patients and methods The case-control study included 231 patients with MM and a control group of 316 healthy blood donors. All subjects were genotyped for three AQP1polymorphisms (rs1049305, rs1476597 and rs28362731). Logistic and Cox regression were used in statistical analysis. Results AQP1 rs1049305 polymorphism was significantly associated with MM risk in dominant model adjusted for gender and age (OR = 0.60, 95% CI = 0.37-0.96, Padj = 0.033). This polymorphism was also significantly associated with cisplatin based treatment related anaemia (unadjusted: OR = 0.49, 95% CI = 0.27-0.90, P = 0.021; adjusted: for CRP: OR = 0.52, 95% CI = 0.27-0.99, P = 0.046), with leukopenia (OR = 2.09, 95% CI = 1.00-4.35, P = 0.049) in dominant model and with thrombocytopenia (OR = 3.06, 95% CI = 1.01-9.28, P = 0.048) and alopecia (OR = 2.92, 95% CI = 1.00-8.46, P = 0.049) in additive model. AQP1 rs28362731 was significantly associated with thrombocytopenia (unadjusted: OR = 3.73, 95% CI = 1.00-13.84, P = 0.049; adjusted for pain: OR = 4.63, 95% CI = 1.13-19.05, P = 0.034) in additive model. Conclusions AQP1 may play a role in the risk of MM. Furthermore, AQP1 genotype information could improve the prediction of MM patients at increased risk for cisplatin toxicity.}, } @article {pmid30834036, year = {2019}, author = {Abbas, H and Rodriguez, JC and Tariq, H and Niazi, M and Alemam, A and Nayudu, SK}, title = {Malignant Peritoneal Mesothelioma Without Asbestos Exposure.}, journal = {Gastroenterology research}, volume = {12}, number = {1}, pages = {48-51}, doi = {10.14740/gr1141}, pmid = {30834036}, issn = {1918-2805}, abstract = {Malignant mesothelioma is a rare neoplasm of the serosal linings. Mesothelioma has been linked to asbestos exposure, with prior asbestos exposure linked to 33-50% of malignant peritoneal mesotheliomas. We describe a case of malignant peritoneal mesothelioma (MPM) without any prior exposure to asbestos in a 40-year-old Hispanic female who presented to the emergency department with worsening abdominal pain and distension. She had a history of beta thalassemia trait and iron deficiency anemia. Examination revealed a distended abdomen with protruding umbilicus and positive shifting dullness. Laboratory tests showed anemia. Computed tomography (CT) of the abdomen revealed massive complex ascites suspicious of a malignant process. Ascitic fluid analysis showed serum ascites albumin gradient (SAAG) of 1.1 g/dL with a total protein of 5.2 g/dL. She underwent laparoscopic peritoneal biopsy which yielded epithelioid type malignant mesothelioma. She was started on chemotherapy with cisplatin and pemetrexed. The last follow-up was 27 months after the diagnosis. MPM is a rare and life-threatening malignancy. Frequently, the symptoms are non-specific. This poses a diagnostic challenge for physicians and probably the reason why the diagnosis is often delayed, especially in the absence of risk factors.}, } @article {pmid29774705, year = {2018}, author = {Terracini, B}, title = {[Parliamentary committee of inquiry about health of Italian soldiers exposed to uranium, asbestos, and vaccines].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {2}, pages = {114-115}, doi = {10.19191/EP18.2.P114.037}, pmid = {29774705}, issn = {1120-9763}, mesh = {*Advisory Committees ; Asbestos/*adverse effects ; Forecasting ; Government Agencies ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/etiology ; *Military Personnel ; Occupational Diseases/*epidemiology/etiology ; *Occupational Exposure ; Uranium/*adverse effects ; Vaccines/*adverse effects ; }, } @article {pmid30815702, year = {2019}, author = {Pasetto, R and Zona, A and Fazzo, L and Binazzi, A and Bruno, C and Pirastu, R and Comba, P and Marinaccio, A}, title = {Proportion of mesothelioma attributable to living in industrially contaminated areas in Italy.}, journal = {Scandinavian journal of work, environment & health}, volume = {}, number = {}, pages = {}, doi = {10.5271/sjweh.3809}, pmid = {30815702}, issn = {1795-990X}, abstract = {Objectives The aim of this study was to estimate the attributable proportion (AP) of mesothelioma resulting from living in or close to major Italian industrially contaminated areas. Methods For populations living close to 39 sites of "national priority for remediation", incident mesothelioma cases were extracted from the Italian National Mesothelioma Registry (ReNaM) in the period 2000‒2011. Each site was classified in one of seven asbestos risk groups (RG) on the basis of the type of industrial plants. RG were ranked by the a priori evidence on asbestos risk. The AP for each RG was calculated as the meta-analytic estimate of AP of sites of the same group by gender and age class (0-64, 65-74, ≥75 years). The sex ratio (men/women) was computed for each RG. Results Among men, the AP by age class had the same gradient in each RG, with the highest values in the age class 0-64 years and the lowest in the ≥75 class; in the age class 0-64 years, the AP was positive in each RG, >90% in the presence of asbestos cement factories and harbors with shipyards. Among women, the overall AP decreased by RG, with negative values in the last two ranked RG; the AP by age class was variable without a definite gradient. The sex ratio was close to one only in the RG "only asbestos-cement factories"; the highest value (9.6) was observed in the age class 0-64 years in the RG "harbors with shipyard". Conclusions The integration of a geographic- and case-based approach provides valuable insights into occupational and environmental determinants of mesothelioma risk in industrially contaminated sites.}, } @article {pmid30809599, year = {2018}, author = {Biersack, B}, title = {Relations between approved platinum drugs and non-coding RNAs in mesothelioma.}, journal = {Non-coding RNA research}, volume = {3}, number = {4}, pages = {161-173}, doi = {10.1016/j.ncrna.2018.08.001}, pmid = {30809599}, issn = {2468-0540}, abstract = {Malignant mesothelioma diseases feature an increasing risk due to their severe forms and their association with asbestos exposure. Platinum(II) complexes such as cisplatin and carboplatin are clinically approved for the therapy of mesothelioma often in combination with antimetabolites such as pemetrexed or gemcitabine. It was observed that pathogenic properties of mesothelioma cells and the response of mesothelioma tumors towards platinum-based drugs are strongly influenced by non-coding RNAs, in particular, by small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These non-coding RNAs controlled drug sensitivity and the development of tumor resistance towards platinum drugs. An overview of the interactions between platinum drugs and non-coding RNAs is given and the influence of non-coding RNAs on platinum drug efficacy in mesothelioma is discussed. Suitable non-coding RNA-modulating agents with potentially beneficial effects on cisplatin treatment of mesothelioma diseases are mentioned. The understanding of mesothelioma diseases concerning the interactions of non-coding RNAs and platinum drugs will optimize existing therapy schemes and pave the way to new treatment options in future.}, } @article {pmid30804167, year = {2019}, author = {Farioli, A and Boffetta, P and Curti, S and Garzaro, G and La Vecchia, C and Mattioli, S and Spatari, G and Violante, FS}, title = {Response to: 'Are children more vulnerable to mesothelioma than adults? A comparison of mesothelioma risk among children and adults exposed non-occupationally to blue asbestos at Wittenoom' by Reid et al.}, journal = {Occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1136/oemed-2018-105637}, pmid = {30804167}, issn = {1470-7926}, } @article {pmid30804166, year = {2019}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, Ø}, title = {Environmental asbestos exposure in childhood and risk of mesothelioma later in life: a long-term follow-up register-based cohort study.}, journal = {Occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1136/oemed-2018-105392}, pmid = {30804166}, issn = {1470-7926}, abstract = {OBJECTIVE: To examine the risk of malignant mesothelioma (MM) in former pupils who attended primary school near an asbestos cement plant.

METHODS: A cohort of 12 111 former pupils, born 1940-1970, was established from individual historical records from four primary schools located at a distance of 100-750 m in the prevailing wind direction from an asbestos cement plant operating from 1928 to 1984 in Aalborg, Denmark. The school cohort and a comparison cohort consisting of 108 987 gender and 5-year frequency-matched subjects were followed up (2015) for MM in the Danish Cancer Registry. Using Cox regression, HRs were estimated for the incidence of MM. Adjustments for occupational and familial asbestos exposure were made with a job exposure matrix. An SIR analysis including latency periods testing the cancer incidence rate was performed with the comparison cohort as the reference rate.

RESULTS: The median person-years of follow-up were 62.5 years in the school cohort and 62.2 years in the comparison cohort. There were 32 males and 6 females of the former pupils who developed MM during the follow-up: HRmale 7.01 (95% CI 4.24 to 11.57), HRfemale 7.43 (95% CI 2.50 to 22.13). Those who attended school 250 m north of the plant had the highest HR for MM, 10.65 (95% Cl 5.82 to 19.48). No significant trend between school distance and risk of MM was established (p=0.35).

CONCLUSION: Our results suggest that boys and girls who attended schools and lived in the neighbourhood of an asbestos cement plant later in life have a significantly increased risk of MM.}, } @article {pmid30804152, year = {2019}, author = {Kim, M and Kim, HS}, title = {Clinicopathological Characteristics of Well-differentiated Papillary Mesothelioma of The Peritoneum: A Single-institutional Experience of 12 Cases.}, journal = {In vivo (Athens, Greece)}, volume = {33}, number = {2}, pages = {633-642}, doi = {10.21873/invivo.11521}, pmid = {30804152}, issn = {1791-7549}, abstract = {BACKGROUND/AIM: Well-differentiated papillary mesothelioma (WDPM) is histologically characterized by papillary architecture with fibrovascular cores, lined by bland mesothelial cells. We recently experienced a case of WDPM associated with multiple peritoneal inclusion cysts, which prompted us to initiate a comprehensive review of previously diagnosed WDPM cases.

MATERIALS AND METHODS: The clinicopathological characteristics and immunophenotype of 12 cases of peritoneal WDPM were investigated using a review of electronic medical records, pathological examination, and immunostaining.

RESULTS: The patients' ages ranged from 23 to 75 years. No patient had endometriosis or a previous history of asbestos exposure. Ten tumors were detected incidentally during surgery for other causes. Most tumors appeared as a small, single nodule on the peritoneal surface, but in three cases, WDPM presented as multiple lesions. All but one patient had no symptoms. All the patients examined are still well without postoperative recurrence. Histologically, all cases demonstrated typical papillary architecture with fibrovascular cores. The mesothelial cells lining the papillae consisted mostly of single row of cells, although areas of proliferation to multiple layers were observed in a few cases. Their nuclei appeared bland, but two cases exhibited mild nuclear atypia and prominent nucleoli. Immunostaining revealed that the mesothelial cells were positive for D2-40, cytokeratin 5/6, cytokeratin 7, and Wilms' tumor 1.

CONCLUSION: We herein demonstrated the clinicopathological characteristics of peritoneal WDPMs. WDPM has distinct pathological features. Although all cases we examined were uneventful after surgery, further surveillance is recommended since the biological behavior of WDPM is still uncertain.}, } @article {pmid30776941, year = {2019}, author = {Wang, F and Chen, Y and Wang, Y and Yin, Y and Qu, G and Song, M and Wang, H}, title = {Ultra-long silver nanowires induced mitotic abnormalities and cytokinetic failure in A549 cells.}, journal = {Nanotoxicology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/17435390.2019.1571645}, pmid = {30776941}, issn = {1743-5404}, abstract = {Asbestos fiber has been associated with mesothelioma and lung cancer. However, the carcinogenic risks of other fiber nanomaterials with morphological similarities to asbestos have not been fully studied. Ultra-long silver nanowires (AgNWs) are increasingly used fiber-shaped nanomaterials with a high aspect ratio, but very few studies have investigated their health risks. Here, proliferation abnormalities of lung epithelial cells induced by ultra-long AgNWs were investigated. Ultra-long AgNW treatment induced dose- and diameter-dependent increase in the ratio of multinucleated cells. Further, proteins involved in mitosis and cytokinesis, including Aurora A, p-Histone 3 (ser10), RhoA, p-MLC, and myosin IIb, were significantly upregulated after an ultra-long AgNW treatment, leading to mitotic abnormalities and cytokinetic failure. Meanwhile, exposure to ultra-long AgNWs induced cell cycle arrest. Interestingly, a series of experiments demonstrated that ROS generation and Ag+ release were not responsible for the multinucleation induced by ultra-long AgNWs, but ultra-long AgNWs in the intercellular bridge might obstruct the contractile ring and inhibit abscission of the cytokinetic furrow by direct physical contact. Altogether, our findings indicate that ultra-long AgNWs can induce chromosomal instability, which has important consequences for the safety of ultra-long AgNWs to human health.}, } @article {pmid30774332, year = {2019}, author = {Cova, E and Pandolfi, L and Colombo, M and Frangipane, V and Inghilleri, S and Morosini, M and Mrakic-Sposta, S and Moretti, S and Monti, M and Pignochino, Y and Benvenuti, S and Prosperi, D and Stella, G and Morbini, P and Meloni, F}, title = {Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study.}, journal = {International journal of nanomedicine}, volume = {14}, number = {}, pages = {773-785}, doi = {10.2147/IJN.S186344}, pmid = {30774332}, issn = {1178-2013}, abstract = {Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.

Methods: MPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).

Results: GNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.

Conclusion: GNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.}, } @article {pmid30770142, year = {2019}, author = {Douglas, T and Van den Borre, L}, title = {Asbestos neglect: Why asbestos exposure deserves greater policy attention.}, journal = {Health policy (Amsterdam, Netherlands)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.healthpol.2019.02.001}, pmid = {30770142}, issn = {1872-6054}, abstract = {While many public health threats are now widely appreciated by the public, the risks from asbestos exposure remain poorly understood, even in high-risk groups. This article makes the case that asbestos exposure is an important, ongoing global health threat, and argues for greater policy efforts to raise awareness of this threat. It also proposes the extension of asbestos bans to developing countries and increased public subsidies for asbestos testing and abatement.}, } @article {pmid30759891, year = {2019}, author = {Bertrand, P and Blanquart, C and Héroguez, V}, title = {The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy.}, journal = {Biomolecules}, volume = {9}, number = {2}, pages = {}, doi = {10.3390/biom9020060}, pmid = {30759891}, issn = {2218-273X}, abstract = {Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.}, } @article {pmid30754975, year = {2019}, author = {Pelclová, D}, title = {Diagnostics and acknowledgement of occupational diseases - topics and challenges in the Czech Republic.}, journal = {Casopis lekaru ceskych}, volume = {157}, number = {8}, pages = {396-399}, pmid = {30754975}, issn = {0008-7335}, abstract = {The causes of occupational diseases are changing, thats why a regular update of Czech List of Occupational Diseases is needed. New compensable occupational diseases, such as cancer of the larynx and ovarian cancer due to asbestos, and chronic obstructive pulmonary diseases due to black coal dust were included in the last two updates of the Czech List. The need of an early examination at the Centers of Occupational Diseases is stressed in this article, especially before a surgery or other treatment of epicondylitis and carpal tunnel syndrome. These treatments may suppress the diagnostic hallmarks requested for acknowledgements of these disorders. Extrinsic allergic alveolitis, allergic rhinitis and bronchial asthma are underdiagnosed, and isocyanates belong among the key factors. Only about 10 % patients with mesotheliomas due to asbestos are compensated. The latency in cancers due to asbestos may reach more than 50 years. Keywords: COPD, mesothelioma, lung cancer, larynx cancer, ovarian cancer, isocyanates, extrinsic allergic alveolitis, epicondylitis, carpal tunnel.}, } @article {pmid30744695, year = {2019}, author = {Weber, DG and Brik, A and Casjens, S and Burek, K and Lehnert, M and Pesch, B and Taeger, D and Brüning, T and Johnen, G and , }, title = {Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study.}, journal = {BMC research notes}, volume = {12}, number = {1}, pages = {77}, doi = {10.1186/s13104-019-4113-7}, pmid = {30744695}, issn = {1756-0500}, abstract = {OBJECTIVE: Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case-control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease.

RESULTS: Using prediagnostic plasma samples collected in median 8.9 months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.}, } @article {pmid30741658, year = {2019}, author = {García-Ibáñez, J and Cayuelas-Rubio, C and Durán-Rivera, A and Mitjana-Biosca, S and Monzó-Cataluña, A and Sánchez Ballester, F and Ramos de Campos, M and Ramos de Campos, M and López-Alcina, E}, title = {[Report of two cases of malignant mesothelioma of the tunica vaginalis.].}, journal = {Archivos espanoles de urologia}, volume = {72}, number = {1}, pages = {85-88}, pmid = {30741658}, issn = {0004-0614}, abstract = {OBJECTIVE: Paratesticular mesothelioma isan infrequent tumor and only 250 cases have been published.It originates in the scrotal tunica vaginalis. It represents0.3-1.4% of mesotheliomas and it predominates inpatients with history of asbestos exposure and old age. Itsdiagnosis is usually casual. Our objective is to present thecases that occurred in our service with malignant paratesticularmesothelioma and to carry out a review of the currentliterature on this pathology.

METHODS: We report two cases diagnosed with malignantparatesticular mesothelioma that happened in the lasttwo years.

RESULT: The first case was a 73-year-old male with asymptomatichydrocele. The second was a 57-year-oldmale who had testicular pain and hydrocele. Both werediagnosed of mesothelioma after hydrocelectomy. The firsttreatment was radical orchiectomy in both cases. The firstpatient did not need more treatments. The second patientpresented pulmonary nodules, lymphadenopathy and localrelapse, which was treated with chemotherapy and localresection.

CONCLUSION: Paratesticular mesothelioma is an infrequenttumor. Scrotal mass associated with hydrocele is thetypical form of presentation. Surgical treatment consists ofradical orchiectomy. They have poor prognosis because inmost cases there is rapid local and dissemination.}, } @article {pmid30719319, year = {2019}, author = {Guo, X and Watanabe, J and Takahashi, K and Hayashi, T and Kurose, N and Sasaguri, Y and Uramoto, H and Iwagaki, H and Nabeshima, K and Yamada, S}, title = {Localized malignant pleural mesothelioma arising in the interlobar fissure: a unique surgical case masquerading clinicopathologically as primary lung adenocarcinoma.}, journal = {SAGE open medical case reports}, volume = {7}, number = {}, pages = {2050313X18824802}, doi = {10.1177/2050313X18824802}, pmid = {30719319}, issn = {2050-313X}, abstract = {An 80-year-old male with previous workplace exposure to asbestos presented with a history of an increase in the pulmonary-to-hilar mass, measuring more than 50 mm in diameter, likely in the right lower lobe. We first interpreted it as suspicious of primary lung adenocarcinoma with direct invasion to the right hilar lymph node. A right middle and lower lobectomy with partial resection of upper lobe was performed, and gross examination showed a hilar tumor lesion, involving the middle/lower lobe to hilar lymph node and looking whitish to yellow-grayish, partly adjacent to the right pulmonary artery. On microscopic examination, the tumor was located on the extrapulmonary, interlobar pleural fissure, predominantly composed of a proliferation of atypical epithelioid cells, often arranged in an irregular and fused tubular growth pattern with an involvement of pulmonary artery. Immunohistochemically, these atypical cells are positive for several mesothelial markers, including calretinin, cytokeratin 5/6, and WT-1, whereas negative for thyroid transcription factor 1. Furthermore, p16 deletions were specifically detected by fluorescence in situ hybridization, and electron microscopy showed numerous, significantly elongated microvilli. Taken together, we finally made a diagnosis of localized malignant pleural mesothelioma, epithelioid-type, arising in the right interlobar fissure between lower and middle lobes. We should be aware that, owing to its characteristic features, clinicians and pathologists might be able to raise interlobar fissure localized malignant pleural mesothelioma as one of the differential diagnoses, based on careful clinicopathological examinations.}, } @article {pmid30711965, year = {2019}, author = {Salo, SAS and Ilonen, I and Laaksonen, S and Myllärniemi, M and Salo, JA and Rantanen, T}, title = {Malignant Peritoneal Mesothelioma: Treatment Options and Survival.}, journal = {Anticancer research}, volume = {39}, number = {2}, pages = {839-845}, doi = {10.21873/anticanres.13183}, pmid = {30711965}, issn = {1791-7530}, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland.

MATERIALS AND METHODS: The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure.

RESULTS: Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009).

CONCLUSION: Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.}, } @article {pmid30706690, year = {2019}, author = {Rojas, L and Cardona, AF and Trejo-Rosales, R and Zatarain-Barrón, ZL and Ramírez-Tirado, LA and Ruiz-Patiño, A and Campos Gómez, S and Corrales, L and Oblitas, G and Bacon, L and Martín, C and de Lima, VCC and Freitas, HC and Mas, L and Vargas, C and Carranza, H and Otero, J and Pérez, MA and González, L and Chirinos, L and Granados, ST and Rodriguez, J and Báez, R and Remolina Bonilla, YA and Núñez Cerrillo, G and Archila, P and Cuello, M and Karachaliou, N and Rosell, R and Arrieta, O and , }, title = {Characteristics and long-term outcomes of advanced pleural mesothelioma in Latin America (MeSO-CLICaP).}, journal = {Thoracic cancer}, volume = {}, number = {}, pages = {}, doi = {10.1111/1759-7714.12967}, pmid = {30706690}, issn = {1759-7714}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor, associated with poor prognosis. There is a lack of information about the clinical and pathological features related with survival in the Latin American population.

METHODS: The MeSO-CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first-line chemotherapy among Latin American patients.

RESULTS: The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first-line platinum-based chemotherapy. The overall response rate to first-line chemotherapy was 40.4%, progression-free survival to first-line treatment was 5.7 months (95% CI 4.9-6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0-20.5), and multivariate analysis found that stage (P = 0.013), and pleurodesis (P = 0.048), were independent prognostic factors for first-line overall survival. The model to predict response to first-line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non-responders.

CONCLUSION: This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes.}, } @article {pmid30706505, year = {2019}, author = {Sun, H}, title = {North-south gradient of mesothelioma and asbestos consumption-production in the United States-Progresses since the 1st asbestos partial ban in 1973.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.22955}, pmid = {30706505}, issn = {1097-0274}, abstract = {BACKGROUND: Temporal trends and broad geographical distributions of asbestos use and the incidence of malignant mesothelioma (MM) in the US still need to be studied.

METHODS: Data on asbestos consumption and production between 1900 and 2015 and MM mortality and incidence rates between 1975 and 2015 in the US were examined. Spatial distributions of MM mortality and incidence rates and their association with climate zone were analyzed.

RESULTS: Decline of MM incidence and mortality rates in the US occurred about 20 years after the peak of asbestos consumption-production in 1973. There are apparent north-south (N-S) gradients in MM mortality and incidence rates in the US.

CONCLUSION: Recent decline of MM incidence and mortality rates in the US may be associated with reduced US asbestos consumption. N-S MM gradients between 1999 and 2015 were likely related to larger asbestos requirements in building materials in the northern states.}, } @article {pmid30702033, year = {2019}, author = {Germine, M and Puffer, JH}, title = {Analytical transmission electron microscopy of amosite asbestos from South Africa.}, journal = {Archives of environmental & occupational health}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/19338244.2018.1556201}, pmid = {30702033}, issn = {1933-8244}, abstract = {Using the recognized amosite standard, we have performed transmission electron microscopy (TEM), scanning electron microscopy (SEM), and chemical analyses. We use high-resolution transmission electron microscopy (HRTEM) and zone-axis selected area electron diffraction (SAED) to describe the molecular structure of the fibers. We find that both microscopic observational evidence and statistical dimensional characteristics indicate that the amosite fibers are formed by longitudinal splitting, with surfaces produced by fine twinning and lateral boundaries formed by parting parallel to the planes of double and triple sheets of amphibole chain structures. Our findings indicate that amosite would not be regulated under current asbestos regulations, which define amphibole asbestos as whole crystals that are not split and that form fibril bundles, not found in our standard. However, it is fully documented that amosite causes mesothelioma, lung cancer, and asbestosis.}, } @article {pmid30687679, year = {2018}, author = {Visonà, SD and Villani, S and Manzoni, F and Chen, Y and Ardissino, G and Russo, F and Moretti, M and Javan, GT and Osculati, A}, title = {Impact of asbestos on public health: a retrospective study on a series of subjects with occupational and non-occupational exposure to asbestos during the activity of Fibronit plant (Broni, Italy).}, journal = {Journal of public health research}, volume = {7}, number = {3}, pages = {1519}, doi = {10.4081/jphr.2018.1519}, pmid = {30687679}, issn = {2279-9028}, abstract = {The goal of this study is to understand more about the role of asbestos in causing human diseases, first of all mesothelioma, by investigating a large series of deaths due to asbestos-related diseases (ARDs). The main aim is to clarify if even very low amounts of asbestos can cause mesothelioma and other ARDs, as well as to find out if a different individual vulnerability can be important. This retrospective study included 188 subjects who died from asbestos related diseases in 2000-2017 in the area around Broni, Italy, where an important asbestos cement factory had been active from 1932 until 1993. In each case, a forensic autopsy has been performed. In order to perform the present study, the records were retrieved, including the clinical files, the autopsy, and the histological report. The statistical analysis performed showed that there was a significant relation between the cause of death (mesothelioma, lung cancer or asbestosis) and the kind of exposure (occupational, neighborhood or household), showing that all the subjects not exposed occupationally (and, therefore, exposed to lower amounts of asbestos) died from mesothelioma, whereas the individuals who used to work at the plant died also from other caused (asbestosis, lung cancer). Significant differences were highlighted examining the distribution of the causes of death according to the smoking habits. Moreover, among the mesothelioma patients, the survival time was shorter in the subjects with a neighborhood or household exposure than in the occupationally exposed individuals. The study provided meaningful data about the role of asbestos in causing human pathologies. In particular, the present data appear to support the hypothesis that even an exposure to a very little amount of asbestos can cause mesothelioma in hypersusceptible subjects (probably, on a genetic basis).}, } @article {pmid30687504, year = {2019}, author = {Matthews, C and Freeman, C and Sharples, LD and Fox-Rushby, J and Tod, A and Maskell, NA and Edwards, JG and Coonar, AS and Sivasothy, P and Hughes, V and Rahman, NM and Waller, DA and Rintoul, RC}, title = {MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial.}, journal = {BMJ open respiratory research}, volume = {6}, number = {1}, pages = {e000368}, doi = {10.1136/bmjresp-2018-000368}, pmid = {30687504}, issn = {2052-4439}, abstract = {Introduction: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand.

Methods and analysis: MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months.

Ethics and dissemination: This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy.

Trial registration: NCT03412357.}, } @article {pmid30686559, year = {2019}, author = {Neviere, Z and Berthet, P and Polycarpe, F and Dubos-Arvis, C and Dô, P and Gervais, R}, title = {[Malignant mesothelioma and constitutional BAP1 gene mutations].}, journal = {Revue des maladies respiratoires}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rmr.2017.11.014}, pmid = {30686559}, issn = {1776-2588}, abstract = {Malignant mesothelioma is a rare tumour, usually the result of asbestos exposure. Several cases of familial aggregation have been reported and recently shown to be associated with constitutional mutations of the BAP1 gene. BAP1 is a deubiquitinating enzyme implicated in several different cellular mechanisms such as the repair or differentiation of DNA. About a half of malignant mesotheliomas present a somatic, bi-allelic inactivation of BAP1, demonstrated by nuclear extinction on histochemistry. Constitutional alterations of BAP1 are extremely rare. Present in the heterozygous state they are transmitted as an autosomal dominant. They are associated with a risk of developing other tumours such as uveal and cutaneous melanomas, benign melanocytic tumours (melanocytic BAP1-mutated atypical intradermal tumour or MBAITS) and clear cell renal carcinomas. The causal link between mesothelioma and germinal mutations of BAP1 has still not been clearly identified. At present there is, in France, no consensus on recommendations for the management of patients with these mutations. This article is a synthesis of the literature on the functions of the BAP1 gene, the tumour risks related to its alteration and the follow up of patients bearing a constitutional mutation.}, } @article {pmid30685089, year = {2019}, author = {Abayasiriwardana, KS and Wood, MK and Prêle, CM and Birnie, KA and Robinson, BW and Laurent, GJ and McAnulty, RJ and Mutsaers, SE}, title = {Inhibition of collagen production delays malignant mesothelioma tumor growth in a murine model.}, journal = {Biochemical and biophysical research communications}, volume = {510}, number = {2}, pages = {198-204}, doi = {10.1016/j.bbrc.2019.01.057}, pmid = {30685089}, issn = {1090-2104}, abstract = {Malignant mesothelioma is an aggressive fibrous tumor, predominantly of the pleura, with a very poor prognosis. Cell-matrix interactions are recognized important determinants of tumor growth and invasiveness but the role of the extracellular matrix in mesothelioma is unknown. Mesothelioma cells synthesize collagen as well as transforming growth factor-beta (TGF-β), a key regulator of collagen production. This study examined the effect of inhibiting collagen production on mesothelioma cell proliferation in vitro and tumor growth in vivo. Collagen production by mesothelioma cells was inhibited by incubating cells in vitro with the proline analogue thiaproline (thiazolidine-4-carboxylic acid) or by oral administration of thiaproline in a murine tumor model. Cell cytotoxicity was measured using neutral red uptake and lactate dehydrogenase assays. Proliferation was measured by tritiated thymidine incorporation, and inflammatory cell influx, proliferation, apoptosis and angiogenesis in tumors examined by immunohistochemical labelling. Tumor size was determined by tumor weight and collagen production was measured by HPLC. Thiaproline at non-toxic doses significantly reduced basal and TGF-β-induced collagen production by over 50% and cell proliferation by over 65%. In vivo thiaproline administration inhibited tumor growth at 10 days, decreasing the median tumor weight by 80%. The mean concentration of collagen was 50% lower in the thiaproline-treated tumors compared with the controls. There were no significant differences in vasculature or inflammatory cell infiltration but apoptosis was increased in thiaproline treated tumors at day 10. In conclusion, these observations strongly support a role for collagen in mesothelioma growth and establish the potential for inhibitors of collagen synthesis in mesothelioma treatment.}, } @article {pmid30684047, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {Managing malignant pleural mesothelioma: experience and perceptions of health care professionals caring for people with mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00520-019-4648-0}, pmid = {30684047}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor prognosis and heavy symptom burden. Here, we investigate health professionals' attitudes to management and decision-making in people with MPM.

METHODS: Survey questions were based on previous interviews with health professionals, MPM patients, and caregivers. Surveys were sent to specialist doctors and nurses who treat MPM.

RESULTS: Surveys were completed by 107 doctors and 19 nurses from January-September 2014. Most doctors were respiratory physicians (50%) or medical oncologists (35%). Overall, 90% of doctors estimated > 10% of eligible MPM patients did not receive chemotherapy; 43% estimated the rate was > 20%. Doctors believed clinical barriers to chemotherapy were clinician nihilism (70%); non-referral to medical oncology (49%); and lack of specialists in rural/regional areas (44%). Nurses perceived barriers as follows: delayed diagnosis (74%); non-referral to medical oncology (63%); lack of clinician knowledge (58%). Patient-related barriers were negative perception of chemotherapy (83%) and belief survival benefit not worthwhile (63%). Doctors' preference in decision-making was for the patient to make the decision while strongly considering the doctor's opinion (33%); equally with the doctor (29%); and using knowledge gained (23%). Nurses described their roles as providing patient support (100%); information (95%); intermediary (74%); and link to palliative care (74%). Overall, 95% believed they enabled better resource allocation and provided patients with holistic care (95%); clearer communication (89%); more time (89%); additional information (89%); timely referrals (89%).

CONCLUSIONS: Caring for patients with MPM is challenging and complex. Health care professionals believe under-utilisation of chemotherapy is occurring, primarily due to clinician nihilism and lack of medical oncology referral.}, } @article {pmid30663400, year = {2019}, author = {Wang, QQ and Zheng, GQ and Yang, DL and Liang, YF and Yin, WJ and Su, SS}, title = {Pretreatment Controlling Nutritional Status Score and Lactate Dehydrogenase as Predictive Markers of Survival in Patients with Malignant Peritoneal Mesothelioma.}, journal = {Nutrition and cancer}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/01635581.2018.1560481}, pmid = {30663400}, issn = {1532-7914}, abstract = {OBJECTIVE: To investigate the relationships between the Controlling Nutritional Status (CONUT) score and ascites fluid lactate dehydrogenase (LDH) level, and prognosis in patients with malignant peritoneal mesothelioma (MPeM).

METHODS: A total of 125 patients with MPeM were selected for the study using a pathological screening method. Once the diagnosis is established, before the treatment their clinical characteristics and nutritional evaluations were recorded including CONUT score and ascites LDH level. The associations between CONUT, ascites LDH, and other clinicopathological features including body mass index, asbestos exposure, pathological type, and treatment method were analyzed. Prognostic parameters predicting overall survival (OS) were analyzed by Cox regression.

RESULTS: High CONUT score, high ascites LDH level were positively associated with poor prognosis in patients with MPeM according to univariate analyses (P < 0.001, P < 0.001, respectively), and CONUT score and ascites LDH were independent predictors of a poor prognosis according to multivariate analysis. When the CONUT score is greater than 3 and the ascites LHD is greater than 474 IU/l, it indicates a poor prognosis.

CONCLUSIONS: CONUT score and ascites LDH are important factors influencing the prognosis of MPeM patients and should thus be considered in clinical applications.}, } @article {pmid30659154, year = {2019}, author = {Villanova, T and Gesmundo, I and Audrito, V and Vitale, N and Silvagno, F and Musuraca, C and Righi, L and Libener, R and Riganti, C and Bironzo, P and Deaglio, S and Papotti, M and Cai, R and Sha, W and Ghigo, E and Schally, AV and Granata, R}, title = {Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {6}, pages = {2226-2231}, doi = {10.1073/pnas.1818865116}, pmid = {30659154}, issn = {1091-6490}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with exposure to asbestos, with poor prognosis and no effective therapies. The strong inhibitory activities of growth hormone-releasing hormone (GHRH) antagonists have been demonstrated in different experimental human cancers, including lung cancer; however, their role in MPM remains unknown. We assessed the effects of the GHRH antagonists MIA-602 and MIA-690 in vitro in MPM cell lines and in primary MPM cells, and in vivo in MPM xenografts. GHRH, GHRH receptor, and its main splice variant SV1 were found in all the MPM cell types examined. In vitro, MIA-602 and MIA-690 reduced survival and proliferation in both MPM cell lines and primary cells and showed synergistic inhibitory activity with the chemotherapy drug pemetrexed. In MPM cells, GHRH antagonists also regulated activity and expression of apoptotic molecules, inhibited cell migration, and reduced the expression of matrix metalloproteinases. These effects were accompanied by impairment of mitochondrial activity and increased production of reactive oxygen species. In vivo, s.c. administration of MIA-602 and MIA-690 at the dose of 5 μg/d for 4 wk strongly inhibited the growth of MPM xenografts in mice, along with reduction of tumor insulin-like growth factor-I and vascular endothelial growth factor. Overall, these results suggest that treatment with GHRH antagonists, alone or in association with chemotherapy, may offer an approach for the treatment of MPM.}, } @article {pmid30651596, year = {2019}, author = {Sépult, C and Bellefroid, M and Rocks, N and Donati, K and Gérard, C and Gilles, C and Ludwig, A and Duysinx, B and Noël, A and Cataldo, D}, title = {ADAM10 mediates malignant pleural mesothelioma invasiveness.}, journal = {Oncogene}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41388-018-0669-2}, pmid = {30651596}, issn = {1476-5594}, support = {7463213F//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; 7457116F//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; 7653418F//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; 7463012F//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; FA/2014/314//Stichting Tegen Kanker (Belgian Foundation Against Cancer)/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options and treatment efficiency. Even if the latency period between asbestos exposure, the main risk factor, and mesothelioma development is very long, the local invasion of mesothelioma is very rapid leading to a mean survival of one year after diagnosis. ADAM10 (A Disintegrin And Metalloprotease) sheddase targets membrane-bound substrates and its overexpression is associated with progression in several cancers. However, nothing is known about ADAM10 implication in MPM. In this study, we demonstrated higher ADAM10 expression levels in human MPM as compared to control pleural samples and in human MPM cell line. This ADAM10 overexpression was also observed in murine MPM samples. Two mouse mesothelioma cell lines were used in this study including one primary cell line obtained by repeated asbestos fibre injections. We show, in vitro, that ADAM10 targeting through shRNA and pharmacological (GI254023X) approaches reduced drastically mesothelioma cell migration and invasion, as well as for human mesothelioma cells treated with siRNA targeting ADAM10. Moreover, ADAM10 downregulation in murine mesothelioma cells significantly impairs MPM progression in vivo after intrapleural cell injection. We also demonstrate that ADAM10 sheddase downregulation decreases the production of a soluble N-cadherin fragment through membrane N-cadherin, which stimulated mesothelioma cell migration. Taken together, we demonstrate that ADAM10 is overexpressed in MPM and takes part to MPM progression through the generation of N-cadherin fragment that stimulates mesothelioma cell migration. ADAM10 inhibition is worth considering as a therapeutic perspective in mesothelioma context.}, } @article {pmid30648431, year = {2019}, author = {Harris, EJA and Musk, A and de Klerk, N and Reid, A and Franklin, P and Brims, FJH}, title = {Diagnosis of asbestos-related lung diseases.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {3}, pages = {241-249}, doi = {10.1080/17476348.2019.1568875}, pmid = {30648431}, issn = {1747-6356}, abstract = {INTRODUCTION: The diagnosis of lung disease in asbestos-exposed individuals is a process that not only requires a detailed occupational and tobacco smoking history, but the correlation with physical signs, appropriate imaging, detailed lung function assessment and histology/cytology when required. Worldwide, the total quantity of asbestos mined is static, having decreased dramatically in developed countries but increased in countries where there is no restriction on mining: for example, Russia, China, Brazil, and Kazakhstan. The predominant diagnostic challenge in most cases of possible asbestos-related disease is the significant interval between exposure and development of the disease. Also challenging is the estimation of an individual's risk of disease, not least because asbestos-induced malignancy can be rapidly fatal, and, in the case of lung cancer, early detection can lead to treatment with curative intent. Areas covered: Discussion of quantitative asbestos exposure estimation and risk assessment, selection of the most appropriate imaging modality and frequency of imaging. Expert commentary: Consideration of the future for asbestos-related lung disease includes screening those at highest risk particularly in relation to ongoing mining operations and the management of in-situ asbestos. In the future, screening programs designed with estimation of risk of malignancy, based on quantitative estimates of asbestos exposure, and smoking history are indicated.}, } @article {pmid30642542, year = {2019}, author = {Wu, L and Dell'Anno, I and Lapidot, M and Sekido, Y and Chan, ML and Kohno, M and Serre-Beinier, V and Felley-Bosco, E and de Perrot, M}, title = {Progress of malignant mesothelioma research in basic science: A review of the 14th international conference of the international mesothelioma interest group (iMig2018).}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {127}, number = {}, pages = {138-145}, doi = {10.1016/j.lungcan.2018.11.034}, pmid = {30642542}, issn = {1872-8332}, abstract = {Here we summarize the most recent update of mesothelioma research in basic science presented at the 14th iMig2018 international conference. The symposium of basic science track mainly focused on the drivers of mesothelioma initiation and progression, molecular pathogenesis, and perspectives on potential therapeutic approaches. This review covers several promising fields including strategies efficiently inhibiting YAP/TAZ functions or their critical downstream targets, heparanase inhibitors, RAN depletion, and MIF/CD74 inhibitors that may be developed as novel therapeutic approaches. In addition, targeting mesothelioma stem cells by depleting M2-polarized macrophages in tumor microenvironment or blocking Tnfsf18 (GITRL)-GITR signalling might be translated into therapeutic modalities in mesothelioma treatment.}, } @article {pmid30629589, year = {2019}, author = {Chicco, D and Rovelli, C}, title = {Computational prediction of diagnosis and feature selection on mesothelioma patient health records.}, journal = {PloS one}, volume = {14}, number = {1}, pages = {e0208737}, doi = {10.1371/journal.pone.0208737}, pmid = {30629589}, issn = {1932-6203}, abstract = {BACKGROUND: Mesothelioma is a lung cancer that kills thousands of people worldwide annually, especially those with exposure to asbestos. Diagnosis of mesothelioma in patients often requires time-consuming imaging techniques and biopsies. Machine learning can provide for a more effective, cheaper, and faster patient diagnosis and feature selection from clinical data in patient records.

METHODS AND FINDINGS: We analyzed a dataset of health records of 324 patients having mesothelioma symptoms from Turkey. The patients had prior asbestos exposure and displayed symptoms consistent with mesothelioma. We compared probabilistic neural network, perceptron-based neural network, random forest, one rule, and decision tree classifiers to predict diagnosis of the patient records. We measured classifiers' performance through standard confusion matrix scores such as Matthews correlation coefficient (MCC). Random forest outperformed all models tried, obtaining MCC = +0.37 on the complete imbalanced dataset and MCC = +0.64 on the under-sampled balanced dataset. We then employed random forest feature selection to identify the two most relevant dataset traits associated with mesothelioma: lung side and platelet count. These two risk factors resulted so predictive, that decision tree focusing on them achieved the second top accuracy on the complete dataset diagnosis prediction (MCC = +0.28), outperforming all other methods and even decision tree itself applied to all features.

CONCLUSIONS: Our results show that machine learning can predict diagnoses of patients having mesothelioma symptoms with high accuracy, sensitivity, and specificity, in few minutes. Additionally, random forest can efficiently select the most important features of this clinical dataset (lung side and platelet count) in few seconds. The importance of pleural plaques in lung sides and blood platelets in mesothelioma diagnosis indicates that physicians should focus on these two features when reading records of patients with mesothelioma symptoms. Moreover, doctors can exploit our machinery to predict patient diagnosis when only lung side and platelet data are available.}, } @article {pmid30623323, year = {2019}, author = {Taghizadeh, F and Jafari, AJ and Gholami, M and Kermani, M and Arfaeinia, H and Mohammadi, S and Dowlati, M and Shahsavani, A}, title = {Monitoring of airborne asbestos fibers in an urban ambient air of Shahryar City, Iran: levels, spatial distribution, seasonal variations, and health risk assessment.}, journal = {Environmental science and pollution research international}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11356-018-4029-0}, pmid = {30623323}, issn = {1614-7499}, support = {31563//Environmental and occupational health center/ ; }, abstract = {Asbestos, as with other pollutants in the air, has adverse effects on the health of human beings and animals. Today, the relationship between presence of asbestos fibers in the air breathed by humans and developing serious diseases such as lung cancer (asbestosis) and mesothelioma has been proven. This study was designed and conducted within the time period of August 2017 and June 2018 to determine the concentration of asbestos fiber in the ambient air of Shahryar City and to evaluate their health effects for the general population of the city. For this purpose, samples were taken from four points, and overall 32 air samples were taken along the year. The samples were then analyzed by the phase contrast microscopy (PCM) method. Also, to investigate the type of asbestos and for more accurate counting of fibers, SEM analysis was utilized. Finally, based on the EPA IRIS method, the health effects resulting from asbestos risks were also evaluated. The results of this study indicated that the mean annual concentration of asbestos fiber in the ambient air of Shahryar City was obtained as 0.0019 f/ml PCM and 0.0072 f/ml SEM. Furthermore, the most polluted point was S1 point (0.0119 -0.0026 f/ml, PCM), while the lowest concentration was related to S4 point (0.001 f/ml PCM-0.0021 f/ml SEM). The mean annual risk resulting from airborne asbestos fiber in the ambient air of Shahryar City for all samples was obtained as 1.72 × 10-6 to 2.2 × 10-4, which was higher than the recommended risk range in some points.}, } @article {pmid30622932, year = {2018}, author = {Lo Russo, G and Tessari, A and Capece, M and Galli, G and de Braud, F and Garassino, MC and Palmieri, D}, title = {MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {650}, doi = {10.3389/fonc.2018.00650}, pmid = {30622932}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a variable incidence among different countries. Occupational asbestos exposure is the most important etiological factor and a very long latency period is widely reported. In the early phase of the disease, clinical signs are absent or not specific. For this reason, the diagnosis is frequently achieved only in the advanced stages. The histopathological diagnosis per se is also very complex, and no known factor can predict the prognosis with certainty. Nonetheless, current survival rates remain very low, despite the use of standard treatments, which include surgery, chemotherapy and radiotherapy. The identification of new prognostic and/or diagnostic biomarkers, and the discovery of therapeutic targets is a priority and could lead to a real significant impact on the management of malignant pleural mesothelioma. In this scenario, the role of microRNAs is becoming increasingly relevant, with the promise of a quick translation in the current clinical practice. Despite the relative novelty of this field, the number of works and candidate microRNAs that are present in literature is striking. Unfortunately, to date the microRNAs with the most clinical relevance for MPM are still matter of debate, probably due to the variety of approaches, techniques, and collected samples. Although specific microRNAs (e.g., let-7, miR-15 and miR-16, miR-21, miR-34a, and the miR-200 family) have been reported several times from different groups, the heterogeneity of published data reinforces the need of more comprehensive and unified studies on this topic. In this review we collect and discuss the studies focused on the involvement of microRNAs in different aspects of MPM, from their biological role in tumorigenesis and progression, to their possible application as diagnostic, prognostic and predictive biomarkers. Lastly, we examine their potential value as for the design of therapeutic approaches that could benefit MPM patients.}, } @article {pmid30618090, year = {2019}, author = {Zha, L and Kitamura, Y and Kitamura, T and Liu, R and Shima, M and Kurumatani, N and Nakaya, T and Goji, J and Sobue, T}, title = {Population-based cohort study on health effects of asbestos exposure in Japan.}, journal = {Cancer science}, volume = {}, number = {}, pages = {}, doi = {10.1111/cas.13930}, pmid = {30618090}, issn = {1349-7006}, support = {15H04774//Japan Society for the Promotion of Science KAKENHI/ ; }, abstract = {Occupational asbestos exposure occurs in many workplaces and is a well-known cause of mesothelioma and lung cancer. However, the association between nonoccupational asbestos exposure and those diseases is not clearly described. The aim of this study was to investigate cause-specific mortality among the residents of Amagasaki, a city in Japan with many asbestos factories, and evaluate the potential excess mortality due to established and suspected asbestos-related diseases. The study population consisted of 143 929 residents in Amagasaki City before 1975 until 2002, aged 40 years or older on January 1, 2002. Follow-up was carried out from 2002 to 2015. Standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated by sex, using the mortality rate of the Japanese population as reference. A total of 38 546 deaths (including 303 from mesothelioma and 2683 from lung cancer) were observed. The SMRs in the long-term residents' cohort were as follows: death due to all causes, 1.12 (95% CI, 1.10-1.13) in men and 1.07 (95% CI, 1.06-1.09) in women; lung cancer, 1.28 (95% CI, 1.23-1.34) in men and 1.23 (95% CI, 1.14-1.32) in women; and mesothelioma, 6.75 (95% CI, 5.83-7.78) in men and 14.99 (95% CI, 12.34-18.06) in women. These SMRs were significantly higher than expected. The increased SMR of mesothelioma suggests the impact of occupational asbestos exposure among men and nonoccupational asbestos exposure among women in the long-term residents' cohort. In addition, the high level of excess mortality from mesothelioma has persisted, despite the mixture of crocidolite and chrysotile no longer being used for three or four decades.}, } @article {pmid30609805, year = {2019}, author = {Turini, S and Bergandi, L and Gazzano, E and Prato, M and Aldieri, E}, title = {Epithelial to Mesenchymal Transition in Human Mesothelial Cells Exposed to Asbestos Fibers: Role of TGF-β as Mediator of Malignant Mesothelioma Development or Metastasis via EMT Event.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, doi = {10.3390/ijms20010150}, pmid = {30609805}, issn = {1422-0067}, abstract = {Asbestos exposure increases the risk of asbestosis and malignant mesothelioma (MM). Both fibrosis and cancer have been correlated with the Epithelial to Mesenchymal Transition (EMT)-an event involved in fibrotic development and cancer progression. During EMT, epithelial cells acquire a mesenchymal phenotype by modulating some proteins. Different factors can induce EMT, but Transforming Growth Factor β (TGF-β) plays a crucial role in promoting EMT. In this work, we verified if EMT could be associated with MM development. We explored EMT in human mesothelial cells (MeT-5A) exposed to chrysotile asbestos: we demonstrated that asbestos induces EMT in MeT-5A cells by downregulating epithelial markers E-cadherin, β-catenin, and occludin, and contemporarily, by upregulating mesenchymal markers fibronectin, α-SMA, and vimentin, thus promoting EMT. In these cells, this mechanism is mediated by increased TGF-β secretion, which in turn downregulates E-cadherin and increases fibronectin. These events are reverted in the presence of TGF-β antibody, via a Small Mother Against Decapentaplegic (SMAD)-dependent pathway and its downstream effectors, such as Zinc finger protein SNAI1 (SNAIL-1), Twist-related protein (Twist), and Zinc Finger E-Box Binding Homeobox 1 (ZEB-1), which downregulate the E-cadherin gene. Since SNAIL-1, Twist, and ZEB-1 have been shown to be overexpressed in MM, these genes could be considered possible predictive or diagnostic markers of MM development.}, } @article {pmid30603603, year = {2019}, author = {Shehata, M and Zaid, F and Ottaviano, P and Shweihat, Y and Munn, N}, title = {Case report: Steroid responsive mesothelioma-related pleural effusion.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {131-135}, doi = {10.1016/j.rmcr.2018.12.006}, pmid = {30603603}, issn = {2213-0071}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related tumor arising in the pleural cavity. Symptoms reflect extension of disease and include shortness of breath and chest pain. Unexplained pleural effusion and pleural pain in patients exposed to asbestos should raise the suspicion of MPM. The most common radiologic presentation is ipsilateral pleural effusion with or without pleural thickening or a mass. Thoracoscopic biopsy remains the most appropriate procedure for definitive diagnosis of mesothelioma. Despite advancement in diagnostic procedures and biomolecular research, this tumor nevertheless has poor prognosis. Mesothelioma remains a diagnostic and therapeutic challenge and is likely to remain one in the years to come. Here we present the first reported case of steroid treatment responsive pleural effusion in a 72 year-old-male that initially was misdiagnosed as rheumatoid related effusion. However, Pleuroscopy with biopsy revealed mesothelioma.}, } @article {pmid30596292, year = {2019}, author = {Ye, L and Ma, S and Robinson, BW and Creaney, J}, title = {Immunotherapy strategies for mesothelioma - the role of tumor specific neoantigens in a new era of precision medicine.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {2}, pages = {181-192}, doi = {10.1080/17476348.2019.1563488}, pmid = {30596292}, issn = {1747-6356}, abstract = {INTRODUCTION: Immunotherapy has long been considered a potential therapy for malignant mesothelioma and is currently being pursued as such. Some of the early phase clinical trials involving immunomodulators have demonstrated encouraging results and numerous clinical trials are underway to further investigate this treatment approach in various treatment settings and larger patient cohorts. Areas covered: This review summarizes the current and emerging clinical evidence for checkpoint blockade and other immunotherapeutic strategies in mesothelioma. The mesothelioma tumor immune microenvironment and mutational landscape are also discussed, including their impact on treatment strategies. We also provide an evaluation of the current evidence for neoantigen targeted personalized immunotherapy. Expert opinion: Immune checkpoint inhibitors work by unleashing the host immune response against probable neoantigens. Despite impressive activity in a small subset of patients and the potential for prolonged responses, most patients experience treatment failure. Neoantigen vaccines provide a potential complementary therapeutic strategy by increasing the immunogenic antigen load, which can lead to an increased tumor specific immune response. Further research is needed explore this treatment option in mesothelioma and technological advances are required to translate this concept into clinical practice.}, } @article {pmid30594459, year = {2019}, author = {McGehee, E and Gerber, DE and Reisch, J and Dowell, JE}, title = {Treatment and Outcomes of Primary Pericardial Mesothelioma: A Contemporary Review of 103 Published Cases.}, journal = {Clinical lung cancer}, volume = {20}, number = {2}, pages = {e152-e157}, doi = {10.1016/j.cllc.2018.11.008}, pmid = {30594459}, issn = {1938-0690}, abstract = {Primary pericardial mesothelioma (PPM) is a rare cancer for which there is no consensus on treatment. We evaluated and summarized a large contemporary population of published PPM cases to characterize risk factors, treatment patterns, and clinical outcomes. Using Ovid and PubMed, literature published from 2000 through 2016 was searched using the terms "primary pericardial mesothelioma," "pericardial mesothelioma," and "malignant pericardial mesothelioma." We identified 6 case series and 84 case reports for a total of 103 PPM cases published from 2000 through 2016. The median age at diagnosis was 55 years, and the median overall survival was 6 months. In univariate analyses of clinical characteristics including gender, asbestos exposure, tobacco use, prior radiation exposure, histologic subtype, and metastasis and/or mediastinal spread, only the presence of metastasis and/or mediastinal spread was a significant predictor of decreased survival (P = .015). Surgery did not provide a statistically significant survival benefit (P = .12). A survival benefit was noted in those who received chemotherapy (median survival, 13 months vs. 0.5 months, P = .002), specifically chemotherapy with a platinum agent with or without pemetrexed. In multivariate analysis, only the receipt of chemotherapy was associated with improved survival. PPM remains a rare and poorly understood malignancy with unclear etiology and a poor prognosis. In this retrospective systematic review, a survival benefit was seen in patients who received chemotherapy.}, } @article {pmid30594195, year = {2018}, author = {Merlo, DF and Bruzzone, M and Bruzzi, P and Garrone, E and Puntoni, R and Maiorana, L and Ceppi, M}, title = {Mortality among workers exposed to asbestos at the shipyard of Genoa, Italy: a 55 years follow-up.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {94}, doi = {10.1186/s12940-018-0439-1}, pmid = {30594195}, issn = {1476-069X}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Neoplasms/*mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Respiratory Tract Diseases/*mortality ; *Ships ; Young Adult ; }, abstract = {BACKGROUND: Exposure to asbestos remains a global issue due to its massive use in the twentieth century and its long environmental persistence. Exposure to asbestos still occurs during dismantling of ships and vessels, buildings renovation, mining operations, and is reported in developing countries. Current estimate report exposure of hundreds of million people in occupational settings in countries where its use remains unregulated.

METHODS: We conducted a historical prospective cohort mortality study aimed at estimating mortality from specific causes, the temporal changes of pleural and lung cancer mortality, and the attributable fraction (AF) of lung cancer deaths following asbestos exposure. The study included 3984 shipyard workers employed at the shipyard of Genoa, Italy, between 1960 and 1981 and followed up to December 2014. Standardized Mortality Ratios (SMR) and their 95% confidence intervals (95%CI) were computed.

RESULTS: Overall deaths recorded were 3331 (83.6%). Excess mortality was observed for all cancers (SMR = 127, 95%CI:120-134), pleural mesothelioma (575, 469-697), cancers of the larynx (183, 134-244) and of the lung (154, 139-170), and for respiratory tract diseases (127, 114-141), including asbestosis (2277, 1525-3270). Ninety out of 399 deaths (22.6%) from lung cancer were attributed to asbestos exposure. The estimated lung cancer AF was 49.3% in workers with the highest SMR for pleural cancer. Median latency times for pleural and lung cancer were 42.8 years (minimum latency: 9.3 years) and 38.7 years (minimum latency: 6 years). The peak of mesothelioma incidence, expected in Italy in the period 2015-2024, was confirmed.

CONCLUSIONS: The long follow-up period of our study allowed the detection of a substantial disease burden following asbestos exposure. These findings support the urgent need for the prevention of asbestos related diseases through the implementation of asbestos ban worldwide, including those countries where asbestos is still mined, manufactured and used.}, } @article {pmid30567579, year = {2018}, author = {Xu, R and Barg, FK and Emmett, EA and Wiebe, DJ and Hwang, WT}, title = {Association between mesothelioma and non-occupational asbestos exposure: systematic review and meta-analysis.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {90}, doi = {10.1186/s12940-018-0431-9}, pmid = {30567579}, issn = {1476-069X}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42ES023720/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Cohort Studies ; Environmental Exposure/*adverse effects ; Humans ; Mesothelioma/*epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: The risk of mesothelioma has been shown to be associated with exposure to asbestos fibers. Most of the existing literature focuses on occupational exposure; however, non-occupational asbestos exposure has also been identified as an important risk factor.

OBJECTIVE: To estimate the association between mesothelioma and non-occupational asbestos exposure, and evaluate control recruitment and exposure measurement methods.

METHODS: A systematic literature review was conducted to identify case-control (CC) and cohort studies that examined the association between mesothelioma and non-occupational exposure to asbestos, including neighborhood, domestic, and household exposure. Meta-analysis was performed to estimate a summary relative risk estimate (SRRE) and 95% confidence interval using random-effects models. Subgroup analyses were also conducted by exposure type, gender, region, and fiber type.

RESULTS: Twenty CC and 7 cohort studies were selected. Controls in CC studies were selected from the general population (55%), hospital records (18%), cancer registry (23%) and a combination of population and hospital records (5%). Multiple methods were used to measure neighborhood exposure (e.g., linear distance and direction of residence from an asbestos factory), domestic (e.g., whether living with an asbestos worker) and household exposure (e.g., whether involved in asbestos-containing home improvement projects). Primary meta-analyses suggested a SRRE of mesothelioma of 5.33 (95%CI: 2.53, 11.23) from neighborhood exposure, 4.31 (95%CI, 2.58, 7.20) from domestic exposure, and 2.41 (95%CI, 1.30, 4.48) from household exposure with large I2 statistics ranging from 83-99%.

CONCLUSIONS: Non-occupational asbestos exposure is significantly associated with an elevated risk of mesothelioma. Funnel plots indicated a potential of publication bias. Some SRREs should be interpreted with cautions because of high between-studies heterogeneity.}, } @article {pmid30561515, year = {2018}, author = {Oddone, E and Terracini, B and Mirabelli, D and Mensi, C and Consonni, D and Barone-Adesi, F}, title = {Comment on: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {}, number = {}, pages = {}, doi = {10.1093/carcin/bgy179}, pmid = {30561515}, issn = {1460-2180}, } @article {pmid30558734, year = {2019}, author = {Kai, Y and Tsutani, Y and Ito, M and Mimura, T and Miyata, Y and Okada, M}, title = {Metachronous Lung Cancer After Pleurectomy/Decortication.}, journal = {The Annals of thoracic surgery}, volume = {107}, number = {1}, pages = {e1-e3}, doi = {10.1016/j.athoracsur.2018.05.087}, pmid = {30558734}, issn = {1552-6259}, abstract = {Pleurectomy/decortication is a surgical procedure for malignant pleural mesothelioma (MPM) and has been proposed as an alternative to extrapleural pneumonectomy. We report a second primary lung cancer developing after pleurectomy/decortication for MPM. A 59-year-old man was diagnosed with MPM on the right side and underwent pleurectomy/decortication. Follow-up computed tomography detected a nodule in the right upper lobe that was diagnosed as adenocarcinoma by wedge resection. Lung cancer and MPM are associated with asbestos exposure. However, predicting lung cancer after treatment for MPM is difficult. Careful follow-up of the spared lung is necessary for detecting second primary lung cancer or MPM recurrence.}, } @article {pmid30557225, year = {2018}, author = {Schnatter, AR and Wojcik, NC and Jorgensen, G}, title = {Mortality Update of a Cohort of Canadian Petroleum Workers.}, journal = {Journal of occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/JOM.0000000000001523}, pmid = {30557225}, issn = {1536-5948}, abstract = {OBJECTIVE: This study updates the mortality experience of over 25,000 workers in a large Canadian petroleum company through December 31, 2006.

METHODS: Standardized Mortality Ratios were generated for all cause and specific cause mortality.

RESULTS: All cause and all cancer mortality were favorable compared to the general Canadian population. Cancers of previous interest were largely consistent with expectation. There is a continuing excess of mesothelioma, which is of similar magnitude as the previous update, although based on larger numbers. This excess is mostly attributable to men who died in their 50's and 60's and who worked in the refining sector.

CONCLUSIONS: Most causes of death show mortality rates lower than the Canadian general population. Given the excess of mesothelioma observed, this study supports ongoing vigilance in asbestos exposure control programs as refineries continue to remove asbestos from their facilities.}, } @article {pmid30545133, year = {2018}, author = {Wörthmüller, J and Oberson, A and Salicio, V and Blum, W and Schwaller, B}, title = {Calretinin Functions in Malignant Mesothelioma Cells Cannot Be Replaced by the Closely Related Ca2+-Binding Proteins Calbindin-D28k and Parvalbumin.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, doi = {10.3390/ijms19124015}, pmid = {30545133}, issn = {1422-0067}, support = {130680, 139226, 147697/1//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, abstract = {Calretinin (CR; CALB2) belonging to the family of EF-hand Ca2+-binding proteins (CaBP) is widely used as a positive marker for the identification of human malignant mesothelioma (MM) and functionally was suggested to play a critical role during carcinogenesis of this highly aggressive asbestos-associated neoplasm. Increasing evidence suggests that CR not only acts as a prototypical Ca2+ buffer protein, i.e., limiting the amplitude of Ca2+ signals but also as a Ca2+ sensor. No studies have yet investigated whether other closely related CaBPs might serve as substitutes for CR's functions(s) in MM cells. Genetically modified MM cell lines with medium (MSTO-211H and ZL5) or low (SPC111) endogenous CR expression levels were generated that overexpress either CR's closest homologue calbindin-D28k (CB) or parvalbumin (PV), the latter considered as a "pure" Ca2+ buffer protein. After lentiviral shCALB2-mediated CR downregulation, in both MSTO-211H and ZL5 cells expressing CB or PV, the CR deficiency-mediated increase in cell death was not prevented by CB or PV. With respect to proliferation and cell morphology of SPC111 cells, CB was able to substitute for CR, but not for CR's other functions to promote cell migration or invasion. In conclusion, CR has a likely unique role in MM that cannot be substituted by "similar" CaBPs.}, } @article {pmid30533375, year = {2019}, author = {Yamazoe, M and Tomioka, H and Kamada, T and Kaneko, M and Katsuyama, E}, title = {Simultaneous presence of lung adenocarcinoma and malignant pleural mesothelioma: A case report.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {45-49}, pmid = {30533375}, issn = {2213-0071}, abstract = {The co-presence of malignant pleural mesothelioma (MPM) and lung cancer is rare. We report a 70-year-old male with exposure to asbestos. Chest computed tomography revealed a right mediastinal mass combined with an enlarged ipsilateral lymph node and left pleural effusion. Transbronchial lung biopsy revealed lung adenocarcinoma. Thoracoscopic examination revealed multiple left pleural nodules, leading to the diagnosis of MPM. Despite aggressive anticancer drug therapy, he expired due to disease progression 2.5 years after diagnosis. Autopsy confirmed an epithelioid MPM in the left pleura. MPM comorbidity in patients diagnosed with lung cancer should be considered, especially in those exposed to asbestos.}, } @article {pmid30530573, year = {2018}, author = {Lee, LJ and Lin, CK and Pan, CH and Cheng, Y and Chang, YY and Liou, SH and Wang, JD}, title = {Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.}, journal = {BMJ open}, volume = {8}, number = {12}, pages = {e021063}, doi = {10.1136/bmjopen-2017-021063}, pmid = {30530573}, issn = {2044-6055}, abstract = {OBJECTIVE: Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency.

METHODS: We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed for each factory where any case of MPM was diagnosed by assuming Poisson distribution with a minimal latency of 20 years.

RESULTS: A total of 18 MPM (17 males, 1 female) in eight factories were found. The incidence rate of MPM for the eight factories was 18.0 per million, ranging from 6.2 per million (military factory) to 268.2 per million (asbestos cement). We observed significantly increased risks for MPM in asbestos cement, thermal insulation and shipbuilding industries, with eRR (genders combined) of 113.6, 87.5 and 15.8, respectively. The sensitivity analyses considering latency showed similar findings in latency ≥30 years, and the shipbuilding industry presented a significant eRR given a latency ≥40 years. The gender-specific eRR showed similar results in men, but high eRR of 729.6 was observed in an asbestos cement factory where a female MPM was diagnosed.

CONCLUSIONS: This nationwide study in Taiwan comprehensively shows that different asbestos manufacturing processes, including asbestos cement, thermal insulation and shipbuilding industries, were at significantly increased risks for MPM. We recommend to establish a medical screening programme for workers previously exposed to asbestos to identify MPM and other asbestos-related diseases at an earlier stage.}, } @article {pmid30527173, year = {2018}, author = {Serio, G and Vimercati, L and Pennella, A and Gentile, M and Cavone, D and Buonadonna, AL and Scattone, A and Fortarezza, F and De Palma, A and Marzullo, A}, title = {Genomic changes of chromosomes 8p23.1 and 1q21: Novel mutations in malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {126}, number = {}, pages = {106-111}, doi = {10.1016/j.lungcan.2018.10.012}, pmid = {30527173}, issn = {1872-8332}, abstract = {INTRODUCTION: Malignant mesothelioma is an aggressive malignancy of the thoracic cavity caused by prior asbestos exposure. In the peritoneum the mesothelioma is an extremely rare condition. In the present preliminary study, high-resolution array-comparative genomic hybridization (a-CGH) was performed to identify genetic imbalances in a series of malignant peritoneal mesothelioma cases.

MATERIALS AND METHODS: Between 1990 and 2008, among the cases recorded in the Apulia Mesothelioma Register, we found 22 peritoneal mesothelioma cases. CGH-array was performed on samples from all patients.

RESULTS: The CGH-array analysis revealed multiple chromosomal imbalances. Interestingly, deletion at 8p23.1 was observed in 12 cases. Furthermore, another novel deletion at 1q21 was present in 11. Often, 1q21 and 8p23.1 losses were present in the same patient (7 cases). Losses of BAP1 and CDKN2A loci were not detected.

DISCUSSION: The region at 8p23.1 contains the beta-defensin gene cluster (DEF) and 1q21 contains ubiquitin conjugating enzyme E2 (UBE2Q1). We hypotesized that the loss of function of ubiquitination, as well as of the defensins, could play an important role in the initial development and subsequent progression of mesothelioma.}, } @article {pmid30518402, year = {2018}, author = {Chee, J and Watson, MW and Chopra, A and Nguyen, B and Cook, AM and Creaney, J and Lesterhuis, WJ and Robinson, BW and Lee, YCG and Nowak, AK and Lake, RA and McDonnell, AM}, title = {Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {864}, pmid = {30518402}, issn = {1756-0500}, support = {CA150787//U.S. Department of Defense/ ; }, abstract = {OBJECTIVE: Pleural effusion (PE) is a common feature of malignant pleural mesothelioma. These effusions typically contain lymphocytes and malignant cells. We postulated that the PE would be a source of lymphocytes for analysis of tumor immune milieu. The aim of this study was to compare the phenotype and T cell receptor usage of pleural effusion T cells with paired concurrently drawn peripheral blood lymphocytes. We used multi-parameter flow cytometry and high-throughput T cell receptor sequencing to analyse peripheral blood and pleural effusion mononuclear cells.

RESULTS: Both CD8+ and CD4+ T cells from effusion showed increased expression of T cell inhibitory receptors PD-1, LAG-3 and Tim-3 compared to blood. Comprehensive T cell receptor sequencing on one of the patients showed a discordant distribution of clonotypes in the antigen-experienced (PD-1+) compartment between effusion and blood, suggesting an enrichment of antigen specific clonotypes in the effusion, with potential as an immunological response biomarker.}, } @article {pmid30506035, year = {2018}, author = {Okita, R and Nojima, Y and Saisho, S and Shimizu, K and Shirai, R and Kanomata, N and Oka, M and Nakata, M}, title = {Deciduoid type malignant pleural mesothelioma: a case report.}, journal = {AME case reports}, volume = {2}, number = {}, pages = {43}, pmid = {30506035}, issn = {2523-1995}, abstract = {Here, we report a patient with deciduoid type malignant pleural mesothelioma (MPM), which rapidly progressed. A 55-year-old man who might have been exposed to asbestos a few decades ago had severe back pain. The chest X-ray scanning and computed tomography (CT) revealed pleural thickness on his right thoracic space, without the presence of a lung mass. A pleural biopsy was performed and the patient was histologically diagnosed with deciduoid type MPM. Although he received two cycles of chemotherapy, his disease rapidly progressed and he died within two months of the diagnosis of deciduoid type MPM.}, } @article {pmid30501113, year = {2018}, author = {Izquierdo-Sánchez, V and Muñiz-Hernández, S and Vázquez-Becerra, H and Pacheco-Yepez, J and Romero-Piña, ME and Arrieta, O and Medina, LA}, title = {Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft.}, journal = {Molecules (Basel, Switzerland)}, volume = {23}, number = {12}, pages = {}, doi = {10.3390/molecules23123138}, pmid = {30501113}, issn = {1420-3049}, support = {PAPIIT IN-225014, IN209916//Universidad Nacional Autónoma de México/ ; 154557//Consejo Nacional de Ciencia y Tecnología/ ; (017/027/IBI)(CEI/1147/17)//Instituto Nacional de Cancerología/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.}, } @article {pmid30513236, year = {2018}, author = {Till, JE and Beck, HL and Boice, JD and Mohler, HJ and Mumma, MT and Aanenson, JW and Grogan, HA}, title = {Asbestos Exposure and Mesothelioma Mortality among Atomic Veterans.}, journal = {International journal of radiation biology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/09553002.2018.1551641}, pmid = {30513236}, issn = {1362-3095}, abstract = {BACKGROUND: During the Cold War the United States (U.S.) conducted 230 above-ground atmospheric nuclear weapons tests between 1945 and 1962 at the Nevada Test Site and the Pacific Proving Grounds. These tests involved over 250,000 military personnel. Asbestos was used on the naval vessels for insulation in the boiler room, engine room, and other areas. This is the first quantitative assessment of asbestos-related mesothelioma, including cancers of the pleura and peritoneum, among military personnel who participated in above-ground nuclear weapons testing.

METHODS: Approximately 114,000 atomic veterans were selected for an epidemiological study because they were in one of eight series of weapons tests that were associated with somewhat higher personnel exposures than the other tests and because they have been previously studied. We were able to categorize specific jobs into potential for asbestos exposure based on a detailed database of the military activities of the atomic veterans, developed using historical records provided by the Defense Threat Reduction Agency. Standardized mortality ratios (SMR) were calculated by service, rank(officer/enlisted) and ratings (occupation code and work location aboard ship) after 65 years of follow-up… Results: Mesothelioma deaths were significantly increased overall (SMR 1.56; 95% CI 1.32-1.82; n= 153). This increase was seen only among those serving in the Pacific Proving Ground (SMR 1.97; 95% CI 1.65-2.34; n= 134), enlisted men (SMR 1.81; 95% CI 1.53-2.13; n= 145) and the 70,309 navy personnel (SMR 2.15; 95% CI 1.80-2.56; n= 130). No increased mortality rates were seen among the other services: army (SMR 0.45), air force (SMR 0.85) or marines (SMR 0.75). Job categories with the highest potential for asbestos exposure (machinist's mates, boiler technicians, water tender, pipe fitters, and fireman) had an of SMR 6.47. Job categories with lower potential (SMR =1.35) or no potential (SMR =1.28) for asbestos exposure had non-significantly elevated mesothelioma mortality.

CONCLUSIONS: Although jobs with high potential for exposure to asbestos products were held by only 20% of the enlisted naval population, sailors with these jobs (machinist's mate, pipe fitter, boiler technician, water tender and fireman) experienced 55% of mesothelioma deaths. The significantly higher mortality rate overall was explained by asbestos exposure among enlisted naval personnel in this low-dose radiation exposed cohort.}, } @article {pmid30500290, year = {2018}, author = {Regragui, M and Guebessi, NB}, title = {Primary Malignant Deciduoid Mesothelioma: A Challenging Diagnosis.}, journal = {Archives of pathology & laboratory medicine}, volume = {}, number = {}, pages = {}, doi = {10.5858/arpa.2017-0461-RS}, pmid = {30500290}, issn = {1543-2165}, abstract = {Primary malignant deciduoid mesothelioma is a rare subtype of epithelioid mesothelioma that was first described in the peritoneum in young women without a history of asbestos exposure. It was thought to be a distinct clinicopathologic entity with ominous prognosis; recent studies have better characterized this entity. On morphology, primary malignant deciduoid mesothelioma is characterized by cytomorphologic features resembling decidualized tissue. Pleomorphism is variable. The immunoprofile is similar to other epithelioid mesotheliomas. The prognosis is the same as other epithelioid mesotheliomas and seems to depend on histological grade.}, } @article {pmid30489434, year = {2018}, author = {Dournes, G and Dubois, A and Benlala, I and Lacourt, A and Paris, C and Gislard, A and Clin, B and Pairon, JC and Baldacci, F and Laurent, F}, title = {3-Dimensional Quantification of Composite Pleural Plaque Volume in Patients Exposed to Asbestos Using High-resolution Computed Tomography: A Validation Study.}, journal = {Journal of thoracic imaging}, volume = {}, number = {}, pages = {}, doi = {10.1097/RTI.0000000000000377}, pmid = {30489434}, issn = {1536-0237}, abstract = {RATIONALE: As pleural plaque has been reported as a risk factor in the occurrence of lung cancer and mesothelioma, a reproducible and precise method of measurement of pleural plaque volume (PPV) is needed to further describe these relationships. The aim of the study was to assess the reproducibility of a 3-dimensional computed tomography (3D-CT) volumetric analysis of PPV in patients with occupational exposure to asbestos.

MATERIAL AND METHODS: A total of 28 patients were retrospectively randomly selected from the multicenter APEXS (Asbestos Post Exposure Survey) study, which was held between 2003 and 2005. All patients underwent a 3D-CT scan. Two readers specialized in chest radiology completed the 3D semiautomated quantification of lung volume using dedicated software. They also had to categorize the visual extent of pleural plaque in terms of thickness and circumference. Reproducibility of the continuous PPV variable was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Reproducibility of categorical variables was assessed using the κ test.

RESULTS: Intraobserver reproducibility of PPV was almost perfect (ICC=0.98 [95% interval: 0.97-0.99]), and interobserver reproducibility was very good (ICC=0.93 [0.88-0.97]). At Bland-Altman analysis, the mean differences were 0.1 (limit of agreement: -11.0 to 11.2) and 3.7 cc (-17.8 to 25.2), respectively. Visual analysis of both plaque in terms of thickness and circumference were fair to moderate, with κ values ranging from 0.30 to 0.60.

CONCLUSIONS: 3D semiautomatic quantification of PPV is feasible and reproducible using CT in patients with occupational exposure to asbestos. PPV measurement may be useful to correlate with other asbestos-related disease outcomes and prognosis.}, } @article {pmid30479777, year = {2018}, author = {Park, S and Park, J and Lee, E and Eom, H and Shin, MY and Kim, J and Kang, D and Lee, S}, title = {Ovarian cancer in a former asbestos textile factory worker: a case report.}, journal = {Annals of occupational and environmental medicine}, volume = {30}, number = {}, pages = {65}, pmid = {30479777}, issn = {2052-4374}, abstract = {Background: The International Agency for Research on Cancer (IARC) defined that asbestos is a group 1 substance that causes lung cancer, mesothelioma (pleura and peritoneum), laryngeal cancer, and ovarian cancer in humans. Many studies on lung cancer, and mesothelioma caused by asbestos exposure have been conducted, but there was no case report of ovarian cancer due to asbestos exposure in Korea. We describe a case of ovarian cancer caused by asbestos exposure in a worker who worked at an asbestos textile factory for 3 years and 7 months in the late 1970s.

Case presentation: A 57-year-old woman visited the hospital because she had difficulty urinating. Ovarian cancer was suspected in radiologic examination, and exploratory laparotomy was performed. She was diagnosed with epithelial ovarian cancer. The patient did not undergo postoperative chemotherapy and recovered. She joined the asbestos factory in March 1976 and engaged in asbestos textile twisting and spinning for 1 year, 2 years and 7 months respectively. In addition, she lived near the asbestos factory for more than 20 years. There was no other specificity or family history.

Conclusion: Considering the patient's occupational and environmental history, it is estimated that she had been exposed to asbestos significantly, so we determined that ovarian cancer in the patient is highly correlated with the occupational exposure of asbestos and environmental exposure is a possible cause as well. Social devices are needed to prevent further exposure to asbestos. It is also necessary to recognize that ovarian cancer can occur in workers who have previously been exposed to asbestos, and the education and social compensation for those workers are needed.}, } @article {pmid30479770, year = {2019}, author = {Tlotleng, N and Sidwell Wilson, K and Naicker, N and Koegelenberg, CF and Rees, D and Phillips, JI}, title = {The significance of non-occupational asbestos exposure in women with mesothelioma.}, journal = {Respirology case reports}, volume = {7}, number = {1}, pages = {e00386}, pmid = {30479770}, issn = {2051-3380}, abstract = {Malignant mesothelioma is a rare and aggressive pleural or peritoneal tumour almost always caused by exposure to asbestos fibres. Exposure to asbestos can cause malignant mesothelioma 30-40 years after exposure. A description of sources of exposure is important for prevention and possible financial compensation. Three women with cases of histologically confirmed malignant mesothelioma diagnosed from non-occupational asbestos exposure are described. Patients were contacted for an interview to assess their exposure history to asbestos. All three cases had mixed exposure histories related to secondary, environmental contamination, and domestic exposure. This case series highlight how ubiquitous asbestos is in the environment and how diverse the exposures may be. It is anticipated that a significant number of cases of non-occupational mesothelioma will be seen in many countries for several decades given the extent of asbestos containing materials.}, } @article {pmid30475941, year = {2019}, author = {Consonni, D and Mensi, C}, title = {Comment on the paper 'Boffetta et al. Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy. Ann Oncol 2018; 29(2): 484-489'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {2}, pages = {340-341}, doi = {10.1093/annonc/mdy521}, pmid = {30475941}, issn = {1569-8041}, } @article {pmid30451473, year = {2018}, author = {Krówczyńska, M and Wilk, E and Pabjanek, P and Olędzka, G}, title = {Pleural mesothelioma in Poland: Spatial analysis of malignant mesothelioma prevalence in the period 1999-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.667}, pmid = {30451473}, issn = {1970-7096}, abstract = {Malignant mesothelioma (MM), a rare and very deadly tumour, can be due to asbestos exposure. To better understand the cause of incidence of MM, spatial autocorrelation analysis with reference to the quantity of asbestos-cement products in use and the localisation of former asbestos manufacturing plants was applied. Geostatistical analysis shows that strong spatial clustering of MM incidence (referring to the general population as well as females and males separately) during the period 1999-2013 in the administrative units of Poland (provinces and counties). Incidence hotspots were found to be concentrated primarily in southern Poland but also seen in the county of Szczecin, which stands out in local autocorrelation analysis in north-western Poland. High incidence rates were discovered, in particular with reference to counties around former plants manufacturing asbestos-containing products, mainly asbestos-cement manufacturers. The highest frequency of MM incidence rate was found in within a 55 km radius of plants in or near the towns Trzebinia, Ogrodzieniec and Szczucin in the South, where asbestos-cement products had been manufactured for close to 40 years. Areas with significantly high incidence rates were also discovered in the provinces of Śląskie, Małopolskie and Świętokrzyskie in southern Poland.}, } @article {pmid30450291, year = {2018}, author = {Broeckx, G and Pauwels, P}, title = {Malignant peritoneal mesothelioma: a review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {537-542}, pmid = {30450291}, issn = {2218-6751}, abstract = {Malignant peritoneal mesothelioma (MPM) is a very rare malignancy of the peritoneum and has a poor prognosis. Of all mesotheliomas, pleural mesothelioma is more common than MPM. In comparison to pleural mesothelioma, the link with asbestos exposure is weaker (33-50% vs. >80%), but it is still the best-defined risk factor. MPM spreads predominantly expansive rather than infiltrative and symptoms are related to tumor spread within the abdominal cavity. Often, MPM is encountered incidentally by diagnostic imaging or by surgery. Computed tomography scan is widely accepted as a first line modality in diagnostic imaging. In diagnostic histopathology, MPM presents some challenges. Firstly, adequate clinical information is of utmost importance to consider the possibility of the diagnosis of MPM. Furthermore, a few morphological subtypes and variants exist. The most sensitive immunohistochemical markers are calretinin (100%), WT1 (94%) and CK5/6 (89%). The malignant character of immunohistochemically demonstrated mesothelial cells is not always obvious. This paradigm somewhat changed with the advent of immunohistochemical demonstration of BAP1 (BRCA-1 associated protein 1). Loss of BAP1 expression supports a diagnosis of malignancy. The gold standard in treatment remains cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Targetable molecular pathways in MPM are being identified. An exciting finding was the demonstration of ALK rearrangements in a small subset of patients with MPM and it is hoped for that at least this small subgroup of patients could benefit from treatment with ALK inhibitors. First-generation tyrosine kinase inhibitors against epidermal growth factor receptor (EGFR) did not show any significant activity in MPM. In contrast, nintedanib, an angiokinase inhibitor, improved progression-free survival and bevacizumab, a humanized anti-VEGF antibody increased overall survival in patients with MPM, when administered in combination with cisplatin and pemetrexed. Ongoing immunotherapy trials will offer a possible new treatment.}, } @article {pmid30450290, year = {2018}, author = {Brusselmans, L and Arnouts, L and Millevert, C and Vandersnickt, J and van Meerbeeck, JP and Lamote, K}, title = {Breath analysis as a diagnostic and screening tool for malignant pleural mesothelioma: a systematic review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {520-536}, pmid = {30450290}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a tumour related to a historical exposure to asbestos fibres. Currently, the definite diagnosis is made only by the histological examination of a biopsy obtained through an invasive thoracoscopy. However, diagnosis is made too late for curative treatment because of non-specific symptoms mainly appearing at advanced stage disease. Hence, due to its biologic aggressiveness and the late diagnosis, survival rate is low and the patients' outcome poor. In addition, radiological imaging, like computed tomographic scans, and blood biomarkers are found not to be sensitive enough to be used as an early diagnostic tool. Detection in an early stage is assumed to improve the patients' outcome but is hampered due to non-specific and late symptomology. Hence, there is a need for a new screening and diagnostic test which could improve the patients' outcome. Despite extensive research has focused on blood biomarkers, not a single has been shown clinically useful, and therefore research recently shifted to "breathomics" techniques to recognize specific volatile organic compounds (VOCs) in the breath of the patient as potential non-invasive biomarkers for disease. In this review, we summarize the acquired knowledge about using breath analysis for diagnosing and monitoring MPM and asbestos-related disorders (ARD). Gas chromatography-mass spectrometry (GC-MS), the gold standard of breath analysis, appears to be the method with the highest accuracy (97%) to differentiate MPM patients from at risk asbestos-exposed subjects. There have already been found some interesting biomarkers that are significantly elevated in asbestosis (NO, 8-isoprostane, leukotriene B4, α-Pinene…) and MPM (cyclohexane) patients. Regrettably, the different techniques and the plethora of studies suffer some limitations. Most studies are pilot studies with the inclusion of a limited number of patients. Nevertheless, given the promising results and easy sampling methods, we can conclude that breath analysis may become a useful tool in the future to screen for MPM, but further research is warranted.}, } @article {pmid30450289, year = {2018}, author = {Nuyts, V and Nawrot, T and Nemery, B and Nackaerts, K}, title = {Hotspots of malignant pleural mesothelioma in Western Europe.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {516-519}, pmid = {30450289}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma, a highly invasive tumour, has been epidemiologically linked to an occupational or environmental exposure to asbestos. Although asbestos has been widely used in diverse industrial applications and in construction, some industrial sectors have been affected much more than others. The objective of this review was to describe the existence of clusters of malignant pleural mesothelioma in Western European countries, based on epidemiological studies published between 2000 and 2015. MEDLINE (PubMed) and Embase were searched for relevant studies on spatial clustering of mesothelioma in Western European countries. Eventually, 16 different studies published between 2000 and 2015 were selected for a comprehensive analysis. Relevant studies on spatial clustering of mesothelioma were found for Belgium, the Netherlands, the United Kingdom, Germany, France, Spain, Italy and Denmark. Clustering of pleural mesothelioma was found mainly around shipyards (16 studies) and asbestos cement industries (10 studies). Although malignant pleural mesothelioma may be found throughout Western Europe, the present study indicates specific areas with higher past and also probable future incidence.}, } @article {pmid30446780, year = {2018}, author = {Feder, IS and Jülich, M and Tannapfel, A and Tischoff, I}, title = {[The German Mesothelioma Register : Current pathological diagnostics and services].}, journal = {Der Pathologe}, volume = {39}, number = {Suppl 2}, pages = {241-246}, doi = {10.1007/s00292-018-0509-8}, pmid = {30446780}, issn = {1432-1963}, abstract = {BACKGROUND: In Germany, asbestos-related diseases (asbestosis, lung cancer, mesothelioma) are recognised and compensated occupational diseases. The histologic diagnosis of mesothelioma is sometimes a challenge; additional immunohistochemical and molecular methods are needed. With lung dust analysis, the current asbestos fibre burden of the lung is measured (biomonitoring). Identification of grade I asbestosis (minimal asbestosis) requires directed histological examinations with up to 400-fold magnification, additional iron staining and possibly in connection with a lung dust analysis.

OBJECTIVES: Demonstration of current pathologic diagnostics in association with mesothelioma and lung dust analysis.

MATERIALS AND METHODS: Analysis of routine data from the German Mesothelioma Register.

RESULTS: Contrary to reactive mesothelial hyperplasia, malignant mesotheliomas have a nuclear BAP1 loss-of-expression in up to 66% of cases. For differential diagnosis between reactive versus malignant, a p16-FISH test may be helpful. BAP1 loss-of-expression and p16-deletion are independent markers. Evaluation of the dataset of the German Mesothelioma Register of patients with repeated tissue sampling proves the detection of asbestos fibres at the same level even after 40 years. The asbestos fibre burden in the human lung remains stable over this long period of time. In the electron microscopic analysis, white asbestos was predominantly found.

CONCLUSIONS: The well-known and industrially appreciated characteristics of asbestos fibres (in ancient ἄσβεστος asbestos "imperishable") as biopersistent have also been experimentally confirmed in human lungs.}, } @article {pmid30426024, year = {2018}, author = {Kumagai-Takei, N and Nishimura, Y and Matsuzaki, H and Lee, S and Yoshitome, K and Otsuki, T}, title = {Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8+ T Cell Line following Long-Term Exposure to Asbestos Fibers.}, journal = {Journal of immunology research}, volume = {2018}, number = {}, pages = {4391731}, pmid = {30426024}, issn = {2314-7156}, mesh = {Asbestos/adverse effects ; Asbestos, Serpentine/adverse effects ; CD8-Positive T-Lymphocytes/*immunology ; Cell Degranulation ; Cell Line ; Environmental Exposure/adverse effects ; Granzymes/metabolism ; Humans ; Interferon-gamma/*metabolism ; Lung Neoplasms/immunology/*metabolism ; Lymphocyte Activation ; Mesothelioma/immunology/*metabolism ; Perforin/*metabolism ; }, abstract = {Although the tumorigenicity of asbestos, which is thought to cause mesothelioma, has been clarified, its effect on antitumor immunity requires further investigation. We previously reported a decrease in the percentage of perforin+ cells of stimulated CD8+ lymphocytes derived from patients with malignant mesothelioma. Therefore, we examined the effects of long-term exposure to asbestos on CD8+ T cell functions by comparing long-term cultures of the human CD8+ T cell line EBT-8 with and without exposure to chrysotile (CH) asbestos as an in vitro model. Exposure to CH asbestos at 5 μg/ml or 30 μg/ml did not result in a decrease in intracellular granzyme B in EBT-8 cells. In contrast, the percentage of perforin+ cells decreased at both doses of CH exposure. CH exposure at 30 μg/ml did not suppress degranulation following stimulation with antibodies to CD3. Secreted production of IFN-γ stimulated via CD3 decreased by CH exposure at 30 μg/ml, although the percentage of IFN-γ+ cells induced by PMA/ionomycin did not decrease. These results indicate that long-term exposure to asbestos can potentially suppress perforin levels and the production of IFN-γ in human CD8+ T cells.}, } @article {pmid30417819, year = {2018}, author = {Røe, OD}, title = {[Asbestos and mesothelioma in Denmark 2017: status of a man-made cancer epidemic].}, journal = {Ugeskrift for laeger}, volume = {180}, number = {46}, pages = {}, pmid = {30417819}, issn = {1603-6824}, abstract = {Asbestos-induced cancer is an increasing problem in Denmark, and 32 years after the closure of the Danish Eternit Factory in Aalborg there are > 140 new mesothelioma cases diagnosed yearly, numbers rapidly increasing. Asbestos-induced lung cancer may be six times this number. The non-occupational exposure and even neighborhood exposure as a risk factor suggests, that compensation for mesothelioma should be universal. At the Aalborg University Hospital a multidisciplinary research team has been formed to do epidemiological, translational and clinical studies through national and international collaborations. Transformative research on asbestos cancer should be stimulated.}, } @article {pmid30410726, year = {2018}, author = {Berzenji, L and Van Schil, P}, title = {Multimodality treatment of malignant pleural mesothelioma.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {}, pmid = {30410726}, issn = {2046-1402}, abstract = {Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which the lung is removed en bloc, and pleurectomy/decortication, in which the lung stays in situ. Chemotherapy usually consists of a platinum-based chemotherapy, such as cisplatin, often combined with a folate antimetabolite, such as pemetrexed. More recently, immunotherapy has emerged as a possible therapeutic strategy for MPM. Evidence suggests that single-modality treatments are not an effective therapeutic approach for MPM. Therefore, researchers have started to explore different multimodality treatment approaches, in which often combinations of surgery, chemotherapy, immunotherapy, and RT are investigated. There is still no definitive answer to the question of which multimodality treatment combinations are most effective in improving the poor prognosis of MPM. Research into the effects of trimodality treatment approaches have found that radical approaches such as EPP and hemithoracic RT post-EPP are less effective than was previously assumed. In general, there are still a great number of unanswered questions and unknown factors regarding the ideal treatment approach for MPM. Hopefully, more research into multimodality therapy will provide insight into which combination of treatment modalities is most effective.}, } @article {pmid30408567, year = {2019}, author = {Guarrera, S and Viberti, C and Cugliari, G and Allione, A and Casalone, E and Betti, M and Ferrante, D and Aspesi, A and Casadio, C and Grosso, F and Libener, R and Piccolini, E and Mirabelli, D and Dianzani, I and Magnani, C and Matullo, G}, title = {Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {3}, pages = {527-539}, doi = {10.1016/j.jtho.2018.10.163}, pmid = {30408567}, issn = {1556-1380}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive tumor strongly associated with asbestos exposure. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive early diagnostic tests to monitor asbestos-exposed people.

METHODS: We used a genome-wide methylation array to identify, in asbestos-exposed subjects, novel blood DNA methylation markers of MPM in 163 MPM cases and 137 cancer-free controls (82 MPM cases and 68 controls, training set; replication in 81 MPM cases and 69 controls, test set) sampled from the same areas.

RESULTS: Evidence of differential methylation between MPM cases and controls was found (more than 800 cytosine-guanine dinucleotide sites, false discovery rate p value (pfdr) < 0.05), mainly in immune system-related genes. Considering the top differentially methylated signals, seven single- cytosine-guanine dinucleotides and five genomic regions of coordinated methylation replicated with similar effect size in the test set (pfdr < 0.05). The top hypomethylated single-CpG (cases versus controls effect size less than -0.15, pfdr < 0.05 in both the training and test sets) was detected in FOXK1 (Forkhead-box K1) gene, an interactor of BAP1 which was found mutated in MPM tissue and as germline mutation in familial MPM. In the test set, comparison of receiver operating characteristic curves and the area under the curve (AUC) of two models, including or excluding methylation, showed a significant increase in case/control discrimination when considering DNA methylation together with asbestos exposure (AUC = 0.81 versus AUC = 0.89, DeLong's test p = 0.0013).

CONCLUSIONS: We identified signatures of differential methylation in DNA from whole blood between asbestos exposed MPM cases and controls. Our results provide the rationale to further investigate, in prospective studies, the potential use of blood DNA methylation profiles for the identification of early changes related to the MPM carcinogenic process.}, } @article {pmid30401981, year = {2018}, author = {Matsushita, A and Sato, T and Mukai, S and Fujishita, T and Mishiro-Sato, E and Okuda, M and Aoki, M and Hasegawa, Y and Sekido, Y}, title = {TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation.}, journal = {Oncogene}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41388-018-0417-7}, pmid = {30401981}, issn = {1476-5594}, support = {25090053//Japan Society for the Promotion of Science (JSPS)/ ; 16H04706//Japan Society for the Promotion of Science (JSPS)/ ; 17K19628//Japan Society for the Promotion of Science (JSPS)/ ; }, abstract = {Malignant mesothelioma (MM) constitutes a very aggressive tumor that is caused by asbestos exposure after long latency. The NF2 tumor suppressor gene is mutated in 40-50% of MM; moreover, one of its downstream signaling cascades, the Hippo signaling pathway, is also frequently inactivated in MM cells. Although the YAP transcriptional coactivator, which is regulated by the Hippo pathway, can function as a pro-oncogenic protein, the role of TAZ, a paralog of YAP, in MM cells has not yet been clarified. Here, we show that TAZ is expressed and underphosphorylated (activated) in the majority of MM cells compared to immortalized mesothelial cells. ShRNA-mediated TAZ knockdown highly suppressed cell proliferation, anchorage-independent growth, cell motility, and invasion in MM cells harboring activated TAZ. Conversely, transduction of an activated form of TAZ in immortalized mesothelial cells enhanced these in vitro phenotypes and conferred tumorigenicity in vivo. Microarray analysis determined that activated TAZ most significantly enhanced the transcription of genes related to "cytokine-cytokine receptor interaction." Among selected cytokines, we found that IL-1 signaling activation plays a major role in proliferation in TAZ-activated MM cells. Both IL1B knockdown and an IL-1 receptor antagonist significantly suppressed malignant phenotypes of immortalized mesothelial cells and MM cells with activated TAZ. Overall, these results indicate an oncogenic role for TAZ in MMs via transcriptional induction of distinct pro-oncogenic genes including cytokines. Among these, IL-1 signaling appears as one of the most important cascades, thus potentially serving as a target pathway in MM cells harboring Hippo pathway inactivation.}, } @article {pmid30376426, year = {2018}, author = {Pastorino, S and Yoshikawa, Y and Pass, HI and Emi, M and Nasu, M and Pagano, I and Takinishi, Y and Yamamoto, R and Minaai, M and Hashimoto-Tamaoki, T and Ohmuraya, M and Goto, K and Goparaju, C and Sarin, KY and Tanji, M and Bononi, A and Napolitano, A and Gaudino, G and Hesdorffer, M and Yang, H and Carbone, M}, title = {A Subset of Mesotheliomas With Improved Survival Occurring in Carriers of BAP1 and Other Germline Mutations.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {}, number = {}, pages = {JCO2018790352}, doi = {10.1200/JCO.2018.79.0352}, pmid = {30376426}, issn = {1527-7755}, abstract = {PURPOSE: We hypothesized that four criteria could help identify malignant mesotheliomas (MMs) most likely linked to germline mutations of BAP1 or of other genes: family history of MM, BAP1-associated cancers, or multiple malignancies; or age younger than 50 years.

PATIENTS AND METHODS: Over the course of 7 years, 79 patients with MM met the four criteria; 22 of the 79 (28%) reported possible asbestos exposure. They were screened for germline BAP1 mutations by Sanger sequencing and by targeted next-generation sequencing (tNGS) for germline mutations in 55 additional cancer-linked genes. Deleterious mutations detected by tNGS were validated by Sanger sequencing.

RESULTS: Of the 79 patients, 43 (16 probands and 27 relatives) had deleterious germline BAP1 mutations. The median age at diagnosis was 54 years and median survival was 5 years. Among the remaining 36 patients with no BAP1 mutation, median age at diagnosis was 45 years, median survival was 9 years, and 12 had deleterious mutations of additional genes linked to cancer. When compared with patients with MMs in the SEER cohort, median age at diagnosis (72 years), median survival for all MM stages (8 months), and stage I (11 months) were significantly different from the 79 patients with MM in the current study (P < .0001).

