@article {pmid32083805, year = {2020}, author = {Quetel, L and Meiller, C and Assié, JB and Blum, Y and Imbeaud, S and Montagne, F and Tranchant, R and de Wolf, J and Caruso, S and Copin, MC and Hofman, V and Gibault, L and Badoual, C and Pintilie, E and Hofman, P and Monnet, I and Scherpereel, A and Le Pimpec-Barthes, F and Zucman-Rossi, J and Jaurand, MC and Jean, D}, title = {Genetic alterations of malignant pleural mesothelioma: association to tumor heterogeneity and overall survival.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.12651}, pmid = {32083805}, issn = {1878-0261}, abstract = {Development of precision medicine for malignant pleural mesothelioma (MPM) requires a deep knowledge of tumor heterogeneity. Histologic and molecular classifications and histo-molecular gradients have been proposed to describe heterogeneity, but a deeper understanding of gene mutations in the context of MPM heterogeneity is required and the associations between mutations and clinical data need to be refined. We characterized genetic alterations on one of the largest MPM series (266 tumor samples), well-annotated with histologic, molecular and clinical data of patients. Targeted next generation sequencing was performed focusing on the major MPM mutated genes and the TERT promoter. Molecular heterogeneity was characterized using predictors allowing classification of each tumor into the previously described molecular subtypes and the determination of the proportion of epithelioïd-like and sarcomatoïd-like components (E/S.scores). The mutation frequencies are consistent with literature data, but this study emphasized that TERT promoter, not considered by previous large sequencing studies, was the third locus most affected by mutations in MPM. Mutations in TERT promoter, NF2 and LATS2 were more frequent in non-epithelioid MPM and positively associated to the S.score. BAP1, NF2, TERT promoter, TP53 and SETD2 mutations were enriched in some molecular subtypes. NF2 mutation rate was higher in asbestos unexposed patient. TERT promoter, NF2 and TP53 mutations were associated with a poorer overall survival. Our findings lead to a better characterization of MPM heterogeneity by identifying new significant associations between mutational status and histologic and molecular heterogeneity. Strikingly, we highlight the strong association between new mutations and overall survival.}, }
@article {pmid32082887, year = {2019}, author = {Döngel, İ and Akbaş, A and Benli, İ and Bayram, M}, title = {Comparison of serum biochemical markers in patients with mesothelioma and pleural plaques versus healthy individuals exposed to environmental asbestos.}, journal = {Turk gogus kalp damar cerrahisi dergisi}, volume = {27}, number = {3}, pages = {374-380}, doi = {10.5606/tgkdc.dergisi.2019.17557}, pmid = {32082887}, issn = {1301-5680}, abstract = {Background: In this study, we aimed to compare serum biochemical markers in patients with malignant pleural mesothelioma and pleural plaques versus healthy individuals exposed to environmental asbestos.<br><br>Methods: Between September 01, 2010 and March 31, 2011, a total of 540 participants (354 males, 186 females; mean age 61.4 years; range, 35 to 89 years) were included in the study. The participants were divided into four groups as follows: (1) patients with pleural plaques (n=277); (2) healthy individuals with normal chest X-rays who were exposed to environmental asbestos (n=121); (3) healthy individuals with normal chest X-rays who were not exposed to environmental asbestos (n=118); and (4) patients with malignant pleural mesothelioma (n=24). Serum levels of carcinoembryonic antigen, cancer antigen 125, 15-3, 19-9, free T3, free T4, thyroidstimulating hormone, vitamin B12, folate, and ferritin were measured.<br><br>Results: Serum cancer antigen 125, 15-3, folic acid, vitamin B12, and ferritin levels were higher with lower free T3 levels in Group 4 than the other groups. The areas under the curve for cancer antigen 125 and 15-3 were 0.78 and 0.67, respectively in the differential diagnosis of mesothelioma from other pathologies (p<0.001 for both). Optimal limits of these biomarkers were 13.63 and 18.43 ng/mL, respectively with 83% and 75% sensitivity and 69% and 48% specificity, respectively.<br><br>Conclusion: The combination or individual use of serum cancer antigen 125, 15-3, folic acid, vitamin B12, and ferritin levels may be helpful for early diagnosis and treatment of malignant pleural mesothelioma.}, }
@article {pmid32081346, year = {2020}, author = {Sinha, S and Swift, AJ and Kamil, MA and Matthews, S and Bull, MJ and Fisher, P and De Fonseka, D and Saha, S and Edwards, JG and Johns, CS}, title = {The role of imaging in malignant pleural mesothelioma: an update after the 2018 BTS guidelines.}, journal = {Clinical radiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.crad.2019.12.001}, pmid = {32081346}, issn = {1365-229X}, abstract = {Malignant pleural mesothelioma (MPM) is a primary malignancy of the pleura and is associated with a poor outcome. The symptoms and signs of malignant mesothelioma present late in the natural history of the disease and are non-specific, making the diagnosis challenging and imaging key. In 2018, the British Thoracic Society (BTS) updated the guideline on diagnosis, staging, and follow-up of patients with MPM. These recommendations are discussed in this review of the current literature on imaging of MPM. It is estimated MPM will continue to cause serious morbidity and mortality in the UK late into the 21st century, and internationally, people continue to be exposed to asbestos. We aim to update the reader on current and future imaging strategies, which could aid early diagnosis of pleural malignancy and provide an update on staging and assessment of tumour response.}, }
@article {pmid32080953, year = {2020}, author = {Okazaki, Y and Misawa, N and Akatsuka, S and Kohyama, N and Sekido, Y and Takahashi, T and Toyokuni, S}, title = {Frequent homozygous deletion of Cdkn2a/2b in tremolite-induced malignant mesothelioma in rats.}, journal = {Cancer science}, volume = {}, number = {}, pages = {}, doi = {10.1111/cas.14358}, pmid = {32080953}, issn = {1349-7006}, abstract = {The onset of malignant mesothelioma (MM) is linked to exposure to asbestos fibers. Asbestos fibers are classified as serpentine (chrysotile) or amphibole, which includes the crocidolite, amosite, anthophyllite, tremolite and actinolite types. Although few studies have been conducted, anthophyllite has been shown to be associated with mesothelioma, and tremolite, a contaminant in talc and chrysotile, is a risk factor for carcinogenicity. Here, after characterizing the length and width of these fibers by scanning electron microscopy, we explored the cytotoxicity induced by tremolite and anthophyllite in cells from an immortalized human mesothelial cell line (MeT5A), murine macrophages (RAW264.7) and in a rat model. Tremolite and short anthophyllite fibers were phagocytosed and localized to vacuoles, while the long anthophyllite fibers were caught on the pseudopod of the MeT5A and Raw 264.7 cells, according to transmission electron microscopy. The results from a two-day time-lapse study revealed that tremolite was engulfed and damaged the MeT5A and RAW264.7 cells, while anthophyllite was not cytotoxic to these cells. Intraperitoneal injection of tremolite in rats induced diffuse serosal thickening, while anthophyllite formed focal fibrosis and granulomas on peritoneal serosal surfaces. Further, the loss of Cdkn2a/2b, which are the most frequently lost foci in human MM, were observed in eight cases of rat MM [homozygous deletion (5/8) and loss of heterozygosity (3/8)] by array-based comparative genomic hybridization techniques. These results indicate that tremolite initiates mesothelial injury and persistently frustrates phagocytes, causing subsequent peritoneal fibrosis and MM. The possible mechanisms of carcinogenicity based on fiber diameter/length are discussed.}, }
@article {pmid32077824, year = {2020}, author = {Loreto, C and Lombardo, C and Caltabiano, R and Ledda, C and Hagnas, M and Filetti, V and Rapisarda, V}, title = {An in vivo immunohistochemical study on MacroH2A.1 in lung and lymph-node tissues exposed to an asbestiform fiber.}, journal = {Current molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.2174/1566524020666200220130023}, pmid = {32077824}, issn = {1875-5666}, abstract = {AIMS: The aim of this study was to investigate MacroH2A.1 immunoexpression in tissues of sheep exposed to FE.<br><br>BACKGROUND: The correlation between asbestiform fibers, lung cancer, pleural mesothelioma and other lung diseases is already well established as the pathophisiological respiratory mechanisms involved by inhalation of Fluoro-edenite (FE). The latter is represented by cell proliferation and inducing release of growth factors, cytokines and reactive oxygen and nitrite species, with DNA damage that cause chronic inflammation and carcinogenesis. MacroH2A.1, and histone variant, seems to play a role in sensing the metabolic state of the cell and linking it with chromatin. Physiologically, MacroH2A.1 is expressed at low levels in stem cells and it became upregulated during differentiation, preventing reprogramming of induced pluripotent stem cells and after nuclear transfer. In particular, MacroH2A.1 has been shown to explicate a potent antitumor mechanism in vivo as it results upregulated in senescent cells determining a permanent growth-arrest.<br><br>OBJECTIVE: Evaluate the possible role the histone variant in the organism response to deep insight the mechanisms of toxicity and the cellular response to FE.<br><br>METHODS: Lung and lymph nodes of exposed sheep were selected. Samples were processed for histological and immunihistochemical evaluations. Densitometric, morphometric and statistical analysis were conducted.<br><br>RESULTS: Tissue sections of FE exposed sheep demonstrated an overexpression of MacroH2A.1 vs unexposed samples. The data suggest an involvement of these molecule in the cellular response triggered by FE directed exposure.<br><br>CONCLUSION: In this contest, MacroH2A.1 overexpression supports its function as an epigenetic stabilizer that helps to establish and maintain differentiated states.}, }