CONCLUSION: We provide criteria that help identify a subset of patients with MM who had significantly improved survival. Most of these patients were not aware of asbestos exposure and carried either pathogenic germline mutations of BAP1 or of additional genes linked to cancer, some of which may have targeted-therapy options. These patients and their relatives are susceptible to development of additional cancers; therefore, genetic counseling and cancer screening should be considered.}, } @article {pmid30375909, year = {2019}, author = {Laaksonen, S and Ilonen, I and Kuosma, E and Sutinen, E and Wolff, H and Vehmas, T and Husgafvel-Pursiainen, K and Salo, JA and Koli, K and Räsänen, J and Myllärniemi, M}, title = {Malignant pleural mesothelioma in Finland: regional and gender variation.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {58}, number = {1}, pages = {38-44}, doi = {10.1080/0284186X.2018.1532599}, pmid = {30375909}, issn = {1651-226X}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare occupational cancer with a poor prognosis. Even with a multimodality treatment approach, the treatment outcomes remain unsatisfactory. The use of asbestos has been banned in most developed countries, but MPM continues to be a significant occupational disease also in these countries. Aim of this study is to identify modern epidemiology and assess equality in care.

METHODS: Our study cohort consists of 1010 patients diagnosed with MPM in Finland during 2000-2012. The data were collected from the Finnish Cancer Registry, the National Workers' Compensation Center Registry and the National Registry of Causes of Death, Statistics Finland.

RESULTS: Women were diagnosed a mean of 4.5 years later than males (p = .001), but survival did not differ (overall median survival 9.7 months). A workers' compensation claim was more common in males (OR 11.0 [95% CI 7.5-16.2]) and in regions with a major asbestos industry (OR 1.7 [95% CI 1.3-2.2]). One-year and three-year survivals did not differ regionally. Patients without chemotherapy treatment had an inferior survival (RR 1.8 [95% CI 1.5-2.0]). The initial survival benefit gained with pemetrexed was diluted at 51 months.

CONCLUSIONS: MPM is a disease with a poor prognosis, although chemotherapy appears to improve survival time. Significant gender and regional variation exists among patients, with notable differences in diagnostic and treatment practices. Long-term outcomes with pemetrexed remain indeterminate.

IMPACT: Emphasize centralized consult services for the diagnosis, treatment and support that patients receive for MPM, facilitating equal outcomes and compensation.}, } @article {pmid30370160, year = {2018}, author = {Plato, N and Martinsen, JI and Kjaerheim, K and Kyyronen, P and Sparen, P and Weiderpass, E}, title = {Mesothelioma in Sweden: Dose-Response Analysis for Exposure to 29 Potential Occupational Carcinogenic Agents.}, journal = {Safety and health at work}, volume = {9}, number = {3}, pages = {290-295}, pmid = {30370160}, issn = {2093-7911}, abstract = {Background: There is little information on the dose-response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma.

Methods: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961-2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratios and 95% confidence intervals.

Results: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25-2.0 fb/ml but also a clear dose-response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix.

Conclusion: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.}, } @article {pmid30366103, year = {2019}, author = {Harris, EJA and Kao, S and McCaughan, B and Nakano, T and Kondo, N and Hyland, R and Nowak, AK and de Klerk, NH and Brims, FJH}, title = {Prediction modelling using routine clinical parameters to stratify survival in Malignant Pleural Mesothelioma patients undergoing cytoreductive surgery.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {288-293}, doi = {10.1016/j.jtho.2018.10.005}, pmid = {30366103}, issn = {1556-1380}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.

METHODS: Data were collected from subjects undergoing cytoreductive surgery for MPM from specialist centers in Hyõgo, Japan, and Sydney, Australia, between 1991 and 2016. The CART model was applied using the combination of clinical variables to stratify subjects into risk groups (1 through 4); survival characteristics were then compared.

RESULTS: Two hundred eighty-nine cases were included (205 from Australia, 84 from Japan). Overall median survival was 34.6 (interquartile range: 17.5-56.1) months; median age was 63.0 (interquartile range: 57.0-67.8) years, and 83.0% (n = 240) were male. There were no clinically meaningful differences between the two cohorts. Survival across the four risk groups was significantly different (p < 0.0001); the model stratified survival well with a Harrell's concordance statistic of 0.62 (95% confidence interval: 0.57-0.66) at 36 months. The group with the longest survival (median, 82.5 months) had: no weight loss, hemoglobin > 153 g/L and serum albumin > 43 g/L at time of referral to the surgical center.

CONCLUSIONS: Using routinely available clinical variables, the CART model was able to stratify surgical patients into risk groups with statistically different survival characteristics with fair to good performance. Presence of weight loss, anemia, and low albumin should confer caution when considering surgical therapy for MPM.}, } @article {pmid30362690, year = {2018}, author = {Trenti, E and Palermo, SM and D'Elia, C and Comploj, E and Pycha, A and Carella, R and Pycha, A}, title = {Malignant mesothelioma of tunica vaginalis testis: Report of a very rare case with review of the literature.}, journal = {Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica}, volume = {90}, number = {3}, pages = {212-214}, doi = {10.4081/aiua.2018.3.212}, pmid = {30362690}, issn = {1124-3562}, abstract = {INTRODUCTION: Mesothelioma of the tunica vaginalis testis is a extremely rare tumor and represents 0.3 to 0.5% of all malignant mesotheliomas. Exposure to asbestos often precedes illness. Because of its low incidence and nonspecific clinical presentation, it is mostly diagnosed accidentally during surgery for other reasons and the prognosis is usually poor. We present a case of a patient with a mesothelioma of tunica vaginalis testis, diagnosed secondarily during hydrocele surgery, with long-term survival after radical surgery.

MATERIALS AND METHODS: a 40 years old patient was admitted to our department for routine surgery of a left hydrocele. During the operation a frozen section analysis was requested because of the unusual nodular thickening of the tunica vaginalis: the examination revealed a diffuse malignant mesothelioma with epithelioid structure and tubular-papillary proliferation. Therefore a left hemi-scrotectomy with left inguinal lymph node dissection was performed.

RESULTS: The definitive histology confirmed the previous report of diffuse malignant mesothelioma with angio-invasion but normal testicle findings and negative lymph nodes. No metastases were found on the CT-scan. For the first 2 years a CT was repeated every 4 months, for other 3 years every 6 months and then yearly. Six years after surgery the patient is classified as no evidence of disease.

CONCLUSIONS: malignant mesothelioma of the tunica vaginalis testis is a rare entity, often initially thought to be a hydrocele or an epididymal cyst. An aggressive approach with hemiscrotectomy with or without inguinal and retroperitoneal lymphadenectomy can reduce the risk of recurrence.}, } @article {pmid30362153, year = {2019}, author = {Matboli, M and Shafei, AE and Ali, MA and Gaber, AI and Galal, A and Tarek, O and Marei, M and Khairy, E and El-Khazragy, N and Anber, N and Abdel-Rahman, O}, title = {Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma.}, journal = {Journal of cellular biochemistry}, volume = {120}, number = {3}, pages = {3203-3211}, doi = {10.1002/jcb.27586}, pmid = {30362153}, issn = {1097-4644}, support = {//Egyptian Science and Technology Development Fund, RSTDG; ID: 22935./ ; }, abstract = {AIM AND BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM.

METHODS: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A (ARSA) gene expression with their epigenetic regulators microRNA (miR-2053) and long noncoding RNA (lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed.

RESULTS: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM.

CONCLUSION: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.}, } @article {pmid30357666, year = {2018}, author = {Pascotto, E and Gianoncelli, A and Calligaro, C and Marcuzzo, T and Melato, M and Rizzardi, C and Pascolo, L}, title = {Ferruginous bodies resolved by synchrotron XRF in a dog with peritoneal malignant mesothelioma.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {35}, pages = {35707-35714}, pmid = {30357666}, issn = {1614-7499}, abstract = {Mesothelioma is a malignant tumor mainly correlated to occupational asbestos exposure. Rare reports describe its occurrence also in animals, mainly linked to asbestos in the environment. Asbestos exposure is demonstrated by the appearance of characteristic histological hallmarks: asbestos containing ferruginous bodies that are iron-based structures forming around fibers and also other dust particles. Here we present a clinical case of a suspect of mesothelioma in the peritoneum of a dog with parallel histological observation of ferruginous bodies. To possibly correlate the dog tumor to environmental exposure, we performed X-ray fluorescence (XRF) analyses at two different synchrotrons to resolve the ferruginous bodies' composition. While the histological examination diagnoses a tubulo-papillary mesothelioma, the XRF analyses show that ferruginous bodies contain Si particles, resembling formations of exogenous origin; however, the morphology is unlikely that of asbestos fibers. We speculate that the peritoneal mesothelioma of this dog could be related to environmental exposure to non-asbestos material.}, } @article {pmid30349836, year = {2018}, author = {Ibrahim, AM and Al-Akchar, M and Obaidi, Z and Al-Johany, H}, title = {Malignant Peritoneal Mesothelioma: A Rare Cause of Ascites.}, journal = {Journal of investigative medicine high impact case reports}, volume = {6}, number = {}, pages = {2324709618807506}, pmid = {30349836}, issn = {2324-7096}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare diagnosis that presents with difficulties in diagnosis and management. This article reports a case of an 88-year-old male who presented with a 2-week history of abdominal distention and bloating. He worked at an insulation production factory between the ages of 23 and 25 years with presumed asbestos exposure. On the computed tomography scan of the abdomen/pelvis, the patient was found to have diffuse omental, peritoneal, and mesenteric nodularity with moderate to large ascites. Omental biopsy revealed MPM. The overall prognosis of MPM remains poor, with a median survival time of 12 months at the time of diagnosis. Treatment modalities offered in the United States include chemotherapy alone, cytoreductive surgery alone, or cytoreductive surgery/chemotherapy combination.}, } @article {pmid30349716, year = {2018}, author = {Grosso, F and Roveta, A and Gallizzi, G and Belletti, M}, title = {Management of recurrent pleural mesothelioma: Successful rechallenge with nintedanib in combination with chemotherapy.}, journal = {Clinical case reports}, volume = {6}, number = {10}, pages = {2000-2004}, pmid = {30349716}, issn = {2050-0904}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm, generally caused by asbestos exposure. This case details how a patient treated with nintedanib during the LUME-Meso study was rechallenged with nintedanib. The findings highlight the benefit of nintedanib rechallenge and the potential use of continuous anti-angiogenic therapy in MPM treatment.}, } @article {pmid30349644, year = {2018}, author = {Adhikary, G and Grun, D and Alexander, HR and Friedberg, JS and Xu, W and Keillor, JW and Kandasamy, S and Eckert, RL}, title = {Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation.}, journal = {Oncotarget}, volume = {9}, number = {77}, pages = {34495-34505}, pmid = {30349644}, issn = {1949-2553}, support = {R01 CA184027/CA/NCI NIH HHS/United States ; R01 CA211909/CA/NCI NIH HHS/United States ; }, abstract = {Mesothelioma is a rare cancer of the mesothelial cell layer of the pleura, peritoneum, pericardium and tunica vaginalis. It is typically caused by asbestos, notoriously resistant to chemotherapy and generally considered incurable with a poor life expectancy. Transglutaminase 2 (TG2), a GTP binding regulatory protein, is an important cancer stem cell survival and therapy resistance factor. We show that TG2 is highly expressed in human mesothelioma tumors and in mesothelioma cancer stem cells (MCS cells). TG2 knockdown or TG2 inhibitor treatment reduces MCS cell spheroid formation, matrigel invasion, migration and tumor formation. Time to tumor first appearance is doubled in TG2 knockout cells as compared to wild-type. In addition, TG2 loss is associated with reduced expression of stemness, and epithelial mesenchymal transition markers, and enhanced apoptosis. These studies indicate that TG2 is an important MCS cell survival protein and suggest that TG2 may serve as a mesothelioma cancer stem cell therapy target.}, } @article {pmid30338612, year = {2018}, author = {Betti, M and Aspesi, A and Ferrante, D and Sculco, M and Righi, L and Mirabelli, D and Napoli, F and Rondón-Lagos, M and Casalone, E and Vignolo Lutati, F and Ogliara, P and Bironzo, P and Gironi, CL and Savoia, P and Maffè, A and Ungari, S and Grosso, F and Libener, R and Boldorini, R and Valiante, M and Pasini, B and Matullo, G and Scagliotti, G and Magnani, C and Dianzani, I}, title = {Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes.}, journal = {Genes, chromosomes & cancer}, volume = {57}, number = {11}, pages = {573-583}, doi = {10.1002/gcc.22670}, pmid = {30338612}, issn = {1098-2264}, support = {IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; 2015 IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; //Istituto Superiore di Sanità (Progetto Amianto)/International ; //Italian Institute for Genomic Medicine/International ; //Ministry of Health - Italy/International ; //Regione Piemonte/International ; GR-2011-02348356//Young Researcher/International ; 2011-02348356//Young Researcher/International ; //INAIL Bric program 2016-2018/International ; }, mesh = {Adult ; Asbestos/*adverse effects ; Cohort Studies ; DNA Repair/genetics ; Environmental Exposure/*analysis ; Female ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/*genetics ; Humans ; Italy ; Male ; Mesothelioma/epidemiology/*genetics ; Middle Aged ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1-TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1-TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5-year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer-predisposing genes. We report here a new pathogenic germline variant in BAP1: c.783 + 2 T > C. The prevalence of pathogenic germline variants in BAP1 was 7.7% among patients with familial MPM (3/39). Patients with pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes showed lower cumulative asbestos exposure than patients without germline variants in 94 cancer-predisposing genes (P = .00002). This suggests an interaction between genetic risk factors and asbestos in the development of mesothelioma.}, } @article {pmid30321262, year = {2018}, author = {Brentisci, C and Gangemi, M and Migliore, E and Mirabelli, D and Stura, A}, title = {Comment on 'Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {29}, number = {12}, pages = {2395-2396}, doi = {10.1093/annonc/mdy463}, pmid = {30321262}, issn = {1569-8041}, } @article {pmid30319235, year = {2018}, author = {Jargin, SV}, title = {Asbestos and Mesothelioma: A Comment.}, journal = {Indian journal of occupational and environmental medicine}, volume = {22}, number = {2}, pages = {113-114}, pmid = {30319235}, issn = {0973-2284}, } @article {pmid30317900, year = {2018}, author = {Duke, KS and Thompson, EA and Ihrie, MD and Taylor-Just, AJ and Ash, EA and Shipkowski, KA and Hall, JR and Tokarz, DA and Cesta, MF and Hubbs, AF and Porter, DW and Sargent, LM and Bonner, JC}, title = {Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes.}, journal = {Nanotoxicology}, volume = {12}, number = {9}, pages = {975-991}, doi = {10.1080/17435390.2018.1502830}, pmid = {30317900}, issn = {1743-5404}, support = {CC999999//Intramural CDC HHS/United States ; P30 ES025128/ES/NIEHS NIH HHS/United States ; R01 ES020897/ES/NIEHS NIH HHS/United States ; T32 ES007046/ES/NIEHS NIH HHS/United States ; }, abstract = {The fiber-like shape of multi-walled carbon nanotubes (MWCNTs) is reminiscent of asbestos, suggesting they pose similar health hazards when inhaled, including pulmonary fibrosis and mesothelioma. Mice deficient in the tumor suppressor p53 are susceptible to carcinogenesis. However, the chronic pathologic effect of MWCNTs delivered to the lungs of p53 heterozygous (p53+/-) mice has not been investigated. We hypothesized that p53+/- mice would be susceptible to lung tumor development after exposure to either tangled (t-) or rod-like (r-) MWCNTs. Wild-type (p53+/+) or p53+/- mice were exposed to MWCNTs (1 mg/kg) via oropharyngeal aspiration weekly over four consecutive weeks and evaluated for cellular and pathologic outcomes 11-months post-initial exposure. No lung or pleural tumors were observed in p53+/+ or p53+/- mice exposed to either t- or rMWCNTs. In comparison to tMWCNTs, the rMWCNTs induced the formation of larger granulomas, a greater number of lymphoid aggregates and greater epithelial cell hyperplasia in terminal bronchioles in both p53+/- and p53+/+ mice. A constitutively larger area of CD45R+/CD3+ lymphoid tissue was observed in p53+/- mice compared to p53+/+ mice. Importantly, p53+/- mice had larger granulomas induced by rMWCNTs as compared to p53+/+ mice. These findings indicate that a combination of p53 deficiency and physicochemical characteristics including nanotube geometry are factors in susceptibility to MWCNT-induced lymphoid infiltration and granuloma formation.}, } @article {pmid30316650, year = {2018}, author = {Fournel, L and Janet-Vendroux, A and Canny-Hamelin, E and Mansuet-Lupo, A and Guinet, C and Bobbio, A and Damotte, D and Alifano, M}, title = {[Malignant pleural mesothelioma: The role of surgery].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {5}, pages = {351-358}, doi = {10.1016/j.pneumo.2018.09.006}, pmid = {30316650}, issn = {0761-8417}, mesh = {Chemotherapy, Adjuvant ; Combined Modality Therapy ; Humans ; Lung Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Mesothelioma/diagnosis/drug therapy/radiotherapy/*surgery ; Pleural Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Pneumonectomy ; Radiotherapy, Adjuvant ; Thoracic Surgical Procedures/*methods ; Thoracoscopy ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease, whose incidence is increasing. Asbestos is the primary causal agent.

STATE OF KNOWLEDGE: Knowledge about MPM has evolved. Thoracoscopy is essential for diagnosis of MPM. It allows performing pleural biopsies, to study the extent of the disease and to relieve dyspnea. The pathological diagnosis is also better codified with immunohistochemistry and with analysis by expert of Mesopath group. Curative surgical treatments are pleurectomy decortication and extended pneumonectomy in combination with chemotherapy and/or radiotherapy. Those heavy treatments improve survival in highly selected patients. For the other patients, supportive measures will be considered to reduce pain and dyspnea.

PROSPECT: Radical surgical treatment is only offered in therapeutic trials or multimodal treatment. Its place is not formally established. New therapies associated to surgical treatment are being studied.

CONCLUSIONS: Surgical management of MPM has to be operated in specialized teams where the survival benefit and quality of life is discussed case by case.}, } @article {pmid30316012, year = {2019}, author = {Mansfield, AS and Peikert, T and Smadbeck, JB and Udell, JBM and Garcia-Rivera, E and Elsbernd, L and Erskine, CL and Van Keulen, VP and Kosari, F and Murphy, SJ and Ren, H and Serla, VV and Schaefer Klein, JL and Karagouga, G and Harris, FR and Sosa, C and Johnson, SH and Nevala, W and Markovic, SN and Bungum, AO and Edell, ES and Dong, H and Cheville, JC and Aubry, MC and Jen, J and Vasmatzis, G}, title = {Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {276-287}, doi = {10.1016/j.jtho.2018.10.001}, pmid = {30316012}, issn = {1556-1380}, support = {K12 CA090628/CA/NCI NIH HHS/United States ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy.

METHODS: We used mate-pair (n = 22), RNA (n = 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome.

RESULTS: We observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival.

CONCLUSIONS: Our findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies.}, } @article {pmid30312759, year = {2019}, author = {Toyokuni, S}, title = {Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention.}, journal = {Free radical biology & medicine}, volume = {133}, number = {}, pages = {206-215}, doi = {10.1016/j.freeradbiomed.2018.10.401}, pmid = {30312759}, issn = {1873-4596}, abstract = {Cancer is the primary cause of human mortality in most countries. This tendency has increased as various medical therapeutics have advanced, which suggests that we cannot escape carcinogenesis, although the final outcome may be modified by exposomes and statistics. Cancer is classified by its cellular differentiation. Mesothelial cells are distinct in that they line somatic cavities, facilitating the smooth movement of organs, but are not exposed to the external environment. Malignant mesothelioma, or simply mesothelioma, develops either in the pleural, peritoneal or pericardial cavities, or in the tunica vaginalis testes. Mesothelioma has been a relatively rare cancer but is socially important due to its association with asbestos exposure, caused by modern industrial development. The major pathogenic mechanisms include oxidative stress either via catalytic reactions against the asbestos surface or frustrated phagocytosis of macrophages, and specific adsorption of hemoglobin and histones by asbestos fibers in the presence of phagocytic activity of mesothelial cells. Multiwall carbon nanotubes of ~50 nm-diameter, additionally adsorbing transferrin, are similarly carcinogenic to mesothelial cells in rodents and were thus classified as Group 2B carcinogens. Genetic alterations found in human and rat mesothelioma notably contain changes found in other excess iron-induced carcinogenesis models. Phlebotomy and iron chelation therapies have been successful in the prevention of mesothelioma in rats. Alternatively, loading of oxidative stress by non-thermal plasma to mesothelioma cells causes ferroptosis. Therefore, carcinogenesis by foreign fibrous inorganic materials may overlap the uncovered molecular mechanisms of birth of life and its evolution.}, } @article {pmid30309369, year = {2018}, author = {Smeele, P and d'Almeida, SM and Meiller, C and Chéné, AL and Liddell, C and Cellerin, L and Montagne, F and Deshayes, S and Benziane, S and Copin, MC and Hofman, P and Le Pimpec-Barthes, F and Porte, H and Scherpereel, A and Grégoire, M and Jean, D and Blanquart, C}, title = {Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis.}, journal = {Molecular cancer}, volume = {17}, number = {1}, pages = {148}, pmid = {30309369}, issn = {1476-4598}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.}, } @article {pmid30309285, year = {2018}, author = {Funahashi, S and Okazaki, Y and Nishiyama, T and Ohyoshi, H and Yasui, H and Nishida, K and Matsui, S and Toyokuni, S}, title = {Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice.}, journal = {Free radical research}, volume = {52}, number = {9}, pages = {1030-1039}, doi = {10.1080/10715762.2018.1514604}, pmid = {30309285}, issn = {1029-2470}, abstract = {Exposure to asbestos fiber is central to mesothelial carcinogenesis, for which iron overload in or near mesothelial cells is a key pathogenic mechanism. Alternatively, iron chelation therapy with deferasirox or regular phlebotomy was significantly preventive against crocidolite-induced mesothelial carcinogenesis in rats. However, the role of iron transporters during asbestos-induced carcinogenesis remains elusive. Here, we studied the role of divalent metal transporter 1 (DMT1; Slc11a2), which is a Fe(II) transporter, that is present not only on the apical plasma membrane of duodenal cells but also on the lysosomal membrane of every cell, in crocidolite-induced mesothelial carcinogenesis using DMT1 transgenic (DMT1Tg) mice. DMT1Tg mice show mucosal block of iron absorption without cancer susceptibility under normal diet. We unexpectedly found that superoxide production was significantly decreased upon stimulation with crocidolite both in neutrophils and macrophages of DMT1Tg mice, and the macrophage surface revealed higher iron content 1 h after contact with crocidolite. Intraperitoneal injection of 3 mg crocidolite ultimately induced malignant mesothelioma in ∼50% of both wild-type and DMT1Tg mice (23/47 and 14/28, respectively); this effect was marginally (p = 0.069) delayed in DMT1Tg mice, promoting survival. The promotional effect of nitrilotriacetic acid was limited, and the liver showed significantly higher iron content both in DMT1Tg mice and after crocidolite exposure. The results indicate that global DMT1 overexpression causes decreased superoxide generation upon stimulation in inflammatory cells, which presumably delayed the promotional stage of crocidolite-induced mesothelial carcinogenesis. DMT1Tg mice with low-stamina inflammatory cells may be helpful to evaluate the involvement of inflammation in various pathologies.}, } @article {pmid30301262, year = {2018}, author = {Sarun, KH and Lee, K and Williams, M and Wright, CM and Clarke, CJ and Cheng, NC and Takahashi, K and Cheng, YY}, title = {Genomic Deletion of BAP1 and CDKN2A Are Useful Markers for Quality Control of Malignant Pleural Mesothelioma (MPM) Primary Cultures.}, journal = {International journal of molecular sciences}, volume = {19}, number = {10}, pages = {}, pmid = {30301262}, issn = {1422-0067}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*standards ; Cell Line, Tumor ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p18/*genetics ; Gene Deletion ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; Primary Cell Culture/methods/*standards ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a deadly cancer that is caused by asbestos exposure and that has limited treatment options. The current standard of MPM diagnosis requires the testing of multiple immunohistochemical (IHC) markers on formalin-fixed paraffin-embedded tissue to differentiate MPM from other lung malignancies. To date, no single biomarker exists for definitive diagnosis of MPM due to the lack of specificity and sensitivity; therefore, there is ongoing research and development in order to identify alternative biomarkers for this purpose. In this study, we utilized primary MPM cell lines and tested the expression of clinically used biomarker panels, including CK8/18, Calretinin, CK 5/6, CD141, HBME-1, WT-1, D2-40, EMA, CEA, TAG72, BG8, CD15, TTF-1, BAP1, and Ber-Ep4. The genomic alteration of CDNK2A and BAP1 is common in MPM and has potential diagnostic value. Changes in CDKN2A and BAP1 genomic expression were confirmed in MPM samples in the current study using Fluorescence In situ Hybridization (FISH) analysis or copy number variation (CNV) analysis with digital droplet PCR (ddPCR). To determine whether MPM tissue and cell lines were comparable in terms of molecular alterations, IHC marker expression was analyzed in both sample types. The percentage of MPM biomarker levels showed variation between original tissue and matched cells established in culture. Genomic deletions of BAP1 and CDKN2A, however, showed consistent levels between the two. The data from this study suggest that genomic deletion analysis may provide more accurate biomarker options for MPM diagnosis.}, } @article {pmid30300743, year = {2019}, author = {White, R and Pulford, E and Elliot, DJ and Thurgood, LA and Klebe, S}, title = {Quantitative mass spectrometry to identify protein markers for diagnosis of malignant pleural mesothelioma.}, journal = {Journal of proteomics}, volume = {192}, number = {}, pages = {374-382}, doi = {10.1016/j.jprot.2018.09.018}, pmid = {30300743}, issn = {1876-7737}, abstract = {Malignant pleural mesothelioma (MPM) is a devastating malignancy with a prognosis of <12 months. Even with bans on the use of asbestos in most Western countries, the incidence is still increasing due to the long latency periods between exposure and development of the disease. Diagnosis is often delayed due to invasive biopsies and lack of distinguishable markers. Patients frequently present with pleural effusions months to years before a radiologically detectable mass appears. This study aimed to investigate the proteome of pleural effusions taken from patients with MPM, adenocarcinoma and benign conditions in an attempt to identify a biomarker for early diagnosis. We identified several proteins that may be possible targets and warrant further investigation. Due to the predominance of up regulated proteins involved in VEGF signalling in MPM, we analysed VEGFA levels in effusions and found a strong correlation between VEGFA levels and survival in MPM.}, } @article {pmid30296019, year = {2018}, author = {Behrens, MA}, title = {Asbestos Trust Transparency.}, journal = {Fordham law review}, volume = {87}, number = {1}, pages = {107-124}, pmid = {30296019}, issn = {0015-704X}, mesh = {Asbestos/*adverse effects ; Asbestos, Amphibole/*adverse effects ; Asbestosis/etiology ; Bankruptcy ; Humans ; Liability, Legal/*economics ; Mesothelioma/etiology ; Occupational Exposure/*legislation & jurisprudence ; *Truth Disclosure ; United States ; }, } @article {pmid30293912, year = {2018}, author = {Mlika, M and Lamzirbi, O and Limam, M and Mejri, N and Ben Saad, S and Chaouch, N and Ben Miled, K and Marghli, A and Mezni, F}, title = {[Clinical and pathological profile of the pleural malignant mesothelioma: A retrospective study about 30 cases].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {6}, pages = {427-435}, doi = {10.1016/j.pneumo.2018.06.004}, pmid = {30293912}, issn = {0761-8417}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/diagnosis/*epidemiology/pathology ; Male ; Mesothelioma/diagnosis/*epidemiology/pathology ; Middle Aged ; Pleural Neoplasms/diagnosis/*epidemiology/pathology ; Retrospective Studies ; Tunisia/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: The malignant pleural mesothelioma (MPM) is a rare tumour usually associated to asbestos exposure. The delay between the exposure and the occurrence of the cancer can reach 40 years. This caused the pick of incidence described in many countries including Tunisia. The diagnosis is suspected based on clinical features but positive diagnosis is microscopic. Our aim was to describe the clinical and microscopic features of MPM through a single institution experience.

PATIENTS AND METHODS: We conducted a retrospective study about 30 MPM diagnosed over a 20-year-period (1995-2015). We included only patients with complete records including clinical, radiologic and microscopic features. All the microscopic diagnoses were reviewed by 2 pathologists. A mean of 12 slides per case was reviewed. The diagnosis was based on the 2015 WHO classification.

RESULTS: The mean age of the patients was 61 years, average 22 to 80 years. The sex ratio was 6,5. An asbetose exposition was reported in 21 cases. The most frequent symptoms was chest pain reported in 25 cases. Physical exam was normal in 9 cases. It revealed pleural syndorm in most patients (60 %). Imaging findings consisted mainly in diffuse pleural thickening in 17 cases. Twelve tumours were classified as stage I, 3 stage II, 14 stage III et 1 stage IV. Pleural biopsy was performed using needle in 18 cases, through thoracoscopy in 16 cases, thoracotomy in 3 cases and allowed the diagnosis in respectively 7 cases/18, 16 cases/16 and 3 cases/3. A lymph node biopsy was performed through mediastinoscopy in one case and yelded the diagnosis. The diagnosis was performed on surgical specimen in 2 patients: one bullectomy and one right upper lobectomy. The microscopic exam concluded to an EM in 17 cases, sarcomatoid mesothelioma (SM) in 4 cases and biphasic mesothelioma (BM) in 9 cases. Pan-cytokeratin antibody was used in all cases in association with 2 antibodies with positive diagnostic value and 2 antibodies with negative diagnostic value. It was repeated in 15 cases and the most used antibodies were the anti-calretinin and the TTF1. This was due to the lack of fixation in one case and in order to reach a quality criteria in the other cases. Surgical resection was possible in 2 patients. 15 patients were lost of view after a mean follow-up period of 3 months. Thirteen patients died before or during the follow-up.

CONCLUSION: This work was about a Tunisian experience in the diagnosis and management of MPM. The major limits faced were the incomplete databases, the small number of patients included. Microsocpic positive diagnosis necessitates a degree of expertise and every laboratory has to determine the most valuable antibodies through its experience in order to optimize the diagnosis and to reduce the delay of diagnosis.}, } @article {pmid30293239, year = {2018}, author = {van Gerwen, M and Wolf, A and Liu, B and Flores, R and Taioli, E}, title = {Short-term outcomes of pleurectomy decortication and extrapleural pneumonectomy in mesothelioma.}, journal = {Journal of surgical oncology}, volume = {118}, number = {7}, pages = {1178-1187}, doi = {10.1002/jso.25260}, pmid = {30293239}, issn = {1096-9098}, support = {NCI CCSG P30 CA196521//National Cancer Institute/ ; }, mesh = {Aged ; Arrhythmias, Cardiac/epidemiology ; Databases, Factual ; Female ; *Hospital Mortality ; Humans ; Male ; Mesothelioma/mortality/*surgery ; Middle Aged ; New York/epidemiology ; Pleura/*surgery ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/*adverse effects ; Postoperative Complications ; Propensity Score ; }, abstract = {BACKGROUND/OBJECTIVES: We evaluated postoperative mortality and complications after extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) to better understand their effectiveness in malignant pleural mesothelioma (MPM).

METHODS: A meta-analysis was done to evaluate 30-day mortality and postoperative complications. In addition, in-patients data of 500 eligible patients with MPM who underwent EPP or P/D was extracted from the New York Statewide Planning and Research Cooperative System (SPARCS). Multivariate analyses and propensity matching were used to compare in-hospital mortality and postoperative complications in EPP vs P/D.

RESULTS: The meta-analysis showed a statistically significant difference in 30-day mortality (5% [95% CI: 4-6] vs P/D 2% [95% CI: 1-3]), proportion of complications (46% [95% CI: 36-56] vs 24% [95% CI: 15-34]) and postoperative arrhythmias (20% [95% CI: 12-31] vs 5% [95% CI: 2-8]) for EPP vs P/D. In-hospital mortality (OR adj : 2.6; 95% CI: 0.86-7.75) and postoperative complications (OR adj : 1.1; 95% CI: 0.68-1.86) were not different in EPP compared with P/D while supraventricular arrhythmia was significantly more frequent after EPP vs P/D (OR adj : 5.2; 95% CI: 2.34-11.33).

CONCLUSIONS: Postoperative mortality, postoperative complications, and particularly supraventricular arrhythmia are less frequent after P/D vs EPP. P/D, a less invasive surgery, may provide a better option when technically feasible for patients with MPM.}, } @article {pmid30288361, year = {2018}, author = {Fear, VS and Tilsed, C and Chee, J and Forbes, CA and Casey, T and Solin, JN and Lansley, SM and Joost Lesterhuis, W and Dick, IM and Nowak, AK and Robinson, BW and Lake, RA and Fisher, SA}, title = {Combination immune checkpoint blockade as an effective therapy for mesothelioma.}, journal = {Oncoimmunology}, volume = {7}, number = {10}, pages = {e1494111}, pmid = {30288361}, issn = {2162-4011}, abstract = {Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma and is now being applied to other cancers, including mesothelioma. However, the efficacy of ICPB and which immune checkpoint combinations constitute the best therapeutic option for mesothelioma have yet to be fully elucidated. Here, we used our well characterised mesothelioma tumour model to investigate the efficacy of different ICBP treatments to generate effective therapy for mesothelioma. We show that tumour resident regulatory T cell co-express high levels of CTLA-4, OX40 and GITR relative to T effector subsets and that these receptors are co-expressed on a large proportion of cells. Targeting any of CTLA-4, OX40 or GITR individually generated effective responses against mesothelioma. Furthermore, the combination of αCTLA-4 and αOX40 was synergistic, with an increase in complete tumour regressions from 20% to 80%. Other combinations did not synergise to enhance treatment outcomes. Finally, an early pattern in T cell response was predictive of response, with activation status and ICP receptor expression profile of T effector cells harvested from tumour and dLN correlating with response to immunotherapy. Taken together, these data demonstrate that combination ICPB can work synergistically to induce strong, durable immunity against mesothelioma in an animal model.}, } @article {pmid30281709, year = {2018}, author = {Kalinke, LP and Kalinke, MA and Sarquis, LMM and Marcondes, L and Halfeld, T and Mensi, C and Consonni, D}, title = {[A proposal for the creation of a system to monitor cases of malignant mesothelioma in Curitiba, Paraná, Brazil].}, journal = {Cadernos de saude publica}, volume = {34}, number = {9}, pages = {e00171917}, doi = {10.1590/0102-311X00171917}, pmid = {30281709}, issn = {1678-4464}, mesh = {Asbestos/*toxicity ; Brazil/epidemiology ; Carcinogens/*toxicity ; Disease Notification/*methods ; Environmental Exposure/*adverse effects ; *Hospital Records ; Humans ; Lung Neoplasms/*epidemiology/etiology ; Mesothelioma/*epidemiology/etiology ; }, abstract = {The study proposes the creation of a system to monitor cases of malignant mesothelioma in the municipality of Curitiba, Paraná State, Brazil, based on the Italian model. This diagnosis-type action-research project featured exploratory and planning phases conducted from July 2015 to May 2017. The following search tools were used: Hospital-Based Cancer Registries Integrator with specific morphologies for mesothelioma; Hospital-Based Cancer Registry with codes C38.4 and C45 of the International Classification of Diseases, 10th revision, and/or records coded by the ICD-O with topographies C38 and C48; Population-Based Cancer Registry of the Curitiba Municipal Health Department, with the same codes. The study also identified, analyzed, and adapted to the Brazilian reality the model, questionnaires, and registry software for mesothelioma from Lombardy, Italy. Fifteen cases of mesothelioma were recorded in the Hospital-Based Cancer Registries Integrator. Two cases were recorded in the University Hospital-Based Cancer Registry and 16 in the Cancer Hospital. There were 317 cases recorded in the Population-Based Cancer Registry during the same period. Although some information was complete, data were lacking on patients' occupational history, thereby preventing the determination of a causal nexus. Given a predicted increase in cases of mesothelioma in the coming decades and the response to court cases, the implementation of registries has become essential to facilitate knowledge and follow-up on the determination of the causal link and specific sources of asbestos exposure in the country.}, } @article {pmid30272283, year = {2018}, author = {Zhang, C and Hao, Y and Wu, L and Dong, X and Jiang, N and Cong, B and Liu, J and Zhang, W and Tang, D and De Perrot, M and Zhao, X}, title = {Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma.}, journal = {International journal of oncology}, volume = {53}, number = {6}, pages = {2531-2541}, pmid = {30272283}, issn = {1791-2423}, abstract = {Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed to evaluate the anticancer effects of curcumin on the RN5 MPM cell line. The inhibitory effects of curcumin on cell viability were determined using the sulforhodamine B assay. In addition, cell cycle progression was analyzed by propidium iodide (PI) staining and flow cytometry, and curcumin‑induced apoptosis was measured by Annexin V/PI double staining. The translocation of apoptosis-inducing factor (AIF) was assessed by western blotting and immunofluorescence, and the expression levels of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (Akt)‑mammalian target of rapamycin (mTOR) signaling pathway proteins and mitochondria-associated proteins were evaluated by western blotting. In vivo antitumor effects were evaluated in a subcutaneous murine model. Briefly, tumors were harvested from the mice, and immunohistochemistry was conducted to evaluate cell proliferation, apoptosis and angiogenesis. The results indicated that curcumin inhibited RN5 cell viability and induced apoptotic cell death. In addition the findings suggested that curcumin-induced cell apoptosis occurred via the mitochondrial pathway, and caspase‑independent and AIF-dependent pathways. Further analysis revealed that curcumin may act as a PI3K-Akt-mTOR signaling pathway inhibitor by downregulating PI3K, p-Akt, p-mTOR and p-p70 ribosomal protein S6 kinase. Furthermore, curcumin inhibited tumor angiogenesis in vivo. In conclusion, curcumin may be potent enough to be developed as a novel therapeutic agent for the treatment of MPM.}, } @article {pmid30266660, year = {2018}, author = {Tsao, AS and Lindwasser, OW and Adjei, AA and Adusumilli, PS and Beyers, ML and Blumenthal, GM and Bueno, R and Burt, BM and Carbone, M and Dahlberg, SE and de Perrot, M and Fennell, DA and Friedberg, J and Gill, RR and Gomez, DR and Harpole, DH and Hassan, R and Hesdorffer, M and Hirsch, FR and Hmeljak, J and Kindler, HL and Korn, EL and Liu, G and Mansfield, AS and Nowak, AK and Pass, HI and Peikert, T and Rimner, A and Robinson, BWS and Rosenzweig, KE and Rusch, VW and Salgia, R and Sepesi, B and Simone, CB and Sridhara, R and Szlosarek, P and Taioli, E and Tsao, MS and Yang, H and Zauderer, MG and Malik, SM}, title = {Current and Future Management of Malignant Mesothelioma: A Consensus Report from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {11}, pages = {1655-1667}, doi = {10.1016/j.jtho.2018.08.2036}, pmid = {30266660}, issn = {1556-1380}, abstract = {On March 28- 29, 2017, the National Cancer Institute (NCI) Thoracic Malignacy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation convened the NCI-International Association for the Study of Lung Cancer- Mesothelioma Applied Research Foundation Mesothelioma Clinical Trials Planning Meeting in Bethesda, Maryland. The goal of the meeting was to bring together lead academicians, clinicians, scientists, and the U.S. Food and Drug Administration to focus on the development of clinical trials for patients in whom malignant pleural mesothelioma has been diagnosed. In light of the discovery of new cancer targets affecting the clinical development of novel agents and immunotherapies in malignant mesothelioma, the objective of this meeting was to assemble a consensus on at least two or three practice-changing multimodality clinical trials to be conducted through NCI's National Clinical Trials Network.}, } @article {pmid30262573, year = {2018}, author = {Arnold, DT and De Fonseka, D and Perry, S and Morley, A and Harvey, JE and Medford, A and Brett, M and Maskell, NA}, title = {Investigating unilateral pleural effusions: the role of cytology.}, journal = {The European respiratory journal}, volume = {52}, number = {5}, pages = {}, doi = {10.1183/13993003.01254-2018}, pmid = {30262573}, issn = {1399-3003}, abstract = {The vast majority of undiagnosed unilateral pleural effusions have fluid sent for cytological analysis. Despite widespread use, there is uncertainty about its sensitivity to diagnose malignant pleural effusions (MPEs). Our aim was to ascertain the utility of cytology using a large prospective cohort.Consecutive patients presenting with an undiagnosed unilateral pleural effusion were recruited to this UK-based study. All had pleural fluid sent for cytological analysis. Cytological sensitivity was based on the final diagnosis at 12 months, confirmed by two consultants.Over 8 years, 921 patients were recruited, of which 515 had a MPE. Overall sensitivity of fluid cytology to diagnose malignancy was 46% (95% CI 42-58%). There was variation in sensitivity depending on cancer primary, with mesothelioma (6%) and haematological malignancies (40%) being significantly lower than adenocarcinomas (79%). MPEs secondary to ovarian cancer had high pick-up rates (95%). In asbestos-exposed males with exudative effusions, the risk of MPE was 60%, but cytological sensitivity was 11%.This is the largest prospective study of pleural fluid cytology and informs discussions with patients about the likely requirement for investigations following thoracentesis. In patients presenting with a clinical suspicion of mesothelioma, cytological sensitivity is low, so more definitive investigations could be performed sooner.}, } @article {pmid30259910, year = {2018}, author = {Ascoli, V and Murer, B and Nottegar, A and Luchini, C and Carella, R and Calabrese, F and Lunardi, F and Cozzi, I and Righi, L}, title = {What's new in mesothelioma.}, journal = {Pathologica}, volume = {110}, number = {1}, pages = {12-28}, pmid = {30259910}, issn = {0031-2983}, abstract = {Malignant pleural mesothelioma is a neoplasm characterized by a very poor prognosis and medico-legal implications. Diagnosis, prognosis and therapy are often challenging and include several issues. Cytological diagnosis is frequently the first step of the diagnostic process, and although its sensitivity may be somewhat lower, diagnostic criteria should be taken into account. When effusion cytology is inconclusive for the diagnosis, tissue biopsies should be taken. Even if the morphologic criteria for deciding whether a mesothelial proliferation is a benign or a malignant process have been defined, the separation of benign from malignant mesothelial proliferation is often a difficult problem for the pathologist, particularly on small biopsies. Thirdly, when the diagnosis is made, despite many efforts have been made to identify possible new biomarkers for early diagnosis, prognostic stratification and also predictive tools should be defined. Nowadays, the main prognostic parameter is still represented by the histological subtype, having the epithelioid MPM a better outcome than the sarcomatoid or biphasic MPM. A nuclear grading system have been also proposed to stratify patient outcome. Reliable predictive biomarkers are still lacking in MPM and a personalized therapeutic concept is eagerly needed. Mesothelioma occurs mostly as sporadic cancer and the main risk factor is asbestos exposure, but it also occurs among blood relatives suggesting possible increased genetic susceptibility besides shared exposures. Recently the study of genetic predisposition syndrome raised new aspect in the occurrence of mesothelioma cases.

This review summarize these most important issues.}, } @article {pmid30257964, year = {2019}, author = {Santarelli, L and Gaetani, S and Monaco, F and Bracci, M and Valentino, M and Amati, M and Rubini, C and Sabbatini, A and Pasquini, E and Zanotta, N and Comar, M and Neuzil, J and Tomasetti, M and Bovenzi, M}, title = {Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {28}, number = {1}, pages = {119-126}, doi = {10.1158/1055-9965.EPI-18-0453}, pmid = {30257964}, issn = {1538-7755}, abstract = {BACKGROUND: Altered miRNA expression is an early event upon exposure to occupational/environmental carcinogens; thus, identification of a novel asbestos-related profile of miRNAs able to distinguish asbestos-induced cancer from cancer with different etiology can be useful for diagnosis. We therefore performed a study to identify miRNAs associated with asbestos-induced malignancies.

METHODS: Four groups of patients were included in the study, including patients with asbestos-related (NSCLCAsb) and asbestos-unrelated non-small cell lung cancer (NSCLC) or with malignant pleural mesothelioma (MPM), and disease-free subjects (CTRL). The selected miRNAs were evaluated in asbestos-exposed population.

RESULTS: Four serum miRNAs, that is miR-126, miR-205, miR-222, and miR-520g, were found to be implicated in asbestos-related malignant diseases. Notably, increased expression of miR-126 and miR-222 were found in asbestos-exposed subjects, and both miRNAs are involved in major pathways linked to cancer development. Epigenetic changes and cancer-stroma cross-talk could induce repression of miR-126 to facilitate tumor formation, angiogenesis, and invasion.

CONCLUSIONS: This study indicates that miRNAs are potentially involved in asbestos-related malignancies, and their expression outlines mechanism(s) whereby miRNAs may be involved in an asbestos-induced pathogenesis.

IMPACT: The discovery of a miRNA panel for asbestos-related malignancies would impact on occupational compensation and may be utilized for screening asbestos-exposed populations.}, } @article {pmid30254313, year = {2018}, author = {Johnen, G and Burek, K and Raiko, I and Wichert, K and Pesch, B and Weber, DG and Lehnert, M and Casjens, S and Hagemeyer, O and Taeger, D and Brüning, T and , }, title = {Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin - a case-control comparison nested into a prospective cohort of asbestos-exposed workers.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14321}, pmid = {30254313}, issn = {2045-2322}, abstract = {Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools - like minimally-invasive biomarkers - are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.}, } @article {pmid30241199, year = {2018}, author = {Boffetta, P and Malvezzi, M and Pira, E and Negri, E and La Vecchia, C}, title = {International Analysis of Age-Specific Mortality Rates From Mesothelioma on the Basis of the International Classification of Diseases, 10th Revision.}, journal = {Journal of global oncology}, volume = {}, number = {4}, pages = {1-15}, pmid = {30241199}, issn = {2378-9506}, abstract = {Past analyses of mortality data from mesothelioma relied on unspecific codes, such as pleural neoplasms. We calculated temporal trends in age-specific mortality rates in Canada, the United States, Japan, France, Germany, Italy, the Netherlands, Poland, the United Kingdom, and Australia on the basis of the 10th version of the International Classification of Diseases, which includes a specific code for mesothelioma. Older age groups showed an increase (in the United States, a weaker decrease) during the study period, whereas in young age groups, there was a decrease (in Poland, a weaker increase, starting, however, from low rates). Results were consistent between men and women and between pleural and peritoneal mesothelioma, although a smaller number of events in women and for peritoneal mesothelioma resulted in less precise results. The results show the heterogeneous effect of the reduction of asbestos exposure on different age groups; decreasing mortality in young people reflects reduced exposure opportunity, and increasing mortality in the elderly shows the long-term effect of early exposures.}, } @article {pmid30209210, year = {2018}, author = {Finkelstein, MM}, title = {Response to: 'The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure' by Marinaccio et al.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {11}, pages = {844}, doi = {10.1136/oemed-2018-105129}, pmid = {30209210}, issn = {1470-7926}, } @article {pmid30209209, year = {2018}, author = {Marinaccio, A and Corfiati, M and Binazzi, A and Di Marzio, D and Scarselli, A and Ferrante, P and Bonafede, M and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Mazzoleni, G and Merler, E and Girardi, P and Negro, C and D'Agostin, F and Romanelli, A and Chellini, E and Silvestri, S and Pascucci, C and Calisti, R and Stracci, F and Romeo, E and Ascoli, V and Trafficante, L and Carrozza, F and Angelillo, I and Cavone, D and Cauzillo, G and Tallarigo, F and Tumino, R and Melis, M and Iavicoli, S and , }, title = {Letter concerning: 'Response to: 'The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure' by Marinaccio et al'.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {11}, pages = {844-845}, doi = {10.1136/oemed-2018-105362}, pmid = {30209209}, issn = {1470-7926}, } @article {pmid30196105, year = {2018}, author = {Kharazmi, E and Chen, T and Fallah, M and Sundquist, K and Sundquist, J and Albin, M and Weiderpass, E and Hemminki, K}, title = {Familial risk of pleural mesothelioma increased drastically in certain occupations: A nationwide prospective cohort study.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {103}, number = {}, pages = {1-6}, doi = {10.1016/j.ejca.2018.07.139}, pmid = {30196105}, issn = {1879-0852}, abstract = {OBJECTIVE: We aimed to explore the effect of occupation on familial risk of pleural mesothelioma in a nationwide cohort study design.

METHOD: The nationwide Swedish Family-Cancer Database includes all Swedes born after 1931 and their biological parents, totalling 16.1 million individuals with about 2.3 million cancer patients. Hazards ratios (HRs) were calculated adjusting for age, sex and region of residence.

RESULTS: Having asbestos-related occupation in the absence of family history of mesothelioma increased risk of mesothelioma more than threefold (adjusted HR = 3.2, 95% confidence interval [CI]: 3.0-3.5). In those who had a history of mesothelioma in their first-degree relatives and an asbestos-related occupation, risk of mesothelioma dramatically increased compared with individuals without such occupations and family history (without chronic obstructive pulmonary disease [COPD] HR = 24, 95% CI: 15-39; with COPD 45, 95% CI: 15-141). In those who had a family history of mesothelioma and no history of an asbestos-related occupation, risk of mesothelioma did not show significant increase compared with those who had no family history of mesothelioma and no asbestos-related occupation (HR = 1.6; 95% CI: 0.7-3.8).

CONCLUSION: First-degree relatives of patients with pleural mesothelioma had a drastic risk of developing this malignancy in case of certain occupations, which shows a gene-environment interaction is probable in risk of mesothelioma.}, } @article {pmid30174219, year = {2019}, author = {Marant Micallef, C and Shield, KD and Vignat, J and Baldi, I and Charbotel, B and Fervers, B and Gilg Soit Ilg, A and Guénel, P and Olsson, A and Rushton, L and Hutchings, SJ and Cléro, E and Laurier, D and Scanff, P and Bray, F and Straif, K and Soerjomataram, I}, title = {Cancers in France in 2015 attributable to occupational exposures.}, journal = {International journal of hygiene and environmental health}, volume = {222}, number = {1}, pages = {22-29}, doi = {10.1016/j.ijheh.2018.07.015}, pmid = {30174219}, issn = {1618-131X}, abstract = {BACKGROUND: Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking.

OBJECTIVES: To estimate the number of new cancer cases attributable to occupational exposures, using a newly developed methodology and the most recent data, for a comprehensive set of occupational carcinogens in France in 2015.

METHODS: Surveys among employees, the national labor force data, a cohort of agricultural workers, national monitoring of workers exposed to ionizing radiation and job-exposure matrix in France were used. The number and proportion of new cancer cases attributable to established occupational carcinogens (Group 1) was estimated using estimation of lifetime exposure and risk estimates from cohort studies. Cancer data were obtained from the French Cancer Registries Network.

RESULTS: In France in 2015, an estimated 7905 new cancer cases, 7336 among men and 569 among women, were attributable to occupational exposures, representing 2.3% of all new cancer cases (3.9% and 0.4% among men and women respectively). Among men and women, lung cancer was impacted the most, followed by mesothelioma and bladder cancer in men, and by mesothelioma and ovary in women. These cancers contributed to 89% of the total cancers attributable to occupational carcinogens in men, and to 80% in women. The main contributing occupational agent was asbestos among men (45%) and women (60%).

CONCLUSIONS: Currently, occupational exposures contribute to a substantial burden of cancer in France. Enhanced monitoring and implementation of protective labor policies could potentially prevent a large proportion of these cancers.}, } @article {pmid30169798, year = {2018}, author = {Terracini, B}, title = {Commentary: Past and current asbestos exposure and future mesothelioma risks in Britain.}, journal = {International journal of epidemiology}, volume = {47}, number = {6}, pages = {1756-1757}, doi = {10.1093/ije/dyy175}, pmid = {30169798}, issn = {1464-3685}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; United Kingdom ; }, } @article {pmid30158318, year = {2018}, author = {Reid, A and Franklin, P and Berry, G and Peters, S and Sodhi-Berry, N and Brims, F and Musk, AW and de Klerk, NH}, title = {Are children more vulnerable to mesothelioma than adults? A comparison of mesothelioma risk among children and adults exposed non-occupationally to blue asbestos at Wittenoom.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {12}, pages = {898-903}, doi = {10.1136/oemed-2018-105108}, pmid = {30158318}, issn = {1470-7926}, abstract = {OBJECTIVES: The presence of asbestos in public buildings is a legacy of past asbestos use in many developed countries. Of particular concern is the amount and current condition in schools and the vulnerability of children to mesothelioma. Our aim was to compare the risk of mesothelioma between those exposed to blue asbestos as children and as adults at Wittenoom.

METHODS: Public sources were used to establish the Wittenoom residents' cohort. Mesothelioma incidence rates per 100 000 person-years at risk were derived for those first exposed to asbestos at Wittenoom as children (<15 years) or adults separately. Proportional hazards survival models examined the slope of the exposure-response relationship between asbestos exposure and incidence of mesothelioma in different sex and age groups.

RESULTS: The mesothelioma rate was lower among those first exposed as children (76.8 per 100 000) than those first exposed as adults (121.3 per 100 000). Adjusting for cumulative exposure to asbestos and sex, those exposed as adults had a greater risk of mesothelioma (adjusted HR 2.5, 95% CI 1.7 to 3.7). The slope of the exposure-response relationship did not differ between those exposed as children and those exposed as adults.

CONCLUSION: We found no greater susceptibility to mesothelioma among those first exposed to asbestos as children than those first exposed as adults. However, given the long latency of mesothelioma, and the greater years of life yet to be lived by the Wittenoom children, it is likely that there will be more cases of mesothelioma in the future among those first exposed as children.}, } @article {pmid30157247, year = {2018}, author = {Rath, EM and Cheng, YY and Pinese, M and Sarun, KH and Hudson, AL and Weir, C and Wang, YD and Håkansson, AP and Howell, VM and Liu, GJ and Reid, G and Knott, RB and Duff, AP and Church, WB}, title = {BAMLET kills chemotherapy-resistant mesothelioma cells, holding oleic acid in an activated cytotoxic state.}, journal = {PloS one}, volume = {13}, number = {8}, pages = {e0203003}, pmid = {30157247}, issn = {1932-6203}, mesh = {Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Cell Line, Tumor ; Cell Membrane/drug effects/metabolism ; Cell Survival/drug effects ; Drug Resistance, Neoplasm/*drug effects ; Humans ; Hydrogen-Ion Concentration ; Lactalbumin/chemistry/*pharmacology ; Lung Neoplasms/*pathology ; Mesothelioma/*pathology ; Mitochondrial Proton-Translocating ATPases/metabolism ; Models, Molecular ; Molecular Conformation ; Oleic Acid/chemistry/*pharmacology ; }, abstract = {Malignant pleural mesothelioma is an aggressive cancer with poor prognosis. Here we have investigated in vitro efficacy of BAMLET and BLAGLET complexes (anti-cancer complexes consisting of oleic acid and bovine α-lactalbumin or β-lactoglobulin respectively) in killing mesothelioma cells, determined BAMLET and BLAGLET structures, and investigated possible biological mechanisms. We performed cell viability assays on 16 mesothelioma cell lines. BAMLET and BLAGLET having increasing oleic acid content inhibited human and rat mesothelioma cell line proliferation at decreasing doses. Most of the non-cancer primary human fibroblasts were more resistant to BAMLET than were human mesothelioma cells. BAMLET showed similar cytotoxicity to cisplatin-resistant, pemetrexed-resistant, vinorelbine-resistant, and parental rat mesothelioma cells, indicating the BAMLET anti-cancer mechanism may be different to drugs currently used to treat mesothelioma. Cisplatin, pemetrexed, gemcitabine, vinorelbine, and BAMLET, did not demonstrate a therapeutic window for mesothelioma compared with immortalised non-cancer mesothelial cells. We demonstrated by quantitative PCR that ATP synthase is downregulated in mesothelioma cells in response to regular dosing with BAMLET. We sought structural insight for BAMLET and BLAGLET activity by performing small angle X-ray scattering, circular dichroism, and scanning electron microscopy. Our results indicate the structural mechanism by which BAMLET and BLAGLET achieve increased cytotoxicity by holding increasing amounts of oleic acid in an active cytotoxic state encapsulated in increasingly unfolded protein. Our structural studies revealed similarity in the molecular structure of the protein components of these two complexes and in their encapsulation of the fatty acid, and differences in the microscopic structure and structural stability. BAMLET forms rounded aggregates and BLAGLET forms long fibre-like aggregates whose aggregation is more stable than that of BAMLET due to intermolecular disulphide bonds. The results reported here indicate that BAMLET and BLAGLET may be effective second-line treatment options for mesothelioma.}, } @article {pmid30144378, year = {2019}, author = {Muscella, A and Cossa, LG and Vetrugno, C and Antonaci, G and Marsigliante, S}, title = {ADP sensitizes ZL55 cells to the activity of cisplatin.}, journal = {Journal of cellular physiology}, volume = {234}, number = {4}, pages = {4409-4417}, doi = {10.1002/jcp.27224}, pmid = {30144378}, issn = {1097-4652}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor in which cisplatin therapy is commonly used, although its effectiveness is limited. It follows that research efforts dedicated to identify promising combinations that can synergistically kill cancer cells are needed. Because we recently demonstrated that ADP inhibits the proliferation of ZL55 cells, an MPM-derived cell line obtained from bioptic samples of asbestos-exposed patients. Our objective in this study was to investigate the hypothesis that ADP also potentiates the cytotoxic activity of cisplatin. Results show that in ZL55 cells ADP enhanced (a) the cytotoxicity of cisplatin by 12-fold, (b) the restraint of cell clonogenic potential cisplatin-mediated, and (c) the number of apoptotic cells. Cisplatin, but not ADP, caused caspases activation; nevertheless, poly(ADP-ribose) polymerase-1 was not only cleaved in cisplatin-treated cells but also in cells treated with ADP alone. Furthermore, ADP, but not cisplatin, decreased mTOR and 6SK phosphorylations. Both ADP and cisplatin increased p53 protein, but ADP was also able to enhance p53 messenger RNA. P53 silencing resulted in a very large decrement of cell death induced by ADP or by cisplatin and reverted ADP effects on mTOR/S6K phosphorylation, suggesting that activated p53 may act as a negative regulator of mTOR. Consistently, the inhibition of mTOR by rapamycin also sensitized cells to cisplatin, and the effects of cisplatin plus rapamycin were identical to those obtained with cisplatin plus ADP. These findings suggest that the combination of ADP and cisplatin may be a promising strategy for the clinical treatment of cisplatin-resistant MPM.}, } @article {pmid30140191, year = {2018}, author = {Kang, DM and Kim, JE and Kim, YK and Lee, HH and Kim, SY}, title = {Occupational Burden of Asbestos-Related Diseases in Korea, 1998-2013: Asbestosis, Mesothelioma, Lung Cancer, Laryngeal Cancer, and Ovarian Cancer.}, journal = {Journal of Korean medical science}, volume = {33}, number = {35}, pages = {e226}, pmid = {30140191}, issn = {1598-6357}, abstract = {Background: Asbestos exposure causes asbestos-related diseases (ARDs) including asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer. Although Korea used substantial amounts of asbestos in the past, no study has focused on its occupational burden of disease (OBD). Therefore, this study aimed to determine the OBDs of ARDs in Korea.

Methods: The CARcinogen Exposure (CAREX) database was used to determine the proportion of exposed population. Relative risks for lung cancer, laryngeal cancer, and ovarian cancer were used to determine the population-attributable fraction. Data for deaths caused by ARDs during 1998-2013 were obtained from the World Health Organization mortality database. The potential years of life lost (PYLL) and annual average PYLL (APYLL) indicated OBDs.

Results: In Korea, the number of ARD-attributable deaths and PYLL due to all ARDs during 1998-2013 were 4,492 and 71,763.7, respectively. The number of attributable deaths and PYLL due to asbestosis, malignant mesothelioma, lung cancer, laryngeal cancer, and ovarian cancer were 37 and 554.2, 808 and 15,877.0, 3,256 and 47,375.9, 120 and 1,605.5, and 271 and 6,331.1, respectively; additionally, the APYLL were 15.0, 19.7, 14.6, 13.4, and 23.4, respectively, and the average age at death was 70.4, 62.6, 69.1, 69.9, and 61.8, respectively. Our study showed that although the use of asbestos has ceased in Korea, the incidence of ARDs tends to increase.

Conclusion: Therefore, efforts to reduce future OBDs of ARDs, including early detection and proper management of ARDs, are needed in Korea.}, } @article {pmid30137349, year = {2018}, author = {Krupoves, A}, title = {Commentary: Asbestos exposure and mesothelioma risk.}, journal = {International journal of epidemiology}, volume = {47}, number = {6}, pages = {1758-1759}, doi = {10.1093/ije/dyy176}, pmid = {30137349}, issn = {1464-3685}, mesh = {Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; United Kingdom ; }, } @article {pmid30137211, year = {2018}, author = {Farioli, A and Mattioli, S and Curti, S and Spatari, G and Violante, FS}, title = {Letter to the editor re: Dragani et al. (2018), "Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure".}, journal = {Carcinogenesis}, volume = {}, number = {}, pages = {}, doi = {10.1093/carcin/bgy111}, pmid = {30137211}, issn = {1460-2180}, } @article {pmid30134140, year = {2018}, author = {Chatfield, EJ}, title = {Measurement of elongate mineral particles: What we should measure and how do we do it?.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {36-46}, doi = {10.1016/j.taap.2018.08.010}, pmid = {30134140}, issn = {1096-0333}, abstract = {The length distributions of single fibrils of Coalinga, UICC-B and wet dispersed chrysotile were measured by transmission electron microscopy (TEM). It was found that the distributions significantly diverged above approximately 10 μm (μm) in length, corresponding to differences in published results of animal experiments. This result is in contrast to published data in which counting of an insufficient number of fibers resulted in an erroneous conclusion that the length distribution of Coalinga chrysotile fibrils was indistinguishable from those of other sources of chrysotile. The size distributions of the respirable particle size fractions from acknowledged tremolite asbestos samples were found to be dominated by elongate particles longer than 5 μm that are within the dimensional range of non-asbestiform amphiboles. Prior studies have shown that these elongate particles obscure a correlation between a specific size range of particles and results of animal implantation studies that used tremolite of various morphologies. In the prior studies, a reference protocol was developed from four crushed non-asbestiform amphiboles to differentiate the size range of amphibole particles that correlates with the mesothelioma frequencies observed in the animal studies. In the work reported here, this correlation was tested with TEM analyses of amphiboles from Libby, MT, Sparta, NJ and Homestake mine, Lead, SD, which represent known environmental/occupational situations. Further TEM analyses of the tremolite samples used in the original animal implantation studies have also shown that the numbers of elongate tremolite particles with lengths ≤5 μm implanted into the animals are not correlated with the observed mesothelioma frequencies.}, } @article {pmid30133855, year = {2018}, author = {Finkelstein, MM}, title = {Letter Concerning: Glynn ME, Keeton KA, Gaffney SH, Sahmel J. Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence Between Urban and Rural Areas in the United States (1973-2012). Risk Analysis 2018;38(3):454-471.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {8}, pages = {1521-1523}, doi = {10.1111/risa.13124}, pmid = {30133855}, issn = {1539-6924}, mesh = {*Asbestos ; Humans ; Incidence ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; United States ; }, } @article {pmid30133854, year = {2018}, author = {Keeton, KA and Glynn, ME and Gaffney, SH and Sahmel, J}, title = {Response to Letter to the Editor Regarding "Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence Between Urban and Rural Areas in the United States (1973-2012)" by Finkelstein.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {8}, pages = {1524-1528}, doi = {10.1111/risa.13169}, pmid = {30133854}, issn = {1539-6924}, mesh = {*Asbestos ; Humans ; Incidence ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; United States ; }, } @article {pmid30123503, year = {2018}, author = {Bosio, M and Salvaterra, E and Datturi, F and Morbini, P and Zorzetto, M and Inghilleri, S and Tomaselli, S and Mangiarotti, P and Meloni, F and Cerveri, I and Stella, GM}, title = {5-hydroxymethylcytosine but not MTAP methylation status can stratify malignant pleural mesothelioma based on the lineage of origin.}, journal = {Multidisciplinary respiratory medicine}, volume = {13}, number = {}, pages = {27}, pmid = {30123503}, issn = {1828-695X}, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, mainly associated with work or environmental exposure to asbestos. MPM's molecular profile is largerly unexplored and effective therapies are still lacking. MPM rarely harbours those somatic genetic lesions that usually characterize solid epithelial-derived tumors. On this basis, our study aims at investigating MPM epigenetic profile.

Methods: We here assessed through immunohistochemistry, FISH and methylation specific PCR, the expression of 5-hydroxymethylcytosine (5- hmC) - an epigenetic marker and an important regulator of embryonic development and carcinogenesis - and the methylation status of the promoter of the MTAP gene - encoding for an enzyme involved in the rescue process of methionine and adenine - in two relevant series of FF-PE MPM samples derived from MPM thoracoscopic biopsies. Tissue sampling was performed at diagnosis.

Results: Within the limitations of the study cohort, the 5-hmC immunophenotype was different among the histological MPM types analysed. In fact, 18% of the epithelial MPMs were negative, 47% weakly positive, and 35% of the cases showed an intense expression of 5-hmC. Sarcomatoid and biphasic MPMs showed intense 5-hmC expression pattern (positive and weakly positive in more than 80% of cases). Among MPM featuring epithelial lineage, none showed methylation of MTAP promoter.

Conclusions: Mesothelial sarcomatoid tumors featured a methylation profile characterized by a permanent gene silencing. Epithelial MPM methylation profile was in-between that of sarcomatoid MPM and the one of epithelial-derived tumors. MTAP promoter methylation level cannot be considered a suitable biomarker of epithelial MPM arousal.}, } @article {pmid30118736, year = {2019}, author = {Smith-Hannah, A and Naous, R}, title = {Primary peritoneal epithelioid mesothelioma of clear cell type with a novel VHL gene mutation: a case report.}, journal = {Human pathology}, volume = {83}, number = {}, pages = {199-203}, doi = {10.1016/j.humpath.2018.07.033}, pmid = {30118736}, issn = {1532-8392}, abstract = {Clear cell variant of epithelioid mesothelioma is an extremely rare tumor with only isolated cases reported so far in the peritoneum. Here, we report a case of peritoneal epithelioid mesothelioma, clear cell variant, in a 63-year-old female patient with a novel VHL gene mutation and an unusual indolent clinical course. The patient, who has no clinical history of asbestos exposure, presented with a 27.2-cm upper abdominal mass and a 5.5-cm liver lesion. Retrospective review of the patient's abdominal computed tomographic scan 4 years ago showed 2 small abdominal lesions that were felt clinically to represent hemangiomas. These were retrospectively considered to have grown in size and represented the current abdominal mass. Both masses were subsequently biopsied and showed a proliferation of monomorphic epithelioid cells with distinct cell membranes, fine chromatin, and clear to finely vacuolated pale eosinophilic cytoplasm arranged in nests and solid sheets. Immunohistochemical staining confirmed it to be malignant mesothelioma. Clear cell variant of peritoneal epithelioid mesothelioma should always be considered in patients with an abdominal or pelvic mass with clear cell features. Given the rarity of such entity, its clinical course and prognosis remains unclear.}, } @article {pmid30113886, year = {2018}, author = {Panou, V and Gadiraju, M and Wolin, A and Weipert, CM and Skarda, E and Husain, AN and Patel, JD and Rose, B and Zhang, SR and Weatherly, M and Nelakuditi, V and Knight Johnson, A and Helgeson, M and Fischer, D and Desai, A and Sulai, N and Ritterhouse, L and Røe, OD and Turaga, KK and Huo, D and Segal, J and Kadri, S and Li, Z and Kindler, HL and Churpek, JE}, title = {Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {36}, number = {28}, pages = {2863-2871}, doi = {10.1200/JCO.2018.78.5204}, pmid = {30113886}, issn = {1527-7755}, abstract = {PURPOSE: The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM).

METHODS: We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM.

RESULTS: Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI, 199 to 76,224; P < .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A (OR, 53; 95% CI, 6 to 249; P < .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P = .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to 135; P = .049) were significantly higher in MM cases than in a noncancer control population. Tumor sequencing identified mutations in a homologous recombination pathway gene in 52% (n = 29 of 54).

CONCLUSION: A significant proportion of patients with MM carry germline mutations in cancer susceptibility genes, especially those with peritoneal MM, minimal asbestos exposure, young age, and a second cancer diagnosis. These data support clinical germline genetic testing for patients with MM and provide a rationale for additional investigation of the homologous recombination pathway in MM.}, } @article {pmid30111295, year = {2018}, author = {Löffler, MW and Steinhilber, J and Hilke, FJ and Haen, SP and Bösmüller, H and Montes-Mojarro, IA and Bonzheim, I and Stäbler, A and Faust, U and Grasshoff, U and Königsrainer, I and Rammensee, HG and Kanz, L and Königsrainer, A and Beckert, S and Riess, O and Schroeder, C}, title = {First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications.}, journal = {BMC medical genetics}, volume = {19}, number = {1}, pages = {144}, pmid = {30111295}, issn = {1471-2350}, support = {Open Access Publishing Fund//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported.

CASE PRESENTATION: We here describe the clinical course of a PHTS patient who, in addition to a typical thyroid carcinoma at the age of 36 years, developed a highly-differentiated oral VC and an epithelioid MPM six years later. The patient with a history of occupational asbestos exposure underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for MPM. The clinical diagnosis of PHTS was consequently corroborated by a germline PTEN deletion. Sequencing of tumor tissue revealed a second hit in PTEN in the thyroid carcinoma and VC, confirmed by a PTEN loss and activation of the PI3K/AKT pathway in immunohistochemistry. Furthermore, additional somatic mutations in the thyroid carcinoma as well as in the VC were detected, whereas the genetics of MPM remained unrevealing.

DISCUSSION AND CONCLUSIONS: We here report the very unusual clinical course of a patient with rare tumors that have a germline mutation first hit in PTEN in common. Since this patient was exposed to asbestos and current evidence suggests molecular mechanisms that might render PHTS patients particularly susceptible to mesothelioma, we strongly recommend PHTS patients to avoid even minimal exposure.}, } @article {pmid30109162, year = {2018}, author = {Salazar, C and Kanter Md, N and Abboud, A}, title = {Malignant Pleural Mesothelioma, Biphasic Type: An Unusual and Insidious Case of Rapidly Progressive Small Blue Cell Tumor.}, journal = {Cureus}, volume = {10}, number = {6}, pages = {e2749}, pmid = {30109162}, issn = {2168-8184}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm. It predominantly affects elderly individuals aged over 70 years presenting with a unilateral pleural tumor usually associated with previous asbestos exposure. The respiratory symptoms are associated with ipsilateral pleural involvement with concomitant pleural effusions. The diagnosis of MPM is established by the morphologic and immunohistochemical features of a cytologic specimen. MPM can present as three histologic subtypes: epithelioid, sarcomatoid, or biphasic. We present a case of an 85-year-old Caucasian female with a history of occupational asbestos exposure. She complained of 1-week history of progressive sharp right flank and scapular pain with mild shortness of breath, dry cough and pleuritic chest pain. CT of the chest showed a large loculated right pleural effusion with adjacent pleural thickening. CT abdomen and pelvis was negative for other neoplastic findings. CT-guided core biopsy of the right pleural-based mass was positive for a spindle to plasmacytoid small blue cell tumor. An extensive immunohistochemical panel was non-specific. A focal OSCAR keratin and WT-1 expression in the absence of carcinoma markers, a malignant mesothelioma, biphasic type was diagnosed. Further workup with PET-CT and cytotoxic chemotherapy combined with immunotherapy or tyrosine kinase inhibitors was recommended by oncology. The patient refused further imaging and treatment, and palliative care was consulted.}, } @article {pmid30104558, year = {2018}, author = {Krówczyńska, M and Wilk, E}, title = {Asbestos Exposure and the Mesothelioma Incidence in Poland.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {8}, pages = {}, pmid = {30104558}, issn = {1660-4601}, mesh = {Asbestos/*adverse effects ; *Carcinogens ; Environmental Exposure/*statistics & numerical data ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/*etiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Poland/epidemiology ; Risk Factors ; }, abstract = {Asbestos is carcinogenic to humans; the exposure to asbestos causes a wide range of diseases.

AIM: Malignant mesothelioma (MM) is unique for asbestos exposure.

METHODS: Based on the physical inventory of asbestos-cement roofing, the social-economic situation of communes, the proximity of asbestos manufacturing plants, the land use data referring to the surface of the built-up area, and the historical data on the annexations, the amount of asbestos-containing products in use was estimated by computing best Random Forest models. Per capita asbestos use is an indicator to compare the state of asbestos use among countries. MM cases in the local administrative units (provinces) were tested by the application of Moran's I and Getis and Ord statistic.

RESULTS: The total amount of asbestos roofing in Poland was estimated at 738,068,000 m² (8.2 million tons). In total there were 28 plants in Poland located in 11 provinces throughout the country. The amount of asbestos-cement roofing in use is correlated primarily with the measurements of asbestos concentration fibers (rs = 0.597). MM raw morbidity rate was calculated, stratified by province, and classified into five groups with respect to incidence. Hotspots of MM cases are in the southern part of Poland.

CONCLUSIONS: MM cases are concentrated in the same geographical areas, which may indicate an increasing impact of environmental exposure. The results of the local and global autocorrelation clearly indicate a statistically significant relationship between incidences of MM in provinces. Poland and other Eastern European countries are among countries with low MM incidence rate. Detailed investigation is desirable since the current MM morbidity rate in Poland seems to be underestimated.}, } @article {pmid30101018, year = {2018}, author = {Negi, Y and Kuribayashi, K and Doi, H and Funaguchi, N and Koda, Y and Fujimoto, E and Mikami, K and Minami, T and Yokoi, T and Kijima, T}, title = {Double cancer comprising malignant pleural mesothelioma and squamous cell carcinoma of the lung treated with radiotherapy: A case report.}, journal = {Molecular and clinical oncology}, volume = {9}, number = {2}, pages = {181-186}, pmid = {30101018}, issn = {2049-9450}, abstract = {Pleurectomy/decortication (P/D) is the surgical treatment of choice for early malignant mesothelioma, but it remains unclear whether radiotherapy along with P/D should be used as multimodal treatment for this disease. We herein present the case of a 76-year-old man with a history of asbestos exposure who was diagnosed with left-sided malignant pleural mesothelioma in February 2010. The patient underwent chemotherapy with a combination of cisplatin and pemetrexed and achieved stable disease, after which time he was kept under observation. A positron emission tomography/computed tomography scan performed in February 2011 revealed nodular shadows with fluorodeoxyglucose uptake in S3 of the left lung; using bronchoscopy, the patient was diagnosed with stage IIB (cT3N0M0) primary squamous cell carcinoma. Chemoradiotherapy with vinorelbine and 60 Gy/20 fr radiotherapy was performed, and a partial response was obtained, suggesting that the radiotherapy used to treat the carcinoma of the lung may have also helped control the disease activity of the pre-existing mesothelioma. The present case indicates the value of radiotherapy in the treatment of malignant mesothelioma. The aim of the present study was to examine the possibility of new multimodal treatments for mesothelioma, along with a discussion of the relevant literature.}, } @article {pmid30098092, year = {2018}, author = {Aida, S and Aida, J and Naoi, M and Kato, M and Tsuura, Y and Natsume, I and Takubo, K}, title = {Measurement of telomere length in cells from pleural effusion: Asbestos exposure causes telomere shortening in pleural mesothelial cells.}, journal = {Pathology international}, volume = {68}, number = {9}, pages = {503-508}, doi = {10.1111/pin.12710}, pmid = {30098092}, issn = {1440-1827}, support = {JP C26460457//JSPS KAKENHI/ ; }, mesh = {Adenocarcinoma of Lung/pathology ; Adult ; Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Biomarkers, Tumor/*metabolism ; Female ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Pleural Effusion/pathology ; Pleural Effusion, Malignant/*pathology ; Telomere/*pathology ; }, abstract = {We estimated the telomere lengths of neoplastic and non-neoplastic mesothelial cells and examined their correlation with asbestos exposure and the expression of markers of mesothelial malignancy. Cell blocks of pleural effusion obtained from 35 cases of non-neoplastic disease (NN), 12 cases of malignant mesothelioma (MM) and 12 cases of carcinomatous effusion due to lung adenocarcinoma (LA) were examined. Fifteen of the 35 NN cases had pleural plaques (NNpp+) suggestive of asbestos exposure, and the other 20 cases had no pleural plaques (NNpp-). Telomere length was measured using the tissue quantitative fluorescence in situ hybridization method, and expressed as normalized telomere-to-centromere ratio. NN cases had significantly longer telomeres than MM (P < 0.001) and LA (P < 0.001) cases. Telomeres in NNpp+ cases were slightly shorter than those of NNpp- cases (P = 0.047). MM and LA showed almost the same telomere length. NN cases with shorter telomeres tended to show aberrant expression of epithelial membrane antigen (EMA), CD146, glucose transporter 1 (GLUT1) and IGF-II messenger RNA-binding protein 3 (IMP3). These results suggest that telomere shortening and subsequent genetic instability play an important role in the development of MM. Measurement of telomere length of cells in pleural effusion might be helpful for earlier detection of MM.}, } @article {pmid30084369, year = {2018}, author = {Lucas, C}, title = {Miracle mineral or mesothelioma: cancer and asbestos in the USA.}, journal = {The Lancet. Oncology}, volume = {19}, number = {7}, pages = {868}, doi = {10.1016/S1470-2045(18)30352-8}, pmid = {30084369}, issn = {1474-5488}, } @article {pmid30077661, year = {2018}, author = {Garabrant, DH and Pastula, ST}, title = {A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {127-136}, doi = {10.1016/j.taap.2018.07.003}, pmid = {30077661}, issn = {1096-0333}, abstract = {We analyzed the mesothelioma mortality in cohorts of workers exposed to crocidolite, amosite, and chrysotile to estimate asbestos fiber potency for mesothelioma, using the method of Hodgson and Darnton (2000). We relied on the original 17 cohort studies in their analysis, along with 3 updates of those studies and 3 new asbestos cohort studies published since 2000. We extended the analyses to examine the mesothelioma potency of tremolite in vermiculite from Libby, Montana, and for non-asbestiform elongate mineral particles (EMPs) in taconite iron ore, talc, and South Dakota gold mining. Mesothelioma potency (RMeso) was calculated as the percent of all expected deaths that were due to mesothelioma per fiber/cc-year of exposure.The RMeso was 0.0012 for chrysotile, 0.099 for amosite, and 0.451 for crocidolite: thus, the relative potency of chrysotile:amosite:crocidolite was 1:83:376, which was not appreciably different from the estimates by Hodgson and Darnton in 2000. The RMeso for taconite mining fibers was 0.069 which was slightly smaller than that for amosite. The RMeso for Libby fibers was 0.028 which was greater than that for chrysotile and less than that for amosite. Talc and gold mining EMPs were non-potent for mesothelioma. Although there are a number of methods for estimating fiber potency of asbestos and non-asbestiform EMPs, the method of Hodgson and Darnton provides a uniform method by which fiber potency can be compared across many fiber types. Our estimates of RMeso provide a useful addition to our knowledge of mesothelioma potency for different asbestos and non-asbestiform EMP fibers.}, } @article {pmid30072200, year = {2019}, author = {Lin, RT and Chang, YY and Wang, JD and Lee, LJ}, title = {Upcoming epidemic of asbestos-related malignant pleural mesothelioma in Taiwan: A prediction of incidence in the next 30 years.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {1 Pt 3}, pages = {463-470}, doi = {10.1016/j.jfma.2018.07.013}, pmid = {30072200}, issn = {0929-6646}, abstract = {BACKGROUND/PURPOSE: Globally, asbestos-related diseases (ARDs) keep rising over the coming decades. The epidemic of ARDs will be a burden on public health. We aimed to predict the malignant pleural mesothelioma (MPM) incidence in the next 30 years for Taiwan based on historical asbestos consumption.

METHODS: We collected annual data on local asbestos consumption during 1939-2015 and sex-specific incidence of pleural cancer as a proxy for MPM during 1979-2013. We applied Poisson log-linear models to predict future MPM numbers under the assumption that latency periods between asbestos exposure and MPM incidence were between 25 and 45 years.

RESULTS: Asbestos consumption reached a peak in the 1980s, with a total of 668 thousand metric tons during 1939-2015. The observed number of MPM incidence increased by 9- and 6-fold in males and females during 1979-2013, with a cumulative number of 907. Given a latency period of 31 years, MPM incidences were expected to peak around 2012-2016 for males and 2016-2020 for females. In 2017-2046, the predicted total number of new MPM might reach 659 cases (95% confidence interval = 579-749); and the male to female ratios ranged from 1.8 to 2.8.

CONCLUSION: The MPM epidemic in Taiwan will likely peak in 2012-2020 as a result of local asbestos consumption. Approximately 659 new MPM cases in the next 30 years warrant an urgent need to implement a total asbestos ban and put more resources on a comprehensive surveillance, diagnosis, and follow-up health care system for ARDs.}, } @article {pmid30060501, year = {2018}, author = {Sage, AP and Martinez, VD and Minatel, BC and Pewarchuk, ME and Marshall, EA and MacAulay, GM and Hubaux, R and Pearson, DD and Goodarzi, AA and Dellaire, G and Lam, WL}, title = {Genomics and Epigenetics of Malignant Mesothelioma.}, journal = {High-throughput}, volume = {7}, number = {3}, pages = {}, pmid = {30060501}, issn = {2571-5135}, abstract = {Malignant mesothelioma is an aggressive and lethal asbestos-related disease. Diagnosis of malignant mesothelioma is particularly challenging and is further complicated by the lack of disease subtype-specific markers. As a result, it is especially difficult to distinguish malignant mesothelioma from benign reactive mesothelial proliferations or reactive fibrosis. Additionally, mesothelioma diagnoses can be confounded by other anatomically related tumors that can invade the pleural or peritoneal cavities, collectively resulting in delayed diagnoses and greatly affecting patient management. High-throughput analyses have uncovered key genomic and epigenomic alterations driving malignant mesothelioma. These molecular features have the potential to better our understanding of malignant mesothelioma biology as well as to improve disease diagnosis and patient prognosis. Genomic approaches have been instrumental in identifying molecular events frequently occurring in mesothelioma. As such, we review the discoveries made using high-throughput technologies, including novel insights obtained from the analysis of the non-coding transcriptome, and the clinical potential of these genetic and epigenetic findings in mesothelioma. Furthermore, we aim to highlight the potential of these technologies in the future clinical applications of the novel molecular features in malignant mesothelioma.}, } @article {pmid30060470, year = {2018}, author = {Jean, D and Jaurand, MC}, title = {Mesotheliomas in Genetically Engineered Mice Unravel Mechanism of Mesothelial Carcinogenesis.}, journal = {International journal of molecular sciences}, volume = {19}, number = {8}, pages = {}, pmid = {30060470}, issn = {1422-0067}, mesh = {Animals ; *Animals, Genetically Modified ; Carcinogenesis/*genetics ; Epithelium/pathology ; Humans ; Lung/pathology ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; *Mice ; Mutation ; Neoplasms, Experimental/*genetics ; Rats ; }, abstract = {Malignant mesothelioma (MM), a rare and severe cancer, mainly caused as a result of past-asbestos exposure, is presently a public health concern. Current molecular studies aim to improve the outcome of the disease, providing efficient therapies based on the principles of precision medicine. To model the molecular profile of human malignant mesothelioma, animal models have been developed in rodents, wild type animals and genetically engineered mice harbouring mutations in tumour suppressor genes, especially selecting genes known to be inactivated in human malignant mesothelioma. Animals were either exposed or not exposed to asbestos or to other carcinogenic fibres, to understand the mechanism of action of fibres at the molecular level, and the role of the selected genes in mesothelial carcinogenesis. The aim of the manuscript was to compare mesothelioma models to human malignant mesothelioma and to specify the clue genes playing a role in mesothelial carcinogenesis. Collectively, MM models recapitulate the clinical features of human MM. At least two altered genes are needed to induce malignant mesothelioma in mice. Two pathways regulated by Cdkn2a and Trp53 seem independent key players in mesothelial carcinogenesis. Other genes and pathways appear as bona fide modulators of the neoplastic transformation.}, } @article {pmid30032843, year = {2018}, author = {Rosskamp, M and De Schutter, H and Henau, K and Nackaerts, K and Van Meerbeeck, JP and Praet, M and Van Eycken, L}, title = {Assessing the completeness and correctness of the registration of malignant mesothelioma in Belgium.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {122}, number = {}, pages = {38-43}, doi = {10.1016/j.lungcan.2018.05.018}, pmid = {30032843}, issn = {1872-8332}, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is a rare and aggressive cancer mostly caused by asbestos exposure, and for which the diagnosis is difficult. This study aimed to assess the completeness and correctness of MM registration using 3 independent national databases: the Belgian Cancer Registry (BCR), the population-based mortality statistics (certificates of death, COD), and the Belgian Mesothelioma Registry (BMR).

METHODS: The study cohort included all MM reported to the BCR and diagnosed between 2004 and 2012 (n = 2292), all patients reviewed by the pathology commission of the BMR (2004-2012; n = 2019), and COD data for all Belgian citizens (2004-2013). Available data were compared in terms of registered cases, histological diagnosis, performed immunohistochemical (IHC) tests, and IHC test results.

RESULTS: Comparison of BCR with BMR registrations showed 94.8% concordant cases. The proportion of MM diagnoses originally reported to BCR with unspecified MM morphology was reduced from 25.8% to less than 1%.

RESULTS: from IHC tests were available for 95.3% of concordant MM cases. Different IHC patterns could be distinguished by MM histology. MM cases registered at BCR for which COD mentioned an MM as underlying cause of death represented 76.4% of deceased cases. MM long-term survivors (survival >3 years; 10.9%) were characterised by distinct clinical and biological characteristics.

CONCLUSIONS: A comparison of independent Belgian MM registration databases elucidated under-registration and misclassification and revealed possible reasons for observed discordances. Combining all the available information resulted in enhanced completeness and correctness of MM registration in Belgium and allowed for the identification and characterisation of MM long-term survivors.}, } @article {pmid30030099, year = {2018}, author = {Sonvico, F and Barbieri, S and Colombo, P and Barocelli, E and Mucchino, C and Cantoni, AM and Petronini, PG and Rusca, M and Carbognani, P and Ampollini, L}, title = {Combined hyaluronate-based films loaded with pemetrexed and cisplatin for the treatment of malignant pleural mesothelioma: Preliminary evaluation in an orthotopic tumor recurrence model.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {123}, number = {}, pages = {89-97}, doi = {10.1016/j.ejps.2018.07.035}, pmid = {30030099}, issn = {1879-0720}, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by a long latency period of 20-50 years after exposure to the main aetiology agent that is asbestos. MPM treatments include surgery, chemotherapy, and radiation therapy, with the combination pemetrexed and cisplatin being the standard chemotherapy approach. Despite this multimodality therapy one of the major issues after surgery is the high rate of local recurrence of the tumor. One possible approach would be the intrapleural application of implants loaded with anticancer drug to be applied during surgery to prevent local tumor recurrence. The implant proposed in the present work is a polymeric film of hyaluronic acid loaded with pemetrexed. The film developed is a hydrophilic, thin and flexible film sufficiently resistant to be applied intrapleurally adhering to the mesothelial surface. The release of pemetrexed from the film was found to be complete within2 h in phosphate buffered saline. In an orthotopic model of mesothelioma recurrence in rats, pemetrexed loaded films showed the same antitumor efficacy of pemetrexed disodium solutions administered intravenously or intrapleurally, while when administered in combination with cisplatin-loaded hyaluronate film, the implants almost completely prevented tumor recurrence. The local administration of drug-loaded polymer implants appears an ideal chemotherapy strategy especially for patients in which surgery is already selected as a viable therapeutic option.}, } @article {pmid30030095, year = {2018}, author = {Mossman, BT}, title = {Mechanistic in vitro studies: What they have told us about carcinogenic properties of elongated mineral particles (EMPs).}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {62-67}, doi = {10.1016/j.taap.2018.07.018}, pmid = {30030095}, issn = {1096-0333}, abstract = {In vitro studies using target and effecter cells of mineral-induced cancers have been critical in determining the mechanisms of pathogenesis as well as the properties of elongated mineral particles (EMPs) important in eliciting these responses. Historically, in vitro models of 'mutagenesis' and immortalized cell lines were first used to test the theory that EMPs were mutagenic to cells, and 'genotoxicity', as defined as damage to DNA often culminating in cell death, was observed in a dose-dependent fashion as responses of many cell types to a number of EMPs. As two-stage and multi-step models of cancer development emerged in the 1970s and 1980s, differentiated 3D organ cultures and monolayers of lung epithelial and mesothelial cells were used to probe the mechanisms of cancer development. These studies demonstrated a spectrum of pre-neoplastic changes, including hyperplasia and squamous metaplasia, in response to long (>5 μm in length) needlelike EMPs whereas long, curly chrysotile fibers caused acute cytotoxicity. Shorter fibers of many types were taken up by cells and encompassed in phagolysosomes. Comparative studies using chemical carcinogens showed that chemical agents interacted directly with DNA whereas long EMPs appeared to be promoters of cancers via a number of mechanisms such as inflammation, generation of oxidants, and instigation of cell division. The multitude of these signaling cascades and epigenetic mechanisms of both lung cancers and mesotheliomas have been most recently studied in normal or telomerase immortalized human cells. Importantly, many of these pathways are elicited by long, straight amphibole asbestos fibers or carbon nanotubes in rodents and not by short (<5 μm) EMPs, fragments, or nonfibrous particles. However, the chemistry and surface properties of long fibers are also critical in cell responses to minerals.}, } @article {pmid30030093, year = {2018}, author = {Abello, A and Steinkeler, J and Das, AK}, title = {A Bilateral Metachronous Mesothelioma of the Tunica Vaginalis.}, journal = {Urology}, volume = {120}, number = {}, pages = {e1-e2}, doi = {10.1016/j.urology.2018.07.003}, pmid = {30030093}, issn = {1527-9995}, abstract = {This is a unique case of bilateral metachronous testicular mesothelioma of the tunica vaginalis. Testicular mesothelioma is a rare entity found in patients with or without asbestos occupational exposure. The tumor most commonly presents as a unilateral testicular mass. More rare presentations include bilateral synchronous or metachronous tumors. Treatment is with surgical resection and prognosis is not generally favorable. The benefits of adjuvant therapy with radiation or chemotherapy remain unknown and further studies are needed.}, } @article {pmid30025147, year = {2019}, author = {Panou, V and Vyberg, M and Meristoudis, C and Hansen, J and Bøgsted, M and Omland, Ø and Weinreich, UM and Røe, OD}, title = {Non-occupational exposure to asbestos is the main cause of malignant mesothelioma in women in North Jutland, Denmark.}, journal = {Scandinavian journal of work, environment & health}, volume = {45}, number = {1}, pages = {82-89}, doi = {10.5271/sjweh.3756}, pmid = {30025147}, issn = {1795-990X}, abstract = {Objectives Diffuse malignant mesothelioma (MM) is mainly caused by asbestos inhalation. The malignancy is rare among women and studies of the prevalence and causative role of non-occupational asbestos exposure among women with MM are scarce. This observational study aimed to elucidate the asbestos exposure patterns among women with MM. Methods All histological and cytological specimens from women diagnosed with MM between 1974-2015 at the Institute of Pathology, Aalborg University Hospital in Denmark, were re-evaluated. Occupational and habitation information were obtained from Danish registries and medical journals based on record linkage via the unique person ID. The number of MM cases in each parish in the region of North Jutland was determined and the incidence density in parishes was used to calculate the spatial relative risk (RR) of MM among women. Results Diagnosis of MM was confirmed in 91 women. Exposure types were classified as occupational (9%), domestic (10%), environmental (22%), combination of domestic and environmental (34%) and unknown (25%). Twenty continuous parishes formed a MM "hotspot" around the asbestos-consuming industries in the city of Aalborg. Of these, the maximum RR was found in a parish housing an asbestos factory [RR 10.5, 95% confidence interval (CI) 5.5-19.4, environmental exposure in particular RR 2.9, 95% CI 0.7-6.1]. Conclusion Non-occupational asbestos exposure is the main cause of MM and may account for up to 66% of MM cases among women in North Jutland, Denmark.}, } @article {pmid30022998, year = {2018}, author = {Nabavi, N and Wei, J and Lin, D and Collins, CC and Gout, PW and Wang, Y}, title = {Pre-clinical Models for Malignant Mesothelioma Research: From Chemical-Induced to Patient-Derived Cancer Xenografts.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {232}, pmid = {30022998}, issn = {1664-8021}, abstract = {Malignant mesothelioma (MM) is a rare disease often associated with environmental exposure to asbestos and other erionite fibers. MM has a long latency period prior to manifestation and a poor prognosis. The survival post-diagnosis is often less than a year. Although use of asbestos has been banned in the United States and many European countries, asbestos is still being used and extracted in many developing countries. Occupational exposure to asbestos, mining, and migration are reasons that we expect to continue to see growing incidence of mesothelioma in the coming decades. Despite improvements in survival achieved with multimodal therapies and cytoreductive surgeries, less morbid, more effective interventions are needed. Thus, identifying prognostic and predictive biomarkers for MM, and developing novel agents for targeted therapy, are key unmet needs in mesothelioma research and treatment. In this review, we discuss the evolution of pre-clinical model systems developed to study MM and emphasize the remarkable capability of patient-derived xenograft (PDX) MM models in expediting the pre-clinical development of novel therapeutic approaches. PDX disease model systems retain major characteristics of original malignancies with high fidelity, including molecular, histopathological and functional heterogeneities, and as such play major roles in translational research, drug development, and precision medicine.}, } @article {pmid30018519, year = {2018}, author = {Strbac, D and Goricar, K and Dolzan, V and Kovac, V}, title = {Matrix Metalloproteinases Polymorphisms as Baseline Risk Predictors in Malignant Pleural Mesothelioma.}, journal = {Radiology and oncology}, volume = {52}, number = {2}, pages = {160-166}, pmid = {30018519}, issn = {1318-2099}, abstract = {Background: Malignant mesothelioma (MM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. Matrix metalloproteinases (MMPs) have been identified as modulators of the tumour microenvironment and carcinogenesis. Polymorphisms of selected MMPs have been studied as potential biomarkers of time to progression (TTP) and overall survival (OS) in MM. The aim of our study was to investigate selected MMP polymorphisms as baseline risk predictors in MM development in combination with other well known risk factors, such as asbestos exposure.

Patients and methods: The study included 236 patients and 161 healthy blood donors as the control group. Ten different polymorphisms in three MMP genes were genotyped using a fluorescence-based competitive allele-specific assay (KASPar): MMP2 rs243865, rs243849 and rs7201, MMP9 rs17576, rs17577, rs2250889 and rs20544, and MMP14 rs1042703, rs1042704 and rs743257. In statistical analyses continuous variables were described using median and range (25%-75%), while frequencies were used to describe categorical variables. Deviation from the Hardy-Weinberg equilibrium (HWE) was assessed using the standard chi-square test. The additive and dominant genetic models were used in statistical analyses. The association of genetic polymorphism with MM risk were examined by logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs).

Results: Carriers of at least one polymorphic MMP2 rs243865 allele tended to have a decreased risk for MM (OR = 0.66, 95% CI = 0.44-1.00; P = 0.050). The association was more pronounced in patients with known asbestos exposure: carriers of at least one polymorphic allele had significantly lower MM risk (OR = 0.55, 95% CI = 0.35-0.86; P = 0.009). None of the other tested polymorphisms showed association with the risk of malignant pleural mesothelioma.