@article {pmid32065212, year = {2020}, author = {Barbieri, PG and Somigliana, A and Chen, Y and Consonni, D and Vignola, R and Finotto, L}, title = {Lung Asbestos Fibre Burden and Pleural Mesothelioma in Women with Non-occupational Exposure.}, journal = {Annals of work exposures and health}, volume = {}, number = {}, pages = {}, doi = {10.1093/annweh/wxaa009}, pmid = {32065212}, issn = {2398-7316}, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) due to environmental and familial (domestic) asbestos exposure is well recognized. However, information on cumulative asbestos dose in subjects affected by MPM is limited.<br><br>OBJECTIVES: To evaluate the residual lung asbestos fibre and asbestos body burden in women with MPM with past environmental and/or familial asbestos exposure.<br><br>METHODS: We collected lung samples from autopsies regarding 15 non-occupationally asbestos-exposed MPM cases, divided in three groups: (i) familial exposure from the Fincantieri shipyards in Monfalcone (No. 7), (ii) environmental and familial asbestos exposure from the asbestos-cement plant Fibronit in Broni (No. 6), and (iii) environmental exposure from the Fibronit plant (No. 2). Asbestos body (AB) and fibres (AF) per gram of dry lung tissue were counted by optical and scanning electron microscopy, respectively, and expressed as geometric means and standard deviations (GM, GSD).<br><br>RESULTS: GM/GSD of AB counts were 6123/9.6 (Group 1), 13 800/10.4 (Group 2), and 8400/1.1 (Group 3); GM/GSD of AF were 0.6/2.1 (Group 1), 7.9/2.1 (Group 2), and 6.0/2.3 (Group 3) million. Pleural plaques were observed in 12 cases.<br><br>CONCLUSIONS: Exclusive familial exposure to asbestos determined cumulative doses close to those observed in moderate occupational exposure circumstances. Our results also suggest that combined environmental and familial exposures may cause unexpectedly high cumulative fibre doses.}, }
@article {pmid32054819, year = {2020}, author = {, }, title = {Global and regional burden of cancer in 2016 arising from occupational exposure to selected carcinogens: a systematic analysis for the Global Burden of Disease Study 2016.}, journal = {Occupational and environmental medicine}, volume = {77}, number = {3}, pages = {151-159}, doi = {10.1136/oemed-2019-106012}, pmid = {32054819}, issn = {1470-7926}, abstract = {OBJECTIVES: This study provides a detailed analysis of the global and regional burden of cancer due to occupational carcinogens from the Global Burden of Disease 2016 study.<br><br>METHODS: The burden of cancer due to 14 International Agency for Research on Cancer Group 1 occupational carcinogens was estimated using the population attributable fraction, based on past population exposure prevalence and relative risks from the literature. The results were used to calculate attributable deaths and disability-adjusted life years (DALYs).<br><br>RESULTS: There were an estimated 349 000 (95% Uncertainty Interval 269 000 to 427 000) deaths and 7.2 (5.8 to 8.6) million DALYs in 2016 due to exposure to the included occupational carcinogens-3.9% (3.2% to 4.6%) of all cancer deaths and 3.4% (2.7% to 4.0%) of all cancer DALYs; 79% of deaths were of males and 88% were of people aged 55 -79 years. Lung cancer accounted for 86% of the deaths, mesothelioma for 7.9% and laryngeal cancer for 2.1%. Asbestos was responsible for the largest number of deaths due to occupational carcinogens (63%); other important risk factors were secondhand smoke (14%), silica (14%) and diesel engine exhaust (5%). The highest mortality rates were in high-income regions, largely due to asbestos-related cancers, whereas in other regions cancer deaths from secondhand smoke, silica and diesel engine exhaust were more prominent. From 1990 to 2016, there was a decrease in the rate for deaths (-10%) and DALYs (-15%) due to exposure to occupational carcinogens.<br><br>CONCLUSIONS: Work-related carcinogens are responsible for considerable disease burden worldwide. The results provide guidance for prevention and control initiatives.}, }
@article {pmid32050546, year = {2020}, author = {Töreyin, ZN and Ghosh, M and Göksel, Ö and Göksel, T and Godderis, L}, title = {Exhaled Breath Analysis in Diagnosis of Malignant Pleural Mesothelioma: Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {3}, pages = {}, doi = {10.3390/ijerph17031110}, pmid = {32050546}, issn = {1660-4601}, abstract = {Malignant pleural mesothelioma (MPM) is mainly related to previous asbestos exposure. There is still dearth of information on non-invasive biomarkers to detect MPM at early stages. Human studies on exhaled breath biomarkers of cancer and asbestos-related diseases show encouraging results. The aim of this systematic review was to provide an overview on the current knowledge about exhaled breath analysis in MPM diagnosis. A systematic review was conducted on MEDLINE (PubMed), EMBASE and Web of Science databases to identify relevant studies. Quality assessment was done by the Newcastle-Ottawa Scale. Six studies were identified, all of which showed fair quality and explored volatile organic compounds (VOC) based breath profile using Gas Chromatography Coupled to Mass Spectrometry (GC-MS), Ion Mobility Spectrometry Coupled to Multi-capillary Columns (IMS-MCC) or pattern-recognition technologies. Sample sizes varied between 39 and 330. Some compounds (i.e, cyclohexane, P3, P5, P50, P71, diethyl ether, limonene, nonanal, VOC IK 1287) that can be indicative of MPM development in asbestos exposed population were identified with high diagnostic accuracy rates. E-nose studies reported breathprints being able to distinguish MPM from asbestos exposed individuals with high sensitivity and a negative predictive value. Small sample sizes and methodological diversities among studies limit the translation of results into clinical practice. More prospective studies with standardized methodologies should be conducted on larger populations.}, }
@article {pmid32050285, year = {2020}, author = {Habbel, VSA and Mahler, EA and Feyerabend, B and Oldhafer, KJ and Lipp, MJ}, title = {[Diffuse malignant peritoneal mesothelioma (DMPM) - a rare diagnosis].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {58}, number = {2}, pages = {146-151}, doi = {10.1055/a-1083-6962}, pmid = {32050285}, issn = {1439-7803}, abstract = {Diffuse malignant peritoneal mesothelioma (DMPM) is a rare diagnosis, found more frequently in men than in women. Symptoms are unspecific abdominal disorders making that diagnosis difficult to set. Causes of DMPM are yet to be discovered in entirety. Asbestos exposure is the reason for approximately 7 % of all peritoneal mesotheliomas. Until the evaluation of systematic cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) DMPM was a fatal diagnosis with a median overall survival (OS) of 4-13 months. The prognosis of DMPM dramatically improved with implementation of CRS and HIPEC to an OS of 30-92 month nowadys. CRS and HIPEC were performed in this case.}, }
@article {pmid32050148, year = {2020}, author = {Singh, R and Cherrie, JW and Rao, B and Asolekar, SR}, title = {Assessment of the future mesothelioma disease burden from past exposure to asbestos in ship recycling yards in India.}, journal = {International journal of hygiene and environmental health}, volume = {225}, number = {}, pages = {113478}, doi = {10.1016/j.ijheh.2020.113478}, pmid = {32050148}, issn = {1618-131X}, abstract = {The recycling of end-of-life vessels is a complex activity that generates an enormous amount of hazardous waste, including asbestos-containing materials (ACM). Efforts by the Government of India to comply with national and international regulations and improved standard operating procedures are expected to lower the exposure risk of the workforce to hazardous substances, including asbestos. The current workers are likely to face lesser risks than did those exposed in the past. The present study assesses the health risks from past exposure of asbestos for those workers engaged in handling and removing ACM in ship recycling yards before environmentally sound recycling of obsolete ships was introduced in the early 2000s. Estimates were made of the number of workers exposed, and the intensity of exposure and these data were used to estimate the likely number of mesothelioma deaths in the future. It was estimated that nearly 15% of the total workforce engaged in ship recycling will suffer from mesothelioma which translates to about 4,513 mesothelioma deaths among the total of 31,000 workers estimated to be ever employed in the yards from 1994 till 2002. Recommendations are made for a practical approach to the safe handling of ACMs in Indian ship recycling yards.}, }
@article {pmid32041759, year = {2020}, author = {Ahmed, ST and Barvo, M and Kamath, N and Alweis, R}, title = {Acute popliteal thrombus workup leads to discovery of primary peritoneal mesothelioma in the absence of any known asbestos exposure.}, journal = {BMJ case reports}, volume = {13}, number = {2}, pages = {}, doi = {10.1136/bcr-2019-232812}, pmid = {32041759}, issn = {1757-790X}, abstract = {A 75-year-old man presented to the emergency department with 1-day history of right lower limb pain and 3-month history of vague abdominal pain. In the emergency department a thrombus was discovered in the right popliteal artery. CT scan of the abdomen and pelvis revealed high-density material in the pelvis, multiple hypodensities on the liver, ascites with omental nodularity, and high-density material along the stomach wall. He underwent thrombectomy and was started on anticoagulation therapy. The core needle biopsy revealed primary omental mesothelioma. There was no history of any known asbestos exposure. He also had to undergo therapeutic paracentesis twice due to abdominal distension. Mesothelioma treatment of carboplatin and pemetrexed was started, and the patient is currently receiving this chemotherapy treatment regimen.}, }
@article {pmid32041124, year = {2020}, author = {Airoldi, C and Ferrante, D and Miligi, L and Piro, S and Stoppa, G and Migliore, E and Chellini, E and Romanelli, A and Sciacchitano, C and Mensi, C and Cavone, D and Romeo, E and Massari, S and Marinaccio, A and Magnani, C}, title = {Estimation of Occupational Exposure to Asbestos in Italy by the Linkage of Mesothelioma Registry (ReNaM) and National Insurance Archives. Methodology and Results.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {3}, pages = {}, doi = {10.3390/ijerph17031020}, pmid = {32041124}, issn = {1660-4601}, abstract = {The identification and monitoring of occupational cancer is an important aspect of occupational health protection. The Italian law on the protection of workers (D. Leg. 81/2008) includes different cancer monitoring systems for high and low etiologic fraction tumors. Record linkage between cancer registries and administrative data is a convenient procedure for occupational cancer monitoring. We aim to: (i) Create a list of industries with asbestos exposure and (ii) identify cancer cases who worked in these industries. The Italian National Mesothelioma Registry (ReNaM) includes information on occupational asbestos exposure of malignant mesothelioma (MM) cases. We developed using data from seven Italian regions a methodology for listing the industries with potential exposure to asbestos linking ReNaM to Italian National Social Security Institute (INPS) data. The methodology is iterative and adjusts for imprecision and inaccuracy in reporting firm names at interview. The list of asbestos exposing firms was applied to the list of cancer cases (all types associated or possibly associated with asbestos according to International Agency for Research on Cancer (IARC) monograph 100C) in two Italian regions for the indication of possible asbestos exposure. Eighteen percent of the cancer cases showed at least one work period in firms potentially exposing to asbestos, 48% of which in regions different from where the cases lived at diagnosis. The methodology offers support for the preliminary screening of asbestos exposing firms in the occupational history of cancer cases.}, }
@article {pmid32040984, year = {2020}, author = {Wylie, AG and Korchevskiy, A and Segrave, AM and Duane, A}, title = {Modeling mesothelioma risk factors from amphibole fiber dimensionality: mineralogical and epidemiological perspective.}, journal = {Journal of applied toxicology : JAT}, volume = {}, number = {}, pages = {}, doi = {10.1002/jat.3923}, pmid = {32040984}, issn = {1099-1263}, abstract = {Amphiboles are common rock-forming minerals but when they form asbestos, they are known carcinogens. Mesothelioma mortality among miners and millers per the unit of asbestiform amphibole exposure varies significantly across cohorts when asbestos exposure measurements are based on the membrane filter method. Because the cohorts were exposed to different occurrences of asbestiform amphibole, variance in mesothelioma potency (RM) among cohorts is likely due to differences in exposure characteristics not reflected by the membrane filter method. In this paper using both linear and nonlinear models we correlate RM from four mining and milling cohorts with two-dimensional parameters of the exposure. The parameters are based on the proportion of elongated minerals that are >5 μm in length from each occurrence that also have either (a) width ≤ 0.15 μm, or (b) width ≤ 0.25 μm. Based on the models we derived, it was possible to quantify RM for the occurrences of asbestiform amphibole associated with mesothelioma excess but for which epidemiologically based RM has not been published. It was demonstrated that modeled RM for amphibole occurrences in nonasbestiform habits are lower (fibrous glaucophane) or not significant (cleavage fragments). The results of the study can be used in a risk assessment of elongated mineral particles and have implications for public policy and regulations.}, }
@article {pmid32035500, year = {2020}, author = {Pais, A and Pinto, N and Cardoso, J and Fernandes, M and Coutinho, AI and Oliveira, AS and Carvalho, L and Bárbara, C}, title = {[Diffuse Intraparenchymal Mesothelioma: An Atypical Presentation].}, journal = {Acta medica portuguesa}, volume = {33}, number = {2}, pages = {143-146}, doi = {10.20344/amp.11406}, pmid = {32035500}, issn = {1646-0758}, abstract = {Pleural mesothelioma is a disease associated with exposure to asbestos. Although rare, it is the most common malignant pleural neoplasm. It is difficult to diagnose and it has a poor prognosis. We report the case of a 62-year-old male patient with a history of prolonged occupational exposure to asbestos, with dyspnea for minor exertion and productive cough, for several months. Imaging studies revealed extensive interstitial involvement with marked thickening of the interlobular and centrilobular septa and tenuous pleural involvement. Several differential diagnoses were considered such as, asbestosis, cryptogenic organizing pneumonia, desquamative interstitial pneumonia, pleuropulmonary metastases, and/or bronchopulmonary infection, but the histological and immunohistochemical results were compatible with pleural mesothelioma - a rare malignant neoplasm, with pleural origin, with a high mortality rate.}, }
@article {pmid32033249, year = {2020}, author = {Aoki, K and Saito, N}, title = {Biocompatibility and Carcinogenicity of Carbon Nanotubes as Biomaterials.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/nano10020264}, pmid = {32033249}, issn = {2079-4991}, abstract = {With the development of nanotechnology in recent years, there have been concerns about the health effects of nanoparticles. Carbon nanotubes (CNTs) are fibrous nanoparticles with a micro-sized length and nano-sized diameter, which exhibit excellent physical properties and are widely studied for their potential application in medicine. However, asbestos has been historically shown to cause pleural malignant mesothelioma and lung cancer by inhalation exposure. Because carbon nanotubes are also fibrous nanotubes, some have raised concerns about its possible carcinogenicity. We have reported that there is no clear evidence of carcinogenicity by local and intravenous administration of multi-walled CNTs to cancer mice models. We firmly believe that CNTs can be a safe, new, and high-performance biomaterials by controlling its type, site of administration, and dosage.}, }
@article {pmid32021524, year = {2020}, author = {Cheng, YY and Rath, EM and Linton, A and Yuen, ML and Takahashi, K and Lee, K}, title = {The Current Understanding Of Asbestos-Induced Epigenetic Changes Associated With Lung Cancer.}, journal = {Lung Cancer (Auckland, N.Z.)}, volume = {11}, number = {}, pages = {1-11}, doi = {10.2147/LCTT.S186843}, pmid = {32021524}, issn = {1179-2728}, abstract = {Asbestos is a naturally occurring mineral consisting of extremely fine fibres that can become trapped in the lungs after inhalation. Occupational and environmental exposures to asbestos are linked to development of lung cancer and malignant mesothelioma, a cancer of the lining surrounding the lung. This review discusses the factors that are making asbestos-induced lung cancer a continuing problem, including the extensive historic use of asbestos and decades long latency between exposure and disease development. Genomic mutations of DNA nucleotides and gene rearrangements driving lung cancer are well-studied, with biomarkers and targeted therapies already in clinical use for some of these mutations. The genes involved in these mutation biomarkers and targeted therapies are also involved in epigenetic mechanisms and are discussed in this review as it is hoped that identification of epigenetic aberrations in these genes will enable the same gene biomarkers and targeted therapies to be used. Currently, understanding of how asbestos fibres trapped in the lungs leads to epigenetic changes and lung cancer is incomplete. It has been shown that oxidoreduction reactions on fibre surfaces generate reactive oxygen species (ROS) which in turn damage DNA, leading to genetic and epigenetic alterations that reduce the activity of tumour suppressor genes. Epigenetic DNA methylation changes associated with lung cancer are summarised in this review, and some of these changes will be due to asbestos exposure. So far, little research has been carried out to separate the asbestos driven epigenetic changes from those due to non-asbestos causes of lung cancer. Asbestos-associated lung cancers exhibit less methylation variability than lung cancers in general, and in a large proportion of samples variability has been found to be restricted to promoter regions. Epigenetic aberrations in cancer are proving to be promising biomarkers for diagnosing cancers. It is hoped that further understanding of epigenetic changes in lung cancer can result in useful asbestos-associated lung cancer biomarkers to guide treatment. Research is ongoing into the detection of lung cancer epigenetic alterations using non-invasive samples of blood and sputum. These efforts hold the promise of non-invasive cancer diagnosis in the future. Efforts to reverse epigenetic aberrations in lung cancer by epigenetic therapies are ongoing but have not yet yielded success.}, }