Conclusions: The MMP2 rs243865 polymorphism may have a protective role in malignant pleural mesothelioma development. This finding is even more evident in patients exposed to asbestos, implying a strong gene-environment interaction.}, } @article {pmid30009035, year = {2018}, author = {An, YS and Kim, HD and Kim, HC and Jeong, KS and Ahn, YS}, title = {The characteristics of asbestos-related disease claims made to the Korea Workers' Compensation and Welfare Service (KCOMWEL) from 2011 to 2015.}, journal = {Annals of occupational and environmental medicine}, volume = {30}, number = {}, pages = {45}, pmid = {30009035}, issn = {2052-4374}, abstract = {Background: This study aimed to enhance understanding of the epidemiologic characteristics of asbestos-related diseases, and to provide information that could inform policy-making aimed at prevention and compensation for occupational asbestos exposure, through analyzing asbestos-related occupational disease claims to Korea Workers' Compensation and Welfare Service from 2011 to 2015.

Methods: We analyzed 113 workers who filed medical care claims or survivor benefits for asbestos exposure and occupational-related disease from 2011 to 2015. Among these claims, we selected approved workers' compensation claims relating to malignant mesothelioma and lung cancer, and analyzed the general characteristics, exposure characteristics, pathological characteristics, and occupation and industry distribution.

Results: Malignant mesothelioma and lung cancer occurred predominantly in males at 89.7 and 94%, respectively. The mean age at the time of diagnosis for malignant mesothelioma and lung cancer was 59.5 and 59.7 years, respectively, while the latency period for malignant mesothelioma and lung cancer was 34.1 and 33.1 years, respectively. The companies involving exposed workers were most commonly situated within the Busan-Ulsan-Gyeongnam region. Histology results for lung cancer indicated adenocarcinoma as the most common form, accounting for approximately one half of all claims, followed by squamous cell carcinoma, and small cell lung cancer. The most common occupation type was construction in respect of malignant mesothelioma, and shipbuilding in respect of lung cancer.

Conclusions: Considering the long latency period of asbestos and that the peak period of asbestos use in Korea was throughout the mid-1990s, damage due to asbestos-related diseases is expected to show a continued long-term increase. Few studies providing an epidemiologic analysis of asbestos-related diseases are available; therefore, this study may provide baseline data to assist in predicting and preparing for future harm due to asbestos exposure.

Trial registration: DUIH 2018-02-004-001. Registered 28 Februrary 2018.}, } @article {pmid30008600, year = {2018}, author = {Aguilar-Madrid, G and Pesch, B and Calderón-Aranda, ES and Burek, K and Jiménez-Ramírez, C and Juárez-Pérez, CA and Ochoa-Vázquez, MD and Torre-Bouscoulet, L and Acosta-Saavedra, LC and Sada-Ovalle, I and García-Figueroa, J and Alvarado-Cabrero, I and Castillo-González, P and Báez-Saldaña, AR and Pérez-Padilla, JR and Osnaya-Juárez, J and Rivera-Rosales, RM and García-Bazán, EM and Bautista-Aragón, YL and Lazcano-Hernandez, E and Munguía-Canales, DA and Argote-Greene, LM and Taeger, D and Weber, DG and Casjens, S and Raiko, I and Brüning, T and Johnen, G}, title = {Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population.}, journal = {International journal of medical sciences}, volume = {15}, number = {9}, pages = {883-891}, pmid = {30008600}, issn = {1449-1907}, mesh = {Aged ; Biomarkers, Tumor/*analysis ; Calbindin 2/*blood ; Case-Control Studies ; Female ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms ; Male ; Mesothelioma/blood/*diagnosis ; Mexico ; Middle Aged ; Pleural Neoplasms/blood/*diagnosis ; }, abstract = {Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.}, } @article {pmid30001711, year = {2018}, author = {Kittaneh, M and Berkelhammer, C}, title = {Detecting germline BAP1 mutations in patients with peritoneal mesothelioma: benefits to patient and family members.}, journal = {Journal of translational medicine}, volume = {16}, number = {1}, pages = {194}, pmid = {30001711}, issn = {1479-5876}, abstract = {Germline mutations in the BRCA-1 associated tumor protein 1 (BAP1) increase susceptibility to mesothelioma and other cancers. We describe a patient with a family history of peritoneal mesothelioma, who developed malignant peritoneal mesothelioma at age 45 in the absence of known asbestos exposure. These findings lead us to hypothesize that the mesothelioma occurred in the setting of germline a BAP1 mutation. This was confirmed by genetic testing. The subsequent therapeutic choices for the patient and testing of at-risk family members highlight the importance of recognizing this genetic syndrome and screening for individuals at high risk.}, } @article {pmid29990795, year = {2018}, author = {Fazzo, L and Minelli, G and De Santis, M and Bruno, C and Zona, A and Conti, S and Comba, P}, title = {Epidemiological surveillance of mesothelioma mortality in Italy.}, journal = {Cancer epidemiology}, volume = {55}, number = {}, pages = {184-191}, doi = {10.1016/j.canep.2018.06.010}, pmid = {29990795}, issn = {1877-783X}, abstract = {BACKGROUND: Malignant mesothelioma (MM) is causally linked to asbestos exposure with an estimated etiological fraction of 80% or more.

METHODS: Standardized rates of all mesothelioma (C45, ICD-10) and malignant pleural mesothelioma (C45.0, ICD-10) mortality in Italy were computed at national and regional levels, for the period 2003-2014. Standardized Mortality Ratios (SMRs, with 95% Confidence Intervals) were calculated for each of the 8047 Italian municipalities, for both diseases, with respect to Regional figures. A geographical clustering analysis at municipal level was performed, applying SatScan methods.

RESULTS: In Italy, 16,086 persons (about 1,340/year) died for MM, in analysed period. National Standardized rates of MM mortality are 3.65/100,000 in men and 1.09/100,000 in women, with an increasing annual trend, among male population. The highest rates were found in men from Northern Regions. Significant clusters (p < 0.10) were found corresponding to areas that hosted major asbestos-cement plants, naval shipyards, petrochemical plants and refineries. Furthermore, excesses were found corresponding to chemical and textile industries; the latter involving, particularly, female population. Excesses were found also in areas near the chrysotile mine of Balangero, and in Biancavilla, a town with a stone quarry contaminated by fluoro-edenitic fibres; an excess of MM mortality was observed among male population living in a minor island where a Navy shipyard is located.

CONCLUSIONS: Mortality for mesothelioma in Italy is still increasing, twenty-six years after the asbestos ban. Epidemiological surveillance of mesothelioma mortality allows to detect the temporal trend of the disease and highlights previously unknown or underestimated sources of asbestos exposure.}, } @article {pmid29982378, year = {2018}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {39}, number = {9}, pages = {1151-1156}, doi = {10.1093/carcin/bgy089}, pmid = {29982378}, issn = {1460-2180}, abstract = {Asbestos exposure is the main etiology of malignant mesothelioma, but there are conflicting data on whether the intensity of exposure modulates the development of this disease. This study considered 594 patients with malignant mesothelioma for whom count data on asbestos bodies and fibers (per gram of wet lung tissue) were available. The relationships between age at diagnosis (a time-to-event outcome variable) and these two measures of internal asbestos exposure, along with other possible modulating factors (sex, tumor location, histological subtype and childhood exposure), were assessed on multivariable Cox proportional hazard models, stratifying by decade of birth year. For both measures of asbestos in lung tissue, younger age at diagnosis was associated with higher internal measures of exposure to asbestos. Stratified Cox analyses showed that for each doubling in asbestos body count patients were 1.07 times more likely to be diagnosed at a younger age [hazard ratio (HR) = 1.07; 95% confidence interval (CI), 1.04-1.09; P = 2.2 × 10-7] and for each doubling in asbestos fiber count patients were 1.13 times more likely to be diagnosed at a younger age (HR = 1.13; 95% CI, 1.09-1.17; P = 8.6 × 10-11). None of the other variables considered were associated with age at diagnosis. Our finding that tumors become clinically apparent at a younger age in heavily exposed subjects suggests that asbestos is involved not only in the malignant mesothelioma tumor initiation but, somehow, also in the progression of the disease.}, } @article {pmid29977434, year = {2018}, author = {Pranay, P and Serafimov, V and Hall, J and Goel, A and Mushtaq, M}, title = {Metastatic biphasic pleural mesothelioma presenting with cauda equina syndrome.}, journal = {Radiology case reports}, volume = {13}, number = {3}, pages = {736-739}, pmid = {29977434}, issn = {1930-0433}, abstract = {Patient with previous asbestos exposure on a watchful wait and watch regime presents acutely with cauda equina syndrome. Radiological imaging confirmed a mass with direct invasion of the spinal cord. Histology confirmed metastatic pleural mesothelioma.}, } @article {pmid29970876, year = {2018}, author = {Jones, RG and Karthik, F and Dugar, A and Kanagarajan, K and Desai, K and Bhandari, M}, title = {Nivolumab Immunotherapy in Malignant Mesothelioma: A Case Report Highlighting a New Opportunity for Exceptional Outcomes.}, journal = {The American journal of case reports}, volume = {19}, number = {}, pages = {783-789}, pmid = {29970876}, issn = {1941-5923}, mesh = {Aged ; Antibodies, Monoclonal/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; Immunotherapy ; Male ; Mesothelioma/*drug therapy ; Nivolumab ; Pleural Neoplasms/*drug therapy ; Treatment Outcome ; }, abstract = {BACKGROUND Malignant pleural mesothelioma (MPM) is a highly lethal cancer with a median survival of ~12 months even with aggressive intervention. Frontline therapy relies on systemic cisplatin and pemetrexed chemotherapy and has a response rate of ~35-41%; currently, there are no US Food and Drug Administration approved second-line therapies for MPM. Herein, we present a patient with MPM who experienced rapid disease progression after standard therapy but who had an exceptional and sustained response to immune checkpoint inhibition with single agent nivolumab. CASE REPORT A 68-year-old male with a history of work-related asbestos exposure was diagnosed with MPM. He was treated with primary resection followed by systemic chemotherapy with cisplatin and pemetrexed. When chemotherapy failed, he was switched to immunotherapy with nivolumab and achieved an exceptional response. CONCLUSIONS We report the first case of a patient with MPM who experienced rapid disease progression after standard therapy but had an exceptional and sustained response to immune checkpoint inhibition with single agent nivolumab. As outcomes with traditional chemotherapy regimens remain disappointing, there is a substantial need for new approaches to MPM; our case highlights a new therapeutic opportunity even in the face of aggressive disease. Indeed, a new era of investigation utilizing immunotherapy for mesothelioma is beginning, with much anticipation.}, } @article {pmid29966799, year = {2018}, author = {Mutti, L and Peikert, T and Robinson, BWS and Scherpereel, A and Tsao, AS and de Perrot, M and Woodard, GA and Jablons, DM and Wiens, J and Hirsch, FR and Yang, H and Carbone, M and Thomas, A and Hassan, R}, title = {Scientific Advances and New Frontiers in Mesothelioma Therapeutics.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {9}, pages = {1269-1283}, doi = {10.1016/j.jtho.2018.06.011}, pmid = {29966799}, issn = {1556-1380}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that arises from the mesothelial surface of the pleural and peritoneal cavities, the pericardium, and rarely, the tunica vaginalis. The incidence of MPM is expected to increase worldwide in the next two decades. However, even with the use of multimodality treatment, MPM remains challenging to treat, with a 5-year survival rate of less than 5%. The International Association for the Study of Lung Cancer has gathered experts in different areas of mesothelioma research and management to summarize the most significant scientific advances and new frontiers related to mesothelioma therapeutics.}, } @article {pmid29961174, year = {2018}, author = {Hylebos, M and Op de Beeck, K and van den Ende, J and Pauwels, P and Lammens, M and van Meerbeeck, JP and Van Camp, G}, title = {Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma.}, journal = {Familial cancer}, volume = {17}, number = {4}, pages = {569-576}, pmid = {29961174}, issn = {1573-7292}, abstract = {Familial clustering of malignant mesothelioma (MM) has been linked to the presence of germline mutations in BAP1. However, families with multiple MM patients, without segregating BAP1 mutation were described, suggesting the existence of other predisposing genetic factors. In this study, we report a previously undescribed Belgian family, in which BAP1 was found to be absent in the epithelial malignant mesothelial cells of the index patient. Whole exome analysis did not reveal a germline or somatic BAP1 variant. Also, no germline or somatic copy number changes in the BAP1 region could be identified. However, germline variants, predicted to be damaging, were detected in 11 other 'Cancer census genes' (i.e. MPL, RBM15, TET2, FAT1, HLA-A, EGFR, KMT2C, BRD3, NOTCH1, RB1 and MYO5A). Of these, the one in RBM15 seems to be the most interesting given its low minor allele frequency and absence in the germline DNA of the index patient's mother. The importance of this 'Cancer census gene' in familial MM clustering needs to be evaluated further. Nevertheless, this study strengthens the suspicion that, next to germline BAP1 alterations, other genetic factors might predispose families to the development of MM.}, } @article {pmid29960000, year = {2018}, author = {Kane, AB and Hurt, RH and Gao, H}, title = {The asbestos-carbon nanotube analogy: An update.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {68-80}, doi = {10.1016/j.taap.2018.06.027}, pmid = {29960000}, issn = {1096-0333}, support = {P42 ES013660/ES/NIEHS NIH HHS/United States ; }, abstract = {Nanotechnology is an emerging industry based on commercialization of materials with one or more dimensions of 100 nm or less. Engineered nanomaterials are currently incorporated into thin films, porous materials, liquid suspensions, or filler/matrix nanocomposites with future applications predicted in energy and catalysis, microelectronics, environmental sensing and remediation, and nanomedicine. Carbon nanotubes are one-dimensional fibrous nanomaterials that physically resemble asbestos fibers. Toxicologic studies in rodents demonstrated that some types of carbon nanotubes can induce mesothelioma, and the World Health Organization evaluated long, rigid multiwall carbon nanotubes as possibly carcinogenic for humans in 2014. This review summarizes key physicochemical similarities and differences between asbestos fibers and carbon nanotubes. The "fiber pathogenicity paradigm" has been extended to include carbon nanotubes as well as other high-aspect-ratio fibrous nanomaterials including metallic nanowires. This paradigm identifies width, length, and biopersistence of high-aspect-ratio fibrous nanomaterials as critical determinants of lung disease, including mesothelioma, following inhalation. Based on recent theoretical modeling studies, a fourth factor, mechanical bending stiffness, will be considered as predictive of potential carcinogenicity. Novel three-dimensional lung tissue platforms provide an opportunity for in vitro screening of a wide range of high aspect ratio fibrous nanomaterials for potential lung toxicity prior to commercialization.}, } @article {pmid29959999, year = {2018}, author = {Roggli, VL}, title = {Measuring EMPs in the lung what can be measured in the lung: Asbestiform minerals and cleavage fragments.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {14-17}, doi = {10.1016/j.taap.2018.06.026}, pmid = {29959999}, issn = {1096-0333}, abstract = {Asbestos mineral fibers have been associated with the development of a variety of diseases in humans and experimental animals, including asbestosis, lung cancer, and mesothelioma. Asbestos includes several mineral types divided into two mineral groups, serpentine and amphibole forms. Chrysotile is the serpentine mineral classified as asbestos, whereas the amphiboles include amosite, crocidolite, tremolite, actinolite and anthophyllite. There are a number of mineral fibers that occur with asbestiform morphology and that have been associated with various asbestos-induced diseases. These include the Libby amphiboles (associated with a vermiculite mine northwest of Libby, MT), erionite (in Turkey and North America), fluoro-edenite (in Sicily), and perhaps balangeroite (in Italy). In addition, each of the asbestos minerals occurs in a non-fibrous form, and these may occur as cleavage fragments that satisfy the definition for a fiber, i.e., particles with an aspect ratio of at least 3:1 and roughly parallel sides. Cleavage fragments of non-asbestiform minerals have not been associated with asbestos-induced diseases nor are these minerals regulated by the Occupational Safety and Health Administration. Finally, there are a number of other mineral species which can occur in human lung samples that satisfy the definition for a fiber as given above. These similarly have not been associated with asbestos-induced diseases. All of these various minerals satisfying the definition for a fiber can be referred to as elongated mineral particles (EMP). It is the purpose of this presentation to discuss the role of scanning electron microscopy (SEM) equipped with an energy dispersive x-ray analyzer (EDXA) in the detection and classification of EMP in human lung samples.}, } @article {pmid29949929, year = {2018}, author = {Colin, DJ and Cottet-Dumoulin, D and Faivre, A and Germain, S and Triponez, F and Serre-Beinier, V}, title = {Experimental Model of Human Malignant Mesothelioma in Athymic Mice.}, journal = {International journal of molecular sciences}, volume = {19}, number = {7}, pages = {}, pmid = {29949929}, issn = {1422-0067}, mesh = {Animals ; Body Fluids/metabolism ; Carcinogenesis/pathology ; Cell Count ; Cell Line, Tumor ; Cell Survival ; Epithelial-Mesenchymal Transition/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics/immunology/*pathology ; Macrophages/metabolism ; Mesothelioma/genetics/immunology/*pathology ; Mice, Nude ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is a thoracic aggressive cancer caused by asbestos exposure, which is difficult to diagnose and treat. Here, we characterized an in vivo orthotopic xenograft model consisting of human mesothelioma cells (designed as H2052/484) derived from a pleural NCI-H2052 tumor injected in partially immunodeficient athymic mice. We assessed tumor formation and tumor-dependent patterns of inflammation. H2052/484 cells conserved their mesothelioma phenotype and most characteristics from the parental NCI-H2052 cells. After intra-thoracic injection of H2052/484 cells, thoracic tumors developed in nearly all mice (86%) within 14 days, faster than from parental NCI-H2052 cells. When the mice were euthanized, the pleural lavage fluid was examined for immune cell profiles. The pleural immune cell population increased with tumor development. Interestingly, the proportion of myeloid-derived suppressor cell and macrophage (especially CD206⁺ M2 macrophages) populations increased in the pleural fluid of mice with large mesothelioma development, as previously observed in immunocompetent mice. This reliable orthotopic model recapitulates human mesothelioma and may be used for the study of new treatment strategies.}, } @article {pmid29946373, year = {2018}, author = {Bensaid, D and Blondy, T and Deshayes, S and Dehame, V and Bertrand, P and Grégoire, M and Errami, M and Blanquart, C}, title = {Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma.}, journal = {Clinical epigenetics}, volume = {10}, number = {}, pages = {79}, pmid = {29946373}, issn = {1868-7083}, abstract = {Background: Malignant pleural mesothelioma (MPM) is a very rare and highly aggressive cancer of the pleura associated in most cases with asbestos exposure. To date, no really efficient treatments are available for this pathology. Recently, it has been shown that epigenetic drugs, particularly DNA methylation or histone acetylation modulating agents, could be very efficient in terms of cytotoxicity for several types of cancer cells. We previously showed that a hypomethylating agent (decitabine) and a histone deacetylase inhibitor (HDACi) (valproic acid (VPA)) combination was immunogenic and led to the induction of an anti-tumor immune response in a mice model of mesothelioma. However, VPA is not very specific, is active at millimolar concentrations and is responsible for side effects in clinic. To improve this approach, we studied four newly synthetized HDACi, two hydroxamates (ODH and NODH) and two benzamides (ODB and NODB), in comparison with VPA and SAHA. We evaluated their toxicity on immune cells and their immunogenicity on MPM cells in combination with decitabine.

Results: All the tested HDACi were toxic for immune cells at high concentrations. Combination with decitabine increased toxicity of HDACi only towards T-cell clone. A decrease in the proportion of regulatory T cells and natural killer cells was observed in particular with VPA and ODH. In MPM cells, all HDACi combinations induced NY-ESO-1 cancer testis antigen (CTA) expression and the recognition of the treated cells by a NY-ESO-1 specific T-CD8 clone. However, for MAGE-A1, MAGE-A3 and XAGE-1b mRNA expression, the results obtained depended on the HDACi used and on the CTA studied. Depending on the MPM cell line studied, molecules alone increased moderately PD-L1 expression. When combined, a higher stimulation of this immune check point inhibitor expression was observed. Decitabine-induced anti-viral response seemed to be inhibited in the presence of HDACi.

Conclusions: This work shows that the combination of decitabine and HDACi could be of interest for MPM immunotherapy. However, this combination induced PD-L1 expression which suggests that an association with anti-PD-L1 therapy should be performed to induce an efficient anti-tumor immune response.}, } @article {pmid29932955, year = {2018}, author = {Cox, LAT}, title = {Biological mechanisms of non-linear dose-response for respirable mineral fibers.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {137-144}, doi = {10.1016/j.taap.2018.06.016}, pmid = {29932955}, issn = {1096-0333}, abstract = {Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3. Lysosomal destabilization, efflux of cytosolic potassium ions and influx of calcium ions, signals from damaged mitochondria, both translational and post-translational controls, and prion-like polymerization have increasingly clear roles in regulating NLRP3 activation. As the molecular biology of inflammation-mediated responses to REMP exposure becomes clearer, a practical question looms: What do these mechanisms imply for the shape of the dose-response function relating exposure concentrations and durations for EMPs to risk of pathological responses? Dose-response thresholds or threshold-like nonlinearities can arise from (a) Cooperativity in assembly of supramolecular signaling complexes; (b) Positive feedback loops and bistability in regulatory networks; (c) Overwhelming of defensive barriers maintaining homeostasis; and (d) Damage thresholds, as in lysosome destabilization-induced activation of NLRP3. Each of these mechanisms holds for NLRP3 activation in response to stimuli such as REMP exposures. It is therefore timely to consider the implications of these advances in biological understanding for human health risk assessment with dose-response thresholds.}, } @article {pmid29928505, year = {2018}, author = {Blum, W and Henzi, T and Châtel-Soulet, HE and Pecze, L and Rodriguez, JW and Vrugt, B and Schwaller, B}, title = {Absence of calretinin protein expression in malignant mesotheliomas from asbestos-exposed NF2+/- mice and mouse mesothelioma cell lines from various mouse strains.}, journal = {Biomarker research}, volume = {6}, number = {}, pages = {19}, pmid = {29928505}, issn = {2050-7771}, abstract = {Background: Calretinin is the most widespread positive marker for the immunohistochemical identification of malignant mesothelioma (MM) and was proposed to serve as a blood-based biomarker. Functionally, evidence has accumulated that calretinin might be implicated in MM tumorigenesis. We aimed to identify calretinin (CR; Calb2) in murine MM and reactive mesothelial cells in granuloma from asbestos-exposed NF2+/- mice, a line heterozygous for the tumor suppressor merlin (NF2), used as a mouse MM model. Additionally, we sought to ascertain the presence of calretinin in MM cell lines from other mouse strains. We also intended to investigate the role of calretinin in mesotheliomagenesis by comparing the survival of asbestos-exposed NF2+/- and NF2+/-CR-/- mice.

Methods: NF2+/- and NF2+/-CR-/- mice, both lines on a C57Bl/6J background, were exposed to asbestos following an established protocol. Tumor histology and asbestos-induced mortality were assessed. MM and granuloma from NF2+/- mice were analyzed with immunohistochemical methods for calretinin expression. Levels of Calb2 mRNA and calretinin expression in tumors and MM cell lines of various mouse strains were determined by RT-qPCR and Western blot analysis, respectively.

Results: No expression of calretinin at the protein level was detected, neither in MM from NF2+/- mice, NF2+/- MM-derived cell lines nor immortalized mesothelial cells of mouse origin. At the mRNA level we detected Calb2 expression in MM cell lines from different mouse strains. Survival of NF2+/- and NF2+/-CR-/- mice exposed to asbestos showed no significant difference in a log-rank (Kaplan-Meier) comparison.

Conclusions: The concomitant determination of calretinin and mesothelin blood levels has been proposed for early detection of human MM. Mouse MM models based on asbestos exposure are assumed to yield helpful information on the time course of appearance of mesothelin and calretinin in the blood of asbestos-treated mice determining the earliest time point for interventions. However, the observed absence of calretinin in MM from NF2+/- mice and derived cell lines, as well as from MM cells from Balb/c and C3H mice likely precludes the use of calretinin as a biomarker for mouse MM. The results also indicate possible species differences with respect to an involvement of calretinin in the formation of MM.}, } @article {pmid29916421, year = {2018}, author = {Granieri, A and Borgogno, FV and Franzoi, IG and Gonella, M and Guglielmucci, F}, title = {Development of a Brief Psychoanalytic Group therapy (BPG) and its application in an asbestos national priority contaminated site.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {54}, number = {2}, pages = {160-166}, doi = {10.4415/ANN_18_02_12}, pmid = {29916421}, issn = {2384-8553}, mesh = {Asbestos/*adverse effects ; Environmental Exposure ; Humans ; Lung Neoplasms/*psychology ; Mesothelioma/*psychology ; Occupational Exposure ; Psychoanalytic Therapy/*methods ; Psychotherapy, Group/*methods ; }, abstract = {The aim of the present paper is to describe the development of a Brief Psychoanalytic Group therapy for contaminated sites and its application in the National Priority Contaminated Site of Casale Monferrato. Before presenting the core of the clinical intervention, a brief examination of some clinical features encountered working with malignant mesothelioma patients and their caregivers is offered. These aspects have been pivotal elements in the construction of a psychoanalytically oriented time-limited (i.e., 12 sessions) group therapy. This model of intervention was designed by one of the Authors (AG) and is aimed at reducing the impact of living in a threatening place where both physical well-being and health are put to the test. At a psychological level, in fact, living in contaminated sites arouses death anxieties, which can deeply compromise the quality of time remaining to live together with loved ones after a fatal cancer diagnosis.}, } @article {pmid29916419, year = {2018}, author = {Comba, P and D'Angelo, M and Fazzo, L and Magnani, C and Marinaccio, A and Mirabelli, D and Terracini, B}, title = {Mesothelioma in Italy: the Casale Monferrato model to a national epidemiological surveillance system.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {54}, number = {2}, pages = {139-148}, doi = {10.4415/ANN_18_02_10}, pmid = {29916419}, issn = {2384-8553}, mesh = {Case-Control Studies ; Cohort Studies ; Environmental Exposure ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/epidemiology ; Mesothelioma/*epidemiology ; Occupational Diseases/epidemiology ; Occupational Exposure ; Pleural Neoplasms/epidemiology ; Population Surveillance ; }, abstract = {The purpose of the present paper is to review the origin and development of the epidemiology of mesothelioma in Italy, starting with the detection and investigation of the major outbreak of the disease observed in Casale Monferrato, Piedmont Region. Over the last four decades, mortality among the cohort of ex-Eternit workers has been measured at three points in time. More recently, population based case-control studies in the area of Casale Monferrato have provided new light on the dose-response curve of the relationship between asbestos exposure and mesotheliomas. The publication of the first Casale Monferrato study had a major impact in the country and contributed to the decision of the Italian Parliament to ban the use of asbestos. The experience of Casale Monferrato represents a lesson in several terms, from the epidemiological surveillance to the health care of the victims and the relationship between epidemiologists, victims, their relatives and residents in contaminated areas.}, } @article {pmid29915796, year = {2018}, author = {Losi, L and Botticelli, L and Taccagni, G and Longinotti, E and Lancellotti, C and Scurani, L and Zannoni, GF}, title = {Malignant peritoneal mesothelioma in a woman with bilateral ovarian serous borderline tumour: Potential interactions between the two diseases.}, journal = {Gynecologic oncology reports}, volume = {24}, number = {}, pages = {39-42}, pmid = {29915796}, issn = {2352-5789}, abstract = {We report a case of a 59-year-old woman with peritoneal malignant mesothelioma and no previous exposure to asbestos with a diagnosis of bilateral ovarian serous borderline tumour with peritoneal implants one year before. We discuss the histopathological and immunohistochemical findings to explain possible and potential interactions between the two diseases. To our knowledge, the association of both serous borderline ovarian tumour and malignant peritoneal mesothelioma has never been described before in the same woman and in such a tight temporal connection. This finding raises numerous issues about the origin of the two tumours and further biomolecular studies are needed to fully understand the carcinogenetic process. From a clinical point of view, this case report can be useful to gynaecologists because it leads to recommend a careful examination of the peritoneal cavity during a surgical resection of borderline serous tumour. Moreover, it may suggest performing a close follow-up associated with a careful surveillance of the patient, especially in the case of micropapillary pattern, to oncologists. A complete clinical approach could help to detect sooner possible relapses or other metachronous malignancies.}, } @article {pmid29914087, year = {2018}, author = {Ledda, C and Senia, P and Rapisarda, V}, title = {Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on.}, journal = {Cancers}, volume = {10}, number = {6}, pages = {}, pmid = {29914087}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MM) is a highly aggressive tumor characterized by a poor prognosis. Although its carcinogenesis mechanism has not been strictly understood, about 80% of MM can be attributed to occupational and/or environmental exposure to asbestos fibers. The identification of non-invasive molecular markers for an early diagnosis of MM has been the subject of several studies aimed at diagnosing the disease at an early stage. The most studied biomarker is mesothelin, characterized by a good specificity, but it has low sensitivity, especially for non-epithelioid MM. Other protein markers are Fibulin-3 and osteopontin which have not, however, showed a superior diagnostic performance. Recently, interesting results have been reported for the HMGB1 protein in a small but limited series. An increase in channel proteins involved in water transport, aquaporins, have been identified as positive prognostic factors in MM, high levels of expression of aquaporins in tumor cells predict an increase in survival. MicroRNAs and protein panels are among the new indicators of interest. None of the markers available today are sufficiently reliable to be used in the surveillance of subjects exposed to asbestos or in the early detection of MM. Our aim is to give a detailed account of biomarkers available for MM.}, } @article {pmid29908246, year = {2018}, author = {Utell, MJ and Maxim, LD}, title = {Refractory ceramic fibers: Fiber characteristics, potential health effects and clinical observations.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {113-117}, doi = {10.1016/j.taap.2018.06.011}, pmid = {29908246}, issn = {1096-0333}, abstract = {Refractory ceramic fibers (RCFs) are amorphous fibers that belong to a class of materials termed synthetic vitreous fibers (SVFs), also called man-made mineral fibers (MMMFs), which includes alkaline earth silicate wool, glass wool, rock (stone) wool, slag wool, and special-purpose glass fibers. RCFs are more durable and biopersistent than several other SVFs, although very much less biopersistent than either amosite or crocidolite asbestos. Chronic inhalation studies indicated that rats and hamsters exposed to RCF fibers developed fibrosis and tumors. Epidemiological studies at the University of Cincinnati funded by the Industry indicated that exposed workers; (1) exhibited symptoms (e.g., dyspnea) similar to those reported in other dust-exposed populations, (2) developed statistically, but not clinically, significant deficits in certain measures of pulmonary function in a cross sectional study, but no excessive decline in a longitudinal study, and (3) a dose related increase in pleural plaques, but no interstitial fibrosis. The 2003 mortality study indicated no incremental lung cancer and no cases of mesothelioma. RCF producers developed a comprehensive industry wide product stewardship program (PSP) beginning in the late 1980s. In conjunction with the PSP, there has been a progressive decrease in the TWA concentration of fibers by manufacturers and end-users. The research program has successfully produced more soluble fibers and undertaken efforts to develop larger diameter fibers. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer.}, } @article {pmid29895204, year = {2018}, author = {Tweedale, G and Castleman, B}, title = {Jock McCulloch (1945-2018): A Tribute.}, journal = {International journal of health services : planning, administration, evaluation}, volume = {48}, number = {3}, pages = {586-591}, doi = {10.1177/0020731418780607}, pmid = {29895204}, issn = {1541-4469}, mesh = {Agent Orange/history/toxicity ; Asbestosis/history ; Australia ; History, 20th Century ; History, 21st Century ; Humans ; Occupational Diseases/history ; Occupational Health/*history ; South Africa ; }, abstract = {Jock William McCulloch, who died at Melbourne, Australia, in January 2018, was one of the foremost historians of occupational health of his generation. This tribute reviews his career and oeuvre, which was tragically ended by his death from mesothelioma.}, } @article {pmid29869702, year = {2018}, author = {Barbiero, F and Zanin, T and Pisa, FE and Casetta, A and Rosolen, V and Giangreco, M and Negro, C and Bovenzi, M and Barbone, F}, title = {Cancer incidence in a cohort of asbestos-exposed workers undergoing health surveillance.}, journal = {International archives of occupational and environmental health}, volume = {91}, number = {7}, pages = {831-841}, pmid = {29869702}, issn = {1432-1246}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Cohort Studies ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Neoplasms/epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Population Surveillance ; }, abstract = {OBJECTIVES: To compare a local cohort of 2488 men occupationally exposed to asbestos and enrolled in a public health surveillance program with the 1995-2009 cancer incidence of the general population of Friuli Venezia Giulia (FVG) region, Northeast Italy, we conducted a historical cohort study.

METHODS: Standardized incidence ratios (SIRs), with 95% confidence interval (95% CI), for specific cancer sites were estimated in the cohort and in subgroups of workers employed in shipbuilding between 1974 and 1994. For internal comparisons, we calculated incidence rate ratios (IRRs) for all cancers, lung cancer and mesothelioma, by level of exposure to asbestos and sector of employment adjusted for smoking habits and age at start of follow-up.

RESULTS: Among cohort members the SIR was 8.82 (95% CI 5.95-12.61) for mesothelioma and 1.61 (95% CI 1.26-2.04) for lung cancer. In subgroup analyses, the SIR for lung cancer in subjects hired in shipbuilding between 1974 and 1984 was 2.09 (95% CI 1.32-3.13). In the overall cohort, a borderline increased incidence was also found for stomach cancer (SIR = 1.53 95% CI 0.96-2.31). Internal comparisons within the cohort show that among men with high asbestos exposure level the relative risk was almost threefold for lung cancer (IRR = 2.94 95% CI 1.01-8.57).

CONCLUSIONS: This cohort experienced an excess in the incidence of both mesothelioma and lung cancer, showing increasing incidence rates at higher level of asbestos exposure. For lung cancer, the relative incidence was highest among workers hired in shipbuilding between 1974 and 1984.}, } @article {pmid29853412, year = {2018}, author = {Fujimoto, N and Aoe, K and Kozuki, T and Oze, I and Kato, K and Kishimoto, T and Hotta, K}, title = {A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol.}, journal = {Clinical lung cancer}, volume = {19}, number = {5}, pages = {e705-e707}, doi = {10.1016/j.cllc.2018.05.001}, pmid = {29853412}, issn = {1938-0690}, abstract = {BACKGROUND: The purpose of this study is to assess the efficacy and safety of combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma (MPM).

PATIENTS AND METHODS: Patients with untreated, advanced, or metastatic MPM who meet the inclusion and exclusion criteria will be included. A total of 18 patients will be enrolled from 4 Japanese institutions within 1 year. Combination chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and nivolumab (360 mg/person) is administered every 3 weeks for a total of 4 to 6 cycles. Then, maintenance therapy with nivolumab will be administered until disease progression, unacceptable toxicities, or the patient's condition meets the withdrawal criteria. The primary end point is the centrally reviewed overall response rate. The secondary end points include the disease control rate, overall survival, progression-free survival, and adverse events.

CONCLUSION: This phase II trial evaluating first-line combination chemotherapy for unresectable MPM commenced in January 2018. This is the first prospective trial to evaluate the effect of an anti-programmed death-1 antibody combined with cisplatin and pemetrexed for unresectable MPM.}, } @article {pmid29850181, year = {2018}, author = {Ahmadzada, T and Reid, G and Kao, S}, title = {Biomarkers in malignant pleural mesothelioma: current status and future directions.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 9}, pages = {S1003-S1007}, pmid = {29850181}, issn = {2072-1439}, } @article {pmid29845703, year = {2018}, author = {Saji, T and Nishita, M and Ogawa, H and Doi, T and Sakai, Y and Maniwa, Y and Minami, Y}, title = {Critical role of the Ror-family of receptor tyrosine kinases in invasion and proliferation of malignant pleural mesothelioma cells.}, journal = {Genes to cells : devoted to molecular & cellular mechanisms}, volume = {23}, number = {7}, pages = {606-613}, doi = {10.1111/gtc.12599}, pmid = {29845703}, issn = {1365-2443}, mesh = {Cell Line, Tumor ; Cell Proliferation ; Humans ; Lung Neoplasms/genetics/*metabolism ; Mesothelioma/genetics/*metabolism ; Receptor Tyrosine Kinase-like Orphan Receptors/genetics/*metabolism/physiology ; Signal Transduction ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis and closely related to exposure to asbestos. MPM is a heterogeneous tumor with three main histological subtypes, epithelioid, sarcomatoid, and biphasic types, among which sarcomatoid type shows the poorest prognosis. The Ror-family of receptor tyrosine kinases, Ror1 and Ror2, is expressed in various types of tumor cells at higher levels and affects their aggressiveness. However, it is currently unknown whether they are expressed in and involved in aggressiveness of MPM. Here, we show that Ror1 and Ror2 are expressed in clinical specimens and cell lines of MPM with different histological features. Studies using MPM cell lines indicate that expression of Ror2 is associated tightly with high invasiveness of MPM cells, whereas Ror1 can contribute to their invasion in the absence of Ror2. However, both Ror1 and Ror2 promote proliferation of MPM cells. We also show that promoted invasion and proliferation of MPM cells by Ror signaling can be mediated by the Rho-family of small GTPases, Rac1, and Cdc42. These findings elucidate the critical role of Ror signaling in promoting invasion and proliferation of MPM cells.}, } @article {pmid29845408, year = {2018}, author = {Tartarone, A and Lerose, R and Aieta, M}, title = {Is there a role for immunotherapy in malignant pleural mesothelioma?.}, journal = {Medical oncology (Northwood, London, England)}, volume = {35}, number = {7}, pages = {98}, pmid = {29845408}, issn = {1559-131X}, mesh = {Antineoplastic Agents/*therapeutic use ; CTLA-4 Antigen/antagonists & inhibitors ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; *Immunotherapy ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; Pleural Neoplasms/*therapy ; Programmed Cell Death 1 Ligand 2 Protein/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; }, abstract = {Malignant pleural mesothelioma (MPM) is a very aggressive malignancy, mainly caused by asbestos exposure. Patients with MPM have a poor prognosis that remained substantially unchanged in the last few years and limited effective therapeutic options with no recognized second or further-line therapy. In this context, also in view of the positive results observed in other tumor types, immunotherapy could play a relevant role. This review focuses on the most promising immunotherapies being investigated in MPM.}, } @article {pmid29794065, year = {2018}, author = {Butnor, KJ and Rueckert, J and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Malignant peritoneal mesothelioma in patients with endometriosis.}, journal = {Journal of clinical pathology}, volume = {71}, number = {11}, pages = {971-974}, doi = {10.1136/jclinpath-2018-205099}, pmid = {29794065}, issn = {1472-4146}, mesh = {Adult ; Asbestos/adverse effects ; Biomarkers, Tumor/analysis ; Biopsy ; Endometriosis/etiology/*pathology ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/chemistry/etiology/*pathology ; Mesothelioma/chemistry/etiology/*pathology ; Middle Aged ; Peritoneal Neoplasms/chemistry/etiology/*pathology ; Peritoneum/chemistry/*pathology ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers ; }, abstract = {AIMS: Florid mesothelial hyperplasia is known to result from endometriosis. Well-differentiated papillary mesothelioma and multiloculated peritoneal inclusion cysts have also been described in women with endometriosis. To our knowledge, peritoneal diffuse malignant mesothelioma (MM) arising in the setting of endometriosis has not been reported. The purpose of this study is to report the clinicopathological characteristics of women with MM and endometriosis.

METHODS: The surgical pathology files of a tertiary academic medical centre and the consultation files of one of the study authors were reviewed for cases of MM in females with and without endometriosis.

RESULTS: Six women with MM and endometriosis ranging in age from 29 to 55 years (median=45 years) were identified. All had peritoneal MM and endometriosis involving the peritoneum and/or adnexa. Five had epithelioid MM and one had biphasic MM. Two had paraoccupational exposure to asbestos. The median age of women with MM and endometriosis (44.5 years) was significantly less than the median age of cases without endometriosis (58.0 years) (p value=0.01).

CONCLUSIONS: To our knowledge, this is the first report of MM in women with endometriosis. Interestingly, MM in the setting of endometriosis has only been observed in the peritoneum and not in other serosal cavities. The findings in the present study suggest that chronic serosal inflammation secondary to endometriosis may be an inducing factor in rare cases of MM of the peritoneum.}, } @article {pmid29792222, year = {2018}, author = {Kerger, BD}, title = {Longevity and pleural mesothelioma: age-period-cohort analysis of incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, 1973-2013.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {337}, pmid = {29792222}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Aging ; Child ; Child, Preschool ; Cohort Studies ; Female ; Humans ; Infant ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Registries/*statistics & numerical data ; United States/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: This study investigates the hypothesis that an increasing fraction of incident pleural mesothelioma (PM) in the US population may be related to longevity, i.e., to expansion of the population over age 75 years with an age-related elevation in risk. An age-period-cohort analysis of the SEER 9 cancer registries (1973-2013) was conducted using 5-year intervals of age, calendar period, and birth cohort after stratification into four gender-age groups (male and female; 0-74 and 75+ years).

RESULTS: Gender-specific time trends in age-adjusted PM incidence by age groups were observed. After adjusting for cohort effects, males in the 0-74-year age group experienced rapidly declining PM incidence rates following the observed peak in 1978-1982, whereas continuously increasing incidence rates were observed among older males. A significant cohort effect was also observed among males in both age groups, with peak incidence rates in the 1926-1930/1928-1932 birth cohorts and thereafter. The distinct period and cohort effects among males age 0-74 years may be driven by declining age-adjusted PM incidence rates corresponding to the decline in occupational asbestos exposures post-World War II, whereas the increasing time trend seen in both genders at age 75+ may reflect an increasing proportion due to longevity-related factors.}, } @article {pmid29779004, year = {2018}, author = {Ugelvig Petersen, K and Volk, J and Kaerlev, L and Lyngbeck Hansen, H and Hansen, J}, title = {Cancer incidence among merchant seafarers: an extended follow-up of a Danish cohort.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {8}, pages = {582-585}, doi = {10.1136/oemed-2018-105037}, pmid = {29779004}, issn = {1470-7926}, abstract = {OBJECTIVES: While maritime safety generally has improved dramatically over the last century, modern seafarers are still faced with numerous occupational hazards potentially affecting their risk of chronic diseases such as cancer. The aim of this study is to offer updated information on the incidence of specific cancers among both male and female seafarers.

METHODS: Using records from the Danish Seafarer Registry, all seafarers employed on Danish ships during 1986-1999 were identified, resulting in a cohort of 33 084 men and 11 209 women. Information on vital status and cancer was linked to each member of the cohort from the Danish Civil Registration System and the Danish Cancer Registry using the unique Danish personal identification number. SIRs were estimated for specific cancers using national rates.

RESULTS: The overall incidence of cancer was increased for both male and female seafarers (SIR 1.19, 95% CI 1.15 to 1.23, and SIR 1.14, 95% CI 1.07 to 1.22) compared with the general population. This excess was primarily driven by increases in gastrointestinal, respiratory and genitourinary cancers. In addition, male seafarers working in areas with asbestos exposure showed significantly increased risk of mesothelioma. Finally, the male seafarers had an increased risk of lip cancer.

CONCLUSIONS: The majority of cancers among seafarers continue to be lifestyle-related. However, occupational exposure to asbestos and ultraviolet radiation seems to affect the cancer pattern among the male seafarers as well.}, } @article {pmid29774711, year = {2018}, author = {Caputo, A and De Santis, M and Manno, V and Cauzillo, G and Bruni, BM and Palumbo, L and Conti, S and Comba, P}, title = {[Health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy)].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {2}, pages = {142-150}, doi = {10.19191/EP18.2.P142.043}, pmid = {29774711}, issn = {1120-9763}, abstract = {OBJECTIVES: to estimate the health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy).

DESIGN: geographic mortality, hospitalization, and incidence study. Setting and participant s: population resident in 12 Municipalities of Mount Pollino area with naturally occurring asbestos fibres.

MAIN OUTCOME MEASURES: standardized mortality ratio (SMR) and standardized hospitalization rate (SHR) for asbestos-related diseases; standardized incidence ratio (SIR) for mesotheliomas. Result s: in the area of Mount Pollino, where asbestos fibres naturally occur, especially in the sub-area in which fibres are close to dwellings and settlements, it was observed: • a significant excess of mesothelioma incidence (SIR: 208; CI95% 111-355; 13 observed); • a non-significant excess of hospitalization for malignant pleural neoplasms (SHR: 176; CI95% 93-335; 9 observed); • a significant excess for mortality and hospitalization for pneumoconiosis (SMR: 534; CI95% 345-824; 20 observed - SHR: 245; CI95% 149-405; 15 observed); • a significant excess for hospitalization (SHR: 852; CI95% 290-2,506; 3 observed) for asbestosis.

CONCLUSION: it is necessary to continue environmental monitoring and environmental remediation in the area with higher asbestos exposure. It is suggested to implement a permanent process of epidemiological surveillance in this same area. A communication plan with local administrators, general practitioners, school teachers, media, and the resident population at large should be realized.}, } @article {pmid29772681, year = {2018}, author = {Furuya, S and Chimed-Ochir, O and Takahashi, K and David, A and Takala, J}, title = {Global Asbestos Disaster.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {5}, pages = {}, pmid = {29772681}, issn = {1660-4601}, mesh = {Asbestosis/diagnosis/*epidemiology/etiology/prevention & control ; Cost of Illness ; Global Health/*statistics & numerical data ; Humans ; Mesothelioma/diagnosis/*epidemiology/etiology/prevention & control ; }, abstract = {Introduction: Asbestos has been used for thousands of years but only at a large industrial scale for about 100⁻150 years. The first identified disease was asbestosis, a type of incurable pneumoconiosis caused by asbestos dust and fibres. The latest estimate of global number of asbestosis deaths from the Global Burden of Disease estimate 2016 is 3495. Asbestos-caused cancer was identified in the late 1930's but despite today's overwhelming evidence of the strong carcinogenicity of all asbestos types, including chrysotile, it is still widely used globally. Various estimates have been made over time including those of World Health Organization and International Labour Organization: 107,000⁻112,000 deaths. Present estimates are much higher. Objective: This article summarizes the special edition of this Journal related to asbestos and key aspects of the past and present of the asbestos problem globally. The objective is to collect and provide the latest evidence of the magnitude of asbestos-related diseases and to provide the present best data for revitalizing the International Labor Organization/World Health Organization Joint Program on Asbestos-related Diseases. Methods: Documentation on asbestos-related diseases, their recognition, reporting, compensation and prevention efforts were examined, in particular from the regulatory and prevention point of view. Estimated global numbers of incidence and mortality of asbestos-related diseases were examined. Results: Asbestos causes an estimated 255,000 deaths (243,223⁻260,029) annually according to latest knowledge, of which work-related exposures are responsible for 233,000 deaths (222,322⁻242,802). In the European Union, United States of America and in other high income economies (World Health Organization regional classification) the direct costs for sickness, early retirement and death, including production losses, have been estimated to be very high; in the Western European countries and European Union, and equivalent of 0.70% of the Gross Domestic Product or 114 × 10⁸ United States Dollars. Intangible costs could be much higher. When applying the Value of Statistical Life of 4 million EUR per cancer death used by the European Commission, we arrived at 410 × 10⁸ United States Dollars loss related to occupational cancer and 340 × 10⁸ related to asbestos exposure at work, while the human suffering and loss of life is impossible to quantify. The numbers and costs are increasing practically in every country and region in the world. Asbestos has been banned in 55 countries but is used widely today; some 2,030,000 tons consumed annually according to the latest available consumption data. Every 20 tons of asbestos produced and consumed kills a person somewhere in the world. Buying 1 kg of asbestos powder, e.g., in Asia, costs 0.38 United States Dollars, and 20 tons would cost in such retail market 7600 United States Dollars. Conclusions: Present efforts to eliminate this man-made problem, in fact an epidemiological disaster, and preventing exposures leading to it are insufficient in most countries in the world. Applying programs and policies, such as those for the elimination of all kind of asbestos use-that is banning of new asbestos use and tight control and management of existing structures containing asbestos-need revision and resources. The International Labor Organization/World Health Organization Joint Program for the Elimination of Asbestos-Related Diseases needs to be revitalized. Exposure limits do not protect properly against cancer but for asbestos removal and equivalent exposure elimination work, we propose a limit value of 1000 fibres/m³.}, } @article {pmid29753121, year = {2018}, author = {Armato, SG and Nowak, AK}, title = {Revised Modified Response Evaluation Criteria in Solid Tumors for Assessment of Response in Malignant Pleural Mesothelioma (Version 1.1).}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {7}, pages = {1012-1021}, doi = {10.1016/j.jtho.2018.04.034}, pmid = {29753121}, issn = {1556-1380}, abstract = {INTRODUCTION: Malignant pleural mesothelioma poses unique difficulties in tumor measurement and response assessment; however, robust and reproducible assessment of response is critically important in the conduct, interpretation, and reporting of clinical trials.

METHODS: The current de facto standard for the assessment of mesothelioma tumor response, "modified RECIST" (Response Evaluation Criteria in Solid Tumors), was published in 2004 as a research paper. Practical application of the modified RECIST guidelines has suffered from varied interpretations, resulting in inaccuracies and inconsistencies in tumor response assessment across and within mesothelioma clinical trials. The presented "modified RECIST 1.1 for mesothelioma" response assessment guidelines provide a much-needed update that incorporates recommendations from RECIST 1.1 and approaches to other practical issues, including: (1) definition of minimally measurable disease; (2) definition of measurable lesions; (3) acceptable measurement location; (4) non-pleural disease considerations; (5) characterization of non-measurable pleural disease; (6) assessment of pathological lymph nodes; (7) establishing progressive disease; and (8) accommodations for bilateral pleural disease.

RESULTS: These modified RECIST 1.1 guidelines for mesothelioma tumor response collate and apply research published since the development of modified RECIST, align modified RECIST with RECIST 1.1, address those aspects of tumor measurement that were neglected or not well characterized in the modified RECIST paper, and clarify ambiguous or difficult measurement issues that have been highlighted through the subsequent decade of clinical trials research.

CONCLUSION: Adoption of the modified RECIST 1.1 guidelines for mesothelioma is recommended to harmonize the application of tumor measurement and response assessment across the next generation of clinical trials in this disease.}, } @article {pmid29742950, year = {2018}, author = {Arnoldussen, YJ and Skaug, V and Aleksandersen, M and Ropstad, E and Anmarkrud, KH and Einarsdottir, E and Chin-Lin, F and Granum Bjørklund, C and Kasem, M and Eilertsen, E and Apte, RN and Zienolddiny, S}, title = {Inflammation in the pleural cavity following injection of multi-walled carbon nanotubes is dependent on their characteristics and the presence of IL-1 genes.}, journal = {Nanotoxicology}, volume = {12}, number = {6}, pages = {522-538}, doi = {10.1080/17435390.2018.1465139}, pmid = {29742950}, issn = {1743-5404}, mesh = {Animals ; Asbestos, Crocidolite/toxicity ; Fibrosis ; Inflammation/*chemically induced ; Interleukin-1/*genetics ; Mice ; Mice, Inbred C57BL ; Nanotubes, Carbon/*toxicity ; Pleural Cavity/*drug effects/pathology ; }, abstract = {Upon inhalation, multi-walled carbon nanotubes (MWCNTs) may reach the subpleura and pleural spaces, and induce pleural inflammation and/or mesothelioma in humans. However, the mechanisms of MWCNT-induced pathology after direct intrapleural injections are still only partly elucidated. In particular, a role of the proinflammatory interleukin-1 (IL-1) cytokines in pleural inflammation has so far not been published. We examined the MWCNT-induced pleural inflammation, gene expression abnormalities, and the modifying role of IL-1α and β cytokines following intrapleural injection of two types of MWCNTs (CNT-1 and CNT-2) compared with crocidolite asbestos in IL-1 wild-type (WT) and IL-1α/β KO (IL1-KO) mice. Histopathological examination of the pleura 28 days post-exposure revealed mesothelial cell hyperplasia, leukocyte infiltration, and fibrosis occurring in the CNT-1 (Mitsui-7)-exposed group. The pleura of these mice also showed the greatest changes in mRNA and miRNA expression levels, closely followed by CNT-2. In addition, the CNT-1-exposed group also presented the greatest infiltrations of leukocytes and proliferation of fibrous tissue. WT mice were more prone to development of sustained inflammation and fibrosis than IL1-KO mice. Prominent differences in genetic and epigenetic changes were also observed between the two genotypes. In conclusion, the fibrotic response to MWCNTs in the pleura depends on the particles' physico-chemical properties and on the presence or absence of the IL-1 genes. Furthermore, we found that CNT-1 was the most potent inducer of inflammatory responses, followed by CNT-2 and crocidolite asbestos.}, } @article {pmid29738812, year = {2018}, author = {Asgharian, B and Owen, TP and Kuempel, ED and Jarabek, AM}, title = {Dosimetry of inhaled elongate mineral particles in the respiratory tract: The impact of shape factor.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {27-35}, doi = {10.1016/j.taap.2018.05.001}, pmid = {29738812}, issn = {1096-0333}, support = {CC999999//Intramural CDC HHS/United States ; }, abstract = {Inhalation exposure to some types of fibers (e.g., asbestos) is well known to be associated with respiratory diseases and conditions such as pleural plaques, fibrosis, asbestosis, lung cancer, and mesothelioma. In recent years, attention has expanded to other types of elongate mineral particles (EMPs) that may share similar geometry with asbestos fibers but which may differ in mineralogy. Inhalability, dimensions and orientation, and density are major determinants of the aerodynamic behavior for fibers and other EMPs; and the resultant internal dose is recognized as being the critical link between exposure and pathogenesis. Insufficient data are available to fully understand the role of specific physicochemical properties on the potential toxicity across various types of fiber materials. While additional information is required to assess the potential health hazards of EMPs, dosimetry models are currently available to estimate the initially deposited internal dose, which is an essential step in linking airborne exposures to potential health risks. Based on dosimetry model simulations, the inhalability and internal dose of EMPs were found to be greater than that of spherical particles having the same mass or volume. However, the complexity of the dependence of internal dose on EMPs dimensions prevented a straightforward formulation of the deposition-dimension (length or diameter) relationship. Because health outcome is generally related to internal dose, consideration of the factors that influence internal dose is important in assessing the potential health hazards of airborne EMPs.}, } @article {pmid29737238, year = {2017}, author = {Metintas, S and Ak, G and Bogar, F and Yilmaz, S and Metintas, M}, title = {Asbestos knowledge and awareness level in central part of Anatolia.}, journal = {International journal of occupational and environmental health}, volume = {23}, number = {3}, pages = {243-249}, pmid = {29737238}, issn = {2049-3967}, mesh = {Adult ; Aged ; *Asbestos ; *Environmental Exposure ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; *Rural Population/statistics & numerical data ; Turkey ; Young Adult ; }, abstract = {Background Asbestos-contaminated soil has been used by people for many years in the rural part of Anatolia. However, there is no program to control usage of asbestos in this region. Objective To determine the knowledge and awareness level about asbestos in a region where asbestos-related diseases are endemic due to environmental exposure to asbestos in the rural setting. Methods This study included 760 participants, recruited using non-probability sampling, who were classified into four groups according to residence and asbestos exposure type (urban, rural; asbestos-exposed, asbestos-unexposed). Asbestos knowledge and awareness was measured via the Asbestos Knowledge and Awareness Questionnaire (AKAQ). The cut-off value of questionnaire was determined by the K-means cluster analysis for sufficient and insufficient knowledge and awareness level. A multiple logistic regression analysis was performed to determine independent factors affecting sufficient knowledge and awareness of participants about asbestos. Results The median and mean score of the AKAQ in study group were 30 and 33.9, respectively. The urban asbestos-exposed group had a higher score than the urban asbestos-unexposed and both rural groups (p < 0.001). Factors affecting asbestos knowledge and awareness were education status (p = 0.035), asbestos exposure (p = 0.003) and living in the rural area (p = 0.005). Sufficient knowledge and awareness (score > 45) was higher among participants who had graduated from university and had asbestos exposure. Insufficient knowledge and awareness level was higher among participants living in rural areas. Conclusion In this region of Anatolia, knowledge and awareness level of asbestos was low among people at risk for environmental asbestos exposure. People should be aware of asbestos and its hazards by a well-designed training program and be monitored for asbestos-related diseases.}, } @article {pmid29733442, year = {2018}, author = {Baur, X}, title = {Review on the adverse health effects of asbestiform antigorite, a non-regulated asbestiform serpentine mineral.}, journal = {American journal of industrial medicine}, volume = {61}, number = {7}, pages = {625-630}, doi = {10.1002/ajim.22857}, pmid = {29733442}, issn = {1097-0274}, abstract = {BACKGROUND: Although antigorite is generally described as platy, its fibrous (asbestiform) variant is present widespread in serpentinite rocks. In addition to its primarily fibrous occurrence, asbestiform antigorite may also be formed from serpentinite with massive appearance during tunneling and mining. It is not of commercial interest, but exposure may occur in the certain environments.

METHODS AND RESULTS: Detailed studies of the structural features of this antigorite type revealed characteristics closely related to those of chrysotile. Therefore, it is plausible that this serpentine mineral may present a similar health risk for exposed subjects. This is in agreement with results from clinical and animal studies, as well as in vitro experiments showing the cytotoxic, fibrogenic, and carcinogenic potential of antigorite, similar to that of chrysotile and amphibole asbestos.

CONCLUSIONS: Current evidence supports a need for an update to existing regulations to include unregulated asbestiform antigorite, similar to regulatory measures taken for asbestos.}, } @article {pmid29723551, year = {2018}, author = {Garcia, E and Newfang, D and Coyle, JP and Blake, CL and Spencer, JW and Burrelli, LG and Johnson, GT and Harbison, RD}, title = {Evaluation of airborne asbestos exposure from routine handling of asbestos-containing wire gauze pads in the research laboratory.}, journal = {Regulatory toxicology and pharmacology : RTP}, volume = {96}, number = {}, pages = {135-141}, doi = {10.1016/j.yrtph.2018.04.020}, pmid = {29723551}, issn = {1096-0295}, mesh = {*Absorbent Pads ; Air Pollution, Indoor/*analysis ; Asbestos/administration & dosage/*analysis ; *Environmental Monitoring ; Humans ; *Laboratories ; *Research ; }, abstract = {Three independently conducted asbestos exposure evaluations were conducted using wire gauze pads similar to standard practice in the laboratory setting. All testing occurred in a controlled atmosphere inside an enclosed chamber simulating a laboratory setting. Separate teams consisting of a laboratory technician, or technician and assistant simulated common tasks involving wire gauze pads, including heating and direct wire gauze manipulation. Area and personal air samples were collected and evaluated for asbestos consistent with the National Institute of Occupational Safety Health method 7400 and 7402, and the Asbestos Hazard Emergency Response Act (AHERA) method. Bulk gauze pad samples were analyzed by Polarized Light Microscopy and Transmission Electron Microscopy to determine asbestos content. Among air samples, chrysotile asbestos was the only fiber found in the first and third experiments, and tremolite asbestos for the second experiment. None of the air samples contained asbestos in concentrations above the current permissible regulatory levels promulgated by OSHA. These findings indicate that the level of asbestos exposure when working with wire gauze pads in the laboratory setting is much lower than levels associated with asbestosis or asbestos-related lung cancer and mesothelioma.}, } @article {pmid29719805, year = {2018}, author = {Sattar, N and Durrance, R and Khan, A and Patel, N and Mora, M and Shalonov, A}, title = {Malignant mesothelioma presenting as recurrent hydro-pneumothorax: An atypical case presentation and literature review.}, journal = {Respiratory medicine case reports}, volume = {23}, number = {}, pages = {152-155}, pmid = {29719805}, issn = {2213-0071}, abstract = {Malignant Pleural Mesothelioma (MPM) is a rare pleural malignancy, with a vague presentation complicated by a decades-long latency period between environmental exposure and clinical manifestations. Spontaneous hydro-pneumothorax is a rare presentation of MPM, most often requiring invasive tissue biopsy to confirm the etiologic diagnosis. We present the case of 79-year-old male smoker with no documented history of asbestos exposure, who was found to have MPM after presenting with dyspnea and subsequently found to have recurrent hydro-pneumothorax. On Literature review of the limited documented cases of MPM with hydro-pneumothorax, we found an exclusively male population with a significant smoking history, a marked right sided pathology predominance, and a generally poor prognosis. While this corresponds with the examined case, and suggests that the presence of hydro-pneumothorax implies a high-grade tumor and significant tissue invasion, and therefore poor prognosis similar to that of stage 4 disease, it differs from more generalized case reviews of MPM, most importantly in their anatomical descriptions, prognostic indicators, and epidemiologic tendencies.}, } @article {pmid29714657, year = {2018}, author = {Barbieri, PG and Mirabelli, D and Magnani, C and Brollo, A}, title = {On the diagnosis of malignant pleural mesothelioma: A necropsy-based study of 171 cases (1997-2016).}, journal = {Tumori}, volume = {}, number = {}, pages = {300891618765538}, doi = {10.1177/0300891618765538}, pmid = {29714657}, issn = {2038-2529}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) diagnosis is known to be difficult. We report on the diagnostic elements available in life in an MPM necropsy case series and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices.

METHODS: We reviewed pathologic and clinical records of an unselected series of autopsies (1977-2016) in patients with MPM employed in the Monfalcone shipyards or living with shipyard workers. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings, with and without immunophenotyping.

RESULTS: Data on 171 cases were available: for 169, autopsy confirmed the MPM diagnosis. In life, 119 cases had histologic confirmation of diagnosis, whereas 7 were negative; all cases without immunophenotypization were autoptic MPMs. Cytology alone had been positive in 18 autoptic MPM cases, negative in 14. Radiologic imaging alone had been positive in another 16, negative in 11. In the 2 cases not confirmed at autopsy, MPM had been suspected by chest computed tomography only. Bilateral pleural plaques were found in 144 and histologic evidence of asbestosis in 62 cases.

CONCLUSIONS: Autopsies confirmed 169/171 cases, including cases that would not be considered as certain based on diagnosis in life. Radiologic imaging, cytologic examination of pleural effusions, or both combined had low sensitivity but high positive predictive value: when they are positive, proceeding to thoracoscopy should be justified. MPM has been correctly diagnosed even without immunohistochemistry. The prevalence of pleural plaques and asbestosis was high due to severity of asbestos exposures in these cases.}, } @article {pmid29709339, year = {2019}, author = {Wu, TH and Lee, LJ and Yuan, CT and Chen, TW and Yang, JC}, title = {Prognostic factors and treatment outcomes of malignant pleural mesothelioma in Eastern Asian patients - A Taiwanese study.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {1 Pt 2}, pages = {230-236}, doi = {10.1016/j.jfma.2018.04.001}, pmid = {29709339}, issn = {0929-6646}, abstract = {BACKGROUND/PURPOSE: There are scarce reports on the prognostic factors and treatment outcomes of patients with malignant pleural mesothelioma (MPM) in Asia. This study aimed to address these matters in a real-world setting.

METHODS: Medical records of patients with histologically proven MPM diagnosed between 1977 and 2016 at the National Taiwan University Hospital were reviewed. Variables including age, gender, performance status, asbestos exposure, smoking history, histology subtype, staging, and treatment received were recorded. All patients were followed until death or March 1st, 2017. Survival and prognostic factors were analyzed by the Kaplan-Meir method and the Cox proportional hazard model.

RESULTS: A total of 93 patients was identified, including 65 men and 28 women. An increasing trend of MPM cases diagnosed was observed in the past 40 years. Stage I/II disease (HR 0.24, 95% CI 0.13-0.46) and epithelioid histology (HR 0.42, 95% CI 0.23-0.75) were associated with favorable prognosis, whereas age ≥70 years (HR 2.66, 95% CI 1.36-5.22) and ECOG ≥2 (HR 5.03, 95% CI 2.69-9.4) were poor prognostic factors. After adjustment for prognostic factors, surgery in stage I-III MPM (HR 0.36, 95% CI 0.15-0.83) and systemic therapy in stage III/IV disease (HR 0.42, 95% CI 0.19-0.94) conferred a survival benefit.

CONCLUSION: This is one of the largest case series of MPM reported in Asia outside of Japan. Prognostic factors in the study population included age, performance status, stage, and histology subtype. Surgery in potentially resectable disease and systemic therapy in advanced MPM confer a survival benefit in Asian patients.}, } @article {pmid29701625, year = {2018}, author = {Barbiero, F and Zanin, T and Pisa, FE and Casetta, A and Rosolen, V and Giangreco, M and Negro, C and Bovenzi, M and Barbone, F}, title = {Mortality in a cohort of asbestos-exposed workers undergoing health surveillance.}, journal = {La Medicina del lavoro}, volume = {109}, number = {2}, pages = {83-86}, doi = {10.23749/mdl.v109i2.5865}, pmid = {29701625}, issn = {0025-7818}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/complications/*mortality ; Carcinogens ; Child ; Child, Preschool ; Cohort Studies ; Construction Materials/adverse effects ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Italy/epidemiology ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/etiology/*mortality ; Population Surveillance ; }, abstract = {BACKGROUND: The coastal area of Friuli Venezia Giulia (FVG) region, north-eastern Italy, was characterized by work activities in which asbestos was used until the early 1990s, particularly in shipbuilding. A public health surveillance program (PHSP) for asbestos-exposed workers was established, although limited evidence exists about the efficacy of such programs in reducing disease occurrence and mortality.

OBJECTIVES: To compare mortality in a cohort of 2,488 men occupationally exposed to asbestos, enrolled in a PHSP in FVG between the early 1990s and 2008, with that of the general population of FVG and Italy.

METHODS: Standardized Mortality Ratios (SMR), with 95% Confidence Interval (95% CI), for all causes, all cancers, lung (LC) and pleural cancer (PC) were estimated in the cohort and in subgroups of workers with the first hire in shipbuilding that caused asbestos exposure (<1974, 1974-1984, 1985-1994).

RESULTS: A strong excess in mortality for PC with reference to FVG (SMR=6.87, 95% CI 4.45-10.17) and Italian population (SMR=13.95, 95% CI 9.02-20.64) was observed. For LC, the FVG-based SMR was 1.49 (95% CI 1.17-1.89) and the Italy-based 1.43 (95% CI 1.12-1.81). Mortality among workers with the first hire in shipbuilding before 1974 was high for PC (FVG-based SMR=8.98, 95% CI 5.56-13.75; Italy-based SMR=18.41, 95% CI 11.40-28.17) and for LC (FVG-based SMR =1.60, 95% CI 1.18-2.11; Italy-based SMR=1.54, 95% CI 1.14-2.03). Further, for LC between 1974 and 1984, the FVG-based SMR was 2.45 (95% CI 1.06-4.82), and the Italy-based SMR was 2.33 (95% CI 1.01-4.60).

CONCLUSIONS: This cohort experienced an excess mortality for pleural and lung cancer, compared with regional and national populations. For lung cancer, the excess was stronger in workers with the first hire in shipbuilding before 1985, suggesting a key role of asbestos exposure.}, } @article {pmid29699512, year = {2018}, author = {Blum, W and Pecze, L and Rodriguez, JW and Steinauer, M and Schwaller, B}, title = {Regulation of calretinin in malignant mesothelioma is mediated by septin 7 binding to the CALB2 promoter.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {475}, pmid = {29699512}, issn = {1471-2407}, support = {130680//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; 139226//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CH)/International ; }, mesh = {Animals ; Base Sequence ; Butyrates/pharmacology ; Calbindin 2/chemistry/*genetics/metabolism ; Cell Cycle Proteins/*metabolism ; Cell Line, Tumor ; Cytokines/metabolism ; Enhancer Elements, Genetic ; *Gene Expression Regulation, Neoplastic/drug effects ; Genes, Reporter ; Humans ; Lung Neoplasms/*genetics/*metabolism/pathology ; Mesothelioma/*genetics/*metabolism/pathology ; Mice ; *Promoter Regions, Genetic ; Protein Binding ; Protein Transport ; Proteolysis ; Response Elements ; Septins/*metabolism ; }, abstract = {BACKGROUND: The calcium-binding protein calretinin (gene name: CALB2) is currently considered as the most sensitive and specific marker for the diagnosis of malignant mesothelioma (MM). MM is a very aggressive tumor strongly linked to asbestos exposure and with no existing cure so far. The mechanisms of calretinin regulation, as well as its distinct function in MM are still poorly understood.

METHODS: We searched for transcription factors binding to the CALB2 promoter and modulating calretinin expression. For this, DNA-binding assays followed by peptide shotgun-mass spectroscopy analyses were used. CALB2 promoter activity was assessed by dual-luciferase reporter assays. Furthermore, we analyzed the effects of CALB2 promoter-binding proteins by lentiviral-mediated overexpression or down-regulation of identified proteins in MM cells. The modulation of expression of such proteins by butyrate was determined by subsequent Western blot analysis. Immunohistochemical analysis of embryonic mouse lung tissue served to verify the simultaneous co-expression of calretinin and proteins interacting with the CALB2 promoter during early development. Finally, direct interactions of calretinin with target proteins were evidenced by co-immunoprecipitation experiments.

RESULTS: Septin 7 was identified as a butyrate-dependent transcription factor binding to a CALB2 promoter region containing butyrate-responsive elements (BRE) resulting in decreased calretinin expression. Accordingly, septin 7 overexpression decreased calretinin expression levels in MM cells. The regulation was found to operate bi-directionally, i.e. calretinin overexpression also decreased septin 7 levels. During murine embryonic development calretinin and septin 7 were found to be co-expressed in embryonic mesenchyme and undifferentiated mesothelial cells. In MM cells, calretinin and septin 7 colocalized during cytokinesis in distinct regions of the cleavage furrow and in the midbody region of mitotic cells. Co-immunoprecipitation experiments revealed this co-localization to be the result of a direct interaction between calretinin and septin 7.

CONCLUSIONS: Our results demonstrate septin 7 not only serving as a "cytoskeletal" protein, but also as a transcription factor repressing calretinin expression. The negative regulation of calretinin by septin 7 and vice versa sheds new light on mechanisms possibly implicated in MM formation and identifies these proteins as transcriptional regulators and putative targets for MM therapy.}, } @article {pmid29698884, year = {2018}, author = {Ismael, H and Cox, S}, title = {Primary intrahepatic mesotheliomas: A case presentation and literature review.}, journal = {International journal of surgery case reports}, volume = {47}, number = {}, pages = {1-6}, pmid = {29698884}, issn = {2210-2612}, abstract = {INTRODUCTION: Primary Intrahepatic mesotheliomas are malignant tumors arising from the mesothelial cell layer covering Glisson's capsule of the liver. They are exceedingly rare with only fourteen cases reported in the literature. They have nonspecific signs and symptoms and need a high index of suspicion and an extensive workup prior to surgery. Surgery remains the mainstay of treatment.

PRESENTATION OF CASE: 48 year old male presented with a 3 months history of abdominal pain, productive cough, anemia and weight loss. He had no history of asbestos exposure. A computed tomography scan and magnetic resonance study demonstrated a heterogeneous subscapular mass within the dome of the right hepatic lobe measuring 11.3 × 6.1 cm involving the diaphragm. Combined resection of the liver and diaphragm was performed to achieve negative margins. Pathology demonstrated an epithelioid necrotic intrahepatic mesothelioma that stained positive for calretinin, CK AE1/AE3, WT-1, D2-40 and CK7.

DISCUSSION: Primary intrahepatic mesotheliomas originate from the mesothelial cells lining Glisson's capsule of the liver. They predominantly invade the liver but may also abut or involve the diaphragm. Surgery should include a diagnostic laparoscopy to rule out occult disease or diffuse peritoneal mesothelioma. Complete resection with negative margins should be attempted while maintaining an adequate future liver remnant. Attempts at dissecting the tumor off the involved diaphragm will result in excessive bleeding and may leave residual disease behind.

CONCLUSION: Intrahepatic mesotheliomas are rare peripherally-located malignant tumors of the liver. They require a high index of suspicion and a comprehensive workup prior to operative intervention.}, } @article {pmid29692597, year = {2018}, author = {Saha, A and Mandal, PK and Manna, A and Khan, K and Pal, S}, title = {Well differentiated papillary mesothelioma of abdomen- a rare case with diagnostic dilemma.}, journal = {Journal of laboratory physicians}, volume = {10}, number = {2}, pages = {248-250}, pmid = {29692597}, issn = {0974-2727}, abstract = {Well-differentiated papillary mesothelioma is a rare tumor occurring predominantly in the peritoneum of young women, a few with history of asbestos exposure. A 28-year-old woman presented with ascites and pain abdomen. Ultrasonography and computed tomography scan of the abdomen revealed a mass in the retroperitoneum measuring 15 cm × 12 cm. Histopathological examination along with immunohistochemistry (IHC) confirmed it to be a papillary mesothelioma in the peritoneum. It is difficult to differentiate from more common malignant mesothelioma and papillary adenocarcinoma, which also have poorer prognosis. The difficulty can be resolved by clinico-radiological correlation along with histopathological examination and IHC.}, } @article {pmid29690982, year = {2018}, author = {Sritharan, SS and Frandsen, JL and Omland, Ø and Bruun, JM}, title = {[Malignant pleural mesothelioma].}, journal = {Ugeskrift for laeger}, volume = {180}, number = {15}, pages = {}, pmid = {29690982}, issn = {1603-6824}, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. The disease is of importance, since the incidence in Denmark is increasing despite cessation of the use of asbestos in the 1980s. MPM has a long latency period, and the first symptom is often dyspnoea, typically caused by pleural effusion. The diagnosis is a challenge, because cytology often is non-conclusive, and thoracoscopy is needed to obtain biopsies for immunohistochemistry. The occupational history is important, since the patients are entitled to compensation. The treatment is often limited to palliation.}, } @article {pmid29685095, year = {2018}, author = {Takemura, Y and Satoh, M and Hatanaka, K and Kubota, S}, title = {Zebularine exerts its antiproliferative activity through S phase delay and cell death in human malignant mesothelioma cells.}, journal = {Bioscience, biotechnology, and biochemistry}, volume = {82}, number = {7}, pages = {1159-1164}, doi = {10.1080/09168451.2018.1459466}, pmid = {29685095}, issn = {1347-6947}, mesh = {Apoptosis/*drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cytidine/*analogs & derivatives/pharmacology ; DNA (Cytosine-5-)-Methyltransferase 1/antagonists & inhibitors ; Dose-Response Relationship, Drug ; Fibroblasts/cytology/drug effects ; Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism ; Humans ; Mesothelioma/enzymology/metabolism/*pathology ; S Phase/*drug effects ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Malignant mesothelioma is an asbestos-related aggressive tumor and current therapy remains ineffective. Zebularine as a DNA methyltransferase (DNMT) inhibitor has an anti-tumor effect in several human cancer cells. The aim of the present study was to investigate whether zebularine could induce antiproliferative effect in human malignant mesothelioma cells. Zebularine induced cell growth inhibition in a dose-dependent manner. In addition, zebularine dose-dependently decreased expression of DNMT1 in all malignant mesothelioma cells tested. Cell cycle analysis indicated that zebularine induced S phase delay. Zebularine also induced cell death in malignant mesothelioma cells. In contrast, zebularine did not induce cell growth inhibition and cell death in human normal fibroblast cells. These results suggest that zebularine has a potential for the treatment of malignant mesothelioma by inhibiting cell growth and inducing cell death.}, } @article {pmid29677456, year = {2018}, author = {Metintas, S and Ak, G and Metintas, M}, title = {A review of the cohorts with environmental and occupational mineral fiber exposure.}, journal = {Archives of environmental & occupational health}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/19338244.2018.1467873}, pmid = {29677456}, issn = {1933-8244}, abstract = {The aim of the study was to examine factors associated with Malignant Mesothelioma (MM) incidence rate of the groups with occupational asbestos and environmental asbestos or erionite exposure in rural area. In this ecological study, a total of 21 cohort datasets (8 environmental and 13 occupational) were evaluated. Data were analyzed using a multiple linear regression analysis model. In environmental cohorts, the risk of MM incidence was higher in women and people exposed to erionite. In this cohort, the incidence rate of MM increased as the median exposure time increased, while the incidence decreased as the median cumulative exposure dose increased. In occupational cohorts, the incidence rate of MM was positively correlated with the median cumulative exposure dose. The risk of mesothelioma was lower in those exposed to tremolite than others. Environmental asbestos exposure is as important as occupational exposure to develop MM, and it has its own unique exposure features on the risk of MM.}, } @article {pmid29676649, year = {2018}, author = {Xi, S and Payabyab, EC and Straughan, DM and Reardon, ES and Zhang, M and Hong, JA and Ripley, RT and Hoang, CD and Schrump, DS}, title = {Asbestos Induces Epigenetic Repression of Ras Association Domain-Containing Protein 1, p16 Kinase 4a Inhibitor, and p14 Alternative Reading Frame in Normal Human Mesothelial Cells.}, journal = {Annals of the American Thoracic Society}, volume = {15}, number = {Supplement_2}, pages = {S123}, doi = {10.1513/AnnalsATS.201707-609MG}, pmid = {29676649}, issn = {2325-6621}, abstract = {RATIONALE: Whereas asbestos burden has been linked to cytogenetic alterations in malignant pleural mesotheliomas, epigenetic aberrations induced by these fibers have not been fully delineated.

OBJECTIVES: The objective of this study was to establish an in vitro model to characterize early epigenetic events potentially contributing to malignant pleural mesothelioma.

METHODS: Normal human mesothelial cells (LP9 and LP3) were cultured with or without crocidolite asbestos fibers (1 or 2 μg/cm2) for up to 10 days. Messenger RNA, microRNA, and protein levels were assessed by quantitative reverse transcriptase-polymerase chain reaction and immunoblot techniques. Methylation-specific polymerase chain reaction, pyrosequencing, and quantitative chromatin immunoprecipitation techniques were used to correlate changes in gene expression with epigenetic alterations in the respective promoters.

RESULTS: Asbestos mediated time- and dose-dependent repression of Ras association domain-containing protein 1 (RASSF1A), p16 kinase 4a inhibitor (p16INK4a), and p14 alternative reading frame (p14ARF) in normal mesothelial cells; this phenomenon coincided with upregulation of DNA methyltransferase 1 (DNMT1) as well as increased expression of enhancer of zeste homolog 2 (EZH2). Upregulation of EZH2 coincided with repression of microRNA 26A and microRNA 101, which target the 3' untranslated region of the EZH2 transcript. Silencing of RASSF1A, p16INK4a, and p14ARF coincided with recruitment of EZH2 and concomitant increases in the PRC-2-mediated repressive histone mark, histone H3 lysine 27 trimethylation (H3K27me3), and decreased levels of histone H3 lysine 27 acetylation (H3K27ac3) (histone activation mark) within the respective promoters. Asbestos induced de novo DNA methylation in the promoter of RASSF1A, but not within the INK4a/ARF locus. 5-Aza-2'-deoxycytidine (0-0.5 μM for 72 h) induced dose-dependent activation of RASSF1A (but not p16/p14) in malignant pleural mesothelioma cells; this phenomenon coincided with DNA demethylation and decreased occupancy of DNA methyltransferase 3B within the RASSF1A promoter.

CONCLUSIONS: Asbestos mediates rapid inactivation of Hippo, Retinoblastoma, and p53 tumor suppressor pathways in normal human mesothelial cells via epigenetic repression of RASSF1A, p16INK4A, and p14ARF, respectively. This in vitro model may prove useful for delineating the sequence of epigenetic events contributing to malignant pleural mesothelioma, and the development of novel strategies for treatment and possible prevention of these neoplasms.}, } @article {pmid29669604, year = {2018}, author = {Fennell, DA and Kirkpatrick, E and Cozens, K and Nye, M and Lester, J and Hanna, G and Steele, N and Szlosarek, P and Danson, S and Lord, J and Ottensmeier, C and Barnes, D and Hill, S and Kalevras, M and Maishman, T and Griffiths, G}, title = {CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial.}, journal = {Trials}, volume = {19}, number = {1}, pages = {233}, pmid = {29669604}, issn = {1745-6215}, support = {C16728/A21400//Cancer Research UK/United Kingdom ; CA209-841//Bristol-Myers Squibb Foundation/ ; }, abstract = {BACKGROUND: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.

METHODS: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints).

DISCUSSION: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK.

TRIAL REGISTRATION: EudraCT Number: 2016-003111-35 (entered on 21 July 2016); ClinicalTrials.gov, ID: NCT03063450 . Registered on 24 February 2017.}, } @article {pmid29666782, year = {2018}, author = {Rossini, M and Rizzo, P and Bononi, I and Clementz, A and Ferrari, R and Martini, F and Tognon, MG}, title = {New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {91}, pmid = {29666782}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches.}, } @article {pmid29664355, year = {2018}, author = {Caltabiano, R and Loreto, C and Vitale, E and Matera, S and Miozzi, E and Migliore, M and Angelico, G and Tumino, R and Ledda, C and Rapisarda, V}, title = {Fibulin-3 immunoexpression in malignant mesothelioma due to fluoro-edenite: a preliminary report.}, journal = {Future oncology (London, England)}, volume = {14}, number = {6s}, pages = {53-57}, doi = {10.2217/fon-2017-0386}, pmid = {29664355}, issn = {1744-8301}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Amphibole/*toxicity ; Biomarkers, Tumor/metabolism ; Biopsy ; Environmental Exposure/*adverse effects ; Extracellular Matrix Proteins/*metabolism ; Female ; Follow-Up Studies ; Humans ; Incidence ; Lung/pathology ; Lung Neoplasms/chemically induced/epidemiology/*pathology ; Male ; Mesothelioma/chemically induced/epidemiology/*pathology ; Middle Aged ; Prognosis ; Retrospective Studies ; Sicily/epidemiology ; }, abstract = {An increased standardized incidence and mortality rate were reported due to malignant mesothelioma (MM) in Biancavilla. Environmental investigations showed the presence of an asbestiform fiber: fluoro-edenite (FE). MM develops with a latency of 20-60 years from exposure and specific and sensitive biomarkers are urgently needed. For this purpose, we evaluated Fibulin-3 (Fb-3) immunoexpression in human cases of MM related to FE exposure and its prognostic role. Immunohistochemical analysis of Fb-3 was carried out in eight MM patients resident in Biancavilla and the analysis showed evidence of environmental exposure to FE fibers. Six MM cases (3 epithelioid and 3 biphasic) showed a high immunoexpression of Fb-3 in neoplastic cells with nuclear and cytoplasmic localization. One epithelioid and one biphasic subtype did not show Fb-3 immunostaining. The results demonstrate the implication of Fb-3 in MM due to FE exposure and may possibly suggest its potential role as a diagnostic and prognostic marker.}, } @article {pmid29664352, year = {2018}, author = {Rapisarda, V and Loreto, C and Castorina, S and Romano, G and Garozzo, SF and Musumeci, A and Migliore, M and Avola, R and Cinà, D and Pomara, C and Ledda, C}, title = {Occupational exposure to fluoro-edenite and prevalence of anti-nuclear autoantibodies.}, journal = {Future oncology (London, England)}, volume = {14}, number = {6s}, pages = {59-62}, doi = {10.2217/fon-2017-0389}, pmid = {29664352}, issn = {1744-8301}, mesh = {Adult ; Antibodies, Antinuclear/*blood/immunology ; Asbestos, Amphibole/*toxicity ; Humans ; Lung/pathology ; Lung Neoplasms/blood/chemically induced/*immunology/mortality ; Male ; Mesothelioma/blood/chemically induced/*immunology/mortality ; Middle Aged ; Occupational Exposure/*adverse effects ; Sicily/epidemiology ; Survival Rate ; }, abstract = {An environmental contamination due to an asbestiform mineral fiber, fluoro-edenite (FE), caused a significantly increased mortality rate for malignant mesothelioma in Biancavilla, Italy. Exposure to fluoro-edenite has been associated with inflammatory processes as an early response to inhaled fibers. The aim was to explore prevalence of anti-nuclear autoantibodies (ANA) in a group of construction workers residing and working in the contaminated area. Prevalences for samples positive to ANA were 60% (n = 9) and 13% (n = 2), for exposed and nonexposed, respectively (p-value <0.05), the odds ratio was 9.75 (95% CI: 1.59-59.69). The significance of elevated ANAs in subjects exposed to fibers is unknown; additional studies may provide a better opportunity to establish a correlation between autoimmunity and environmental exposure.}, } @article {pmid29663493, year = {2018}, author = {Munson, P and Lam, YW and MacPherson, M and Beuschel, S and Shukla, A}, title = {Mouse serum exosomal proteomic signature in response to asbestos exposure.}, journal = {Journal of cellular biochemistry}, volume = {119}, number = {7}, pages = {6266-6273}, doi = {10.1002/jcb.26863}, pmid = {29663493}, issn = {1097-4644}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; }, abstract = {Asbestos-induced diseases like fibrosis and mesothelioma are very aggressive, without any treatment options. These diseases are diagnosed only at the terminal stages due to lack of early stage biomarkers. The recent discovery of exosomes as circulating biomarkers led us to look for exosomal biomarkers of asbestos exposure in mouse blood. In our model, mice were exposed to asbestos as a single bolus dose by oropharyngeal aspiration. Fifty-six days later blood was collected, exosomes were isolated from plasma and characterized and subjected to proteomic analysis using Tandem Mass Tag labeling. We identified many proteins, some of which were more abundant in asbestos exposed mouse serum exosomes, and three selected proteins were validated by immunoblotting. Our study is the first to show that serum exosomal proteomic signatures can reveal some important proteins relevant to asbestos exposure that have the potential to be validated as candidate biomarkers. We hope to extrapolate the positive findings of this study to humans in future studies.}, } @article {pmid29659015, year = {2018}, author = {Barbarino, M and Cesari, D and Intruglio, R and Indovina, P and Namagerdi, A and Bertolino, FM and Bottaro, M and Rahmani, D and Bellan, C and Giordano, A}, title = {Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A pre-clinical assessment.}, journal = {Journal of cellular physiology}, volume = {233}, number = {9}, pages = {7391-7401}, doi = {10.1002/jcp.26579}, pmid = {29659015}, issn = {1097-4652}, abstract = {Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, whose incidence is increasing worldwide. Unfortunately, no effective therapies are currently available and the prognosis is extremely poor. Recently, the anti-helminthic drug pyrvinium pamoate has attracted a strong interest for its anti-cancer activity, which has been demonstrated in many cancer models. Considering the previously established inhibitory effect of pyrvinium pamoate on the Wnt/β-catenin pathway and given the important role of this pathway in MM, we investigated the potential anti-tumor activity of this drug in MM cell lines. We observed that pyrvinium pamoate significantly impairs MM cell proliferation, cloning efficiency, migration, and tumor spheroid formation. At the molecular level, our data show that pyrvinium pamoate down-regulates the expression of β-catenin and Wnt-regulates genes. Overall, our study suggests that the repurposing of pyrvinium pamoate for MM treatment could represent a new promising therapeutic approach.}, } @article {pmid29656754, year = {2018}, author = {Sneddon, S and Dick, I and Lee, YCG and Musk, AWB and Patch, AM and Pearson, JV and Waddell, N and Allcock, RJN and Holt, RA and Robinson, BWS and Creaney, J}, title = {Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {119}, number = {}, pages = {64-70}, doi = {10.1016/j.lungcan.2018.03.009}, pmid = {29656754}, issn = {1872-8332}, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70% of MM patients develop pleural effusions which contain tumour cells, representing a readily accessible source of malignant cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions could provide novel insights but is little studied.

MATERIALS AND METHODS: DNA and RNA were extracted from cells from short term cultures of 27 human MM pleural effusion samples. Whole exome and transcriptome sequencing was performed using the Ion Torrent platform. Somatic mutations were identified using VarScan2 and SomaticSniper. Copy number alterations were identified using ExomeCNV in R. Significant copy number alterations were identified across all samples using GISTIC2.0. The association between tumour intrinsic properties and survival was analyzed using the Cox proportional hazards regression model.

RESULTS: We identified BAP1, CDKN2A and NF2 alterations in the cells from MM pleural effusions at a higher frequency than what is typically seen in MM tumours from surgical series. The median mutation rate was 1.09 mutations/Mb. TRAF7 and LATS2 alterations were also identified at a high frequency (66% and 59% respectively). Novel regions of interest were identified, including alterations in FGFR3, and the regions 19p13.3, 8p23.1 and 1p36.32.

CONCLUSION: Short term cultures of tumour cells from MM pleural effusions offer an accessible alternative to surgical tumour biopsies in the study of MM genomics and reveal novel mutations of interest. Pleural effusion tumour cells provide an opportunity for the monitoring of tumour dynamics, treatment response and the clonal evolution of MM tumours.}, } @article {pmid29651248, year = {2018}, author = {Sinis, SI and Hatzoglou, C and Gourgoulianis, KI and Zarogiannis, SG}, title = {Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on Mesothelial Cells and Mesothelial Membranes.}, journal = {Frontiers in physiology}, volume = {9}, number = {}, pages = {295}, pmid = {29651248}, issn = {1664-042X}, abstract = {Nanoparticles have great potential for numerous applications due to their unique physicochemical properties. However, concerns have been raised that they may induce deleterious effects on biological systems. There is accumulating evidence that, like asbestos, inhaled nanomaterials of >5 μm and high aspect ratio (3:1), particularly rod-like carbon nanotubes, may inflict pleural disease including mesothelioma. Additionally, a recent set of case reports suggests that inhalation of polyacrylate/nanosilica could in part be associated with inflammation and fibrosis of the pleura of factory workers. However, the adverse outcomes of nanoparticle exposure to mesothelial tissues are still largely unexplored. In that context, the present review aims to provide an overview of the relevant pathophysiological implications involving toxicological studies describing effects of engineered nanoparticles on mesothelial cells and membranes. In vitro studies primarily emphasize on simulating cellular uptake and toxicity of nanotubes on benign or malignant cell lines. On the other hand, in vivo studies focus on illustrating endpoints of serosal pathology in rodent animal models. From a molecular aspect, some nanoparticle categories are shown to be cytotoxic and genotoxic after acute treatment, whereas chronic incubation may lead to malignant-like transformation. At an organism level, a number of fibrous shaped nanotubes are related with features of chronic inflammation and MWCNT-7 is the only type to consistently inflict mesothelioma.}, } @article {pmid29641489, year = {2018}, author = {Felley-Bosco, E and Rehrauer, H}, title = {Non-Coding Transcript Heterogeneity in Mesothelioma: Insights from Asbestos-Exposed Mice.}, journal = {International journal of molecular sciences}, volume = {19}, number = {4}, pages = {}, pmid = {29641489}, issn = {1422-0067}, mesh = {Animals ; Asbestos/toxicity ; *Genetic Heterogeneity ; Mesothelioma/etiology/*genetics ; Mice ; RNA, Untranslated/*genetics ; Transcriptome ; }, abstract = {Mesothelioma is an aggressive, rapidly fatal cancer and a better understanding of its molecular heterogeneity may help with making more efficient therapeutic strategies. Non-coding RNAs represent a larger part of the transcriptome but their contribution to diseases is not fully understood yet. We used recently obtained RNA-seq data from asbestos-exposed mice and performed data mining of publicly available datasets in order to evaluate how non-coding RNA contribute to mesothelioma heterogeneity. Nine non-coding RNAs are specifically elevated in mesothelioma tumors and contribute to human mesothelioma heterogeneity. Because some of them have known oncogenic properties, this study supports the concept of non-coding RNAs as cancer progenitor genes.}, } @article {pmid29635378, year = {2018}, author = {Schelch, K and Wagner, C and Hager, S and Pirker, C and Siess, K and Lang, E and Lin, R and Kirschner, MB and Mohr, T and Brcic, L and Marian, B and Holzmann, K and Grasl-Kraupp, B and Krupitza, G and Laszlo, V and Klikovits, T and Dome, B and Hegedus, B and Garay, T and Reid, G and van Zandwijk, N and Klepetko, W and Berger, W and Grusch, M and Hoda, MA}, title = {FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural mesothelioma cells via a MAPKinase/MMP1 signal.}, journal = {Carcinogenesis}, volume = {39}, number = {4}, pages = {534-545}, doi = {10.1093/carcin/bgy018}, pmid = {29635378}, issn = {1460-2180}, mesh = {Cell Line, Tumor ; Epidermal Growth Factor/*metabolism ; Epithelial-Mesenchymal Transition/*physiology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibroblast Growth Factor 2/*metabolism ; Humans ; Lung Neoplasms/metabolism/*pathology ; Matrix Metalloproteinase 1/metabolism ; Mesothelioma/metabolism/*pathology ; Pleural Neoplasms/metabolism/*pathology ; Signal Transduction/physiology ; }, abstract = {Malignant pleural mesothelioma (MPM), an aggressive malignancy affecting pleural surfaces, occurs in three main histological subtypes. The epithelioid and sarcomatoid subtypes are characterized by cuboid and fibroblastoid cells, respectively. The biphasic subtype contains a mixture of both. The sarcomatoid subtype expresses markers of epithelial-mesenchymal transition (EMT) and confers the worst prognosis, but the signals and pathways controlling EMT in MPM are not well understood. We demonstrate that treatment with FGF2 or EGF induced a fibroblastoid morphology in several cell lines from biphasic MPM, accompanied by scattering, decreased cell adhesion and increased invasiveness. This depended on the MAP-kinase pathway but was independent of TGFβ or PI3-kinase signaling. In addition to changes in known EMT markers, microarray analysis demonstrated differential expression of MMP1, ESM1, ETV4, PDL1 and BDKR2B in response to both growth factors and in epithelioid versus sarcomatoid MPM. Inhibition of MMP1 prevented FGF2-induced scattering and invasiveness. Moreover, in MPM cells with sarcomatoid morphology, inhibition of FGF/MAP-kinase signaling induced a more epithelioid morphology and gene expression pattern. Our findings suggest a critical role of the MAP-kinase axis in the morphological and behavioral plasticity of mesothelioma.}, } @article {pmid29616141, year = {2018}, author = {de Fonseka, D and Underwood, W and Stadon, L and Rahman, N and Edey, A and Rogers, C and Maskell, NA}, title = {Randomised controlled trial to compare the diagnostic yield of positron emission tomography CT (PET-CT) TARGETed pleural biopsy versus CT-guided pleural biopsy in suspected pleural malignancy (TARGET trial).}, journal = {BMJ open respiratory research}, volume = {5}, number = {1}, pages = {e000270}, pmid = {29616141}, issn = {2052-4439}, abstract = {Introduction: Pleural malignancy, particularly malignant pleural mesothelioma (MPM) is increasing in incidence due to the long latency period from exposure to asbestos to development of the disease. MPM can be challenging to diagnose. For patients presenting without a pleural effusion, CT-guided biopsy remains the primary choice of biopsy, but the diagnostic sensitivity of this investigation is 70%-75%. Therefore, a proportion of patients will go on to require further biopsies. If the first biopsy is non-diagnostic, the chances of further non-diagnostic biopsies are high in MPM.

Methods: Target is a multicentre randomised controlled trial, aiming to recruit 78 patients over a 30-month period, from 10 centres in the UK. Patients will be randomised to either the standard arm which is a second CT-guided biopsy, or the interventional arm, a positron emission tomography-CT scan followed by a targeted CT-guided biopsy. Patients will be followed up for 12 months (patients recruited in the last 6 months of recruitment will have 6 months of follow-up). MPM biomarker mesothelin will be checked at baseline, 6 month and 12 month follow-up appointments where patients are able to attend these appointments.

Ethics and dissemination: Ethical approval for this trial was granted by the South West-Exeter research and ethics committee (reference number 15/SW/0156). Results of the trial will be published in a peer-reviewed journal and presented at an international conference.

Trial registration number: ISRCTN 14024829; Pre-results.}, } @article {pmid29608538, year = {2018}, author = {Liu, Y and Marsh, GM and Roggli, VL}, title = {Asbestos Fiber Concentrations in the Lungs of Brake Repair Workers: An Updated Analysis Using Several Regression Methods to Handle Nondetectable Measurements.}, journal = {Journal of occupational and environmental medicine}, volume = {60}, number = {7}, pages = {661-671}, doi = {10.1097/JOM.0000000000001320}, pmid = {29608538}, issn = {1536-5948}, abstract = {OBJECTIVES: The aim of the study was to reanalyze an updated database of lung asbestos fiber levels for 21 brake repair workers who died of mesothelioma using robust maximum likelihood-based regression methods to address nondetectable measurements.

METHODS: We applied bivariate normal regression to address the doubly left-censored situation where both the lung fiber concentration of noncommercial (TAA) and commercial amphiboles (AC) were subject to detection limits. For the single left-censored situation, we applied censored normal regression to study the relationship between duration of employment (DOE) and TAA.

RESULTS: We found a statistically significant positive relationship between TAA and AC (β = 0.49, 95% confidence interval [CI], 0.11 to 0.86) and a not statistically significant relationship between DOE and TAA (β = 0.02, 95% CI, -0.03 to 0.06).

CONCLUSIONS: Our results provide additional support for the conclusion that exposure to commercial amphibole asbestos, and not chrysotile, is related to the occurrence of mesothelioma among some brake workers.}, } @article {pmid29587685, year = {2018}, author = {Nagamatsu, Y and Oze, I and Aoe, K and Hotta, K and Kato, K and Nakagawa, J and Hara, K and Kishimoto, T and Fujimoto, N}, title = {Quality of life of survivors of malignant pleural mesothelioma in Japan: a cross sectional study.}, journal = {BMC cancer}, volume = {18}, number = {1}, pages = {350}, pmid = {29587685}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/*epidemiology/therapy ; Male ; Mesothelioma/*epidemiology/therapy ; Middle Aged ; Palliative Care ; Pleural Neoplasms/*epidemiology/therapy ; *Quality of Life ; Surveys and Questionnaires ; *Survivors ; }, abstract = {BACKGROUND: Previous studies have indicated that people with malignant pleural mesothelioma (MPM) have a poor quality of life (QOL); however, information about the QOL of people with MPM in Japan is anecdotal. The aims of this study were to investigate the QOL of survivors of MPM in Japan and to determine the factors that correlate with their QOL.

METHODS: This was a cross sectional study. The included patients were those diagnosed with MPM in Japan. We created a self-administered questionnaire consisting of 64 questions. The questionnaires were sent to hospitals and patient advocacy groups, distributed to the patients, completed, and sent back to the researchers by postal mail. QOL was assessed with the European Organization for Research and Treatment of Cancer 16 questionnaire (QLQ) and the short version of the core domains of the Comprehensive Quality of Life Outcome questionnaire (CoQoLo).

RESULTS: In total, 133 questionnaires were collected. The QLQ assessments demonstrated that the survivors of MPM most frequently complained of fatigue, pain, sleep disturbances, and dyspnea. The symptom scales were acceptable, but the functional scales were significantly poorer for the patients with poor performance statuses (PSs). The short CoQoLo assessment was very unfavorable for 'Being free from physical pain.' Being a long-term survivor and a survivor with a poor PS were significantly correlated with poor global health status.

CONCLUSIONS: Survivors of MPM have impaired function, a variety of symptoms, and lower QOL. Survivors of MPM, even those in good physical condition, need broad support.}, } @article {pmid29587439, year = {2018}, author = {Sato, T and Sekido, Y}, title = {NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma.}, journal = {International journal of molecular sciences}, volume = {19}, number = {4}, pages = {}, pmid = {29587439}, issn = {1422-0067}, mesh = {Actins/metabolism ; Antineoplastic Agents/pharmacology/therapeutic use ; Gene Expression Regulation, Neoplastic/drug effects ; *Genetic Variation ; Humans ; Lung Neoplasms/drug therapy/*genetics/metabolism ; Mesothelioma/drug therapy/*genetics/metabolism ; Neurofibromin 2/*genetics/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {The neurofibromatosis type 2 (NF2) gene encodes merlin, a tumor suppressor protein frequently inactivated in schwannoma, meningioma, and malignant mesothelioma (MM). The sequence of merlin is similar to that of ezrin/radixin/moesin (ERM) proteins which crosslink actin with the plasma membrane, suggesting that merlin plays a role in transducing extracellular signals to the actin cytoskeleton. Merlin adopts a distinct closed conformation defined by specific intramolecular interactions and regulates diverse cellular events such as transcription, translation, ubiquitination, and miRNA biosynthesis, many of which are mediated through Hippo and mTOR signaling, which are known to be closely involved in cancer development. MM is a very aggressive tumor associated with asbestos exposure, and genetic alterations in NF2 that abrogate merlin's functional activity are found in about 40% of MMs, indicating the importance of NF2 inactivation in MM development and progression. In this review, we summarize the current knowledge of molecular events triggered by NF2/merlin inactivation, which lead to the development of mesothelioma and other cancers, and discuss potential therapeutic targets in merlin-deficient mesotheliomas.}, } @article {pmid29580185, year = {2018}, author = {Beaucham, C and King, B and Feldmann, K and Harper, M and Dozier, A}, title = {Assessing occupational erionite and respirable crystalline silica exposure among outdoor workers in Wyoming, South Dakota, and Montana.}, journal = {Journal of occupational and environmental hygiene}, volume = {15}, number = {6}, pages = {455-465}, doi = {10.1080/15459624.2018.1447116}, pmid = {29580185}, issn = {1545-9632}, abstract = {Erionite is a naturally occurring fibrous mineral found in many parts of the world, including the western United States. Inhalational exposure to erionite fibers in some localities is associated with health effects similar to those caused by asbestos exposure, including malignant mesothelioma. Therefore, there is concern regarding occupational exposures in the western United States. Currently, there are no standard sampling and analytical methods for airborne erionite fibers, as well as no established occupational exposure limits. Due to the potential adverse health effects, characterizing and minimizing exposures is prudent. Crystalline silica also occurs naturally in areas where erionite is found, principally as the mineral quartz. Work activities involving rocks containing quartz and soils derived from those rocks can lead to exposure to respirable crystalline silica (RCS). The typically dry and dusty environment of the western United States can increase the likelihood of exposures to aerosolized rocks and soils, but inhalation exposure is also possible in more humid conditions. In this case study, we describe several outdoor occupational environments with potential exposures to erionite and RCS. We describe our method for evaluating those exposures and demonstrate: (1) the occurrence of occupational exposures to airborne erionite and RCS, (2) that the chemical make-up of the erionite mineral can be determined, and (3) that effective dust control practices are needed to reduce employee exposures to these minerals.}, } @article {pmid29577057, year = {2018}, author = {Field, Z and Zori, A and Khullar, V and Mota, M and Feely, M and Firpi, RJ}, title = {Malignant Peritoneal Mesothelioma Presenting as Mucinous Ascites.}, journal = {ACG case reports journal}, volume = {5}, number = {}, pages = {e23}, pmid = {29577057}, issn = {2326-3253}, abstract = {We present a rare case of a 46-year-old man presenting with mucinous ascites secondary to malignant peritoneal mesothelioma (MPM) that was diagnosed via colonoscopy with biopsies. Both our findings and the clinical presentation were unique. While it is widely known that asbestos exposure is commonly associated with pleural mesothelioma, 6-10% of malignant mesotheliomas arise from the peritoneum. To date, only 4 cases of MPM with the primary tumor site in the colon have been described in the literature.}, } @article {pmid29575036, year = {2018}, author = {Bonafede, M and Ghelli, M and Corfiati, M and Rosa, V and Guglielmucci, F and Granieri, A and Branchi, C and Iavicoli, S and Marinaccio, A}, title = {The psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects: A systematic review of published studies.}, journal = {American journal of industrial medicine}, volume = {61}, number = {5}, pages = {400-412}, doi = {10.1002/ajim.22831}, pmid = {29575036}, issn = {1097-0274}, abstract = {BACKGROUND: The purpose of this study is to present the results of a systematic review of published research that focuses on psychological aspects of malignant mesothelioma patients and asbestos-exposed people.

METHODS: Our research includes primary studies published between 1980 and 2016, using information from the Cochrane Library, the Psychology Behavioral Sciences Collection, PsychINFO, PubMed, PubGet, PubPsych, and Scopus, in compliance with PRISMA guidelines.

RESULTS: We identified 12 papers that investigated the psychological distress and care needs of mesothelioma patients, and nine papers for asbestos-exposed subjects.

CONCLUSIONS: This paper highlights the paucity of studies on the psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects. It confirms that malignant mesothelioma is associated with the physical, emotional, and social functioning of patients, while also suggesting that the risk of developing asbestos-related diseases among asbestos-exposed subjects is associated with high levels of psychological distress, despair, and mental health difficulties.}, } @article {pmid29574645, year = {2018}, author = {Vimercati, L and Cavone, D and Lovreglio, P and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Environmental asbestos exposure and mesothelioma cases in Bari, Apulia region, southern Italy: a national interest site for land reclamation.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {16}, pages = {15692-15701}, pmid = {29574645}, issn = {1614-7499}, mesh = {Aged ; Antineoplastic Agents/therapeutic use ; Asbestos/*toxicity ; Carcinogens, Environmental/*toxicity ; Cities ; *Environmental Exposure ; Fatal Outcome ; Female ; Humans ; Italy ; Lung Neoplasms/chemically induced/diagnosis/*drug therapy/*surgery ; Male ; Mesothelioma/chemically induced/diagnosis/*drug therapy/*surgery ; Middle Aged ; Treatment Outcome ; }, abstract = {Asbestos is an environmental carcinogen, and asbestos-related diseases are a global-scale public health issue. We report three cases (one male and two females) of pleural malignant mesothelioma (PMM) caused by environmental asbestos exposure reported by the Apulia Regional Operating Centre (COR) to the National Mesothelioma Registry (ReNaM). The patients revealed no history of asbestos exposure even after detailed assessment. The environmental (neighborhood) asbestos exposure for each of the three cases was due to both the residential history of the subjects and their workplace, close to a military barracks, at a distance of between 45 and 100 m. Moreover, in addition to this new source of pollution, an asbestos cement factory was located in the urban area of Bari municipality, in the Apulia region, southern Italy. Environmental-residential/neighborhood asbestos exposure in the city of Bari, a contaminated area classified as a site of national concern for land reclamation, is discussed also with reference to the military barracks.}, } @article {pmid29574404, year = {2018}, author = {Marsh, GM and Riordan, AS and Keeton, KA and Benson, SM}, title = {Response to: 'Reanalysis of non-occupational exposure to asbestos and the risk of pleural mesothelioma' by Finkelstein.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {6}, pages = {473-474}, doi = {10.1136/oemed-2018-105020}, pmid = {29574404}, issn = {1470-7926}, } @article {pmid29571785, year = {2018}, author = {Kato, K and Gemba, K and Ashizawa, K and Arakawa, H and Honda, S and Noguchi, N and Honda, S and Fujimoto, N and Kishimoto, T}, title = {Low-dose chest computed tomography screening of subjects exposed to asbestos.}, journal = {European journal of radiology}, volume = {101}, number = {}, pages = {124-128}, doi = {10.1016/j.ejrad.2018.02.017}, pmid = {29571785}, issn = {1872-7727}, mesh = {Aged ; Aged, 80 and over ; *Asbestos ; Cross-Sectional Studies ; Female ; Humans ; Lung/diagnostic imaging/pathology ; Lung Neoplasms/*diagnostic imaging/*epidemiology/pathology ; Male ; Mesothelioma/diagnostic imaging/epidemiology/pathology ; Middle Aged ; Prevalence ; Prospective Studies ; *Radiation Dosage ; Tomography, X-Ray Computed/*methods ; }, abstract = {OBJECTIVES: The primary aim was to reveal the prevalence of lung cancer (LC) and malignant pleural mesothelioma (MPM) in subjects with past asbestos exposure (AE). We also examined pulmonary or pleural changes correlated with the development of LC.

MATERIALS AND METHODS: This was a prospective, multicenter, cross-sectional study. There were 2132 subjects enrolled between 2010 and 2012. They included 96.2% men and 3.8% women, with a mean age of 76.1 years; 78.8% former or current smokers; and 21.2% never smokers. We screened subjects using low-dose computed tomography (CT). The CT images were taken with a CT dose Index of 2.7 mGy. The evaluated CT findings included subpleural curvilinear shadow/subpleural dots, ground glass opacity or interlobular reticular opacity, traction bronchiectasia, honeycombing change, parenchymal band, emphysema changes, pleural effusion, diffuse pleural thickening, rounded atelectasis, pleural plaques (PQs), and tumor formation.

RESULTS: The PQs were detected in most of subjects (89.4%) and emphysema changes were seen in 46.0%. Fibrotic changes were detected in 565 cases (26.5%). A pathological diagnosis of LC was confirmed in 45 cases (2.1%) and MPM was confirmed in 7 cases (0.3%). The prevalence of LC was 2.5% in patients with a smoking history, which was significantly higher than that in never smokers (0.7%, p = 0.027). The prevalence of LC was 2.8% in subjects with emphysema changes, which was higher than that of subjects without those findings (1.6%); although, the difference was not statistically significant (p = 0.056). The prevalence of LC in subjects with both fibrotic plus emphysema changes was 4.0%, which was significantly higher than that of subjects with neither of those findings (1.8%, p = 0.011). Logistic regression analysis revealed smoking history, fibrotic plus emphysema changes, and pleural effusion as significant explanatory variables.

CONCLUSIONS: Smoking history, fibrotic plus emphysema changes, and pleural effusion were correlated with the prevalence of LC.}, } @article {pmid29564943, year = {2018}, author = {Maxim, LD and Utell, MJ}, title = {Review of refractory ceramic fiber (RCF) toxicity, epidemiology and occupational exposure.}, journal = {Inhalation toxicology}, volume = {30}, number = {2}, pages = {49-71}, doi = {10.1080/08958378.2018.1448019}, pmid = {29564943}, issn = {1091-7691}, abstract = {This literature review on refractory ceramic fibers (RCF) summarizes relevant information on manufacturing, processing, applications, occupational exposure, toxicology and epidemiology studies. Rodent toxicology studies conducted in the 1980s showed that RCF caused fibrosis, lung cancer and mesothelioma. Interpretation of these studies was difficult for various reasons (e.g. overload in chronic inhalation bioassays), but spurred the development of a comprehensive product stewardship program under EPA and later OSHA oversight. Epidemiology studies (both morbidity and mortality) were undertaken to learn more about possible health effects resulting from occupational exposure. No chronic animal bioassay studies on RCF have been conducted since the 1980s. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer. Evidence supporting a finding that urinary tumors are associated with RCF exposure remains, but is weaker. One reported, but unconfirmed, mesothelioma was found in an individual with prior occupational asbestos exposure. An elevated SMR for leukemia was found, but was absent in the highly exposed group and has not been observed in studies of other mineral fibers. The industry will continue the product stewardship program including the mortality study.}, } @article {pmid29553831, year = {2018}, author = {Munson, P and Lam, YW and Dragon, J and MacPherson, M and Shukla, A}, title = {Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {32}, number = {8}, pages = {4328-4342}, pmid = {29553831}, issn = {1530-6860}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*toxicity ; Carcinogens/toxicity ; Cell Line ; Epithelial Cells/drug effects/*physiology ; Epithelial-Mesenchymal Transition/drug effects/physiology ; Epithelium/drug effects/*physiology ; Exosomes/*genetics ; Gene Expression/drug effects/*genetics ; Humans ; Inhalation Exposure/adverse effects ; Lung/drug effects/*physiology ; Macrophages/drug effects/physiology ; }, abstract = {Asbestos exposure is a determinate cause of many diseases, such as mesothelioma, fibrosis, and lung cancer, and poses a major human health hazard. At this time, there are no identified biomarkers to demarcate asbestos exposure before the presentation of disease and symptoms, and there is only limited understanding of the underlying biology that governs asbestos-induced disease. In our study, we used exosomes, 30-140 nm extracellular vesicles, to gain insight into these knowledge gaps. As inhaled asbestos is first encountered by lung epithelial cells and macrophages, we hypothesize that asbestos-exposed cells secrete exosomes with signature proteomic cargo that can alter the gene expression of mesothelial cells, contributing to disease outcomes like mesothelioma. In the present study using lung epithelial cells (BEAS2B) and macrophages (THP-1), we first show that asbestos exposure causes changes in abundance of some proteins in the exosomes secreted from these cells. Furthermore, exposure of human mesothelial cells (HPM3) to these exosomes resulted in gene expression changes related to epithelial-to-mesenchymal transition and other cancer-related genes. This is the first report to indicate that asbestos-exposed cells secrete exosomes with differentially abundant proteins and that those exosomes have a gene-altering effect on mesothelial cells.-Munson, P., Lam, Y.-W., Dragon, J. MacPherson, M., Shukla, A. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.}, } @article {pmid29547510, year = {2018}, author = {Allen, LP and Baez, J and Stern, MEC and Takahashi, K and George, F}, title = {Trends and the Economic Effect of Asbestos Bans and Decline in Asbestos Consumption and Production Worldwide.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {3}, pages = {}, pmid = {29547510}, issn = {1660-4601}, support = {001//World Health Organization/International ; }, mesh = {*Asbestos/economics/toxicity ; Environmental Exposure/*prevention & control ; Gross Domestic Product ; Humans ; }, abstract = {Although some countries have reduced asbestos consumption and instituted bans, other countries continue to produce and consume asbestos even as asbestos-related deaths mount and the associated societal costs are high. Asbestos production and consumption has declined globally; the number of bans has increased; and the speed at which countries have tapered off consumption has increased. Using country-level data, we study the economic impact of historical changes in the production and use of asbestos. We compare changes in gross domestic product (GDP) following the enactment of asbestos bans. We do not find any significant effect on GDP following an asbestos ban. In a regional case study, we compare changes in GDP and employment with changes in asbestos production. Regional-level data revealed a temporary employment decline at the local level that was then reversed.}, } @article {pmid29545973, year = {2018}, author = {Naeini, YB and Arcega, R and Hirschowitz, S and Rao, N and Xu, H}, title = {Post-irradiation pericardial malignant mesothelioma with deletion of p16: a case report.}, journal = {Cancer biology & medicine}, volume = {15}, number = {1}, pages = {97-102}, pmid = {29545973}, issn = {2095-3941}, abstract = {Malignant mesotheliomas are rather uncommon neoplasms associated primarily with asbestos exposure; however, they may also arise as second primary malignancies after radiation therapy, with a latency period of 15-25 years. Numerous studies have reported an association between pleural malignant mesothelioma and chest radiation performed for other malignancies; on the other hand, post-irradiation mesotheliomas of the pericardium have been reported in only a few published cases to date, and no homozygous deletion of 9p21 has been described in such cases. We report the case of a 48-year-old man with a history of Hodgkin's lymphoma and no prior asbestos exposure who developed pericardial malignant epithelioid mesothelioma. We further discuss the cytologic, histologic, immunophenotypic, and fluorescence in situ hybridization findings in this case. To our knowledge, this is the first well-documented case of post-radiation pericardial malignant mesothelioma showing homozygous deletion of 9p21. Homozygous deletion of 9p21, the locus harboring the p16 gene, is present in post-irradiation pericardial malignant mesothelioma.}, } @article {pmid29534192, year = {2018}, author = {Gilham, C and Rake, C and Hodgson, J and Darnton, A and Burdett, G and Peto Wild, J and Newton, M and Nicholson, AG and Davidson, L and Shires, M and Treasure, T and Peto, J and , }, title = {Past and current asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS).}, journal = {International journal of epidemiology}, volume = {47}, number = {6}, pages = {1745-1756}, pmid = {29534192}, issn = {1464-3685}, support = {//Cancer Research UK/United Kingdom ; }, abstract = {Background: Occupational and environmental airborne asbestos concentrations are too low and variable for lifetime exposures to be estimated reliably, and building workers and occupants may suffer higher exposure when asbestos in older buildings is disturbed or removed. Mesothelioma risks from current asbestos exposures are therefore not known.

Methods: We interviewed and measured asbestos levels in lung samples from 257 patients treated for pneumothorax and 262 with resected lung cancer, recruited in England and Wales. Average lung burdens in British birth cohorts from 1940 to 1992 were estimated for asbestos-exposed workers and the general population.

Results: Regression analysis of British mesothelioma death rates and average lung burdens in birth cohorts born before 1965 suggests a lifetime mesothelioma risk of approximately 0.01% per fibre/mg of amphiboles in the lung. In those born since 1965, the average lung burden is ∼1 fibre/mg among those with no occupational exposure.

Conclusions: The average lifetime mesothelioma risk caused by recent environmental asbestos exposure in Britain will be about 1 in 10 000. The risk is an order of magnitude higher in a subgroup of exposed workers and probably in occupants in the most contaminated buildings. Further data are needed to discover whether asbestos still present in buildings, particularly schools, is a persistent or decreasing hazard to workers who disturb it and to the general population, and whether environmental exposure occurs predominantly in childhood or after beginning work. Similar studies are needed in other countries to estimate continuing environmental and occupational mesothelioma hazards worldwide, including the contribution from chrysotile.}, } @article {pmid29531907, year = {2018}, author = {van Zandwijk, N and McDiarmid, J and Brahmbhatt, H and Reid, G}, title = {Response to "An innovative mesothelioma treatment based on mir-16 mimic loaded EGFR targeted minicells (TargomiRs)".}, journal = {Translational lung cancer research}, volume = {7}, number = {Suppl 1}, pages = {S60-S61}, pmid = {29531907}, issn = {2218-6751}, } @article {pmid29524617, year = {2018}, author = {McCambridge, AJ and Napolitano, A and Mansfield, AS and Fennell, DA and Sekido, Y and Nowak, AK and Reungwetwattana, T and Mao, W and Pass, HI and Carbone, M and Yang, H and Peikert, T}, title = {Progress in the Management of Malignant Pleural Mesothelioma in 2017.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {5}, pages = {606-623}, doi = {10.1016/j.jtho.2018.02.021}, pmid = {29524617}, issn = {1556-1380}, abstract = {Malignant pleural mesothelioma (MPM) is an uncommon, almost universally fatal, asbestos-induced malignancy. New and effective strategies for diagnosis, prognostication, and treatment are urgently needed. Herein we review the advances in MPM achieved in 2017. Whereas recent epidemiological data demonstrated that the incidence of MPM-related death continued to increase in United States between 2009 and 2015, new insight into the molecular pathogenesis and the immunological tumor microenvironment of MPM, for example, regarding the role of BRCA1 associated protein 1 and the expression programmed death receptor ligand 1, are highlighting new potential therapeutic strategies. Furthermore, there continues to be an ever-expanding number of clinical studies investigating systemic therapies for MPM. These trials are primarily focused on immunotherapy using immune checkpoint inhibitors alone or in combination with other immunotherapies and nonimmunotherapies. In addition, other promising targeted therapies, including pegylated adenosine deiminase (ADI-PEG20), which focuses on argininosuccinate synthase 1-deficient tumors, and tazemetostat, an enhancer of zeste 2 polycomb repressive complex 2 subunit inhibitor of BRCA1 associated protein 1 gene (BAP1)-deficient tumors, are currently being explored.}, } @article {pmid29523930, year = {2018}, author = {Casalone, E and Allione, A and Viberti, C and Pardini, B and Guarrera, S and Betti, M and Dianzani, I and Aldieri, E and Matullo, G}, title = {DNA methylation profiling of asbestos-treated MeT5A cell line reveals novel pathways implicated in asbestos response.}, journal = {Archives of toxicology}, volume = {92}, number = {5}, pages = {1785-1795}, doi = {10.1007/s00204-018-2179-y}, pmid = {29523930}, issn = {1432-0738}, support = {IG 17464//Associazione Italiana per la Ricerca sul Cancro/ ; }, abstract = {Occupational and environmental asbestos exposure is the main determinant of malignant pleural mesothelioma (MPM), however, the mechanisms by which its fibres contribute to cell toxicity and transformation are not completely clear. Aberrant DNA methylation is a common event in cancer but epigenetic modifications involved specifically in MPM carcinogenesis need to be better clarified. To investigate asbestos-induced DNA methylation and gene expression changes, we treated Met5A mesothelial cells with different concentrations of crocidolite and chrysotile asbestos (0.5 ÷ 5.0 µg/cm2, 72 h incubation). Overall, we observed 243 and 302 differentially methylated CpGs (≥ 10%) between the asbestos dose at 5 µg/cm2 and untreated control, in chrysotile and crocidolite treatment, respectively. To examine the dose-response effect, Spearman's correlation test was performed and significant CpGs located in genes involved in migration/cell adhesion processes were identified in both treatments. Moreover, we found that both crocidolite and chrysotile exposure induced a significant up-regulation of CA9 and SRGN (log2 fold change > 1.5), previously reported as associated with a more aggressive MPM phenotype. However, we found no correlation between methylation and gene expression changes, except for a moderate significant inverse correlation at the promoter region of DKK1 (Spearman rho = - 1, P value = 0.02) after chrysotile exposure. These results describe for the first time the relationship between DNA methylation modifications and asbestos exposure. Our findings provide a basis to further explore and validate asbestos-induced DNA methylation changes, that could influence MPM carcinogenesis and possibly identifying new chemopreventive target.}, } @article {pmid29520212, year = {2018}, author = {Franko, A and Kotnik, N and Goricar, K and Kovac, V and Dodic-Fikfak, M and Dolzan, V}, title = {The Influence of Genetic Variability on the Risk of Developing Malignant Mesothelioma.}, journal = {Radiology and oncology}, volume = {52}, number = {1}, pages = {105-111}, pmid = {29520212}, issn = {1318-2099}, abstract = {Background: Malignant mesothelioma is a rare cancer with poor outcome, associated with asbestos exposure. Reactive oxygen species may play an important role in the mechanism of carcinogenesis; therefore, genetic variability in antioxidative defence may modify an individual's susceptibility to this cancer. This study investigated the influence of functional polymorphisms of NQO1, CAT, SOD2 and hOGG1 genes, gene-gene interactions and gene-environment interactions on malignant mesothelioma risk.

Patients and methods: In total, 150 cases with malignant mesothelioma and 122 controls with no asbestos-related disease were genotyped for NQO1, CAT, SOD2 and hOGG1 polymorphisms.

Results: The risk of malignant mesothelioma increased with smoking, odds ratio (OR) 9.30 [95% confidence interval (CI): 4.83-17.98] and slightly with age, OR 1.10 (95% CI: 1.08-1.14). Medium and high asbestos exposures represented 7-times higher risk of malignant mesothelioma compared to low exposure, OR 7.05 (95% CI 3.59-13.83). NQO1 rs1800566 was significantly associated with increased malignant mesothelioma risk, OR 1.73 (95% CI 1.02-2.96). Although there was no independent association between either CAT rs1001179 or hOGG1 rs1052133 polymorphism and malignant mesothelioma, interaction between both polymorphisms showed a protective effect, ORint 0.27 (95% CI 0.10-0.77).

Conclusions: Our findings suggest a role of both genetic variability in antioxidative defence and repair as well as the impact of gene-gene interactions in the development of malignant mesothelioma. The results of this study could add to our understanding of pathogenesis of malignant mesothelioma and contribute to prevention and earlier diagnosis of this aggressive cancer.}, } @article {pmid29508763, year = {2018}, author = {Scherpereel, A and Wallyn, F and Albelda, SM and Munck, C}, title = {Novel therapies for malignant pleural mesothelioma.}, journal = {The Lancet. Oncology}, volume = {19}, number = {3}, pages = {e161-e172}, doi = {10.1016/S1470-2045(18)30100-1}, pmid = {29508763}, issn = {1474-5488}, support = {P01 CA066726/CA/NCI NIH HHS/United States ; R01 CA172921/CA/NCI NIH HHS/United States ; }, mesh = {Angiogenesis Inhibitors/adverse effects/*therapeutic use ; Animals ; Antineoplastic Agents, Immunological/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Humans ; Lung Neoplasms/*drug therapy/immunology/metabolism/pathology ; Mesothelioma/*drug therapy/immunology/metabolism/pathology ; Molecular Targeted Therapy/adverse effects/*methods ; Pleural Neoplasms/*drug therapy/immunology/metabolism/pathology ; Signal Transduction/drug effects ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma is a rare cancer that is typically associated with exposure to asbestos. Patients with malignant pleural mesothelioma have poor outcomes with suboptimal therapeutic options and currently no treatment is curative. The standard frontline treatment, cisplatin plus pemetrexed chemotherapy, has only short and insufficient efficacy, and no validated treatment beyond first-line therapy is available. New therapeutic strategies are therefore needed. The addition of bevacizumab (an anti-VEGF antibody) combined with cisplatin plus pemetrexed has shown some promise. However, immunotherapy, especially immune checkpoint inhibitors, has generated a lot of excitement because of data suggesting the potential value of immune checkpoint inhibitors for patients who have failed chemotherapy. In this Review, we describe immune checkpoint inhibitors, other immunotherapies, targeted therapies, or combinations of novel drugs being investigated in malignant pleural mesothelioma, as well as the issues surrounding the selection of the best candidates for these treatments.}, } @article {pmid29507806, year = {2018}, author = {Foddis, R and Bonotti, A and Landi, S and Fallahi, P and Guglielmi, G and Cristaudo, A}, title = {Biomarkers in the prevention and follow-up of workers exposed to asbestos.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S360-S368}, pmid = {29507806}, issn = {2072-1439}, abstract = {Although in most developed countries the use of asbestos is banned, there is still a consistent portion of the world where asbestos extraction, trading and manufacturing of asbestos-made products is largely diffuse. Worldwide, hundreds of millions of people are at risk of developing an asbestos caused disease because of occupational, environmental or domestic exposure. The WHO estimates that asbestos is responsible for more than 100,000 deaths yearly. This scenario has prompted the research on biomarkers potentially useful for early diagnosis, prognosis and preventive programs on exposed population as well. Here we reviewed the up-to-date literature on this field of research highlighting that along with mesothelin and osteopontin (OPN), some more recently investigated molecules, such as high mobility group box 1 (HMGB1) protein, fibulin-3 and some miRNAs showed very promising. Most of the carried-out studies showed an interesting diagnostic and prognostic performance of some biomarkers, but since they usually lack adequate either specificity or sensitivity, their use in screening or in preventive programs is still not recommended on a routine basis. However, this review suggests the need for more reliable experimental design involving larger population and preferring longitudinal screening of asbestos exposed individuals rather than a single baseline assessment investigation. In addition, given their better diagnostic accuracy, the use of panels including several biomarkers is highly recommended.}, } @article {pmid29507805, year = {2018}, author = {Cristaudo, A and Bonotti, A and Guglielmi, G and Fallahi, P and Foddis, R}, title = {Serum mesothelin and other biomarkers: what have we learned in the last decade?.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S353-S359}, pmid = {29507805}, issn = {2072-1439}, abstract = {In the last decade there is been much interest in noninvasive, economic and well-accepted diagnostic tests for screening of subjects exposed to asbestos, and in patients with malignant pleuric mesothelioma (MPM) for diagnosis or monitoring response to treatment. Several biomarkers have been suggested as tools for screening and early diagnosis of MPM. Currently, in patients with MPM, have been reported high levels of soluble mesothelin-related peptides (SMRP), plasmatic osteopontin (pOPN), vimentin, fibulin-3 and many others as promising marker for diagnosis, even their use in prevention monitoring is still discussed. In this type of disease, a key role could be played by miRNAs, which expression has been investigated in a large series of MPM to examine new pathways useful in diagnosis, prognosis and therapy. An altered expression of some proteins has been reported, useful as biomarkers, in comparative proteomic analysis of malignant pleural mesothelioma. New promising markers are nowadays under study and alone or better in combination, they'll be very helpful in diagnosing, monitoring mesothelioma patients or for screening of risk groups.}, } @article {pmid29507804, year = {2018}, author = {Bruno, R and Alì, G and Fontanini, G}, title = {Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S342-S352}, pmid = {29507804}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor associated with asbestos exposure. Histopathological analysis of pleural tissues is the gold standard for diagnosis; however, it can be difficult to differentiate malignant from benign pleural lesions. The purpose of this review is to describe the most important biomarkers and new diagnostic tools suggested for this differential diagnosis. There are many studies concerning the separation between MPM and benign pleural proliferations from both pleural tissues or effusions; most of them are based on the evaluation of one or few biomarkers by immunohistochemistry (IHC) or enzyme-linked immunosorbent assays (ELISAs), whereas others focused on the identification of MPM signatures given by microRNA (miRNA) or gene expression profiles as well as on the combination of molecular data and classification algorithms. None of the reported biomarkers showed adequate diagnostic accuracy, except for p16 [evaluated by fluorescent in situ hybridization (FISH)] and BAP1 (evaluated by IHC), both biomarkers are recommended by the International Mesothelioma Interest Group guidelines for histological and cytological diagnosis. BAP1 and p16 showed a specificity of 100% in discerning malignant from benign lesions because they are exclusively unexpressed or deleted in MPM. However, their sensitivity, even when used together, is not completely sufficient, and absence of their alterations cannot confirm the benign nature of the lesion. Recently, the availability of new techniques and increasing knowledge regarding MPM genetics led to the definition of some molecular panels, including genes or miRNAs specifically deregulated in MPM, that are extremely valuable for differential diagnosis. Moreover, the development of classification algorithms is facilitating the application of molecular data for clinical practice. Data regarding new diagnostic tools and MPM signatures are absolutely promising; however, before their application in clinical practice, a prospective validation is necessary, as these approaches could surely improve the differential diagnosis between malignant and benign pleural lesions.}, } @article {pmid29507796, year = {2018}, author = {Alì, G and Bruno, R and Fontanini, G}, title = {The pathological and molecular diagnosis of malignant pleural mesothelioma: a literature review.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S276-S284}, pmid = {29507796}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM), an asbestos-induced tumor, represents significant diagnostic challenges for pathologists. Its histological diagnosis is stepwise and should be based on morphological assessment, supported by clinical and radiological findings, and supplemented with immunohistochemistry (IHC) and, more recently, molecular tests. The main diagnostic dilemmas are the differential diagnoses with benign mesothelial proliferations and other pleural malignant tumors. The present review is an update regarding the morphological, immunohistochemical, and molecular features with respect to MPM diagnosis. Data sources include a survey of the biomedical literature from PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and textbooks focusing on the pathological diagnosis of MPM and associated immunohistochemical and molecular markers. The histological findings of MPM could facilitate its diagnosis and provide important prognostic information. The immunohistochemical approach should rest on the application of a panel including positive (mesothelial-related) and negative markers with greater than 80% sensitivity and specificity, which need to be selected based on morphology and clinical information. Moreover, in challenging cases, fluorescent in situ hybridization (FISH) testing for the p16 deletion and IHC to evaluate the loss of BRCA1-associated protein 1 (BAP1) expression could be useful in distinguishing benign from malignant pleural proliferations.}, } @article {pmid29507795, year = {2018}, author = {Ceruti, P and Lonni, S and Baglivo, F and Marchetti, G}, title = {Endoscopic diagnosis and management of pleural effusion in malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S269-S275}, pmid = {29507795}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is an asbestos-related aggressive tumor, that requires proper diagnosis and management. Symptoms are nonspecific and chest computed tomography (CT) and chest ultrasound (US) are important radiological tools in the initial workup to identify early pathological signs. Performing a medical thoracoscopy (MT) is essential for a definitive diagnosis of MPM. The procedure, integrated with a prior US, allows a global evaluation of the pleural cavity and the execution of multiple targeted biopsies, with low risk of complications. Some different endoscopic patterns are recognized. Thoracoscopic biopsies provide enough material to allow a thorough pathological and immunohistochemical characterization. The presence of extensive pleural adhesions and critical patient conditions are the only absolute contraindications. The clinical course of MPM is characterized by chronic symptoms such as chest pain and progressive dyspnea, the latter caused mainly by recurrent pleural effusion. Palliative interventions are required in order to relieve symptoms and improve the quality of life (QoL). These include thoracentesis, pleurodesis and the placement of an indwelling pleural catheter.}, } @article {pmid29507794, year = {2018}, author = {Falaschi, F and Romei, C and Fiorini, S and Lucchi, M}, title = {Imaging of malignant pleural mesothelioma: it is possible a screening or early diagnosis program?-a systematic review about the use of screening programs in a population of asbestos exposed workers.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S262-S268}, pmid = {29507794}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) in an uncommon neoplasia with high mortality rate, mostly related to professional asbestos exposure. Clinical manifestations are not specific so that diagnosis is performed at advanced stage and screening protocols are not feasible now. On the other hand, asbestos-exposed workers have a high incidence of developing lung cancer. Low-dose computed tomography (LDCT) is a volumetric acquisition technique with high spatial resolution and a low dose exposure; it is used in many trials to detect lung tumours at an early stage in screening protocols, reducing mortality rate in smoker subjects. In recent papers, the possibly role of lung cancer screening was evaluated and recommended also in subjects exposed to asbestos. This article summarizes previous and present clinical trials validated for lung cancer screening, to discuss the possibility of early diagnosis or screening programs in a population of asbestos exposed workers by LDCT.}, } @article {pmid29507793, year = {2018}, author = {Bianco, A and Valente, T and De Rimini, ML and Sica, G and Fiorelli, A}, title = {Clinical diagnosis of malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S253-S261}, pmid = {29507793}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is a tumour which, despite progress in diagnostic procedures and biomolecular research, has poor prognosis. Symptoms reflect extension of disease and include shortness of breath and chest pain. Unexplained pleural effusion and pleural pain in patients exposed to asbestos should raise the suspicion of MPM. MPM diagnosis requires imaging procedures X-ray and computed tomography (CT) scans; magnetic resonance imaging (MRI) better defines the extension of the tumor while PET scanning provides additional information on metabolic activity, metastases, and response to treatment. Thoracoscopic biopsy remains the most appropriate procedure for definitive diagnosis of mesothelioma. Multimodality treatment including surgery, chemotherapy and radiotherapy has been associated with a better survival in selected patients. Clinical translational research including new approaches targeting immune-checkpoints is opening new horizons which may lead to personalised treatments.}, } @article {pmid29507792, year = {2018}, author = {Melaiu, O and Gemignani, F and Landi, S}, title = {The genetic susceptibility in the development of malignant pleural mesothelioma.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S246-S252}, pmid = {29507792}, issn = {2072-1439}, abstract = {Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity whose main risk factor is exposure to asbestos. However, it has been shown that only a minority of exposed people develops MPM. In fact, the incidence among professionally exposed workers was shown to vary between 0.5% and 18.0%. Various hints suggested that other important cofactors could play a role, in particular the genetic susceptibility. Impressive is the case of Cappadocians families exposed to erionite and affected by an "epidemic" of MPM with about half of the inhabitants dying for the disease. However, no results for a "Cappadocia" gene of susceptibility to MPM have been obtained yet and more studies are needed. Among asbestos-exposed workers, several studies reported familial cases of MPM, suggesting that heredity could be important in the tumor development. However, large studies on familial clusters showed only weak increased risks that could be attributable also to indirect exposures in a contaminated household. Moreover, the risk of developing MPM is increased of a limited extent among people exposed to asbestos with a positive history of familial cancers. A particular is represented by carriers of germline mutations within BAP1 gene. In families and in animal models, mutations within BAP1 are strongly predisposing to develop MPM. However, also other types of cancer (such as uveal melanoma) are present, thus BAP1 mutations are considered as responsible for a hereditary form of a multi-cancer syndrome. In any case, among sporadic MPM, the prevalence of germline BAP1 mutations is negligible. Finally, genetic studies highlighted the presence of low-risk susceptibility alleles, such as those within XRCC3, NAT2 or GSTM1. Two different genome-wide association studies could not find positive associations reaching the genome-wide statistical significance threshold, however, both were concordant in showing a weak signal within the SDK1 gene region. Overall, it could be concluded that, as for other types of sporadic cancers, the susceptibility to develop MPM following asbestos exposure is modulated moderately by the individual genetic background. Further studies on larger series could help in a better characterization of more genes predisposing to MPM, being this tumor a rare disease.}, } @article {pmid29507791, year = {2018}, author = {Pira, E and Donato, F and Maida, L and Discalzi, G}, title = {Exposure to asbestos: past, present and future.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S237-S245}, pmid = {29507791}, issn = {2072-1439}, abstract = {This paper summarises the past, present and future of asbestos exposure. The future scenarios as to the mesothelioma incidence in countries, where asbestos has been banned, are discussed.}, } @article {pmid29507789, year = {2018}, author = {Marinaccio, A and Binazzi, A and Bonafede, M and Di Marzio, D and Scarselli, A and , }, title = {Epidemiology of malignant mesothelioma in Italy: surveillance systems, territorial clusters and occupations involved.}, journal = {Journal of thoracic disease}, volume = {10}, number = {Suppl 2}, pages = {S221-S227}, pmid = {29507789}, issn = {2072-1439}, abstract = {Background: As a legacy of the large asbestos consumption until the definitive ban in 1992, Italy is currently suffering a severe epidemic of asbestos related diseases. The aim of this paper is to describe the surveillance system for mesothelioma incidence and to provide evidences regarding the occurrence of the disease in Italy and the circumstances of asbestos exposure.

Methods: Italian National Register of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with Regional Operating Centres (CORs) active in each Italian region, identifying incident malignant mesothelioma (MM) cases from health care structures. Occupational history, lifestyle habits and residential history are obtained using a standardised questionnaire, administered by a trained interviewer, to the subject or to the next of kin. Descriptive epidemiological figures, occupations involved in exposures and territorial maps of MM cases have been produced.

Results: At December 2016, ReNaM has collected 27,356 MM cases for the incidence period 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 interviewed cases (14,818). Non-occupational exposure is still relevant with 4.9% and 4.4% of cases for which respectively a familial exposure (due to the cohabitation with an occupational exposed subject) and an environmental exposure (due to the residence near a contaminated site) has been detected.

Discussion: The epidemiological surveillance of MM incident cases, by the means of a national register for estimating the occurrence of the disease and identifying the circumstances of asbestos exposure, is a relevant tool for preventing asbestos exposure, for supporting the effectiveness of insurance system and for estimating reliable epidemiological figures.}, } @article {pmid29507420, year = {2018}, author = {Rehrauer, H and Wu, L and Blum, W and Pecze, L and Henzi, T and Serre-Beinier, V and Aquino, C and Vrugt, B and de Perrot, M and Schwaller, B and Felley-Bosco, E}, title = {How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations.}, journal = {Oncogene}, volume = {37}, number = {20}, pages = {2645-2659}, pmid = {29507420}, issn = {1476-5594}, mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Asbestos, Crocidolite/*adverse effects ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Lung Neoplasms/chemically induced/*genetics/metabolism ; Macrophage Activation ; Mesothelioma/chemically induced/*genetics/metabolism ; Mice ; Mutation ; Phosphoproteins ; Polymorphism, Single Nucleotide ; *RNA Editing ; *Transcriptional Activation ; }, abstract = {Chronic exposure to intraperitoneal asbestos triggered a marked response in the mesothelium well before tumor development. Macrophages, mesothelial precursor cells, cytokines, and growth factors accumulated in the peritoneal lavage. Transcriptome profiling revealed YAP/TAZ activation in inflamed mesothelium with further activation in tumors, paralleled by increased levels of cells with nuclear YAP/TAZ. Arg1 was one of the highest upregulated genes in inflamed tissue and tumor. Inflamed tissue showed increased levels of single-nucleotide variations, with an RNA-editing signature, which were even higher in the tumor samples. Subcutaneous injection of asbestos-treated, but tumor-free mice with syngeneic mesothelioma tumor cells resulted in a significantly higher incidence of tumor growth when compared to naïve mice supporting the role of the environment in tumor progression.}, } @article {pmid29506546, year = {2018}, author = {Yin, W and Zheng, G and Yang, K and Song, H and Liang, Y}, title = {Analysis of prognostic factors of patients with malignant peritoneal mesothelioma.}, journal = {World journal of surgical oncology}, volume = {16}, number = {1}, pages = {44}, pmid = {29506546}, issn = {1477-7819}, support = {1213018ZD//Cangzhou Science and Technology Research and Development Plan/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/*analysis ; Cisplatin/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/drug therapy/*pathology ; Lymphocytes/*pathology ; Male ; Mesothelioma/drug therapy/*pathology ; Middle Aged ; Neutrophils/*pathology ; Pemetrexed/administration & dosage ; Peritoneal Neoplasms/drug therapy/*pathology ; Prognosis ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: The study aims to find out independent prognostic factors for patients with malignant peritoneal mesothelioma (MPeM).

METHODS: Patients with pathologically proven MPeM were retrospectively reviewed. Potential prognostic factors were analyzed, including age, gender, asbestos exposure, body mass index (BMI), treatment, and laboratory results, such as blood routine examination and liver functions. The influences of various risk factors on the prognoses were analyzed by univariate analysis. A Cox regression model analysis established independent factors for the survival prognosis of the patients.

RESULTS: Seventy MPeM patients, including 33 patients who received intraperitoneal chemotherapy with cisplatin, 14 patients who received systemic chemotherapy with cisplatin + pemetrexed, and 21 untreated patients were included in this study. The 1-year survival was 32.9%, the 2-year survival was 10%, and the 3-year survival was 2.9%. The median age of MPeM was 62 years, and the female-to-male ratio was 1:0.56. The univariate and multivariate analyses showed that treatment, albumin (ALB), and blood neutrophil-to-lymphocyte ratio (NLR) were independent factors that affected the overall survival (OS) of MPeM patients.

CONCLUSION: High blood NLR and hypoalbuminemia are adverse prognostic factors for MPeM patients. Systemic chemotherapy and intraperitoneal chemotherapy can prolong the survival period.}, } @article {pmid29498660, year = {2018}, author = {Pietrofesa, RA and Chatterjee, S and Park, K and Arguiri, E and Albelda, SM and Christofidou-Solomidou, M}, title = {Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605) Reduces Asbestos-Induced Cytotoxicity in an Nrf2-Dependent and -Independent Manner.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {7}, number = {3}, pages = {}, pmid = {29498660}, issn = {2076-3921}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R21 AT008291/AT/NCCIH NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; }, abstract = {Asbestos exposure triggers inflammatory processes associated with oxidative stress and tissue damage linked to malignancy. LGM2605 is the synthetic lignan secoisolariciresinol diglucoside (SDG) with free radical scavenging, antioxidant, and anti-inflammatory properties in diverse inflammatory cell and mouse models, including exposure to asbestos fibers. Nuclear factor-E2 related factor 2 (Nrf2) activation and boosting of endogenous tissue defenses were associated with the protective action of LGM2605 from asbestos-induced cellular damage. To elucidate the role of Nrf2 induction by LGM2605 in protection from asbestos-induced cellular damage, we evaluated LGM2605 in asbestos-exposed macrophages from wild-type (WT) and Nrf2 disrupted (Nrf2-/-) mice. Cells were pretreated with LGM2605 (50 µM and 100 µM) and exposed to asbestos fibers (20 µg/cm²) and evaluated 8 h and 24 h later for inflammasome activation, secreted cytokine levels (interleukin-1β (IL-1β), interleukin-18 (IL-18), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα)), cytotoxicity and cell death, nitrosative stress, and Nrf2-regulated enzyme levels. Asbestos exposure induced robust oxidative and nitrosative stress, cell death and cytotoxicity, which were equally mitigated by LGM2605. Inflammasome activation was significantly attenuated in Nrf2-/- macrophages compared to WT, and the protective action of LGM2605 was seen only in WT cells. In conclusion, in a cell model of asbestos-induced toxicity, LGM2605 acts via protective mechanisms that may not involve Nrf2 activation.}, } @article {pmid29495596, year = {2018}, author = {Angelico, G and Caltabiano, R and Loreto, C and Ieni, A and Tuccari, G and Ledda, C and Rapisarda, V}, title = {Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report.}, journal = {International journal of molecular sciences}, volume = {19}, number = {3}, pages = {}, pmid = {29495596}, issn = {1422-0067}, mesh = {Aged ; Aged, 80 and over ; Aquaporin 1/genetics/*metabolism ; Asbestos, Amphibole/*adverse effects ; Biomarkers, Tumor ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/*etiology/*metabolism/mortality/pathology ; Male ; Mesothelioma/*etiology/*metabolism/mortality/pathology ; Middle Aged ; Pleural Neoplasms/*etiology/*metabolism/pathology ; Prognosis ; Proportional Hazards Models ; }, abstract = {BACKGROUND: The immunohistochemical expression of aquaporin-1 (AQP1) in asbestos-related malignant pleural mesothelioma (MPM) is emerging as a useful prognostic indicator of improved survival. A significantly increased incidence of MPM in a small town in southern Italy was ascribed to exposure to fluoro-edenite (FE), a naturally occurring asbestos fiber. We investigated the immunohistochemical expression of AQP1 in patients affected by FE-related MPM; taking into consideration its suggested independent prognostic role, its possible correlation with clinicopathological parameters and patient outcome was also evaluated.

METHODS: Ten patients were selected for this study, as neoplastic tissue blocks, clinical and follow-up data were available. The immunohistochemical overexpression of AQP1 was defined as ≥50% of tumor cells showing membranous staining.

RESULTS: Six cases showed AQP1 expression in ≥50% of tumor cells; in this group, a significant association of AQP1 overexpression with an increased median overall survival (OS) of 26.3 months was observed. By contrast, four patients exhibited an AQP1 score of <50% of stained cells, with a shorter median OS of 8.9 months.

CONCLUSIONS: The present study represents further confirmation of the hypothesized prognostic role of AQP1, which seems a reliable prognostic indicator.}, } @article {pmid29480760, year = {2018}, author = {Attanoos, RL and Churg, A and Galateau-Salle, F and Gibbs, AR and Roggli, VL}, title = {Malignant Mesothelioma and Its Non-Asbestos Causes.}, journal = {Archives of pathology & laboratory medicine}, volume = {142}, number = {6}, pages = {753-760}, doi = {10.5858/arpa.2017-0365-RA}, pmid = {29480760}, issn = {1543-2165}, abstract = {CONTEXT: - Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma.

OBJECTIVE: - To provide a review of non-asbestos causes for malignant mesothelioma.

DATA SOURCES: - Review of relevant published literature via PubMed and other search engines.

CONCLUSIONS: - Currently, most pleural mesotheliomas (70% to 90%) in men in Europe and North America are attributable to asbestos exposure; for peritoneal mesothelioma the proportion is lower. In North America few mesotheliomas in women at any site are attributable to asbestos exposure, but in Europe the proportion is higher and varies considerably by locale. In certain geographic locations other types of mineral fibers (erionite, fluoro-edenite, and probably balangeroite) can induce mesothelioma. Therapeutic radiation for other malignancies is a well-established cause of mesothelioma, with relative risks as high as 30. Carbon nanotubes can also induce mesotheliomas in animals but there are no human epidemiologic data that shed light on this issue. Chronic pleural inflammation may be a cause of mesothelioma but the data are scanty. Although SV40 can induce mesotheliomas in animals, in humans the epidemiologic data are against a causative role. A small number of mesotheliomas (probably in the order of 1%) are caused by germline mutations/deletions of BRCA1-associated protein-1 (BAP1) in kindreds that also develop a variety of other cancers. All of these alternative etiologies account for a small proportion of tumors, and most mesotheliomas not clearly attributable to asbestos exposure are spontaneous (idiopathic).}, } @article {pmid29473898, year = {2018}, author = {Soeberg, M and Vallance, DA and Keena, V and Takahashi, K and Leigh, J}, title = {Australia's Ongoing Legacy of Asbestos: Significant Challenges Remain Even after the Complete Banning of Asbestos Almost Fifteen Years Ago.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {2}, pages = {}, pmid = {29473898}, issn = {1660-4601}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*epidemiology/*etiology/prevention & control ; Australia/epidemiology ; Female ; *Health Policy ; Humans ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Middle Aged ; Occupational Exposure/adverse effects/*legislation & jurisprudence ; }, abstract = {The most effective way of reducing the global burden of asbestos-related diseases is through the implementation of asbestos bans and minimising occupational and non-occupational exposure to respirable asbestos fibres. Australia's asbestos consumption peaked in the 1970s with Australia widely thought to have had among the highest per-capita asbestos consumption level of any country. Australia's discontinuation of all forms of asbestos and asbestos-containing products and materials did not occur at a single point of time. Crocidolite consumption ceased in the late 1960s, followed by amosite consumption stopping in the mid 1980s. Despite significant government reports being published in 1990 and 1999, it was not until the end of 2003 that a complete ban on all forms of asbestos (crocidolite, amosite, and chrysotile) was introduced in Australia. The sustained efforts of trade unions and non-governmental organisations were essential in forcing the Australian government to finally implement the 2003 asbestos ban. Trade unions and non-government organisations continue to play a key role today in monitoring the government's response to Australian asbestos-related disease epidemic. There are significant challenges that remain in Australia, despite a complete asbestos ban being implemented almost fifteen years ago. The Australian epidemic of asbestos-related disease has only now reached its peak. A total of 16,679 people were newly diagnosed with malignant mesothelioma between 1982 and 2016, with 84% of cases occurring in men. There has been a stabilisation of the age-standardised malignant mesothelioma incidence rate in the last 10 years. In 2016, the incidence rate per 100,000 was 2.5 using the Australian standard population and 1.3 using the Segi world standard population. Despite Australia's complete asbestos ban being in place since 2003, public health efforts must continue to focus on preventing the devastating effects of avoidable asbestos-related diseases, including occupational and non-occupational groups who are potentially at risk from exposure to respirable asbestos fibres.}, } @article {pmid29458304, year = {2017}, author = {Barlow, CA and Grespin, M and Best, EA}, title = {Asbestos fiber length and its relation to disease risk.}, journal = {Inhalation toxicology}, volume = {29}, number = {12-14}, pages = {541-554}, doi = {10.1080/08958378.2018.1435756}, pmid = {29458304}, issn = {1091-7691}, mesh = {Animals ; Asbestos/metabolism/*toxicity ; Carcinogens/metabolism/*toxicity ; Cells, Cultured ; Environmental Exposure/adverse effects ; Humans ; Lung/*drug effects/metabolism/pathology ; Mineral Fibers/*toxicity ; Occupational Exposure/adverse effects ; Pulmonary Fibrosis/chemically induced/metabolism/pathology ; Risk Factors ; }, abstract = {Differences in chemical and crystalline composition, fiber dimension, aerodynamic characteristics and biodurability are among the critical factors that define the toxicological and pathological consequences of asbestos exposure. Specifically, fiber dimension can impact whether the fiber is respired, whether and how deeply it is deposited in the lung, and how efficiently and rapidly it may be cleared. This paper provides a current, comprehensive evaluation of the weight of evidence regarding the relationship between asbestos fiber length and disease potency (for malignant and nonmalignant endpoints). In vitro studies, animal exposure studies and epidemiology data were reviewed. We found that the data reported over the last several decades consistently support the conclusions that exposure to fibers longer than 10 µm and perhaps 20 µm are required to significantly increase the risk of developing asbestos-related disease in humans and that there is very little, if any, risk associated with exposure to fibers shorter than 5 µm. Fiber length as a predictor of potency has been evaluated by several federal agencies in the U.S. and could significantly influence future regulatory decisions for elongated mineral particles (EMPs) and high-aspect ratio nanoparticles (HARNs).}, } @article {pmid29438360, year = {2018}, author = {Linton, A and Cheng, YY and Griggs, K and Schedlich, L and Kirschner, MB and Gattani, S and Srikaran, S and Chuan-Hao Kao, S and McCaughan, BC and Klebe, S and van Zandwijk, N and Reid, G}, title = {An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {118}, number = {6}, pages = {e13}, doi = {10.1038/bjc.2018.3}, pmid = {29438360}, issn = {1532-1827}, abstract = {This corrects the article DOI: 10.1038/bjc.2017.85.}, } @article {pmid29435293, year = {2018}, author = {Yano, M and Ikeda, Y and Kato, T and Sakaki, M and Sato, S and Yabuno, A and Kozawa, E and Yasuda, M}, title = {A case of peritoneal malignant mesothelioma following radiation therapy for cervical cancer.}, journal = {Molecular and clinical oncology}, volume = {8}, number = {2}, pages = {302-305}, pmid = {29435293}, issn = {2049-9450}, abstract = {The present study presents a case of peritoneal malignant mesothelioma (PMM) following radiation therapy for cervical cancer. A 34-year-old Japanese woman, without asbestos exposure, was referred to the Department of Gynecologic Oncology, Saitama Medical University International Medical Center due to a cervical mass, and was diagnosed with cervical squamous cell carcinoma (SCC). The serum levels of tumor markers, including SCC antigen and cancer antigen 125 (CA125) were 229.0 ng/ml and 54.4 U/ml, respectively. The patient underwent concurrent chemoradiotherapy (CCRT), and a complete response was achieved. After 54 months, ascites was found at the rectouterine pouch, but peritoneal cytology suggested reactive mesothelial cell. After 62 months of CCRT, magnetic resonance imaging revealed masses in both the salpinges. The serum levels of SCC and CA125 were 0.9 ng/ml and 506.1 U/ml, respectively. Following this, left salpingectomy and peritoneal biopsy were performed laparoscopically. Histologic examination revealed atypical mesothelial cells with no continuity of background tubal epithelium. Immunohistochemistry showed positive staining for calretinin, thrombomodulin, mesothelin and glucose transporter 1. Based on these findings, the patient was diagnosed with PMM epithelioid type and underwent systemic chemotherapy; stable disease status has been obtained for 3 months. This case demonstrates the possibility of PMM occurrence within 10 years after radiotherapy, and indicates the importance of histological and immunohistochemical examination, particularly in cases of an atypical tumorigenesis pattern from the primary cancer.}, } @article {pmid29434985, year = {2018}, author = {Yoneda, K and Chikaishi, Y and Kuwata, T and Ohnaga, T and Tanaka, F}, title = {Capture of mesothelioma cells with 'universal' CTC-chip.}, journal = {Oncology letters}, volume = {15}, number = {2}, pages = {2635-2640}, pmid = {29434985}, issn = {1792-1074}, abstract = {Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM.}, } @article {pmid29430704, year = {2018}, author = {Tanaka, H and Akiyama, Y and Kitamura, A and Matsumoto, N and Tomita, M and Kataoka, H}, title = {Malignant mesothelioma with squamous differentiation.}, journal = {Histopathology}, volume = {72}, number = {7}, pages = {1216-1220}, doi = {10.1111/his.13482}, pmid = {29430704}, issn = {1365-2559}, mesh = {Carcinoma, Squamous Cell/*diagnosis/pathology ; Diagnosis, Differential ; Humans ; Lung Neoplasms/*diagnosis/pathology ; Male ; Mesothelioma/*diagnosis/pathology ; Middle Aged ; Pleural Neoplasms/*diagnosis/pathology ; }, abstract = {AIMS: We report the autopsy findings of a 58-year-old man with malignant mesothelioma in the left pleural cavity.

METHODS AND RESULTS: The patient had a history of asbestos exposure, and the chest computed tomography scan on initial admission demonstrated an extrapleural sign, suggesting a nodular lesion in the chest wall. However, no nodular lesions were detectable in either of his lungs. In spite of chemotherapy, he died 4 months after the initial admission. An autopsy revealed markedly thickened pleura in a large section of the left pleural cavity without visible intrapulmonary primary tumour lesions. Histological examination of a biopsy specimen obtained prior to chemotherapy and that of an autopsy specimen showed that the pleural tumour was composed of a mixture of mesothelioma and tumour cells with squamous differentiation mimicking squamous cell carcinoma.

CONCLUSIONS: To the best of our knowledge, this is the first case report of mesothelioma with extensive squamous differentiation in the English-language literature. The extensive squamous differentiation reminiscent of squamous cell carcinoma can be a pitfall in the pathological diagnosis of pleural cytology and that of biopsy specimens from patients with mesothelioma. Here, we report autopsy findings of a case of malignant mesothelioma with portions of extensive squamous differentiation, mimicking a squamous cell carcinoma.}, } @article {pmid29424961, year = {2018}, author = {Abdel-Rahman, O}, title = {Global trends in mortality from malignant mesothelioma: Analysis of WHO mortality database (1994-2013).}, journal = {The clinical respiratory journal}, volume = {12}, number = {6}, pages = {2090-2100}, doi = {10.1111/crj.12778}, pmid = {29424961}, issn = {1752-699X}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Databases, Factual ; Female ; Global Health ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; *Registries ; Retrospective Studies ; Sex Distribution ; Survival Rate/trends ; }, abstract = {BACKGROUND AND OBJECTIVE: Little is known about the extent to which asbestos use ban has affected global trends in malignant mesothelioma. This study investigated recent global mortality trends of malignant mesothelioma.

METHODS: Data were collected from International Agency for Research on Cancer/World Health Organization mortality database to examine age-standardized, gender-specific mortality rates for malignant mesothelioma (ICD10-C45). Cross-sectional mortality rates (2009-2013) as well as trends over time (1994-2013) were also reported. Gender-specific annual percent change (APC) was calculated to examine trends over time for each country.

RESULTS: Among the 30 countries with highest mesothelioma mortality in men, there is almost 10-fold variation in mortality rates during 2009-2013 ranging from 6.25 per 100 000 for United Kingdom to 0.64 per 100 000 in Portugal; whereas, among the 30 countries with highest mesothelioma mortality in women, there is a 4-fold variation in mortality rates during 2009-2013 ranging from 1.08 per 100 000 for United Kingdom to 0.26 per 100 000 in Ireland. Mortality rates were higher in men compared to women in 32 out of 35 evaluable countries. Among males and over the last 10 years of covered years, mesothelioma mortality was significantly declining in 9 countries (United Kingdom, Sweden, France, Germany, Netherlands, Canada, United States, Australia, and New Zealand); whereas, it was significantly rising in 5 countries (Poland, Spain, China-Hong Kong, Japan, and Republic of Korea). In the remaining countries, APC was stable. Among females and over the last 10 years of covered years, mesothelioma mortality was significantly declining in 1 country only (Italy); whereas, it was significantly rising in 3 countries (Poland, Argentina, and Republic of Korea). In the remaining countries, APC was stable.

CONCLUSIONS: There is a worldwide variability in the burden and trends of mesothelioma mortality; and despite the ban on asbestos in many countries, mesothelioma still represents an important cause of mortality.}, } @article {pmid29421994, year = {2017}, author = {Fathi Fathabadi, MK and Abdolahnejad, A and Teiri, H and Hajizadeh, Y}, title = {Spatio-seasonal variation of airborne asbestos concentration in urban areas of Shiraz, Iran.}, journal = {International journal of occupational and environmental health}, volume = {23}, number = {2}, pages = {143-150}, pmid = {29421994}, issn = {2049-3967}, mesh = {Air Pollutants, Occupational/*analysis ; Asbestos/*analysis ; Cities ; *Construction Industry ; *Environmental Monitoring ; Geographic Information Systems ; Iran ; Microscopy, Electron, Scanning ; Microscopy, Phase-Contrast ; Seasons ; Spatial Analysis ; }, abstract = {Background Asbestos fiber is mainly released from friction product in brakes and clutch linings and from reinforcing agent in the asbestos-cement industry. It leads to serious health problem such as mesothelioma and lung cancer. The objectives of this study were to monitor the levels of asbestos fibers in ambient air of Shiraz, Iran during 2014, and to draw its GIS distribution map for the city. Methods Samples were collected by mixed cellulose ester filters mounted on an open-faced filter holder using a SKC sampling pump. Fiber counting was conducted using both phase contrast microscopy (PCM) method to determine total fibers, and scanning electron microscopy (SEM) method to identify non-asbestos from asbestos fibers. Results The average concentrations of asbestos fibers in ambient air of the city were 1.11 ± 0.25 PCM f/l and 12.21 ± 2.52 SEM f/l. The highest concentration of asbestos fibers was measured in Valiasr square amounting 1.96 ± 0.34 PCM f/l and 16.87 ± 2.14 SEM f/l. Conclusions The average of asbestos fibers in all sampling points was higher than the WHO guideline (0.05 PCM f/l, 2.2 SEM f/l). This may be attributed to the frequently occurrence of heavy traffic, the existence of relevant industries in and around the city, and the topographic characteristics of the city. Thus, product substitution, traffic smoothing and industrial sites relocating are suggested to eliminate the asbestos fibers emission.}, } @article {pmid29419731, year = {2018}, author = {Kumagai-Takei, N and Yamamoto, S and Lee, S and Maeda, M and Masuzzaki, H and Sada, N and Yu, M and Yoshitome, K and Nishimura, Y and Otsuki, T}, title = {Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos.}, journal = {International journal of molecular sciences}, volume = {19}, number = {2}, pages = {}, pmid = {29419731}, issn = {1422-0067}, mesh = {Animals ; Apoptosis ; Asbestos/administration & dosage/*adverse effects/metabolism ; Biomarkers ; Carcinogens ; Cytokines ; Environmental Exposure ; Humans ; Inflammation/*etiology/metabolism/pathology ; Inflammation Mediators ; Lung Neoplasms/etiology ; Mesothelioma/etiology ; T-Lymphocytes/*drug effects/immunology/metabolism ; }, abstract = {Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous exposure to asbestos fibers for more than eight months, MT-2 sublines showed acquisition of resistance to asbestos-induced apoptosis with decreased death signals and increased surviving signals. These sublines showed various characteristics that suggested a reduction in anti-tumor immunity. On the other hand, inflammatory changes such as expression of MMP7, CXCR5, CXCL13 and CD44 was found to be markedly higher in sublines continuously exposed to asbestos compared with original MT-2 cells. All of these molecules contribute to lung inflammation, T and B cell interactions and connections between mesothelial cells and T cells. Thus, further investigation focusing on these molecules may shed light on the role of chronic inflammation caused by asbestos exposure and the occurrence of malignant mesothelioma. Finally, regarding peripheral T cells from healthy donors (HD) and asbestos-exposed patients with pleural plaque (PP) or malignant pleural mesothelioma (MPM), following stimulation of CD4+ T cells, T cells from MPM patients showed reduced potential of interferon (IFN)-γ expression. Moreover, levels of interleukin (IL)-6, one of the most important cytokines in chronic inflammation, in cultured supernatants were higher in PP and MPM patients compared with HD. Overall, asbestos-induced chronic inflammation in the lung as well as the pleural cavity may facilitate the onset of asbestos-induced cancers due to alterations in the interactions among fibers, immune cells such as T and B cells and macrophages, and mesothelial and lung epithelial cells. Further investigations regarding chronic inflammation caused by asbestos fibers may assist in identifying molecular targets for preventive and therapeutic strategies related to the effects of asbestos exposure.}, } @article {pmid29416614, year = {2018}, author = {Thompson, JK and Shukla, A and Leggett, AL and Munson, PB and Miller, JM and MacPherson, MB and Beuschel, SL and Pass, HI and Shukla, A}, title = {Extracellular signal regulated kinase 5 and inflammasome in progression of mesothelioma.}, journal = {Oncotarget}, volume = {9}, number = {1}, pages = {293-305}, pmid = {29416614}, issn = {1949-2553}, abstract = {Malignant mesothelioma is an aggressive cancer in desperate need of treatment. We have previously shown that extracellular signaling regulated kinase 5 (ERK5) plays an important role in mesothelioma pathogenesis using ERK5 silenced human mesothelioma cells exhibiting significantly reduced tumor growth in immunocompromised mice. Here, we used a specific ERK 5 inhibitor, XMD8-92 in various in vitro and in vivo models to demonstrate that inhibition of ERK5 can slow down mesothelioma tumorigenesis. First, we show a dose dependent toxicity of XMD8-92 to 2 human mesothelioma cell lines growing as a monolayer. We also demonstrate the inhibition of ERK5 phosphorylation in various human mesothelioma cell lines by XMD8-92. We further confirmed the toxicity of XMD8-92 towards mesothelioma cell lines grown as spheroids in a 3-D model as well as in intraperitoneal (immune-competent) and intrapleural (immune-deficient) mouse models with and without chemotherapeutic drugs. To ascertain the mechanism, we explored the role of the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in the process. We found XMD8-92 attenuated naïve and chemotherapeutic-induced inflammasome priming and activation in mesothelioma cells. It can thus be concluded that ERK5 inhibition attenuates mesothelioma tumor growth and this phenomenon in part is regulated by the inflammasome.}, } @article {pmid29415822, year = {2018}, author = {Scherpereel, A and Willemin, MC and Wasielewski, E and Dhalluin, X}, title = {[Anti-tumor immunotherapy in malignant pleural mesothelioma].}, journal = {Revue des maladies respiratoires}, volume = {35}, number = {4}, pages = {465-476}, doi = {10.1016/j.rmr.2017.07.025}, pmid = {29415822}, issn = {1776-2588}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bevacizumab/administration & dosage/adverse effects ; Cisplatin/administration & dosage/adverse effects ; Combined Modality Therapy ; Humans ; Immunotherapy/*methods ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Pemetrexed/administration & dosage/adverse effects ; Pleural Neoplasms/*drug therapy ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a quite rare cancer, but with increasing incidence, that is usually induced by previous asbestos exposure. Its prognosis is poor and there is no validated curative therapy to date. Surgery of MPM, done only by few expert teams within a multimodal treatment is of limited and still disputed value. The standard treatment of MPM, relying on first-line chemotherapy by combined cisplatin-pemetrexed is often poorly effective, even if combination with bevacizumab anti-VEGF antibodies has slightly improved the results. Moreover, no second line treatment is recommended in case of failure of this chemotherapy. Therefore, the search of new therapies or strategies is crucial and the recruitment of patients in clinical trials is highly encouraged.

BACKGROUND: Among the treatments under investigation, various anti-tumour immunotherapies, in particular immune checkpoints inhibitors (ICI), currently exhibit the most promising preliminary results. First data from the phase II, randomized "IFCT MAPS-2", recently presented during the 2017 ASCO meeting, confirmed the value of ICI in MPM patients in cases of chemotherapy failure.

OUTLOOK AND CONCLUSIONS: However, several exciting immunotherapies other than ICI are presently being evaluated in MPM and are reported in this article. Moreover, many questions still need to be answered about immunotherapy: what is its potential value as first line treatment? How to target the best candidates for these treatments? Which combinations between immunotherapy and standard chemotherapy, targeted therapies, surgery or radiotherapy? Finally, it is now essential that every clinician has sufficient knowledge about the possible toxicities of immunotherapy.}, } @article {pmid29413505, year = {2018}, author = {Blyth, KG and Murphy, DJ}, title = {Progress and challenges in Mesothelioma: From bench to bedside.}, journal = {Respiratory medicine}, volume = {134}, number = {}, pages = {31-41}, doi = {10.1016/j.rmed.2017.11.015}, pmid = {29413505}, issn = {1532-3064}, support = {ETM/285//Chief Scientist Office/United Kingdom ; }, mesh = {Biomarkers, Tumor/metabolism ; Biopsy ; Humans ; Lung Neoplasms/*diagnostic imaging/genetics/pathology/*therapy ; Magnetic Resonance Imaging ; Mesothelioma/*diagnostic imaging/genetics/pathology/*therapy ; Mutation ; Neoplasm Staging ; Positron Emission Tomography Computed Tomography ; Translational Medical Research/methods/*trends ; }, abstract = {Malignant Pleural Mesothelioma (MPM) is currently an incurable cancer with a typical survival of 1 year from the time of diagnosis. The recent genomic and transcriptomic characterization of MPM presents new opportunities and challenges for MPM researchers. Recent advances in clinical and laboratory diagnostics, and proposals for an updated, data-driven, staging system, also present new challenges for clinicians and hospital services involved in MPM care. The aim of this review is first to introduce the reader to the topic of MPM, a disease that is causally linked to prior, typically occupational, exposure to asbestos fibres. Secondly, we will discuss MPM from the clinical and laboratory perspectives, including reviews of current and evolving therapies and our present understanding of the molecular basis of the disease. Finally, we will attempt to identify critical knowledge gaps that currently prevent more effective treatment, including the challenges involved in early detection and chemoprophylaxis.}, } @article {pmid29395477, year = {2018}, author = {Soloukey Tbalvandany, SS and Maat, AAPWM and Cornelissen, RR and Nuyttens, JJJME and Takkenberg, JJJM}, title = {WWW mesothelioma information: Surfing on unreliable waters. A cross-sectional study into the content and quality of online informational resources for mesothelioma patients.}, journal = {Patient education and counseling}, volume = {101}, number = {6}, pages = {1088-1094}, doi = {10.1016/j.pec.2018.01.009}, pmid = {29395477}, issn = {1873-5134}, mesh = {Benchmarking ; Consumer Health Information ; Cross-Sectional Studies ; Decision Making ; Humans ; Information Services/*standards ; *Information Storage and Retrieval ; *Internet ; Mesothelioma/*diagnosis/*therapy ; Netherlands ; Patients/*psychology ; }, abstract = {OBJECTIVE: Malignant Mesothelioma (MM) is a rare asbestos related disease mostly diagnosed in low-skilled patients. The decision-making process for MM treatment is complicated, making an adequate provision of information necessary. The objective of this study is to assess the content and quality of online informational resources available for Dutch MM patients.

METHODS: The first 100 hits of a Google search were studied using the JAMA benchmarks, the Modified Information Score (MIS) and the International Patient Decision Aid Standard Scoring (IPDAS).

RESULTS: A total of 37 sources were included. Six of the 37 resources were published by hospitals. On average, the informational resources scored 37 points on the MIS (scale 0-100). The resources from a (bio)medical sources scored the best on this scale. However, on the domain of use of language, these resources scored the worst.

CONCLUSIONS: The current level of medical content and quality of online informational resources for patient with MM is below average and cannot be used as decision-aids for patients.

PRACTICE IMPLICATIONS: The criteria used in this article could be used for future improvements of online informational resources for patients, both online, offline and through health education in the care path.}, } @article {pmid29387394, year = {2018}, author = {Tian, D and Wen, H and Brown, HE and Wang, X and Zhang, L and Fu, M}, title = {Multiple intracranial metastases from postoperative giant sarcomatoid malignant pleural mesothelioma: A case report and literature review.}, journal = {Molecular and clinical oncology}, volume = {8}, number = {1}, pages = {34-37}, pmid = {29387394}, issn = {2049-9450}, abstract = {Sarcomatoid malignant pleural mesothelioma (SMPM) is a rare tumor with poor response to treatment and a dismal prognosis. Distant metastases are not uncommon and usually appear at the late stages of the disease. However, cerebral metastases have rarely been documented. We herein report a case of a giant sarcomatoid carcinoma of the pleura in a 41-year-old male patient with no history of exposure to asbestos, who presented with a chief complaint of left-sided chest pain for 1 month. Extrapleural pneumonectomy and rib excision were performed. At 5 months after the surgery, the patient was diagnosed with multiple intracranial metastatic neoplasms and succumbed to the disease soon thereafter. The aim of the present case report was to emphasize this rare metastatic pattern and aggressive clinical course of SMPM, with a supplementary review of the previously published literature.}, } @article {pmid29386699, year = {2017}, author = {Cheng, YY and Mok, E and Tan, S and Leygo, C and McLaughlin, C and George, AM and Reid, G}, title = {SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {2536187}, pmid = {29386699}, issn = {1875-8630}, mesh = {Asbestos/*toxicity ; Biomarkers, Tumor/blood/*genetics/metabolism ; Carcinogens/*toxicity ; Cell Line, Tumor ; DNA Methylation/drug effects ; Epigenesis, Genetic ; Eye Proteins/blood/*genetics/metabolism ; Humans ; Lung Neoplasms/blood/*genetics ; Membrane Proteins/blood/*genetics/metabolism ; Mesothelioma/blood/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM. SFRP genes are antagonists of Wnt pathway, and SFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation of SFRP genes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation of SFRP2 (56%) and SFRP5 (70%) in MPM. SFRP2 and SFRP5 tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of the SFRP1 and SFRP2 genes in the mesothelium (MeT-5A) via epigenetic alterations. Finally, DNA methylation of SFRPs is detectable in MPM patient plasma samples, with methylated SFRP2 and SFRP5 showing a tendency towards greater abundance in patients. These data suggested that SFRP genes have tumour-suppresive activity in MPM and that methylated DNA from SFRP gene promoters has the potential to serve as a biomarker for MPM patient plasma.}, } @article {pmid29375946, year = {2017}, author = {Arda, E and Arıkan, MG and Cetin, G and Kuyumcuoğlu, U and Usta, U}, title = {Malignant Mesothelioma of Tunica Vaginalis Testis: Macroscopic and Microscopic Features of a Very Rare Malignancy.}, journal = {Cureus}, volume = {9}, number = {11}, pages = {e1860}, pmid = {29375946}, issn = {2168-8184}, abstract = {Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is an extremely rare tumour, usually mimicking benign pathologies of the scrotum. Our case is an 84-year-old male patient who appealed with a painless, left-sided scrotal swelling longer than 2 months. Although the level of tumour markers was normal, ultrasonographic examination results forced us to perform an inguinal scrotal exploration. Multiple small papillary tumours, both on tunica vaginalis and tunica albuginea, were detected intraoperatively. Due to these findings, radical orchiectomy was performed. A pathological evaluation showed malignant mesothelioma (MM) of the tunica vaginalis testis. Exposure to asbestos is a well-known risk factor. Furthermore, a history of trauma, herniorrhaphy and chronic hydroceles is blamed as a possible risk factor. Scrotal ultrasonography is the mainstay of primary diagnosis and, therefore, it should not be overlooked when dealing with benign scrotal cysts or hydroceles, which are very common pathologies at these decades, too. Radical inguinal orchiectomy is the primary treatment choice for localised MMTVT disease, whereas in signs of lymph node metastasis, inguinal lymph node dissection is required. Radical resection should be completed with chemotherapy and/or radiotherapy for an advanced or recurrent disease. This case, which is very rarely reported in the literature and detected during inguinal exploration, along with the pathological works that supported the diagnosis, was presented with this report.}, } @article {pmid29375377, year = {2017}, author = {Oien, DB and Garay, T and Eckstein, S and Chien, J}, title = {Cisplatin and Pemetrexed Activate AXL and AXL Inhibitor BGB324 Enhances Mesothelioma Cell Death from Chemotherapy.}, journal = {Frontiers in pharmacology}, volume = {8}, number = {}, pages = {970}, pmid = {29375377}, issn = {1663-9812}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; P30 GM103326/GM/NIGMS NIH HHS/United States ; }, abstract = {Reactive oxygen species (ROS) can promote or inhibit tumorigenesis. In mesothelioma, asbestos exposure to serous membranes induces ROS through iron content and chronic inflammation, and ROS promote cell survival signaling in mesothelioma. Moreover, a current chemotherapy regimen for mesothelioma consisting of a platinum and antifolate agent combination also induce ROS. Mesothelioma is notoriously chemotherapy-resistant, and we propose that ROS induced by cisplatin and pemetrexed may promote cell survival signaling pathways, which ultimately may contribute to chemotherapy resistance. In The Cancer Genome Atlas datasets, we found AXL kinase expression is relatively high in mesothelioma compared to other cancer samples. We showed that ROS induce the phosphorylation of AXL, which was blocked by the selective inhibitor BGB324 in VMC40 and P31 mesothelioma cells. We also showed that cisplatin and pemetrexed induce the phosphorylation of AXL and Akt, which was also blocked by BGB324 as well as by N-acetylcysteine antioxidant. AXL knockdown in these cells enhances sensitivity to cisplatin and pemetrexed. Similarly, AXL inhibitor BGB324 also enhances sensitivity to cisplatin and pemetrexed. Finally, higher synergy was observed when cells were pretreated with BGB324 before adding chemotherapy. These results demonstrate cisplatin and pemetrexed induce ROS that activate AXL, and blocking AXL activation enhances the efficacy of cisplatin and pemetrexed. These results suggest AXL inhibition combined with the current chemotherapy regimen may represent an effective strategy to enhance the efficacy of chemotherapy in mesothelioma. This is the first study, to our knowledge, on chemotherapy-induced activation of AXL and cell survival pathways associated with ROS signaling.}, } @article {pmid29371938, year = {2017}, author = {Hylebos, M and Van Camp, G and Vandeweyer, G and Fransen, E and Beyens, M and Cornelissen, R and Suls, A and Pauwels, P and van Meerbeeck, JP and Op de Beeck, K}, title = {Large-scale copy number analysis reveals variations in genes not previously associated with malignant pleural mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {69}, pages = {113673-113686}, pmid = {29371938}, issn = {1949-2553}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor that is often causally associated with asbestos exposure. Comparative genomic hybridization techniques and arrays demonstrated a complex set of copy number variations (CNVs) in the MPM-genome. These techniques however have a limited resolution, throughput and flexibility compared to next-generation sequencing platforms. In this study, the presence of CNVs in the MPM-genome was investigated using an MPM-cohort (N = 85) for which genomic microarray data are available through 'The Cancer Genome Atlas' (TCGA). To validate these results, the genomes of MPMs and matched normal samples (N = 21) were analyzed using low-pass whole genome sequencing on an 'Illumina HiSeq' platform. CNVs were detected using in-house developed analysis pipelines and frequencies of copy number loss and gain were calculated. In both datasets, losses on chromosomes 1, 3, 4, 6, 9, 13 and 22 and gains on chromosomes 1, 5, 7 and 17 were found in at least 25% and 15% of MPMs, respectively. Besides the well-known MPM-associated genes, CDKN2A, NF2 and BAP1, other interesting cancer-associated genes were listed as frequently involved in a copy number loss (e.g. EP300, SETD2 and PBRM1). Moreover, four cancer-associated genes showed a high frequency of copy number gain in both datasets (i.e. TERT, FCGR2B, CD79B and PRKAR1A). A statistically significant association between overall survival and the presence of copy number loss in the CDKN2A-containing region was observed in the TCGA-set. In conclusion, recurrent CNVs were detected in both datasets, occurring in regions harboring known MPM-associated genes and genes not previously linked to MPM.}, } @article {pmid29342862, year = {2018}, author = {Tolani, B and Acevedo, LA and Hoang, NT and He, B}, title = {Heterogeneous Contributing Factors in MPM Disease Development and Progression: Biological Advances and Clinical Implications.}, journal = {International journal of molecular sciences}, volume = {19}, number = {1}, pages = {}, pmid = {29342862}, issn = {1422-0067}, mesh = {*Disease Progression ; Genes, Tumor Suppressor ; Genome ; Humans ; Lung Neoplasms/genetics/immunology/*pathology ; Mesothelioma/genetics/immunology/*pathology ; Pleural Neoplasms/genetics/immunology/*pathology ; Tumor Microenvironment ; }, abstract = {Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5-12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure. Several molecular pathways have been implicated in the MPM tumor microenvironment; such as angiogenesis; apoptosis; cell-cycle regulation and several growth factor-related pathways predicted to be amenable to therapeutic intervention. Furthermore, the availability of genomic data has improved our understanding of the pathobiology of MPM. The MPM genomic landscape is dominated by inactivating mutations in several tumor suppressor genes; such as CDKN2A; BAP1 and NF2. Given the complex heterogeneity of the tumor microenvironment in MPM; a better understanding of the interplay between stromal; endothelial and immune cells at the molecular level is required; to chaperone the development of improved personalized therapeutics. Many recent advances at the molecular level have been reported and several exciting new treatment options are under investigation. Here; we review the challenges and the most up-to-date biological advances in MPM pertaining to the molecular pathways implicated; progress at the genomic level; immunological progression of this fatal disease; and its link with developmental cell pathways; with an emphasis on prognostic and therapeutic treatment strategies.}, } @article {pmid29338319, year = {2018}, author = {Matboli, M and Shafei, AE and Azazy, AE and Reda, M and El-Khazragy, N and Nagy, AA and Ali, MA and Sobhi, M and Abdel-Rahman, O}, title = {Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant pleural mesothelioma patients.}, journal = {Biomarkers in medicine}, volume = {12}, number = {2}, pages = {129-139}, doi = {10.2217/bmm-2017-0224}, pmid = {29338319}, issn = {1752-0371}, abstract = {AIM: miRNAs may act as promising diagnostic and prognostic biomarkers of mesothelioma. This study integrates serum miR-548a-3p and miR-20a expression based on in silico data analysis followed by clinical validation in malignant mesothelioma patients (malignant pleural mesothelioma [MPM]).

PATIENTS & METHODS: Serum miR-548a-3p and miR-20a level was assessed in the serum of patients with MPM, chronic asbestos exposure and healthy volunteers by quantitative real-time PCR.

RESULTS: The expression of serum miR-548a-3p and miR-20a was positive in 91.6 and 96.7% MPM patients, respectively. Both miRNAs were able to segregate between cases and controls. The sensitivity of the combined chosen serum miRNAs reached 100% in the diagnosis of MPM.

CONCLUSION: The current work revealed that sera miR-548a-3p and miR-20a may serve as promising novel diagnostic tools for MPM.}, } @article {pmid29337930, year = {2018}, author = {Baur, X}, title = {Asbestos-Related Disorders in Germany: Background, Politics, Incidence, Diagnostics and Compensation.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {1}, pages = {}, pmid = {29337930}, issn = {1660-4601}, mesh = {Asbestos/*toxicity ; Compensation and Redress ; Germany/epidemiology ; Humans ; Incidence ; Occupational Diseases/*chemically induced/diagnosis/economics/epidemiology ; Occupational Exposure/*adverse effects/economics/legislation & jurisprudence ; Politics ; }, abstract = {There was some limited use of asbestos at end of the 19th century in industrialized countries including Germany, but its consumption dramatically increased after World War II. The increase in use and exposure was followed by the discovery of high numbers of asbestos-related diseases with a mean latency period of about 38 years in Germany. The strong socio-political pressure from the asbestos industry, its affiliated scientists and physicians has successfully hindered regulatory measures and an asbestos ban for many years; a restrictive stance that is still being unravelled in compensation litigation. This national experience is compared with the situation in other industrialized countries and against the backdrop of the constant efforts of the WHO to eliminate asbestos-related diseases worldwide.}, } @article {pmid29320538, year = {2018}, author = {Patch, AM and Nones, K and Kazakoff, SH and Newell, F and Wood, S and Leonard, C and Holmes, O and Xu, Q and Addala, V and Creaney, J and Robinson, BW and Fu, S and Geng, C and Li, T and Zhang, W and Liang, X and Rao, J and Wang, J and Tian, M and Zhao, Y and Teng, F and Gou, H and Yang, B and Jiang, H and Mu, F and Pearson, JV and Waddell, N}, title = {Germline and somatic variant identification using BGISEQ-500 and HiSeq X Ten whole genome sequencing.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0190264}, pmid = {29320538}, issn = {1932-6203}, mesh = {*Genome, Human ; *Germ Cells ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; INDEL Mutation ; Polymorphism, Single Nucleotide ; }, abstract = {Technological innovation and increased affordability have contributed to the widespread adoption of genome sequencing technologies in biomedical research. In particular large cancer research consortia have embraced next generation sequencing, and have used the technology to define the somatic mutation landscape of multiple cancer types. These studies have primarily utilised the Illumina HiSeq platforms. In this study we performed whole genome sequencing of three malignant pleural mesothelioma and matched normal samples using a new platform, the BGISEQ-500, and compared the results obtained with Illumina HiSeq X Ten. Germline and somatic, single nucleotide variants and small insertions or deletions were independently identified from data aligned human genome reference. The BGISEQ-500 and HiSeq X Ten platforms showed high concordance for germline calls with genotypes from SNP arrays (>99%). The germline and somatic single nucleotide variants identified in both sequencing platforms were highly concordant (86% and 72% respectively). These results indicate the potential applicability of the BGISEQ-500 platform for the identification of somatic and germline single nucleotide variants by whole genome sequencing. The BGISEQ-500 datasets described here represent the first publicly-available cancer genome sequencing performed using this platform.}, } @article {pmid29316066, year = {2018}, author = {Kimura, N and Hasegawa, M and Hiroshima, K}, title = {SMARCB1/INI1/BAF47- deficient pleural malignant mesothelioma with rhabdoid features.}, journal = {Pathology international}, volume = {68}, number = {2}, pages = {128-132}, doi = {10.1111/pin.12623}, pmid = {29316066}, issn = {1440-1827}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; Lung Neoplasms/*metabolism/pathology ; Male ; Mesothelioma/metabolism/*pathology ; Middle Aged ; Rhabdoid Tumor/metabolism/*pathology ; SMARCB1 Protein/*deficiency ; Tumor Suppressor Proteins/deficiency ; Ubiquitin Thiolesterase/deficiency ; }, abstract = {Malignant mesothelioma (MM) with rhabdoid features is an MM variant. Fifteen cases have been reported previously, all of which were combined with other types of MM. Herein, we report an autopsy case of pleural MM with monomorphic rhabdoid features. The patient was a 62-year-old male without a history of asbestos exposure. An autopsy revealed a soft, granular tumor that replaced the entire left pleura and had invaded to the diaphragm and lower lobe of the lung. The tumor cells, which had eosinophilic plump cytoplasm and eccentric nuclei, were loosely cohesive. Immunohistochemistry showed that the cells were diffusely positive for calretinin, D2-40, vimentin, CAM5.2, and AE1/AE3; and negative for WT-1, TTF-1, CK7, CEA, desmin, CD34, BCL-2, S100 protein, and p40. Neither homozygous deletion of p16 nor BAP-1 protein loss was observed. Loss of INI1/BAF47 protein, an indicator of malignant rhabdoid tumor, was observed. Therefore, MM with rhabdoid features was confirmed.}, } @article {pmid29306869, year = {2018}, author = {Solbes, E and Harper, RW}, title = {Biological responses to asbestos inhalation and pathogenesis of asbestos-related benign and malignant disease.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {66}, number = {4}, pages = {721-727}, doi = {10.1136/jim-2017-000628}, pmid = {29306869}, issn = {1708-8267}, abstract = {Asbestos comprises a group of fibrous minerals that are naturally occurring in the environment. Because of its natural properties, asbestos gained popularity for commercial applications in the late 19th century and was used throughout the majority of the 20th century, with predominant use in the construction, automotive, and shipbuilding industries. Asbestos has been linked to a spectrum of pulmonary diseases, such as pleural fibrosis and plaques, asbestosis, benign asbestos pleural effusion, small cell lung carcinoma, non-small cell lung carcinoma, and malignant mesothelioma. There are several mechanisms through which asbestos can lead to both benign and malignant disease, and they include alterations at the chromosomal level, activation of oncogenes, loss of tumor suppressor genes, alterations in cellular signal transduction pathways, generation of reactive oxygen and nitrogen species, and direct mechanical damage to cells from asbestos fibers. While known risk factors exist for the development of asbestos-related malignancies, there are currently no effective means to determine which asbestos-exposed patients will develop malignancy and which will not. There are also no established screening strategies to detect asbestos-related malignancies in patients who have a history of asbestos exposure. In this article, we present a case that highlights the different biological responses in human hosts to asbestos exposure.}, } @article {pmid29303291, year = {Wint}, author = {Kolek, V}, title = {[Malign pleural mesothelioma - so far an undefeated tumor].}, journal = {Vnitrni lekarstvi}, volume = {63}, number = {11}, pages = {884-888}, pmid = {29303291}, issn = {0042-773X}, mesh = {Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Combined Modality Therapy ; Humans ; Immunotherapy/methods ; *Lung Neoplasms/diagnosis/therapy ; *Mesothelioma/diagnosis/therapy ; *Pleural Neoplasms/diagnosis/therapy ; Pneumonectomy/methods ; }, abstract = {Malign pleural mesothelioma is the most frequent primary tumor of the pleura of high aggressiveness. Its most frequent cause is contact with asbestos and, although working with asbestos is already prohibited in developed countries, its incidence is on the increase so far. Diagnostics primarily considers anamnesis, clinical symptoms and immunohistochemical examination of a tumor sample. The basic therapy used over the past 10 years is chemotherapy with cisplatin - pemetrexed combinations. Numerous studies are going on with a different biologically targeted therapy, immunotherapy and other drugs which may improve patients prognosis. The surgical approach is limited by a suitable choice of patients and sufficient experience of the medical center. Extrapleural pneumonectomy or extended pleurectomy are performed. However even the combined therapy with adjuvant or neoadjuvant chemotherapy or radiotherapy has not considerably extended survival.Key words: diagnostics - epidemiology - malign pleural mesothelioma - therapy.}, } @article {pmid29298805, year = {2018}, author = {}, title = {Correction: Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer.}, journal = {Cancer research}, volume = {78}, number = {1}, pages = {309}, doi = {10.1158/0008-5472.CAN-17-3445}, pmid = {29298805}, issn = {1538-7445}, } @article {pmid29298350, year = {2018}, author = {Tatsuta, T and Satoh, T and Sugawara, S and Hara, A and Hosono, M}, title = {Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0190653}, pmid = {29298350}, issn = {1932-6203}, mesh = {Amphibian Proteins/isolation & purification/*pharmacology ; Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Drug Synergism ; Female ; Humans ; In Vitro Techniques ; Lectins/isolation & purification/*pharmacology ; Male ; Mesothelioma/*pathology ; Mice, Inbred BALB C ; Mice, Nude ; Ovum/*chemistry ; Pemetrexed/administration & dosage ; Rana catesbeiana ; Ribonucleases/isolation & purification/*pharmacology ; Weight Loss/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant mesothelioma is an aggressive cancer that results from exposure to asbestos. The therapeutic options for this type of cancer are limited; therefore, the development of novel therapeutic agents is urgently required. Sialic acid-binding lectin isolated from Rana catesbeiana oocytes (cSBL) is a novel therapeutic candidate for cancer, which exhibits antitumor activity mediated through RNA degradation. In the present study, we evaluated the effect of cSBL in vitro and in vivo. Xenograft-competent H2452 and MSTO human mesothelioma cell lines were treated with cSBL, and the pathway by which cSBL induces apoptosis was analyzed. In vivo studies were performed using nude mice inoculated with one of the two cell lines, and the effects of cSBL and pemetrexed were monitored simultaneously. Furthermore, the pharmacological interactions between the three agents (pemetrexed, cisplatin and cSBL) were statistically assessed. It was demonstrated that cSBL treatments caused morphological and biochemical apoptotic changes in both cell lines. Caspase cascade analysis revealed that an intrinsic pathway mediated cSBL-induced apoptosis. The administration of cSBL significantly inhibited tumor growth in two xenograft models, without any adverse effects. Furthermore, the combination index and dose reduction index values indicated that the cSBL + pemetrexed combination showed the highest synergism, and thus potential for reducing dosage of each drug, compared with the other combinations, including the existing pemetrexed + cisplatin regimen. cSBL exerted prominent antitumor effects on malignant mesothelioma cells in vitro and in vivo, and showed favorable effects when combined with pemetrexed. These results suggest that cSBL has potential as a novel drug for the treatment of malignant mesothelioma.}, } @article {pmid29296529, year = {2017}, author = {Schürch, CM and Forster, S and Brühl, F and Yang, SH and Felley-Bosco, E and Hewer, E}, title = {The "don't eat me" signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma.}, journal = {Oncoimmunology}, volume = {7}, number = {1}, pages = {e1373235}, pmid = {29296529}, issn = {2162-4011}, abstract = {Diffuse malignant mesothelioma (DMM) is one of the prognostically most discouraging cancers with median survivals of only 12-22 months. Due to its insidious onset and delayed detection, DMM is often at an advanced stage at diagnosis and is considered incurable. Combined chemo- and radiotherapy followed by surgery only marginally affect outcome at the cost of significant morbidity. Because of the long time period between exposure to asbestos and disease onset, the incidence of DMM is still rising and predicted to peak around 2020. Novel markers for the reliable diagnosis of DMM in body cavity effusion specimens as well as more effective, targeted therapies are urgently needed. Here, we show that the "don't eat me" signalling molecule CD47, which inhibits phagocytosis by binding to signal regulatory protein α on macrophages, is overexpressed in DMM cells. A two-marker panel of high CD47 expression and BRCA1-associated protein 1 (BAP-1) deficiency had a sensitivity of 78% and specificity of 100% in discriminating DMM tumour cells from reactive mesothelial cells in effusions, which is superior to the currently used four-marker combination of BAP-1, glucose transporter type 1, epithelial membrane antigen and desmin. In addition, blocking CD47 inhibited growth and promoted phagocytosis of DMM cell lines by macrophages in vitro. Furthermore, DMM tumours in surgical specimens from patients as well as in a mouse DMM model expressed high levels of CD47 and were heavily infiltrated by macrophages. Our study demonstrates that CD47 is an accurate novel diagnostic DMM biomarker and that blocking CD47 may represent a promising therapeutic strategy for DMM.}, } @article {pmid29289945, year = {2018}, author = {Finkelstein, MM}, title = {Reanalysis of non-occupational exposure to asbestos and the risk of pleural mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {6}, pages = {472-473}, doi = {10.1136/oemed-2017-104783}, pmid = {29289945}, issn = {1470-7926}, } @article {pmid29284684, year = {2017}, author = {Carder, M and Darnton, A and Gittins, M and Stocks, SJ and Ross, D and Barber, CM and Agius, RM}, title = {Chest physician-reported, work-related, long-latency respiratory disease in Great Britain.}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.00961-2017}, pmid = {29284684}, issn = {1399-3003}, mesh = {Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Occupational Diseases/*chemically induced/*epidemiology ; *Occupational Exposure ; Physicians ; Respiration Disorders/*chemically induced/*epidemiology ; Sex Distribution ; Silicon Dioxide/toxicity ; United Kingdom/epidemiology ; Young Adult ; }, abstract = {Much of the current burden of long-latency respiratory disease (LLRD) in Great Britain is attributed to historical asbestos exposure. However, continuing exposure to other agents, notably silica, also contributes to disease burden. The aim of this study was to investigate the incidence of work-related LLRD reported by chest physicians in Great Britain, including variations by age, gender, occupation and suspected agent.LLRD incidence and incidence rate ratios by occupation were estimated (1996-2014). Mesothelioma cases by occupation were compared with proportional mortality ratios.Cases were predominantly in men (95%) and 92% of all cases were attributed to asbestos. Annual average incidence rates (males) per 100 000 were: benign pleural disease, 7.1 (95% CI 6.0-8.2); mesothelioma, 5.4 (4.8-6.0); pneumoconiosis, 1.9 (1.7-2.2); lung cancer, 0.8 (0.6-1.0); chronic obstructive pulmonary disease (COPD), 0.3 (0.2-0.4). Occupations with a particularly high incidence of LLRD were miners and quarrymen (COPD), plumbers and gas fitters (asbestosis), and shipyard and dock workers (all other categories). There was a clear concordance between cases of SWORD mesothelioma and proportional mortality ratios by occupation.Occupationally caused LLRD continues to contribute to a significant disease burden. Many cases are attributable to past exposure to agents such as asbestos and silica, but the potential for occupational exposures persists.}, } @article {pmid29279043, year = {2018}, author = {Yanamala, N and Kisin, ER and Gutkin, DW and Shurin, MR and Harper, M and Shvedova, AA}, title = {Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {81}, number = {4}, pages = {60-79}, doi = {10.1080/15287394.2017.1408201}, pmid = {29279043}, issn = {1528-7394}, abstract = {Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma.}, } @article {pmid29277245, year = {2018}, author = {Tranchant, R and Montagne, F and Jaurand, MC and Jean, D}, title = {[Molecular heterogeneity of malignant pleural mesotheliomas].}, journal = {Bulletin du cancer}, volume = {105}, number = {1}, pages = {35-45}, doi = {10.1016/j.bulcan.2017.11.007}, pmid = {29277245}, issn = {1769-6917}, mesh = {Asbestos/toxicity ; Carcinogens/toxicity ; Chromosome Aberrations ; Epigenesis, Genetic ; Humans ; Lung Neoplasms/classification/etiology/*genetics/therapy ; Mesothelioma/classification/etiology/*genetics/therapy ; Pleural Neoplasms/classification/etiology/*genetics/therapy ; Prognosis ; Transcription, Genetic ; }, abstract = {Malignant pleural mesothelioma (MPM) is predominantly an occupational cancer, most often linked to asbestos exposure. Malignant pleural mesothelioma prognosis is poor with a short survival median, due to the aggressiveness of tumor cells and the weak efficiency of conventional anti-cancer therapies. Clinical, histological, and molecular data suggest tumor heterogeneity between patients as it was also shown for other cancer types. Consequently, there is an urgent need to develop new therapies that take into account this heterogeneity and the molecular characteristics of malignant pleural mesothelioma, in particular by identifying new anti-cancer drugs targeting the molecular specificities of each malignant pleural mesothelioma. Malignant pleural mesothelioma is characterized by numerous molecular alterations at the chromosomal, genetic and epigenetic levels. Molecular classification based on gene expression profile has firstly defined two tumor groups, C1 and C2, and more recently, four groups. By integrating genetic and transcriptomic analysis, a C2LN tumor subgroup of the C2 group has been identified and characterized. In addition to tumor heterogeneity between patients, intra-tumor heterogeneity is supported by several evidences. Most therapeutic strategies that take into account the tumor molecular characteristics have focused on targeted therapies based on mutated genes. A more appropriate strategy would be to consider better-defined tumor groups on the basis of several molecular alterations types as it has been proposed for the C2LN subgroup. A robust definition of homogeneous tumor groups sharing common molecular characteristics is necessary for the development of effective precision medicine for malignant pleural mesothelioma.}, } @article {pmid29269588, year = {2017}, author = {Feder, IS and Tischoff, I and Theile, A and Schmitz, I and Merget, R and Tannapfel, A}, title = {Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate".}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.02204-2017}, pmid = {29269588}, issn = {1399-3003}, mesh = {*Asbestos ; *Asbestos, Serpentine ; Humans ; Lung ; Lung Neoplasms ; Mesothelioma ; }, } @article {pmid29269586, year = {2017}, author = {Sartorelli, P}, title = {Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate".}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.02188-2017}, pmid = {29269586}, issn = {1399-3003}, mesh = {*Asbestos ; *Asbestos, Serpentine ; Humans ; Lung ; Lung Neoplasms ; Mesothelioma ; }, } @article {pmid29269580, year = {2017}, author = {Oliver, LC and Belpoggi, F and Budnik, LT and Egilman, D and Frank, AL and Mandrioli, D and Soskolne, CL and Terracini, B and Welch, L and Baur, X}, title = {Correspondence regarding the article "The asbestos fibre burden in human lungs: new insights into the chrysotile debate".}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.01644-2017}, pmid = {29269580}, issn = {1399-3003}, mesh = {*Asbestos ; *Asbestos, Serpentine ; Humans ; Lung ; Lung Neoplasms ; Mesothelioma ; }, } @article {pmid29269578, year = {2017}, author = {Lamote, K and Vynck, M and Thas, O and Van Cleemput, J and Nackaerts, K and van Meerbeeck, JP}, title = {Exhaled breath to screen for malignant pleural mesothelioma: a validation study.}, journal = {The European respiratory journal}, volume = {50}, number = {6}, pages = {}, doi = {10.1183/13993003.00919-2017}, pmid = {29269578}, issn = {1399-3003}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Belgium ; *Breath Tests ; Case-Control Studies ; Cross-Sectional Studies ; Exhalation ; Female ; Humans ; Logistic Models ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Pleural Neoplasms/*diagnosis ; ROC Curve ; Volatile Organic Compounds/analysis ; }, abstract = {Malignant pleural mesothelioma (MPM) is predominantly caused by asbestos exposure and has a poor prognosis. Breath contains volatile organic compounds (VOCs) and can be explored as an early detection tool. Previously, we used multicapillary column/ion mobility spectrometry (MCC/IMS) to discriminate between patients with MPM and asymptomatic high-risk persons with a high rate of accuracy. Here, we aim to validate these findings in different control groups.Breath and background samples were obtained from 52 patients with MPM, 52 healthy controls without asbestos exposure (HC), 59 asymptomatic former asbestos workers (AEx), 41 patients with benign asbestos-related diseases (ARD), 70 patients with benign non-asbestos-related lung diseases (BLD) and 56 patients with lung cancer (LC).After background correction, logistic lasso regression and receiver operating characteristic (ROC) analysis, the MPM group was discriminated from the HC, AEx, ARD, BLD and LC groups with 65%, 88%, 82%, 80% and 72% accuracy, respectively. Combining AEx and ARD patients resulted in 94% sensitivity and 96% negative predictive value (NPV). The most important VOCs selected were P1, P3, P7, P9, P21 and P26.We discriminated MPM patients from at-risk subjects with great accuracy. The high sensitivity and NPV allow breath analysis to be used as a screening tool for ruling out MPM.}, } @article {pmid29269563, year = {2018}, author = {Marinaccio, A and Corfiati, M and Binazzi, A and Di Marzio, D and Scarselli, A and Ferrante, P and Bonafede, M and Verardo, M and Mirabelli, D and Gennaro, V and Mensi, C and Schallemberg, G and Mazzoleni, G and Merler, E and Girardi, P and Negro, C and D'Agostin, F and Romanelli, A and Chellini, E and Silvestri, S and Pascucci, C and Calisti, R and Stracci, F and Romeo, E and Ascoli, V 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 Iavicoli, S and , }, title = {The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {4}, pages = {254-262}, pmid = {29269563}, issn = {1470-7926}, abstract = {INTRODUCTION: The epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register.