@article {pmid32006662, year = {2020}, author = {Gaetani, S and Monaco, F and Alessandrini, F and Tagliabracci, A and Sabbatini, A and Bracci, M and Valentino, M and Neuzil, J and Amati, M and Santarelli, L and Tomasetti, M}, title = {Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy.}, journal = {The international journal of biochemistry &amp; cell biology}, volume = {}, number = {}, pages = {105700}, doi = {10.1016/j.biocel.2020.105700}, pmid = {32006662}, issn = {1878-5875}, abstract = {MiR-222 and miR-126 are associated with asbestos exposure and the ensuing malignancy, but the mechanism(s) of their regulation remain unclear. We evaluated the mechanism by which asbestos regulates miR-222 and miR-126 expression in the context of cancer etiology. An 'in vitro' model of carcinogen-induced cell transformation was used based on exposing bronchial epithelium BEAS-2B cells to three different carcinogens including asbestos. Involvement of the EGFR pathway and the role of epigenetics have been investigated in carcinogen-transformed cells and in malignant mesothelioma, a neoplastic disease associated with asbestos exposure. Increased expression of miR-222 and miR-126 were found in asbestos-transformed cells, but not in cells exposed to arsenic and chrome. Asbestos-mediated activation of the EGFR pathway and macrophages-induced inflammation resulted in miR-222 upregulation, which was reversed by EGFR inhibition. Conversely, asbestos-induced miR-126 expression was affected neither by EGFR modulation nor inflammation. Rather than methylation of the miR-126 host gene EGFL7, epigenetic mechanism involving DNMT1- and PARP1-mediated chromatin remodeling was found to upregulate of miR-126 in asbestos-exposed cells, while miR-126 was downregulated in malignant cells. Analysis of MM tissue supported the role of PARP1 in miR-126 regulation. Therefore, activation of the EGFR pathway and the PARP1-mediated epigenetic regulation both play a role in asbestos-induced miRNA expression, associated with in asbestos-induced carcinogenesis and tumor progression.}, }
@article {pmid32005436, year = {2020}, author = {Fels Elliott, DR and Jones, KD}, title = {Diagnosis of Mesothelioma.}, journal = {Surgical pathology clinics}, volume = {13}, number = {1}, pages = {73-89}, doi = {10.1016/j.path.2019.10.001}, pmid = {32005436}, issn = {1875-9157}, abstract = {Mesothelioma is a rare neoplasm that arises from mesothelial cells lining body cavities including the pleura, pericardium, peritoneum, and tunica vaginalis. Most malignant mesotheliomas occur in the chest and are frequently associated with a history of asbestos exposure. The diagnosis of malignant mesothelioma is challenging and fraught with pitfalls, particularly in small biopsies. This article highlights what the pathologist needs to know regarding the clinical and radiographic presentation of mesothelioma, histologic features including subtypes and variants, and recent advances in immunohistochemical markers and molecular testing.}, }
@article {pmid32002299, year = {2020}, author = {Ma, S and Chee, J and Fear, VS and Forbes, CA and Boon, L and Dick, IM and Robinson, BWS and Creaney, J}, title = {Pre-treatment tumor neo-antigen responses in draining lymph nodes are infrequent but predict checkpoint blockade therapy outcome.}, journal = {Oncoimmunology}, volume = {9}, number = {1}, pages = {1684714}, doi = {10.1080/2162402X.2019.1684714}, pmid = {32002299}, issn = {2162-4011}, abstract = {Immune checkpoint blockade (ICPB) is a powerfully effective cancer therapy in some patients. Tumor neo-antigens are likely main targets for attack but it is not clear which and how many tumor mutations in individual cancers are actually antigenic, with or without ICPB therapy and their role as neo-antigen vaccines or as predictors of ICPB responses. To examine this, we interrogated the immune response to tumor neo-antigens in a murine model in which the tumor is induced by a natural human carcinogen (i.e. asbestos) and mimics its human counterpart (i.e. mesothelioma). We identified and screened 33 candidate neo-antigens, and found T cell responses against one candidate in tumor-bearing animals, mutant UQCRC2. Interestingly, we found a high degree of inter-animal variation in the magnitude of neo-antigen responses in otherwise identical mice. ICPB therapy with Cytotoxic T-lymphocyte-associated protein (CTLA-4) and α-glucocorticoid-induced TNFR family related gene (GITR) in doses that induced tumor regression, increased the magnitude of responses and unmasked functional T cell responses against another neo-antigen, UNC45a. Importantly, the magnitude of the pre-treatment draining lymph node (dLN) response to UNC45a closely corresponded to ICPB therapy outcomes. Surprisingly however, boosting pre-treatment UNC45a-specific T cell numbers did not improve response rates to ICPB. These observations suggest a novel biomarker approach to the clinical prediction of ICPB response and have important implications for the development of neo-antigen vaccines.}, }
@article {pmid32002298, year = {2020}, author = {Sneddon, S and Rive, CM and Ma, S and Dick, IM and Allcock, RJN and Brown, SD and Holt, RA and Watson, M and Leary, S and Lee, YCG and Robinson, BWS and Creaney, J}, title = {Identification of a CD8+ T-cell response to a predicted neoantigen in malignant mesothelioma.}, journal = {Oncoimmunology}, volume = {9}, number = {1}, pages = {1684713}, doi = {10.1080/2162402X.2019.1684713}, pmid = {32002298}, issn = {2162-4011}, abstract = {Neoantigens present unique and specific targets for personalized cancer immunotherapy strategies. Given the low mutational burden yet immunotherapy responsiveness of malignant mesothelioma (MM) when compared to other carcinogen-induced malignancies, identifying candidate neoantigens and T cells that recognize them has been a challenge. We used pleural effusions to gain access to MM tumor cells as well as immune cells in order to characterize the tumor-immune interface in MM. We characterized the landscape of potential neoantigens from SNVs identified in 27 MM patients and performed whole transcriptome sequencing of cell populations from 18 patient-matched pleural effusions. IFNγ ELISpot was performed to detect a CD8+ T cell responses to predicted neoantigens in one patient. We detected a median of 68 (range 7-258) predicted neoantigens across the samples. Wild-type non-binding to mutant binding predicted neoantigens increased risk of death in a model adjusting for age, sex, smoking status, histology and treatment (HR: 33.22, CI: 2.55-433.02, p = .007). Gene expression analysis indicated a dynamic immune environment within the pleural effusions. TCR clonotypes increased with predicted neoantigen burden. A strong activated CD8+ T-cell response was identified for a predicted neoantigen produced by a spontaneous mutation in the ROBO3 gene. Despite the challenges associated with the identification of bonafide neoantigens, there is growing evidence that these molecular changes can provide an actionable target for personalized therapeutics in difficult to treat cancers. Our findings support the existence of candidate neoantigens in MM despite the low mutation burden of the tumor, and may present improved treatment opportunities for patients.}, }
@article {pmid31987436, 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 = {31987436}, issn = {1569-8041}, }
@article {pmid31987095, year = {2019}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {11}, pages = {1844}, doi = {10.1093/annonc/mdz217}, pmid = {31987095}, issn = {1569-8041}, }