METHODS: Incident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated.

RESULTS: In the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries.

CONCLUSIONS: The consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies.}, } @article {pmid29265930, year = {2018}, author = {Crovella, S and Moura, RR and Cappellani, S and Celsi, F and Trevisan, E and Schneider, M and Brollo, A and Nicastro, EM and Vita, F and Finotto, L and Zabucchi, G and Borelli, V}, title = {A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {81}, number = {5}, pages = {98-105}, doi = {10.1080/15287394.2017.1416911}, pmid = {29265930}, issn = {1528-7394}, abstract = {The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRP1 rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRP1 rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.}, } @article {pmid29260910, year = {2018}, author = {Khella, MS and Salem, AM and Abdel-Rahman, O and Saad, AS}, title = {The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study.}, journal = {Genetic testing and molecular biomarkers}, volume = {22}, number = {2}, pages = {79-84}, doi = {10.1089/gtmb.2017.0146}, pmid = {29260910}, issn = {1945-0257}, mesh = {Adult ; Aged ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/*genetics ; Case-Control Studies ; Female ; Humans ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; Pleural Neoplasms/*genetics/pathology ; *Polymorphism, Genetic ; Risk ; Young Adult ; }, abstract = {AIMS: Despite the established link between malignant pleural mesothelioma (MPM) and asbestos exposure, genetic risk factors may play a key role in MPM pathogenesis. The rs9939609 polymorphism in the FTO gene has recently been implicated as a risk factor for some types of cancer, such as breast, pancreatic, and prostate cancers. FTO variation is associated with altered adipocytokine expression and oxidative stress inflammation, which may influence asbestos mediated-carcinogenesis. This is the first study to investigate a possible association between this polymorphism and MPM risk.

MATERIALS AND METHODS: FTO rs9939609 (T >A) genotypes were screened using a TaqMan® Genotyping Assay in a total of 235 Egyptian subjects (86 MPM patients versus 149 controls). The chi-square test and logistic regression were used to evaluate the association between the candidate variant and MPM risk using a case-control design.

RESULTS: In the additive genetic model, the AT and AA genotypes were associated with a 2.48-fold (95% confidence intervals [CI] = 1.04-5.92, p = 0.04) and a 3.46-fold (95% CI = 0.99-12.01, p = 0.051) increase in the odds of developing MPM, respectively, when compared to the TT genotype after adjustment for body mass index, age, and gender. Additionally, in the dominant genetic model AT/AA genotypes were associated with a 2.63-fold increase in the odds of developing MPM (95% CI = 1.13-6.12, p = 0.025).

CONCLUSIONS: The present study shows for the first time that rs9939609 polymorphism in the FTO gene may be a genetic risk factor for MPM. This study highlights the association of this genetic polymorphism with cancer susceptibility, and therefore, it should be investigated in various other populations, in relation to different types of cancer, and with larger sample sizes.}, } @article {pmid29260624, year = {2018}, author = {Brosseau, S and Dhalluin, X and Zalcman, G and Scherpereel, A}, title = {Immunotherapy in relapsed mesothelioma.}, journal = {Immunotherapy}, volume = {10}, number = {2}, pages = {77-80}, doi = {10.2217/imt-2017-0144}, pmid = {29260624}, issn = {1750-7448}, mesh = {Antibodies, Monoclonal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/*adverse effects ; Clinical Trials as Topic ; Costimulatory and Inhibitory T-Cell Receptors/immunology ; Humans ; Immunotherapy/*methods ; Lung Neoplasms/mortality/*therapy ; Mesothelioma/mortality/*therapy ; Occupational Diseases/immunology/*therapy ; Pleural Neoplasms/immunology/mortality/*therapy ; Recurrence ; Survival Analysis ; Vascular Endothelial Growth Factor A/immunology ; }, } @article {pmid29253374, year = {2017}, author = {Korda, RJ and Clements, MS and Armstrong, BK and Law, HD and Guiver, T and Anderson, PR and Trevenar, SM and Kirk, MD}, title = {Risk of cancer associated with residential exposure to asbestos insulation: a whole-population cohort study.}, journal = {The Lancet. Public health}, volume = {2}, number = {11}, pages = {e522-e528}, doi = {10.1016/S2468-2667(17)30192-5}, pmid = {29253374}, issn = {2468-2667}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Australia/epidemiology ; Cohort Studies ; Environmental Exposure/*adverse effects ; Female ; Housing/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Neoplasms/*chemically induced/epidemiology ; Risk ; }, abstract = {BACKGROUND: The health risks associated with living in houses insulated with asbestos are unknown. Loose-fill asbestos was used to insulate some houses in the Australian Capital Territory (ACT). We compared the incidence of mesothelioma and other cancers in residents of the ACT who did and did not live in these houses.

METHODS: Our cohort study included all ACT residents identified using Medicare enrolment data. These data were linked to addresses of affected residential properties in the ACT to ascertain exposure. We followed up residents by linking data to the Australian Cancer Database and National Death Index. Outcomes were diagnosis of mesothelioma and selected other cancers. Effects were estimated for males and females separately using standardised incidence ratios (SIRs), adjusting for age and calendar time of diagnosis.

FINDINGS: Between Nov 1, 1983, and Dec 31, 2013, 1 035 578 ACT residents were identified from the Medicare database. Of these, 17 248 (2%) had lived in an affected property, including seven (2%) of 285 people diagnosed with mesothelioma. The adjusted incidence of mesothelioma in males who had lived at an affected property was 2·5 times that of unexposed males (SIR 2·54, 95% CI 1·02-5·24). No mesotheliomas were reported among females who had lived at an affected property. Among individuals who had lived at an affected property, there was an elevated incidence of colorectal cancer in women (SIR 1·73, 95% CI 1·29-2·26) and prostate cancer in men (1·29, 1·07-1·54); colorectal cancer was increased, although not significantly, in males (SIR 1·32, 95% CI 0·99-1·72), with no significant increase in the other cancers studied.

INTERPRETATION: Residential asbestos insulation is likely to be unsafe. Our findings have important health, social, financial, and legal implications for governments and communities in which asbestos has been used to insulate houses.

FUNDING: ACT Government.}, } @article {pmid29253372, year = {2017}, author = {de Klerk, N and Reid, A}, title = {Hazards of residential exposure to household asbestos.}, journal = {The Lancet. Public health}, volume = {2}, number = {11}, pages = {e490-e491}, doi = {10.1016/S2468-2667(17)30200-1}, pmid = {29253372}, issn = {2468-2667}, mesh = {*Asbestos ; Housing ; Humans ; *Mesothelioma ; }, } @article {pmid29248759, year = {2018}, author = {Croce, A and Capella, S and Belluso, E and Grosso, F and Mariani, N and Libener, R and Rinaudo, C}, title = {Asbestos fibre burden in gallbladder: A case study.}, journal = {Micron (Oxford, England : 1993)}, volume = {105}, number = {}, pages = {98-104}, doi = {10.1016/j.micron.2017.12.001}, pmid = {29248759}, issn = {1878-4291}, abstract = {The methods conventionally used to determine the burden of asbestos fibres inhaled/incorporated in lung require chemical digestion of the biological matrix before counting/characterising the inorganic fibrous phases under scanning electron microscopy and energy dispersive spectroscopy (SEM/EDS). Asbestos fibres can also be present in extra-pulmonary organs, and we set out to quantify the fibres in gallbladder. Although the standardised procedure requires approximately 5 × 10-1 g of wet tissue, this amount of tissue is not always available. We applied the procedure on about 9 × 10-4 g of gallbladder from a patient with known environmental and workplace exposure to asbestos. The patient died of malignant pleural mesothelioma and was also affected by severe bile-tract problems. The traditional procedure of digesting tissue samples in NaClO and filtering the resulting suspension was carried out. The filter was then examined under SEM/EDS using two methods 1. following the standardised procedure to assess the fibre burden in lung by investigating only 2 mm2 of the filter (660 microscopic fields), and 2. analysing all the microscopic fields in one-quarter of the filter (about 82 mm2). In parallel, histological sections (prepared in the usual way for medical diagnosis) were analysed without digestion or manipulation of the sample using variable pressure SEM/EDS. The fibre counts obtained using the two methods were of the same order of magnitude, i.e., ∼105 fibres/g of wet tissue. We showed that the counting of fibres in human tissue may be successfully carried out even when a limited amount of tissue is available. We also found that, when exposure to asbestos is considerable, the number of asbestos fibres accumulating in the gallbladder may be significant.}, } @article {pmid29247244, year = {2017}, author = {Cerruti, F and Jocollè, G and Salio, C and Oliva, L and Paglietti, L and Alessandria, B and Mioletti, S and Donati, G and Numico, G and Cenci, S and Cascio, P}, title = {Proteasome stress sensitizes malignant pleural mesothelioma cells to bortezomib-induced apoptosis.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {17626}, pmid = {29247244}, issn = {2045-2322}, abstract = {Based on promising results in preclinical models, clinical trials have been performed to evaluate the efficacy of the first-in-class proteasome inhibitor bortezomib towards malignant pleural mesothelioma (MPM), an aggressive cancer arising from the mesothelium of the serous cavities following exposure to asbestos. Unexpectedly, only minimal therapeutic benefits were observed, thus implicating that MPM harbors inherent resistance mechanisms. Identifying the molecular bases of this primary resistance is crucial to develop novel pharmacologic strategies aimed at increasing the vulnerability of MPM to bortezomib. Therefore, we assessed a panel of four human MPM lines with different sensitivity to bortezomib, for functional proteasome activity and levels of free and polymerized ubiquitin. We found that highly sensitive MPM lines display lower proteasome activity than more bortezomib-resistant clones, suggesting that reduced proteasomal capacity might contribute to the intrinsic susceptibility of mesothelioma cells to proteasome inhibitors-induced apoptosis. Moreover, MPM equipped with fewer active proteasomes accumulated polyubiquitinated proteins, at the expense of free ubiquitin, a condition known as proteasome stress, which lowers the cellular apoptotic threshold and sensitizes mesothelioma cells to bortezomib-induced toxicity as shown herein. Taken together, our data suggest that an unfavorable load-versus-capacity balance represents a critical determinant of primary apoptotic sensitivity to bortezomib in MPM.}, } @article {pmid29244982, year = {2017}, author = {Qin, KR and Dua, D}, title = {Diagnostic Dilemma: Primary Peritoneal Mesothelioma With Para-Occupational Asbestos Exposure.}, journal = {Journal of global oncology}, volume = {3}, number = {6}, pages = {828-832}, pmid = {29244982}, issn = {2378-9506}, mesh = {Antineoplastic Agents/therapeutic use ; *Asbestos ; Carboplatin/therapeutic use ; *Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*diagnosis/drug therapy/pathology ; Mesothelioma/*diagnosis/drug therapy/pathology ; Middle Aged ; Pemetrexed/therapeutic use ; Peritoneal Neoplasms/*diagnosis/drug therapy/pathology ; Tomography, X-Ray Computed ; }, } @article {pmid29240325, year = {2017}, author = {}, title = {Tort Law--Expert Testimony in Asbestos Litigation--District of South Carolina Holds the Every Exposure Theory Insufficient to Demonstrate Specific Causation Even If Legal Conclusions are Scientifically Sound.--Haskins v. 3m Co., Nos. 2:15-cv-02086, 3:15-cv-02123, 2017 WL 3118017 (D.S.C. July 21, 2017).}, journal = {Harvard law review}, volume = {131}, number = {2}, pages = {658-665}, pmid = {29240325}, issn = {0017-811X}, mesh = {Asbestosis/*etiology ; *Causality ; Expert Testimony/*legislation & jurisprudence ; Humans ; Mesothelioma/*etiology ; Science ; South Carolina ; }, } @article {pmid29229551, year = {2018}, author = {Nuvoli, B and Camera, E and Mastrofrancesco, A and Briganti, S and Galati, R}, title = {Modulation of reactive oxygen species via ERK and STAT3 dependent signalling are involved in the response of mesothelioma cells to exemestane.}, journal = {Free radical biology & medicine}, volume = {115}, number = {}, pages = {266-277}, doi = {10.1016/j.freeradbiomed.2017.12.008}, pmid = {29229551}, issn = {1873-4596}, abstract = {Pleural mesothelioma is a deadly form of cancer. The prognosis is extremely poor due to the limited treatment modalities. Uptake of asbestos fibres, the leading cause of mesothelioma, lead to the accumulation of reactive-oxygen-species (ROS). Interestingly, increasing ROS production by using ROS-generating drugs may offer a strategy to selectively trigger cell death. Exemestane, an aromatase inhibitor, has previously shown anti-tumor properties in mesothelioma preclinical models suggesting a role of G protein-coupled receptor 30 (GPR30) in the drug response. As exemestane, in addition to blocking estrogen biosynthesis, generates ROS that are able to arrest the growth of breast cancer, we explored the role of ROS, antioxidant defense system, and ROS-induced signalling pathways in mesothelioma cells during exemestane response. Here we report that exemestane treatment reduced cell proliferation with an increase in ROS production and reduction of cyclic adenosine monophosphate (cAMP) levels in MSTO-H211, Ist-Mes1, Ist-Mes2 and MPP89 exemestane-sensitive mesothelioma cell lines, but not in NCI-H2452 exemestane-insensitive mesothelioma cells. Exemestane induced a significant antioxidant response in NCI-H2452 cells, as highlighted by an increase in γ-glutamylcysteine levels, catalase (Cat), superoxide-dismutase and (SOD) and glutathione-peroxidase (GSH-Px) activity and nuclear factor E2-related factor 2 (Nrf2) activation, responsible for drug insensitivity. Conversely, exemestane elevated ROS levels along with increased ERK phosphorylation and a reduction of p-STA3 in exemestane-sensitive mesothelioma cells. ROS generation was the crucial event of exemestane action because ROS inhibitor N-acetyl-L-cysteine (NAC) abrogated p-ERK and p-STAT3 modulation and cellular death. Exemestane also modulates ERK and STAT3 signalling via GPR30. Results indicate an essential role of ROS in the antiproliferative action of exemestane in mesothelioma cells. It is likely that the additional oxidative insults induced by exemestane results in the lethal effects of mesothelioma cells by increasing ROS production. As such, manipulating ROS levels with exemestane seems to be a feasible strategy to selectively kill mesothelioma cells with less toxicity to normal cells by regulating ERK and STAT3 activity.}, } @article {pmid29209316, year = {2017}, author = {Agostinis, C and Vidergar, R and Belmonte, B and Mangogna, A and Amadio, L and Geri, P and Borelli, V and Zanconati, F and Tedesco, F and Confalonieri, M and Tripodo, C and Kishore, U and Bulla, R}, title = {Complement Protein C1q Binds to Hyaluronic Acid in the Malignant Pleural Mesothelioma Microenvironment and Promotes Tumor Growth.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {1559}, pmid = {29209316}, issn = {1664-3224}, abstract = {C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos. We found that C1q was highly expressed in all MPM histotypes, particularly in epithelioid rather than in sarcomatoid histotype. C1q avidly bound high and low molecular weight hyaluronic acid (HA) via its globular domain. C1q bound to HA was able to induce adhesion and proliferation of mesothelioma cells (MES) via enhancement of ERK1/2, SAPK/JNK, and p38 phosphorylation; however, it did not activate the complement cascade. Consistent with the modular organization of the globular domain, we demonstrated that C1q may bind to HA through ghA module, whereas it may interact with human MES through the ghC. In conclusion, C1q highly expressed in MPM binds to HA and enhances the tumor growth promoting cell adhesion and proliferation. These data can help develop novel diagnostic markers and molecular targets for MPM.}, } @article {pmid29207669, year = {2017}, author = {Lamote, K and Brinkman, P and Vandermeersch, L and Vynck, M and Sterk, PJ and Van Langenhove, H and Thas, O and Van Cleemput, J and Nackaerts, K and van Meerbeeck, JP}, title = {Breath analysis by gas chromatography-mass spectrometry and electronic nose to screen for pleural mesothelioma: a cross-sectional case-control study.}, journal = {Oncotarget}, volume = {8}, number = {53}, pages = {91593-91602}, pmid = {29207669}, issn = {1949-2553}, abstract = {Rationale: Malignant pleural mesothelioma (MPM) is mainly caused by previous exposure to asbestos fibers and has a poor prognosis. Due to a long latency period between exposure and diagnosis, MPM incidence is expected to peak between 2020-2025. Screening of asbestos-exposed individuals is believed to improve early detection and hence, MPM management. Recent developments focus on breath analysis for screening since breath contains volatile organic compounds (VOCs) which reflect the cell's metabolism.

Objectives: The goal of this cross-sectional, case-control study is to identify VOCs in exhaled breath of MPM patients with gas chromatography-mass spectrometry (GC-MS) and to assess breath analysis to screen for MPM using an electronic nose (eNose).

Methods: Breath and background samples were taken from 64 subjects: 16 healthy controls (HC), 19 asymptomatic former asbestos-exposed (AEx) individuals, 15 patients with benign asbestos-related diseases (ARD) and 14 MPM patients. Samples were analyzed with both GC-MS and eNose.

Results: Using GC-MS, AEx individuals were discriminated from MPM patients with 97% accuracy, with diethyl ether, limonene, nonanal, methylcyclopentane and cyclohexane as important VOCs. This was validated by eNose analysis. MPM patients were discriminated from AEx+ARD participants by GC-MS and eNose with 94% and 74% accuracy, respectively. The sensitivity, specificity, positive and negative predictive values were 100%, 91%, 82%, 100% for GC-MS and 82%, 55%, 82%, 55% for eNose, respectively.

Conclusion: This study shows accurate discrimination of patients with MPM from asymptomatic asbestos-exposed persons at risk by GC-MS and eNose analysis of exhaled VOCs and provides proof-of-principle of breath analysis for MPM screening.}, } @article {pmid29206890, year = {2018}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {29}, number = {2}, pages = {484-489}, doi = {10.1093/annonc/mdx762}, pmid = {29206890}, issn = {1569-8041}, abstract = {Background: Diagnosis of mesothelioma based on death certificate is subject to misclassification, which may bias the results of epidemiology studies. A high proportion of mesothelioma harbor mutations in the BRCA1-associated protein 1 (BAP1) gene.

Methods: We searched medical and pathology records and specimens for 127 workers from a textile-asbestos factory in Italy who died during 1963-2013 with a diagnosis of pleural or peritoneal neoplasm or mesothelioma on death certificate, to confirm the diagnosis with immunohistochemistry markers. We calculated the odds ratio of confirmation by selected characteristics and asbestos exposure variables. When sufficient pathology material was available, we analyzed BAP1 protein expression.

Results: The diagnosis of mesothelioma was histologically confirmed for 35 cases (27.6%); 5 cases were classified as non-mesothelioma (3.9%), for 33 cases a mention of mesothelioma was found on record but no sufficient material was available for revision (26.0%); no records were available for 54 cases (death-certificate-only 42.5%). Diagnostic confirmation was not associated with sex, location of the neoplasm, age, or duration of employment; however, there was a significant association with time since first employment (P for linear trend 0.04). An association between duration of employment and time since first employment was observed for confirmed cases but not for death-certificate-only cases. BAP1 protein was lost in 18/35 cases (51.4%), without an association with sex, location, age, indices of asbestos exposure, or survival.

Conclusions: We were able to confirm by immunohistochemistry a small proportion of mesothelioma diagnoses on certificates of deceased asbestos workers, and confirmation correlated with latency of asbestos exposure but not other characteristics. BAP1 protein loss is a frequent event in mesothelioma of asbestos-exposed workers, but does not correlate with exposure.}, } @article {pmid29200597, year = {2017}, author = {Jiang, Z and Ying, S and Shen, W and He, X and Chen, J and Xia, H and Yu, M and Xiao, Y and Feng, L and Zhu, L and Ju, L and Guo, X and Zhang, Y and Shen, JW and Tong, Y and Zhang, X and Lou, J}, title = {Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {1725354}, pmid = {29200597}, issn = {1875-8630}, mesh = {Aged ; Asbestos/adverse effects ; Asbestosis/*blood/epidemiology ; Biomarkers/blood ; Case-Control Studies ; China ; Extracellular Matrix Proteins/*blood ; Female ; Humans ; Lung Neoplasms/*blood/epidemiology ; Male ; Mesothelioma/*blood/epidemiology ; Middle Aged ; Occupational Exposure/statistics & numerical data ; }, abstract = {Fibulin-3 has been reported as a potential biomarker for mesothelioma. However, little is known about the diagnostic efficacies of fibulin-3 for asbestos-related diseases (ARDs) in China. This study was to investigate the utility of fibulin-3 for asbestos exposure and ARDs. A total of 430 subjects were recruited from Southeast China, including healthy individuals, asbestos-exposed (AE) individuals, and patients with pleural plaques (PP), asbestosis, and malignant pleural mesothelioma (MPM). Plasma fibulin-3 was measured using the enzyme-linked immunosorbent assay. Linear regression analyses were applied to explore the influencing factors of fibulin-3. Receiver operating characteristic curves were used to determine the cutoff values. The median fibulin-3 level of subjects in the mesothelioma group was higher than that in other groups. Subjects in the asbestosis group had higher median fibulin-3 level than those in the control group. A higher fibulin-3 level was found in the group with ≥10 years of asbestos exposure as compared with control groups. The AUCs of fibulin-3 for distinguishing MPM subjects from control, AE, PP, and asbestosis subjects were 0.92, 0.88, 0.90, and 0.81, respectively. Our study provided evidence that fibulin-3 could be a potential biomarker for the early screening of MPM, but not of other nonmalignant ARDs in Chinese populations.}, } @article {pmid29197906, year = {2017}, author = {Glass, WI and Clayson, H}, title = {Asbestos-worker exposure, family disease.}, journal = {The New Zealand medical journal}, volume = {130}, number = {1466}, pages = {90-91}, pmid = {29197906}, issn = {1175-8716}, mesh = {Asbestos/*toxicity ; *Family Health/economics/legislation & jurisprudence ; Humans ; *Inhalation Exposure ; Lung Neoplasms/chemically induced/economics ; Mesothelioma/chemically induced/economics ; *Occupational Exposure ; *Workers' Compensation/economics/legislation & jurisprudence ; }, abstract = {Family members, mostly female, can be at risk of asbestos-related disease as a result of the transfer of asbestos from the workplace to the home on the hair, boots and clothes of the worker. It is argued that in these cases the home should be recognised as an extension of the workplace and that the employer has a duty of care to contain and control the asbestos. Given these circumstances, the family member with the disease should be entitled to cover under the Accidence Compensation Legislation.}, } @article {pmid29197848, year = {2017}, author = {Gravito-Soares, M and Gravito-Soares, E and Almeida, J and Fraga, J and Tomé, L}, title = {Challenging and uncommon diagnosis of long-evolution ascites.}, journal = {BMJ case reports}, volume = {2017}, number = {}, pages = {}, doi = {10.1136/bcr-2017-222565}, pmid = {29197848}, issn = {1757-790X}, mesh = {Alcoholism/*complications ; Ascites/*complications/pathology ; Biopsy ; Humans ; Liver/pathology ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Peritoneal Neoplasms/*etiology/pathology ; Peritoneum/pathology ; }, abstract = {This is a case report of a 45-year-old Caucasian man with chronic alcoholism. No history of liver disease or asbestos exposure. He complained of ascites during the last 3 years with worsening in the last year with severe ascites development. Diagnostic paracentesis showed SAAG 1.1 and high cellularity with neutrophil count >250 cells/µL. Ascitic fluid cytology revealed reactive mesothelial hyperplasia. Thoracoabdominopelvic ultrasonography/CT/MRI and fludeoxyglucose positron emission tomography/CT showed 'omental cake' pattern suggesting peritoneal carcinomatosis. An exploratory laparoscopy revealed moderate interloop adhesions and necrosis with whitish exudate in the right pelvic excavation. Biochemical/cytological/histological/microbiological study only revealed reactive mesothelial cells, necrosis and lymphohistiocytic inflammatory infiltrate. A second exploratory laparoscopy with liver and peritoneal biopsies and appendectomy/mesoappendix excision showed a well-differentiated tubulopapillary mesothelioma. The patient was referred for intraperitoneal chemotherapy and is undergoing monthly therapeutic paracentesis.}, } @article {pmid29193587, year = {2018}, author = {Ohara, Y and Chew, SH and Shibata, T and Okazaki, Y and Yamashita, K and Toyokuni, S}, title = {Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male rats.}, journal = {Cancer science}, volume = {109}, number = {2}, pages = {330-339}, pmid = {29193587}, issn = {1349-7006}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Disease Models, Animal ; Iron/blood ; Lung Neoplasms/blood/*chemically induced/pathology/*prevention & control ; Male ; Mesothelioma/blood/*chemically induced/pathology/*prevention & control ; Phlebotomy/*methods ; Rats ; Survival Analysis ; Treatment Outcome ; Tumor Burden ; }, abstract = {Malignant mesothelioma (MM) is a rare but socially important neoplasm due to its association with asbestos exposure. Malignant mesothelioma is difficult to diagnose at an early stage, yet there are no particularly effective treatments available at the advanced stage, thus necessitating efficient strategies to prevent MM in individuals already exposed to asbestos. We previously showed that persistent oxidative damage caused by foreign body reaction and affinity of asbestos both to hemoglobin and histones is one of the major pathogeneses. Accordingly, as an effective strategy to prevent asbestos-induced MM, we undertook the use of an iron chelator, deferasirox, which decreased the epithelial-mesenchymal transition in a crocidolite-induced rat MM model. However, this agent may show adverse effects. Here, we studied the effects of iron removal by phlebotomy as a realistic measure on the same rat model. We injected a total of 5 mg crocidolite i.p. to F1 hybrid rats between the Fischer-344 and Brown-Norway strains at the age of 6 weeks. We repeated weekly or biweekly phlebotomy of 6-8 mL/kg/time from 10 to 60 weeks of age. The animals were observed until 120 weeks. In male rats, phlebotomy significantly decreased the weight and nuclear grade of MM, and modestly reduced the associated ascites and the fraction of more malignant sarcomatoid subtype. Weekly phlebotomy prolonged long-term survival. Our results indicate that appropriate phlebotomy may be a practical preventive measure to attenuate the initiation and promotion capacity of asbestos towards MM by reducing iron in individuals exposed to asbestos.}, } @article {pmid29187476, year = {2017}, author = {Matsubara, T and Toyokawa, G and Yamada, Y and Nabeshima, K and Haratake, N and Kozuma, Y and Akamine, T and Takamori, S and Shoji, F and Okamoto, T and Maehara, Y}, title = {A Case of the Resected Lymphohistiocytoid Mesothelioma: BAP1 Is a Key of Accurate Diagnosis.}, journal = {Anticancer research}, volume = {37}, number = {12}, pages = {6937-6941}, doi = {10.21873/anticanres.12158}, pmid = {29187476}, issn = {1791-7530}, mesh = {Aged, 80 and over ; Biomarkers, Tumor/analysis ; Diagnosis, Differential ; Fluorodeoxyglucose F18 ; Humans ; Immunohistochemistry ; Lung Neoplasms/diagnosis/diagnostic imaging/*surgery ; Male ; Mesothelioma/diagnosis/diagnostic imaging/*surgery ; Positron-Emission Tomography/methods ; Tomography, X-Ray Computed/methods ; Tumor Suppressor Proteins/analysis ; Ubiquitin Thiolesterase/analysis ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a well-known malignant tumor that occurs in the pleura and is histopathologically classified into three subtypes. Lymphohistiocytoid mesothelioma (LHM) is considered a variant of epithelioid MM, and few cases have been reported. First case of LHM was reported by Henderson et al. in 1988. It is difficult to precisely diagnose LHM, and it is often misdiagnosed as reactive mesothelial cell proliferation.

CASE REPORT: An 82-year-old man, with the smoking history of nine pack-years, was referred to our Department due to an abnormal shadow and pleural effusion in the left lung field on the chest X-ray imaging. His occupation was a teacher through his life without any asbestos exposure. Computed tomography (CT) and 18F-fluorodeoxyglucose-position emission tomography showed a tumor which was suggestive of malignancy on the left chest wall, with the possible invasion into the left 2nd to 4th ribs. He underwent a CT-guided biopsy and a thoracentesis, but the tumor was shown to be a benign tumor indicative of a reactive mesothelial cell proliferation. Then, he underwent a surgical resection and the tumor was suspected of liposarcoma macroscopically. Histological and immunohistochemical findings were suggestive of mesothelial lesion, such as nodular histiocytic or mesothelial hyperplasia. However, loss of BAP1 and no p16 homozygous deletion in the tumor cells led to the diagnosis of LHM, not a benign lesion.}, } @article {pmid29182465, year = {2017}, author = {}, title = {Author's response to: "Letter to the Editor" regarding content of "Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States" by R. A. Lemen, Journal of Toxicology and Environmental Health, Part B 2016; 19: 250-265.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {20}, number = {8}, pages = {389}, doi = {10.1080/10937404.2017.1400769}, pmid = {29182465}, issn = {1521-6950}, mesh = {Asbestos/*analysis ; Environmental Health ; Lung Neoplasms ; *Mesothelioma ; Pleural Neoplasms ; United States ; }, } @article {pmid29165392, year = {2017}, author = {Westerholm, P and Remaéus, B and Svartengren, M}, title = {The Tale of Asbestos in Sweden 1972-1986-The Pathway to a Near-Total Ban.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29165392}, issn = {1660-4601}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Asbestosis/*epidemiology ; Environmental Exposure/*statistics & numerical data ; Humans ; Incidence ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Occupational Exposure/statistics & numerical data ; Sweden ; }, abstract = {This paper provides a narrative of the national intervention strategy in Sweden aimed to restrict the industrial use of asbestos. For many years, asbestos was imported for widespread industrial use, resulting in large amounts throughout Swedish society. In 1972, the whistle was blown in a Communist Party parliamentary motion describing asbestos as a health hazard and requesting action to prohibit its use. Although the motion was rejected, it initiated the extensive charting of asbestos sources on a tripartite basis, involving government agencies, and employer and trade-union organizations. Restrictive asbestos management practices were enforced from July 1982. The year 1985 saw the Government Asbestos Commission review, covering use-determining factors, international regulations, and assessments of cancer risks. The relative risks of chrysotile and amphibole were considered internationally (by the IARC), since chrysotile (a Canadian export) was regarded as unharmful in Canada at that time. Prohibiting asbestos use resulted in its virtual disappearance as an import to Sweden from the early 1980s. However, asbestos has undergone a transition from an occupational to a public-health hazard (although some work-related hazards, such as handling and disposal, remain). The transition reflects the public's exposure to existing stocks, in homes, workplaces, etc. Mesothelioma incidence has come to be regarded as an indicator of prevention effectiveness.}, } @article {pmid29165150, year = {2017}, author = {Matsuzaki, H and Kumagai-Takei, N and Lee, S and Maeda, M and Sada, N and Hatayama, T and Yamamoto, S and Ikeda, M and Yoshitome, K and Min, Y and Nishimura, Y and Otsuki, T}, title = {Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos.}, journal = {Environmental health and preventive medicine}, volume = {22}, number = {1}, pages = {53}, pmid = {29165150}, issn = {1347-4715}, mesh = {Asbestos/*adverse effects/*immunology ; Asbestosis/immunology ; Biomarkers/*analysis/blood ; CD8-Positive T-Lymphocytes ; Humans ; Killer Cells, Natural/*immunology ; Lung Neoplasms/chemically induced/immunology ; Mesothelioma/chemically induced/immunology ; Mucosal-Associated Invariant T Cells/*immunology ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; }, abstract = {The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells. These findings were used to explore biological markers associated with asbestos exposure and asbestos-induced cancers and suggested the usefulness of serum/plasma IL-10 and TGF-β, surface CXCR3 expression in Tresp, the secreting potential of IFN-γ in Tresp, intracellular perforin level in CTL, and surface expression NKp46 in NK cells. Although other unexplored cytokines in serum/plasma and molecules in these immunological cells, including Th17, should be investigated by experimental procedures in addition to a comprehensive analysis of screening methods, biomarkers based on immunological alterations may be helpful in clinical situations to screen the high-risk population exposed to asbestos and susceptible to asbestos-related cancers such as mesothelioma.}, } @article {pmid29149911, year = {2017}, author = {Winata, P and Williams, M and McGowan, E and Nassif, N and van Zandwijk, N and Reid, G}, title = {The analysis of novel microRNA mimic sequences in cancer cells reveals lack of specificity in stem-loop RT-qPCR-based microRNA detection.}, journal = {BMC research notes}, volume = {10}, number = {1}, pages = {600}, pmid = {29149911}, issn = {1756-0500}, support = {11/TPG/3-06//Cancer Institute NSW/ ; 11/TPG/3-06//Cancer Institute NSW/ ; PhD Scholarship//Sydney Catalyst/ ; RG14-17//Cancer Council NSW/ ; }, mesh = {Antineoplastic Agents/administration & dosage/*analysis/therapeutic use ; Cell Line, Tumor ; *Drug Delivery Systems ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; MicroRNAs/administration & dosage/*analysis/chemical synthesis/therapeutic use ; Molecular Mimicry ; *Molecular Probe Techniques ; Nucleic Acid Probes ; *Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR.

RESULTS: The custom assays efficiently and specifically amplified the consensus mimics. However, we found that these assays gave a signal when total RNA from untransfected and control mimic-transfected cells were used as templates. Further investigation revealed that the reverse transcription step using stem-loop primers appeared to introduce substantial non-specific amplification with either total RNA or synthetic RNA templates. This suggests that reverse transcription using stem-loop primers suffers from an intrinsic lack of specificity for the detection of highly similar microRNAs in the same family, especially when analysing total RNA. These results suggest that RT-qPCR is unlikely to be an effective means to detect delivery of microRNA mimic-based drugs to tumour cells in patients.}, } @article {pmid29137208, year = {2017}, author = {Marsili, D and Angelini, A and Bruno, C and Corfiati, M and Marinaccio, A and Silvestri, S and Zona, A and Comba, P}, title = {Asbestos Ban in Italy: A Major Milestone, Not the Final Cut.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29137208}, issn = {1660-4601}, mesh = {*Air Pollutants, Occupational ; *Asbestos ; Environmental Health ; *Environmental Policy ; Humans ; Italy ; Occupational Exposure/*prevention & control ; }, abstract = {Background and history: Italy was the main asbestos producer and one of the greatest consumers in 20th century Europe until the asbestos ban was introduced in 1992. Asbestos exposure affected the population in a wide range of working environments, namely mining and marketing of asbestos, asbestos cement production, shipyards and textile industries. This also determined a widespread environmental asbestos exposure affecting the surrounding communities. Methods: To investigate the drivers and difficulties of the process leading to the asbestos ban and its subsequent implementation, we focused on stakeholder involvement, environmental health policies, capacity building and communication. Results: In the past three decades, stakeholder involvement has been instrumental in advancing the industrial asbestos replacement process, prevention and remediation interventions. Furthermore, involvement also contributed to the integration of environmental and health policies at national, regional and local levels, including capacity building and communication. In a global public health perspective, international scientific cooperation has been established with countries using and producing asbestos. Discussion and Conclusions: Key factors and lessons learnt in Italy from both successful and ineffective asbestos policies are described to support the relevant stakeholders in countries still using asbestos contributing to the termination of its use.}, } @article {pmid29131723, year = {2017}, author = {Magnani, C and Mirabelli, D and Terracini, B}, title = {Comment on "Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States" by R A Lemen, Journal of Toxicology and Environmental Health, Part B 2016;19:250-265.}, journal = {Journal of toxicology and environmental health. Part B, Critical reviews}, volume = {20}, number = {8}, pages = {387-388}, doi = {10.1080/10937404.2017.1400762}, pmid = {29131723}, issn = {1521-6950}, mesh = {*Asbestos ; Environmental Health ; Humans ; Lung Neoplasms ; *Mesothelioma ; United States ; }, } @article {pmid29129162, year = {2017}, author = {Musk, ABW and de Klerk, N and Brims, FJ}, title = {Mesothelioma in Australia: a review.}, journal = {The Medical journal of Australia}, volume = {207}, number = {10}, pages = {449-452}, pmid = {29129162}, issn = {1326-5377}, mesh = {Antineoplastic Agents/therapeutic use ; *Asbestos ; Australia/epidemiology ; Compensation and Redress ; Humans ; Incidence ; Mesothelioma/drug therapy/*epidemiology ; Occupational Diseases/drug therapy/*epidemiology ; Occupational Exposure/statistics & numerical data ; Pleural Neoplasms/drug therapy/*epidemiology ; Prognosis ; }, abstract = {The incidence of malignant mesothelioma in Australia is among the highest in the world as a result of widespread use of asbestos by industry and in construction throughout the 20th century. The risk of developing malignant mesothelioma after asbestos exposure is dose-related; a transient, low dose exposure confers a correspondingly very low risk of disease. Malignant mesothelioma is a heterogeneous disease, partly explaining the limited role of biomarkers in screening and diagnosis. The prognosis remains poor, and early advice on medico-legal compensation and a collaborative team approach to managing malignant mesothelioma are both essential. Chemotherapy can have a modest treatment effect in some people. New therapies, such as immunotherapy, do not yet have a defined role in the treatment of malignant mesothelioma. As treatment options for malignant mesothelioma are limited and no cure is available, there is no established role for early detection or screening of at risk populations. A multidisciplinary approach to caring for patients with malignant mesothelioma and their carers is vital.}, } @article {pmid29124998, year = {2017}, author = {Pierce, JS and Riordan, AS and Miller, EW and Gaffney, SH and Hollins, DM}, title = {Evaluation of the presence of asbestos in cosmetic talcum products.}, journal = {Inhalation toxicology}, volume = {29}, number = {10}, pages = {443-456}, doi = {10.1080/08958378.2017.1392656}, pmid = {29124998}, issn = {1091-7691}, mesh = {Asbestos, Amphibole/*analysis ; Cosmetics/*chemistry ; Humans ; Microscopy, Electron, Transmission ; Spectrometry, X-Ray Emission ; Talc/*chemistry ; X-Ray Diffraction ; }, abstract = {Talc has been used for over a century in a variety of cosmetic products. While pure cosmetic talc (free of asbestos) is not considered a risk factor for mesothelioma, it has been recently suggested that inhalation of cosmetic talc containing trace levels of asbestos is a risk factor for mesothelioma. Bulk analyses of cosmetic talcum products were performed in the 1960s and 1970s, however, the analytical methods used at that time were incapable of determining whether asbestos minerals were present in the asbestiform versus non-asbestiform habit. The distinction between these two mineral habits is critical, as non-asbestiform amphibole minerals do not present an asbestos-related cancer risk via inhalation. As such, we evaluated six historical talcum powders using modern-era analytical methods to determine if asbestos is present, and if so, to identify the mineral habit (asbestiform versus non-asbestiform) of the asbestos. Based on their labels, the products were produced by four manufacturers and sold between 1940 and 1977. The products were analyzed in duplicate by two laboratories using standard protocols. Laboratory A analyzed samples using X-ray diffraction (XRD) and polarized light microscopy (PLM), and Laboratory B analyzed samples using PLM and transmission electron microscopy (TEM) with energy dispersive X-ray analysis (EDX) and selected area electron diffraction (SAED). No asbestiform minerals were found in any of the products. Nonetheless, even if some historical cosmetic talcum products contained trace amounts (≤0.1%) of asbestiform minerals, any resulting asbestos exposure would be expected to be exceedingly low, and comparable to exposures from breathing ambient air.}, } @article {pmid29124996, year = {2017}, author = {LeMasters, G and Lockey, JE and Hilbert, TJ and Levin, LS and Burkle, JW and Shipley, R and Perme, C and Meyer, CA and Rice, CH}, title = {A 30-year mortality and respiratory morbidity study of refractory ceramic fiber workers.}, journal = {Inhalation toxicology}, volume = {29}, number = {10}, pages = {462-470}, doi = {10.1080/08958378.2017.1394931}, pmid = {29124996}, issn = {1091-7691}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kaolin/*toxicity ; Male ; Middle Aged ; Mineral Fibers/*toxicity ; Neoplasms/etiology ; *Occupational Exposure ; Odds Ratio ; Respiratory Tract Diseases/*etiology/*mortality ; Risk Factors ; Young Adult ; }, abstract = {AIM: Report mortality (n = 1119), cancer incidence (n = 1207) and radiographic (n = 1451) findings from a 30-year investigation of current and former refractory ceramic fiber (RCF) workers.

METHODS: Cause of death, health and work histories, radiographs and spirometry were collected. Mortality and cancer incidence were analyzed. Logistic regression analysis investigated the associations of latency and cumulative fiber exposure (CFE) on radiographic changes.

RESULTS: The mortality study showed no increase in standardized mortality rates (SMR) for lung cancer, but urinary cancers were significantly elevated in the higher exposed group (SMR = 3.62, 95% CI: 1.33-7.88) and leukemia in the total cohort (SMR = 2.51, 95% CI: 1.08-4.94). One death attributed to mesothelioma was identified (SMR = 2.86, 95% CI: 0.07-15.93) in a worker reporting some asbestos exposure. The overall rate of pleural changes was 6.1%, attaining 21.4% in the highest CFE category for all subjects (adjusted odds ratio (aOR) = 6.9, 95% CI: 3.6-13.4), and 13.0% for those with no reported asbestos exposure (OR= 9.1, 95% CI: 2.5-33.6). Prevalence for recent hires (≥1985) was similar to the background. Interstitial changes were not elevated. Localized pleural thickening was associated with small decreases in spirometry results.

CONCLUSION: Increases in leukemia and urinary cancer but not lung cancer mortality were found. One death attributed to mesothelioma was observed in a worker with self-reported asbestos exposure and a work history where occupational asbestos exposure may have occurred, rendering uncertainties in assigning causation. Radiographic analyses indicated RCF exposure alone is associated with increased pleural but not interstitial changes. Reductions in RCF exposure should continue. The mortality study is ongoing.}, } @article {pmid29113949, year = {2018}, author = {Johnson, TG and Schelch, K and Cheng, YY and Williams, M and Sarun, KH and Kirschner, MB and Kao, S and Linton, A and Klebe, S and McCaughan, BC and Lin, RCY and Pirker, C and Berger, W and Lasham, A and van Zandwijk, N and Reid, G}, title = {Dysregulated Expression of the MicroRNA miR-137 and Its Target YBX1 Contribute to the Invasive Characteristics of Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {13}, number = {2}, pages = {258-272}, doi = {10.1016/j.jtho.2017.10.016}, pmid = {29113949}, issn = {1556-1380}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive malignancy linked to asbestos exposure. On a genomic level, MPM is characterized by frequent chromosomal deletions of tumor suppressors, including microRNAs. MiR-137 plays a tumor suppressor role in other cancers, so the aim of this study was to characterize it and its target Y-box binding protein 1 (YBX1) in MPM.

METHODS: Expression, methylation, and copy number status of miR-137 and its host gene MIR137HG were assessed by polymerase chain reaction. Luciferase reporter assays confirmed a direct interaction between miR-137 and Y-box binding protein 1 gene (YBX1). Cells were transfected with a miR-137 inhibitor, miR-137 mimic, and/or YBX1 small interfering RNA, and growth, colony formation, migration and invasion assays were conducted.

RESULTS: MiR-137 expression varied among MPM cell lines and tissue specimens, which was associated with copy number variation and promoter hypermethylation. High miR-137 expression was linked to poor patient survival. The miR-137 inhibitor did not affect target levels or growth, but interestingly, it increased miR-137 levels by means of mimic transfection suppressed growth, migration, and invasion, which was linked to direct YBX1 downregulation. YBX1 was overexpressed in MPM cell lines and inversely correlated with miR-137. RNA interference-mediated YBX1 knockdown significantly reduced cell growth, migration, and invasion.

CONCLUSIONS: MiR-137 can exhibit a tumor-suppressive function in MPM by targeting YBX1. YBX1 knockdown significantly reduces tumor growth, migration, and invasion of MPM cells. Therefore, YBX1 represents a potential target for novel MPM treatment strategies.}, } @article {pmid29112873, year = {2017}, author = {Port, J and Murphy, DJ}, title = {Mesothelioma: Identical Routes to Malignancy from Asbestos and Carbon Nanotubes.}, journal = {Current biology : CB}, volume = {27}, number = {21}, pages = {R1173-R1176}, doi = {10.1016/j.cub.2017.07.026}, pmid = {29112873}, issn = {1879-0445}, abstract = {Exposure of laboratory mice to carbon nanotubes mimics exposure to asbestos, from initial and chronic inflammation, through loss of the same tumour-suppressor pathways and eventual sporadic development of malignant mesothelioma. Fibres of a similar nature may pose significant health risks to humans.}, } @article {pmid29112861, year = {2017}, author = {Chernova, T and Murphy, FA and Galavotti, S and Sun, XM and Powley, IR and Grosso, S and Schinwald, A and Zacarias-Cabeza, J and Dudek, KM and Dinsdale, D and Le Quesne, J and Bennett, J and Nakas, A and Greaves, P and Poland, CA and Donaldson, K and Bushell, M and Willis, AE and MacFarlane, M}, title = {Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf).}, journal = {Current biology : CB}, volume = {27}, number = {21}, pages = {3302-3314.e6}, pmid = {29112861}, issn = {1879-0445}, support = {MC_U132685863//Medical Research Council/United Kingdom ; MC_UP_1203/1//Medical Research Council/United Kingdom ; MC_UP_A600_1023//Medical Research Council/United Kingdom ; MC_UP_A600_1024//Medical Research Council/United Kingdom ; }, mesh = {Aged ; Animals ; Asbestos/*toxicity ; Carcinogenesis/chemically induced/genetics ; Cell Proliferation/drug effects ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16/genetics/*metabolism ; Cyclin-Dependent Kinase Inhibitor p19/genetics/*metabolism ; Female ; Humans ; Lung Neoplasms/*chemically induced/genetics/*pathology ; Male ; Mesothelioma/*chemically induced/genetics/*pathology ; Methylation/drug effects ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Nanotubes, Carbon/*toxicity ; }, abstract = {Mesothelioma is a fatal tumor of the pleura and is strongly associated with asbestos exposure. The molecular mechanisms underlying the long latency period of mesothelioma and driving carcinogenesis are unknown. Moreover, late diagnosis means that mesothelioma research is commonly focused on end-stage disease. Although disruption of the CDKN2A (INK4A/ARF) locus has been reported in end-stage disease, information is lacking on the status of this key tumor suppressor gene in pleural lesions preceding mesothelioma. Manufactured carbon nanotubes (CNTs) are similar to asbestos in terms of their fibrous shape and biopersistent properties and thus may pose an asbestos-like inhalation hazard. Here we show that instillation of either long CNTs or long asbestos fibers into the pleural cavity of mice induces mesothelioma that exhibits common key pro-oncogenic molecular events throughout the latency period of disease progression. Sustained activation of pro-oncogenic signaling pathways, increased proliferation, and oxidative DNA damage form a common molecular signature of long-CNT- and long-asbestos-fiber-induced pathology. We show that hypermethylation of p16/Ink4a and p19/Arf in CNT- and asbestos-induced inflammatory lesions precedes mesothelioma; this results in silencing of Cdkn2a (Ink4a/Arf) and loss of p16 and p19 protein, consistent with epigenetic alterations playing a gatekeeper role in cancer. In end-stage mesothelioma, silencing of p16/Ink4a is sustained and deletion of p19/Arf is detected, recapitulating human disease. This study addresses the long-standing question of which early molecular changes drive carcinogenesis during the long latency period of mesothelioma development and shows that CNT and asbestos pose a similar health hazard.}, } @article {pmid29111984, year = {2018}, author = {Ripabelli, G and Tamburro, M and Di Tella, D and Carrozza, F and Sammarco, ML}, title = {Asbestos Exposures, Mesothelioma Incidence and Mortality, and Awareness by General Practitioners in the Molise Region, Central Italy.}, journal = {Journal of occupational and environmental medicine}, volume = {60}, number = {2}, pages = {e90-e97}, doi = {10.1097/JOM.0000000000001211}, pmid = {29111984}, issn = {1536-5948}, abstract = {OBJECTIVE: The aim of this study was to evaluate environmental asbestos sources, mesothelioma incidence and mortality, and awareness on asbestos-related diseases (ARDs) by general practitioners (GPs) in Molise Region.

METHODS: The contaminated sites in three towns were identified by census; mesothelioma incidence (2000 to 2012) and mortality (2003 to 2013) was achieved from local registries; GPs were interviewed on practiced population's exposures and ARDs diagnosis.

RESULTS: About 54.3% of visited sites were contaminated (71.2% by friable asbestos) and 38.8% was extremely damaged. Over above time-periods, 32 mesothelioma cases (62.5% males, 25% in people aged 70 to 75 years) and 27 deaths (90% males, 69 ± 10 years, 70.4% pleural mesothelioma) have been reported. A total of 122 GPs were interviewed who had diagnosed 40 mesothelioma and 28 asbestosis cases.

CONCLUSION: There is the need of remediation/removal interventions for contaminated sites and of strategies to increase GPs awareness on asbestos risks for better patients' management.}, } @article {pmid29100460, year = {2017}, author = {Birnie, KA and Prêle, CM and Thompson, PJ and Badrian, B and Mutsaers, SE}, title = {Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {44}, pages = {78193-78207}, pmid = {29100460}, issn = {1949-2553}, abstract = {Malignant mesothelioma is an aggressive and often fatal cancer associated with asbestos exposure. The disease originates in the mesothelial lining of the serosal cavities, most commonly affecting the pleura. Survival rates are low as diagnosis often occurs at an advanced stage and current treatments are limited. Identifying new diagnostic and therapeutic targets for mesothelioma remains a priority, particularly for the new wave of victims exposed to asbestos through do-it-yourself renovations and in countries where asbestos is still mined and used. Recent advances have demonstrated a biological role for the small but powerful gene regulators microRNA (miRNA) in mesothelioma. A number of potential therapeutic targets have been identified. MiRNA have also become popular as potential biomarkers for mesothelioma due to their stable expression in bodily fluid and tissues. In this review, we highlight the current challenges associated with the diagnosis and treatment of mesothelioma and discuss how targeting miRNA may improve diagnostic, prognostic and therapeutic approaches.}, } @article {pmid29099505, year = {2018}, author = {Feder, IS and Theile, A and Tannapfel, A}, title = {Histological findings and lung dust analysis as the basis for occupational disease compensation in asbestos-related lung cancer in Germany.}, journal = {International journal of occupational medicine and environmental health}, volume = {31}, number = {3}, pages = {293-305}, doi = {10.13075/ijomeh.1896.01148}, pmid = {29099505}, issn = {1896-494X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*analysis ; Asbestosis/*diagnosis/diagnostic imaging/pathology ; Dust/analysis ; Germany ; Histological Techniques ; Humans ; Lung Diseases/*diagnosis/pathology ; Middle Aged ; Occupational Diseases/*diagnosis/pathology ; Occupational Exposure/statistics & numerical data ; Pleural Diseases/diagnosis/pathology ; Workers' Compensation ; }, abstract = {OBJECTIVES: This study has researched the significance of histologically raised findings and lung dust analyses in the context of claiming the recognition of and thus compensation for an asbestos-associated occupational disease.

MATERIAL AND METHODS: For this approach, all findings from the German Mesothelioma Register in 2015 that included lung dust analyses were evaluated and were compared with information on asbestos fiber exposure at work based on fiber years, and with the results of radiological findings.

RESULTS: For 68 insured persons, recognition of an asbestos-induced lung disease according to Section 4104 of the German Ordinance on Occupational Diseases (Berufskrankheitenverordnung - BKV) could be recommended solely on the basis of the histological examinations of lung tissues and complementary lung dust analyses. Neither did the calculation of the cumulative asbestos dust exposure at work yield 25 fiber years, nor could bridge findings (e.g., plaques) be identified. In addition, the autopsies of 12 patients revealed plaques that had not been diagnosed during radiological examinations. These results show that - irrespective of the prescribed working techniques and radiological diagnosis - pathological/anatomical and histological diagnostics are often the only way for the insureds to demonstrate the causal connection between asbestos and their disease. Even after long intervals of up to 40 years post last exposure, the asbestos fibers would still be easily detectable in the lung tissues evaluated.

CONCLUSIONS: Whenever suitable tissue is available, it should be examined for mild asbestosis with the aid of a lung dust analysis. Otherwise there is a risk that an occupational disease is wrongfully rejected. In the context of health insurance, the lung dust analysis and the resulting proof of the presence of asbestosis often constitute one option of providing evidence of an occupational disease. Int J Occup Med Environ Health 2018;31(3):293-305.}, } @article {pmid29094504, year = {2018}, author = {Schelch, K and Kirschner, MB and Williams, M and Cheng, YY and van Zandwijk, N and Grusch, M and Reid, G}, title = {A link between the fibroblast growth factor axis and the miR-16 family reveals potential new treatment combinations in mesothelioma.}, journal = {Molecular oncology}, volume = {12}, number = {1}, pages = {58-73}, pmid = {29094504}, issn = {1878-0261}, mesh = {Cell Line, Tumor ; Down-Regulation ; Fibroblast Growth Factor 2/*therapeutic use ; Fibroblast Growth Factors/*metabolism ; Humans ; Lung Neoplasms/*drug therapy/*metabolism ; Mesothelioma/*drug therapy/*metabolism ; MicroRNAs/genetics/*metabolism ; Pleura/pathology ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; Receptors, Fibroblast Growth Factor/genetics/metabolism ; Recombinant Proteins/*therapeutic use ; Up-Regulation ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy with very limited therapeutic options. Fibroblast growth factor (FGF) signals play important roles in mesothelioma cell growth. Several FGFs and FGF receptors (FGFRs) are predicted targets of the miR-15/16 family, which is downregulated in MPM. The aim of this study was to explore the link between the miR-15/16 family and the FGF axis in MPM. Expression analyses via RT-qPCR showed downregulation of the FGF axis after transfection with miR-15/16 mimics. Direct interaction was confirmed by luciferase reporter assays. Restoration of miR-15/16 led to dose-dependent growth inhibition in MPM cell lines, which significantly correlated with their sensitivity to FGFR inhibition. Treatment with recombinant FGF2 prevented growth inhibition and further reduced the levels of FGF/R-targeting microRNAs, indicating a vicious cycle between miR-15/16 down- and FGF/FGFR signaling upregulation. Combined inhibition of two independent miR-15/16 targets, the FGF axis and Bcl-2, resulted in additive or synergistic activity. Our data indicate that post-transcriptional repression of FGF-mediated signals contributes to the tumor suppressor function of the microRNA-15/16 family. Inhibiting hyperactivated FGF signals and Bcl-2 might serve as a novel therapeutic combination strategy in MPM.}, } @article {pmid29086761, year = {2017}, author = {Buresti, G and Colonna, F and Corfiati, M and Valenti, A and Persechino, B and Marinaccio, A and Rondinone, BM and Iavicoli, S}, title = {Economic impact of malignant mesothelioma in Italy: an estimate of the public and social costs.}, journal = {La Medicina del lavoro}, volume = {108}, number = {5}, pages = {358-366}, doi = {10.23749/mdl.v108i5.6505}, pmid = {29086761}, issn = {0025-7818}, mesh = {Aged ; Aged, 80 and over ; *Cost of Illness ; Female ; *Health Care Costs ; Humans ; Italy ; Lung Neoplasms/*economics ; Male ; Mesothelioma/*economics ; Middle Aged ; Occupational Diseases/*economics ; Public Health/*economics ; }, abstract = {BACKGROUND: Despite their considerable interest for public health policies and for occupational disease management and assessment, the economic costs of asbestos-related diseases (ARDs) for society have not been fully estimated or even frequently discussed.

OBJECTIVES: The aim of this study was to estimate the economic burden of mesothelioma in Italy by assessing the overall societal cost of the disease, applying an econometric model.

METHODS: We analyzed two main cost groups, public and social. The first includes expenditure borne by the State and other public bodies (medical care costs, insurance, tax and benefits), while the latter uses the human capital approach to measure the loss of productivity suffered by the economy as a whole.

RESULTS: We provide an estimate of euro 33,000 per patient for medical care costs and euro 25,000 for insurance and compensation; tax and benefits seem to roughly compensate. We estimated a loss of more than euro 200,000 per patient, in terms of loss of production.

CONCLUSIONS: This study offers a practical approach for estimating the economic impact of mesothelioma, and provides empirical evidence of the huge economic burden linked to this disease, with its high etiologic fraction.}, } @article {pmid29085453, year = {2017}, author = {Kim, YR and Song, MH and Lee, JW and Bae, JH and Kim, JE and Kang, DM and Lee, SY}, title = {Identification of tumor antigens in malignant mesothelioma.}, journal = {Oncology letters}, volume = {14}, number = {4}, pages = {4557-4562}, pmid = {29085453}, issn = {1792-1074}, abstract = {Serological analysis of recombinant tumor cDNA expression library (SEREX) is a powerful and widely used method to explore the cancer immune environment. In the present study, immunoscreening of normal testicular tissues and malignant mesothelioma (MM) cancer MSTO-211H cell line cDNA libraries with sera from 5 MM patients led to the isolation of 16 independent antigens, which were designated 'Korea Pusan-Malignant Mesothelioma' (KP-MM)-1 to -16. In total, 3/16 antigens were identified using the results of previous SEREX analyses, and 13 were newly identified. Of these, KP-MM-8, which was subsequently identified as amyotrophic lateral sclerosis 2 chromosome region candidate 11, was shown to be tissue-restricted. Reverse transcription-polymerase chain reaction demonstrated KP-MM-8 to be expressed strongly only in the normal testis, and weakly in the spleen, prostate, ovary, heart and skeletal muscle. In addition, KP-MM-8 mRNA was identified in MM cell lines, and in various other cancer cell lines, including MM (3/4), lung cancer (5/7), melanoma (5/7) and liver cancer (5/5) cell lines. Additionally, 2/16 antigens (KP-MM-2 and KP-MM-6) exclusively reacted with sera from cancer patients. However, KP-MM-8 reacted with 1 of 8 MM sera. Notably, 8/8 patients with MM and 8/8 normal individuals exhibited antibodies reactive to KP-MM-5, which was identified as cell division cycle 25B, a known oncogene. Overall, this data suggests that KP-MM-8 may be considered as a cancer/testis-like antigen and KP-MM-5 as an immunogenic tumor antigen in MM patients.}, } @article {pmid29084128, year = {2017}, author = {Mangone, L and Di Felice, E and Storchi, C and Romanelli, A and Broccoli, S and Vicentini, M and Giorgi Rossi, P}, title = {The effects of improving the mesothelioma surveillance network on sensitivity, timeliness in reporting and asbestos exposure assessment.}, journal = {La Medicina del lavoro}, volume = {108}, number = {5}, pages = {367-376}, doi = {10.23749/mdl.v108i5.5929}, pmid = {29084128}, issn = {0025-7818}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; *Epidemiological Monitoring ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Exposure/*statistics & numerical data ; Registries/*statistics & numerical data ; Sensitivity and Specificity ; Time Factors ; }, abstract = {BACKGROUND: In Italy, Mesothelioma Registries (MRs) have been established by law for the epidemiological surveillance of occupational cancers. MRs collect information about asbestos exposure of incident cases, through interviews. In the Emilia-Romagna region, MR was implemented in 1996 and extended its network of health professionals who report suspected mesothelioma in 2001 and 2007.

OBJECTIVES: This study evaluated the impact of the extension of the network on MR sensitivity and timeliness.

METHODS: Mesothelioma cases were analysed in three subsequent periods: 1996-2001 (before any network extension), 2002-2007 (after first extension) and 2008-2014 (after second extension). Sensitivity was evaluated by the proportion of cases directly reported by the network out of the total number of incident cases; reporting and interview timeliness were assessed by median times between diagnosis and, respectively, reporting and interview. Pleural mesothelioma reporting timeliness was also evaluated by use of quantile regression models, stratified by diagnostic certainty and adjusted by sex and age.

RESULTS: Sensitivity increased from 79.4% (1996-2001), to 89.0% (2002-2007) and to 91.4% (2008-2013). For mesothelioma with diagnostic certainty, we recorded considerably reduced reporting times from the 50th percentile on, whereas for uncertain mesothelioma relevant reductions were observed also in the lower percentiles. A reduced time to interview was observed too, which was more significant for uncertain cases. The proportion of patients directly interviewed increased from 33.5% (1996-2001), to 39.1% (2002-2007), to 49.5% (2008-2014).

CONCLUSIONS: The extended network improved the MR sensitivity and allowed shorter reporting and interview times and more frequent patient interviews, thus improving accuracy of exposure definition.}, } @article {pmid29083343, year = {2017}, author = {Chiesa, V and Odone, A and Signorelli, C}, title = {Forensic Epidemiology in Italy: principles and practice.}, journal = {Acta bio-medica : Atenei Parmensis}, volume = {88}, number = {3}, pages = {360-364}, doi = {10.23750/abm.v88i3.6742}, pmid = {29083343}, issn = {0392-4203}, mesh = {*Epidemiology ; *Forensic Sciences ; Humans ; Italy ; }, abstract = {Forensic epidemiology (FE) implies the use of epidemiological data in the processes and the involvement of epidemiologists in judicial proceedings. FE is essential for the assessment of causal association between the exposure to specific agents and the occurrence of diseases. In this paper we describe FE principles and applications in the Italian context as in recent years FE emerged increasingly as well as the need of experienced and trained epidemiological experts able to navigate legal proceedings. In the literature, the principles of FE have been widely described by different authors, among them: Kennet Rothman who introduced the definition of cause, Sir Austin Bradford Hill who proposed an analytic framework to assess the causal association, and recently by Sana Loue who described the actual legislation and application of FE in the United States. Despite the legislation varies among different countries epidemiological methods and theories represent the foundation for the application of FE we illustrate in this paper. The association between environmental pollution and disease, mobile phones and cancer, vaccines and autism, asbestos and pleural mesothelioma are all situations that underscore the need for FE investigations in criminal acts. Causal association is a complex process: in real life only in limited cases causal associations are assessed by gathering robust scientific evidence, while cases with doubts and situations where different approaches to questions may lead to discordant arguments to questions may lead to discordant arguments are more frequent. Therefore, during the assessment of causation in civil and criminal matters the choice the epidemiological expert - with his knowledge and expertise - and the evidence from well-designed studies are crucial to fill the gaps between clinical and epidemiological data and the low.}, } @article {pmid29080447, year = {2017}, author = {Salo, SAS and Ilonen, I and Laaksonen, S and Myllärniemi, M and Salo, JA and Rantanen, T}, title = {Epidemiology of malignant peritoneal mesothelioma: A population-based study.}, journal = {Cancer epidemiology}, volume = {51}, number = {}, pages = {81-86}, doi = {10.1016/j.canep.2017.10.008}, pmid = {29080447}, issn = {1877-783X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/mortality/pathology ; Male ; Mesothelioma/*epidemiology/mortality/pathology ; Middle Aged ; Peritoneal Neoplasms/*epidemiology/mortality/pathology ; Registries ; Retrospective Studies ; Survival Analysis ; Young Adult ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the mesothelial cells in the peritoneum with poor prognosis. Earlier reports from other countries indicate an incidence of 0.2-3 new cases per million per year. No previous studies have examined the national epidemiology of MPeM in Nordic countries. This study aimed to clarify the epidemiology of MPeM in Finland over a 12-year period.

METHODS: The data consisted of cancer notifications, laboratory notifications, and death certificate information in the Finnish Cancer Registry (FCR) and Statistics Finland (SF) of all MPeM patients from 2000 to 2012 in Finland. We also collected data on occupational disease compensations from the Workers' Compensation Center (WCC) of Finland. Any missing information was collected from the respective patient's file of every patient obtained from health institutions that had treated the patients.

RESULTS: Between January 1, 2000 and December 31, 2012, 90 new MPeM cases (56 males, 34 females) occurred in Finland. Median annual incidence was four new cases, which corresponded to 0.74 new cases per million per year. MPeM was deemed an occupational disease in 21 patients (23.3%). 71 patients (78.9%) of whom had a known cause of death, with a median survival of 4 months. The number of deaths linked to other disease than mesothelioma was 28/74 (37.8%).

CONCLUSIONS: Our study indicates that MPeM in Finland is rare and fatal, which is in accordance with previous reports from other countries. MPeM is also a fatal disease, since most of the patients died due to MPeM.}, } @article {pmid29078648, year = {2017}, author = {Perikleous, P and Waller, DA}, title = {Video assisted thoracoscopic and open chest surgery in diagnosis and treatment of malignant pleural diseases.}, journal = {Journal of visualized surgery}, volume = {3}, number = {}, pages = {85}, pmid = {29078648}, issn = {2221-2965}, abstract = {Parenchymal cancers of lung, breast, gastrointestinal tract and ovaries as well as lymphomas and mesotheliomas are among the most common cancer types causing malignant effusions, though almost all tumour types have been reported to cause a malignant effusion. The prognosis heavily depends on patients' response to systemic therapy however, regardless of the causing pathology and histopathologic form, malignant pleural disease is normally associated with a poor prognosis. To date, there are not sufficient data to allow accurate predictions of survival that would facilitate decision making for managing patients with malignant pleural diseases. Interventions are directed towards drainage of the effusion and, when appropriate, concurrent or subsequent pleurodesis or establishing long-term drainage to prevent re-accumulation. The rate of re-accumulation of the pleural effusion, the patient's prognosis, and the severity of the patient's symptoms should guide the subsequent choice of therapy. In contemporary medicine, not many cancers have managed to generate as intense debates concerning treatment, as malignant pleural mesothelioma. The relative advantages of surgery, radiation, chemotherapy and any combination of the three are continuously reassessed and reconsidered, even though not always based on scientific evidence. The aim of surgery in mesothelioma may be prolongation of life, in addition to palliation of symptoms. Longer recovery periods from more extensive surgical procedures could be justified, in carefully selected patients. Surgical options include: Video assisted thoracoscopic (VATS) pleurodesis, VATS partial pleurectomy (VATS PP)-both parietal and visceral; open pleurectomy decortication (PD)-with an extended option (EPD) and extrapleural pneumonectomy (EPP). Current evidence implies that EPD can be performed reliably in specialised centres with good results, both in terms of mortality and survival; however, no operation has yet been shown to be beneficial in a prospective randomized controlled clinical trial.}, } @article {pmid29073511, year = {2017}, author = {Mensi, C and Mendola, M and Dallari, B and Sokooti, M and Tabibi, R and Riboldi, L and Consonni, D}, title = {Differences between peritoneal and pleural mesothelioma in Lombardy, Italy.}, journal = {Cancer epidemiology}, volume = {51}, number = {}, pages = {68-73}, doi = {10.1016/j.canep.2017.10.003}, pmid = {29073511}, issn = {1877-783X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Italy/epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Peritoneal Neoplasms/*epidemiology ; Pleural Neoplasms/*epidemiology ; Registries ; }, abstract = {BACKGROUND: We examined characteristics of peritoneal (PEM) and pleural (PLM) mesothelioma in Lombardy, Italy.

METHODS: From the Lombardy Mesothelioma Registry we selected PEM (N=300) and PLM (N=5011) cases diagnosed in 2000-2014. We investigated asbestos exposure and presence of asbestosis or pleural plaques.

RESULTS: Incidence rates (per 1,000,000 person-years, world standardized) of PEM were 1.2 (men) and 0.9 (women), compared with 22.6 and 8.4 for PLM. Asbestosis (both genders) and pleural plaques (men) were more frequent among PEM cases. Occupational asbestos exposure was similar in PEM and PLM cases. We found higher proportions of PEMs employed in the asbestos cement production.

CONCLUSION: The higher frequency of pleural plaques in PEM cases confirm the association between asbestos and peritoneal mesothelioma. The higher proportions of asbestosis and of past employment in the asbestos-cement sector among PEM cases suggest a possible role of high exposures to asbestos in the peritoneal mesothelioma genesis.}, } @article {pmid29072598, year = {2017}, author = {Lemen, RA and Landrigan, PJ}, title = {Toward an Asbestos Ban in the United States.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29072598}, issn = {1660-4601}, mesh = {Animals ; Asbestos/*history/toxicity ; Carcinogens/*history/toxicity ; Government Regulation ; History, 19th Century ; History, 20th Century ; Humans ; Occupational Exposure/*legislation & jurisprudence/*prevention & control ; United States ; }, abstract = {Many developed countries have banned the use of asbestos, but not the United States. There have, however, been multiple efforts in the US to establish strict exposure standards, to limit asbestos use, and to seek compensation through the courts for asbestos-injured workers' In consequence of these efforts, asbestos use has declined dramatically, despite the absence of a legally mandated ban. This manuscript presents a historical review of these efforts.}, } @article {pmid29072053, year = {2017}, author = {Emami, H and Ilbeigi, A and Khodadad, K}, title = {An Overview of Asbestos and Malignant Pleural Mesothelioma: An Iranian Perspective.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {18}, number = {10}, pages = {2619-2623}, pmid = {29072053}, issn = {2476-762X}, } @article {pmid29068368, year = {2017}, author = {Metintaş, S and Batırel, HF and Bayram, H and Yılmaz, Ü and Karadağ, M and Ak, G and Metintaş, M}, title = {Turkey National Mesothelioma Surveillance and Environmental Asbestos Exposure Control Program.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {11}, pages = {}, pmid = {29068368}, issn = {1660-4601}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Environmental Exposure/*prevention & control ; Environmental Monitoring ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; *Population Surveillance ; Risk ; Rural Population/statistics & numerical data ; Turkey/epidemiology ; Young Adult ; }, abstract = {Malignant mesothelioma (MM) is an important health problem due to ongoing asbestos exposure. Environmental asbestos exposure leads to a high risk of MM in Turkey. The Turkish Mesothelioma Working Group and the Turkish Public Health Institute designed and performed the Turkey National Mesothelioma Surveillance and Environmental Asbestos Exposure Control Program (TUNMES-EAECP). The aim of this study was to analyze the results of the TUNMES-EAECP. Patients diagnosed with MM (code C45.0-C45.9) between 2008 and 2012 were identified. The "from case to the field" method was used to determine the villages with current or previous asbestos exposure. Special public health teams took soil samples from these villages, which were then examined using an X-ray diffractometer. Direct Standardized Average Annual Mesothelioma Incidence Rate (AMIR) and relative risk (RR) of MM were calculated. Finally, a projection on the incidence of MM between 2013 and 2033 was made. The number of confirmed MM cases was 5617 with a male to female ratio of 1.36. Mean age was 61.7 ± 13.4 (20-96) years. The median survival was eight (95% CI 7.6-8.4) months. Asbestos exposure continues in 379 villages, with 158,068 people still living in high risk areas. The standardized AMIR was 2.33/100,000 per year. The risk of MM was higher in males, in both sexes over the age of 40, in asbestos-containing provinces, and in those where the TUNMES was organized. Among the population with continuing asbestos exposure in rural areas, the number of MM cases between 2013 and 2033 was estimated as 2511. As such, the incidence of MM in Turkey is as high as in industrialized countries. Asbestos exposure in rural areas continues to be a serious problem in Turkey, which obviates the necessity for effective preventive measures.}, } @article {pmid29061909, year = {2018}, author = {Lacourt, A and Leveque, E and Goldberg, M and Leffondre, K}, title = {Dose-time response association between occupational asbestos exposure and pleural mesothelioma: authors' response.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {2}, pages = {161-162}, doi = {10.1136/oemed-2017-104802}, pmid = {29061909}, issn = {1470-7926}, } @article {pmid29059207, year = {2017}, author = {Alfaleh, MA and Howard, CB and Sedliarou, I and Jones, ML and Gudhka, R and Vanegas, N and Weiss, J and Suurbach, JH and de Bakker, CJ and Milne, MR and Rumballe, BA and MacDiarmid, JA and Brahmbhatt, H and Mahler, SM}, title = {Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models.}, journal = {PloS one}, volume = {12}, number = {10}, pages = {e0186137}, pmid = {29059207}, issn = {1932-6203}, mesh = {Animals ; *Cell Proliferation ; Humans ; Mesothelioma/*pathology ; Mice ; Receptors, Cell Surface/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV) are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs) which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN). Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.}, } @article {pmid29034666, year = {2017}, author = {Serrier, H and Sultan-Taïeb, H and Luce, D and Béjean, S}, title = {[Respiratory cancers attributable to occupational exposures: what is the cost to society in France].}, journal = {Sante publique (Vandoeuvre-les-Nancy, France)}, volume = {29}, number = {4}, pages = {509-524}, doi = {10.3917/spub.174.0509}, pmid = {29034666}, issn = {0995-3914}, mesh = {Female ; France/epidemiology ; Humans ; Male ; Occupational Diseases/*economics/epidemiology ; Occupational Exposure/*adverse effects/*economics ; Respiratory Tract Neoplasms/chemically induced/*economics/epidemiology ; Risk Factors ; }, abstract = {OBJECTIVE: To estimate the social cost of respiratory cancers attributable to occupational risk factors in France in 2010.

METHODS: We estimated the number of cases of respiratory cancers attributable to each identified occupational risk factor according to the attributable fractions method. We also estimated direct (costs of hospital stays, drugs, outpatient care) and indirect costs (production losses) related to morbidity (absenteeism and presenteeism) and mortality (years of lost production). Production losses for paid work and unpaid domestic activities were taken into account.

RESULTS: The social cost of respiratory cancers (lung, larynx, sinonasal, pleural mesothelioma) attributable to exposure to asbestos, chromium, diesel engine exhaust, polycyclic aromatic hydrocarbons, painting occupations (unidentified carcinogen), crystalline silica, wood and leather dust in France in 2010 was estimated to be between €960 and 1,866 million. The cost of lung cancer represents between €804 and 1,617 million. The three risk factors with the greatest impact are asbestos (€530 to 890 million), diesel engine exhaust (€227 to 394 million), and crystalline silica (€116 to 268 million).

CONCLUSION: These results provide a conservative estimate of the public health and economic burden of respiratory cancers attributable to occupational risk factors from a societal perspective.}, } @article {pmid29030093, year = {2018}, author = {Cherrie, JW and McElvenny, D and Blyth, KG}, title = {Estimating past inhalation exposure to asbestos: A tool for risk attribution and disease screening.}, journal = {International journal of hygiene and environmental health}, volume = {221}, number = {1}, pages = {27-32}, doi = {10.1016/j.ijheh.2017.09.013}, pmid = {29030093}, issn = {1618-131X}, support = {ETM/285//Chief Scientist Office/United Kingdom ; }, mesh = {Asbestos/*administration & dosage ; Humans ; Inhalation Exposure/*analysis ; Risk Assessment ; }, abstract = {INTRODUCTION: Late presentation is common in mesothelioma. Reliable assessment of past exposure to asbestos is a necessary first step for risk attribution and for the development of a future screening programme. Such a programme could maximise access to trials of novel therapies and would pave the way for development of novel chemoprophylaxis strategies. This paper describes a method for individual exposure reconstruction along with data from a validation study.

METHODS: The exposure assessment method uses only descriptive information about the circumstances of the work that could be obtained from questioning the worker. The assessment is based on the tasks carried out and includes parameters for substance emission potential, activity emission potential, the effectiveness of any local control measures, passive emission, the fractional time the asbestos source is active and the efficiency of any respiratory protection worn.

RESULTS: There was a good association between the estimated and measured exposure levels. Pearson's correlation coefficient between the log-transformed measurements and estimates from the model was 0.86, and 95% of the estimated individual values were within about a factor of ten of the associated measured value. The method described would be suitable for pre-selecting individuals at high risk of malignant pleural mesothelioma for screening using appropriate tools and/or enrolment in clinical trials of chemo-prophylaxis.

DISCUSSION: This method is of potential clinical value in developing novel treatment approaches for mesothelioma. Pilot studies to test this approach are urgently needed.}, } @article {pmid29020669, year = {2017}, author = {Gogali, A and Ntzani, EE and Manda-Stachouli, C and Peristeri, S and Tzarouchi, L and Laiou, E and Konstantinidis, A and Constantopoulos, SH and Dalavanga, Y}, title = {Evidence Suggesting the End of Universal Domestic Asbestos Exposure in Metsovo, NW Greece.}, journal = {Respiration; international review of thoracic diseases}, volume = {94}, number = {6}, pages = {510-517}, doi = {10.1159/000480151}, pmid = {29020669}, issn = {1423-0356}, mesh = {Adult ; Asbestos/adverse effects/*analysis ; Asbestosis/*diagnostic imaging ; Bronchoalveolar Lavage Fluid/chemistry ; Calcinosis/diagnostic imaging/*etiology ; Environmental Exposure/adverse effects/*analysis ; Female ; Greece/epidemiology ; Humans ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; Radiography, Thoracic ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Inhabitants of Metsovo, NW Greece, had been domestically exposed to asbestos from a gradually abandoned whitewash ("luto") that resulted in a declining epidemic of malignant mesothelioma.

OBJECTIVES: We aimed to evaluate whether other sources of asbestos exposure exist following "luto" abandonment.

METHODS: Chest computed tomography (CT) and bronchoalveolar lavage (BAL) were used to evaluate residual asbestos exposure in younger Metsovites through the identification of pleural calcifications and asbestos bodies, respectively. In order to provide a historical universally exposed group for comparison, we used the accumulated chest CTs and chest roentgenograms of our previous studies, performed in Metsovites with confirmed exposure but negative chest roentgenogram. As an additional external comparison group, we also assessed CT scans and chest roentgenograms of Metsovites being older than our target group obtained from the records of the Radiology Department between 2009 and 2011. In order to be able to compare our BAL findings, we sought historical controls among BAL studies performed in Metsovites with known exposure to "luto," in the 1980s-1990s, mainly to evaluate alveolitis. Those belonging to individuals of the same age range were used for further comparison.

RESULTS: Twenty-two Metsovites born between 1960 and 1980 consented to undergo a chest CT scan, while another 14 CTs were retrieved from the records of the Radiology Department (among 86 of all ages), thus increasing the number of individuals studied to 36. Five of the 36 Metsovites studied were former "luto" users for a short period of time. Minimal pleural calcifications were present in 2 of them, while all chest CTs of nonusers were negative. All 8 BAL studies were negative for asbestos bodies.

CONCLUSION: "Luto" use seems to have been the only source of considerable asbestos exposure in Metsovo.}, } @article {pmid28986649, year = {2017}, author = {Tischoff, I and Tannapfel, A}, title = {[Mesothelioma].}, journal = {Der Pathologe}, volume = {38}, number = {6}, pages = {547-560}, pmid = {28986649}, issn = {1432-1963}, abstract = {Malignant mesotheliomas are rare and aggressive tumours arising from mesothelial cells of the pleura and peritoneum. Infrequent sites of origin are the pericardium and tunica vaginalis testis. More than 80% of mesotheliomas are localized in the pleura. Men are more frequently affected than women. The median age is >60 years. Asbestos exposure is the best known aetilogical risk factor and is reported in 54-90% of patients. In Germany, malignant mesotheliomas caused by occupational asbestos exposure are compensated as occupational disease since 1977. Several neoplastic and non-neoplastic lesions like metastasis, sarcomas, lymphomas or pleuritis with reactive mesothelial proliferation have to be distinguished from malignant mesotheliomas. Especially, the pathohistological differentiation between atypical reactive mesothelial proliferation from malignant mesothelioma is a diagnostic challenge.}, } @article {pmid28985440, year = {2017}, author = {Binazzi, A and Marinaccio, A and Corfiati, M and Bruno, C and Fazzo, L and Pasetto, R and Pirastu, R and Biggeri, A and Catelan, D and Comba, P and Zona, A}, title = {Mesothelioma incidence and asbestos exposure in Italian national priority contaminated sites.}, journal = {Scandinavian journal of work, environment & health}, volume = {43}, number = {6}, pages = {550-559}, doi = {10.5271/sjweh.3676}, pmid = {28985440}, issn = {1795-990X}, mesh = {Asbestos/*toxicity ; Bayes Theorem ; Environmental Exposure/statistics & numerical data ; Female ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Occupational Exposure/*statistics & numerical data ; Registries/*statistics & numerical data ; }, abstract = {Objectives This study aimed to (i) describe mesothelioma incidence in the Italian national priority contaminated sites (NPCS) on the basis of data available from the Italian National Mesothelioma Registry (ReNaM) and (ii) profile NPCS using Bayesian rank analysis. Methods Incident cases of mesothelioma and standardized incidence ratios (SIR) were estimated for both genders in each of the 39 selected NPCS in the period 2000-2011. Age-standardized rates of Italian geographical macro areas were used to estimate expected cases. Rankings of areas were produced by a hierarchical Bayesian model. Asbestos exposure modalities were discussed for each site. Results In the study period, 2683 incident cases of mesothelioma (1998 men, 685 women) were recorded. An excess of mesothelioma incidence was confirmed in sites with a known past history of direct use of asbestos (among men) such as Balangero (SIR 197.1, 95% CI 82.0-473.6), Casale Monferrato (SIR 910.7, 95% CI 816.5-1012.8), and Broni (SIR 1288.5, 95% CI 981.9-1691.0), in sites with shipyards and harbors (eg, Trieste, La Spezia, Venice, and Leghorn), and in settings without documented direct use of asbestos. The analysis ranked the sites of Broni and Casale Monferrato (both genders) and Biancavilla (only for women) the highest. Conclusions The present study confirms that asbestos pollution is a risk for people living in polluted areas, due to not only occupational exposure in industrial settings with direct use of asbestos but also the presence of asbestos in the environment. Epidemiological surveillance of asbestos-related diseases is a fundamental tool for monitoring the health profile in NPCS.}, } @article {pmid28984470, year = {2017}, author = {Sobhani, N and Corona, SP and Bonazza, D and Ianza, A and Pivetta, T and Roviello, G and Cortale, M and Guglielmi, A and Zanconati, F and Generali, D}, title = {Advances in systemic therapy for malignant mesothelioma: future perspectives.}, journal = {Future oncology (London, England)}, volume = {13}, number = {23}, pages = {2083-2101}, doi = {10.2217/fon-2017-0224}, pmid = {28984470}, issn = {1744-8301}, mesh = {Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Immunotherapy ; Lung Neoplasms/mortality/pathology/*therapy ; Mesothelioma/mortality/pathology/*therapy ; Molecular Targeted Therapy ; Treatment Outcome ; }, abstract = {Malignant mesothelioma is a rare and aggressive form of cancer affecting the mesothelium. This mainly occupational disease is becoming more common in those countries where asbestos has been used for industrial applications. Notwithstanding the progress made in the field, patients do not survive more than 12 months on average with standard treatment. With the advent of next generation sequencing, it is now possible to study the mutational landscape of each tumor with the aim of identifying the genetic aberrations driving tumorigenesis. This review encompasses the latest research in the field, with particular attention to new chemotherapy combinatorial regimens, molecular targets and immunotherapies, providing a comprehensive picture of the current and future treatment options for malignant mesothelioma patients.}, } @article {pmid28979837, year = {2017}, author = {Ju, L and Wu, W and Yin, X and Xiao, Y and Jia, Z and Lou, J and Yu, M and Ying, S and Chen, T and Jiang, Z and Li, W and Chen, J and Zhang, X and Zhu, L}, title = {miR-30d is related to asbestos exposure and inhibits migration and invasion in NCI-H2452 cells.}, journal = {FEBS open bio}, volume = {7}, number = {10}, pages = {1469-1479}, pmid = {28979837}, issn = {2211-5463}, abstract = {Pleural malignant mesothelioma (MM) is a highly aggressive tumor that is typically related to asbestos exposure and has a latency of 20-60 years. Several microRNA contribute to MM initiation and progression, but the mechanisms are not clear. Here, we found that miR-30d is downregulated in the pleural MM cell line NCI-H2452, in the plasma of asbestos-exposed individuals, and in asbestos-exposed mesothelial cells. Furthermore, we investigated the influence of the overexpression of miR-30d in pleural MM cells. We demonstrated that miR-30d overexpression could suppress pleural MM cell proliferation, migration, and invasion in vitro and could promote cell apoptosis but could not significantly influence cell cycle. The mRNA and protein expression of vimentin and TWIST1 decreased, and the mRNA expression of CDH1 increased in NCI-H2452 cells that overexpressed miR-30d. We therefore conclude that miR-30d is related to asbestos exposure and inhibits cell migration and invasion by regulating the epithelial-mesenchymal transition in NCI-H2452 cells.}, } @article {pmid28960945, year = {2017}, author = {Yamaji, M and Ota, A and Wahiduzzaman, M and Karnan, S and Hyodo, T and Konishi, H and Tsuzuki, S and Hosokawa, Y and Haniuda, M}, title = {Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells.}, journal = {Cancer medicine}, volume = {6}, number = {11}, pages = {2646-2659}, pmid = {28960945}, issn = {2045-7634}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Benzylamines/pharmacology ; Caspase 3/metabolism ; Caspase 7/metabolism ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Forkhead Box Protein O1/metabolism ; G1 Phase Cell Cycle Checkpoints/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Glycogen Synthase Kinase 3 beta/metabolism ; Heterocyclic Compounds, 3-Ring/pharmacology ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Inhibitory Concentration 50 ; Mesothelioma/*drug therapy ; Oxadiazoles/pharmacology ; Phosphorylation/drug effects ; Phosphorylcholine/analogs & derivatives/pharmacology ; Pleural Neoplasms/*drug therapy ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/metabolism ; Pyrazoles/*pharmacology ; Pyrimidines/pharmacology ; Pyrroles/pharmacology ; Quinoxalines/pharmacology ; Sulfonamides/pharmacology ; Thiadiazoles/pharmacology ; Thiophenes/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPM), an asbestos-related occupational disease, is an aggressive and incurable tumor of the thoracic cavity. Despite recent advances in MPM treatment, overall survival of patients with MPM is very low. Recent studies have implicated that PI3K/Akt signaling is involved in MPM cell survival and development. To investigate the effects of Akt inhibitors on MPM cell survival, we examined the effects of nine selective Akt inhibitors, namely, afuresertib, Akti-1/2, AZD5363, GSK690693, ipatasertib, MK-2206, perifosine, PHT-427, and TIC10, on six MPM cell lines, namely, ACC-MESO-4, Y-MESO-8A, MSTO-211H, NCI-H28, NCI-H290, and NCI-H2052, and a normal mesothelial cell line MeT-5A. Comparison of IC50 values of the Akt inhibitors showed that afuresertib, an ATP-competitive specific Akt inhibitor, exerted tumor-specific effects on MPM cells. Afuresertib significantly increased caspase-3 and caspase-7 activities and apoptotic cell number among ACC-MESO-4 and MSTO-211H cells. Moreover, afuresertib strongly arrested the cell cycle in the G1 phase. Western blotting analysis showed that afuresertib increased the expression of p21WAF1/CIP1 and decreased the phosphorylation of Akt substrates, including GSK-3β and FOXO family proteins. These results suggest that afuresertib-induced p21 expression promotes G1 phase arrest by inducing FOXO activity. Furthermore, afuresertib significantly enhanced cisplatin-induced cytotoxicity. Interestingly, results of gene set enrichment analysis showed that afuresertib modulated the expression E2F1 and MYC, which are associated with fibroblast core serum response. Together, these results suggest that afuresertib is a useful anticancer drug for treating patients with MPM.}, } @article {pmid28960045, year = {2017}, author = {Kim, JS and Lim, SY and Hwang, J and Kang, EJ and Choi, YJ}, title = {A Case Report of Primary Pericardial Malignant Mesothelioma Treated with Pemetrexed and Cisplatin.}, journal = {Journal of Korean medical science}, volume = {32}, number = {11}, pages = {1879-1884}, pmid = {28960045}, issn = {1598-6357}, mesh = {Aged ; Antineoplastic Agents/*therapeutic use ; Calbindin 2/metabolism ; Cardiac Tamponade/diagnosis ; Cisplatin/*therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Keratins/metabolism ; Lung Neoplasms/diagnosis/*drug therapy ; Mesothelioma/diagnosis/*drug therapy ; Pemetrexed/*therapeutic use ; Pleural Neoplasms/diagnosis/*drug therapy ; Thorax/diagnostic imaging ; Tomography, X-Ray Computed ; Treatment Outcome ; Ultrasonography ; Vimentin/metabolism ; }, abstract = {Primary pericardial malignant mesothelioma (PPM) is a very rare malignancy, with an incidence of less than 0.002% and represents less than 5% of all mesotheliomas. The cause of pericardial mesothelioma is uncertain that differ from pleural mesothelioma which is associated with asbestos exposure. This malignancy is terribly aggressive and has very poor prognosis with less than six months of overall survival. We present a case of a 71-year-old woman who was diagnosed with cardiac tamponade caused by PPM and received chemotherapy with pemetrexed and cisplatin for six months. During two years she was alive without disease progression. To better understand the clinical, pathologic features and treatment outcome of this entity, we reviewed 23 cases described in the English literature from 2009, together with our case, provided a total of 24 cases. Based on this review, we suggest that PPM must be considered in patients who have unexplained massive pericardial effusion and recommend chemotherapy with pemetrexed and cisplatin for the better outcome of PPM.}, } @article {pmid28951802, year = {2017}, author = {MacLeod, JS and Harris, MA and Tjepkema, M and Peters, PA and Demers, PA}, title = {Cancer Risks among Welders and Occasional Welders in a National Population-Based Cohort Study: Canadian Census Health and Environmental Cohort.}, journal = {Safety and health at work}, volume = {8}, number = {3}, pages = {258-266}, pmid = {28951802}, issn = {2093-7911}, abstract = {BACKGROUND: Welders are exposed to many known and suspected carcinogens. An excess lung cancer risk among welders is well established, but whether this is attributable to welding fumes is unclear. Excess risks of other cancers have been suggested, but not established. We investigated welding cancer risks in the population-based Canadian Census Health and Environmental Cohort.

METHODS: Among 1.1 million male workers, 12,845 welders were identified using Standard Occupational Classification codes and followed through retrospective linkage of 1991 Canadian Long Form Census and Canadian Cancer Registry (1992-2010) records. Hazard ratios (HRs) were calculated using Cox proportional hazards models based on estimated risks of lung cancer, mesothelioma, and nasal, brain, stomach, kidney, and bladder cancers, and ocular melanoma. Lung cancer histological subtypes and risks by industry group and for occasional welders were examined. Some analyses restricted comparisons to blue-collar workers to minimize effects of potential confounders.

RESULTS: Among welders, elevated risks were observed for lung cancer [HR: 1.16, 95% confidence interval (CI): 1.03-1.31], mesothelioma (HR: 1.78, 95% CI: 1.01-3.18), bladder cancer (HR: 1.40, 95% CI: 1.15-1.70), and kidney cancer (HR: 1.30, 95% CI: 1.01-1.67). When restricted to blue-collar workers, lung cancer and mesothelioma risks were attenuated, while bladder and kidney cancer risks increased.

CONCLUSION: Excess risks of lung cancer and mesothelioma may be partly attributable to factors including smoking and asbestos. Welding-specific exposures may increase bladder and kidney cancer risks, and particular sources of exposure should be investigated. Studies that are able to disentangle welding effects from smoking and asbestos exposure are needed.}, } @article {pmid28949000, year = {2018}, author = {Jiang, Z and Chen, T and Chen, J and Ying, S and Gao, Z and He, X and Miao, C and Yu, M and Feng, L and Xia, H and Wu, W and Chen, R and Morinaga, K and Lou, J and Zhang, X}, title = {Hand-spinning chrysotile exposure and risk of malignant mesothelioma: A case-control study in Southeastern China.}, journal = {International journal of cancer}, volume = {142}, number = {3}, pages = {514-523}, doi = {10.1002/ijc.31077}, pmid = {28949000}, issn = {1097-0215}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos, Serpentine/*poisoning ; Case-Control Studies ; China/epidemiology ; Female ; Humans ; Logistic Models ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*statistics & numerical data ; Retrospective Studies ; Risk ; Textile Industry/statistics & numerical data ; }, abstract = {While chrysotile has been commonly used by Chinese textile industry for many years, investigations on the association of chrysotile exposure with risk of mesothelioma in China are scarce. We conducted a case-control study in a county located at Southeastern China, including 46 cases and 230 individually matched controls. A semi-quantitative method based on experts' assessment was used for evaluating hand-spinning chrysotile exposure. Conditional logistic regression models were used to assess the association of asbestos exposure with risk of mesothelioma. We found that hand-spinning chrysotile exposure was associated with significantly elevated risk of mesothelioma, reaching OR =10 (95% CIs: 1.4-65) for possible exposure and 64 (12-328) for definite exposure. Our data suggested a dose-response relationship of chrysotile exposure duration with risk of mesothelioma, reaching 28 (6-134) for <6 years, 51 (11-247) for 7-17 years and 56 (9-351) for ≥18 years. A dose-response relationship of cumulative exposure index (CEI) with risk of mesothelioma was found, reaching 28 (6-137) for CEI at 0-0.5 fibers per milliliter years (f/mL-year), 36 (7-184) for CEI at 0.5-28.6 f/mL-years and 79 (14-451) for CEI > 28.6 f/mL-years. We found a dose-response relationship of chrysotile exposure duration and CEI with risk of mesothelioma in Southeastern China, adding valuable information on health hazards of chrysotile exposure in China where chrysotile is still used nationwide.}, } @article {pmid28947868, year = {2017}, author = {Zhao, J and Zuo, T and Zheng, R and Zhang, S and Zeng, H and Xia, C and Yang, Z and Chen, W}, title = {Epidemiology and trend analysis on malignant mesothelioma in China.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {29}, number = {4}, pages = {361-368}, pmid = {28947868}, issn = {1000-9604}, abstract = {OBJECTIVE: Population-based cancer registration data were used to analyze the epidemiology and trend of malignant mesothelioma in China, and the result would provide basic data for its prevention and control.

METHODS: Malignant mesothelioma data in 2013 were retrieved from the database of National Cancer Registry. Malignant mesothelioma incidence and mortality were estimated using age-specific rate by urban/rural and gender according to the national population in 2013. Malignant mesothelioma data from 22 cancer registries were used for trend analysis during 2000-2013.

RESULTS: It is estimated that there were 2,041 new malignant mesothelioma cases and 1,659 malignant mesothelioma deaths occurred in 2013. The crude incidence rate in China were 1.50/106 (males 1.67/106, females 1.32/106), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 1.03/106 and 1.02/106, respectively. The crude mortality rate in China was 1.22/106 (males 1.67/106, females 1.32/106), age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 0.83/106 and 0.81/106, respectively. There was an increasing trend of incidence rate for malignant mesothelioma in registration areas of China during 2000-2013 with annual percentage change (APC) of 2.5% [95% confidence interval (95% CI): 0.6%-4.5%]. After age standardization, no significant differences were observed. No matter for crude mortality rates or age-standardized mortality rates, no significant differences were observed during 2000-2013.

CONCLUSIONS: Malignant mesothelioma is the major occupational and environmental neoplasm associated with asbestos exposure. The increasing incidence trend suggests that more attention should be paid on this disease.}, } @article {pmid28947493, year = {2017}, author = {Landrigan, PJ}, title = {Data on mesothelioma mortality: a powerful tool for preventing asbestos-related disease.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {12}, pages = {849-850}, doi = {10.1136/oemed-2017-104688}, pmid = {28947493}, issn = {1470-7926}, mesh = {Asbestos/adverse effects ; Female ; Humans ; Male ; Mesothelioma/*mortality/*prevention & control ; Occupational Exposure/adverse effects/statistics & numerical data ; }, } @article {pmid28940402, year = {2017}, author = {Kradin, RL and Eng, G and Christiani, DC}, title = {Diffuse peritoneal mesothelioma: A case series of 62 patients including paraoccupational exposures to chrysotile asbestos.}, journal = {American journal of industrial medicine}, volume = {60}, number = {11}, pages = {963-967}, doi = {10.1002/ajim.22768}, pmid = {28940402}, issn = {1097-0274}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/*toxicity ; Carcinogens/*toxicity ; Female ; Humans ; Male ; Mesothelioma/*etiology/pathology ; Middle Aged ; Occupational Exposure/*adverse effects/legislation & jurisprudence ; Peritoneal Neoplasms/*etiology/pathology ; Time Factors ; }, abstract = {BACKGROUND: Diffuse peritoneal malignant mesothelioma (DPM) is caused by exposure to asbestos. The medical literature has linked DPM primarily to high levels of asbestos exposure, in particular amosite. Controversy persists as to whether chrysotile is capable of causing DPM, especially when exposures are paraoccupational.

METHODS: Sixty-two subjects (51 men, 11 women) with DPM were reviewed in medical-legal consultation with deposition and product identification evidence.

RESULTS: All had pathologically confirmed DPM. Most were exposed to both amphibole and chrysotile, but chrysotile alone was documented in 14/62 (26%) cases. A total of 7/14 (50%) cases of the paraoccupational exposures were to chrysotile alone. Women were younger than men as were those with paraoccupational versus those with occupational exposure. The mean duration of exposure for all cases was 17.9 ± 10 years and latency from time of first exposure was 45.9 + 11.6 years.

CONCLUSIONS: DPM occurs with both occupational and paraoccupational exposures to asbestos and may be seen in paraoccupational exposures to chrysotile asbestos.}, } @article {pmid28937307, year = {2017}, author = {Møller, P and Jacobsen, NR}, title = {Weight of evidence analysis for assessing the genotoxic potential of carbon nanotubes.}, journal = {Critical reviews in toxicology}, volume = {47}, number = {10}, pages = {867-884}, doi = {10.1080/10408444.2017.1367755}, pmid = {28937307}, issn = {1547-6898}, mesh = {*DNA Damage ; Hazardous Substances/*toxicity ; Humans ; Mutagenicity Tests ; Nanotubes, Carbon/*toxicity ; }, abstract = {Carbon nanotube (CNT) is a nanomaterial that has received interest because of its high-tensile strength and low weight. Although CNTs differ substantially in physico-chemical properties, they share high aspect ratio which resembles that of asbestos and other fibers causing lung cancer and mesothelioma. One type of multi-walled CNTs (i.e. MWCNT-7) has been classified as possibly carcinogenic to humans by IARC (Group 2B) based on experimental animal data, whereas other types of MWCNTs and single-walled CNTs (SWCNT) could not be classified due to lack of data from epidemiologic studies and insufficient mechanistic evidence. Damage to DNA is considered to be a key mechanistic step in the development of fiber-induced cancer. Thus, the genotoxic potential can be a cornerstone in the evaluation of hazards of CNTs. The present study used a weight of evidence (WoE) analysis to evaluate the genotoxicity of different types of CNTs. Genotoxicity endpoints close to cancer (mutations and chromosome aberrations) and animal models had highest weight in the WoE analysis. Eight CNT materials out of 130, which had been assessed in several studies, were evaluated in the WoE analysis. The results demonstrated that MWCNT-7 has strongest WoE for a genotoxic hazard among the MWCNTs. Two types of SWCNTs have a similar WoE for genotoxicity as MWCNT-7. Several reference materials from the Joint Research Centre have less WoE for genotoxicity. The WoE analysis demonstrates a difference in genotoxicity for CNTs, but further research is required to unravel the physico-chemical characteristics that govern the differences in genotoxic hazard.}, } @article {pmid28935666, year = {2017}, author = {Marsh, GM and Riordan, AS and Keeton, KA and Benson, SM}, title = {Non-occupational exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {11}, pages = {838-846}, doi = {10.1136/oemed-2017-104383}, pmid = {28935666}, issn = {1470-7926}, mesh = {Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; Environmental Exposure/*adverse effects/analysis ; Female ; *Housing ; Humans ; Lung Neoplasms/*chemically induced ; Male ; Mesothelioma/*chemically induced ; Occupational Exposure ; Pleural Neoplasms/*chemically induced ; *Residence Characteristics ; Risk Assessment ; }, abstract = {OBJECTIVE: To conduct an updated literature review and meta-analysis of studies of pleural malignant mesothelioma (PMM) risk among persons exposed to asbestos non-occupationally (household and neighbourhood).

METHODS: We performed a literature search for articles available in the National Center for Biotechnology Information's PubMed database published between 1967 and 2016. Meta-analyses were conducted to calculate pooled PMM risk estimates, stratifying for household or neighbourhood exposure to asbestos and/or predominant asbestos fibre type (chrysotile, amphibole or mixed).

RESULTS: Eighteen studies in 12 countries comprising 665 cases met the meta-analysis inclusion criteria. We identified 13 estimates of PMM risk from neighbourhood exposures, 10 from household and one from mixed exposure, and combined the estimates using random-effects models. The overall meta-relative risk (meta-RR) was 5.9 (95% CI 4.4 to 8.7). The meta-RRs for household and neighbourhood exposures were 5.4 (95% CI 2.6 to 11.2) and 6.9 (95% CI 4.2 to 11.4), respectively. We observed trends in risk in relation to fibre type for both household and neighbourhood studies. For chrysotile, mixed and amphibole fibres, respectively, meta-RRs for neighbourhood studies were 3.8 (95% CI 0.4 to 38.4), 8.4 (95% CI 4.7 to 14.9) and 21.1 (95% CI 5.3 to 84.5) and meta-RRs for household studies were 4.0 (95% CI 0.8 to 18.8), 5.3 (95% CI 1.9 to 15.0) and 21.1 (95% CI 2.8 to 156.0).

CONCLUSIONS: PMM risks from non-occupational asbestos exposure are consistent with the fibre-type potency response observed in occupational settings. By relating our findings to knowledge of exposure-response relationships in occupational settings, we can better evaluate PMM risks in communities with ambient asbestos exposures from industrial or other sources.}, } @article {pmid28929108, year = {2017}, author = {Ju, L and Wu, W and Yu, M and Lou, J and Wu, H and Yin, X and Jia, Z and Xiao, Y and Zhu, L and Yang, J}, title = {Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure.}, journal = {BioMed research international}, volume = {2017}, number = {}, pages = {2747215}, pmid = {28929108}, issn = {2314-6141}, mesh = {Asbestos/*toxicity ; Carcinogens ; Cell Line ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; DNA Damage/drug effects ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Nanotubes, Carbon/*toxicity ; Time Factors ; }, abstract = {Despite being a commercially important product, multiwalled carbon nanotubes (MWCNTs) continue to raise concerns over human health due to their structural similarity to asbestos. Indeed, exposure to MWCNT has been shown to induce lung cancer and even mesothelioma, but contradictory results also exist. To clarify the potentially carcinogenic effects of rigid and rod-like MWCNT and to elucidate the underlying mechanisms, the effects of MWCNT on human mesothelial cell MeT-5A were examined throughout 3 months of continuous exposure, including cytotoxicity, genotoxicity, and cell motility. It was found that MWCNT did not affect MeT-5A cell proliferation at 10 μg/cm2 within 72 h treatment, but under the same condition, MWCNT induced genotoxicity and perturbed cell motility. In addition, MeT-5A cells demonstrated different cellular responses to MWCNT after short-term and long-term exposure. Taken together, our results indicated a possible carcinogenic potential for MWCNT after long-term treatment, in which Annexin family proteins might be involved.}, } @article {pmid28925565, year = {2017}, author = {Egilman, D}, title = {Response to Hessel.}, journal = {American journal of industrial medicine}, volume = {60}, number = {10}, pages = {915-920}, doi = {10.1002/ajim.22773}, pmid = {28925565}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Australia ; *Automobiles ; Humans ; Industry/*legislation & jurisprudence ; Mesothelioma/*etiology ; Occupational Diseases/*etiology ; Research Support as Topic/*ethics ; }, } @article {pmid28915695, year = {2017}, author = {Pouliquen, DL and Nawrocki-Raby, B and Nader, J and Blandin, S and Robard, M and Birembaut, P and Grégoire, M}, title = {Evaluation of intracavitary administration of curcumin for the treatment of sarcomatoid mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {34}, pages = {57552-57573}, pmid = {28915695}, issn = {1949-2553}, abstract = {A rat model of sarcomatoid mesothelioma, mimicking some of the worst clinical conditions encountered, was established to evaluate the therapeutic potential of intracavitary curcumin administration. The M5-T1 cell line, selected from a collection established from F344 rats induced with asbestos, produces tumors within three weeks, with extended metastasis in normal tissues, after intraperitoneal inoculation in syngeneic rats. The optimal concentration/time conditions for killing M5-T1 cells with curcumin were first determined in vitro. Secondly, the potential of intraperitoneal curcumin administration to kill tumor cells in vivo was evaluated in tumor-bearing rats, in comparison with a reference epigenetic drug, SAHA. Both agents administered at days 21 and 26 after tumor challenge produced necrosis within the solid tumors at day 28. However, tumor tissue necrosis induced with curcumin was much more extensive than with SAHA, and was characterized by infiltration with mononuclear phagocytic cells. In contrast, tumor tissue treated with SAHA contained foci of resistant cells and was infiltrated by many isolated CD8+ cells. The treatment of tumor-bearing rats with 1.5 mg/kg curcumin on days 7, 9, 11 and 14 after tumor challenge dramatically reduced the mean total tumor mass at day 16. Clusters of CD8+ T lymphocytes were observed at the periphery of small residual tumor masses in the peritoneal cavity, which presented a significant reduction in mitotic index, IL6 and vimentin expression compared with tumors in untreated rats. These data open up interesting new prospects for the therapy of sarcomatoid mesothelioma with curcumin and its derivatives.}, } @article {pmid28914691, year = {2017}, author = {Zadnik, V and Primic Zakelj, M and Jarm, K and Zagar, T}, title = {Time trends and spatial patterns in the mesothelioma incidence in Slovenia, 1961-2014.}, journal = {European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)}, volume = {26 Joining forces for better cancer registration in Europe}, number = {}, pages = {S191-S196}, doi = {10.1097/CEJ.0000000000000384}, pmid = {28914691}, issn = {1473-5709}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Male ; Mesothelioma/diagnosis/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects ; Registries/*statistics & numerical data ; Slovenia/epidemiology ; Time Factors ; }, abstract = {We aimed to explore the temporal and spatial variations in mesothelioma incidence in Slovenia for the last 50 years and, among these, to evaluate the consequences of asbestos usage. The incidence data from the population-based Cancer Registry of Republic of Slovenia for the period 1961-2014 were analysed. The data of asbestos imported to Slovenia were used as a proxy for asbestos exposure in manufacturing areas. Log-linear joinpoint regression and age-period-cohort Poisson models were used in the time-trend analysis. The mesothelioma maps were produced according to the method of local standardized incidence ratio estimates and are presented together with the map of Slovenian major asbestos-exposed locations. The maximum value of the asbestos import curve corresponds to the peak of mesothelioma curve exactly 30 years later. Both increases before the peak are comparable in time interval and steepness. The highest mesothelioma risk was detected for the cohort born between 1940 and 1944. In maps, the mesothelioma clusters manifest around known asbestos sources predominantly in the years 1980-1990, but in the last few years, the geographical distribution is more dispersed. The data from our long-existing population-based cancer registry provide a good insight into the on-going mesothelioma epidemic in Slovenia. Our results imply that the mesothelioma peak has already been reached in Slovenia. In the future, new cases will emerge more randomly throughout the country.}, } @article {pmid28913871, year = {2017}, author = {Greenberg, M}, title = {Experimental asbestos studies in the UK: 1912-1950.}, journal = {American journal of industrial medicine}, volume = {60}, number = {11}, pages = {956-962}, doi = {10.1002/ajim.22762}, pmid = {28913871}, issn = {1097-0274}, mesh = {Animals ; Asbestos/*history/toxicity ; Asbestosis/*history ; Biomedical Research/*history/methods ; Carcinogens/*history/toxicity ; Guinea Pigs ; History, 19th Century ; History, 20th Century ; Humans ; Lung Neoplasms/etiology/*history ; Mesothelioma/etiology/*history ; *Mining ; Occupational Exposure/adverse effects/*history ; Pulmonary Fibrosis/etiology/history ; Rats ; Schools, Medical/history ; United Kingdom ; }, abstract = {The asbestos industry originated in the UK in the 1870s. By 1898, asbestos had many applications and was reported to be one of the four leading causes of severe occupational disease. In 1912, the UK government sponsored an experimental study that reported that exposure to asbestos produced no more than a modicum of pulmonary fibrosis in guinea pigs. In the 1930s, the newly established Medical Research Council, with assistance from industry, sponsored a study of the effects of exposing animals to asbestos by injection (intratracheal and subcutaneous) and by inhalation in the factory environment. Government reports, publications, and contemporary records obtained by legal discovery have been reviewed in the context of the stage of scientific development and the history of the times. Experimenters were engaged in a learning process during the 1912-1950 period, and their reports of the effects of asbestos were inconsistent. Pathologists who studied the effects of asbestos experimentally, at whole animal, tissue and cellular levels, advanced experimental methodology and mechanistic knowledge. In the hands of public relations experts, however, research was exploited to preserve an industry and perpetuate preventable diseases, a practice that continues to this day.}, } @article {pmid28910456, year = {2018}, author = {Hung, YP and Dong, F and Watkins, JC and Nardi, V and Bueno, R and Dal Cin, P and Godleski, JJ and Crum, CP and Chirieac, LR}, title = {Identification of ALK Rearrangements in Malignant Peritoneal Mesothelioma.}, journal = {JAMA oncology}, volume = {4}, number = {2}, pages = {235-238}, pmid = {28910456}, issn = {2374-2445}, abstract = {Importance: Malignant peritoneal mesothelioma is a rare, aggressive tumor arising from the peritoneal lining, induced by asbestos, therapeutic radiation, or germline mutations. Nevertheless, the molecular features remain largely unknown.

Objective: To investigate anaplastic lymphoma kinase (ALK) rearrangements in a large series of peritoneal mesothelioma and characterize the mutational landscape of these tumors.

We studied 88 consecutive patients (39 men, 49 women; median age 61, range 17-84 years) with peritoneal mesotheliomas diagnosed at a single institution between 2005 and 2015. We identified ALK-positive mesotheliomas by immunohistochemistry and confirmed ALK rearrangement by fluorescence in situ hybridization (FISH). In ALK-rearranged cases, we characterized the fusion partners using targeted next-generation sequencing of both tumor DNA and RNA. In select cases, we quantified asbestos fibers by combined scanning electron microscopy and x-ray spectroscopy. We also explored ALK rearrangement in a separate series of 205 patients with pleural mesothelioma.

Main Outcomes and Measures: Identification and characterization of novel ALK rearrangements and correlations with clinicopathologic characteristics.

Results: Anaplastic lymphoma kinase was positive by immunohistochemistry in 11 (13%) peritoneal mesotheliomas (focal weak in 8, diffuse strong in 3). In focal weak ALK-positive cases, no ALK rearrangement was detected by FISH or next-generation sequencing. In strong diffuse ALK-positive cases, FISH confirmed ALK rearrangements, and next-generation sequencing identified novel fusion partners ATG16L1, STRN, and TPM1. Patients with ALK-rearranged peritoneal mesotheliomas were women and younger than patients without ALK rearrangement (median age 36 vs 62; Mann-Whitney test, P = .02), but all other clinicopathologic characteristics (size of tumor nodules, histology, treatment, and survival) were not different. No asbestos fibers were detected in ALK-rearranged cases. Furthermore, loss of chromosomal region 9p or 22q or genetic alterations in BAP1, SETD2, or NF2 typically present in peritoneal mesothelioma were absent in the ALK-rearranged cases. All pleural mesotheliomas were ALK-negative by immunohistochemistry.

Conclusions and Relevance: We identified unique ALK rearrangements in a subset of patients with peritoneal mesothelioma, each lacking asbestos fibers, therapeutic radiation, and cytogenetic and molecular alterations typically found in these tumors. Identification of clinically actionable ALK rearrangements may represent a novel pathogenetic mechanism of malignant peritoneal mesothelioma with promise for targeted therapy.}, } @article {pmid28884745, year = {2018}, author = {Vivero, M and Bueno, R and Chirieac, LR}, title = {Clinicopathologic and genetic characteristics of young patients with pleural diffuse malignant mesothelioma.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {31}, number = {1}, pages = {122-131}, pmid = {28884745}, issn = {1530-0285}, support = {R01 CA120528/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cyclin-Dependent Kinase Inhibitor p18/genetics ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/genetics/mortality/*pathology ; Male ; Mesothelioma/genetics/mortality/*pathology ; Middle Aged ; Pleural Neoplasms/genetics/mortality/*pathology ; Proportional Hazards Models ; Young Adult ; }, abstract = {Pleural diffuse malignant mesothelioma typically presents during the seventh decade of life and has poor prognosis. Recent epidemiologic studies have shown differences between young and older mesothelioma patients, but the biology of pleural mesothelioma in young patients is poorly understood. We studied the clinicopathologic and genetic characteristics in pleural mesothelioma patients aged 35 years and younger. Thirty-six consecutive pleural mesothelioma patients aged 35 years and younger were compared with 48 older patients. We examined demographic and clinical characteristics, histologic type, growth patterns, mitotic index, and nuclear grade on hematoxylin and eosin-stained slides, BAP1 protein expression by immunohistochemistry, and CDKN2A and NF2 deletions by fluorescence in situ hybridization. Clinicopathologic and cytogenetic results were compared between young and older groups, and correlated with overall survival. Young patients were more frequently women, reported less asbestos exposure, and had a greater frequency of prior therapeutic radiation and family history of breast cancer than older patients (P<0.05 each). There were no histologic differences between young and older patients (all P>0.05). CDKN2A deletion was less prevalent in young patients (P=0.01), loss of BAP1 protein expression less frequent in young patients (P=0.06), and NF2 deletion rates similar between groups (P>0.05 each). Median overall survival was 40 vs 26 months (P=0.10) in young and older patients, respectively, and 47 vs 31 months (P=0.04) when comparing patients with epithelioid histology only. High mitotic index and non-epithelioid histology were the only characteristics associated with a poor overall survival in young patients. Young patients with pleural mesothelioma have an equal sex distribution and are more likely to have a history of mantle radiation, family history of breast cancer, and lower rates of CDKN2A deletion than older patients. Our results suggest that pleural mesothelioma in young patients has distinctive clinical and genetic characteristics, despite some similarities to pleural mesothelioma in older patients.}, } @article {pmid28881848, year = {2017}, author = {Lagniau, S and Lamote, K and van Meerbeeck, JP and Vermaelen, KY}, title = {Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moonshot?.}, journal = {Oncotarget}, volume = {8}, number = {32}, pages = {53751-53762}, pmid = {28881848}, issn = {1949-2553}, abstract = {Early diagnosis of malignant pleural mesothelioma (MPM) is a challenge for clinicians. The disease is usually detected in an advanced stage which precludes curative treatment. We assume that only new and non-invasive biomarkers allowing earlier detection will result in better patient management and outcome. Many efforts have already been made to find suitable biomarkers in blood and pleural effusions, but have not yet resulted in a valid and reproducible diagnostic one. In this review, we will highlight the strengths and shortcomings of blood and fluid based biomarkers and highlight the potential of breath analysis as a non-invasive screening tool for MPM. This method seems very promising in the early detection of diverse malignancies, because exhaled breath contains valuable information on cell and tissue metabolism. Research that focuses on breath biomarkers in MPM is in its early days, but the few studies that have been performed show promising results. We believe a breathomics-based biomarker approach should be further explored to improve the follow-up and management of asbestos exposed individuals.}, } @article {pmid28870611, year = {2017}, author = {van Zandwijk, N and Pavlakis, N and Kao, SC and Linton, A and Boyer, MJ and Clarke, S and Huynh, Y and Chrzanowska, A and Fulham, MJ and Bailey, DL and Cooper, WA and Kritharides, L and Ridley, L and Pattison, ST and MacDiarmid, J and Brahmbhatt, H and Reid, G}, title = {Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study.}, journal = {The Lancet. Oncology}, volume = {18}, number = {10}, pages = {1386-1396}, doi = {10.1016/S1470-2045(17)30621-6}, pmid = {28870611}, issn = {1474-5488}, mesh = {Adult ; Aged ; Australia ; Biopsy, Needle ; Cancer Care Facilities ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Infusions, Intravenous ; Kaplan-Meier Estimate ; Lung Neoplasms/diagnostic imaging/*drug therapy/mortality/pathology ; Male ; Maximum Tolerated Dose ; Mesothelioma/diagnostic imaging/*drug therapy/mortality/pathology ; MicroRNAs/*administration & dosage ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy/mortality/pathology ; *Patient Safety ; Patient Selection ; Pleural Neoplasms/diagnostic imaging/*drug therapy/mortality/pathology ; Positron Emission Tomography Computed Tomography/methods ; Risk Assessment ; Survival Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: TargomiRs are minicells (EnGeneIC Dream Vectors) loaded with miR-16-based mimic microRNA (miRNA) and targeted to EGFR that are designed to counteract the loss of the miR-15 and miR-16 family miRNAs, which is associated with unsuppressed tumour growth in preclinical models of malignant pleural mesothelioma. We aimed to assess the safety, optimal dosing, and activity of TargomiRs in patients with malignant pleural mesothelioma.

METHODS: In this first-in-man, open-label, dose-escalation phase 1 trial at three major cancer centres in Sydney (NSW, Australia), we recruited adults (aged ≥18 years) with a confirmed diagnosis of malignant pleural mesothelioma, measurable disease, radiological signs of progression after previous chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 3 months or more, immunohistochemical evidence of tumour EGFR expression, and adequate bone marrow, liver, and renal function. Patients were given TargomiRs via 20 min intravenous infusion either once or twice a week (3 days apart) in a traditional 3 + 3 dose-escalation design in five dose cohorts. The dose-escalation steps planned were 5 × 109, 7 × 109, and 9 × 109 TargomiRs either once or twice weekly, but after analysis of data from the first eight patients, all subsequent patients started protocol treatment at 1 × 109 TargomiRs. The primary endpoints were to establish the maximum tolerated dose of TargomiRs as measured by dose-limiting toxicity, define the optimal frequency of administration, and objective response (defined as the percentage of assessable patients with a complete or partial response), duration of response (defined as time from the first evidence of response to disease progression in patients who achieved a response), time to response (ie, time from start of treatment to the first evidence of response) and overall survival (defined as time from treatment allocation to death from any cause). Analyses were based on the full analysis set principle, including every patient who received at least one dose of TargomiRs. The study was closed for patient entry on Jan 3, 2017, and registered with ClinicalTrials.gov, number NCT02369198, and the Australian Registry of Clinical Trials, number ACTRN12614001248651.

FINDINGS: Between Sept 29, 2014, and Nov 24, 2016, we enrolled 27 patients, 26 of whom received at least one TargomiR dose (one patient died before beginning treatment). Overall, five dose-limiting toxicities were noted: infusion-related inflammatory symptoms and coronary ischaemia, respectively, in two patients given 5 × 109 TargomiRs twice weekly; anaphylaxis and cardiomyopathy, respectively, in two patients given 5 × 109 TargomiRs once weekly but who received reduced dexamethasone prophylaxis; and non-cardiac pain in one patient who received 5 × 109 TargomiRs once weekly. We established that 5 × 109 TargomiRs once weekly was the maximum tolerated dose. TargomiR infusions were accompanied by transient lymphopenia (25 [96%] of 26 patients), temporal hypophosphataemia (17 [65%] of 26 patients), increased aspartate aminotransferase or alanine aminotranferase (six [23%] of 26 patients), and increased alkaline phosphatase blood concentrations (two [8%]). Cardiac events occurred in five patients: three patients had electrocardiographic changes, one patient had ischaemia, and one patient had Takotsubo cardiomyopathy. Of the 22 patients who were assessed for response by CT, one (5%) had a partial response, 15 (68%) had stable disease, and six (27%) had progressive disease. The proportion of patients who achieved an objective response was therefore one (5%) of 22, and the duration of the objective response in that patient was 32 weeks. Median overall survival was 200 days (95% CI 94-358). During the trial, 21 deaths occurred, of which 20 were related to tumour progression and one was due to bowel perforation.

INTERPRETATION: The acceptable safety profile and early signs of activity of TargomiRs in patients with malignant pleural mesothelioma support additional studies of TargomiRs in combination with chemotherapy or immune checkpoint inhibitors.

FUNDING: Asbestos Diseases Research Foundation.}, } @article {pmid28866609, year = {2017}, author = {Odgerel, CO and Takahashi, K and Sorahan, T and Driscoll, T and Fitzmaurice, C and Yoko-O, M and Sawanyawisuth, K and Furuya, S and Tanaka, F and Horie, S and Zandwijk, NV and Takala, J}, title = {Estimation of the global burden of mesothelioma deaths from incomplete national mortality data.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {12}, pages = {851-858}, pmid = {28866609}, issn = {1470-7926}, mesh = {Asbestos/*adverse effects ; Databases, Factual ; Environmental Exposure/*adverse effects ; Female ; *Global Health ; Humans ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; World Health Organization ; }, abstract = {BACKGROUND: Mesothelioma is increasingly recognised as a global health issue and the assessment of its global burden is warranted.

OBJECTIVES: To descriptively analyse national mortality data and to use reported and estimated data to calculate the global burden of mesothelioma deaths.

METHODS: For the study period of 1994 to 2014, we grouped 230 countries into 59 countries with quality mesothelioma mortality data suitable to be used for reference rates, 45 countries with poor quality data and 126 countries with no data, based on the availability of data in the WHO Mortality Database. To estimate global deaths, we extrapolated the gender-specific and age-specific mortality rates of the countries with quality data to all other countries.

RESULTS: The global numbers and rates of mesothelioma deaths have increased over time. The 59 countries with quality data recorded 15 011 mesothelioma deaths per year over the 3 most recent years with available data (equivalent to 9.9 deaths per million per year). From these reference data, we extrapolated the global mesothelioma deaths to be 38 400 per year, based on extrapolations for asbestos use.

CONCLUSIONS: Although the validity of our extrapolation method depends on the adequate identification of quality mesothelioma data and appropriate adjustment for other variables, our estimates can be updated, refined and verified because they are based on commonly accessible data and are derived using a straightforward algorithm. Our estimates are within the range of previously reported values but higher than the most recently reported values.}, } @article {pmid28863229, year = {2018}, author = {Glynn, ME and Keeton, KA and Gaffney, SH and Sahmel, J}, title = {Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence between Urban and Rural Areas in the United States (1973-2012).}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {3}, pages = {454-471}, doi = {10.1111/risa.12887}, pmid = {28863229}, issn = {1539-6924}, mesh = {Age Factors ; Asbestos/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/*chemically induced/*epidemiology ; Registries ; Rural Population ; SEER Program ; Sex Factors ; United States ; Urban Population ; }, abstract = {Over the past 40 years, measured ambient asbestos concentrations in the United States have been higher in urban versus rural areas. The purpose of this study was to determine whether variations in ambient asbestos concentrations have influenced pleural mesothelioma risk in females (who generally lacked historic occupational asbestos exposure relative to males). Male pleural mesothelioma incidence trends were analyzed to provide perspective for female trends. Annual age-adjusted incidence rates from 1973 to 2012 were obtained from the SEER 9, 13, and 18 databases for urban and rural locations, and standardized rate ratios were calculated. Female rural rates exceeded urban rates in almost half of the years analyzed, although the increases were not statistically significant, which is in line with expectations if there was no observable increased risk for urban locations. In contrast, male urban rates were elevated over rural rates for nearly all years examined and were statistically significantly elevated for 22 of the 40 years. Trend analyses demonstrated that trends for females remained relatively constant over time, whereas male urban and rural incidence increased into the 1980s and 1990s, followed by a decrease/leveling off. Annual female urban and rural incidence rates remained approximately five- to six-fold lower than male urban and rural incidence rates on average, consistent with the comparatively increased historical occupational asbestos exposure for males. The results suggest that differences in ambient asbestos concentrations, which have been reported to be 10-fold or greater across regions in the United States, have not influenced the risk of pleural mesothelioma.}, } @article {pmid28855951, year = {2017}, author = {Eisenhawer, C and Felten, MK and Hager, T and Gronostayskiy, M and Bruners, P and Tannapfel, A and Kraus, T}, title = {Migrating pleural plaque in a patient with asbestos induced pleural disease: a case report.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {12}, number = {}, pages = {25}, pmid = {28855951}, issn = {1745-6673}, abstract = {BACKGROUND: Health surveillance of formerly asbestos exposed individuals focus on early detection of asbestos related diseases, such as lung fibrosis (asbestosis), pleural plaques, mesothelioma and lung cancer in particular. One main concern is the early and clear identification of lesions with a high risk of malignant changes and their undelayed clinical work-up. False positive results may lead to unnecessary and often painful diagnostic interventions, which create high costs when applied to a large cohort and also may discredit the whole program. We describe an unusual presentation of a common lesion among asbestos exposed individuals, which has to our knowledge never been described before. Being aware of this pathological pathway may prevent inadequate clinical decisions with disadvantages for the patient. Underlying implications regarding health surveillance and the reading of CT-scans of the thorax are important for the management of formerly asbestos exposed individuals.

CASE PRESENTATION: During follow-up of an asbestos exposed 72 year old former power plant worker with known pleural changes, a nodule located next to the left costophrenic angle was newly discovered on CT-scan. As the previous scan 1 year before did not show any changes in that area, a fast growing tumour was suspected and an immediate biopsy performed. The tissue showed the characteristics of a pleural plaque with no signs of malignancy. After carefully reviewing all previous radiographs a rounded opacity attached to the mediastinal pleura close to the oesophagus and slightly cranial to the position of the removed nodule could be discerned. That nodule had increased in size over several years and was no longer visible on the latest scan. It appeared that the originally slow growing plaque had migrated to the costophrenic angle some time before it was discovered in the latest scan thus imposing as a fast growing tumour.

CONCLUSIONS: We concluded that asbestos related pleural plaques can under special circumstances get separated from the pleura and migrate to another position in the pleural cavity. The case provides new insights in the development and properties of pleural lesions and may offer new options for the management of formerly asbestos exposed patients.}, } @article {pmid28852644, year = {2017}, author = {Ndlovu, N and Rees, D and Murray, J and Vorajee, N and Richards, G and teWaterNaude, J}, title = {Asbestos-related diseases in mineworkers: a clinicopathological study.}, journal = {ERJ open research}, volume = {3}, number = {3}, pages = {}, pmid = {28852644}, issn = {2312-0541}, support = {D43 ES018744/ES/NIEHS NIH HHS/United States ; }, abstract = {The accurate diagnosis of asbestos-related diseases is important because of past and current asbestos exposures. This study evaluated the reliability of clinical diagnoses of asbestos-related diseases in former mineworkers using autopsies as the reference standard. Sensitivity, specificity, positive predictive value and negative predictive value were calculated. The 149 cases identified had clinical examinations 0.3-7.4 years before death. More asbestos-related diseases were diagnosed at autopsy rather than clinically: 77 versus 52 for asbestosis, 27 versus 14 for mesothelioma and 22 versus 3 for lung cancer. Sensitivity and specificity values for clinical diagnoses were 50.6% and 81.9% for asbestosis, 40.7% and 97.5% for mesothelioma, and 13.6% and 100.0% for lung cancer. False-negative diagnoses of asbestosis were more likely using radiographs of acceptable (versus good) quality and in cases with pulmonary tuberculosis at autopsy. The low sensitivity values are indicative of the high proportion of false-negative diagnoses. It is unlikely that these were the result of disease manifestation between the last clinical assessment and autopsy. Where clinical features suggest asbestos-related diseases but the chest radiograph is negative, more sophisticated imaging techniques or immunohistochemistry for asbestos-related cancers should be used. Autopsies are useful for the detection of previously undiagnosed and misdiagnosed asbestos-related diseases, and for monitoring clinical practice and delivery of compensation.}, } @article {pmid28845826, year = {2017}, author = {Cardinale, L and Ardissone, F and Gned, D and Sverzellati, N and Piacibello, E and Veltri, A}, title = {Diagnostic Imaging and workup of Malignant Pleural Mesothelioma.}, journal = {Acta bio-medica : Atenei Parmensis}, volume = {88}, number = {2}, pages = {134-142}, doi = {10.23750/abm.v88i2.5558}, pmid = {28845826}, issn = {0392-4203}, mesh = {Humans ; Lung Neoplasms/*diagnostic imaging ; Magnetic Resonance Imaging ; Mesothelioma/*diagnostic imaging ; Pleural Neoplasms/*diagnostic imaging ; Positron Emission Tomography Computed Tomography ; Radiography, Thoracic ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {Malignant pleural mesothelioma is the most frequent primary neoplasm of the pleura and its incidence is still increasing.This tumor has a strong association with exposure to occupational or environmental asbestos, often after a long latent period of 30-40 years.Plain chest radiography (CXR) is usually the first-line radiologic examination, but the radiographic findings are nonspecific due to its limited contrast resolution and they need to be complemented by other imaging modalities such as computed tomography (CT), magnetic resonance Imaging (MRI), Positron emission tomography-computed tomography (PET-CT) and ultrasound (US).The aim of this paper is to describe the imaging features of this malignancy, underlining the peculiarity of CXR, CT, MRI, PET-CT and US and also focusing on diagnostic workup, based on the literature evidence and according to our experience.}, } @article {pmid28838403, year = {2017}, author = {Lau, B and Kumar, S and Yan, T and Burn, J and Kennedy, C and McLean, J and Boyer, M and McCaughan, B and Kao, S}, title = {Pathological complete response in malignant pleural mesothelioma patients following induction chemotherapy: Predictive factors and outcomes.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {111}, number = {}, pages = {75-78}, doi = {10.1016/j.lungcan.2017.07.010}, pmid = {28838403}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Induction Chemotherapy ; Kaplan-Meier Estimate ; Lung Neoplasms/*drug therapy/mortality/*pathology ; Male ; Mesothelioma/*drug therapy/mortality/*pathology ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/*drug therapy/mortality/*pathology ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {A small proportion of patients with malignant pleural mesothelioma (MPM) achieve pathological complete response (CR) following treatment with current practice induction chemotherapy. Our analysis of 58 patients with MPM treated with platinum-based chemotherapy showed 4 patients (7%) attained pathological CR at subsequent extrapleural pneumonectomy (EPP). Patient and tumour factors such as age, gender, smoking habit, histological subtype, and clinical stage were not found to be associated with pathological CR. Patients with pathological CR had longer disease-free survival (29.2 vs. 13.8 months; p=0.08) and overall survival (76.4 vs. 23.4 months; p=0.06) but this did not reach statistical significance. Our study suggests that patients who achieve pathological CR after chemotherapy may have improved survival in MPM.}, } @article {pmid28838385, year = {2017}, author = {Scarlata, S and Finamore, P and Giannunzio, G and Santangelo, S and Antonelli Incalzi, R}, title = {Chest ultrasonography in health surveillance of asbestos related pleural disease.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {111}, number = {}, pages = {139-142}, doi = {10.1016/j.lungcan.2017.07.019}, pmid = {28838385}, issn = {1872-8332}, mesh = {Adult ; Asbestos/*adverse effects ; Carcinogens ; Female ; Humans ; Male ; Mass Screening ; Middle Aged ; Occupational Exposure/*adverse effects ; Pleural Diseases/*diagnosis/epidemiology/*etiology ; *Public Health Surveillance ; Time Factors ; Tomography, X-Ray Computed ; *Ultrasonography ; }, abstract = {High resolution computed tomography, (HRCT), is currently considered the diagnostic gold standard to diagnose early stage malignant pleural mesothelioma and other non-malignant pleural conditions, but it is expensive and exposes the patient to radiation dose. In a screening and population medicine perspective, Thoracic Ultrasounds may become a valuable alternative because it can detect minimal changes in pleural surface, is widely available and safe. On these bases, we therefore validated thoracic US in subjects with history of exposure to asbestos, having HRCT as the reference standard. One hundred-fifty subjects were screened and 117 were recruited. Pleural abnormalities at US and/or HRCT were detected in 66 out of 117 subjects (prevalence=57%), and their prevalence was unrelated to both mansion and smoking habit, while mean age and mean length of exposure were higher in those having pleural abnormalities (age=47±5 vs 44±6years, p<0.05;years of exposure=20±7 vs 17±5, p<0.05). Thirteen out of 19 subjects with pleural abnormalities at HRCT were also identified by thoracic US, whereas 47 participants had lesions seen at US, but not at the HRCT scan. Positive and negative percent agreement were 66.6% and 51.8%, respectively; the McNemar's test for equality showed a p-value <0.001. In conclusion, chest US might complement HRCT in the health surveillance of asbestos exposed population to detect earlier lesions or to follow up US approachable lesions. Further research is needed to clarify whether this approach may enhance early recognition of pleural mesothelioma and ameliorate prognosis.}, } @article {pmid28833303, year = {2017}, author = {Oddone, E and Ferrante, D and Tunesi, S and Magnani, C}, title = {Mortality in asbestos cement workers in Pavia, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {60}, number = {10}, pages = {852-866}, doi = {10.1002/ajim.22750}, pmid = {28833303}, issn = {1097-0274}, mesh = {Adult ; Asbestos/adverse effects ; Asbestosis/*mortality ; Cohort Studies ; Construction Industry/*statistics & numerical data ; Construction Materials ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure ; Peritoneal Neoplasms/mortality ; Pleural Neoplasms/mortality ; }, abstract = {BACKGROUND: The aim of this study was to describe the mortality of a cohort of asbestos-cement workers in the largest plant in the most industrialized Italian region (Lombardy).

METHODS: A cohort study was carried out on 1818 subjects, corresponding to 47 536.1 person-years of observation. Standardized mortality ratios (SMRs) were computed for the major causes of death.

RESULTS: Increased SMRs were observed for pleural, peritoneal and lung cancers, and for asbestosis (SMR 26.73, 95% Confidence Interval (CI) 20.99-33.55; 9.15, 95%CI 5.00-15.34; 1.48, 95%CI 1.27-1.72; and 368.05, 95%CI 214.40-589.29, respectively). No excess in mortality for laryngeal cancer was observed (SMR 0.70, 95%CI 0.30-1.39). An increased mortality for ovarian cancer (SMR 3.64, 95%CI 0.99-9.33) was observed, although it was not statistically significant. Among men, mortality for pleural malignant mesothelioma was observed to be related to the duration of exposure, though not to latency.

CONCLUSIONS: The results of this study are generally consistent with present knowledge. Conversely, our results do not support the hypothesis that pleural malignant mesothelioma risk indefinitely increases after exposure, suggesting instead that the alternative hypothesis of a risk plateau or decrease after a time since first exposure of more than 40 years is more consistent with the observed data.}, } @article {pmid28829357, year = {2017}, author = {Serio, G and Pezzuto, F and Marzullo, A and Scattone, A and Cavone, D and Punzi, A and Fortarezza, F and Gentile, M and Buonadonna, AL and Barbareschi, M and Vimercati, L}, title = {Peritoneal Mesothelioma with Residential Asbestos Exposure. Report of a Case with Long Survival (Seventeen Years) Analyzed by Cgh-Array.}, journal = {International journal of molecular sciences}, volume = {18}, number = {8}, pages = {}, pmid = {28829357}, issn = {1422-0067}, mesh = {Adult ; Asbestos/*adverse effects ; Biopsy ; Comparative Genomic Hybridization ; *Environmental Exposure ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/*etiology ; Male ; Mesothelioma/*diagnosis/*etiology ; Peritoneal Neoplasms/*diagnosis/*etiology ; }, abstract = {Malignant mesothelioma is a rare and aggressive tumor with limited therapeutic options. We report a case of a malignant peritoneal mesothelioma (MPM) epithelioid type, with environmental asbestos exposure, in a 36-year-old man, with a long survival (17 years). The patient received standard treatment which included cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

METHODS AND RESULTS: Molecular analysis with comparative genomic hybridization (CGH)-array was performed on paraffin-embedded tumoral samples. Multiple chromosomal imbalances were detected. The gains were prevalent. Losses at 1q21, 2q11.1→q13, 8p23.1, 9p12→p11, 9q21.33→q33.1, 9q12→q21.33, and 17p12→p11.2 are observed. Chromosome band 3p21 (BAP1), 9p21 (CDKN2A) and 22q12 (NF2) are not affected. Conclusions: the defects observed in this case are uncommon in malignant peritoneal mesothelioma. Some chromosomal aberrations that appear to be random here, might actually be relevant events explaining the response to therapy, the long survival and, finally, may be considered useful prognostic factors in peritoneal malignant mesothelioma (PMM).}, } @article {pmid28827980, year = {2017}, author = {Khmou, M and Echcharif, S and Kabbaj, R and Khannoussi, BE}, title = {Malignant Deciduoid Mesothelioma: case presentation of an exceptional variant and review of the literature.}, journal = {BMC clinical pathology}, volume = {17}, number = {}, pages = {13}, pmid = {28827980}, issn = {1472-6890}, abstract = {BACKGROUND: Malignant Deciduoid Mesothelioma (MDM) is an extremely rare variant of epithelioid mesothelioma. It was first described in young females, in the peritoneum, and its relation with asbestos was not well defined. Later reports, have shown that this variant may also occur in the pleura, the pericardium and the tunica vaginalis of elderly people, who had been exposed to asbestos.

CASE PRESENTATION: We report a case of malignant deciduoid mesothelioma that occurred in the peritoneal cavity, and the omentum of a 35-year-old woman. The patient had never been exposed to asbestos.

CONCLUSIONS: Through this observation, we describe clinical, histopathological, and immunohistochemical findings of deciduoid mesothelioma, and review the literature reports.}, } @article {pmid28823988, year = {2018}, author = {Boffetta, P and Pira, E and Romano, C and Violante, FS and Farioli, A and Zocchetti, C and La Vecchia, C}, title = {Response to: 'Dose-time-response association between occupational asbestos exposure and pleural mesothelioma' by Lacourt et al.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {2}, pages = {160}, doi = {10.1136/oemed-2017-104570}, pmid = {28823988}, issn = {1470-7926}, } @article {pmid28823918, year = {2017}, author = {Hattori, K and Nakadate, K and Morii, A and Noguchi, T and Ogasawara, Y and Ishii, K}, title = {Exposure to nano-size titanium dioxide causes oxidative damages in human mesothelial cells: The crystal form rather than size of particle contributes to cytotoxicity.}, journal = {Biochemical and biophysical research communications}, volume = {492}, number = {2}, pages = {218-223}, doi = {10.1016/j.bbrc.2017.08.054}, pmid = {28823918}, issn = {1090-2104}, mesh = {Cell Line ; Crystallization ; DNA Damage/*drug effects ; Epithelial Cells/cytology/*drug effects/metabolism/pathology ; Humans ; Nanostructures/*toxicity ; Oxidative Stress/*drug effects ; Particle Size ; Pleura/cytology/drug effects/metabolism/pathology ; Reactive Oxygen Species/metabolism ; Titanium/*toxicity ; }, abstract = {Exposure to nanoparticles such as carbon nanotubes has been shown to cause pleural mesothelioma similar to that caused by asbestos, and has become an environmental health issue. Not only is the percutaneous absorption of nano-size titanium dioxide particles frequently considered problematic, but the possibility of absorption into the body through the pulmonary route is also a concern. Nevertheless, there are few reports of nano-size titanium dioxide particles on respiratory organ exposure and dynamics or on the mechanism of toxicity. In this study, we focused on the morphology as well as the size of titanium dioxide particles. In comparing the effects between nano-size anatase and rutile titanium dioxide on human-derived pleural mesothelial cells, the anatase form was shown to be actively absorbed into cells, producing reactive oxygen species and causing oxidative damage to DNA. In contrast, we showed for the first time that the rutile form is not easily absorbed by cells and, therefore, does not cause oxidative DNA damage and is significantly less damaging to cells. These results suggest that with respect to the toxicity of titanium dioxide particles on human-derived mesothelial cells, the crystal form rather than the particle size has a greater effect on cellular absorption. Also, it was indicated that the difference in absorption is the primary cause of the difference in the toxicity against mesothelial cells.}, } @article {pmid28817672, year = {2017}, author = {Kwak, KM and Paek, D and Hwang, SS and Ju, YS}, title = {Estimated future incidence of malignant mesothelioma in South Korea: Projection from 2014 to 2033.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0183404}, pmid = {28817672}, issn = {1932-6203}, mesh = {History, 21st Century ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Registries ; Republic of Korea/epidemiology ; }, abstract = {Malignant mesothelioma is a malignant tumor on the pleura or the peritoneum caused mostly by asbestos. Although asbestos is not currently used in South Korea, the incidence of mesothelioma is increasing due to its long latent period. This study predicted the incidence of malignant mesothelioma in South Korea over the next 20 years using an age-period-cohort (APC) model. Data regarding mesothelioma incidence from 1994-2013 were acquired from the Korea Central Cancer Registry (KCCR). Demographic data, including prospective resident data, were acquired from the Korean Statistical Information Service (KOSIS) for 1994-2033. An APC model with Møller's power-link function was utilized to predict the incidence of mesothelioma. It was predicted that 2,380 and 1,199 new cases of mesothelioma in men and women, respectively, would occur over the next 20 years. For both sexes, the mesothelioma incidence rate was predicted to be greater in 2029-2033 compared to that in 2009-2013 (men, 0.282 vs 0.563; women, 0.155 vs 0.217). For men, the age-standardized incidence rate was predicted to be slightly greater in 2029-2033 relative to the rate in 2009-2013 (0.228 vs 0.235), while the age-standardized incidence rate in women decreased within the same timeframe (0.113 vs 0.109). The changes in mesothelioma incidence were mostly caused by changes in the population structure due to aging and not by changes in the mesothelioma risk ratio. The results of this study project a continuous increase in mesothelioma incidence in South Korea over the next 20 years. Although the projected increase in mesothelioma incidence was not related to an increase in the mesothelioma risk ratio, continuous preventive efforts are necessary to reduce the exposure to asbestos and prevent the trend from worsening.}, } @article {pmid28810297, year = {2017}, author = {Wei, MC and Yang, SJ}, title = {[Clinical and pathologic features of extrapleural sarcomatoid mesothelioma].}, journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology}, volume = {46}, number = {8}, pages = {559-564}, doi = {10.3760/cma.j.issn.0529-5807.2017.08.008}, pmid = {28810297}, issn = {0529-5807}, mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis ; Bone Neoplasms/chemistry/*pathology ; Calbindin 2/analysis ; Diagnosis, Differential ; Female ; Fibrosarcoma/pathology ; Head and Neck Neoplasms/chemistry/*pathology ; Humans ; Immunohistochemistry ; Keratins/analysis ; Male ; Mesothelioma/chemistry/diagnosis/*pathology ; Middle Aged ; Neoplasm Recurrence, Local ; Peritoneal Neoplasms/chemistry/*pathology ; Prognosis ; Sarcoma/pathology ; Vimentin/analysis ; }, abstract = {Objective: To investigate the morphological features, diagnosis and differential diagnosis of extrapleural sarcomatoid malignant mesothelioma (SMM). Methods: Six cases of extrapleural SMM were evaluated for their clinical, histological, immunohistochemical features, and prognosis. Results: Patients included 3 men and 3 women, with a median age of 60 years (range 41-75 years). All patients had no asbestos exposure in history and no pleural lesions. The tumors involved peritoneum (3 cases), bone (2 cases), and neck soft tissue (1 case). Histologically, the tumors were mainly composed of slender to plump spindle cells with occasional polymorphic cells, arranged in fascicular to storiform pattern or haphazardly organized, closely resembling those of fibromatosis, fibrosarcoma or malignant fibrous histiocytoma. The tumor cells were imunohistochemically positive for cytokeratin (pan, 6/6), calretinin (5/6), podoplanin (6/6), D2-40 (4/6), vimentin (6/6), WT1 (4/6), CD10 (3/6), SMA (4/6), and variably positive for CK7, and CK8/18, but were negative for other linage-specific markers. The Ki-67 proliferation indexes ranged from 25% to 55%, consistent with the diagnosis of malignant mesothelioma of the sarcomatous type. Ultrastructurally, the tumor cells possessed discontinuous external lamina, cytoplasmic processes, microfilaments and desmosomal intercellular junctions. Local recurrence or metastasis was seen in 1 case and 4 cases, respectively, after surgery, and all the patients died of the disease within 9 months. Conclusions: Extrapleural SMM, although rare, should be considered as a differential diagnosis among other benign or malignant sarcomatoid tumors and sarcomas. Along with clinical and radiological presentation, the combination of broad-spectrum cytokeratin, vimentin, and a series of mesothelial markers are useful for diagnosis of SMM.}, } @article {pmid28791466, year = {2017}, author = {Velasco-García, MI and Cruz, MJ and Diego, C and Montero, MA and Álvarez-Simón, D and Ferrer, J}, title = {First Identification of Pulmonary Asbestos Fibres in a Spanish Population.}, journal = {Lung}, volume = {195}, number = {5}, pages = {671-677}, pmid = {28791466}, issn = {1432-1750}, support = {Fis PI07/90478//Instituto de Salud Carlos III/ ; CP12/03101//Instituto de Salud Carlos III/ ; }, mesh = {Aged ; Aged, 80 and over ; *Asbestos, Amphibole ; Asbestosis/*pathology ; Case-Control Studies ; Female ; Humans ; *Lung ; Lung Neoplasms/*pathology/surgery ; Male ; Mesothelioma/*pathology ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Middle Aged ; Mineral Fibers ; *Occupational Exposure ; Pleural Neoplasms/*pathology ; Spain ; Spectrometry, X-Ray Emission ; }, abstract = {INTRODUCTION: This study aimed to characterize, for the first time in Spain, the type of asbestos fibres (AF) in the lungs of exposed and non-exposed populations.

MATERIALS AND METHODS: Lung samples from 38 subjects living in Barcelona and Ferrol, Spain, were studied, which were divided into three groups: Group A-five subjects without known respiratory disease; Group B-20 ex-shipyard workers and Group C-13 patients with lung cancer. After eliminating the organic material, the inorganic residue was analysed using electronic microscopy (EM). To identify the type of fibre, the samples were analysed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX).

RESULTS: All the fibres identified corresponded to amphiboles (crocidolite 45%, anthophyllite 22%, tremolite 16%, amosite 15% and actinolite 3%). In 14 patients (37%), a single type of asbestos was found in the lungs (amosite in two, actinolite in one, anthophyllite in four, crocidolite in five and tremolite in two). Forty-six percent of the AF analysed had a length > 5 µm and a diameter < 0.2 µm.

CONCLUSIONS: The results of this study provide the first data on the type of asbestos retained in the lung of Spanish population. A particularly striking finding is the exclusive retention of amphiboles, which suggests that chrysotile is eliminated after inhalation. Our findings support estimations considering Spain and other southern European countries with similar asbestos imports and consumption at a high risk to develop asbestos-related diseases in the years to come.}, } @article {pmid28791219, year = {2017}, author = {Shaikh, AA and Naik, KV and Shetty, SN and Ansari, NN and Babhale, PS}, title = {Bilateral Malignant Mesothelioma of Tunica Vaginalis A Case Report on Rare Presentation.}, journal = {Urology case reports}, volume = {14}, number = {}, pages = {53-55}, pmid = {28791219}, issn = {2214-4420}, abstract = {Malignant mesothelioma involving the para-testicular tunica is extremely rare and an aggressive tumor. Bilateral malignant mesothelioma of the tunica vaginalis is not reported previously in the literature. Rarity of the disease, absence of any specific clinical and radiological findings makes the preoperative diagnosis difficult. Aggressive surgical approach is the key to successful management with high inguinal orchiectomy and scrotectomy appears to be optimal treatment in patients with localized disease.}, } @article {pmid28777435, year = {2018}, author = {Muscella, A and Cossa, LG and Vetrugno, C and Antonaci, G and Marsigliante, S}, title = {Inhibition of ZL55 cell proliferation by ADP via PKC-dependent signalling pathway.}, journal = {Journal of cellular physiology}, volume = {233}, number = {3}, pages = {2526-2536}, doi = {10.1002/jcp.26128}, pmid = {28777435}, issn = {1097-4652}, mesh = {Adenosine Diphosphate/analogs & derivatives/*pharmacology ; Antineoplastic Agents/*pharmacology ; Asbestos/adverse effects ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Dose-Response Relationship, Drug ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mesothelioma/*drug therapy/enzymology/genetics/pathology ; Phosphorylation ; Protein Kinase C-alpha/genetics/*metabolism ; Protein Kinase C-delta/genetics/*metabolism ; Protein Stability ; Purinergic P2Y Receptor Agonists/*pharmacology ; RNA Interference ; Receptors, Purinergic P2Y1/*drug effects/metabolism ; Signal Transduction/*drug effects ; Thionucleotides/pharmacology ; Time Factors ; Transfection ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Extracellular nucleotides can regulate cell proliferation in both normal and tumorigenic tissues. Here, we studied how extracellular nucleotides regulate the proliferation of ZL55 cells, a mesothelioma-derived cell line obtained from bioptic samples of asbestos-exposed patients. ADP and 2-MeS-ADP inhibited ZL55 cell proliferation, whereas ATP, UTP, and UDP were inactive. The nucleotide potency profile and the blockade of the ADP-mediated inhibitory effect by the phospholipase C inhibitor U-73122 suggest that P2Y1 receptor controls ZL55 cell proliferation. The activation of P2Y1 receptor by ADP leads to activation of intracellular transduction pathways involving [Ca2+ ]i , PKC-δ/PKC-α, and MAPKs, ERK1/2 and JNK1/2. Cell treatment with ADP or 2-MeS-ADP also provokes the activation of p53, causing an accumulation of the G1 cyclin-dependent kinase inhibitors p21WAF1 and p27Kip . Inhibition of ZL55 cell proliferation by ADP was completely reversed by inhibiting MEK1/2, or JNK1/2, or PKC-δ, and PKC-α. Through the inhibition of ADP-activated transductional kinases it was found that PKC-δ was responsible for JNK1/2 activation. JNK1/2 has a role in transcriptional up-regulation of p53, p21WAF1/CIP1 , and p27kip1 . Conversely, the ADP-activated PKC-α provoked ERK1/2 phosphorylation. ERK1/2 increased p53 stabilization, required to G1 arrest of ZL55 cells. Concluding, the importance of the study is twofold: first, results shed light on the mechanism of cell cycle inhibition by ADP; second, results suggest that extracellular ADP may inhibit mesothelioma progression.}, } @article {pmid28775133, year = {2017}, author = {Ferrante, D and Chellini, E and Merler, E and Pavone, V and Silvestri, S and Miligi, L and Gorini, G and Bressan, V and Girardi, P and Ancona, L and Romeo, E and Luberto, F and Sala, O and Scarnato, C and Menegozzo, S and Oddone, E and Tunesi, S and Perticaroli, P and Pettinari, A and Cuccaro, F and Mattioli, S and Baldassarre, A and Barone-Adesi, F and Cena, T and Legittimo, P and Marinaccio, A and Mirabelli, D and Musti, M and Pirastu, R and Ranucci, A and Magnani, C and , }, title = {Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {12}, pages = {887-898}, doi = {10.1136/oemed-2016-104100}, pmid = {28775133}, issn = {1470-7926}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Asbestosis/mortality ; Carcinogens ; Cause of Death/trends ; Cohort Studies ; Construction Materials ; Female ; Humans ; Italy/epidemiology ; Lung ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Occupational Diseases/etiology/*mortality ; Occupational Exposure/*adverse effects ; Ovarian Neoplasms/etiology/*mortality ; Ovary ; Peritoneal Neoplasms/etiology/*mortality ; Peritoneum ; Pleura ; Pleural Neoplasms/etiology/*mortality ; }, abstract = {OBJECTIVE: Asbestos is a known human carcinogen, with evidence for malignant mesothelioma (MM), cancers of lung, ovary, larynx and possibly other organs. MM rates are predicted to increase with a power of time since first exposure (TSFE), but the possible long-term attenuation of the trend is debated. The asbestos ban enforced in Italy in 1992 gives an opportunity to measure long-term cancer risk in formerly exposed workers.

METHODS: Pool of 43 previously studied Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding), with mortality follow-up updated to 2010. SMRs were computed for the 1970â€"2010 period, for the major causes, with consideration of duration and TSFE, using reference rates by age, sex, region and calendar period.

RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Mortality was significantly increased for all deaths (SMR: men: 1.05, 95% CI 1.03 to 1.06; women: 1.17, 95% CI to 1.12 to 1.22), all malignancies combined (SMR: men: 1.17, 95% CI to 1.14 to 1.20; women: 1.33, 95% CI 1.24 to 1.43), pleural and peritoneal malignancies (SMR: men: 13.28 and 4.77, 95% CI 12.24 to 14.37 and 4.00 to 5.64; women: 28.44 and 6.75, 95% CI 23.83 to 33.69 and 4.70 to 9.39), lung (SMR: men: 1.26, 95% CI 1.21 to 1.31; women: 1.43, 95% CI 1.13 to 1.78) and ovarian cancer (SMR=1.38, 95% CI 1.00 to 1.87) and asbestosis (SMR: men: 300.7, 95% CI 270.7 to 333.2; women: 389.6, 95% CI 290.1 to 512.3). Pleural cancer rate increased during the first 40 years of TSFE and reached a plateau after.

DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. Pleural cancer mortality reached a plateau at long TSFE, coherently with recent reports.}, } @article {pmid28757678, year = {2017}, author = {Mozzoni, P and Ampollini, L and Goldoni, M and Alinovi, R and Tiseo, M and Gnetti, L and Carbognani, P and Rusca, M and Mutti, A and Percesepe, A and Corradi, M}, title = {MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {9645940}, pmid = {28757678}, issn = {1875-8630}, mesh = {Aged ; Asbestosis/*blood/metabolism/pathology ; Case-Control Studies ; Female ; Humans ; Lung/metabolism ; Lung Neoplasms/*blood/metabolism/pathology ; Male ; Mesothelioma/*blood/metabolism/pathology ; MicroRNAs/*blood/genetics/metabolism ; Middle Aged ; Pilot Projects ; }, abstract = {BACKGROUND: The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression.

AIMS: To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients.

METHODS: miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients.

CONCLUSIONS: All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.}, } @article {pmid28756416, year = {2017}, author = {Tompa, E and Kalcevich, C and McLeod, C and Lebeau, M and Song, C and McLeod, K and Kim, J and Demers, PA}, title = {The economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {11}, pages = {816-822}, pmid = {28756416}, issn = {1470-7926}, mesh = {Aged ; Asbestos/*adverse effects ; *Cost of Illness ; Female ; Health Care Costs ; Humans ; Lung/drug effects ; Lung Neoplasms/chemically induced/*economics ; Male ; Mesothelioma/chemically induced/*economics ; Middle Aged ; Occupational Diseases/chemically induced/*economics ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/chemically induced/*economics ; Quality of Life ; Quality-Adjusted Life Years ; Work ; }, abstract = {OBJECTIVES: To estimate the economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure in Canada.

METHODS: We estimate the lifetime cost of newly diagnosed lung cancer and mesothelioma cases associated with occupational and para-occupational asbestos exposure for calendar year 2011 based on the societal perspective. The key cost components considered are healthcare costs, productivity and output costs, and quality of life costs.

RESULTS: There were 427 cases of newly diagnosed mesothelioma cases and 1904 lung cancer cases attributable to asbestos exposure in 2011 for a total of 2331 cases. Our estimate of the economic burden is $C831 million in direct and indirect costs for newly identified cases of mesothelioma and lung cancer and $C1.5 billion in quality of life costs based on a value of $C100 000 per quality-adjusted life year. This amounts to $C356 429 and $C652 369 per case, respectively.

CONCLUSIONS: The economic burden of lung cancer and mesothelioma associated with occupational and para-occupational asbestos exposure is substantial. The estimate identified is for 2331 newly diagnosed, occupational and para-occupational exposure cases in 2011, so it is only a portion of the burden of existing cases in that year. Our findings provide important information for policy decision makers for priority setting, in particular the merits of banning the mining of asbestos and use of products containing asbestos in countries where they are still allowed and also the merits of asbestos removal in older buildings with asbestos insulation.}, } @article {pmid28756413, year = {2018}, author = {Reid, A and Merler, E and Peters, S and Jayasinghe, N and Bressan, V and Franklin, P and Brims, F and de Klerk, NH and Musk, AW}, title = {Migration and work in postwar Australia: mortality profile comparisons between Australian and Italian workers exposed to blue asbestos at Wittenoom.}, journal = {Occupational and environmental medicine}, volume = {75}, number = {1}, pages = {29-36}, doi = {10.1136/oemed-2017-104322}, pmid = {28756413}, issn = {1470-7926}, mesh = {Adult ; Asbestos/*adverse effects ; Asbestos, Crocidolite/*adverse effects ; Asbestosis/etiology/*mortality ; Cohort Studies ; *Emigrants and Immigrants ; Employment ; *Ethnic Groups ; Female ; Humans ; Italy ; Lung Neoplasms/etiology/*mortality ; Male ; Manufacturing Industry ; Mesothelioma/etiology/*mortality ; Mining ; Occupational Exposure/*adverse effects/analysis ; Proportional Hazards Models ; Transients and Migrants ; Western Australia ; Young Adult ; }, abstract = {OBJECTIVES: Three hundred and thirty thousand Italians arrived in Australia between 1945 and 1966, many on assisted passage schemes where the worker agreed to a 2-year unskilled employment contract. Italians were the largest of 52 migrant groups employed at the Wittenoom blue asbestos mining and milling operation. We compare mortality from asbestos-related diseases among Italian and Australian workers employed at Wittenoom.

METHODS: A cohort of 6500 male workers was established from employment records and followed up at state and national mortality and cancer registries. SMRs were calculated to compare mortality with the Western Australian male population. Time-varying Cox proportional hazards models compared the risk of mesothelioma between Australian and Italian workers.

RESULTS: 1031 Italians and 3465 Australians worked at Wittenoom between 1943 and 1966. Duration of employment was longer for the Italian workers, although the concentration of exposure was similar. The mesothelioma mortality rate per 100 000 was higher in Italians (184, 95% CI 148 to 229) than Australians (128, 95% CI 111 to 149). The risk of mesothelioma was greater than twofold (HR 2.27, 95% CI 1.43 to 3.60) in Italians at the lowest asbestos exposure category (<10 fibre years/per mL).

CONCLUSIONS: A hierarchy in migration, isolation and a shortage of workers led to Italians at Wittenoom incurring higher cumulative exposure to blue asbestos and subsequently a greater rate of malignant mesothelioma than Australian workers.

IMPACT: Poor working conditions and disparities between native and foreign-born workers has had a detrimental and differential impact on the long-term health of the workforce.}, } @article {pmid28749105, year = {2017}, author = {Sawanyawisuth, K and Furuya, S and Park, EK and Myong, JP and Ramos-Bonilla, JP and Chimed Ochir, O and Takahashi, K}, title = {Compensation for Asbestos-Related Diseases in Japan: Utilization of Standard Classifications of Industry and Occupations.}, journal = {Asian Pacific journal of cancer prevention : APJCP}, volume = {18}, number = {7}, pages = {1779-1782}, pmid = {28749105}, issn = {2476-762X}, } @article {pmid28744908, year = {2017}, author = {Kohyama, N and Fujiki, M and Kishimoto, T and Morinaga, K}, title = {Lung cancer in a patient with predominantly short tremolite fibers in his lung.}, journal = {American journal of industrial medicine}, volume = {60}, number = {9}, pages = {831-838}, doi = {10.1002/ajim.22748}, pmid = {28744908}, issn = {1097-0274}, mesh = {Aged, 80 and over ; Asbestos, Amphibole/*isolation & purification/toxicity ; *Extraction and Processing Industry ; Humans ; Lung/pathology ; Lung Neoplasms/*etiology ; Male ; Occupational Diseases/*etiology ; Parenchymal Tissue/pathology ; Particle Size ; }, abstract = {The carcinogenicity of short tremolite fibers in human has not been cleared and has been argued hitherto. A lung cancer patient had worked at a gabbro quarry. Particles isolated from the excised lung parenchyma of the patient were measured for asbestos bodies (ABs) and asbestos fibers (AFs). The concentrations of ABs were 3964 AB/g dry lung, and AFs were 5.60 × 106 fibers/g dry lung (>5 um in length) and 22.5 × 106 fibers/g dry lung (>1 um in length). AFs were mostly tremolite fibers and under 7 um in length (mean length 4.0 um, standard deviation 2.8 um). Almost all fibers were <10 um in length and an aspect ratio (AR) of <20:1 and ≥3:1. The patient had never smoked. His wife, who had worked with him in the quarry, had died of pleural mesothelioma. This study strongly indicates that such short tremolite fibers will induce lung cancer and possibly mesothelioma in human.}, } @article {pmid28740198, year = {2017}, author = {Granieri, A}, title = {The Drive For Self-Assertion And The Reality Principle In A Patient With Malignant Pleural Mesothelioma: The History of Giulia.}, journal = {American journal of psychoanalysis}, volume = {77}, number = {3}, pages = {285-294}, doi = {10.1057/s11231-017-9099-0}, pmid = {28740198}, issn = {1573-6741}, mesh = {Asbestos/*adverse effects ; Family/*psychology ; Humans ; Italy ; Mesothelioma/*psychology ; Pleural Neoplasms/*psychology ; *Social Support ; *Truth Disclosure ; }, abstract = {Life in a contaminated environment is often marked by a cumulative psychological trauma that exhibits a variety of social-environmental aspects. This is why I suggested a psychotherapeutic group intervention for the population of Casale Monferrato, a municipality in Northern Italy that is sadly renowned for asbestos-related events and the high mortality rate of its inhabitants. Groupality appears to show the point of contact between psyche and soma, while also promoting the birth of a more realistic approach to the various levels of suffering and their configuration. The multifamily approach seemed to be the most adequate to elaborate the feelings of rage and fear that are concurrent with the aerial contagion. In the "long wave" of group work we have learned to work with participants as well as with empty chairs, the ghosts of the dead: live traces in the mind. Whereas the mind recovers the possibility of entering into a dialogue with the feelings connected to the trauma, without bypassing them towards actions that are apparently more assertive of one's sense of Ego, the will of conciliation can reactivate a thought that is oriented towards the plane of reality.}, } @article {pmid28724330, year = {2017}, author = {Bakker, E and Guazzelli, A and Ashtiani, F and Demonacos, C and Krstic-Demonacos, M and Mutti, L}, title = {Immunotherapy advances for mesothelioma treatment.}, journal = {Expert review of anticancer therapy}, volume = {17}, number = {9}, pages = {799-814}, doi = {10.1080/14737140.2017.1358091}, pmid = {28724330}, issn = {1744-8328}, mesh = {Adaptive Immunity/immunology ; Animals ; Biomarkers/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunity, Innate/immunology ; Immunotherapy/*methods ; Mesothelioma/immunology/pathology/*therapy ; Prognosis ; Survival Rate ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: Mesothelioma is a rare type of cancer that is strongly tied to asbestos exposure. Despite application of different modalities such as chemotherapy, radiotherapy and surgery, patient prognosis remains very poor and therapies are ineffective. Much research currently focuses on the application of novel approaches such as immunotherapy towards this disease. Areas covered: The types, stages and aetiology of mesothelioma are detailed, followed by a discussion of the current treatment options such as radiotherapy, surgery, and chemotherapy. A description of innate and adaptive immunity and the principles and justification of immunotherapy is also included. Clinical trials for different immunotherapeutic modalities are described, and lastly the article closes with an expert commentary and five-year view, the former of which is summarised below. Expert commentary: Current efforts for novel mesothelioma therapies have been limited by attempting to apply treatments from other cancers, an approach which is not based on a solid understanding of mesothelioma biology. In our view, the influence of the hostile, hypoxic microenvironment and the gene expression and metabolic changes that resultantly occur should be characterised to improve therapies. Lastly, clinical trials should focus on overall survival rather than surrogate endpoints to avoid bias and inaccurate reflections of treatment effects.}, } @article {pmid28713671, year = {2017}, author = {Chen, Z and Gaudino, G and Pass, HI and Carbone, M and Yang, H}, title = {Diagnostic and prognostic biomarkers for malignant mesothelioma: an update.}, journal = {Translational lung cancer research}, volume = {6}, number = {3}, pages = {259-269}, pmid = {28713671}, issn = {2218-6751}, support = {R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, abstract = {Malignant mesothelioma (MM) is an aggressive and lethal cancer, mostly related to inhalation of asbestos and erionite fibers. MM is associated with poor prognosis, because of its resistance to current therapies, even if higher survival occurs in patients diagnosed and treated when at stage I of the disease. However, these do not exceed 5% of the total number of cases, due to the inadequacy of the existing biomarkers for early and accurate diagnosis. Therefore, new effective biomarkers are needed for MM detection at earlier stages and to develop tailored therapies. Here we review the most promising biomarkers in MM to date: mesothelin, soluble mesothelin-related peptides (SMRPs), megakaryocyte potentiating factor (MPF), Osteopontin (OPN), Fibulin-3, high mobility group B1 (HMGB1), microRNAs (miRNAs), multiplex protein signatures. The validation of these biomarkers will allow their use, alone or in combination, for monitoring individuals from cohorts at risk of MM and attaining early detection of MM that is instrumental in improving patient survival.}, } @article {pmid28713670, year = {2017}, author = {Singh, A and Pruett, N and Hoang, CD}, title = {In vitro experimental models of mesothelioma revisited.}, journal = {Translational lung cancer research}, volume = {6}, number = {3}, pages = {248-258}, pmid = {28713670}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a biologically unusual, highly aggressive cancer that defies current multimodality treatments. Epidemiologic data suggest that this malignancy has not abated despite increasingly strict environmental regulations on asbestos, the putative causative agent for sporadic cases. An incomplete understanding of all the factors mechanistically driving mesothelioma is largely responsible for the current lack of curative treatments. Many approaches have been employed to ascertain the step-by-step molecular events involved in mesothelioma oncogenesis including in vitro, small animal in vivo, and human experimental models; though clearly defined, druggable mechanisms still are elusive. Importantly, the foundation of the latest accepted model of tumor initiation is derived from in vitro systems. A thorough review of in vitro mesothelioma oncogenesis models may suggest further opportunities for discovery.}, } @article {pmid28706912, year = {2017}, author = {Sun, HH and Vaynblat, A and Pass, HI}, title = {Diagnosis and prognosis-review of biomarkers for mesothelioma.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {244}, pmid = {28706912}, issn = {2305-5839}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural cell lining and is associated with asbestos exposure. Today, there is a rising incidence of MPM reaching 3,000 annual cases nationally, primarily from the large population occupationally exposed to asbestos between 1940 and 1980. With a prolonged latency period, presenting clinically 10 to 40 years after exposure, MPM is often diagnosed in late stages and presents median survival time of less than 12 months. There is a serious need for improvement in prognostic and diagnostic tools for MPM. Recent investigation and discovery of various biomarkers has shown promise, including Osteopontin, Fibulin-3, Soluble Mesothelin-Related Proteins (SMRP), High Mobility Group Box 1 (HMGB1), micro-RNA's, peripheral blood-based markers, and Slow Off-rate Modified Aptamer (SOMAmer) proteomic assays. In this review, we explore these current major biomarkers and their prognostic and diagnostic potential, highlighting the most recent large studies and developments for each. While progress has been made in mesothelioma research, many questions remain unanswered. Increased international cooperation is necessary for improving validity of results for current biomarkers through repeated investigation and increasing cohort sizes, as well as for the continued search for new and better markers.}, } @article {pmid28706907, year = {2017}, author = {Emri, SA}, title = {The Cappadocia mesothelioma epidemic: its influence in Turkey and abroad.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {239}, pmid = {28706907}, issn = {2305-5839}, abstract = {The epidemic of mesothelioma in Cappadocia, Turkey, is unprecedented in medical history. In three Cappadocian villages, Karain, Tuzkoy and "old" Sarihidir, about 50% of all deaths (including neonatal deaths and traffic fatalities) have been caused by mesothelioma. No other epidemic in medical history has caused such a high incidence of death. This is even more unusual when considering that (I) epidemics are caused by infectious agents, not cancer, and (II) mesothelioma is a rare cancer. World-wide mesothelioma incidence varies between 1/106 in areas with no asbestos industry to about 10-30/106 in areas with asbestos industry. This article reviews how the mesothelioma epidemic was discovered in Cappadocia by Dr. Baris (my mentor), how we initially linked the epidemic to erionite exposure, and later (with Dr. Carbone) to the interaction between genetic predisposition and environmental exposure. Our team's work had an important positive impact on the lives of those living in Cappadocia and also in many genetically predisposed families living around the world. I will discuss how the work that started in three remote Cappadocian villages led to the award of a NCI P01 grant to support our studies. Our studies proved that genetics modulates mineral fiber carcinogenesis and led to the discovery that carriers of germline BAP1 mutations have a very high risk of developing mesothelioma and other malignancies. A new, very active field of research developed following our discoveries to elucidate the mechanism by which BAP1 modulates mineral fiber carcinogenesis as well as to identify additional genes that when mutated increase the risk of mesothelioma and other environmentally related cancers. I am the only surviving member of this research team who saw all the phases of this research and I believe it is important to provide an accurate report, which hopefully will inspire others.}, } @article {pmid28706906, year = {2017}, author = {Carbone, M and Yang, H}, title = {Mesothelioma: recent highlights.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {238}, pmid = {28706906}, issn = {2305-5839}, support = {R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, abstract = {Recent discoveries have elucidated some of the mechanisms responsible for the development of mesothelioma. These discoveries are: (I) the critical role of chronic inflammation in promoting mesothelioma growth, driven by the release of high mobility group box protein-1 (HMGB1) following asbestos deposition in tissues and its potential role as a biomarker to identify asbestos exposed individuals and mesothelioma patients; (II) the discovery that inherited heterozygous germline mutations of the deubiquitylase BRCA-associated protein 1 (BAP1) cause a high incidence of mesothelioma in some families; and that (III) germline BAP1 mutations lower the threshold of asbestos required to cause mesothelioma in mice, evidence of gene X environment interaction. These findings together with the identification of novel serum biomarkers, including HMGB1, Fibulin-3, etc., promise to revolutionize screening and treatment of this malignancy in the coming years.}, } @article {pmid28706904, year = {2017}, author = {Kim, J and Bhagwandin, S and Labow, DM}, title = {Malignant peritoneal mesothelioma: a review.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {236}, pmid = {28706904}, issn = {2305-5839}, abstract = {Mesothelioma is a malignancy of serosal membranes. It is most commonly encountered in the visceral pleura with the second most common location in the peritoneum. The diagnosis is very rare and has been linked to toxic exposure to industrial pollutants, especially asbestos. Malignant peritoneal mesothelioma (MPM) commonly presents with diffuse, extensive spread throughout the abdomen with rare metastatic spread beyond the abdominal cavity. Due to its rarity and nonspecific symptoms, it is usually diagnosed late when the disease burden is extensive. Because pleural mesothelioma is more common than MPM, most research has been on the pleural variant and extrapolated for MPM. While treatment advances have been made for MPM, the disease is universally fatal from either abdominal complications secondary to the spread of disease or starvation. Untreated, the life expectancy is less than a year. Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) has become the mainstay of therapy with systemic therapies still being developed. We will review the epidemiology of MPM and discuss diagnostic and treatment strategies.}, } @article {pmid28706903, year = {2017}, author = {Murphy, DJ and Gill, RR}, title = {Overview of treatment related complications in malignant pleural mesothelioma.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {235}, pmid = {28706903}, issn = {2305-5839}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignant neoplasm of the pleura related to asbestos exposure. Despite recent advances in therapy for MPM, the prognosis remains poor, with considerable treatment associated morbidity. Radiological assessment plays a central role in the timely identification and subsequent management of treatment related complications in MPM. This review highlights common and uncommon complications associated with and encountered in the post treatment phase.}, } @article {pmid28706902, year = {2017}, author = {Noonan, CW}, title = {Environmental asbestos exposure and risk of mesothelioma.}, journal = {Annals of translational medicine}, volume = {5}, number = {11}, pages = {234}, pmid = {28706902}, issn = {2305-5839}, support = {P30 GM103338/GM/NIGMS NIH HHS/United States ; }, abstract = {Mesothelioma is commonly considered an occupational disease occurring as a result of asbestos exposure in the workplace. Several avenues for environmental asbestos exposures have been described and may be associated with asbestos related disease, including mesothelioma. Worker take-home asbestos, or para-occupational exposure, has been well documented and is the most commonly reported pathway for asbestos exposure among mesothelioma cases that do not have history of occupational asbestos exposure. Observational studies have evaluated several communities with elevated mesothelioma incidence and environmental exposures attributed to local asbestos-related industries. Potential, but uncertain, mesothelioma risk also may be associated with general population asbestos exposure through contact with asbestos-containing commercial products, particularly housing materials that can be easily disturbed through normal activity. Finally, studies have described elevated mesothelioma incidence in several areas where populations are exposed to naturally occurring asbestos materials. These various environmental asbestos exposure pathways are poorly understood, and further studies should be pursued to evaluate their respective importance for population mesothelioma risk.}, } @article {pmid28704762, year = {2017}, author = {Bonelli, MA and Digiacomo, G and Fumarola, C and Alfieri, R and Quaini, F and Falco, A and Madeddu, D and La Monica, S and Cretella, D and Ravelli, A and Ulivi, P and Tebaldi, M and Calistri, D and Delmonte, A and Ampollini, L and Carbognani, P and Tiseo, M and Cavazzoni, A and Petronini, PG}, title = {Combined Inhibition of CDK4/6 and PI3K/AKT/mTOR Pathways Induces a Synergistic Anti-Tumor Effect in Malignant Pleural Mesothelioma Cells.}, journal = {Neoplasia (New York, N.Y.)}, volume = {19}, number = {8}, pages = {637-648}, pmid = {28704762}, issn = {1476-5586}, mesh = {Antineoplastic Agents/pharmacology ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cellular Senescence/drug effects ; Cyclin-Dependent Kinase 4/*antagonists & inhibitors ; Cyclin-Dependent Kinase 6/*antagonists & inhibitors ; Drug Synergism ; Humans ; Lung Neoplasms/metabolism ; Mesothelioma/metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Piperazines/pharmacology ; Protein Kinase Inhibitors/*pharmacology ; Proto-Oncogene Proteins c-akt/*metabolism ; Pyridines/pharmacology ; Signal Transduction/*drug effects ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Malignant pleural mesothelioma (MPM) is a progressive malignancy associated to the exposure of asbestos fibers. The most frequently inactivated tumor suppressor gene in MPM is CDKN2A/ARF, encoding for the cell cycle inhibitors p16INK4a and p14ARF, deleted in about 70% of MPM cases. Considering the high frequency of alterations of this gene, we tested in MPM cells the efficacy of palbociclib (PD-0332991), a highly selective inhibitor of cyclin-dependent kinase (CDK) 4/6. The analyses were performed on a panel of MPM cell lines and on two primary culture cells from pleural effusion of patients with MPM. All the MPM cell lines, as well as the primary cultures, were sensitive to palbociclib with a significant blockade in G0/G1 phase of the cell cycle and with the acquisition of a senescent phenotype. Palbociclib reduced the phosphorylation levels of CDK6 and Rb, the expression of myc with a concomitant increased phosphorylation of AKT. Based on these results, we tested the efficacy of the combination of palbociclib with the PI3K inhibitors NVP-BEZ235 or NVP-BYL719. After palbociclib treatment, the sequential association with PI3K inhibitors synergistically hampered cell proliferation and strongly increased the percentage of senescent cells. In addition, AKT activation was repressed while p53 and p21 were up-regulated. Interestingly, two cycles of sequential drug administration produced irreversible growth arrest and senescent phenotype that were maintained even after drug withdrawal. These findings suggest that the sequential association of palbociclib with PI3K inhibitors may represent a valuable therapeutic option for the treatment of MPM.}, } @article {pmid28691999, year = {2017}, author = {Pira, E and Coggiola, M and Ciocan, C and Romano, C and La Vecchia, C and Pelucchi, C and Boffetta, P}, title = {Mortality of Talc Miners and Millers From Val Chisone, Northern Italy: An Updated Cohort Study.}, journal = {Journal of occupational and environmental medicine}, volume = {59}, number = {7}, pages = {659-664}, doi = {10.1097/JOM.0000000000000992}, pmid = {28691999}, issn = {1536-5948}, mesh = {Cause of Death ; Cohort Studies ; Gastrointestinal Neoplasms/mortality ; Humans ; Italy/epidemiology ; Lung Neoplasms/mortality ; Male ; Mesothelioma/mortality ; *Mining ; Mouth Neoplasms/mortality ; Neoplasms/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/mortality ; Silicosis/*mortality ; Talc/*adverse effects ; Urinary Bladder Neoplasms/mortality ; }, abstract = {OBJECTIVE: The aim of this study was to update the analysis of mortality of a cohort of talc miners and millers in Northern Italy.

METHODS: We analyzed the mortality during 1946 to 2013 of 1722 male workers in an asbestos-free talc mine (1166 miners and 556 millers) employed during 1946 to 1995.

RESULTS: The overall standardized mortality ratio (SMR) was 1.24 [95% confidence interval (95% CI) 1.17 to 1.32]; no deaths were observed from pleural cancer; mortality from lung cancer was not increased. Mortality from pneumoconiosis was increased (SMR 26.62; 95% CI 20.71 to 33.69), in particular among miners, and was associated with duration of employment and time since first employment.

CONCLUSIONS: We confirmed the lack of association between exposure to asbestos-free talc, lung cancer, and mesothelioma. Increased mortality from pneumoconiosis among miners is attributable to past exposure to silica.}, } @article {pmid28687356, year = {2017}, author = {Betti, M and Casalone, E and Ferrante, D and Aspesi, A and Morleo, G and Biasi, A and Sculco, M and Mancuso, G and Guarrera, S and Righi, L and Grosso, F and Libener, R and Pavesi, M and Mariani, N and Casadio, C and Boldorini, R and Mirabelli, D and Pasini, B and Magnani, C and Matullo, G and Dianzani, I}, title = {Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma.}, journal = {Cancer letters}, volume = {405}, number = {}, pages = {38-45}, doi = {10.1016/j.canlet.2017.06.028}, pmid = {28687356}, issn = {1872-7980}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Carcinogens/*toxicity ; DNA Repair/*genetics ; Environmental Exposure/*adverse effects ; Environmental Pollutants/*toxicity ; Female ; *Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Middle Aged ; Pleural Neoplasms/etiology/*genetics ; Risk Factors ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer caused by asbestos exposure. An inherited predisposition has been suggested to explain multiple cases in the same family and the observation that not all individuals highly exposed to asbestos develop the tumor. Germline mutations in BAP1 are responsible for a rare cancer predisposition syndrome that includes predisposition to mesothelioma. We hypothesized that other genes involved in hereditary cancer syndromes could be responsible for the inherited mesothelioma predisposition. We investigated the prevalence of germline variants in 94 cancer-predisposing genes in 93 MPM patients with a quantified asbestos exposure. Ten pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC. All these genes are involved in DNA repair pathways, mostly in homologous recombination repair. Patients carrying PTVs represented 9.7% of the panel and showed lower asbestos exposure than did all the other patients (p = 0.0015). This suggests that they did not efficiently repair the DNA damage induced by asbestos and leading to carcinogenesis. This study shows that germline variants in several genes may increase MPM susceptibility in the presence of asbestos exposure and may be important for specific treatment.}, } @article {pmid28685333, year = {2018}, author = {Cui, Y and Ma, J and Ye, W and Han, Z and Dong, F and Deng, J and Zhang, Q}, title = {Chrysotile and rock wool fibers induce chromosome aberrations and DNA damage in V79 lung fibroblast cells.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {23}, pages = {22328-22333}, pmid = {28685333}, issn = {1614-7499}, support = {41130746//Key Program of National Nature Science Project of China/ ; 41472046//National Natural Fund Project of China/ ; 14JC0126//Department of Sichuan Province Natural Science Foundation of China/ ; }, abstract = {According to global estimates, at least 107,000 people die each year from asbestos-related lung cancer, mesothelioma, and asbestosis resulting from occupational exposure. Chrysotile accounts for approximately 90% of asbestos used worldwide. Artificial substitutes can also be cytotoxic to the same degree as chrysotile. But only a few researchers focused on their genetic effects and mutagenicity information which is useful in evaluating the carcinogenicity of chemicals. In this study, chrysotile from Mangnai, Qinghai, China, and an artificial substitute, rock wool fiber were prepared as suspensions and were tested at concentrations of 50, 100, and 200 μg/ml in V79 lung fibroblasts. Chromosome aberrations were detected by micronucleus assay after exposure for 24 h, and DNA damage were estimated by single cell gel electrophoresis after exposure for 12, 24, or 48 h. According to the results, chrysotile and rock wool fibers caused micronuclei to form in a dose-dependent manner in V79 cells; olive tail moment values increased in a dose- and time-dependent manner. When V79 cells were exposed to a concentration of 200 μg/ml, the degree of DNA damage induced by chrysotile fibers was greater than rock wool fibers. Our study suggests that both chrysotile and rock wool fibers could induce chromosome aberrations and DNA damage. These materials are worthy of further study.}, } @article {pmid28685091, year = {2017}, author = {Uguen, M and Dewitte, JD and Marcorelles, P and Loddé, B and Pougnet, R and Saliou, P and De Braekeleer, M and Uguen, A}, title = {Asbestos-related lung cancers: A retrospective clinical and pathological study.}, journal = {Molecular and clinical oncology}, volume = {7}, number = {1}, pages = {135-139}, pmid = {28685091}, issn = {2049-9450}, abstract = {Exposure to asbestos results in serious risks of developing mesothelioma and lung cancer. The link between asbestos exposure and lung carcinoma is well established. Nevertheless, precise histopathological data are poorly considered when investigating the asbestos-cancer link in a compensatory approach. In the present study, we aim to describe the features of individuals with compensated lung cancer who were referred to an occupational disease center, regarding occupational exposure to asbestos, smoking history and pathological data. We led a retrospective study of compensated ARLC cases seen in our occupational disease center between 2003 and 2013. A total of 146 men were included (mean age at diagnosis, 63.2 years) of whom approximately 90% were heavy current or former smokers (mean value, 30.4 packs/year). The major industries associated with the lung cancer cases were shipbuilding (69.9%), and building construction (7.5%) in this harbor region. The results of the present study showed that lung upper lobe was most prevalent (61.6%) and an excess of adenocarcinoma was found (45.9%), followed by squamous cell carcinoma (38.4%) as well as thoracic sarcomas (2.1%). Neoplasm was not histologically proven in 6.8% of the cases. Subsequent pathology examinations also reclassified 2 tumors as metastases from esophageal and laryngeal origins. In conclusion, smoking prevention should be encouraged in asbestos-exposed workers as reflected by the number of smokers with asbestos-related lung cancer. Thus, histological data should be considered further to evaluate the potent relationship between asbestos exposure and lung malignancy, especially in a compensatory approach.}, } @article {pmid28680295, year = {2017}, author = {Abós-Herràndiz, R and Rodriguez-Blanco, T and Garcia-Allas, I and Rosell-Murphy, IM and Albertí-Casas, C and Tarrés, J and Krier-Günther, I and Martinez-Artés, X and Orriols, R and Grimau-Malet, I and Canela-Soler, J}, title = {Risk Factors of Mortality from All Asbestos-Related Diseases: A Competing Risk Analysis.}, journal = {Canadian respiratory journal}, volume = {2017}, number = {}, pages = {9015914}, pmid = {28680295}, issn = {1916-7245}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestosis/*mortality ; Cohort Studies ; Environmental Exposure/statistics & numerical data ; Female ; Humans ; Incidence ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Mortality ; Occupational Diseases/mortality ; Occupational Exposure/*statistics & numerical data ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Sex Factors ; Smoking/epidemiology ; Spain/epidemiology ; }, abstract = {BACKGROUND: The mortality from all malignant and nonmalignant asbestos-related diseases remains unknown. The authors assessed the incidence and risk factors for all asbestos-related deaths.