@article {pmid31977466, year = {2020}, author = {Fernández-Rodríguez, P and Martín-Marcuartu, JJ and Acevedo Báñez, I and Masero Carretero, JM and Jiménez-Hoyuela García, JM}, title = {99mTc-HDP Bone Scintigraphy, SPECT/CT, and 18F-FDG PET/CT Diagnosis Imaging of Incidental Pleural Mesothelioma in a Patient With Biochemical Recurrences of Prostate Cancer: Is it Really a Coincidence?.}, journal = {Clinical nuclear medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/RLU.0000000000002908}, pmid = {31977466}, issn = {1536-0229}, abstract = {We present the case of a 69-year-old man with history of prostate carcinoma treated with prostatectomy and subsequently with external beam radiotherapy and hormone therapy because of biochemical recurrences. More than 10 years after the diagnosis, follow-up Tc-HDP bone scans and SPECT/CT images demonstrated an incidental diagnosis of osteoblastic pleural plaques that quickly evolve to mesothelioma. PET/CT achieved the definitive diagnosis by guiding the biopsy to the highest and most accessible focus of glucidic hypermetabolism. Our case report raises the association between prostate cancer patients treated with external beam radiotherapy and the development of pleural mesothelioma despite having no history of exposure to asbestos.}, }
@article {pmid31967100, year = {2019}, author = {Vimercati, L and Cavone, D and Mansi, F and Cannone, ESS and DE Maria, L and Caputi, A and Delfino, MC and Serio, G}, title = {Health impact of exposure to asbestos in polluted area of Southern Italy.}, journal = {Journal of preventive medicine and hygiene}, volume = {60}, number = {4}, pages = {E407-E418}, doi = {10.15167/2421-4248/jpmh2019.60.4.1330}, pmid = {31967100}, issn = {2421-4248}, abstract = {The three main sources of asbestos pollution in the city of Bari, Puglia, the former Fibronit asbestos factory, the Torre Quetta beach, the former Rossani barracks and the history of their reclamation are described. The results of cohort studies on factory workers and case-control studies on asbestos exposure to the resident population and the onset of mesothelioma are also reported. Finally, the data of the regional register of mesothelioma related to residents in the city of Bari and four new cases with environmental exposure due to the former Rossani barracks are presented.}, }
@article {pmid31965908, year = {2019}, author = {Peterson, MK and Mohar, I and Lam, T and Cook, TJ and Engel, AM and Lynch, H}, title = {Critical review of the evidence for a causal association between exposure to asbestos and esophageal cancer.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {7}, pages = {597-613}, doi = {10.1080/10408444.2019.1692190}, pmid = {31965908}, issn = {1547-6898}, abstract = {Esophageal cancers comprise about 1% of all cancers diagnosed in the US but are more prevalent in other regions of the world. Several regulatory agencies have classified asbestos as a known human carcinogen, and it is linked to multiple diseases and malignancies, including lung cancer and mesothelioma. In a 2006 review of the epidemiological literature, the Institute of Medicine (IOM) did not find sufficient evidence to demonstrate a causal relationship between asbestos exposure and esophageal cancer. To reevaluate this conclusion, we performed a critical review of the animal toxicological, epidemiological, and mechanism of action literature on esophageal cancer and asbestos, incorporating studies published since 2006. Although there is some evidence in the epidemiological literature for an increased risk of esophageal cancer in asbestos-exposed occupational cohorts, these studies generally did not control for critical esophageal cancer risk factors (e.g. smoking, alcohol consumption). Furthermore, data from animal toxicological studies do not indicate that asbestos exposure increases esophageal cancer risk. Based on our evaluation of the literature, and reaffirming the IOM's findings, we conclude that there is insufficient evidence to demonstrate a causal link between asbestos exposure and esophageal cancer.}, }
@article {pmid31963601, year = {2020}, author = {Oddone, E and Bollon, J and Nava, CR and Bugani, M and Consonni, D and Marinaccio, A and Magnani, C and Barone-Adesi, F}, title = {Predictions of Mortality from Pleural Mesothelioma in Italy After the Ban of Asbestos Use.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {2}, pages = {}, doi = {10.3390/ijerph17020607}, pmid = {31963601}, issn = {1660-4601}, support = {research triennial plan of action 2016-2018, project BRIC n. 59//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; }, abstract = {Even if the epidemic of malignant pleural mesothelioma (MPM) is still far from being over worldwide, the health effects of regulations banning asbestos can be evaluated in the countries that implemented them early. Estimates of MPM future burden can be useful to inform and support the implementation of anti-asbestos health policies all around the world. With this aim we described the trends of MPM deaths in Italy (1970-2014) and predicted the future number of cases in both sexes (2015-2039), with consideration of the national asbestos ban that was issued in 1992. The Italian National Statistical Institute (ISTAT) provided MPM mortality figures. Cases ranging from 25 to 89 years of age were included in the analysis. For each five-year period from 1970 to 2014, mortality rates were calculated and age-period-cohort Poisson models were used to predict future burden of MPM cases until 2039. During the period 1970-2014 a total number of 28,907 MPM deaths were observed. MPM deaths increased constantly over the study period, ranging from 1356 cases in 1970-1974 to 5844 cases in 2010-2014. The peak of MPM cases is expected to be reached in the period 2020-2024 (about 7000 cases). The decrease will be slow: about 26,000 MPM cases are expected to occur in Italy during the next 20 years (2020-2039). The MPM epidemic in Italy is far from being concluded despite the national ban implemented in 1992, and the peak is expected in 2020-2024, in both sexes. Our results are consistent with international literature.}, }
@article {pmid31929796, year = {2019}, author = {Borchert, S and Suckrau, PM and Wessolly, M and Mairinger, E and Hegedus, B and Hager, T and Herold, T and Eberhardt, WEE and Wohlschlaeger, J and Aigner, C and Bankfalvi, A and Schmid, KW and Walter, RFH and Mairinger, FD}, title = {Screening of Pleural Mesothelioma Cell Lines for Kinase Activity May Identify New Mechanisms of Therapy Resistance in Patients Receiving Platin-Based Chemotherapy.}, journal = {Journal of oncology}, volume = {2019}, number = {}, pages = {2902985}, doi = {10.1155/2019/2902985}, pmid = {31929796}, issn = {1687-8450}, abstract = {Background: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumor associated with a dismal prognosis. Multimodal therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons underlying the rather poor efficacy of platinum compounds remain largely unknown. Kinase activity might influence cellular response to these regimens.<br><br>Materials and Methods: For this exploratory study, we screened MPM cell lines (NCI-H2452, NCI-H2052, and MSTO-211H) differing in response to cisplatin and benign control fibroblasts (MRC-5) for overall phosphorylation patterns as well as kinase activity with respect to cellular response to cisplatin-based therapeutics. We analysed the cell lines for cellular kinases in a high-throughput manner using the highly innovative technique PamGene. Cell state analysis including apoptosis, necrosis, and cell viability was performed by using enzyme activity and fluorescent-based assays.<br><br>Results: Cisplatin alters cellular phosphorylation patterns affecting cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis. In cisplatin-responsive cell lines, phosphorylation of AKT1 and GSK3B was decreased but could not be influenced in cisplatin-resistant NCI-H2452 cells. Cisplatin-responsive cell lines showed increased phosphorylation levels of JNK1/2/3 but decreased phosphorylation in cisplatin-resistant NCI-H2452 cells.<br><br>Conclusion: Kinase phosphorylation and activity might play a crucial role in cellular response to cytostatic agents. Cisplatin influences phosphorylation patterns with distinct features in cisplatin-resistant cells. These alterations exert a significant impact on cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis of the respective tumor cells. Based on our results, the induction of p38 or JNK1/3, or inhibition of AKT1 by, for example, BIA-6, might offer a positive synergistic effect by induction of an apoptotic response to cisplatin-based treatment, thus potentially enhancing the clinical outcome of MPM patients.}, }
@article {pmid31927297, year = {2019}, author = {Cox, LA}, title = {Nonlinear dose-time-response functions and health-protective exposure limits for inflammation-mediated diseases.}, journal = {Environmental research}, volume = {182}, number = {}, pages = {109026}, doi = {10.1016/j.envres.2019.109026}, pmid = {31927297}, issn = {1096-0953}, abstract = {Why have occupational safety regulations in the United States not been more successful in protecting worker health from mesothelioma risks, while apparently succeeding relatively well in reducing silicosis risks? This paper briefly discusses biological bases for thresholds and nonlinearities in exposure-response functions for respirable crystalline silica (RCS) and asbestos, based on modeling a chronic inflammation mode of action (mediated by activation of the NLRP3 inflammasome, for both RCS and asbestos). It applies previously published physiologically based pharmacokinetic (PBPK) models to perform computational experiments illuminating how different time courses of exposure with the same time-weighted average (TWA) concentration affect internal doses in target tissues (lung for RCS and mesothelium for asbestos). Key conclusions are that (i) For RCS, but not asbestos, limiting average (TWA) exposure concentrations also tightly constrains internal doses and ability to trigger chronic inflammation and resulting increases in disease risks (ii) For asbestos, excursions (i.e., spikes in concentrations); and especially the times between them are crucial drivers of internal doses and time until chronic inflammation; and hence (iii) These dynamic aspects of exposure, which are not addressed by current occupational safety regulations, should be constrained to better protect worker health. Adjusting permissible average exposure concentration limits (PELs) and daily excursion limits (ELs) is predicted to have little impact on reducing mesothelioma risks, but increasing the number of days between successive excursions is predicted to be relatively effective in reducing worker risks, even if it has little or no impact on TWA average concentrations.}, }