METHODS: The sample included 544 patients from an asbestos-exposed community in the area of Barcelona (Spain), between Jan 1, 1970, and Dec 31, 2006. Competing risk regression through a subdistribution hazard analysis was used to estimate risk factors for the outcomes.

RESULTS: Asbestos-related deaths were observed in 167 (30.7%) patients and 57.5% of these deaths were caused by some type of mesothelioma. The incidence rate after diagnosis was 3,600 per 100,000 person-years. In 7.5% of patients death was non-asbestos-related, while pleural and peritoneal mesothelioma were identified in 87 (16.0%) and 18 (3.3%) patients, respectively.

CONCLUSIONS: Age, sex, household exposure, cumulative nonmalignant asbestos-related disease, and single malignant pathology were identified as risk factors for asbestos-related death. These findings suggest the need to develop a preventive approach to the community and to improve the clinical follow-up process of these patients.}, } @article {pmid28669341, year = {2018}, author = {Zanellato, I and Colangelo, D and Osella, D}, title = {JQ1, a BET Inhibitor, Synergizes with Cisplatin and Induces Apoptosis in Highly Chemoresistant Malignant Pleural Mesothelioma Cells.}, journal = {Current cancer drug targets}, volume = {18}, number = {8}, pages = {816-828}, doi = {10.2174/1568009617666170623101722}, pmid = {28669341}, issn = {1873-5576}, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an asbestos-associated tumor with poor prognosis and few therapeutic options. JQ1, a selective antagonist of BRD4, modulates transcription of oncogenes, including MPM chemoresistance-associated c-Myc and Fra-1.

OBJECTIVE: We investigated if JQ1 could enhance the efficacy of cisplatin against MPM.

METHODS: The antiproliferative activity of cisplatin in combination with JQ1 was assessed on MPM cell lines representative of the cellular phenotypes of this tumor (epithelioid, sarcomatoid and biphasic), and on one cisplatin resistant sub-line. The combination schedule was optimized adopting a 3Dspheroid model. Drug combination effects were correlated with cell cycle distribution and senescence- associated β-galactosidase positive cells. The expression of c-Myc and Fra-1 proteins and some apoptosis markers was assessed by immunoblotting and RT-qPCR. DNA damage and repair were evaluated by means of alkaline comet assay.

RESULTS: JQ1 in combination with cisplatin elicited additive or synergistic (superadditive) antiproliferative effects on MPM cells, depending on the cell line. The combination showed tumor regression on the 3D-spheroid model. It induced increased apoptosis, along with decreased c-Myc and, sometimes, Fra-1 expression. JQ1 decreased cisplatin-induced DNA breaks in all MPM cells and increased senescence even in less proficient cells, thus enhancing the DNA Damage Response (DDR).

CONCLUSION: The superadditive effect is due to c-Myc repression. The consequent DDR enhancement triggers to apoptosis induction and/or permanent growth arrest (senescence), depending on the MPM cellular context, leading to tumor regression. Thus, the pharmacological modulation of BET activity could represent a promising tool for future MPM therapy.}, } @article {pmid28663314, year = {2017}, author = {Feder, IS and Tischoff, I and Theile, A and Schmitz, I and Merget, R and Tannapfel, A}, title = {The asbestos fibre burden in human lungs: new insights into the chrysotile debate.}, journal = {The European respiratory journal}, volume = {49}, number = {6}, pages = {}, pmid = {28663314}, issn = {1399-3003}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/*adverse effects/*analysis ; Autopsy ; Germany ; Humans ; Longitudinal Studies ; Lung/pathology ; Lung Neoplasms/*etiology/surgery ; Male ; Mesothelioma/*etiology/surgery ; Microscopy, Electron ; Middle Aged ; Occupational Exposure/*adverse effects ; Registries ; }, abstract = {The traceability of asbestos fibres in human lungs is a matter of discussion especially for chrysotile. This issue is of high significance for differential diagnosis, risk assessment and occupational compensation. At present no intra-individual longitudinal information is available. This study addresses the question whether the asbestos fibre burden in human lungs decreases with time after exposure cessation.The database of the German Mesothelioma Register was screened for patients with asbestos body counts of at least 500 fibres per gram of wet lung, which had been analysed twice from different tissue excisions at minimum intervals of 4 years.Twelve datasets with individual longitudinal information were discovered with a median interval of about 8 years (range 4-21 years). Both examinations were performed after exposure cessation (median: surgery, 9.5 years; autopsy, 22 years). Pulmonary asbestos fibre burden was stable between both examinations (median 1623/4269 asbestos bodies per gram wet lung). Electron microscopy demonstrated a preponderance of chrysotile (median 80%).This study is the first to present longitudinal intra-individual data about the asbestos fibre burden in living human lungs. The high biopersistence of amphiboles, but also of chrysotile, offers mechanistic explanations for fibre toxicity, especially the long latency period of asbestos-related diseases.}, } @article {pmid28651470, year = {2017}, author = {Finley, BL and Benson, SM and Marsh, GM}, title = {Cosmetic talc as a risk factor for pleural mesothelioma: a weight of evidence evaluation of the epidemiology.}, journal = {Inhalation toxicology}, volume = {29}, number = {4}, pages = {179-185}, doi = {10.1080/08958378.2017.1336187}, pmid = {28651470}, issn = {1091-7691}, mesh = {*Cosmetics ; Humans ; Mesothelioma/*chemically induced ; *Occupational Exposure ; Pleural Neoplasms/*chemically induced ; Risk Factors ; Talc/chemistry/*toxicity ; }, abstract = {OBJECTIVE: Due to some historical (and inaccurate) reports that asbestos might be present in some cosmetic talc products, questions are occasionally raised regarding the potential pleural mesothelioma risks associated with cosmetic talc products. Our objective was to determine the incidence of pleural mesothelioma of individuals exposed to cosmetic talc.

MATERIALS AND METHODS: We conducted a systematic review of the epidemiological literature for cosmetic talc miners and millers and found three occupational cohort studies that evaluated pleural mesothelioma incidence in workers in Italy, Norway, France, and Austria. We conducted a second literature review to evaluate the incidence and mortality of pleural mesothelioma among patients who received talc pleurodesis treatments before 1965 and found retrospective clinical studies including over 300 patients with follow-up ranging from 14 to 40 years.

RESULTS: There were no mesotheliomas reported in any of the cosmetic talc miner and miller cohorts. A pooled analysis of data from the cohort mortality studies indicated that four mesothelioma deaths would have been expected from the 90,022 person-years of observation, and this was associated with 84% and 67% statistical power to observe a 3-fold or 2.5-fold increase in pleural mesothelioma mortality, respectively. None of the patients who received talc pleurodesis treatments developed mesothelioma.

CONCLUSION: We conclude that there is no epidemiological evidence to support the hypothesis that exposure to cosmetic talc is associated with the development of pleural mesothelioma.}, } @article {pmid28634559, year = {2017}, author = {Ideguchi, R and Ashizawa, K and Akashi, S and Shindo, M and Minami, K and Fukuda, T and Irie, J and Fukuda, M and Uetani, M}, title = {Malignant Pleural Mesothelioma with Marked Lymphatic Involvement: A Report of Two Autopsy Cases.}, journal = {Case reports in oncological medicine}, volume = {2017}, number = {}, pages = {6195898}, pmid = {28634559}, issn = {2090-6706}, abstract = {We herein report two cases of malignant pleural mesothelioma with marked lymphangiosis. The patients included a 68-year-old man and a 67-year-old man who both had a history of exposure to asbestos. Computed tomography (CT) on admission showed pleural effusion with pleural thickening. In both cases, a histopathological examination of the pleura confirmed the diagnosis of epithelioid malignant mesothelioma. They received chemotherapy, but the treatment was only palliative. The chest CT assessments during admission revealed marked pleural effusion and mediastinal lymphadenopathy. CT also showed a consolidative mass with bronchovascular bundle and septal thickening in the lungs suggesting pulmonary parenchymal involvement and the lymphangitic spread of the tumor. These CT findings mimicked lung cancer with pleuritis and lymphangitic carcinomatosis. Autopsy was performed in both cases. Macroscopically, the tumor cells infiltrated the lung with the marked lymphatic spread of the tumor. Microscopy also revealed that the tumor had invaded the pulmonary parenchyma with the marked lymphatic spread of the tumor. Although this growth pattern is unusual, malignant pleural mesothelioma should be considered as the differential diagnosis, especially in patients with pleural lesions.}, } @article {pmid28629895, year = {2017}, author = {Kao, SC and Cheng, YY and Williams, M and Kirschner, MB and Madore, J and Lum, T and Sarun, KH and Linton, A and McCaughan, B and Klebe, S and van Zandwijk, N and Scolyer, RA and Boyer, MJ and Cooper, WA and Reid, G}, title = {Tumor Suppressor microRNAs Contribute to the Regulation of PD-L1 Expression in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {9}, pages = {1421-1433}, doi = {10.1016/j.jtho.2017.05.024}, pmid = {28629895}, issn = {1556-1380}, mesh = {Aged ; B7-H1 Antigen/*biosynthesis/metabolism ; Female ; Humans ; Lung Neoplasms/*genetics/*metabolism/pathology ; Male ; Mesothelioma/*genetics/*metabolism/pathology ; MicroRNAs/*genetics ; Pleural Neoplasms/*genetics/*metabolism/pathology ; Prognosis ; Up-Regulation ; }, abstract = {INTRODUCTION: The upregulation of programmed death ligand 1 (PD-L1) is found in many cancers and contributes to evasion of the host's immune defense. In malignant pleural mesothelioma (MPM), PD-L1 expression is associated with the nonepithelioid histological subtype and poor prognosis, but the pathways involved in control of PD-L1 expression in MPM are poorly understood. To address one possible means of PD-L1 regulation we investigated the relationship between dysregulated microRNA levels and PD-L1 expression.

METHODS: PD-L1 expression was analyzed by immunohistochemistry in tissue microarrays prepared from samples from patients undergoing an operation (pleurectomy with or without decortication). MicroRNA expression was analyzed by reverse-transcriptase quantitative polymerase chain reaction. Regulation of PD-L1 expression in cell lines was assessed after transfection with microRNA mimics and small interfering RNAs. Interaction between microRNAs and PD-L1 was analyzed by using argonaute-2 immunoprecipitation and a luciferase reporter assay.

RESULTS: In a series of 72 patients with MPM, 18 (25%) had positive PD-L1 staining, and this was more common in patients with the nonepithelioid subtype (p = 0.01). PD-L1 expression was associated with poor survival (median overall survival 4.0 versus 9.2 months with positive versus negative PD-L1 expression [p < 0.001]), and in multivariate analyses, PD-L1 expression remained a significant adverse prognostic indicator (hazard ratio = 2.2, 95% confidence interval: 1.2-4.1, p < 0.01). In the same patient series, PD-L1 expression was also associated with downregulation of microRNAs previously shown to have tumor suppressor activity in MPM. The median microRNA expression levels of miR-15b, miR-16, miR-193a-3p, miR-195, and miR-200c were significantly lower in the PD-L1-positive samples. Transfecting MPM cell lines with mimics corresponding to miR-15a and miR-16, both of which are predicted to target PD-L1, led to downregulation of PD-L1 mRNA and protein. In addition, miR-193a-3p, with an alternative G-U-containing target site, also caused PD-L1 downregulation.

CONCLUSIONS: Together, these data suggest that tumor suppressor microRNAs contribute to the regulation of PD-L1 expression in MPM.}, } @article {pmid28625623, year = {2017}, author = {Świątkowska, B and Szeszenia-Dąbrowska, N}, title = {Mesothelioma continues to increase even 40 years after exposure - Evidence from long-term epidemiological observation.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {108}, number = {}, pages = {121-125}, doi = {10.1016/j.lungcan.2017.03.012}, pmid = {28625623}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Mesothelioma/*epidemiology/*etiology ; Middle Aged ; Occupational Diseases/epidemiology/etiology ; *Occupational Exposure ; Odds Ratio ; Pleural Neoplasms/epidemiology/etiology ; Poland/epidemiology ; Risk ; Time Factors ; }, abstract = {BACKGROUND: Because asbestos dust is considered one of the most dangerous types of dust for people's health, issues related to the effects of asbestos exposure still remain questions about the role of cessation of exposure.

OBJECTIVES: The aim of the present study was to determine the importance of temporal patterns, especially the time since the end of exposure in the risk of pleural mesothelioma.

METHODS: A total of 131 patients with pleural mesothelioma and 655 frequency matched by gender and year of birth controls enrolled in the health surveillance programme for asbestos-related diseases over the years 2000-2014, were included in the analysis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).

RESULTS: The results show that the risk of pleural mesothelioma continued to increase even after 40 years since the last exposure. The estimated odds ratio for the subjects who had their last exposure 40 years ago, compared with the odds ratio of those who had their last exposure 5 years ago, was 2.68 (95%CI: 1.16-.621). We also observed that crocidolite exposure was associated with a very high significant mesothelioma risk, 5-fold higher for those working with mixed exposure compared to the subjects who worked only with chrysotile.

CONCLUSIONS: Dose-response relationships in populations occupationally exposed are critical to the study related to environment asbestos contamination. Our findings confirm the strong evidence that mesothelioma risk increases along with the increasing time since exposure termination.}, } @article {pmid28619093, year = {2017}, author = {McDonnell, AM and Cook, A and Robinson, BWS and Lake, RA and Nowak, AK}, title = {Serial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {417}, pmid = {28619093}, issn = {1471-2407}, mesh = {Antibodies, Monoclonal/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Biomarkers ; CD40 Antigens/antagonists & inhibitors ; Cisplatin/administration & dosage ; Clinical Trials, Phase I as Topic ; Dendritic Cells/*immunology/metabolism ; Female ; Humans ; Immunomodulation/*drug effects ; Immunophenotyping ; Lymphocyte Activation ; Lymphocyte Count ; Male ; Neoplasms/diagnosis/drug therapy/*immunology/metabolism ; Prognosis ; Proportional Hazards Models ; T-Lymphocyte Subsets/*immunology/metabolism ; }, abstract = {BACKGROUND: CD40 signalling can synergise with chemotherapy in preclinical cancer models, and early clinical studies are promising. We set out to define the immunological changes associated with this therapeutic combination to identify biomarkers for a response to the therapy. Here, we present serial immunomonitoring examining dendritic cell and T cell subpopulations over sequential courses of chemoimmunotherapy.

METHODS: Fifteen patients with mesothelioma received up to six 21-day cycles of pemetrexed plus cisplatin chemotherapy and anti-CD40 (CP-870,893). Peripheral blood was collected weekly, and analysed by flow cytometry. Longitudinal immunophenotyping data was analysed by linear mixed modelling, allowing for variation between patients. Exploratory analyses testing for any correlation between overall survival and immunophenotyping data were undertaken up to the third cycle of treatment.

RESULTS: Large statistically significant cyclical variations in the proportions of BDCA-1+, BDCA-2+ and BDCA-3+ dendritic cells were observed, although all subsets returned to baseline levels after each cycle and no significant changes were observed between start and end of treatment. Expression levels of CD40 and HLA-DR on dendritic cells were also cyclically modulated, again without significant change between start and end of treatment. CD8 and CD4 T cell populations, along with regulatory T cells, effector T cells, and markers of proliferation and activation, showed similar patterns of statistically significant cyclical modulation in response to therapy without changes between start and end of treatment. Exploratory analysis of endpoints revealed that patients with a higher than average proportion of BDCA-2+ dendritic cells (p = 0.010) or a higher than average proportion of activated (ICOS+) CD8 T cells (0.022) in pretreatment blood samples had better overall survival. A higher than average proportion of BDCA-3+ dendritic cells was associated with poorer overall survival at both the second (p = 0.008) and third (p = 0.014) dose of anti-CD40.

CONCLUSIONS: Substantial cyclical variations in DC and T cell populations during sequential cycles of chemoimmunotherapy highlight the critical importance of timing of immunological biomarker assessments in interpretation of results and the value of linear mixed modelling in interpretation of longitudinal change over a full treatment course.

TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry number ACTRN12609000294257 (18th May 2009).}, } @article {pmid28614305, year = {2017}, author = {Bononi, A and Giorgi, C and Patergnani, S and Larson, D and Verbruggen, K and Tanji, M and Pellegrini, L and Signorato, V and Olivetto, F and Pastorino, S and Nasu, M and Napolitano, A and Gaudino, G and Morris, P and Sakamoto, G and Ferris, LK and Danese, A and Raimondi, A and Tacchetti, C and Kuchay, S and Pass, HI and Affar, EB and Yang, H and Pinton, P and Carbone, M}, title = {BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation.}, journal = {Nature}, volume = {546}, number = {7659}, pages = {549-553}, pmid = {28614305}, issn = {1476-4687}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis/genetics ; Asbestos/toxicity ; Calcium/*metabolism ; Calcium Signaling ; Cell Nucleus/metabolism ; Cell Survival ; *Cell Transformation, Neoplastic/drug effects/radiation effects ; Cells, Cultured ; Cytoplasm/*metabolism ; DNA Damage ; Endoplasmic Reticulum/*metabolism ; Epithelium ; Fibroblasts ; Gene-Environment Interaction ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/*metabolism ; Mitochondria/*metabolism ; Protein Binding ; Protein Stability ; Tumor Suppressor Proteins/deficiency/genetics/*metabolism ; Ubiquitin/metabolism ; Ubiquitin Thiolesterase/deficiency/genetics/*metabolism ; }, abstract = {BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1+/-) developed one and often several BAP1-/- malignancies in their lifetime, mostly malignant mesothelioma, uveal melanoma, and so on. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity. The possible activity of BAP1 in the cytoplasm is unknown. Cells with reduced levels of BAP1 exhibit chromosomal abnormalities and decreased DNA repair by homologous recombination, indicating that BAP1 dosage is critical. Cells with extensive DNA damage should die and not grow into malignancies. Here we discover that BAP1 localizes at the endoplasmic reticulum. Here, it binds, deubiquitylates, and stabilizes type 3 inositol-1,4,5-trisphosphate receptor (IP3R3), modulating calcium (Ca2+) release from the endoplasmic reticulum into the cytosol and mitochondria, promoting apoptosis. Reduced levels of BAP1 in BAP1+/- carriers cause reduction both of IP3R3 levels and of Ca2+ flux, preventing BAP1+/- cells that accumulate DNA damage from executing apoptosis. A higher fraction of cells exposed to either ionizing or ultraviolet radiation, or to asbestos, survive genotoxic stress, resulting in a higher rate of cellular transformation. We propose that the high incidence of cancers in BAP1+/- carriers results from the combined reduced nuclear and cytoplasmic activities of BAP1. Our data provide a mechanistic rationale for the powerful ability of BAP1 to regulate gene-environment interaction in human carcinogenesis.}, } @article {pmid28611824, year = {2017}, author = {Kresoja-Rakic, J and Sulemani, M and Kirschner, MB and Ronner, M and Reid, G and Kao, S and Schwaller, B and Weder, W and Stahel, RA and Felley-Bosco, E}, title = {Posttranscriptional Regulation Controls Calretinin Expression in Malignant Pleural Mesothelioma.}, journal = {Frontiers in genetics}, volume = {8}, number = {}, pages = {70}, pmid = {28611824}, issn = {1664-8021}, abstract = {Calretinin (CALB2) is a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM). We previously reported that calretinin expression is regulated at the mRNA level. The presence of a medium-sized (573 nucleotide) 3' untranslated region (3'UTR) predicted to contain binding sites for miR-30a/b/c/d/e and miR-9 as well as an adenine/uridine-rich element (ARE) in all three transcripts arising from the CALB2 gene, suggests that calretinin expression is regulated via posttranscriptional mechanisms. Our aim was to investigate the role of the CALB2-3'UTR in the posttranscriptional regulation of calretinin expression in MPM. CALB2-3'UTR was inserted downstream of the luciferase reporter gene using pmiRGLO vector and reporter expression was determined after transfection into MPM cells. Targeted mutagenesis was used to generate variants harboring mutated miR-30 family and ARE binding sites. Electrophoretic mobility shift assay was used to test for the presence of ARE binding proteins. CALB2-3'UTR significantly decreased luciferase activity in MPM cells. Analysis of mutation in the ARE site revealed a further destabilization of the reporter and human antigen R (HuR) binding to the ARE sequence was detected. The mutation of two miR-30 binding sites abolished CALB2-3'UTR destabilization effect; a transient delivery of miR-30e-5p mimics or anti-miR into MPM cells resulted in a significant decrease/increase of the luciferase reporter expression and calretinin protein, respectively. Moreover, overexpression of CALB2-3'UTR quenched the effect of miR-30e-5p mimics on calretinin protein levels, possibly by sequestering the mimics, thereby suggesting a competitive endogenous RNA network. Finally, by data mining we observed that expression of miR-30e-5p was negatively correlated with the calretinin expression in a cohort of MPM patient samples. Our data show the role of (1) adenine-uridine (AU)-binding proteins in calretinin stabilization and (2) miR-30e-5p in the posttranscriptional negative regulation of calretinin expression via interaction with its 3'UTR. Furthermore, our study demonstrates a possible physiological role of calretinin's alternatively spliced transcripts.}, } @article {pmid28603777, year = {2016}, author = {Napolitano, A and Carbone, M}, title = {Malignant Mesothelioma: Time to Translate?.}, journal = {Trends in cancer}, volume = {2}, number = {9}, pages = {467-474}, pmid = {28603777}, issn = {2405-8033}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Humans ; *Lung Neoplasms/drug therapy/genetics/metabolism ; *Mesothelioma/drug therapy/genetics/metabolism ; Molecular Targeted Therapy ; Translational Medical Research ; }, abstract = {Malignant mesothelioma is an aggressive cancer largely associated with asbestos exposure. In this review, we will discuss the significant advancements in our understanding of its genetics and molecular biology and their translational relevance. Remarkable findings included the discovery of germline and somatic mutations of BRCA1 associated protein-1 (BAP1) in patients, and the genome-wide characterization of pathways altered in mesothelioma that could be potentially exploited to design novel therapeutic approaches. Nevertheless, the clinical translation of these molecular findings has been slow and insufficient. In order to rapidly move translation from the bench to the bedside, we believe that cooperative research efforts have to be further endorsed and promoted at all levels.}, } @article {pmid28594258, year = {2017}, author = {Fujimoto, E and Kijima, T and Kuribayashi, K and Negi, Y and Kanemura, S and Mikami, K and Doi, H and Kitajima, K and Nakano, T}, title = {First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma.}, journal = {Expert review of anticancer therapy}, volume = {17}, number = {9}, pages = {865-872}, doi = {10.1080/14737140.2017.1340157}, pmid = {28594258}, issn = {1744-8328}, mesh = {Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Disease-Free Survival ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Male ; Mesothelioma/*drug therapy/pathology ; Middle Aged ; Pemetrexed/administration & dosage ; Pleural Neoplasms/*drug therapy/pathology ; Positron-Emission Tomography ; Retrospective Studies ; Survival Rate ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {BACKGROUND: Mesothelioma of peritoneal origin has wider variation in treatment outcomes than mesothelioma of pleural origin, likely because peritoneal mesothelioma comprises borderline malignant variants and aggressive malignant peritoneal mesothelioma (MPeM). This study retrospectively evaluates the efficacy of first-line systemic pemetrexed and cisplatin chemotherapy in MPeM.

RESEARCH DESIGN AND METHODS: Twenty-four patients with histologically proven MPeM were treated with pemetrexed plus cisplatin as a first-line systemic chemotherapy. The response was evaluated radiologically according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Twenty-two patients underwent 18F-fluorodeoxyglucose positron emission tomography/(FDG-PET)/computed tomography(CT) at baseline, and 13 were eligible for metabolic assessment.

RESULTS: Two complete responses and 9 partial responses were achieved. Overall response rate and disease control rate were 45.8% and 91.7%, respectively. Median progression-free survival and median overall survival were 11.0 months and 15.8 months, respectively. Wet- type MPeM had significantly longer survival (40.9 months median) than other clinical types (15.5 months) (P = 0.045). The baseline maximum standardized uptake value in 22 patients was 8.93 (range, 2.5-16.77).

CONCLUSIONS: Systemic pemetrexed plus cisplatin is active for MPeM. Disparity with the outcome of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) needs to receive more emphasis, since peritoneal mesothelioma has a 5-year survival rate of 50%.}, } @article {pmid28593073, year = {2017}, author = {Nynäs, P and Pukkala, E and Vainio, H and Oksa, P}, title = {Cancer Incidence in Asbestos-Exposed Workers: An Update on Four Finnish Cohorts.}, journal = {Safety and health at work}, volume = {8}, number = {2}, pages = {169-174}, pmid = {28593073}, issn = {2093-7911}, abstract = {BACKGROUND: We assessed the cancer risks of four different Finnish asbestos-exposed cohorts. We also explored if the cohorts with varying profiles of asbestos exposure exhibited varying relative risks of cancer.

METHODS: The incident cancer cases for the asbestos-exposed worker cohorts were updated to the end of 2012 using the files of the Finnish Cancer Registry. The previously formed cohorts consisted of asbestos mine workers, asbestosis patients, asbestos sprayers, and workers who had taken part in a screening study based on asbestos exposure at work.

RESULTS: The standardized incidence ratio (SIR) for mesothelioma varied from about threefold to > 100-fold in the different cohorts. In the screening cohort the SIR for mesothelioma was highest in 2003-2007, In other cohorts it was more constant in 5-year period inspection. The SIR for lung cancer was about twofold to tenfold in all except the screening cohort. Asbestos sprayers were at the highest risk of mesothelioma and lung cancer.

CONCLUSION: The SIR for mesothelioma is high in all of the cohorts that represent different kinds of asbestos exposure. The smaller SIR for mesothelioma in the screening cohort with lowest level of asbestos exposure might suggest dose-responsiveness between asbestos exposure and mesothelioma. It does seem that the highest risk of lung cancer in these cohorts except in the youngest of the cohorts, the screening cohort, is over. The highest SIR for lung cancer of the asbestosis patient and sprayers cohort is explained by their heavy asbestos exposure.}, } @article {pmid28577549, year = {2017}, author = {Sneddon, S and Patch, AM and Dick, IM and Kazakoff, S and Pearson, JV and Waddell, N and Allcock, RJN and Holt, RA and Robinson, BWS and Creaney, J}, title = {Whole exome sequencing of an asbestos-induced wild-type murine model of malignant mesothelioma.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {396}, pmid = {28577549}, issn = {1471-2407}, mesh = {Animals ; Asbestos/*toxicity ; DNA Copy Number Variations/genetics ; Disease Models, Animal ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mice ; Mutation ; Neoplasm Proteins/*genetics ; Signal Transduction/drug effects/genetics ; *Whole Exome Sequencing ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is an aggressive cancer of the pleural and peritoneal cavities caused by exposure to asbestos. Asbestos-induced mesotheliomas in wild-type mice have been used extensively as a preclinical model because they are phenotypically identical to their human counterpart. However, it is not known if the genetic lesions in these mice tumours are similar to in the human disease, a prerequisite for any new preclinical studies that target genetic abnormalities.

METHODS: We performed whole exome sequencing of fifteen asbestos-induced murine MM tumour cell lines from BALB/c, CBA and C57BL/6 mouse strains and compared the somatic mutations and copy number variations with those recurrently reported in human MM. We then catalogued and characterised the mutational landscape of the wild-type murine MM tumours. Quantitative RT-PCR was used to interrogate the expression of key MM genes of interest in the mRNA.

RESULTS: Consistent with human MM tumours, we identified homozygous loss of the tumour suppressor Cdkn2a in 14/15 tumours. One tumour retained the first exon of both of the p16INK4a and p19ARF isoforms though this tumour also contained genetic amplification of Myc resulting in increased expression of the c-Myc proto-oncogene in the mRNA. There were no chromosomal losses in either the Bap1 or Nf2 regions. One tumour harbored homozygous loss of Trp53 in the DNA. Mutation rates were similar in tumours generated in the CBA and C57BL/6 strains when compared to human MM. Interestingly, all BALB/c tumour lines displayed high mutational loads, consistent with the known mutator phenotype of the host strain. The Wnt, MAPK and Jak-STAT signaling pathways were found to be the most commonly affected biological pathways. Mutations and copy number deletions also occurred in the Hedgehog and Hippo pathways.

CONCLUSIONS: These data suggest that in the wild-type murine model asbestos causes mesotheliomas in a similar way to in human MM. This further supports the notion that the murine model of MM represents a genuine homologue of the human disease, something uncommon in cancer, and is thus a valuable tool to provide insight into MM tumour development and to aide the search for novel therapeutic strategies.}, } @article {pmid28572505, year = {2017}, author = {}, title = {Correction: Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer.}, journal = {Cancer research}, volume = {77}, number = {11}, pages = {3124}, doi = {10.1158/0008-5472.CAN-17-0575}, pmid = {28572505}, issn = {1538-7445}, } @article {pmid28562724, year = {2017}, author = {Trotta, A and Santana, VS and Alazraqui, M}, title = {[Mesothelioma mortality in Argentina, 1980-2013].}, journal = {Salud colectiva}, volume = {13}, number = {1}, pages = {35-44}, doi = {10.18294/sc.2017.1027}, pmid = {28562724}, issn = {1851-8265}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Argentina/epidemiology ; Female ; Heart Neoplasms/*mortality ; Humans ; Male ; Mesothelioma/*mortality ; Middle Aged ; Pericardium ; Peritoneal Neoplasms/*mortality ; Pleural Neoplasms/*mortality ; Young Adult ; }, abstract = {Mesothelioma mortality and its socio-demographic and temporal patterns in Argentina from 1980 to 2013 were estimated using data from death certificates obtained from the Vital Statistics System of Argentina's National Ministry of Health. There were 3,259 mesothelioma deaths corresponding to an age-adjusted mortality of 3.1/1,000,000 in 1980 and 5.7/1,000,000 in 2013, an average increase of 84.1% in 34 years. This raising trend became clearer after 1997. Males had higher mortality estimates compared with women in every year of the series; these findings suggest past exposure to asbestos. It is plausible that the asbestos exposure was mostly occupational, which is more common among men. Actions related to reinforcing the asbestos ban already in place and strengthening health surveillance directed at workplaces, previously exposed workers, and the population in general are recommended.}, } @article {pmid28558669, year = {2017}, author = {Johnen, G and Gawrych, K and Raiko, I and Casjens, S and Pesch, B and Weber, DG and Taeger, D and Lehnert, M and Kollmeier, J and Bauer, T and Musk, AW and Robinson, BWS and Brüning, T and Creaney, J}, title = {Calretinin as a blood-based biomarker for mesothelioma.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {386}, pmid = {28558669}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Australia ; Biomarkers, Tumor/*blood ; Calbindin 2/*blood/genetics ; Germany ; Humans ; Lung Neoplasms/*blood/chemically induced/pathology ; Male ; Mesothelioma/*blood/chemically induced/pathology ; Middle Aged ; Pleural Neoplasms/*blood/pathology ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin.

METHODS: For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype.

RESULTS: Calretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10-3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30-4.00).

CONCLUSIONS: Calretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.}, } @article {pmid28553954, year = {2017}, author = {Kato, T and Sato, T and Yokoi, K and Sekido, Y}, title = {E-cadherin expression is correlated with focal adhesion kinase inhibitor resistance in Merlin-negative malignant mesothelioma cells.}, journal = {Oncogene}, volume = {36}, number = {39}, pages = {5522-5531}, doi = {10.1038/onc.2017.147}, pmid = {28553954}, issn = {1476-5594}, mesh = {Antigens, CD ; Apoptosis/drug effects ; Cadherins/*biosynthesis ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm ; Focal Adhesion Kinase 1/*antagonists & inhibitors ; Gene Expression ; Humans ; Lung Neoplasms/*drug therapy/*metabolism/pathology ; Mesothelioma/*drug therapy/*metabolism/pathology ; Neurofibromin 2/*deficiency/metabolism ; Protein Kinase Inhibitors/*pharmacology ; Signal Transduction ; }, abstract = {Malignant mesothelioma (MM) is an aggressive tumor commonly caused by asbestos exposure after a long latency. Focal adhesion kinase (FAK) inhibitors inhibit the cell growth of Merlin-deficient MM cells; however, their clinical efficacy has not been clearly determined. The aim of this study was to evaluate the growth inhibitory effect of the FAK inhibitor VS-4718 on MM cell lines and identify biomarkers for its efficacy. Although most Merlin-deficient cell lines were sensitive to VS-4718 compared with control MeT-5A cells, a subset of these cell lines exhibited resistance to this drug. Microarray and qRT-PCR analyses using RNA isolated from Merlin-deficient MM cell lines revealed a significant correlation between E-cadherin mRNA levels and VS-4718 resistance. Merlin- and E-cadherin-negative Y-MESO-22 cells underwent apoptosis upon treatment with a low concentration of VS-4718, whereas Merlin-negative, E-cadherin-positive Y-MESO-9 cells did not undergo VS-4718-induced apoptosis. Furthermore, E-cadherin knockdown in Merlin-negative MM cells significantly sensitized cells to VS-4718 and induced apoptotic cell death upon VS-4718 treatment. Together, our results suggest that E-cadherin serves as a predictive biomarker for molecular target therapy with FAK inhibitors for patients with mesothelioma and that its expression endows MM cells with resistance to FAK inhibitors.}, } @article {pmid28551647, year = {2017}, author = {Rizzardi, C and Athanasakis, E and Cammisuli, F and Monego, SD and DE Spelorzi, YCC and Costantinides, F and Giudici, F and Pinamonti, M and Canzonieri, V and Melato, M and Pascolo, L}, title = {Puzzling Results from BAP1 Germline Mutations Analysis in a Group of Asbestos-Exposed Patients in a High-risk Area of Northeast Italy.}, journal = {Anticancer research}, volume = {37}, number = {6}, pages = {3073-3083}, doi = {10.21873/anticanres.11663}, pmid = {28551647}, issn = {1791-7530}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Female ; Germ-Line Mutation ; Humans ; Italy ; Lung Neoplasms/etiology/*genetics ; Male ; Mesothelioma/etiology/*genetics ; Middle Aged ; Risk ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {BACKGROUND: Germline mutations of the oncosuppressor gene breast cancer 1-associated protein 1 (BAP1) were recently related to an autosomal-dominant tumor predisposition syndrome (BAP1-TPDS), characterized by uveal melanoma, malignant mesothelioma (MM), cutaneous melanoma, and other malignancies. The demonstration that BAP1 mutations are strongly associated with MM has provided a real breakthrough in the study of genetic predisposition in MM, that may explain why only a fraction of asbestos-exposed individuals go on to develop MM.

MATERIALS AND METHODS: To evaluate the possible role of BAP1 mutations in the epidemiology of sporadic MM, and their relationship with asbestos exposure, we determined the prevalence of germline BAP1 mutations by the Sanger method in a group of 29 asbestos-exposed patients, 21 of which were diagnosed with MM. They were residents of Trieste, a ship-building town in Northeast Italy with a very high incidence of mesothelioma.

RESULTS: We identified non-obviously pathogenetic germline sequence variants of BAP1 in 3/29 patients and in 2/21 MM cases (10%).

CONCLUSION: Non obviously pathogenic germline sequence variants of BAP1 were found. Nevertheless, limitations of predictive web tools allowed us to comment on some interesting peculiarities of our findings.}, } @article {pmid28534416, year = {2017}, author = {Xu, R and Mesaros, C and Weng, L and Snyder, NW and Vachani, A and Blair, IA and Hwang, WT}, title = {Comparison of statistical methods for detection of serum lipid biomarkers for mesothelioma and asbestos exposure.}, journal = {Biomarkers in medicine}, volume = {11}, number = {7}, pages = {547-556}, pmid = {28534416}, issn = {1752-0371}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; T32 ES019851/ES/NIEHS NIH HHS/United States ; R03 CA211820/CA/NCI NIH HHS/United States ; K22 ES026235/ES/NIEHS NIH HHS/United States ; }, mesh = {Asbestos/*adverse effects ; Biomarkers, Tumor/*blood ; Blood Chemical Analysis/*methods ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Humans ; Lipids/*blood ; Mesothelioma/*blood ; Statistics as Topic/*methods ; }, abstract = {AIM: We compared three statistical methods in selecting a panel of serum lipid biomarkers for mesothelioma and asbestos exposure.

MATERIALS & METHODS: Serum samples from mesothelioma, asbestos-exposed subjects and controls (40 per group) were analyzed. Three variable selection methods were considered: top-ranked predictors from univariate model, stepwise and least absolute shrinkage and selection operator. Crossed-validated area under the receiver operating characteristic curve was used to compare the prediction performance.

RESULTS: Lipids with high crossed-validated area under the curve were identified. Lipid with mass-to-charge ratio of 372.31 was selected by all three methods comparing mesothelioma versus control. Lipids with mass-to-charge ratio of 1464.80 and 329.21 were selected by two models for asbestos exposure versus control.

CONCLUSION: Different methods selected a similar set of serum lipids. Combining candidate biomarkers can improve prediction.}, } @article {pmid28527639, year = {2017}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Epidemiology of mesothelioma of the pericardium and tunica vaginalis testis.}, journal = {Annals of epidemiology}, volume = {27}, number = {5}, pages = {348-359.e11}, doi = {10.1016/j.annepidem.2017.04.001}, pmid = {28527639}, issn = {1873-2585}, mesh = {Asbestos/*toxicity ; Female ; Heart Neoplasms/pathology ; Humans ; Male ; Mesothelioma/*pathology ; Middle Aged ; Occupational Diseases ; Pericardium/*pathology ; Registries ; Testicular Neoplasms/*pathology ; Testis/*pathology ; United States ; }, abstract = {PURPOSE: Malignant mesothelioma most commonly arises in the pleura and peritoneum but also occurs rarely at other anatomical sites with mesothelial tissue, namely, the pericardium and tunica vaginalis testis (TVT). This review provides a better understanding of the epidemiology of mesothelioma of these extrapleural sites.

METHODS: We conducted a systematic review of the epidemiologic and clinical literature on pericardial mesothelioma and mesothelioma of the TVT. We also analyzed U.S. Surveillance, Epidemiology, and End Results cancer registry data to describe incidence patterns of these malignancies.

RESULTS: An etiologic role of asbestos exposure has been hypothesized for pericardial and TVT mesotheliomas, but no analytical case-control epidemiologic studies exist to test this relationship. A substantial proportion of cases with these malignancies report no known asbestos exposure. In large occupational cohorts with heavy asbestos exposures, no cases of pericardial or TVT mesothelioma have been reported. Trends in the incidence of these malignancies do not match those of pleural mesothelioma, which correspond to historical trends of commercial asbestos use. A male preponderance of pericardial mesothelioma is not evident.

CONCLUSIONS: In the absence of analytic epidemiologic studies, the etiologic role of environmental risk factors for mesothelioma of the pericardium and TVT remains elusive.}, } @article {pmid28523158, year = {2017}, author = {D'Agostin, F and De Michieli, P and Chermaz, C and Negro, C}, title = {Pleural and peritoneal mesotheliomas in the Friuli Venezia Giulia register: data analysis from 1995 to 2015 in Northeastern Italy.}, journal = {Journal of thoracic disease}, volume = {9}, number = {4}, pages = {1032-1045}, pmid = {28523158}, issn = {2072-1439}, abstract = {BACKGROUND: The Friuli Venezia Giulia Mesothelioma Register contains a case-list of 1,109 mesotheliomas (1,034 pleural, 75 peritoneal) during 1995-2015. Exposure data are available for almost all cases. The aim was to assess mesothelioma incidence in the Region, an area with several shipyards, and to investigate determinants of mesothelioma latency among occupational cases.

METHODS: Incidence rates were calculated. Univariate and multivariate analyses were performed to estimate latency time by anatomical site, gender, diagnostic period and industry sector.

RESULTS: Mesothelioma incidence rates among men were higher than among women during the overall period. The incidence of pleural mesothelioma in men leveled off until 2009 (6.50 per 100,000) with a slight decrease thereafter. For women, the rate increased until 2006 (1.31 per 100,000) and then remained relatively stable. The incidence of peritoneal mesothelioma in men was constant whereas rate among women increased during 2010-2015. The number of cases diagnosed during three-year periods remained level. In multivariate model, site and gender were not relevant for latency period whereas construction workers had a shorter latency than shipyard workers.

CONCLUSIONS: Despite the asbestos ban since 1992, occupational exposure is still at risk. This highlights the need to assess exposure levels and to find a reliable health surveillance tool.}, } @article {pmid28505004, year = {2017}, author = {Desmeules, P and Joubert, P and Zhang, L and Al-Ahmadie, HA and Fletcher, CD and Vakiani, E and Delair, DF and Rekhtman, N and Ladanyi, M and Travis, WD and Antonescu, CR}, title = {A Subset of Malignant Mesotheliomas in Young Adults Are Associated With Recurrent EWSR1/FUS-ATF1 Fusions.}, journal = {The American journal of surgical pathology}, volume = {41}, number = {7}, pages = {980-988}, pmid = {28505004}, issn = {1532-0979}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA140146/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Biomarkers, Tumor/*genetics ; Child ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; *Oncogene Fusion ; Oncogene Proteins, Fusion/*genetics ; Peritoneal Neoplasms/*genetics/pathology ; Pleural Neoplasms/*genetics/pathology ; RNA-Binding Protein FUS/*genetics ; Young Adult ; }, abstract = {Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality. As both index cases occurred as intra-abdominal tumors in young adults, we searched our files for pleural and peritoneal MM occurring in adults younger than age of 40. All cases were tested by fluorescence in situ hybridization using custom bacterial artificial chromosomes probes for EWSR1, FUS, and ATF1 genes. When available, immunohistochemistry for BAP1 was performed. A total of 25 MM from patients aged 40 or less were screened, either from peritoneum (n=13) or pleura (n=12), with a median age of 31 (range: 7 to 40 y). Two additional ATF1-rearranged tumors were identified at pleural and peritoneal sites with EWSR1 and FUS as fusion partners, respectively, for a total of 4 cases (16%, 4/25). The fusion-positive cases displayed classic epithelioid morphology, immunoreactivity for cytokeratins and WT1, and negativity for S100. BAP1 expression was retained in the 3 fusion-positive cases with available material, and in 80% (12/15) of the fusion-negative cases. Our results expand the spectrum of tumor types harboring EWSR1/FUS-ATF1 gene fusions to include a subgroup of conventional epithelioid MM. Other features of this unique MM subset include young age at presentation, lack of asbestos exposure and retained BAP1 expression.}, } @article {pmid28501798, year = {2017}, author = {Lacourt, A and Lévêque, E and Guichard, E and Gilg Soit Ilg, A and Sylvestre, MP and Leffondré, K}, title = {Dose-time-response association between occupational asbestos exposure and pleural mesothelioma.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {9}, pages = {691-697}, doi = {10.1136/oemed-2016-104133}, pmid = {28501798}, issn = {1470-7926}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Case-Control Studies ; Dose-Response Relationship, Drug ; Female ; France ; Humans ; Logistic Models ; Lung Neoplasms/*etiology ; Male ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Odds Ratio ; Pleura/*drug effects/pathology ; Pleural Neoplasms/*etiology/pathology ; Risk Factors ; }, abstract = {OBJECTIVES: Early occupational exposure to asbestos has been shown to be associated with an increased risk of pleural mesothelioma (PM), which suggests that the timing of exposure might play a role in the dose-response relationship. However, none studies has evaluated the relative impact of increasing the annual intensity of occupational exposure to asbestos at each time of the whole exposure history. Yet such evaluation would allow the comparison of the risks of PM associated with different longitudinal profiles of occupational exposure to asbestos. Our objective was to estimate the time-dependent relative impact of asbestos exposure intensity over the whole occupational history and to compare the resulting estimated risks of PM associated with different profiles of exposure, using data from a large French case-control study.

METHODS: This study included 1196 male cases recruited in 1987-2006 and 2369 matched controls on birth year. Occupational exposure to asbestos was assessed using a job exposure matrix and represented in logistic regression models using a flexible weighted cumulative index of exposure.

RESULTS: Due to much stronger weights of early doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their entire job history with high doses during the first years and low doses thereafter were at higher risk of PM than those who accumulated most of the doses later (OR=2.37 (95% CI 2.01 to 2.87)).

CONCLUSION: This study provides new insights on the dose-time-response relationship between occupational asbestos and PM and illustrates the importance of considering timing of exposure in its association with cancer risk.}, } @article {pmid28500034, year = {2017}, author = {Freitas, DMM and Ramos, RL and Serpa Pinto, L and Ribeiro, R}, title = {Primary pericardial mesothelioma and asbestos exposure: a rare fatal disease.}, journal = {BMJ case reports}, volume = {2017}, number = {}, pages = {}, doi = {10.1136/bcr-2017-219949}, pmid = {28500034}, issn = {1757-790X}, mesh = {Aged ; Disease Progression ; Environmental Exposure/*adverse effects ; Female ; Heart Diseases/*chemically induced ; Humans ; Lung Neoplasms/*chemically induced ; Mesothelioma/*chemically induced ; Pericardial Effusion/*chemically induced ; Pericardium ; Rare Diseases/*chemically induced ; }, } @article {pmid28498408, year = {2017}, author = {Maeda, M and Chen, Y and Lee, S and Kumagai-Takei, N and Yoshitome, K and Matsuzaki, H and Yamamoto, S and Hatayama, T and Ikeda, M and Nishimura, Y and Otsuki, T}, title = {Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure.}, journal = {International journal of oncology}, volume = {50}, number = {6}, pages = {2024-2032}, doi = {10.3892/ijo.2017.3991}, pmid = {28498408}, issn = {1791-2423}, mesh = {Asbestos/toxicity ; CD4-Positive T-Lymphocytes/drug effects/immunology ; Coculture Techniques ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Interferon-gamma/*genetics ; Interleukin-17/*genetics/immunology ; Ionomycin/administration & dosage ; Lung Neoplasms/chemically induced/*genetics/immunology/pathology ; Mesothelioma/chemically induced/*genetics/immunology/pathology ; Phorbol Esters/administration & dosage ; Receptors, Antigen, T-Cell/genetics ; Receptors, CXCR3/*genetics ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; Th17 Cells/drug effects/immunology ; }, abstract = {We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes (CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules such as granzyme B and perforin, as well as suppressed proliferation of CTLs. Additionally, analysis of T helper cells showed that surface CXCR3, chemokine receptor, and the productive potential of interferon (IFN)γ were reduced following asbestos exposure in an in vitro cell line model and in peripheral CD4+ cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos exposure enhanced regulatory T cell (Treg) function. This study also focused on CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell receptor and co-culture with various concentrations of chrysotile fibers using freshly isolated CD4+ surface CXCR3 positive and negative fractions, the intracellular expression of CXCR3, IFNγ and IL-17 remained unchanged when co-cultured with chrysotile. However, subsequent re-stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production and expression, particularly in CD4+ surface CXCR3 positive cells. These results indicated that the balance and polarization between Treg and Th-17 fractions play an important role with respect to the immunological effects of asbestos and the associated reduction in antitumor immunity.}, } @article {pmid28481375, year = {2017}, author = {D' Agostin, F and de Michieli, P and Negro, C}, title = {Pleural mesothelioma in household members of asbestos-exposed workers in Friuli Venezia Giulia, Italy.}, journal = {International journal of occupational medicine and environmental health}, volume = {30}, number = {3}, pages = {419-431}, doi = {10.13075/ijomeh.1896.00890}, pmid = {28481375}, issn = {1896-494X}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/epidemiology/etiology ; Environmental Exposure/*adverse effects ; *Family Characteristics ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; }, abstract = {OBJECTIVES: Malignant mesothelioma is closely associated to asbestos exposure. One such exposure may occur through contact with occupationally exposed household members and their belongings. This study examines the features of pleural mesothelioma attributable only to asbestos brought home by another family member.

MATERIAL AND METHODS: The data sources were 1063 mesothelioma cases diagnosed between 1995 and 2014, from the Friuli Venezia Giulia Mesothelioma Register. In all cases the diagnosis of mesothelioma was based on the pathology report. Exposure information and demographic data were acquired by an occupational medical standardized questionnaire/interview.

RESULTS: Household-exposure mesothelioma cases included 33 women and 2 men. Relationships were: wives (N = 22), daughters (N = 9), sons (N = 2), and mothers (N = 2). Asbestos exposure in the workers predominantly occurred in shipyards. Out of the 35 pleural cases, 19 were epithelial, 9 biphasic, 3 sarcomatoid, and 4 not specified. The mean age at diagnosis was 77 years old. The mean latency was 59 years, with wives having a significant shorter latency than offspring. Latency was not significantly related to morphology and asbestosis. The overall mean survival was 16 months (median 11 months) but treatment was beneficial (mean 16 months vs. 7 months). Biphasic/sarcomatoid histology and presence of asbestosis were associated with a decreased survival, although not with statistical significance.

CONCLUSIONS: Our data confirms that household exposure increases the risk for pleural mesothelioma amongst women with no history of occupational asbestos exposure. This is an ongoing problem in many countries, as well as in Italy, where the evaluation of a framework for the compensation of these cases is under debate. Int J Occup Med Environ Health 2017;30(3):419-431.}, } @article {pmid28472171, year = {2017}, author = {Cavalleri, T and Angelici, L and Favero, C and Dioni, L and Mensi, C and Bareggi, C and Palleschi, A and Rimessi, A and Consonni, D and Bordini, L and Todaro, A and Bollati, V and Pesatori, AC}, title = {Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease.}, journal = {PloS one}, volume = {12}, number = {5}, pages = {e0176680}, pmid = {28472171}, issn = {1932-6203}, mesh = {Aged ; Asbestos/*toxicity ; Biomarkers, Tumor/*metabolism ; Female ; Humans ; Male ; Mesothelioma/chemically induced/*genetics ; MicroRNAs/*genetics ; Middle Aged ; Pleural Neoplasms/chemically induced/*genetics ; }, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer mainly caused by asbestos exposure and refractory to current therapies. Specific diagnostic markers for early MPM diagnosis are needed. Changes in miRNA expression have been implicated in several diseases and cancers, including MPM. We examined if a specific miRNA signature in plasmatic extracellular vesicles (EV) may help to discriminate between malignant pleural mesothelioma patients (MPM) and subjects with Past Asbestos Exposure (PAE).

We investigated 23 MPM patients and 19 cancer-free subjects with past asbestos exposure (PAE). We screened 754 miRNAs in plasmatic EVs by OpenArray and found 55 differential miRNAs using logistic regression models adjusted for age, sex, BMI, and smoking. Among the top-20 differential miRNAs chosen for validation by Real time PCR, 16 were confirmed. Using receiver operating characteristic (ROC) curve analysis, the most discriminating miRNA combination was given by miR-103a-3p + miR-30e-3p, which generated an AUC of 0.942 (95% CI 0.87-1.00), with a sensitivity of 95.5% and a specificity of 80.0%. Using multivariate Cox regression analysis including gender, age, BMI and smoking we found a Hazard Ratio for miR-103a-3p above the median of 0.37 (95%CI 0.13-1.13) and of 0.51 (95%CI 0.17-1.52) for miR-30e-3p.

CONCLUSIONS: This study suggests EV-associated miR-103a-3p and miR-30e-3p are able to discriminate MPM from PAE subjects. Larger and prospective studies are needed to confirm these two-miRNA signature alone or in combination with other biomarkers as diagnostic tools for MPM.}, } @article {pmid28446737, year = {2017}, author = {Barbieri, PG and Somigliana, AB and Lombardi, S and Festa, R and Girelli, R and Sarnico, M}, title = {Pleural mesothelioma in doll manufacture: possible asbestos exposure.}, journal = {La Medicina del lavoro}, volume = {108}, number = {2}, pages = {111-117}, doi = {10.23749/mdl.v108i2.6115}, pmid = {28446737}, issn = {0025-7818}, mesh = {Aged ; Asbestos/*adverse effects ; *Carcinogens ; Female ; Humans ; *Industry ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/*adverse effects ; Play and Playthings ; Pleural Neoplasms/*etiology ; }, abstract = {BACKGROUND: The occurrence of malignant mesothelioma is almost always causally associated to asbestos exposure but, considering women occurrences, this association is often difficult to demonstrate and consequently the asbestos exposure is defined as 'unknown'.

OBJECTIVES: To describe the working activity and to give occupational asbestos exposure probability estimation related to an uncommon and poorly investigated productive sector: doll manufacture.

METHODS: From the Province of Brescia Mesothelioma Registry, established in 1993 on population-based criteria, we have extracted the certified mesothelioma diagnosis cases, related to patients who were employed for some time in doll manufacture.

RESULTS: Among the 757 total cases of malignant mesothelioma registered and studied up to 2016, we found 3 cases of pleural epithelial mesothelioma histologically diagnosed in young women who had worked in two doll manufacturing companies and whose asbestos exposure had been initially defined as 'unknown', because an environmental, family or extra-professional asbestos exposure was considered unlikely. However, the judicial autopsy performed on one of the 3 women had allowed examining lung tissue samples with Scanning Electron Microscopy. This technique showed a concentration of amphiboles fibers of about 12,000,000 per gram of dry lung tissue, with a consequent re-classification of asbestos exposure from 'unknown' to 'occupational certified'.

DISCUSSION: Mesotheliomas in women with no apparent occupational asbestos exposure are normally referred to life or family environmental exposure. Moreover, it is known that occupational asbestos exposure in women is difficult to recognize. Previously, only one publication had reported two cases of mesothelioma in cloth doll manufacture. The occurrence of two mesothelioma cases in the same company out of the three here presented was suggesting an occupational exposure. The finding of a high amphibole fibers lung concentration confirmed the previous hypothesis, despite the impossibility to determine the circumstances with good evidence.

CONCLUSION: The three cases of mesothelioma in doll production workers suggest that also in this restricted manufacturing sector had occurred an occupational asbestos exposure, which is up to now unknown and isn't due only to the use of sewing or ironing machines. The lung asbestos fibers burden analysis is confirmed to be a decisive factor in the assessment of mesothelioma cases with 'unknown' exposure.}, } @article {pmid28438787, year = {2017}, author = {Pira, E and Romano, C and Donato, F and Pelucchi, C and Vecchia, C and Boffetta, P}, title = {Mortality from cancer and other causes among Italian chrysotile asbestos miners.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {8}, pages = {558-563}, doi = {10.1136/oemed-2016-103673}, pmid = {28438787}, issn = {1470-7926}, mesh = {Aged ; Aged, 80 and over ; Asbestos, Serpentine/*adverse effects ; Cause of Death ; Chronic Disease/mortality ; Cohort Studies ; Environmental Monitoring ; Humans ; Italy/epidemiology ; Lung Neoplasms/*mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Mining ; Mortality ; Neoplasms/mortality ; Occupational Diseases/*mortality ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*mortality ; Poisson Distribution ; }, abstract = {OBJECTIVE: To investigate the long-term mortality of a cohort of Italian asbestos miners.

METHODS: The cohort included 1056 men employed in a chrysotile mine between 1930 and 1990, who were followed up during 1946-2014, for a total of 37 471 person-years of observation. Expected deaths and SMRs were computed using national and local (after 1980, when available) reference.

RESULTS: A total of 294 (27.8%) subjects were alive and at the end of follow-up, 722 (68.4%) were dead and 40 (3.8%) were lost to follow-up. The SMR for overall mortality was 1.35 (95%CI 1.25 to 1.45). The SMR for pleural cancer, based on seven observed deaths, was 5.54 (95% CI 2.22 to 11.4) and related to time since first exposure, but not to duration of employment, cumulative exposure or time since last exposure. The SMR for lung cancer was 1.16 (95% CI 0.87 to 1.52; 53 observed deaths), with no excess among workers with cumulative exposure below 100 fibre/mL-years (SMR 0.82; 95% CI 0.44 to 1.40).

CONCLUSIONS: The update of the follow-up of this cohort confirmed an increased mortality from pleural cancer mortality in miners exposed to chrysotile and a lack of significant increase in lung cancer mortality.}, } @article {pmid28435764, year = {2017}, author = {Bazine, A and Fetohi, M and Namad, T and Benzekri, A and Zainoun, B and Tanz, R and Ichou, M}, title = {A Case of Well-Differentiated Papillary Mesothelioma of the Male Peritoneum: Successful Treatment by Systemic Chemotherapy.}, journal = {Cureus}, volume = {9}, number = {3}, pages = {e1104}, pmid = {28435764}, issn = {2168-8184}, abstract = {Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare subtype of epithelioid mesothelioma, which is usually seen in young women without a history of asbestos exposure, and generally, has an indolent course. The relative rarity of this neoplasm in males prompted us to report this case of a well-differentiated papillary mesothelioma of the peritoneum in a 36-year-old man. The patient, who had no history of asbestos exposure, presented with abdominal pain and ascites of unknown etiology. Computed tomography showed abundant ascites with nodules of the peritoneal cavity. Laparoscopic examination revealed a large number of white miliary nodules diffusely covering the peritoneum. Pathology revealed a diagnosis of well-differentiated papillary mesothelioma of the peritoneum, based on histomorphology and immunohistochemistry. The patient started chemotherapy with cisplatin and pemetrexed. After six cycles of chemotherapy, the effectiveness of this chemotherapy was checked by only the computed tomography. PET scan was not used because it is not routinely recommended in WDPMP. Few data are currently available in the literature regarding the performance of the PET scan in WDPMP. Nine months later, the patient was free of symptoms. Based on reviewing the literature and our observations in this case, consultation of other pathologists is highly recommended to discern WDPMP from other disseminated peritoneal diseases, in order to offer the most effective and safe therapeutic strategy. Chemotherapy should be strongly considered if the tumor is unresectable and accompanied by symptoms. Cisplatin and pemetrexed chemotherapy could be a promising therapeutic choice.}, } @article {pmid28412495, year = {2017}, author = {Liu, B and van Gerwen, M and Bonassi, S and Taioli, E and , }, title = {Epidemiology of Environmental Exposure and Malignant Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {7}, pages = {1031-1045}, doi = {10.1016/j.jtho.2017.04.002}, pmid = {28412495}, issn = {1556-1380}, mesh = {Asbestos/*adverse effects ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*epidemiology/pathology ; Male ; Mesothelioma/*epidemiology/pathology ; }, abstract = {Although the association between exposure to asbestos and malignant mesothelioma (particularly malignant pleural mesothelioma) has been well established, the health impact of environmental exposure (EE) to asbestos has been less studied. This review summarizes the most recent studies on the association between malignant mesothelioma and EE with asbestos to identify features associated with EE and quantify the association with malignant mesothelioma. There were 44 studies from 18 countries that met our selection criteria, with a considerable amount of heterogeneity in their study design, measures of exposure, and health outcomes. The male-to-female ratio was close to or less than 1 and generally lower than the ratio reported when both occupational and environmental exposures were considered. Although recent studies have continued to improve our understanding of environmental exposure to asbestos, challenges remain. We have highlighted a few new research directions, such as a need for reliable matrices to identify common and less recognized types of EE, asbestos biomarker studies specifically focusing on EE, and research on populations and geographic areas that have not been previously studied.}, } @article {pmid28409856, year = {2017}, author = {Mensi, C and Ciullo, F and Barbieri, GP and Riboldi, L and Somigliana, A and Rasperini, G and Pesatori, AC and Consonni, D}, title = {Pleural malignant mesothelioma in dental laboratory technicians: A case series.}, journal = {American journal of industrial medicine}, volume = {60}, number = {5}, pages = {443-448}, doi = {10.1002/ajim.22716}, pmid = {28409856}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*adverse effects ; Dental Casting Technique ; Dentistry ; Female ; Humans ; Italy ; Laboratory Personnel ; Lung Neoplasms/*chemically induced/diagnostic imaging ; Male ; Mesothelioma/*chemically induced/diagnostic imaging ; Middle Aged ; Occupational Diseases/*chemically induced/diagnostic imaging ; Occupational Exposure/*adverse effects ; Registries ; Surveys and Questionnaires ; }, abstract = {Asbestos was used in dentistry as a binder in periodontal dressings and as lining material for casting rings and crucible. However, until now, only one case of malignant mesothelioma with occupational exposure to asbestos in dental practice has been reported. We present 4 pleural mesotheliomas out of 5344 cases identified in Lombardy, Italy, in 2000-2014. Three men had been working as dental laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one woman had been helping her husband for 30 years in manufacturing dental prostheses. The men described the use of asbestos as a lining material for casting rings, while the woman was not able to confirm this use. We confirm the association of malignant mesothelioma with dental technician work. Dental technicians suffering from mesothelioma should be questioned about past occupational asbestos exposure.}, } @article {pmid28399779, year = {2017}, author = {Domen, A and De Laet, C and Vanderbruggen, W and Gielis, J and Hendriks, JM and Lauwers, P and Janssens, A and Hiddinga, B and Van Meerbeeck, JP and Van Schil, PE}, title = {Malignant pleural mesothelioma: single-institution experience of 101 patients over a 15-year period.}, journal = {Acta chirurgica Belgica}, volume = {117}, number = {3}, pages = {157-163}, doi = {10.1080/00015458.2016.1272253}, pmid = {28399779}, issn = {0001-5458}, mesh = {Adult ; Aged ; Aged, 80 and over ; Belgium ; Combined Modality Therapy ; Female ; Humans ; Lung Neoplasms/mortality/*pathology/therapy ; Male ; Mesothelioma/mortality/*pathology/therapy ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but aggressive neoplasm that typically originates from the mesothelial surfaces of the pleural cavity. Exposure to asbestos is the principal etiological agent of MPM. The disease is characterized by difficult stage classification and limited consensus on therapeutic approach. We have evaluated the experience with MPM in the Antwerp University Hospital over the past 15 years.

METHODS: A database was created with all patients diagnosed with or treated for a MPM between 2001 and 2015. A total of 101 patients were included on which different survival analyses were performed combined with a reproduction of demographic, clinical, histologic and therapeutic data, and these were compared to literature data.

RESULTS: Vast majority of our 101 patients were male (80%) with a median age of 66 years at diagnosis with predominantly epitheloid histology (81%). Overall median survival was 18.3 months and overall 1-, 2- and 5-year survival rates were 68%, 37% and 7%, respectively. Kaplan-Meier analysis showed a non-significant difference in survival between the several best (b) TNM-stages (p = .356). A significant difference in survival was observed in patients undergoing surgery versus no surgery (p = .008), between the different histological types (p < .0001) and treatment with chemotherapy alone versus chemotherapy with surgery (p < .0001). Smoking at diagnosis and epitheloid histology have been identified as significant prognostic factors in the multivariate Cox regression model (HR 3.13 and 0.53, respectively).

CONCLUSION: Descriptive and survival analysis of our patient database confirmed the limitations of the current staging system and were concordant with literature regarding MPM.}, } @article {pmid28395242, year = {2017}, author = {Rapisarda, V and Caltabiano, R and Musumeci, G and Castrogiovanni, P and Ferrante, M and Ledda, C and Lombardo, C and Graziano, ACE and Cardile, V and Loreto, C}, title = {Analysis of fibulin-3 after exposure to asbestos-like fibers.}, journal = {Environmental research}, volume = {156}, number = {}, pages = {381-387}, doi = {10.1016/j.envres.2017.03.055}, pmid = {28395242}, issn = {1096-0953}, mesh = {Air Pollutants/toxicity ; Animals ; Asbestos, Amphibole/*toxicity ; Biomarkers/*blood ; Calcium-Binding Proteins/*genetics/metabolism ; Disease Models, Animal ; Female ; Fibroblasts/*drug effects ; Gene Expression/*drug effects ; Humans ; Immunohistochemistry ; Italy ; Lung/*drug effects ; Male ; Sheep ; }, abstract = {A significantly increased incidence of malignant mesothelioma in Biancavilla (Sicily, Italy) has been ascribed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. Fibulin-3 is a highly conserved glycoprotein proposed as a biomarker for malignant mesothelioma that belongs to the family of extracellular matrix proteins. Previous studies demonstrated high Fibulin-3 plasma levels in workers with pleural plaques exposed to fluoro-edenite. Therefore, in order to gain insight into the biomolecular mechanisms of fluoro-edenite toxicity, we performed the analysis of Fibulin-3 expression by immunohistochemistry in the lung samples derived from sheep belonging to the area of Biancavilla. Furthermore, an in vitro model of exposed fluoro-edenite fibroblasts was used to perform functional experiments to better understand the modulation of Fibulin-3 expression. The percentage of immunostained area by Fibulin-3 was very much higher in exposed lungs compared with non-exposed ones. The Fibulin-3 protein level was significantly expressed in primary human lung fibroblasts exposed to 50 and 100µg/ml of fluoro-edenite fibers for 72h, compared to the unexposed controls. The results from the present study further demonstrate the implication of Fibulin-3 during fluoro-edenite exposure. This would endorse our previous results regarding the use of Fibulin-3 as a possible screening biomarker for fluoro-edenite exposed individuals, thereby contributing to the monitoring of the population at risk. The present study also suggested that the Fibulin-3 overexpression may reflect a defensive response of the tissues after exogenous stimuli and may be implicated in cancer development, especially in the context of fluoro-edenite contamination. However, further studies are necessary in order to make Fibulin-3 a customized screening tool.}, } @article {pmid28387650, year = {2017}, author = {Creaney, J and Dick, IM and Leon, JS and Robinson, BW}, title = {A Proteomic Analysis of the Malignant Mesothelioma Secretome Using iTRAQ.}, journal = {Cancer genomics & proteomics}, volume = {14}, number = {2}, pages = {103-117}, pmid = {28387650}, issn = {1790-6245}, mesh = {Aged ; Cell Line, Tumor ; Cells, Cultured ; Cluster Analysis ; Exosomes/genetics/metabolism ; Female ; Gene Ontology ; Humans ; Isotope Labeling/*methods ; Lung Neoplasms/metabolism/pathology ; Male ; Mass Spectrometry/*methods ; Mesothelioma/metabolism/pathology ; Middle Aged ; Principal Component Analysis ; Proteome/classification/genetics/*metabolism ; Proteomics/*methods ; }, abstract = {Backgound/Aim: Malignant mesothelioma (MM) is an aggressive and fatal pleural cancer. The cell secretome offers information allowing insight into the pathogenesis of MM while offering the possibility to identify potential therapeutic targets and biomarkers. In the present study the secretome protein profile of MM cell lines was compared to normal mesothelial cells.

MATERIALS AND METHODS: Six MM cell lines were compared against three primary mesothelial cell culture preparations using iTRAQ® mass spectrometry.

RESULTS: MM cell lines more abundantly secreted exosome-associated proteins than mesothelial cells. MM cell secretomes were enriched in proteins that are involved in response to stress, carbon metabolism, biosynthesis of amino acids, antigen processing and presentation and protein processing in the endoplasmic reticulum.

CONCLUSION: The MM cell secretome is enriched in proteins that are likely to enhance its growth and response to stress and help it inhibit an adaptive immune response. These are potential targets for therapeutic and biomarker discovery.}, } @article {pmid28377727, year = {2017}, author = {Rouka, E and Vavougios, GD and Solenov, EI and Gourgoulianis, KI and Hatzoglou, C and Zarogiannis, SG}, title = {Transcriptomic Analysis of the Claudin Interactome in Malignant Pleural Mesothelioma: Evaluation of the Effect of Disease Phenotype, Asbestos Exposure, and CDKN2A Deletion Status.}, journal = {Frontiers in physiology}, volume = {8}, number = {}, pages = {156}, pmid = {28377727}, issn = {1664-042X}, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor primarily associated with asbestos exposure. Early detection of MPM is restricted by the long latency period until clinical presentation, the ineffectiveness of imaging techniques in early stage detection and the lack of non-invasive biomarkers with high sensitivity and specificity. In this study we used transcriptome data mining in order to determine which CLAUDIN (CLDN) genes are differentially expressed in MPM as compared to controls. Using the same approach we identified the interactome of the differentially expressed CLDN genes and assessed their expression profile. Subsequently, we evaluated the effect of tumor histology, asbestos exposure, CDKN2A deletion status, and gender on the gene expression level of the claudin interactome. We found that 5 out of 15 studied CLDNs (4, 5, 8, 10, 15) and 4 out of 27 available interactors (S100B, SHBG, CDH5, CXCL8) were differentially expressed in MPM specimens vs. healthy tissues. The genes encoding the CLDN-15 and S100B proteins present differences in their expression profile between the three histological subtypes of MPM. Moreover, CLDN-15 is significantly under-expressed in the cohort of patients with previous history of asbestos exposure. CLDN-15 was also found significantly underexpressed in patients lacking the CDKN2A gene. These results warrant the detailed in vitro investigation of the role of CDLN-15 in the pathobiology of MPM.}, } @article {pmid28361969, year = {2017}, author = {Tsuji, S and Washimi, K and Kageyama, T and Yamashita, M and Yoshihara, M and Matsuura, R and Yokose, T and Kameda, Y and Hayashi, H and Morohoshi, T and Tsuura, Y and Yusa, T and Sato, T and Togayachi, A and Narimatsu, H and Nagasaki, T and Nakamoto, K and Moriwaki, Y and Misawa, H and Hiroshima, K and Miyagi, Y and Imai, K}, title = {HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {45768}, pmid = {28361969}, issn = {2045-2322}, mesh = {Antibodies, Monoclonal/*immunology/metabolism ; Biomarkers, Tumor/immunology/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Glycosylation ; Humans ; Lung Neoplasms/*diagnosis/*immunology/metabolism ; Membrane Proteins/genetics/*immunology/metabolism ; Mesothelioma/*diagnosis/*immunology/metabolism ; Sensitivity and Specificity ; }, abstract = {The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM.}, } @article {pmid28351431, year = {2017}, author = {Mensi, C and Romano, A and Berti, A and Dore, R and Riboldi, L}, title = {A second case of pericardial mesothelioma mimicking systemic lupus erythematosus in the literature in over 30 years: a case report.}, journal = {Journal of medical case reports}, volume = {11}, number = {1}, pages = {85}, pmid = {28351431}, issn = {1752-1947}, mesh = {Diagnosis, Differential ; Echocardiography ; Fatal Outcome ; Female ; Heart Neoplasms/*diagnosis/pathology ; Humans ; Lupus Erythematosus, Systemic/*diagnosis ; Mesothelioma/complications/*diagnosis/pathology ; Middle Aged ; Pericardial Effusion/etiology/therapy ; Pericardiocentesis ; *Pericardium/diagnostic imaging ; Radiography ; Time Factors ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Mesothelioma is a rare neoplasm which commonly develops in the pleura of people exposed to asbestos. Pericardial mesothelioma accounts for only 0.7 % of all malignant mesotheliomas and it usually presents with pericardial effusion, mimicking serositis. To date, there are approximately 200 cases of pericardial mesothelioma described in the medical literature, and little knowledge exists about the systemic manifestations of this pathology. The first and only described case of pericardial mesothelioma with autoimmune features dates back to 1984 and, in our case report, we describe the second.

CASE PRESENTATION: We report a case of a 45-year-old white woman whose pericardial mesothelioma was initially misdiagnosed as pericardial involvement of an autoimmune disease (systemic lupus erythematosus). After several relapses of pericardial effusion, a computed tomography scan and a biopsy with histological analysis were performed revealing neoplastic growth.

CONCLUSIONS: We describe a rare case of pericardial mesothelioma in a patient with a clinical presentation compatible with lupus serositis. Clinicians should consider malignant mesothelioma in the differential diagnosis of pericardial effusion, especially when it is recurrent and not clearly explained by other causes. Cytological samples should always be obtained and, if imaging tools are suggestive for solid processes, histological confirmation is mandatory.}, } @article {pmid28348451, year = {2017}, author = {Ying, S and Jiang, Z and He, X and Yu, M and Chen, R and Chen, J and Ru, G and Chen, Y and Chen, W and Zhu, L and Li, T and Zhang, Y and Guo, X and Yin, X and Zhang, X and Lou, J}, title = {Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {5756102}, pmid = {28348451}, issn = {1875-8630}, mesh = {Aged ; Asbestosis/*blood ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Female ; HMGB1 Protein/*blood ; Humans ; Lung Neoplasms/*blood ; Male ; Matrix Metalloproteinase 2/blood ; Matrix Metalloproteinase 9/blood ; Mesothelioma/*blood ; Middle Aged ; }, abstract = {High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs.}, } @article {pmid28348450, year = {2017}, author = {Bonotti, A and Foddis, R and Landi, S and Melaiu, O and De Santi, C and Giusti, L and Donadio, E and Ciregia, F and Mazzoni, MR and Lucacchini, A and Bovenzi, M and Comar, M and Pantani, E and Pistelli, A and Cristaudo, A}, title = {A Novel Panel of Serum Biomarkers for MPM Diagnosis.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {3510984}, pmid = {28348450}, issn = {1875-8630}, mesh = {Aged ; Biomarkers, Tumor/*blood ; Blood Proteins/metabolism ; Case-Control Studies ; Female ; Humans ; Lung Neoplasms/*blood ; Male ; Mesothelioma/*blood ; Middle Aged ; Proteome/metabolism ; }, abstract = {Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.}, } @article {pmid28344849, year = {2017}, author = {Choi, S and Kang, D and Park, D and Lee, H and Choi, B}, title = {Developing Asbestos Job Exposure Matrix Using Occupation and Industry Specific Exposure Data (1984-2008) in Republic of Korea.}, journal = {Safety and health at work}, volume = {8}, number = {1}, pages = {105-115}, pmid = {28344849}, issn = {2093-7911}, abstract = {BACKGROUND: The goal of this study is to develop a general population job-exposure matrix (GPJEM) on asbestos to estimate occupational asbestos exposure levels in the Republic of Korea.

METHODS: Three Korean domestic quantitative exposure datasets collected from 1984 to 2008 were used to build the GPJEM. Exposure groups in collected data were reclassified based on the current Korean Standard Industrial Classification (9th edition) and the Korean Standard Classification of Occupations code (6th edition) that is in accordance to international standards. All of the exposure levels were expressed by weighted arithmetic mean (WAM) and minimum and maximum concentrations.

RESULTS: Based on the established GPJEM, the 112 exposure groups could be reclassified into 86 industries and 74 occupations. In the 1980s, the highest exposure levels were estimated in "knitting and weaving machine operators" with a WAM concentration of 7.48 fibers/mL (f/mL); in the 1990s, "plastic products production machine operators" with 5.12 f/mL, and in the 2000s "detergents production machine operators" handling talc containing asbestos with 2.45 f/mL. Of the 112 exposure groups, 44 groups had higher WAM concentrations than the Korean occupational exposure limit of 0.1 f/mL.

CONCLUSION: The newly constructed GPJEM which is generated from actual domestic quantitative exposure data could be useful in evaluating historical exposure levels to asbestos and could contribute to improved prediction of asbestos-related diseases among Koreans.}, } @article {pmid28343162, year = {2017}, author = {De Santi, C and Pucci, P and Bonotti, A and Melaiu, O and Cipollini, M and Silvestri, R and Vymetalkova, V and Barone, E and Paolicchi, E and Corrado, A and Lepori, I and Dell'Anno, I and Pellè, L and Vodicka, P and Mutti, L and Foddis, R and Cristaudo, A and Gemignani, F and Landi, S}, title = {Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {6}, pages = {456-463}, doi = {10.1136/oemed-2016-104024}, pmid = {28343162}, issn = {1470-7926}, mesh = {Aged ; Alleles ; Analysis of Variance ; Asbestos/adverse effects ; Biomarkers, Tumor/blood/*genetics ; Female ; GPI-Linked Proteins/*blood/*genetics ; Genotype ; Humans ; Italy ; Luciferases ; Lung Neoplasms/blood/*diagnosis/*genetics ; Male ; Mesothelioma/blood/*diagnosis/*genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a promising diagnostic biomarker for malignant pleural mesothelioma (MPM), but various confounders hinder its usefulness in surveillance programmes. We previously showed that a single nucleotide polymorphism (SNP) within the 3'untranslated region (3'UTR) of the mesothelin (MSLN) gene could affect the levels of SMRP.

OBJECTIVES: To focus on SNPs located within MSLN promoter as possible critical genetic variables in determining SMRP levels.

METHODS: The association between SMRP and SNPs was tested in 689 non-MPM subjects and 70 patients with MPM. Reporter plasmids carrying the four most common haplotypes were compared in a dual luciferase assay, and in silico analyses were performed to investigate the putative biological role of the SNPs.

RESULTS: We found a strong association between serum SMRP and variant alleles of rs3764247, rs3764246 (in strong linkage disequilibrium with rs2235504) and rs2235503 in non-MPM subjects. Inclusion of the genotype information led to an increase in SMRP specificity from 79.9% to 85.5%. Although not statistically significant, the group with MPM showed the same trend of association. According to the in vitro luciferase study, rs3764247 itself had a functional role. In silico approaches showed that the binding sites for transcription factors such as Staf and ZNF143 could be affected by this SNP. The other SNPs were shown to interact with each other in a more complex way.

CONCLUSIONS: These data support the suggestion that SMRP performance is affected by individual (ie, genetic) variables and that MSLN expression is influenced by SNPs located within the promoter regulatory region.}, } @article {pmid28337371, year = {2017}, author = {Huang, L and Cai, M and Zhang, X and Wang, F and Chen, L and Xu, M and Yang, K and Chen, Z and Wang, X and Fu, L}, title = {Combinational therapy of crizotinib and afatinib for malignant pleural mesothelioma.}, journal = {American journal of cancer research}, volume = {7}, number = {2}, pages = {203-217}, pmid = {28337371}, issn = {2156-6976}, abstract = {Malignant pleural mesothelioma (MPM) is a relative rare but highly aggressive neoplasm which is associated with asbestos exposure in most patients. The majority of patients are diagnosed in advanced stages so patients neither benefit from chemotherapy (e.g. pemetrexed-platinum combination) nor from surgery. It has been reported that cellular-mesenchymal to epithelial transition factor (MET) and epidermal growth factor receptor (EGFR) were critical for MPM cell proliferation. Moreover, targeting MET and EGFR drugs have gained promising results on anti-tumor therapy. Here, a striking difference in overall survival was observed between the MET and EGFR co-expression group (median survival time = 13.5 months) and non-co-expression group (median survival time = 20.5 months). In addition, treatment with combination of crizotinib and afatinib showed stronger inhibition on cell proliferation of MPM than the treatment by either one in vitro and in vivo. In conclusion, our data illustrated that crizotinib combined with afatinib may be a potentially effective strategy for treating MPM patients with over-expression of MET and EGFR.}, } @article {pmid28335760, year = {2017}, author = {Ak, G and Tada, Y and Shimada, H and Metintas, S and Ito, M and Hiroshima, K and Tagawa, M and Metintas, M}, title = {Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin.}, journal = {BMC cancer}, volume = {17}, number = {1}, pages = {212}, pmid = {28335760}, issn = {1471-2407}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*blood ; Cohort Studies ; Cytokines/*blood ; Female ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/*blood/diagnosis/*epidemiology ; Male ; Mesothelioma/*blood/diagnosis/*epidemiology ; Middle Aged ; Midkine ; Prognosis ; ROC Curve ; Turkey/epidemiology ; }, abstract = {BACKGROUND: We evaluated possible diagnostic and prognostic values of serum midkine in malignant pleural mesothelioma in comparison with those of serum mesothelin, a well-established diagnostic biomarker.

METHODS: Serum mesothelin and midkine levels were determined with an enzyme-linked immunosorbent assay. We examined specimens from 95 Turkish cases with malignant pleural mesothelioma, 56 metastatic cancers to pleura, 27 other types of benign pleural diseases and 20 benign asbestos pleurisy. The cut-off values were 1.5 nmol/L for mesothelin and 421 pg/mL for midkine.

RESULTS: Sensitivity and specificity of mesothelin were 51.6 and 71.4%, 51.6 and 85.2%, and 51.6 and 85% for differentiating mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Sensitivity and specificity of midkine were 61.1 and 41.1%, 61.1 and 48.1%, and 61.1 and 75% to distinguish mesothelioma from metastatic cancers to pleura, other benign pleural diseases and benign asbestos pleurisy, respectively. Combination of both biomarkers did not improve the differential diagnostic efficacy. Mesothelin levels were elevated in the epitheloid type and in the advanced cases, but were not related to the prognosis. In contrast, elevated baseline levels of midkine were independently associated with a poor prognosis of mesothelioma patients after adjusting for the stage, the histological subtypes and treatment schedules (HR = 1.84; 95% CI: 1.09-3.09) (p = 0.022).

CONCLUSIONS: Serum mesothelin showed moderate sensitivity and high specificity to differentiate malignant pleural mesothelioma from metastatic malignancy to pleura and from benign pleural diseases. In contrast, midkine was a useful marker for predicting prognosis of mesothelioma patients.}, } @article {pmid28322788, year = {2017}, author = {Raiko, I and Rihs, HP and Gleichenhagen, J and Sander, I and Kollmeier, J and Lehnert, M and Brüning, T and Johnen, G}, title = {A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma.}, journal = {Biochemical and biophysical research communications}, volume = {486}, number = {2}, pages = {526-532}, doi = {10.1016/j.bbrc.2017.03.077}, pmid = {28322788}, issn = {1090-2104}, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Antibodies/chemistry/isolation & purification ; Area Under Curve ; Biomarkers, Tumor/*blood/immunology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay/*methods ; Escherichia coli/genetics/metabolism ; Female ; GPI-Linked Proteins/*blood/immunology ; HeLa Cells ; Humans ; Lung Neoplasms/blood/*diagnosis/immunology/pathology ; Male ; Mesothelioma/blood/*diagnosis/immunology/pathology ; Middle Aged ; Peptides/administration & dosage/*immunology/metabolism ; ROC Curve ; Rabbits ; Recombinant Proteins/administration & dosage/biosynthesis/immunology ; }, abstract = {Malignant mesothelioma (MM) is a fatal disease mostly associated with asbestos exposure and difficult to detect by non-invasive methods. This study aimed to use recombinant fragments of the megakaryocyte potentiating factor (MPF) for the development of cost-effective MPF ELISAs. Three polypeptides spanning the MPF region (MPF1-148, MPF 34-288, MPF/MSLN254-400) were produced in E.coli as maltose-binding protein hybrids. After isolation, Factor Xa digest, and purification, the polypeptides were used for the generation of rabbit antibodies and development of ELISAs. Forty-one MM patients with known histological subtype before tumor-specific treatment and 70 asbestos-exposed individuals free of any cancer were matched according to age, gender, and smoking. Plasma of all subjects was tested with the three newly developed polyclonal antibody-based ELISAs and a commercial mesothelin assay (MESOMARK™). The latter differentiated patients (median concentration 1.95 nM) from controls (median 1.07 nM, p < 0.0001) and showed an area under curve (AUC) of 0.77 in receiver operating characteristics (ROC) analysis. Of the MPF variants, exclusively the ELISA based on antibodies against the MPF34-288 fragment displayed significantly (p = 0.0002) higher values in patients than in controls (median 1.61 nM versus 0.88 nM; AUC = 0.72). The combination of the MPF34-288 and mesothelin displayed an improved ROC performance (AUC = 0.80). The MPF34-288 ELISA could be a cost-effective and minimal-invasive contribution to support a diagnosis of mesothelioma, especially in regions with a limited medical care.}, } @article {pmid28321148, year = {2017}, author = {Weber, DG and Gawrych, K and Casjens, S and Brik, A and Lehnert, M and Taeger, D and Pesch, B and Kollmeier, J and Bauer, TT and Johnen, G and Brüning, T}, title = {Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma.}, journal = {Disease markers}, volume = {2017}, number = {}, pages = {9280170}, pmid = {28321148}, issn = {1875-8630}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/blood/*genetics ; Early Detection of Cancer ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/*diagnosis/genetics ; Male ; Mesothelioma/*diagnosis/genetics ; MicroRNAs/*blood ; Middle Aged ; Oligonucleotide Array Sequence Analysis/*methods ; Sensitivity and Specificity ; }, abstract = {The use of circulating microRNAs as biomarkers has opened new opportunities for diagnosis of cancer because microRNAs exhibit tumor-specific expression profiles. The aim of this study was the identification of circulating microRNAs in human plasma as potential biomarkers for the diagnosis of malignant mesothelioma. For discovery, TaqMan Low Density Array Human MicroRNA Cards were used to analyze 377 microRNAs in plasma samples from 21 mesothelioma patients and 21 asbestos-exposed controls. For verification, individual TaqMan microRNA assays were used for quantitative real-time PCR in plasma samples from 22 mesothelioma patients and 44 asbestos-exposed controls. The circulating miR-132-3p showed different expression levels between mesothelioma patients and asbestos-exposed controls. For discrimination, sensitivity of 86% and specificity of 61% were calculated. Circulating miR-132-3p in plasma was not affected by hemolysis and no impact of age or smoking status on miR-132-3p levels could be observed. For the combination of miR-132-3p with the previously described miR-126, sensitivity of 77% and specificity of 86% were calculated. The results of this study indicate that miR-132-3p might be a new promising diagnostic biomarker for malignant mesothelioma. It is indicated that the combination of miR-132-3p with other individual biomarkers improves the biomarker performance.}, } @article {pmid28279517, year = {2017}, author = {Diego Roza, C and Cruz Carmona, MJ and Fernández Álvarez, R and Ferrer Sancho, J and Marín Martínez, B and Martínez González, C and Rodríguez Portal, JA and Romero Valero, F and Villena Garrido, V}, title = {Recommendations for the Diagnosis and Management of Asbestos-Related Pleural and Pulmonary Disease.}, journal = {Archivos de bronconeumologia}, volume = {53}, number = {8}, pages = {437-442}, doi = {10.1016/j.arbres.2016.12.014}, pmid = {28279517}, issn = {1579-2129}, mesh = {Asbestos/classification/toxicity ; Asbestosis/*diagnosis/diagnostic imaging/prevention & control/*therapy ; Biomarkers, Tumor ; Carcinoma, Bronchogenic/diagnosis/etiology/therapy ; Humans ; Lung Neoplasms/diagnosis/etiology/therapy ; Mass Screening ; Mesothelioma/diagnosis/etiology/therapy ; Mineral Fibers/analysis/toxicity ; Occupational Exposure ; Occupational Health/legislation & jurisprudence ; Pleural Diseases/diagnosis/diagnostic imaging/therapy ; Pleural Neoplasms/diagnosis/etiology/therapy ; Positron Emission Tomography Computed Tomography ; Respiratory Function Tests ; Smoking/epidemiology ; Spain ; }, abstract = {Asbestos is the term used for a set of mineral silicates that tend to break up into fibers. Its use has been associated with numerous diseases affecting the lung and pleura in particular, all of which are characterized by their long period of latency. Asbestos, moreover, has been recognized by the WHO as a Group IA carcinogen since 1987 and its use was banned in Spain in 2002. The publication in 2013 of the 3rd edition of the specific asbestos health monitoring protocol, together with the development of new diagnostic techniques, prompted the SEPAR EROM group to sponsor publication of guidelines, which review the clinical, radiological and functional aspects of the different asbestos-related diseases. Recommendations have also been made for the diagnosis and follow-up of exposed patients. These recommendations were drawn up in accordance with the GRADE classification system.}, } @article {pmid28272659, year = {2018}, author = {Bianchi, C and Bianchi, T}, title = {Non-Hodgkin Lymphoma and Pleural Mesothelioma in a Person Exposed to Asbestos.}, journal = {Turk patoloji dergisi}, volume = {34}, number = {2}, pages = {190-193}, doi = {10.5146/tjpath.2015.01332}, pmid = {28272659}, issn = {1309-5730}, mesh = {Aged ; Asbestos/*adverse effects ; Female ; Humans ; Lung Neoplasms/etiology/*pathology ; Lymphoma, Non-Hodgkin/etiology/*pathology ; Mesothelioma/etiology/*pathology ; Neoplasms, Multiple Primary/*etiology/pathology ; Occupational Exposure/adverse effects ; Pleural Neoplasms/etiology/*pathology ; }, abstract = {Non-Hodgkin lymphoma and pleural mesothelioma may co-exist in the same patient. A large cell non-Hodgkin lymphoma of the inguinal lymph nodes was diagnosed in a 73-year-old woman. The patient was treated by chemotherapy. She did not receive radiotherapy. The patient had been exposed to asbestos having worked in a cotton mill and in a distillery. Four years after the diagnosis of lymphoma, she presented with a left pleural effusion. Large biopsies of the pleura showed a malignant mesothelioma, biphasic type, and pleural plaques. Epidemiological studies about the asbestos-lymphoma relationship gave conflicting results. The lymphoma-mesothelioma association is not exceptional, and suggests that asbestos plays a role in the etiology of both malignancies.}, } @article {pmid28253224, year = {2017}, author = {Mazurek, JM and Syamlal, G and Wood, JM and Hendricks, SA and Weston, A}, title = {Malignant Mesothelioma Mortality - United States, 1999-2015.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {66}, number = {8}, pages = {214-218}, pmid = {28253224}, issn = {1545-861X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Cause of Death ; Female ; Humans ; Inhalation Exposure/adverse effects ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Mineral Fibers/adverse effects ; Occupational Diseases/etiology/mortality ; Occupational Exposure/adverse effects ; United States/epidemiology ; }, abstract = {Malignant mesothelioma is a neoplasm associated with occupational and environmental inhalation exposure to asbestos* fibers and other elongate mineral particles (EMPs) (1-3). Patients have a median survival of approximately 1 year from the time of diagnosis (1). The latency period from first causative exposure to malignant mesothelioma development typically ranges from 20 to 40 years but can be as long as 71 years (2,3). Hazardous occupational exposures to asbestos fibers and other EMPs have occurred in a variety of industrial operations, including mining and milling, manufacturing, shipbuilding and repair, and construction (3). Current exposures to commercial asbestos in the United States occur predominantly during maintenance operations and remediation of older buildings containing asbestos (3,4). To update information on malignant mesothelioma mortality (5), CDC analyzed annual multiple cause-of-death records† for 1999-2015, the most recent years for which complete data are available. During 1999-2015, a total of 45,221 deaths with malignant mesothelioma mentioned on the death certificate as the underlying or contributing cause of death were reported in the United States, increasing from 2,479 deaths in 1999 to 2,597 in 2015 (in the same time period the age-adjusted death rates§ decreased from 13.96 per million in 1999 to 10.93 in 2015). Malignant mesothelioma deaths increased for persons aged ≥85 years, both sexes, persons of white, black, and Asian or Pacific Islander race, and all ethnic groups. Despite regulatory actions and the decline in use of asbestos the annual number of malignant mesothelioma deaths remains substantial. The continuing occurrence of malignant mesothelioma deaths underscores the need for maintaining measures to prevent exposure to asbestos fibers and other causative EMPs and for ongoing surveillance to monitor temporal trends.}, } @article {pmid28244608, year = {2017}, author = {Markowitz, SB and Moline, JM}, title = {Malignant mesothelioma due to asbestos exposure in dental tape.}, journal = {American journal of industrial medicine}, volume = {60}, number = {5}, pages = {437-442}, doi = {10.1002/ajim.22696}, pmid = {28244608}, issn = {1097-0274}, mesh = {Aged ; Asbestos/*adverse effects ; Dental Casting Technique/adverse effects ; Dentists ; Female ; Humans ; Lung Neoplasms/*chemically induced/diagnostic imaging ; Male ; Mesothelioma/*chemically induced/diagnostic imaging ; Middle Aged ; Occupational Diseases/*chemically induced ; Occupational Exposure/*adverse effects ; United States ; }, abstract = {Although most cases of malignant mesothelioma of the pleura are caused by one or more readily recognized sources of exposure to asbestos, cases of the disease with more occult exposure occur, especially since asbestos has been used in over 3,000 products. Dental lining tape contained asbestos from the 1930s until at least the 1970s and was used in the lost wax method of casting crowns, bridges, and other metal dental prosthetic devices. We report six cases of pathology-verified malignant mesothelioma, mostly among dentists, following exposure to airborne dust from asbestos dental tape, which resulted in asbestos tort litigation. According to evidence available at present, chrysotile asbestos was the type of asbestos used in dental tape in the past in the United States, and the described cases followed relatively brief and intermittent exposure to this type of asbestos. These cases underscore the need for comprehensive exposure histories to determine exposure scenarios. Am. J. Ind. Med. 60:437-442, 2017. © 2017 Wiley Periodicals, Inc.}, } @article {pmid28244606, year = {2017}, author = {Musk, B and Gordon, L and Alfonso, H and Reid, A and Olsen, N and Mina, R and Franklin, P and Peters, S and Brims, F and Hui, J and de Klerk, N}, title = {Risk factors for malignant mesothelioma in people with no known exposure to asbestos.}, journal = {American journal of industrial medicine}, volume = {60}, number = {5}, pages = {432-436}, doi = {10.1002/ajim.22695}, pmid = {28244606}, issn = {1097-0274}, mesh = {Asbestos/*adverse effects ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Humans ; Interviews as Topic ; Lung Neoplasms/epidemiology/*etiology ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/etiology ; Occupational Exposure/adverse effects ; Registries ; Risk Factors ; Smoking ; Western Australia/epidemiology ; }, abstract = {OBJECTIVES: Malignant mesothelioma (MM) is a rare and generally fatal cancer, usually caused by asbestos, although about 5-10% of cases report no asbestos exposure. This study aimed to identify sources whereby people in Western Australia (WA) may be unknowingly exposed to asbestos or to other exposures which may cause MM.

METHODS: Cases with no known asbestos exposure were selected from the WA Mesothelioma Register (WAMR). Matched controls were selected from hospital patients admitted for conditions unrelated to asbestos. Occupational histories were coded by an industrial hygienist. Data were analyzed using conditional logistic regression.

RESULTS: Thirty-eight MM participants and 134 controls were recruited. Risk of MM was increased (OR = 3.1, 95%CI 1.0-9.6) after no known, but likely, exposure to asbestos at work.