@article {pmid31921422, year = {2020}, author = {Kim, MK and Kim, HW and Jang, M and Oh, SS and Yong, SJ and Jeong, Y and Jung, SH and Choi, JW}, title = {LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma.}, journal = {Biomarker research}, volume = {8}, number = {}, pages = {1}, doi = {10.1186/s40364-019-0180-0}, pmid = {31921422}, issn = {2050-7771}, abstract = {Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database.<br><br>Methods: Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction.<br><br>Results: We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&amp;2 (LOXL1&amp; LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11).<br><br>Conclusions: LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities.}, }
@article {pmid31917456, year = {2020}, author = {Ugelvig Petersen, K and Pukkala, E and Martinsen, JI and Lynge, E and Tryggvadottir, L and Weiderpass, E and Kjærheim, K and Heikkinen, S and Hansen, J}, title = {Cancer incidence among seafarers and fishermen in the Nordic countries.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {}, number = {}, pages = {}, doi = {10.5271/sjweh.3879}, pmid = {31917456}, issn = {1795-990X}, abstract = {Objectives Maritime workers may be exposed to several occupational hazards at sea. The aim of this study was to assess cancer incidence among seafarers and fishermen in the Nordic countries and identify patterns in morbidity in the context of existing studies in this field. Methods A cohort of 81 740 male seafarers and 66 926 male fishermen was established from census data on 15 million citizens in the five Nordic countries. Using personal identity codes, information on vital status and cancer was linked to members of the cohort from the national population and cancer registries for the follow-up period 1961-2005. Standardized incidence ratios (SIR) were calculated applying national cancer incidence rates for each country and pooling results. Results The overall incidence of cancer was increased among the male seafarers [SIR 1.22, 95% confidence interval (CI) 1.19-1.23]. Significant excesses were observed for multiple cancer sites among the seafarers, while results for the fishermen were mixed. Lip cancer incidence was increased among both maritime populations. For mesothelioma (SIR 2.17, 95% CI 1.83-2.56 seafarers) and non-melanoma skin cancer (SIR 1.23, 95% CI 1.14-1.32 seafarers), incidence was increased among the seafarers. Conclusion In our cohort, seafaring was associated with a higher overall incidence of cancer compared to the general population. While the majority of cancers could not be linked to specific occupational factors, increases in mesothelioma, lip and non-melanoma-skin cancer indicate previous exposure to asbestos, ultraviolet radiation and potentially also chemicals with dermal carcinogenic properties at sea.}, }
@article {pmid31905913, year = {2019}, author = {Klebe, S and Leigh, J and Henderson, DW and Nurminen, M}, title = {Asbestos, Smoking and Lung Cancer: An Update.}, journal = {International journal of environmental research and public health}, volume = {17}, number = {1}, pages = {}, doi = {10.3390/ijerph17010258}, pmid = {31905913}, issn = {1660-4601}, abstract = {This review updates the scientific literature concerning asbestos and lung cancer, emphasizing cumulative exposure and synergism between asbestos exposure and tobacco smoke, and proposes an evidence-based and equitable approach to compensation for asbestos-related lung cancer cases. This update is based on several earlier reviews written by the second and third authors on asbestos and lung cancer since 1995. We reevaluated the peer-reviewed epidemiologic studies. In addition, selected in vivo and in vitro animal studies and molecular and cellular studies in humans were included. We conclude that the mechanism of lung cancer causation induced by the interdependent coaction of asbestos fibers and tobacco smoke at a biological level is a multistage stochastic process with both agents acting conjointly at all times. The new knowledge gained through this review provides the evidence for synergism between asbestos exposure and tobacco smoke in lung cancer causation at a biological level. The evaluated statistical data conform best to a multiplicative model for the interaction effects of asbestos and smoking on the lung cancer risk, with no requirement for asbestosis. Any asbestos exposure, even in a heavy smoker, contributes to causation. Based on this information, we propose criteria for the attribution of lung cancer to asbestos in smokers and non-smokers.}, }
@article {pmid31905042, year = {2020}, author = {Cox, LA}, title = {Dose-response modeling of NLRP3 inflammasome-mediated diseases: asbestos, lung cancer, and malignant mesothelioma as examples.}, journal = {Critical reviews in toxicology}, volume = {}, number = {}, pages = {1-22}, doi = {10.1080/10408444.2019.1692779}, pmid = {31905042}, issn = {1547-6898}, abstract = {Can a single fiber of amphibole asbestos increase the risk of lung cancer or malignant mesothelioma (MM)? Traditional linear no-threshold (LNT) risk assessment assumptions imply that the answer is yes: there is no safe exposure level. This paper draws on recent scientific progress in inflammation biology, especially elucidation of the activation thresholds for NLRP3 inflammasomes and resulting chronic inflammation, to model dose-response relationships for malignant mesothelioma and lung cancer risks caused by asbestos exposures. The modeling integrates a physiologically based pharmacokinetics (PBPK) front end with inflammation-driven two-stage clonal expansion (I-TSCE) models of carcinogenesis to describe how exposure leads to chronic inflammation, which in turn promotes carcinogenesis. Together, the combined PBPK and I-TSCE modeling predict that there are practical thresholds for exposure concentration below which asbestos exposure does not cause chronic inflammation in less than a lifetime, and therefore does not increase chronic inflammation-dependent cancer risks. Quantitative examples using model parameter estimates drawn from the literature suggest that practical thresholds may be within about a factor of 2 of some past exposure levels for some workers. The I-TSCE modeling framework explains previous puzzling aspects of asbestos epidemiology, such as why age at first exposure is a better predictor of lifetime MM risk than exposure duration. It may be a valuable tool for risk analysts when LNT assumptions are not justified due to inflammation response thresholds mediating dose-response relationships.}, }
@article {pmid31904012, year = {2019}, author = {Colin, DJ and Bejuy, O and Germain, S and Triponez, F and Serre-Beinier, V}, title = {Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {154}, pages = {}, doi = {10.3791/60272}, pmid = {31904012}, issn = {1940-087X}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor arising in the mesothelium that covers the lungs, the heart, and the thoracic cavity. MPM development is mainly associated with asbestos. Treatments provide only modest survival since the median survival average is 9-18 months from the time of diagnosis. Therefore, more effective treatments must be identified. Most data describing new therapeutic targets were obtained from in vitro experiments and need to be validated in reliable in vivo preclinical models. This article describes one such reliable MPM orthotopic model obtained after injection of a human MPM cell line H2052/484 into the pleural cavity of immunodeficient athymic mice. Transplantation in the orthotopic site allows studying the progression of tumor in the natural in vivo environment. Positron emission tomography/computed tomography (PET/CT) molecular imaging using the clinical [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG) radiotracer is the diagnosis method of choice for examining patients with MPM. Accordingly, [18F]FDG-PET/CT was used to longitudinally monitor the disease progression of the H2052/484 orthotopic model. This technique has a high 3R potential (Reduce the number of animals, Refine to lessen pain and discomfort, and Replace animal experimentation with alternatives) since the tumor development can be monitored non-invasively and the number of animals required could be significantly reduced. This model displays a high development rate, a rapid tumor growth, is cost-efficient and allows for rapid clinical translation. By using this orthotopic xenograft MPM model, researchers can assess biological responses of a reliable MPM model following therapeutic interventions.}, }
@article {pmid31901768, year = {2019}, author = {Lam, WS and Creaney, J and Chen, FK and Chin, WL and Muruganandan, S and Arunachalam, S and Attia, MS and Read, C and Murray, K and Millward, M and Spiro, J and Chakera, A and Gary Lee, YC and Nowak, AK}, title = {A phase II trial of single oral FGF inhibitor, AZD4547, as second or third line therapy in malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {140}, number = {}, pages = {87-92}, doi = {10.1016/j.lungcan.2019.12.018}, pmid = {31901768}, issn = {1872-8332}, abstract = {OBJECTIVES: Currently, there is no optimal salvage therapy for patients with malignant pleural mesothelioma (MPM) who relapse after treatment with first-line chemotherapy. In line with the strong preclinical rationale for targeting fibroblast growth factor receptor (FGFR) signalling in malignant mesothelioma, we conducted a phase II study assessing the efficacy of AZD4547, an oral tyrosine multi-kinase FGFR 1-3 inhibitor, as a second or third-line treatment.<br><br>MATERIALS AND METHODS: We conducted a single-center, open-label, single-arm phase II study of AZD4547 in eligible patients with confirmed, measurable MPM and radiological progression after first or second-line systemic chemotherapy. Patients received continuous, twice-daily oral AZD4547 on a 3-weekly cycle. The primary end point was 6-month progression free survival (PFS6). Response was assessed with CT scan every 6 weeks according to the modified RECIST criteria for mesothelioma (mRECIST) and toxicities were also assessed. The study used a Simon's two-stage design: 26 patients would be recruited to the first stage and more than 7 (27 %) of 26 patients were required to achieve PFS6 to continue to stage two, for a potential total cohort of 55 patients.<br><br>RESULTS: 3 of 24 patients (12 %) were progression-free at 6 months. Hence, the study fulfilled stopping criteria regardless of further recruitment and warranted discontinuation. The most common toxicities (across all grades) were hyperphosphatemia, xerostomia, mucositis, retinopathy, dysgeusia, and fatigue. Maximum toxicities were grade 2 or below for all patients across all cycles. There was no association between tumour BAP1 protein loss and clinical outcomes.<br><br>CONCLUSIONS: The FGFR 1-3 inhibitor AZD4547 did not demonstrate efficacy in patients with MPM who had progressed after first line treatment with platinum-based chemotherapy.}, }
@article {pmid31900296, year = {2020}, author = {Hinkamp, CA and Dalal, SN and Butt, Y and Cabo Chan, AV}, title = {Diffuse epithelioid malignant mesothelioma of the pleura presenting as a hydropneumothorax and vertebral body invasion.}, journal = {BMJ case reports}, volume = {13}, number = {1}, pages = {}, doi = {10.1136/bcr-2019-231987}, pmid = {31900296}, issn = {1757-790X}, abstract = {Malignant mesothelioma is an uncommon form of neoplastic transformation of the mesothelial cells that line the serosal surfaces of the body. It most commonly affects the pleura and is often associated with pleural effusions and pleural-based masses. The annual incidence in the United States is only 3300 cases, representing less than 0.3% of all cancers worldwide, although this is likely underestimated. We present a case of diffuse epithelioid malignant pleural mesothelioma in a patient with remote, short-term asbestos exposure complicated by recurrent left-sided hydropneumothoraces and pleural-based invasion of the T12 vertebral body, which represent two rare coexisting complications. This case illustrates the importance of maintaining a broad differential for hydropneumothorax, particularly as the risk factors may be decades removed and the degree of asbestos exposure to induce a malignant mesothelioma may be smaller than has been traditionally thought.}, }
@article {pmid31895128, year = {2019}, author = {Walters, GI}, title = {Occupational exposures and idiopathic pulmonary fibrosis.}, journal = {Current opinion in allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ACI.0000000000000610}, pmid = {31895128}, issn = {1473-6322}, abstract = {PURPOSE OF REVIEW: A recent meta-analysis of data from international case-control studies reports a population attributable fraction of 16% for occupational factors in the cause of idiopathic pulmonary fibrosis (IPF). Smoking, genetic factors and other prevalent diseases only partly explain IPF, and so this review aims to summarize recent progress in establishing which occupational exposures are important in cause.<br><br>RECENT FINDINGS: IPF is a rare disease, although it is the commonest idiopathic interstitial pneumonia. Epidemiological study suggests that incidence of IPF is increasing, particularly in older men. There are significant associations with IPF and occupational exposures to organic dust, including livestock, birds and animal feed, metal dust, wood dust and silica/minerals. Estimates of effect vary between studies, and are influenced by the distribution of employment, study design and case definition. Inhalation of asbestos fibres is a known cause of usual interstitial pneumonia (as seen histologically in IPF), though there are significant linear relationships between asbestos consumption, and mortality from both IPF and mesothelioma, leading to the hypothesis that low-level asbestos exposure may cause IPF.<br><br>SUMMARY: Research must focus on exposure-response relationships between asbestos and other occupational inhaled hazards, and IPF. Funding bodies and policy makers should acknowledge the significant occupational burden on IPF.}, }
@article {pmid31887736, year = {2019}, author = {Totaro, M and Giorgi, S and Filippetti, E and Gallo, A and Frendo, L and Privitera, G and Baggiani, A}, title = {[Asbestos in drinking water and hazards to human health: a narrative synthesis].}, journal = {Igiene e sanita pubblica}, volume = {75}, number = {4}, pages = {303-312}, pmid = {31887736}, issn = {0019-1639}, abstract = {The term asbestos refers to six unique fibrous minerals mostly used in the production of asbestos cement sheets and pipes. According to the World Health Organization and the International Agency for Research on Cancer (IARC), there exists at least &amp;quot;sufficient evidence&amp;quot; that all types of asbestos may cause cancer in humans (mesothelioma, lung cancer, laryngeal tumor and ovarian cancer). The only asbestos limit in drinking water is 7 million fiber/liter. This study is a narrative synthesis about the possible hazards to human health related to the presence of asbestos in drinking water. The various scientific studies and epidemiological reports examined highlight that there is an ongoing debate on the possible carcinogenic risk associated with asbestos exposure through ingestion. Nevertheless, considering the latency with which diseases caused by asbestos may emerge, control measures should be adopted.}, }
@article {pmid31878930, year = {2019}, author = {Vimercati, L and Cavone, D and Delfino, MC and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Response to the &quot;Letter to the Editor&quot; by Gabor Mezei et al., Comments on Vimercati et al., 2019, &quot;Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (Southern Italy) mesothelioma register&quot;.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {112}, doi = {10.1186/s12940-019-0553-8}, pmid = {31878930}, issn = {1476-069X}, }
@article {pmid31878926, year = {2019}, author = {Mezei, G and Chang, ET and Mowat, FS and Moolgavkar, SH}, title = {Comments on Vimercati et al., 2019, &quot;Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (southern Italy) mesothelioma register&quot;.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {111}, doi = {10.1186/s12940-019-0552-9}, pmid = {31878926}, issn = {1476-069X}, }
@article {pmid31876833, year = {2019}, author = {Kodama, E and Kodama, T and Ichikawa, T and Ikoma, H and Hashimoto, J}, title = {18F-FDG Uptake of Localized Malignant Peritoneal Mesothelioma.}, journal = {Clinical nuclear medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/RLU.0000000000002901}, pmid = {31876833}, issn = {1536-0229}, abstract = {We present 2 cases of malignant peritoneal mesothelioma (MPM) characterized by a localized solid mass without ascites and showing F-FDG uptake. A 79-year-old man with a history of asbestos exposure suffered from an epithelioid MPM originating from the hepatoduodenal ligament with FDG uptake (SUVmax 16.8). Another 80-year-old man with esophageal cancer showed desmoplastic MPM of the small bowel mesentery with FDG uptake (SUVmax 4.0). Desmoplastic MPM is more aggressive and yields poorer prognosis compared with the epithelioid type. However, the present desmoplastic MPM case showed mild FDG uptake because of rich fibrosis.}, }