CONCLUSIONS: Because of its extensive use, few people in WA have never been exposed to asbestos. Unrecognized exposure may cause most MM cases initially regarded as "no exposure." Am. J. Ind. Med. 60:432-436, 2017. © 2017 Wiley Periodicals, Inc.}, } @article {pmid28241714, year = {2017}, author = {Ying, SB and Tong, Y and Jiang, ZQ}, title = {[Molecular mechanisms of HMGB1 extracellular secretion in asbestos-induced 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 = {35}, number = {1}, pages = {76-78}, doi = {10.3760/cma.j.issn.1001-9391.2017.01.022}, pmid = {28241714}, issn = {1001-9391}, } @article {pmid28241368, year = {2017}, author = {Lipp, MJ and Jusufi, MS and Backer, C and Feyerabend, B and Weilert, H and Oldhafer, KJ}, title = {[Benign multicystic peritoneal mesothelioma (BMPM) - a surprising differential diagnosis in case of an expected intraabdominal abscess formation].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {55}, number = {3}, pages = {267-273}, doi = {10.1055/s-0043-100104}, pmid = {28241368}, issn = {1439-7803}, mesh = {Abdominal Abscess/*diagnosis/*etiology/therapy ; Adult ; Diagnosis, Differential ; Female ; Humans ; Mesothelioma, Cystic/*complications/*diagnostic imaging/therapy ; Peritoneal Neoplasms/*complications/*diagnostic imaging/therapy ; }, abstract = {The benign multicystic peritoneal mesothelioma is a rare disease. Most frequently, young women in reproductive age are affected by this disease. Nevertheless, there are known cases of multicystic peritoneal mesothelioma in male patients. The pathogenesis remains uncertain. Whereas asbestos fibers can cause the development of malignant mesothelioma, the exposure to asbestos particles cannot induce this type of mesothelioma. An inflammatory genesis is discussed as well as the idea of a neoplastic development. Since a high rate of recurrence after surgery is observed, an aggressive surgical treatment is recommended. The complete resection of affected tissue is recently considered to be the therapy of choice. The combination of complete surgical tumor reduction with an intraperitoneal hyperthermic chemotherapy (HIPEC) seems to be promising. Although malignant transformation is detected very rarely a close follow up in centers with high surgical and oncological expertise is recommended.}, } @article {pmid28236494, year = {2017}, author = {Ferrer, J and Sampol, J and Cruz, MJ}, title = {Malignant pleural mesothelioma in a young adult with no known exposure to asbestos. Can asbestos exposure be truly ruled out?.}, journal = {Archivos de bronconeumologia}, volume = {53}, number = {8}, pages = {469}, doi = {10.1016/j.arbres.2017.01.007}, pmid = {28236494}, issn = {1579-2129}, mesh = {Adult ; *Asbestos ; Environmental Exposure ; Humans ; Lung Neoplasms ; *Mesothelioma ; Occupational Exposure ; Pleural Neoplasms ; Young Adult ; }, } @article {pmid28210162, year = {2016}, author = {Patel, SC and Dowell, JE}, title = {Modern management of malignant pleural mesothelioma.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {7}, number = {}, pages = {63-72}, pmid = {28210162}, issn = {1179-2728}, abstract = {Malignant pleural mesothelioma (MPM) is a deadly disease that produces a significant worldwide health care burden. The majority of cases are associated with prior asbestos exposure, but recent studies have identified a possible genetic predisposition in a minority of patients. Historically, obtaining a pathologic diagnosis of MPM was challenging, but with current pathological techniques, a secure diagnosis is possible in the majority of patients. Curative therapy for MPM remains elusive, and the primary treatment option for fit patients is platinum-based chemotherapy. Encouraging recent reports suggest that there may be a benefit to the addition of bevacizumab to standard chemotherapy as well as with the use of immune checkpoint inhibitors in MPM. Selected patients may be considered for aggressive surgical approaches, but there is considerable controversy regarding the true benefit of surgery and multimodality therapy in this disease.}, } @article {pmid28204714, year = {2017}, author = {Swiatkowska, B and Szeszenia-Dabrowska, N}, title = {Long-term epidemiological observation of asbestos-related diseases in Poland, 1970-2015.}, journal = {Occupational medicine (Oxford, England)}, volume = {67}, number = {3}, pages = {182-187}, doi = {10.1093/occmed/kqx011}, pmid = {28204714}, issn = {1471-8405}, mesh = {Asbestos/*toxicity ; Asbestosis/epidemiology/etiology ; Female ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Male ; Mesothelioma/chemically induced/epidemiology ; Occupational Diseases/chemically induced/*epidemiology ; Occupational Exposure ; Pleural Diseases/chemically induced/epidemiology ; Poland/epidemiology ; Population Surveillance ; }, abstract = {Background: Occupational exposure to asbestos constitutes a major public health concern. Despite this in many countries, data and registration systems for occupational asbestos-related diseases are non-existent or poorly developed.

Aims: To analyse the incidence of occupational asbestos-related diseases in Poland between the years 1970 and 2015, with particular emphasis on the periods after introduction of a ban on asbestos and following introduction of a surveillance programme.

Methods: Analysis based on all medically recognized cases, certified as occupational diseases and reported obligatorily from all over the country to the Central Register of Occupational Diseases.

Results: During the period 1970-2015, 4983 cases were reported as asbestos-related diseases. The most prevalent were asbestosis, lung cancer, diseases of pleura or pericardium and mesothelioma. A considerable increase in the number of such cases from the beginning of their registration until 2004 occurred after introduction of the Amiantus programme, a nationwide programme of periodic medical examinations for former asbestos workers.

Conclusions: Introduction of a medical surveillance programme improved case recognition and allowed a more reliable estimate of the number of reported asbestos-related diseases.}, } @article {pmid28197633, year = {2017}, author = {Mawas, AS and Amatya, VJ and Suzuki, R and Kushitani, K and Mohi El-Din, MM and Takeshima, Y}, title = {PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells.}, journal = {International journal of oncology}, volume = {50}, number = {3}, pages = {1029-1034}, doi = {10.3892/ijo.2017.3863}, pmid = {28197633}, issn = {1791-2423}, mesh = {Apoptosis/genetics ; Cell Line, Tumor ; Cell Movement/*genetics ; Cell Proliferation/*genetics ; Cell Survival/genetics ; G1 Phase Cell Cycle Checkpoints/*genetics ; Humans ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Neoplasm Invasiveness/genetics ; Proto-Oncogene Proteins c-pim-1/*genetics ; RNA Interference ; RNA, Small Interfering/genetics ; }, abstract = {Malignant mesothelioma is a major asbestos-related cancer with prolonged time lapse from the first exposure of asbestos to the development of mesothelioma. Most of mesothelioma patients show very poor prognosis, thus, an urgent improvement of its treatment is required by development of novel therapeutic strategies. RNA interference (RNAi) is a powerful tool in post-genomic research and cancer therapy through inhibition of gene expression. In the present study, we analyzed the function of PIM1 on mesothelioma cell lines with its knockdown by siRNA transfection. Here, we report that the downregulation of PIM1 led to suppression of cell proliferation by cell cycle arrest at G1 phase and suppression of cell invasion and migration. Considering the mesothelioma as rapidly growing invasive cancer, downregulation of PIM1 may have a potential role for therapeutic management of malignant mesothelioma.}, } @article {pmid28197626, year = {2017}, author = {Cregan, S and Breslin, M and Roche, G and Wennstedt, S and MacDonagh, L and Albadri, C and Gao, Y and O'Byrne, KJ and Cuffe, S and Finn, SP and Gray, SG}, title = {Kdm6a and Kdm6b: Altered expression in malignant pleural mesothelioma.}, journal = {International journal of oncology}, volume = {50}, number = {3}, pages = {1044-1052}, doi = {10.3892/ijo.2017.3870}, pmid = {28197626}, issn = {1791-2423}, mesh = {Apoptosis/drug effects ; Benzazepines/*therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects/genetics ; Cell Survival/drug effects ; Cisplatin/therapeutic use ; Cytokines/*biosynthesis ; Gene Expression Regulation, Neoplastic ; Histone Demethylases/*biosynthesis/genetics ; Humans ; Jumonji Domain-Containing Histone Demethylases/*biosynthesis/genetics ; Lung Neoplasms/*drug therapy/genetics/pathology ; Mesothelioma/*drug therapy/genetics/pathology ; Nuclear Proteins/*biosynthesis/genetics ; Pemetrexed/therapeutic use ; Pyrimidines/*therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes. As such these genes could potentially represent novel candidate targets for intervention in MPM. Using RT-PCR we examined the expression of Kdm6aA and Kdm6b in a panel of MPM cell lines and in a cohort of snap-frozen patient samples isolated at surgery comprising benign, epithelial, biphasic and sarcomatoid histologies. Both Kdm6a and Kdm6b were found to be significantly overexpressed in MPM at the mRNA level. However, tests examining if targeting therapeutically Kdm6a/b using a specific small molecule inhibitor (GSK-J4) was potentially useful for treating MPM, revealed that anti-proliferative activity was higher at lower drug concentrations in cell lines derived from normal mesothelial cells compared to those derived from malignant cells. Treatments with GSK-J4 were found to be associated with the induction of apoptosis and increased expression of pro-inflammatory cytokines. As such our results demonstrate that whilst members of the Kdm6 family are overexpressed in MPM they may not be suitable candidates for therapy and may elicit a cytokine storm.}, } @article {pmid28191281, year = {2016}, author = {Nabavi, N and Bennewith, KL and Churg, A and Wang, Y and Collins, CC and Mutti, L}, title = {Switching off malignant mesothelioma: exploiting the hypoxic microenvironment.}, journal = {Genes & cancer}, volume = {7}, number = {11-12}, pages = {340-354}, pmid = {28191281}, issn = {1947-6019}, abstract = {Malignant mesotheliomas are aggressive, asbestos-related cancers with poor patient prognosis, typically arising in the mesothelial surfaces of tissues in pleural and peritoneal cavity. The relative unspecific symptoms of mesotheliomas, misdiagnoses, and lack of precise targeted therapies call for a more critical assessment of this disease. In the present review, we categorize commonly identified genomic aberrations of mesotheliomas into their canonical pathways and discuss targeting these pathways in the context of tumor hypoxia, a hallmark of cancer known to render solid tumors more resistant to radiation and most chemo-therapy. We then explore the concept that the intrinsic hypoxic microenvironment of mesotheliomas can be Achilles' heel for targeted, multimodal therapeutic intervention.}, } @article {pmid28188891, year = {2017}, author = {Bonassi, S and Cellai, F and Munnia, A and Ugolini, D and Cristaudo, A and Neri, M and Milić, M and Bonotti, A and Giese, RW and Peluso, ME}, title = {3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers.}, journal = {Toxicology letters}, volume = {270}, number = {}, pages = {1-7}, doi = {10.1016/j.toxlet.2017.02.008}, pmid = {28188891}, issn = {1879-3169}, support = {P42 ES017198/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Asbestos/blood/*toxicity ; Biomarkers/blood ; Cross-Sectional Studies ; DNA Adducts/*blood ; Deoxyguanosine/blood/*toxicity ; Educational Status ; Humans ; Italy ; Lipid Peroxidation/drug effects ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Oxidative Stress/drug effects ; Purine Nucleosides/blood/*toxicity ; Reactive Oxygen Species/metabolism ; Smoking ; }, abstract = {Asbestos is the commercial name for a group of silicate minerals naturally occurring in the environment and widely used in the industry. Asbestos exposure has been associated with pulmonary fibrosis, mesothelioma, and malignancies, which may appear after a period of latency of 20-40 years. Mechanisms involved in the carcinogenic effects of asbestos are still not fully elucidated, although the oxidative stress theory suggests that phagocytic cells produce large amounts of reactive oxygen species, due to their inability to digest asbestos fiber. We have conducted a mechanistic study to evaluate the association between 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and lipid peroxidation, and asbestos exposure in the peripheral blood of 327 subjects living in Tuscany and Liguria, Italy, stratified by occupational exposure to asbestos. Adduct frequency was significantly greater into exposed subjects with respect to the controls. M1dG per 108 normal nucleotides were 4.0±0.5 (SE) in 156 asbestos workers, employed in mechanic, naval, petrochemical, building industries, and in pottery and ceramic plants, versus a value of 2.3±0.1 (SE) in 171 controls (p<0.001). After stratification for occupational history, the effects persisted in 54 current asbestos workers, mainly employed in building renovation industry (2.9±0.3 (SE)), and in 102 former asbestos workers (4.5±0.7 (SE)), with p-values of 0.033, and <0.001, respectively. A significant effect of smoking on heavy smokers was found (p=0.005). Our study gives additional support to the oxidative stress theory, where M1dG may reflect an additional potential mechanism of asbestos-induced toxicity.}, } @article {pmid28186988, year = {2017}, author = {Pellegrini, L and Xue, J and Larson, D and Pastorino, S and Jube, S and Forest, KH and Saad-Jube, ZS and Napolitano, A and Pagano, I and Negi, VS and Bianchi, ME and Morris, P and Pass, HI and Gaudino, G and Carbone, M and Yang, H}, title = {HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma.}, journal = {Oncotarget}, volume = {8}, number = {14}, pages = {22649-22661}, pmid = {28186988}, issn = {1949-2553}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Biomarkers, Tumor/*metabolism ; Cell Movement ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic/*drug effects ; HMGB1 Protein/*antagonists & inhibitors/metabolism ; Humans ; Mesothelioma/metabolism/pathology/*prevention & control ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Staging ; Prognosis ; Pyruvates/*pharmacology ; Signal Transduction ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Human malignant mesothelioma (MM) is an aggressive cancer linked to asbestos and erionite exposure. We previously reported that High-Mobility Group Box-1 protein (HMGB1), a prototypic damage-associated molecular pattern, drives MM development and sustains MM progression. Moreover, we demonstrated that targeting HMGB1 inhibited MM cell growth and motility in vitro, reduced tumor growth in vivo, and prolonged survival of MM-bearing mice. Ethyl pyruvate (EP), the ethyl ester of pyruvic acid, has been shown to be an effective HMGB1 inhibitor in inflammation-related diseases and several cancers. Here, we studied the effect of EP on the malignant phenotype of MM cells in tissue culture and on tumor growth in vivo using an orthotopic MM xenograft model. We found that EP impairs HMGB1 secretion by MM cells leading to reduced RAGE expression and NF-κB activation. As a consequence, EP impaired cell motility, cell proliferation, and anchorage-independent growth of MM cells. Moreover, EP reduced HMGB1 serum levels in mice and inhibited the growth of MM xenografts.Our results indicate that EP effectively hampers the malignant phenotype of MM, offering a novel potential therapeutic approach to patients afflicted with this dismal disease.}, } @article {pmid28168071, year = {2017}, author = {Ramirez Sevilla, C and Admella Salvador, C and Feliu Canaleta, J and Llopis Manzanera, J and Barranco Sanz, MA and Romero Martin, JA and Bernal Salguero, S}, title = {Two Case Reports of Benign Testicular Mesothelioma and Review of the Literature.}, journal = {Case reports in oncological medicine}, volume = {2017}, number = {}, pages = {5419635}, pmid = {28168071}, issn = {2090-6706}, abstract = {Mesothelioma is usually diagnosed in people over the age of 50 with large history of asbestos-related exposure. It is frequently located in pleural cavity, peritoneum, and pericardium. At the testicles the mesothelioma had been reported first in 1957 like a malignant non-germ-cells tumor. The objective is to present two case reports of benign testicular mesothelioma and review of the literature.}, } @article {pmid28166467, year = {2018}, author = {Rusiecki, J and Stewart, P and Lee, D and Alexander, M and Krstev, S and Silverman, D and Blair, A}, title = {Mortality among Coast Guard Shipyard workers: A retrospective cohort study of specific exposures.}, journal = {Archives of environmental & occupational health}, volume = {73}, number = {1}, pages = {4-18}, doi = {10.1080/19338244.2017.1289891}, pmid = {28166467}, issn = {1933-8244}, mesh = {Adult ; Baltimore/epidemiology ; Cohort Studies ; Construction Industry/*statistics & numerical data ; Environmental Pollutants/*toxicity ; Female ; Humans ; Lung Neoplasms/chemically induced/epidemiology/*mortality ; Male ; Mesothelioma/chemically induced/epidemiology/*mortality ; Middle Aged ; Occupational Diseases/chemically induced/epidemiology/*mortality ; *Occupational Exposure ; Respiratory Tract Neoplasms/chemically induced/epidemiology/*mortality ; Retrospective Studies ; *Ships ; Young Adult ; }, abstract = {In a previous analysis of a cohort of shipyard workers, we found excess mortality from all causes, lung cancer, and mesothelioma for longer work durations and in specific occupations. Here, we expand the previous analyses by evaluating mortality associated with 5 chemical exposures: asbestos, solvents, lead, oils/greases, and wood dust. Data were gathered retrospectively for 4,702 workers employed at the Coast Guard Shipyard, Baltimore, MD (1950-1964). The cohort was traced through 2001 for vital status. Associations between mortality and these 5 exposures were calculated via standardized mortality ratios (SMRs). We found all 5 substances to be independently associated with mortality from mesothelioma, cancer of the respiratory system, and lung cancer. Findings from efforts to evaluate solvents, lead, oils/greases, and wood dust in isolation of asbestos suggested that the excesses from these other exposures may be due to residual confounding from asbestos exposure.}, } @article {pmid28162043, year = {2017}, author = {Smargiassi, A and Pasciuto, G and Pedicelli, I and Lo Greco, E and Calvello, M and Inchingolo, R and Schifino, G and Capoluongo, P and Patriciello, P and Manno, M and Cirillo, A and Corbo, GM and Soldati, G and Iavicoli, I}, title = {Chest ultrasonography in health surveillance of asbestos-related lung diseases.}, journal = {Toxicology and industrial health}, volume = {33}, number = {6}, pages = {537-546}, doi = {10.1177/0748233716686916}, pmid = {28162043}, issn = {1477-0393}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/*diagnostic imaging ; Body Mass Index ; Cohort Studies ; Humans ; Lung/*diagnostic imaging/drug effects ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {OBJECTIVES: Exposure to asbestos fibers can lead to different lung diseases, such as pleural thickening and effusion, asbestosis, mesothelioma, and lung cancer. These diseases are expected to peak in the next few years. The aim of the study was to validate ultrasonography (US) as a diagnostic tool in the management of lung diseases in subjects with a history of occupational exposure to asbestos.

METHODS: Fifty-nine retired male workers previously exposed to asbestos were enrolled in the study. Chest US was performed in all the subjects. The US operator was blinded to earlier performed computed tomography (CT) scan reports and images. The sonographic pathological findings were pleural thickening (with or without calcifications), peripheral lung consolidation, and focal sonographic interstitial syndrome and diffuse pneumogenic sonographic interstitial syndrome (pulmonary asbestosis). Significant US findings were recorded, stored, and subsequently compared with CT scans.

RESULTS: With some patients falling into more than one category, on CT scan, pleural thickening was reported in 33 cases (56%, 26 with calcifications), focal interstitial peripheral alterations in 23 (39%), asbestosis in 6 (10%), and peripheral lung consolidation in 13 cases (22%). Comparing each pathological condition to CT scan reports, US findings had high levels of sensitivity, specificity, positive, and negative predictive values. US did not prove effective for the detection of central lung nodules or diaphragmatic pleural thickenings. Chest US was considered to be the best technique to detect minimal pleural effusions (six subjects, 10%).

CONCLUSIONS: Chest US might be considered an additional tool to follow up subjects occupationally exposed to asbestos who have already undergone CT scan examination and whose pathology is detectable by US as well.}, } @article {pmid28153512, year = {2017}, author = {Petrella, F and Coccè, V and Masia, C and Milani, M and Salè, EO and Alessandri, G and Parati, E and Sisto, F and Pentimalli, F and Brini, AT and Pessina, A and Spaggiari, L}, title = {Paclitaxel-releasing mesenchymal stromal cells inhibit in vitro proliferation of human mesothelioma cells.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {87}, number = {}, pages = {755-758}, doi = {10.1016/j.biopha.2017.01.118}, pmid = {28153512}, issn = {1950-6007}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Drug Delivery Systems/methods ; Drug Liberation ; Humans ; Lung Neoplasms/*drug therapy ; Mesenchymal Stem Cells/*drug effects ; Mesothelioma/*drug therapy ; Paclitaxel/*pharmacology ; Pemetrexed/pharmacology ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare fatal asbestos-related malignancy originating in the mesothelial cells of the pleura. A platinum-based doublet containing a third-generation antifolate is the front-line standard of care whilst there are no approved second-line treatments for MPM which remains a disease setting to test the efficacy of new therapeutic agents.

METHODS: Bone marrow mesenchymal stromal cells (BM-MSCs) were loaded with pemetrexed (PMX) and paclitaxel (PTX) according to a standardized procedure. Drug release by both PMX- and PTX-primed BM-MSCs (BM-MSCs/PMX and BM-MSCs/PTX) was tested on the in vitro proliferation of a panel of tumor cell lines including NCI-H28 mesothelioma.

RESULTS: The in vitro anticancer activity of pure PTX was significantly higher than that of PMX against all the cell lines tested (14.7 times higher than that of PMX against NCI-H28). Whereas BM-MSCs did not take up and release PMX in amounts effective on mesothelioma, PTX-loaded BM-MSCs dramatically inhibited mesothelioma proliferation.

CONCLUSIONS: PTX-primed mesenchymal stromal cells successfully inhibit the in vitro proliferation of human mesothelioma cells. Further studies and in vivo testing are required to confirm our preliminary in vitro results as a potential new mesothelioma therapy based on cell drug delivery.}, } @article {pmid28151477, year = {2017}, author = {Zonca, S and Pinton, G and Wang, Z and Soluri, MF and Tavian, D and Griffin, M and Sblattero, D and Moro, L}, title = {Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia.}, journal = {Cell death & disease}, volume = {8}, number = {2}, pages = {e2592}, pmid = {28151477}, issn = {2041-4889}, mesh = {Adaptation, Biological/genetics ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Cell Survival/*genetics ; GTP-Binding Proteins/*genetics ; Gene Expression Regulation, Neoplastic ; Gene Silencing/physiology ; Humans ; Hypoxia/*genetics/pathology ; Lung Neoplasms/*genetics/pathology ; Mesothelioma/*genetics/pathology ; Pleural Neoplasms/*genetics/pathology ; Transglutaminases/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment.}, } @article {pmid28139858, year = {2017}, author = {Linton, A and Soeberg, M and Broome, R and Kao, S and van Zandwijk, N}, title = {Geographic and socioeconomic factors in patients with malignant pleural mesothelioma in New South Wales and their impact upon clinical outcomes.}, journal = {Respirology (Carlton, Vic.)}, volume = {22}, number = {5}, pages = {978-985}, doi = {10.1111/resp.12981}, pmid = {28139858}, issn = {1440-1843}, mesh = {Adult ; Aged ; Female ; Humans ; Incidence ; Lung Neoplasms/*diagnosis/*epidemiology/therapy ; Male ; Mesothelioma/*diagnosis/*epidemiology/therapy ; Middle Aged ; Multivariate Analysis ; New South Wales/epidemiology ; Pleural Neoplasms/*diagnosis/*epidemiology/therapy ; Pneumonectomy ; Prognosis ; Proportional Hazards Models ; Registries ; Socioeconomic Factors ; }, abstract = {BACKGROUND AND OBJECTIVE: Whilst the impact of clinicopathological factors on the prognosis of malignant pleural mesothelioma (MPM) is well understood, socioeconomic and geographic factors have received less attention. We analysed the relationship between geographic and socioeconomic factors upon survival and treatment provision in a large series of patients with MPM.

METHODS: We assessed MPM patients awarded compensation between 2002 and 2009 with additional MPM incidence data from the New South Wales (NSW) Cancer Registry. The impact of geographic remoteness, distance from oncological multidisciplinary team (MDT) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) upon survival, clinical features and treatment received was analysed.

RESULTS: We identified 910 patients (67% residing in major cities; 92% <50 km from MDT). Median overall survival was 10.0 months. On multivariate analysis, age >70 (hazard ratio (HR) = 1.39), male gender (HR =1.36), non-epithelioid histological subtype (HR = 2.18) and IRSAD status by decreasing quintile (HR = 1.06) were independent prognostic factors. There was no significant advantage for patients residing in major cities (10.6 months vs 8.8 months; P = 0.162) or within 50 km of MDT (10.3 months vs 7.8 months; P = 0.539). Patient's geographic location and distance to MDT did not impact chemotherapy, adjuvant radiotherapy or extrapleural pneumonectomy provision. Socioeconomically disadvantaged patients were significantly less likely to receive chemotherapy (37.4% vs 54.8%; P = 0.001).

CONCLUSION: This study provides evidence for differences in the treatment and survival according to socioeconomic status for compensated MPM patients in NSW. Further research is warranted to seek additional explanations for the differences noted by comparing the treatments and outcomes of compensated and non-compensated MPM patients in NSW.}, } @article {pmid28133921, year = {2017}, author = {Gualtieri, AF}, title = {Sharing different perspectives to understand asbestos-induced carcinogenesis: A comment to Jiang et al. (2016).}, journal = {Cancer science}, volume = {108}, number = {1}, pages = {156-157}, pmid = {28133921}, issn = {1349-7006}, mesh = {*Asbestos ; *Carcinogenesis ; Humans ; Mesothelioma/chemically induced ; }, } @article {pmid28133000, year = {2017}, author = {Micolucci, L and Rippo, MR and Olivieri, F and Procopio, AD}, title = {Progress of research on microRNAs with diagnostic value in asbestos exposure: A call for method standardization.}, journal = {Bioscience trends}, volume = {11}, number = {1}, pages = {105-109}, doi = {10.5582/bst.2016.01249}, pmid = {28133000}, issn = {1881-7823}, mesh = {Asbestos/*adverse effects ; Biomarkers, Tumor/metabolism ; Environmental Exposure/*analysis ; Humans ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; MicroRNAs/*genetics/metabolism ; Reference Standards ; }, abstract = {Malignant mesothelioma (MM) is an insidious, lethal asbestos-related cancer that is poorly responsive to current treatments. Specific and sensitive biomarkers providing early MM diagnosis in exposed subjects, who are at high-risk of developing it, are sorely needed. MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs with a well-established diagnostic role in cancer and pollution exposure. In a recent systematic review and qualitative meta-analysis followed by a functional investigation, we examined all the available data on the miRNA biomarkers involved in asbestos exposure and MM pathways. This invited commentary aims to provide an insightful critique into the state of the art of the research into clinically relevant miRNA biomarkers, highlighting the strengths and weaknesses of current research efforts in this field. It also reviews the suggestions advanced to improve biomarker development productivity and the translation of research results into clinical practice, stressing that multicenter multidisciplinary studies adopting standardized methods and protocol sharing are the key to move from the workbench to the clinic.}, } @article {pmid28132991, year = {2016}, author = {Kaneko, M and Minamikawa, T and Taniguchi, H and Yamada, Y and Nakamura, J and Okihara, K and Nakauchi, H}, title = {MALIGNANT MESOTHELIOMA OF THE TUNICA VAGINALIS TESTIS: A CASE REPORT.}, journal = {Nihon Hinyokika Gakkai zasshi. The japanese journal of urology}, volume = {107}, number = {1}, pages = {44-47}, doi = {10.5980/jpnjurol.107.44}, pmid = {28132991}, issn = {0021-5287}, mesh = {Aged, 80 and over ; Cytodiagnosis ; Humans ; Lung Neoplasms/complications/*diagnosis/pathology/*surgery ; Magnetic Resonance Imaging ; Male ; Mesothelioma/complications/*diagnosis/pathology/*surgery ; Orchiectomy/methods ; Testicular Hydrocele/etiology/pathology/surgery ; Testicular Neoplasms/complications/*diagnosis/pathology/*surgery ; Ultrasonography ; }, abstract = {We report here a case of malignant mesothelioma of the tunica vaginalis testis. A 93-year-old man with no history of asbestos exposure complained of increase of right scrotum size with pain. Ultrasonography and magnetic resonance imaging revealed a right hydrocele testis. A cytologic examination of the hydrocele fluid demonstrated mesothelial cells but show less atypicality and lack of obvious malignant features (class IIIa). We performed right hydrocelectomy for hydrocele testis. The pathological diagnosis was epithelial type of malignant mesothelioma of the tunica vaginalis testis, therefore we performed radical orchidectomy with wide excision of hemi-scrotal wall. There is no evidence of recurrence after 6 months of follow up. Malignant mesothelioma of the tunica vaginalis is rare, and accurate preoperative diagnosis is difficult. When a rapid increasing hemorrhagic hydrocele testis or nodular masses of the tunica vaginalis was observed, malignant mesothelioma should be considered. Malignant mesothelioma is highly fatal disease. Even two stage operation, radical orchidectomy should be performed.}, } @article {pmid28123552, year = {2017}, author = {Nakamura, K and Nakayama, K and Nagaoka, R and Nishisako, K and Ishikawa, M and Katagiri, H and Ishibashi, T and Sato, E and Amano, C and Kyo, S}, title = {The diagnostic utility of PAX8 immunostaining of malignant peritoneal mesothelioma presenting as serous ovarian carcinoma: A single-center report of two cases.}, journal = {Oncology letters}, volume = {13}, number = {1}, pages = {263-266}, pmid = {28123552}, issn = {1792-1074}, abstract = {Malignant peritoneal mesotheliomas (MPMs) are rare and progressive tumors, which may present similarly to primary peritoneal carcinoma or ovarian carcinoma (OC). The current study reports two cases of MPM that initially presented with the features of OC, for which paired box 8 (PAX8) immunostaining was found to be useful for diagnosis. The two patients were women, aged 58 and 56 years, respectively. The primary presenting symptoms and clinical findings included prolonged abdominal pain, abdominal swelling and cough. The two cases were initially diagnosed as OC and were treated with primary debulking surgery. The patient in case 1 had no history of asbestos exposure, while the patient in case 2 did. Final diagnoses were determined based on histological and immunohistochemical results, which included negative PAX8 immunostaining, and which were consistent with MPM. The present cases demonstrated that PAX8 negativity may be a useful diagnostic biomarker for differentiating MPM from OC.}, } @article {pmid28105159, year = {2016}, author = {Fasano, M and Della Corte, CM and Vicidomini, G and Scotti, V and Rambaldi, PF and Fiorelli, A and Accardo, M and De Vita, F and Santini, M and Ciardiello, F and Morgillo, F}, title = {Small bowel metastasis from pancreatic cancer in a long-term survival patient with synchronous advanced malignant pleural mesothelioma: A case report and literature review.}, journal = {Oncology letters}, volume = {12}, number = {6}, pages = {4505-4509}, pmid = {28105159}, issn = {1792-1074}, abstract = {Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor that originates from the surface of the pleura. Approximately 70% of cases are associated with chronic asbestos exposure. MPM is regarded as an incurable disease, with a median survival of ~2 years following intensive multimodality treatment. Pancreatic cancer is a malignancy also associated with a poor prognosis, with only 2% of patients surviving for 5 years. The majority of patients with pancreatic cancer are diagnosed with an advanced stage of disease and experience a poor response to therapy. The development of synchronous MPM and other types of cancer is rare. The present study describes a patient with synchronous, biphasic MPM and pancreatic adenocarcinoma, who was treated with a multimodal therapeutic approach with stereotactic body radiation therapy. Due to a suspected diagnosis of 'acute abdomen', an emergency small intestine resection was performed and a subsequent diagnosis of moderately-differentiated adenocarcinoma was confirmed. During a further immunohistochemical examination, pathologists determined that the small bowel metastasis descended from pancreatic cancer. The onset of bowel metastasis is an event rarely associated with MPM, and has not been previously described in the literature for cases of pancreatic cancer. Therefore, to the best of our knowledge, the present study describes the first case of intestinal metastasis from pancreatic cancer in a long-term survival patient with biphasic MPM.}, } @article {pmid28095707, year = {2018}, author = {Si, S and Peters, S and Reid, A}, title = {Variations in mesothelioma mortality rates among migrants to Australia and Australian-born.}, journal = {Ethnicity & health}, volume = {23}, number = {5}, pages = {480-487}, doi = {10.1080/13557858.2017.1280138}, pmid = {28095707}, issn = {1465-3419}, mesh = {Adolescent ; Adult ; Africa/ethnology ; Aged ; Asia/ethnology ; Australia/epidemiology ; Emigrants and Immigrants/*statistics & numerical data ; Europe/ethnology ; Female ; Humans ; Lung Neoplasms/mortality ; Male ; Mesothelioma/*mortality ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Australia's use and consumption of asbestos occurred at the same time as its immigration boom. Our objective was to investigate mesothelioma death rates among migrants and Australian-born between 1981 and 2012.

METHODS: Australian national mesothelioma deaths from 1981 to 2002 and 2006 to 2012 together with national censuses from 1981 to 2011 were extracted and combined. Directly standardised rates and negative binomial regression were applied examining differences in mesothelioma death rates with regard to country of birth.

RESULTS: Migrants from the UK and Ireland, Italy and Germany had significantly higher mesothelioma death rates than Australian-born; lower rates were observed among migrants from other countries.

CONCLUSIONS: Our findings suggest there may have been differences in occupational health and safety between foreign and Australian-born. Because of changes in the demographics of migrants to Australia since the 1970s and changes in occupational circumstances over time, further comparisons of occupational-related health outcomes between foreign and Australian-born could identify potential occupational inequalities that may still exist today.}, } @article {pmid28090191, year = {2016}, author = {Sohn, EJ and Won, G and Lee, J and Yoon, SW and Lee, I and Kim, HJ and Kim, SH}, title = {Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell.}, journal = {International journal of biological sciences}, volume = {12}, number = {11}, pages = {1279-1288}, pmid = {28090191}, issn = {1449-2288}, mesh = {Apoptosis/drug effects ; Blotting, Western ; Cell Cycle/drug effects ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition/*drug effects ; Humans ; Lung Neoplasms/*metabolism/*pathology ; Mesothelioma/*metabolism/*pathology ; MicroRNAs/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Transfection ; Triterpenes/*pharmacology ; }, abstract = {Malignant pleural mesothelioma (MPN), which is caused by asbestos exposure, is one of aggressive lung tumors. In the present study, we elucidated the anti-tumor mechanism of ursolic acid in malignant mesotheliomas. Ursolic acid significantly exerted cytotoxicity in a time and dose dependent manner in H28, H2452 and MSTO-211H mesothelioma cells and inhibited cell proliferation by colony formation assay in a dose-dependent fashion. Also, ursolic acid treatment accumulated the sub-G1 population, attenuated the expression of procapase 9, cyclin D1, pAKT, p-glycogen synthase kinase 3-alpha/beta (pGSK3α/β), β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and also cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in mesothelioma cells. Furthermore, ursolic acid treatment blocked epithelial and mesenchymal transition (EMT) molecules by activating E-cadherin as an epithelial marker and attenuating Vimentin, and Twist as mesenchymal molecules. Interestingly, miRNA array revealed that 23 miRNAs (>2 folds) including let-7b and miRNA3613-5p, miRNA134 and miRNA196b were significantly upregulated while 33 miRNAs were downregulated in ursolic acid treated H2452 cells. Furthermore, overexpression of let 7b using let-7b mimics enhanced the antitumor effect of ursolic acid to attenuate the expression of procaspases 3, pro-PARP, pAKT, β-catenin and Twist and increase sub-G1 accumulation in H2452 mesothelioma cells. Overall, our findings suggest that ursolic acid induces apoptosis via inhibition of EMT and activation of let7b in mesothelioma cells as a potent chemotherapeutic agent for treatment of malignant mesotheliomas.}, } @article {pmid28079278, year = {2017}, author = {Egilman, D and Monárrez, R}, title = {Corporate corruption of science-Another asbestos example.}, journal = {American journal of industrial medicine}, volume = {60}, number = {2}, pages = {152-162}, doi = {10.1002/ajim.22686}, pmid = {28079278}, issn = {1097-0274}, mesh = {Asbestos/*toxicity ; Australia/epidemiology ; Automobiles ; Carcinogens/*toxicity ; Humans ; *Industry ; Mesothelioma/epidemiology/*etiology ; Occupational Diseases/epidemiology/*etiology ; Occupational Exposure/adverse effects ; Registries ; Research Design ; *Research Support as Topic ; }, abstract = {BACKGROUND: Kelsh et al. [2007]: Occup Med (Lond) 57:581-589 published a paper reanalyzing one of the few data sources publicly available on mesothelioma amongst brake workers, the Australian Mesothelioma Surveillance Registry (AMSR). This reanalysis was commissioned by lawyers representing the automobile manufacturing companies and did not align with an independent analysis published by Leigh and Driscoll [2003]: Occup Environ Health 9:206-217.

METHODS: We sought to reevaluate the AMSR data ourselves to understand how the company-sponsored research categorized the data.

RESULTS: In our re-analysis of the 78 brake-related folios in the AMSR, we determined that 57 were employed brake mechanics, 35 were employed brake mechanics with no other asbestos exposure besides brake work or repair, and 41 of these cases had no other asbestos exposure besides brake work or repair. Our classifications differed significantly from Kelsh et al.

CONCLUSIONS: We discuss how Kelsh et al. methodically reduced the relevant cases by following overly stringent criteria for inclusion. Am. J. Ind. Med. 60:152-162, 2017. © 2017 Wiley Periodicals, Inc.}, } @article {pmid28066892, year = {2017}, author = {Grosso, F and Croce, A and Trincheri, NF and Mariani, N and Libener, R and Degiovanni, D and Rinaudo, C}, title = {Asbestos fibres detected by scanning electron microscopy in the gallbladder of patients with malignant pleural mesothelioma (MPM).}, journal = {Journal of microscopy}, volume = {266}, number = {1}, pages = {48-54}, doi = {10.1111/jmi.12517}, pmid = {28066892}, issn = {1365-2818}, abstract = {Gallbladders from patients affected by both malignant pleural mesothelioma (MPM) and important gallbladder disorders were analyzed to verify the presence of asbestos fibres. Histological thin sections were analyzed by optical microscope and variable pressure scanning electron microscopy coupled with energy dispersive spectroscopy, allowing morphological and chemical characterization of each inorganic phase observed. Fibres of chrysotile and crocidolite, minerals regulated as asbestos, were identified. By immunohistochemical analysis, connective tissue was recognized as the incorporation site. These findings confirm that asbestos fibres can reach the gallbladders of patients with MPM, for whom the development of respiratory diseases confirms asbestos exposure.}, } @article {pmid28066660, year = {2016}, author = {Wang, XB and Yin, Y and Miao, Y and Eberhardt, R and Hou, G and Herth, FJ and Kang, J}, title = {Flex-rigid pleuroscopic biopsy with the SB knife Jr is a novel technique for diagnosis of malignant or benign fibrothorax.}, journal = {Journal of thoracic disease}, volume = {8}, number = {11}, pages = {E1555-E1559}, pmid = {28066660}, issn = {2072-1439}, abstract = {Diagnosing pleural effusion is challenging, especially in patients with malignant or benign fibrothorax, which is difficult to sample using standard flexible forceps (SFF) via flex-rigid pleuroscopy. An adequate sample is crucial for the differential diagnosis of malignant fibrothorax (malignant pleural mesothelioma, metastatic lung carcinoma, etc.) from benign fibrothorax (benign asbestos pleural disease, tuberculous pleuritis, etc.). Novel biopsy techniques are required in flex-rigid pleuroscopy to improve the sample size and quality. The SB knife Jr, which is a scissor forceps that uses a mono-pole high frequency, was developed to allow convenient and accurate resection of larger lesions during endoscopic dissection (ESD). Herein, we report two patients with fibrothorax who underwent a pleural biopsy using an SB knife Jr to investigate the potential use of this tool in flex-rigid pleuroscopy when pleural lesions are difficult to biopsy via SFF. The biopsies were successful, with sufficient size and quality for definitive diagnosis. We also successfully performed adhesiolysis with the SB knife Jr in one case, and adequate biopsies were conducted. No complications were observed. Electrosurgical biopsy with the SB knife Jr during flex-rigid pleuroscopy allowed us to obtain adequate samples for the diagnosis of malignant versus benign fibrothorax, which is usually not possible with SFF. The SB knife Jr also demonstrated a potential use for pleuropulmonary adhesions.}, } @article {pmid28056339, year = {2017}, author = {Thompson, JK and MacPherson, MB and Beuschel, SL and Shukla, A}, title = {Asbestos-Induced Mesothelial to Fibroblastic Transition Is Modulated by the Inflammasome.}, journal = {The American journal of pathology}, volume = {187}, number = {3}, pages = {665-678}, pmid = {28056339}, issn = {1525-2191}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Asbestos/*adverse effects ; Biomarkers/metabolism ; Caspase 1/metabolism ; Cell Line ; Cell Shape/genetics ; Epithelial Cells/metabolism/pathology ; Epithelium/metabolism/*pathology ; Fibroblasts/metabolism/*pathology ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Inflammasomes/*metabolism ; Interleukin-1beta/metabolism ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Peritoneum/metabolism/pathology ; Signal Transduction/genetics ; }, abstract = {Despite the causal relationship established between malignant mesothelioma (MM) and asbestos exposure, the exact mechanism by which asbestos induces this neoplasm and other asbestos-related diseases is still not well understood. MM is characterized by chronic inflammation, which is believed to play an intrinsic role in the origin of this disease. We recently found that asbestos activates the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in a protracted manner, leading to an up-regulation of IL-1β and IL-18 production in human mesothelial cells. Combined with biopersistence of asbestos fibers, we hypothesize that this creates an environment of chronic IL-1β signaling in human mesothelial cells, which may promote mesothelial to fibroblastic transition (MFT) in an NLRP3-dependent manner. Using a series of experiments, we found that asbestos induces a fibroblastic transition of mesothelial cells with a gain of mesenchymal markers (vimentin and N-cadherin), whereas epithelial markers, such as E-cadherin, are down-regulated. Use of siRNA against NLRP3, recombinant IL-1β, and IL-1 receptor antagonist confirmed the role of NLRP3 inflammasome-dependent IL-1β in the process. In vivo studies using wild-type and various inflammasome component knockout mice also revealed the process of asbestos-induced mesothelial to fibroblastic transition and its amelioration in caspase-1 knockout mice. Taken together, our data are the first to suggest that asbestos induces mesothelial to fibroblastic transition in an inflammasome-dependent manner.}, } @article {pmid28054314, year = {2017}, author = {Plönes, T and Fischer, M and Höhne, K and Sato, H and Müller-Quernheim, J and Zissel, G}, title = {Turning back the Wheel: Inducing Mesenchymal to Epithelial Transition via Wilms Tumor 1 Knockdown in Human Mesothelioma Cell Lines to Influence Proliferation, Invasiveness, and Chemotaxis.}, journal = {Pathology oncology research : POR}, volume = {23}, number = {4}, pages = {723-730}, pmid = {28054314}, issn = {1532-2807}, mesh = {Cell Line, Tumor ; Cell Proliferation/genetics ; Chemotaxis/genetics ; Drug Resistance, Neoplasm/genetics ; Gene Knockdown Techniques ; Humans ; Lung Neoplasms/*genetics/*pathology ; Mesothelioma/*genetics/*pathology ; Neoplasm Invasiveness/genetics ; Pleural Neoplasms/*genetics/*pathology ; WT1 Proteins/*genetics ; }, abstract = {Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from the surface of the pleura and is associated with a history of asbestos exposure. The tumor is characterized by a strong local invasiveness and a poor response to any single modality therapy. Therefore clinical outcome of patients with MPM is poor and median survival time of untreated patients with MPM is 7 months from initial diagnosis. The Wilms Tumor Protein 1 (WT1) is a transcription factor which is highly expressed by MPM and is involved in cellular development and survival. We evaluated the role of WT1 in two human MPM cell lines (MSTO and H2052) expressing high levels of WT1. We performed a knockdown of WT1 using siRNA. Knockdown of WT1 was confirmed by Westernblotting. After knockdown of WT1 we investigated the effect on proliferation, chemoresistance, chemotaxis and migration. We could demonstrate that knockdown of WT1 suppresses chemoresistance in both cell lines compared with control (scrambled siRNA). Additionally, WT1 knockdown reduces proliferation, chemotaxis and invasiveness of mesothelioma cell lines. WT1 reduces malignancy of malignant mesothelioma cell lines and might be a new molecular target in mesothelioma therapy. Further investigations are needed to discover the mechanisms of chemoresistance depending on WT1.}, } @article {pmid28051835, year = {2016}, author = {Fallahi, P and Ragusa, F}, title = {Mesothelioma and interferon-γ-dependent chemokine IP-10.}, journal = {La Clinica terapeutica}, volume = {167}, number = {6}, pages = {e192-e197}, pmid = {28051835}, issn = {1972-6007}, mesh = {Adult ; Animals ; Apoptosis/drug effects ; Asbestos/adverse effects ; Asbestosis/immunology ; CD8-Positive T-Lymphocytes ; Chemokine CXCL10/*metabolism ; Female ; Humans ; Interferon-gamma/metabolism ; Lung Neoplasms/*immunology ; Male ; Mesothelioma/*immunology ; Rats ; Receptors, CXCR3 ; }, abstract = {Recently it has been shown that interferon (IFN)-γ plays an important role in mesothelioma, mediated by the main IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ- induced protein 10 (IP-10). IP-10 is up-regulated in malignant mesothelioma (MM), suggesting a relationship with development of these tumors. Nanoparticles containing nickel, that increase the risk for pleural diseases, induced increased levels of IP-10 in rat pleural mesothelial cells. Chemokine (C-X-C motif) receptor (CXCR)3 expression in CD4(+) T cells from pleural plaques and MMs was significantly decreased compared with that from healthy donors suggesting that CXCR3, IFN-γ, and IP-10 may be candidates to detect and monitor disease status. In a patient with asbestos-related malignant pleural mesothelioma the oncolytic adenovirus (ONCOS-102) induced prominent infiltration of CD8(+) lymphocytes to tumor, marked induction of systemic antitumor CD8(+) T-cells and expression of IP-10. Furthermore, increased IP- 10 concentrations were observed in the sera of the asbestos-exposed workers and were associated with the severity of asbestos-related diseases. These findings suggest that IP-10 chemokine may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by nonmalignant asbestos-related diseases.}, } @article {pmid28050426, year = {2016}, author = {Batahar, SA and Ouradi, O and Elidrissi, S and Amro, L}, title = {Pleural Mesothelioma with No Asbestos Exposure: A Case Report.}, journal = {Journal of clinical and diagnostic research : JCDR}, volume = {10}, number = {11}, pages = {OD07-OD08}, pmid = {28050426}, issn = {2249-782X}, abstract = {Malignant Pleural Mesothelioma (MPM) is the primary malignant tumour of the pleura. It is highly aggressive and linked to the exposure to asbestos fibers. The prognosis of this cancer is bad with a median of survival around 12 months. The diagnosis of pleural mesothelioma is often done at an advanced stage of the disease because of the lack of specific clinical and radiological signs differentiating it from any malignant pleural effusion. The absence of an explicit asbestos exposure is another diagnosis problem. We report the case of a 60-year-old patient without any prior exposure to asbestos who presented for pleural effusion and a nodular thickening of the pleura on the CT scan. The diagnosis of MPM was confirmed after pathology study of the biopsies obtained by video assisted thoracoscopy.}, } @article {pmid28038708, year = {2017}, author = {Wu, D and Hiroshima, K and Yusa, T and Ozaki, D and Koh, E and Sekine, Y and Matsumoto, S and Nabeshima, K and Sato, A and Tsujimura, T and Yamakawa, H and Tada, Y and Shimada, H and Tagawa, M}, title = {Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma.}, journal = {Annals of diagnostic pathology}, volume = {26}, number = {}, pages = {31-37}, doi = {10.1016/j.anndiagpath.2016.10.010}, pmid = {28038708}, issn = {1532-8198}, mesh = {Aged ; Biomarkers, Tumor/analysis ; Cyclin-Dependent Kinase Inhibitor p18/*genetics ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry/methods ; In Situ Hybridization, Fluorescence/methods ; Male ; Mesothelioma/*diagnosis/*genetics ; Middle Aged ; Pleural Neoplasms/*diagnosis/genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.}, } @article {pmid28034829, year = {2017}, author = {Leblay, N and Leprêtre, F and Le Stang, N and Gautier-Stein, A and Villeneuve, L and Isaac, S and Maillet, D and Galateau-Sallé, F and Villenet, C and Sebda, S and Goracci, A and Byrnes, G and McKay, JD and Figeac, M and Glehen, O and Gilly, FN and Foll, M and Fernandez-Cuesta, L and Brevet, M}, title = {BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {4}, pages = {724-733}, doi = {10.1016/j.jtho.2016.12.019}, pmid = {28034829}, issn = {1556-1380}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers, Tumor/genetics/metabolism ; *DNA Copy Number Variations ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/genetics/metabolism/*pathology ; Male ; Mesothelioma/genetics/metabolism/*pathology ; Middle Aged ; *Mutation ; Neoplasm Staging ; Peritoneal Neoplasms/genetics/metabolism/*pathology ; Pleural Neoplasms/genetics/metabolism/*pathology ; Prognosis ; Survival Rate ; Tumor Suppressor Proteins/*genetics/*metabolism ; Ubiquitin Thiolesterase/*genetics/*metabolism ; Young Adult ; }, abstract = {INTRODUCTION: Malignant mesothelioma is a deadly disease that is strongly associated with asbestos exposure. Peritoneal mesotheliomas account for 10% of all the cases. BRCA1 associated protein 1 (BAP1) is a deubiquitinating hydrolase that plays a key role in various cellular processes. Germline and somatic inactivation of BRCA1 associated protein 1 gene (BAP1) is frequent in pleural mesothelioma; however, little is known about its status in peritoneal mesothelioma.

METHODS: Taking advantage of the extensive French National Network for the Diagnosis of Malignant Pleural Mesothelioma and Rare Peritoneal Tumors and the French National Network for the Treatment of Rare Peritoneal Surface Malignancies, we collected biological material and clinical and epidemiological data for 46 patients with peritoneal mesothelioma. The status of BAP1 was evaluated at the mutational and protein expression levels and combined with our previous data on copy number alterations assessed in the same samples.

RESULTS: We detected mutations in 32% of the malignant peritoneal mesotheliomas analyzed. In addition, we have previously reported that copy number losses occurred in 42% of the samples included in this series. Overall, 73% of the malignant peritoneal mesotheliomas analyzed carried at least one inactivated BAP1 allele, but only 57% had a complete loss of its protein nuclear expression. Better overall survival was observed for patients with BAP1 mutations (p = 0.04), protein expression loss (p = 0.016), or at least one of these alterations (p = 0.007) independently of tumor histological subtype, age, and sex.

CONCLUSIONS: As in pleural mesothelioma, inactivation of BAP1 is frequent in peritoneal mesotheliomas. We found that BAP1 protein nuclear expression is a good prognostic factor and a more reliable marker for the complete loss of BAP1 activity than mutation or copy number loss.}, } @article {pmid28026144, year = {2018}, author = {Paliogiannis, P and Putzu, C and Ginesu, GC and Cossu, ML and Feo, CF and Attene, F and Scognamillo, F and Nonnis, R and Cossu, A and Palmieri, G and Pirina, P and Fois, A}, title = {Deciduoid mesothelioma of the thorax: A comprehensive review of the scientific literature.}, journal = {The clinical respiratory journal}, volume = {12}, number = {3}, pages = {848-856}, doi = {10.1111/crj.12599}, pmid = {28026144}, issn = {1752-699X}, mesh = {Adolescent ; Adult ; Aged ; Asbestos/adverse effects ; Chest Pain/etiology ; Cough/etiology ; Deciduoma/*pathology ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/diagnostic imaging/metabolism/*pathology ; Male ; Mesothelioma/diagnostic imaging/metabolism/*pathology ; Middle Aged ; Pleura/diagnostic imaging/*pathology ; Pleural Neoplasms/diagnostic imaging/*pathology ; Prognosis ; Radiography, Thoracic/methods ; Thoracic Neoplasms/diagnostic imaging/pathology ; Tomography, X-Ray Computed/methods ; Weight Loss ; Young Adult ; }, abstract = {OBJECTIVE: Deciduoid mesothelioma is a rare variant of malignant epithelioid mesothelioma. It often involves the peritoneum, but also thoracic cases have been reported. The aim of the present review is to describe the demographic, clinical, radiological, and pathological features of such a rare variant of thoracic mesothelioma, and the state of the art regarding the therapeutic approaches currently available.

DATA SOURCE: English-language articles published from 1985 to June 2016, and related to thoracic deciduoid mesothelioma cases were retrieved using the Pubmed database.

STUDY SELECTION: The search terms were "mesothelioma," "thoracic mesothelioma," "epithelial mesothelioma," "pleural mesothelioma," and "deciduoid mesothelioma."

RESULTS: Forty-four cases included in 16 articles, published in the period under investigation, were analyzed in detail.

CONCLUSIONS: The mean age of the patients was 63 years, and the male to female ratio 1.7:1. Approximately 58% had exposure to asbestos, and 73% had a smoking history; familiarity was rarely reported. The most common anatomical site of origin was the right pleura, and the most frequent clinical manifestations were chest pain, dyspnea, cough, and weight loss. Thoracic X-ray and computed tomography were the imaging techniques most employed for diagnosis and surgical planning. The pathological diagnosis was obtained by examination of surgical or biopsy specimens in most cases. The best treatment strategy of deciduoid mesothelioma is a matter of debate; nevertheless a multidisciplinary approach is currently the best option for the choice of the adequate therapeutic scheme.}, } @article {pmid28025765, year = {2017}, author = {Lehnert, M and Kraywinkel, K and Heinze, E and Wiethege, T and Johnen, G and Fiebig, J and Brüning, T and Taeger, D}, title = {Incidence of malignant mesothelioma in Germany 2009-2013.}, journal = {Cancer causes & control : CCC}, volume = {28}, number = {2}, pages = {97-105}, doi = {10.1007/s10552-016-0838-y}, pmid = {28025765}, issn = {1573-7225}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/toxicity ; Female ; Germany/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Registries ; }, abstract = {PURPOSE: The malignant mesothelioma is a rare malignancy and mainly caused by occupational exposure to asbestos. German cancer registries are providing a national database to investigate temporal and regional patterns of mesothelioma incidence. These may be of interest for healthcare planning and for surveillance programs aiming at the formerly exposed workforce.

METHODS: We analyzed population-based incidence data of malignant mesothelioma by site, type, sex, age, as well as district and state of patient's residence. Age-standardized incidence rates (AIRs40+) were calculated according to the European standard population truncated to the age of 40 years and older. We present rates at national, state, and district level and trends of incidence of northern states of Germany.

RESULTS: In total, 7,547 malignant mesotheliomas were reported to German cancer registries diagnosed between 2009 and 2013-90% located to the pleura. On average, 1,198 men and 312 women were affected each year. We estimated AIR40+ of 4.77 in 100,000 German men and 0.98 in 100,000 German women. Regional clusters were predominantly located to the seaports of West Germany. The highest regional AIR40+ was 20 per 100,000 men. Corresponding rates in northeast Germany were between 2 and 4 per 100,000 men.

CONCLUSION: Regional clusters of high incidence indicate districts with former shipyards and steel industry, but predominantly in the western part of Germany. The West-to-East difference corresponds to patterns of mortality. Twenty years after banning asbestos in Germany, Bremen and Hamburg are presenting the highest mesothelioma incidence but show steadily decreasing trends.}, } @article {pmid28013367, year = {2017}, author = {MacPherson, M and Westbom, C and Kogan, H and Shukla, A}, title = {Actin polymerization plays a significant role in asbestos-induced inflammasome activation in mesothelial cells in vitro.}, journal = {Histochemistry and cell biology}, volume = {147}, number = {5}, pages = {595-604}, pmid = {28013367}, issn = {1432-119X}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; }, mesh = {Actins/antagonists & inhibitors/*metabolism ; Asbestos/*adverse effects/antagonists & inhibitors ; Cell Survival/drug effects ; Cells, Cultured ; Cytochalasin D/pharmacology ; Dose-Response Relationship, Drug ; Epithelial Cells/*drug effects/metabolism ; Humans ; Inflammasomes/*drug effects/metabolism ; Polymerization/drug effects ; Structure-Activity Relationship ; }, abstract = {Asbestos exposure leads to malignant mesothelioma (MM), a deadly neoplasm of mesothelial cells of various locations. Although there is no doubt about the role of asbestos in MM tumorigenesis, mechanisms are still not well explored. Recently, our group demonstrated that asbestos causes inflammasome priming and activation in mesothelial cells, which in part is dependent on oxidative stress. Our current study sheds light on yet another mechanism of inflammasome activation by asbestos. Here we show the role of actin polymerization in asbestos-induced activation of the nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. Using human mesothelial cells, we first demonstrate that asbestos and carbon nanotubes induced caspase-1 activation and high-mobility group box 1, interleukin 1 beta and interleukin 18 secretion was blocked by Cytochalasin D (Cyto D) an actin polymerization inhibitor. Next, to understand the mechanism, we assessed whether phagocytosis of fibers by mesothelial cells is affected by actin polymerization inhibition. Transmission electron microscopy showed the inhibition of fiber uptake by mesothelial cells in the presence of Cyto D. Furthermore, localization of components of the inflammasome, apoptotic speck-like protein containing a CARD domain (ASC) and NLRP3, to the perinuclear space in mitochondria or endoplasmic reticulum in response to fiber exposure was also interrupted in the presence of Cyto D. Taken together, our studies suggest that actin polymerization plays important roles in inflammasome activation by fibers via regulation of phagocytosis and/or spatial localization of inflammasome components.}, } @article {pmid28007630, year = {2017}, author = {Guo, Z and Carbone, M and Zhang, X and Su, D and Sun, W and Lou, J and Gao, Z and Shao, D and Chen, J and Zhang, G and Hu, J and Chen, K and Wang, F and Pass, HI and Yu, H and Napolitano, A and Yang, H and Mao, W}, title = {Improving the Accuracy of Mesothelioma Diagnosis in China.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {12}, number = {4}, pages = {714-723}, pmid = {28007630}, issn = {1556-1380}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adenocarcinoma/diagnosis/epidemiology ; Adult ; Aged ; Biomarkers, Tumor/analysis ; Carcinoma, Squamous Cell/diagnosis/epidemiology ; Case-Control Studies ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*diagnosis/epidemiology ; Male ; Mesothelioma/*diagnosis/epidemiology ; Middle Aged ; Neoplasm Staging ; Peritoneal Neoplasms/*diagnosis/epidemiology ; Pleural Neoplasms/*diagnosis/epidemiology ; Prognosis ; Young Adult ; }, abstract = {INTRODUCTION: In the Western world, malignant mesothelioma (MM) is most prevalent in the pleura of older males who have been professionally exposed to asbestos. Information about MM from rapidly industrializing countries such as China is minimal. There is concern that a proportion of MM diagnoses in China may be incorrect because most Chinese physicians do not have experience diagnosing this rare cancer. We recently reported an unusually high incidence of peritoneal MM among eastern Chinese female patients. Here, we review the accuracy of MM diagnoses in China and provide suggestions to improve the accuracy of diagnosis.

METHODS: We reviewed 92 pathological diagnosis of MM in 2002-2015 from two reference centers in the province of Zhejiang in eastern China. We performed a large set of immunohistochemistry analyses to increase the reliability of the diagnosis.

RESULTS: We confirmed the MM diagnosis in 12 of 34 of the pleural tumors (35.3%), in 38 of 56 of the peritoneal tumors (67.9%), and in two of two of the MMs of the tunica vaginalis (100%). MMs were characterized by tumor cells showing nuclear Wilms tumor 1 and calretinin staining and by strong membranous staining for cytokeratin CAM5.2. The results of staining for the epithelial markers carcinoembryonic antigen, thyroid transcription factor-1, MOC31, BerEP4, p63, p40, paired box 8, ER and PR were negative. BRCA1 associated protein 1 nuclear staining was lost in percentages similar to what has been reported for samples from Western countries.

CONCLUSIONS: Our findings suggest that MM-especially in its pleural localization-is often misdiagnosed in eastern China. Identifying pitfalls and possible solutions in the pathological diagnosis of MM will affect both the standard of care and research in China.}, } @article {pmid28007619, year = {2017}, author = {Creaney, J and Robinson, BWS}, title = {Malignant Mesothelioma Biomarkers: From Discovery to Use in Clinical Practice for Diagnosis, Monitoring, Screening, and Treatment.}, journal = {Chest}, volume = {152}, number = {1}, pages = {143-149}, doi = {10.1016/j.chest.2016.12.004}, pmid = {28007619}, issn = {1931-3543}, mesh = {Biomarkers, Tumor/blood ; Early Detection of Cancer/*methods ; GPI-Linked Proteins/*blood ; Humans ; *Lung Neoplasms/blood/pathology/therapy ; *Mesothelioma/blood/pathology/therapy ; *Pleural Neoplasms/blood/pathology/therapy ; Prognosis ; }, abstract = {Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis with a median survival of < 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management, and the search for a mesothelioma biomarker has been ongoing for the last 30 years. Many traditional soluble (glyco)protein biomarkers have been evaluated over this time, and an ever-increasing list of new biomarkers, including messenger RNA, DNA, microRNA, and antibodies, is being reported from biomarker discovery projects. To date, soluble mesothelin is the only tumor biomarker to receive US Food and Drug Administration approval for clinical use in mesothelioma. Mesothelin is a glycoprotein normally expressed on the surface of mesothelial cells, and in the cancerous state it can be present in circulation. Mesothelin has a limited expression on normal, nonmalignant tissue and is thus an attractive therapeutic target for mesothelin-positive tumors. In this review we will focus on the discovery and clinical usages of mesothelin and provide an update on other mesothelioma biomarkers and show how such biomarker studies might impact on the management of this deadly tumor in the future.}, } @article {pmid28002541, year = {2016}, author = {Raşcu, A and Naghi, E and OŢelea, MR and NiŢu, FM and Arghir, OC}, title = {Distinction between mesothelioma and lung adenocarcinoma based on immunohistochemistry in a patient with asbestos bodies in bronchoalveolar fluid - case report.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {57}, number = {3}, pages = {1171-1174}, pmid = {28002541}, issn = {1220-0522}, mesh = {Adenocarcinoma/*immunology/pathology ; Adenocarcinoma of Lung ; Asbestosis/pathology ; Bronchoalveolar Lavage Fluid/*cytology ; Humans ; Immunohistochemistry ; Lung Neoplasms/*immunology/pathology ; Male ; Mesothelioma/*immunology/pathology ; Middle Aged ; }, abstract = {Asbestos is a mineral-mined form the rocks, consisting in amosite (brown asbestos), crocidolite (blue asbestos) and÷or chrysotile (white asbestos) used in many industries. Researches about the exposure to asbestos dust and asbestosis related diseases started almost a century ago. The first case report of fatal asbestosis disease was published in 1906, in England, by Dr. Hubert Montague Murray. A decade after, asbestos "curious bodies" were firstly described in the lung tissue by Cooke (1926) and McDonald (1927). Occupational exposure to asbestos is now regulated in Romania, but past exposure is still a cause of asbestosis-related diseases (ARDs), including lung cancer. A peculiar association between a lung adenocarcinoma, a previously healed pulmonary tuberculosis (PTB) disease, is reported in a 61-year-old nonsmoker white man, a former factory worker with 29 years of occupational exposure history to cement and asbestos fibers. The positive diagnosis of asbestos exposure was facilitated by asbestos bodies determined in bronchoalveolar lavage fluid. The main purpose of this case report is to describe the development of a right pleural effusion which was not revelatory for a mesothelioma but for an adenocarcinoma of the lung. An accurate morphologic and immunohistochemistry assessment of a pleural biopsy sample excluded mesothelioma and was crucial in the positive diagnosis of adenocarcinoma. In conclusion, unilateral paraneoplastic pleural effusion in a nonsmoker male with occupational exposure to asbestosis fibers was suggestive for adenocarcinoma related asbestosis of the lung. Lung cancer and malignant pleural exudate developed after a long latency cumulative retention time of asbestos fibers.}, } @article {pmid27993826, year = {2016}, author = {Yildiz, H and Andreea, SI and Hoton, D and Yombi, JC}, title = {Minimal change disease associated with malignant pleural mesothelioma: case report and review of the literature.}, journal = {BMJ case reports}, volume = {2016}, number = {}, pages = {}, doi = {10.1136/bcr-2016-217958}, pmid = {27993826}, issn = {1757-790X}, mesh = {Aged ; Biopsy ; Fatal Outcome ; Humans ; Kidney/*diagnostic imaging ; Lung Neoplasms/complications/*diagnosis ; Male ; Mesothelioma/complications/*diagnosis ; Nephrosis, Lipoid/complications/*diagnosis ; Pleura/*diagnostic imaging ; Pleural Neoplasms/complications/*diagnosis ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; }, abstract = {A 77-year-old man with a history of asbestos exposure was admitted to our internal medicine division for generalised weakness, fatigue, loss of weight, night sweats and difficulty for breathing since 3 months. Clinical examination revealed left fine crackles and bilateral leg oedema. Blood test showed elevated C reactive protein level at 142 mg/L, lactate dehydrogenase level at 421 UI, creatinine level at 5.75 mg/dL. Serum albumin level at 30 g/L, urinalysis showed significant proteinuria at 6.4 g/L. Chest X-ray showed left pleural effusion. Renal ultrasonography was normal. Thoracic CT and positron emission tomography showed mediastinal enlargement with lymphadenopathies and left pleural effusion and thickening. A pleural biopsy showed features compatible with malignant epithelioid mesothelioma. Renal biopsy showed minimal change disease and acute tubular necrosis. A diagnosis of malignant mesothelioma associated with minimal change disease and acute tubular necrosis secondary was then made. Given the poor general condition, palliative care was initiated and the patient died from respiratory failure 3 months later.}, } @article {pmid27980793, year = {2016}, author = {Kang, DM and Kim, JE and Lee, YJ and Lee, HH and Lee, CY and Moon, SJ and Kang, MS}, title = {Environmental health centers for asbestos and their health impact surveys and activities.}, journal = {Annals of occupational and environmental medicine}, volume = {28}, number = {}, pages = {68}, pmid = {27980793}, issn = {2052-4374}, abstract = {In 2009, Korea banned the import, transport, and use of asbestos, and the Asbestos Injury Relief Act (AIRA) was promulgated in 2011. Two environmental health centers for asbestos (EHCA), including Pusan National University Yangsan Hospital (PNUYH) and SoonChunHyang University Cheonan Hospital (SCHUCH), were adapted to find environmental asbestos-related diseases (ARDs) and to support the purposes of AIRA. EHCA conducted a health impact survey (HIS) on persons who resided or reside near asbestos factories or mines. A total of 13,433 persons have taken screening examinations in PNUYH EHCA, and 623 persons (4.6%) have had secondary examinations. Of the 21,014 persons who had screening examinations in SCHUCH EHCA, 2490 persons (11.8%) had secondary examinations. Some of those who tested positive for ARDs through HISs filed applications for the asbestos victims' medical pocketbook (AVMP). Approximately 116 and 612 persons received AVMPs as a result of PNUYH and SCHUCH examinees, respectively. EHCAs have conducted HISs, public relations, and education for asbestos victims, ordinary citizens, and physicians. As HISs are based on voluntary participation, they does not monitor high-risk groups. Active surveillance focusing on high-risk groups has been blocked by the personal information protection act. Although important work has been performed in finding environmental asbestos victims and increasing public awareness on asbestos, it is necessary to improve the current system and registration.}, } @article {pmid27979465, year = {2017}, author = {Siegert, CJ and Fisichella, PM and Moseley, JM and Shoni, M and Lebenthal, A}, title = {Open access phone triage for veterans with suspected malignant pleural mesothelioma.}, journal = {The Journal of surgical research}, volume = {207}, number = {}, pages = {108-114}, doi = {10.1016/j.jss.2016.08.031}, pmid = {27979465}, issn = {1095-8673}, mesh = {Aged ; Boston ; Feasibility Studies ; Health Services Accessibility/*statistics & numerical data ; Humans ; Male ; Mesothelioma/*diagnosis ; Pleural Neoplasms/*diagnosis ; Referral and Consultation/statistics & numerical data ; Retrospective Studies ; Telemedicine/*methods/statistics & numerical data ; Telephone ; Triage/*methods/statistics & numerical data ; United States ; United States Department of Veterans Affairs ; *Veterans Health ; }, abstract = {BACKGROUND: Phone triaging patients with suspected malignant pleural mesothelioma (MPM) within the Veterans Healthcare Administration (VHA) system offers a model for rapid, expert guided evaluation for patients with rare and treatable diseases within a national integrated healthcare system. To assess feasibility of national open access telephone triage using evidence-based treatment recommendations for patients with MPM, measure timelines of the triage and referral process and record the impact on "intent to treat" for patients using our service.

METHODS: A retrospective study. The main outcome measures were: (1) ability to perform long distance phone triage, (2) to assess the speed of access to a mesothelioma surgical specialist for patients throughout the entire VHA, and (3) to determine if access to a specialist would alter the plan of care.

RESULTS: Sixty veterans were screened by our phone triage program, 38 traveled an average of 997 miles to VA Boston Healthcare system. On average, 14 d elapsed from initial phone contact until the patient was physically evaluated in our general thoracic clinic in Boston. The treatment plan was altered for 71% of patients evaluated at VA Boston Healthcare system based on 2012 International Mesothelioma Interest Group guidelines.

CONCLUSIONS: Our initial experience demonstrates that in-network centralized care for Veterans with MPM is feasible within the VHA. National open access phone triage improves access to expert surgical advice and can be delivered in a timely manner for Veterans using our service. Guideline-based treatment recommendations ("intent to treat") changed the therapeutic course for the majority of patients who used our service.}, } @article {pmid27941034, year = {2017}, author = {Ferrante, D and Mirabelli, D and Tunesi, S and Terracini, B and Magnani, C}, title = {Pleural mesothelioma and asbestos exposure: a case-control study with quantitative risk assessment-response to Marsh and Benson's letter.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {2}, pages = {157-158}, doi = {10.1136/oemed-2016-104091}, pmid = {27941034}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Exposure ; Pleura ; *Pleural Neoplasms ; Risk Assessment ; }, } @article {pmid27941033, year = {2017}, author = {Marsh, GM and Benson, SM}, title = {Response to: 'Pleural mesothelioma and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment' by Ferrante et al.}, journal = {Occupational and environmental medicine}, volume = {74}, number = {2}, pages = {156-157}, doi = {10.1136/oemed-2016-104002}, pmid = {27941033}, issn = {1470-7926}, mesh = {*Asbestos ; Case-Control Studies ; Humans ; Mesothelioma ; Occupational Exposure ; *Pleural Neoplasms ; Risk Assessment ; }, } @article {pmid27919155, year = {2016}, author = {Di Ciaula, A and Gennaro, V}, title = {[Possible health risks from asbestos in drinking water].}, journal = {Epidemiologia e prevenzione}, volume = {40}, number = {6}, pages = {472-475}, doi = {10.19191/EP16.6.P472.129}, pmid = {27919155}, issn = {1120-9763}, mesh = {Animals ; Asbestos/*adverse effects ; *Carcinogens ; Drinking Water/*analysis ; Environmental Exposure/*adverse effects ; *Gastrointestinal Neoplasms/epidemiology/etiology/prevention & control ; Humans ; Italy/epidemiology ; Mesothelioma/epidemiology/etiology/prevention & control ; Mineral Fibers/adverse effects ; Pleural Neoplasms/epidemiology/etiology/prevention & control ; Risk Assessment ; Risk Factors ; Time Factors ; Water Pollutants, Chemical/*toxicity ; }, abstract = {The recent finding of asbestos fibres in drinking water (up to 700.000 fibres/litres) in Tuscany (Central Italy) leads to concerns about health risks in exposed communities. Exposure to asbestos has been linked with cancer at several levels of the gastrointestinal tract, and it has been documented, in an animal model, a direct cytotoxic effect of asbestos fibres on the ileum. It has been recently described a possible link between asbestos and intrahepatic cholangiocarcinoma, and asbestos fibres have been detected in humans in histological samples from colon cancer and in gallbladder bile. Taken together, these findings suggest the possibility of an enterohepatic translocation of asbestos fibres, alternative to lymphatic translocation from lungs. In animal models, asbestos fibres ingested with drinking water act as a co-carcinogen in the presence of benzo(a) pyrene and, according to the International Agency for Research on Cancer (IARC), there is evidence pointing to a causal effect of ingested asbestos on gastric and colorectal cancer. The risk seems to be proportional to the concentration of ingested fibres, to the extent of individual water consumption, to exposure timing, and to the possible exposure to other toxics (i.e., benzo(a)pyrene). Furthermore, the exposure to asbestos by ingestion could explain the epidemiological finding of mesothelioma in subjects certainly unexposed by inhalation. In conclusion, several findings suggest that health risks from asbestos could not exclusively derive from inhalation of fibres. Health hazards might also be present after ingestion, mainly after daily ingestion of drinking water for long periods. In Italy, a systemic assessment of the presence of asbestos fibres in drinking water is still lacking, although asbestos-coated pipelines are widely diffused and still operating. Despite the fact that the existence of a threshold level for health risks linked to the presence of asbestos in drinking water is still under debate, the precautionary principle should impose all possible efforts in order to revise health policies concerning this topic, and a systematic monitoring of drinking water to quantify the presence of asbestos is certainly needed in all regions. Further epidemiological studies aimed to the identification of exposed communities and to an adequate health risk assessment in their specific geographical areas are urgently needed.}, } @article {pmid27918607, year = {2017}, author = {Mao, W and Zhang, X and Guo, Z and Gao, Z and Pass, HI and Yang, H and Carbone, M}, title = {Association of Asbestos Exposure With Malignant Mesothelioma Incidence in Eastern China.}, journal = {JAMA oncology}, volume = {3}, number = {4}, pages = {562-564}, pmid = {27918607}, issn = {2374-2445}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; }, } @article {pmid27914752, year = {2017}, author = {Cruz, MJ and Curull, V and Pijuan, L and Álvarez-Simón, D and Sánchez-Font, A and de Gracia, J and Culebras, M and Ferrer, J}, title = {Utility of Bronchoalveolar Lavage for the Diagnosis of Asbestos-Related Diseases.}, journal = {Archivos de bronconeumologia}, volume = {53}, number = {6}, pages = {318-323}, doi = {10.1016/j.arbres.2016.08.016}, pmid = {27914752}, issn = {1579-2129}, mesh = {Aged ; Asbestos/adverse effects/*analysis ; Asbestosis/diagnosis/etiology/pathology ; Bronchoalveolar Lavage Fluid/*chemistry ; Bronchoscopy ; Carcinoma/chemistry/diagnosis/etiology/pathology ; Female ; Humans ; Lung Diseases/diagnosis/*etiology/pathology ; Lung Neoplasms/chemistry/diagnosis/etiology/pathology ; Male ; Mesothelioma/chemistry/diagnosis/etiology/pathology ; Middle Aged ; Mineral Fibers/*analysis ; Occupations ; Pleural Neoplasms/chemistry/diagnosis/etiology/pathology ; Predictive Value of Tests ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; }, abstract = {INTRODUCTION: Bronchoalveolar lavage (BAL) analysis has been proposed as an objective technique for confirming asbestos exposure. However, the reliability and diagnostic yield of this procedure has not been studied in Spain. The aim of this study was to assess the usefulness of the analysis of asbestos bodies (AB) in bronchoalveolar lavage (BAL) for the diagnosis of asbestos-related diseases (ARD).

METHODS: BAL samples from 72 patients (66 male, mean age 66 years) undergoing bronchoscopy were analyzed. Lung tissue from 23 of these patients was also analyzed. Asbestos exposure was assessed by anamnesis and a review of the patient's medical records. BAL and lung samples were processed and AB count was determined by light microscopy. The accepted threshold value to diagnose asbestos-related diseases was 1 AB/ml BAL or 1000 AB/gr dry tissue.

RESULTS: Thirty-nine patients reported exposure to asbestos. Of these, 13 (33%) presented AB values above 1 AB/ml BAL. In the 33 non-exposed patients, 5 (15%) presented AB values above 1 AB/ml BAL. There was a significant difference between the AB levels of exposed and non-exposed patients (P=.006). The ROC curve showed that a value of 0.5 AB/ml BAL achieved the most satisfactory sensitivity, 46%, and a specificity of 83%. The correlation between AB levels in BAL and lung was 0.633 (P=.002).

CONCLUSIONS: BAL study provides objective evidence of exposure to asbestos. The good correlation between the AB counts in BAL and lung tissue indicates that both techniques are valid for the analysis of asbestos content.}, } @article {pmid27908590, year = {2017}, author = {Neyens, T and Lawson, AB and Kirby, RS and Nuyts, V and Watjou, K and Aregay, M and Carroll, R and Nawrot, TS and Faes, C}, title = {Disease mapping of zero-excessive mesothelioma data in Flanders.}, journal = {Annals of epidemiology}, volume = {27}, number = {1}, pages = {59-66.e3}, pmid = {27908590}, issn = {1873-2585}, support = {R01 CA172805/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Age Distribution ; Aged ; Bayes Theorem ; Belgium/epidemiology ; Female ; Geographic Mapping ; Humans ; Incidence ; Lung Neoplasms/diagnosis/*epidemiology/ethnology ; Male ; Mesothelioma/diagnosis/*epidemiology/ethnology ; Middle Aged ; Pericardium ; Peritoneal Neoplasms/*epidemiology/ethnology/pathology ; Pleural Neoplasms/*epidemiology/ethnology/pathology ; Poisson Distribution ; *Registries ; Risk Assessment ; Sex Distribution ; Survival Analysis ; }, abstract = {PURPOSE: To investigate the distribution of mesothelioma in Flanders using Bayesian disease mapping models that account for both an excess of zeros and overdispersion.

METHODS: The numbers of newly diagnosed mesothelioma cases within all Flemish municipalities between 1999 and 2008 were obtained from the Belgian Cancer Registry. To deal with overdispersion, zero inflation, and geographical association, the hurdle combined model was proposed, which has three components: a Bernoulli zero-inflation mixture component to account for excess zeros, a gamma random effect to adjust for overdispersion, and a normal conditional autoregressive random effect to attribute spatial association. This model was compared with other existing methods in literature.

RESULTS: The results indicate that hurdle models with a random effects term accounting for extra variance in the Bernoulli zero-inflation component fit the data better than hurdle models that do not take overdispersion in the occurrence of zeros into account. Furthermore, traditional models that do not take into account excessive zeros but contain at least one random effects term that models extra variance in the counts have better fits compared to their hurdle counterparts. In other words, the extra variability, due to an excess of zeros, can be accommodated by spatially structured and/or unstructured random effects in a Poisson model such that the hurdle mixture model is not necessary.

CONCLUSIONS: Models taking into account zero inflation do not always provide better fits to data with excessive zeros than less complex models. In this study, a simple conditional autoregressive model identified a cluster in mesothelioma cases near a former asbestos processing plant (Kapelle-op-den-Bos). This observation is likely linked with historical local asbestos exposures. Future research will clarify this.}, } @article {pmid27907819, year = {2017}, author = {Haji Ali, R and Khalife, M and El Nounou, G and Zuhri Yafi, R and Nassar, H and Aidibe, Z and Raad, R and Abou Eid, R and Faraj, W}, title = {Giant primary malignant mesothelioma of the liver: A case report.}, journal = {International journal of surgery case reports}, volume = {30}, number = {}, pages = {58-61}, pmid = {27907819}, issn = {2210-2612}, abstract = {INTRODUCTION: Malignant mesothelioma is a rare neoplasm of mesothelial cells arising most frequently in the pleura or peritoneum and less frequently in the liver.

CASE PRESENTATION: We present a case of primary hepatic mesothelioma of 41year old woman. She had no history of asbestos exposure or cancer. Abdominal computed tomography (CT) showed 21cm intrahepatic mass in the right lobe with many cystic lesions and few small calcifications. Pathology showed a biphasic cellular pattern. In addition, the tumor cells were positive for Calretinin, Creatine Kinase (CK)5/6, CK7, CKAEI 1/3, Wilms Tumor protein (WT-1), and Vimentin, but were negative for Alpha Feto protein (AFP), Thrombotic Thrombocytopenic Purpura (TTP-1), Anti-Hepatocyte Specific Antigen (HSA), Synaptophysin, CK20, and Homeobox protein (CDx-2).

DISCUSSION: Primary intrahepatic mesothelioma (PIHMM) is not included in the classification of the World Health Organization classification of hepatic tumors. Mesothelial cells are not normally found in the liver, but some reported cases suggest it may grow from the mesothelial cells of the Glisson's capsule.

CONCLUSION: The probability of hepatic mesothelioma should not be ruled out, even in a young woman without a clear history of asbestos exposure.}, } @article {pmid27903668, year = {2016}, author = {Bibby, AC and Tsim, S and Kanellakis, N and Ball, H and Talbot, DC and Blyth, KG and Maskell, NA and Psallidas, I}, title = {Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {25}, number = {142}, pages = {472-486}, doi = {10.1183/16000617.0063-2016}, pmid = {27903668}, issn = {1600-0617}, support = {ETM/285//Chief Scientist Office/United Kingdom ; }, mesh = {Humans ; Lung Neoplasms/*diagnosis/pathology/*therapy ; Mesothelioma/*diagnosis/pathology/*therapy ; Pleural Neoplasms/*diagnosis/pathology/*therapy ; Predictive Value of Tests ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years.This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised.}, } @article {pmid27900083, year = {2016}, author = {Kurosawa, T and Sugino, K and Isobe, K and Hata, Y and Fukasawa, Y and Homma, S}, title = {Primary malignant pericardial mesothelioma with increased serum mesothelin diagnosed by surgical pericardial resection: A case report.}, journal = {Molecular and clinical oncology}, volume = {5}, number = {5}, pages = {553-556}, pmid = {27900083}, issn = {2049-9450}, abstract = {A 37-year-old female smoker without a history of exposure to asbestos was referred to our hospital with persistent pericardial effusion. Chest computed tomography imaging examination revealed an irregular thickened pericardium with large amounts of pericardial effusion and a small pleural effusion. Fluorodeoxyglucose (FDG) positron emission tomography imaging demonstrated intrapericardial FDG accumulation. Blood tests revealed an increase in serum mesothelin levels. Examination of a surgically resected specimen revealed a grayish-white thickening of the pericardium, with a straw-colored mucinous pericardial effusion. Histopathological examination confirmed the diagnosis of epithelioid malignant mesothelioma. Although the patient's condition temporarily improved, with decreased levels of serum mesothelin during chemotherapy with carboplatin and pemetrexed, she succumbed to cardiac tamponade 18 months after the initial onset of the symptoms. Primary malignant pericardial mesothelioma (PMPM) is an extremely rare and refractory disorder. Thus, an early definitive diagnosis and timely treatment are crucial for the management of PMPM.}, } @article {pmid27900005, year = {2016}, author = {Rapisarda, V and Salemi, R and Marconi, A and Loreto, C and Graziano, AC and Cardile, V and Basile, MS and Candido, S and Falzone, L and Spandidos, DA and Fenga, C and Libra, M}, title = {Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells.}, journal = {Oncology letters}, volume = {12}, number = {5}, pages = {3363-3367}, pmid = {27900005}, issn = {1792-1074}, abstract = {Exposure to asbestos is associated with the development of mesothelioma. In addition to asbestos, other fibers have been identified as risk factors for malignant and non-malignant diseases of the lungs. Among these, fluoro-edenite (FE) was found in patients from Biancavilla (Sicily, Italy) with pleural and lung disease, suggesting its role for tumor expansion. In this context, the identification of early biomarkers useful for the diagnosis of cancer is mandatory. Fibulin-3 represents an important marker for the diagnosis of mesothelioma. However, it remains to be determined whether it is directly associated with exposure to asbestos-like fibers. In the present study, peripheral blood levels of fibulin-3 from 40 asbestos-exposed workers were compared with those detected in 27 street cleaners from Biancavilla. Intriguingly, the results showed that fibulin-3 levels were higher in the group of street cleaners compared with those of the asbestos-exposed workers, suggesting that these workers used the personal protective equipment according to the current regulations. These data suggest that subjects exposed to FE should be monitored for the risk of mesothelioma. FE and volcanic particulates are probably contained within dust inhaled by street cleaners from Biancavilla during their work activities. Based on these criteria, in this study, such fibers were used to treat mesothelial cells (MeT5A) in order to verify whether fibulin-3 levels are affected by these treatments. The results showed that only treatment with FE was associated with fibulin-3 overexpression at both the transcript and protein levels. It was previously demonstrated that mesothelial cells exhibited low levels of p27 following treatment with FE. Notably, p27 downregulation is associated with stathmin upregulation in cancer, conferring an aggressive phenotype of tumor cells. This observation prompted us to perform a computational evaluation demonstrating the activation of stathmin in lung cancer in patients exposed to asbestos. Overall, it can be speculated that both fibulin-3 and stathmin overexpression may be associated with the malignant transformation of mesothelial cells following exposure to asbestos-like fibers.}, } @article {pmid27889700, year = {2017}, author = {Reinstein, L and Bersin, B}, title = {Clarence Borel.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {26}, number = {4}, pages = {622-629}, doi = {10.1177/1048291116679964}, pmid = {27889700}, issn = {1541-3772}, mesh = {*Asbestos ; Asbestosis/*history ; History, 20th Century ; Humans ; Jurisprudence/*history ; Lung Neoplasms ; Male ; Mesothelioma ; Middle Aged ; United States ; }, abstract = {Borel v. Fibreboard Paper Products Corporation is the 1973 landmark case that paved the way for successful litigation against the asbestos industry. Clarence Borel's granddaughter shares recollections of the reluctant man behind the court case.}, } @article {pmid27886205, year = {2016}, author = {Lansley, SM and Pedersen, B and Robinson, C and Searles, RG and Sterrett, G and van Bruggen, I and Lake, RA and Mutsaers, SE and Prêle, CM}, title = {A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {36349}, pmid = {27886205}, issn = {2045-2322}, mesh = {Adult ; Alkaline Phosphatase/metabolism ; Animals ; Biomarkers/*metabolism ; Cell Differentiation ; Cell Line, Tumor ; Core Binding Factor Alpha 1 Subunit/metabolism ; Dexamethasone/pharmacology/therapeutic use ; Female ; Humans ; Integrin-Binding Sialoprotein/genetics/metabolism ; Lung Neoplasms/drug therapy/genetics/*metabolism ; Mesothelioma/drug therapy/genetics/*metabolism ; Mice ; Neoplasm Transplantation ; Osteoblasts/*cytology/metabolism ; *Osteogenesis/drug effects ; Osteonectin/metabolism ; }, abstract = {Malignant mesothelioma (MM) is an aggressive serosal tumor associated with asbestos exposure. We previously demonstrated that mesothelial cells differentiate into cells of different mesenchymal lineages and hypothesize that osseous tissue observed in a subset of MM patients is due to local differentiation of MM cells. In this study, the capacity of human and mouse MM cells to differentiate into osteoblast-like cells was determined in vitro using a functional model of bone nodule formation and in vivo using an established model of MM. Human and murine MM cell lines cultured in osteogenic medium expressed alkaline phosphatase and formed mineralized bone-like nodules. Several human and mouse MM cell lines also expressed a number of osteoblast phenotype markers, including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors identified areas of ossification within the tumor, similar to those observed in human MM biopsies. These data demonstrate the ability of MM to differentiate into another mesenchymal cell type and suggest that MM cells may contribute to the formation of the heterologous elements observed in MM tumors.}, } @article {pmid27884852, year = {2016}, author = {Tsim, S and Kelly, C and Alexander, L and McCormick, C and Thomson, F and Woodward, R and Foster, JE and Stobo, DB and Paul, J and Maskell, NA and Chalmers, A and Blyth, KG}, title = {Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study.}, journal = {BMJ open}, volume = {6}, number = {11}, pages = {e013324}, pmid = {27884852}, issn = {2044-6055}, support = {ETM/285//Chief Scientist Office/United Kingdom ; }, mesh = {Biomarkers, Tumor/blood ; Cross-Sectional Studies ; Extracellular Matrix Proteins/*blood ; GPI-Linked Proteins/*blood ; Humans ; Lung Neoplasms/*blood/*diagnostic imaging ; Magnetic Resonance Imaging ; Mesothelioma/*blood/*diagnostic imaging ; Prognosis ; Prospective Studies ; Proteomics/methods ; ROC Curve ; Research Design ; Scotland ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.

METHODS AND ANALYSIS: Serum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13-20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be <5% for each marker and their performance will be compared with serum mesothelin. Blood levels will be compared with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested substudy. The prognostic value of each marker will be assessed and a large bioresource created.

ETHICS AND DISSEMINATION: The study has been approved by the West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management Group meets on a monthly basis. Results will be published in peer-reviewed journals, presented at international meetings and disseminated to patient groups.

TRIAL REGISTRATION NUMBER: ISRCTN10079972, Pre-results.}, } @article {pmid27878235, year = {2017}, author = {Lee, S and Matsuzaki, H and Maeda, M and Yamamoto, S and Kumagai-Takei, N and Hatayama, T and Ikeda, M and Yoshitome, K and Nishimura, Y and Otsuki, T}, title = {Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers.}, journal = {International journal of oncology}, volume = {50}, number = {1}, pages = {66-74}, pmid = {27878235}, issn = {1791-2423}, mesh = {CD4-Positive T-Lymphocytes/immunology/pathology ; Cell Cycle/drug effects/immunology ; Cyclin D1/biosynthesis/blood/*immunology ; Forkhead Box Protein O1/*biosynthesis/immunology ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-10/biosynthesis/blood/immunology ; Killer Cells, Natural/immunology ; Lung Neoplasms/blood/chemically induced/*immunology/pathology ; Mesothelioma/blood/chemically induced/*immunology/pathology ; Natural Cytotoxicity Triggering Receptor 1/biosynthesis/blood/immunology ; Receptors, CXCR3/biosynthesis/immunology ; T-Lymphocytes, Cytotoxic/drug effects/immunology ; T-Lymphocytes, Regulatory/drug effects/*immunology ; Transforming Growth Factor beta/biosynthesis/blood/immunology ; }, abstract = {Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma. In addition to these findings, regulatory T cells (Treg) showed enhanced function through cell-cell contact and increased secretion of typical soluble factors, interleukin (IL)-10 and transforming growth factor (TGF)-β, in a cell line model using the MT-2 human polyclonal T cells and its sublines exposed continuously to asbestos fibers. Since these sublines showed a remarkable reduction of FoxO1 transcription factor, which regulates various cell cycle regulators in asbestos-exposed sublines, the cell cycle progression in these sublines was examined and compared with that of the original MT-2 cells. Results showed that cyclin D1 expression was markedly enhanced, and various cyclin-dependent kinase-inhibitors were reduced with increased S phases in the sublines. Furthermore, the increase of cyclin D1 expression was regulated by FoxO1. The overall findings indicate that antitumor immunity in asbestos-exposed individuals may be reduced in Treg through changes in the function and volume of Treg.}, } @article {pmid27872401, year = {2017}, author = {Castleman, B}, title = {Criminality and Asbestos in Industry.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {26}, number = {4}, pages = {557-580}, doi = {10.1177/1048291116678435}, pmid = {27872401}, issn = {1541-3772}, mesh = {*Asbestos ; *Crime ; Disasters ; Humans ; Industry/*legislation & jurisprudence ; Italy ; Mesothelioma ; *Occupational Exposure ; }, abstract = {Criminal prosecutions of individuals in the asbestos industry are reviewed, particularly the case of asbestos owner-executive Stephan Schmidheiny. Italian courts sentenced Schmidheiny to sixteen to eighteen years in jail for creating an environmental disaster causing three thousand deaths. The convictions were overturned on a technicality, and a murder case against Schmidheiny has started. His firm, Eternit, made asbestos-cement building products in many countries. Schmidheiny directed a cover-up that the Italian Court of Appeal blamed for delaying the ban of asbestos in Italy by ten years. Today, the asbestos industry is a criminal industry, profiting only by minimizing its costs for the prevention and compensation of occupational and environmental illness. The asbestos industry should only be consulted by governments for the purpose of closing it and dealing with the legacy of in-place asbestos.}, } @article {pmid27870118, year = {2016}, author = {Boffetta, P}, title = {Re: Terracini et al. Comments on the causation of malignant mesothelioma: Rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma. Am J Ind Med 2016;59:506-507.}, journal = {American journal of industrial medicine}, volume = {59}, number = {12}, pages = {1177-1179}, doi = {10.1002/ajim.22672}, pmid = {27870118}, issn = {1097-0274}, } @article {pmid27869238, year = {2016}, author = {Smolková, P and Nakládalová, M and Zapletalová, J}, title = {Response to the letter to editors concerning "Validity of mesothelin in occupational medicine practice".}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {6}, pages = {881}, doi = {10.13075/ijomeh.1896.01101}, pmid = {27869238}, issn = {1896-494X}, mesh = {Asbestos ; *GPI-Linked Proteins ; Humans ; Mesothelioma ; Occupational Exposure ; *Occupational Medicine ; Pleural Neoplasms ; }, } @article {pmid27869237, year = {2016}, author = {Taeger, D and Gawrych, K and Brüning, T}, title = {Validity of mesothelin in occupational medicine practice.}, journal = {International journal of occupational medicine and environmental health}, volume = {29}, number = {6}, pages = {879-880}, doi = {10.13075/ijomeh.1896.01062}, pmid = {27869237}, issn = {1896-494X}, mesh = {Asbestos ; *GPI-Linked Proteins ; Humans ; Mesothelioma ; Occupational Exposure ; *Occupational Medicine ; Pleural Neoplasms ; }, } @article {pmid27866405, year = {2016}, author = {Plato, N and Martinsen, JI and Sparén, P and Hillerdal, G and Weiderpass, E}, title = {Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban.}, journal = {Epidemiology and health}, volume = {38}, number = {}, pages = {e2016039}, pmid = {27866405}, issn = {2092-7193}, mesh = {Adult ; Asbestos/poisoning ; Asbestosis/epidemiology ; Female ; Humans ; Incidence ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Diseases/chemically induced/*epidemiology ; Registries ; Sweden/epidemiology ; }, abstract = {OBJECTIVES: We updated the Swedish component of the Nordic Occupational Cancer (NOCCA) Study through 2009 in order to investigate the incidence of mesothelioma of the peritoneum and pleura in both genders, and explored occupational exposures that may be associated with mesothelioma.

METHODS: The Swedish component of the NOCCA Study includes 6.78 million individuals. Data from this cohort were linked to the population-based Swedish Cancer Registry and Swedish Total Population Registry for three periods between 1961 and 2009, and then further linked to the Swedish NOCCA job-exposure matrix, which includes 25 carcinogenic substances and the corresponding exposure levels for 280 occupations. Multivariate analysis was used to calculate standardized incidence ratios (SIRs) for mesothelioma of the peritoneum and pleura by gender, occupational category, carcinogenic substance, and for multiple occupational exposures simultaneously.

RESULTS: A total of 3,716 incident mesotheliomas were recorded (21.1% in women). We found a significantly increased risk of mesothelioma in 24 occupations, as well as clear differences between the genders. Among men, increased risks of mesothelioma of the pleura were observed in male-dominated occupations, with the greatest elevation of risk among plumbers (SIR, 4.99; 95% confidence interval, 4.20 to 5.90). Among women, increased risks were observed in sewing workers, canning workers, packers, cleaners, and postal workers. In multivariate analysis controlling for multiple occupational exposures, significant associations were only observed between asbestos exposure and mesothelioma.

CONCLUSIONS: Asbestos exposure was associated with mesothelioma incidence in our study. The asbestos ban of 1982 has yet to show any clear effect on the occurrence of mesothelioma in this cohort. Among women, the occupations of canning workers and cleaners showed increased risks of mesothelioma of the pleura without evidence of asbestos exposure.}, } @article {pmid27859460, year = {2017}, author = {Shinozaki-Ushiku, A and Ushiku, T and Morita, S and Anraku, M and Nakajima, J and Fukayama, M}, title = {Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma.}, journal = {Histopathology}, volume = {70}, number = {5}, pages = {722-733}, doi = {10.1111/his.13123}, pmid = {27859460}, issn = {1365-2559}, mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Enhancer of Zeste Homolog 2 Protein/analysis/*biosynthesis ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/*diagnosis/mortality/pathology ; Male ; Mesothelioma/*diagnosis/mortality/pathology ; Middle Aged ; Proportional Hazards Models ; Tumor Suppressor Proteins/analysis/*biosynthesis ; Ubiquitin Thiolesterase/analysis/*biosynthesis ; }, abstract = {AIMS: Malignant mesothelioma is a highly aggressive cancer that is usually diagnosed at advanced stages; thus, highly sensitive and specific markers are necessary for its early definitive diagnosis. The aim of this study was to evaluate the diagnostic utility and prognostic significance of BAP1 and EZH2 in malignant mesothelioma.

METHODS AND RESULTS: The expression of BAP1 and EZH2 was investigated by immunohistochemistry in 32 malignant mesotheliomas and 44 benign mesothelial proliferative lesions, including well-differentiated papillary mesothelioma (n = 4), mesothelial inclusion cyst (n = 22), and reactive mesothelial hyperplasia (n = 18). BAP1 loss and high EZH2 expression were observed in 17 (53%) and 22 (66%) malignant mesothelioma cases, respectively, whereas none of the benign lesions showed BAP1 loss or high EZH2 expression. The combination of BAP1 loss and high EZH2 expression as markers to differentiate epithelioid/biphasic malignant mesothelioma from benign mesothelial lesions was highly sensitive (90%) and specific (100%). There were no statistically significant associations between parameters such as age and sex of patients, tumour location, asbestos exposure, treatment, histology, and BAP1 or EZH2 expression. Survival analysis revealed that BAP1 loss, but not high EZH2 expression, was associated with a better prognosis.

CONCLUSIONS: BAP1 loss and high EZH2 expression were highly specific to malignant mesothelioma in differentiating it from benign mesothelial proliferations, and the combination of these two markers improved the diagnostic accuracy.}, } @article {pmid27840913, year = {2016}, author = {Kato, T and Lee, D and Wu, L and Patel, P and Young, AJ and Wada, H and Hu, HP and Ujiie, H and Kaji, M and Ka