@article {pmid31876584, year = {2019}, author = {Pavlisko, EN and Liu, B and Green, C and Sporn, TA and Roggli, VL}, title = {Malignant Diffuse Mesothelioma in Women: A Study of 354 Cases.}, journal = {The American journal of surgical pathology}, volume = {}, number = {}, pages = {}, doi = {10.1097/PAS.0000000000001418}, pmid = {31876584}, issn = {1532-0979}, abstract = {We reviewed 354 cases of malignant diffuse mesothelioma (MM) in women from a database of 2858 histologically confirmed MM cases. There was a pleural predominance with 78% pleural MM and 22% peritoneal MM. The pleural tumors consisted of 72% epithelioid, 19% biphasic, and 9% sarcomatoid variant. The peritoneal tumors consisted of 82% epithelioid, 13% biphasic, and 5% sarcomatoid. The immunohistochemical profile was typical of what is well-accepted and previously described for MM. When examining tumor subtype and location, there was a trend toward epithelioid subtype and peritoneal location; however, this did not reach statistical significance. Age at the time of diagnosis ranged from 19 to 93 years with a mean of 60 years. The median age at time of diagnosis for pleural MM was 65 years and for peritoneal MM was 52 years. A further look at age and histologic subtype showed no statistically significant difference in age between MM subtypes. Survival was greatest for epithelioid variant, and this was magnified in the peritoneum. A majority of our cases were exposed to asbestos through a household contact. Asbestosis and parietal pleural plaque were present in 5% and 50% of cases with data, respectively. Fiber analysis data was available in 67 cases; 38 cases had elevated asbestos fiber burden, and tremolite was the most common asbestos fiber type detected. Commercial and noncommercial amphibole asbestos fibers were elevated in nearly equal numbers of cases.}, }
@article {pmid31867277, year = {2019}, author = {Chu, GJ and van Zandwijk, N and Rasko, JEJ}, title = {The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1366}, doi = {10.3389/fonc.2019.01366}, pmid = {31867277}, issn = {2234-943X}, abstract = {Although mesothelioma is the consequence of a protracted immune response to asbestos fibers and characterized by a clear immune infiltrate, novel immunotherapy approaches show less convincing results as compared to those seen in melanoma and non-small cell lung cancer. The immune suppressive microenvironment in mesothelioma is likely contributing to this therapy resistance. Therefore, it is important to explore the characteristics of the tumor microenvironment for explanations for this recalcitrant behavior. This review describes the stromal, cytokine, metabolic, and cellular milieu of mesothelioma, and attempts to make connection with the outcome of immunotherapy trials.}, }
@article {pmid31850200, year = {2019}, author = {Tomasetti, M and Gaetani, S and Monaco, F and Neuzil, J and Santarelli, L}, title = {Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {1293}, doi = {10.3389/fonc.2019.01293}, pmid = {31850200}, issn = {2234-943X}, abstract = {Asbestos exposure leads to epigenetic and epigenomic modifications that, in association with ROS-induced DNA damage, contribute to cancer onset. Few miRNAs epigenetically regulated in MM have been described in literature; miR-126, however, is one of them, and its expression is regulated by epigenetic mechanisms. Asbestos exposure induces early changes in the miRNAs, which are reversibly expressed as protective species, and their inability to reverse reflects the inability of the cells to restore the physiological miRNA levels despite the cessation of carcinogen exposure. Changes in miRNA expression, which results from genetic/epigenetic changes during tumor formation and evolution, can be detected in fluids and used as cancer biomarkers. This article has reviewed the epigenetic mechanisms involved in miRNA expression in MM, focusing on their role as biomarkers of early diagnosis and therapeutic effects.}, }
@article {pmid31846450, year = {2019}, author = {Apostoli, P and Boffetta, P and Bovenzi, M and Cocco, PL and Consonni, D and Cristaudo, A and Discalzi, G and Farioli, A and Manno, M and Mattioli, S and Pira, E and Soleo, L and Taino, G and Violante, FS and Zocchetti, C}, title = {Position Paper on Asbestos of the Italian Society of Occupational Medicine.}, journal = {La Medicina del lavoro}, volume = {110}, number = {6}, pages = {459-485}, doi = {10.23749/mdl.v110i6.9022}, pmid = {31846450}, issn = {0025-7818}, abstract = {The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML's Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.}, }
@article {pmid31842309, year = {2019}, author = {Vernez, D and Duperrex, O and Herrera, H and Perret, V and Rossi, I and Regamey, F and Guillemin, M}, title = {Exposure to Amosite-Containing Ceiling Boards in a Public School in Switzerland: A Case Study.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/ijerph16245069}, pmid = {31842309}, issn = {1660-4601}, abstract = {The measurement of an airborne concentration in Amosite fibers above 5035 F/m3 in a school prompted a retrospective quantitative health risk assessment. Dose estimates were built using air measurements, laboratory experiments, previous exposure data, and interviews. A dose response model was adapted for amosite-only exposure and adjusted for the life expectancy and lung cancer incidence in the Swiss population. The average yearly concentrations found were 52-320 F/m3. The high concentration previously observed was not representative of the average exposure in the building. Overall, the risk estimates for the different populations of the school were low and in the range of 2 × 10-6 to 3 × 10-5 for mesothelioma and 4 × 10-7 to 8 × 10-6 for lung cancer. The results evidenced however that children have to be considered at higher risk when exposed to asbestos, and that the current reference method and target values are of limited use for amphibole-only exposures. This study confirmed that quantitative health risk assessments and participatory approaches are powerful tools to support public decisions and build constructive communication between exposed people, experts, and policy-makers.}, }
@article {pmid31833271, year = {2019}, author = {Pellegrini, I and Sibille, A and Paulus, A and Vaillant, F and Radermecker, MA and Corhay, JL and Louis, R and Duysinx, B}, title = {[How I manage... Malignant pleural mesothelioma in 2019].}, journal = {Revue medicale de Liege}, volume = {74}, number = {12}, pages = {627-632}, pmid = {31833271}, issn = {0370-629X}, mesh = {Antineoplastic Combined Chemotherapy Protocols ; Bevacizumab ; Combined Modality Therapy ; Humans ; *Mesothelioma/drug therapy ; Pemetrexed ; *Pleural Neoplasms/drug therapy ; }, abstract = {Malignant pleural mesothelioma is a rare disease originating from mesothelial cells of the pleura and is related to asbestos exposure. The tumor is generally extended at the time of diagnosis and the treatment consists of a systemic palliative therapy. Radical approach is limited to very selected patients and is performed in expert centers but without validated schema. Radiotherapy alone is mainly used in palliative intent. Platinum-based chemotherapy in association with pemetrexed is the frontline standard of care and provides a 12-month overall survival. The addition of bevacizumab, an antiangiogenic drug, shows an improvement in median survival. To date, there is no second-line treatment approved for this disease and therefore inclusion in trials is recommended. Currently, various studies are investigating target therapy, immunotherapy and intrapleural perioperative treatment.}, }
@article {pmid31823764, year = {2019}, author = {Kishimoto, T and Fujimoto, N and Ebara, T and Omori, T and Oguri, T and Niimi, A and Yokoyama, T and Kato, M and Usami, I and Nishio, M and Yoshikawa, K and Tokuyama, T and Tamura, M and Yokoyama, Y and Tsuboi, K and Matsuo, Y and Xu, J and Takahashi, S and Abdelgied, M and Alexander, WT and Alexander, DB and Tsuda, H}, title = {Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {1204}, doi = {10.1186/s12885-019-6419-1}, pmid = {31823764}, issn = {1471-2407}, support = {14030101-01//Ministry of Health, Labour and Welfare/ ; 13801370//Ministry of Health, Labour and Welfare/ ; 16768893//Ministry of Health, Labour and Welfare/ ; H24//Princess Takamatsu Cancer Research Fund/ ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients.<br><br>METHODS: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA.<br><br>RESULTS: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM.<br><br>CONCLUSIONS: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.}, }
@article {pmid31821579, year = {2019}, author = {Ferrante, D and Mirabelli, D and Silvestri, S and Azzolina, D and Giovannini, A and Tribaudino, P and Magnani, C}, title = {Mortality and mesothelioma incidence among chrysotile asbestos miners in Balangero, Italy: A cohort study.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23071}, pmid = {31821579}, issn = {1097-0274}, support = {//This study was partially supported by Istituto Superiore di Sanità - Progetto Amianto (to C.M)/ ; }, abstract = {BACKGROUND: We studied cancer mortality and mesothelioma incidence in 974 male workers employed at least 6 months at the Balangero mine (Italy), the largest chrysotile mine in Western Europe, active from 1917 to 1985.<br><br>METHODS: Vital status as of 31 May 2013, causes of deaths and mesothelioma incidence from 1990 were ascertained. Past exposure to asbestos by working area and calendar period was estimated, based on historical data of fibers concentrations. Individual cumulative exposure was assessed by applying estimates to the job history of cohort members. Standardized mortality ratios (SMRs) for selected causes and standardized incidence ratios for malignant mesothelioma (MM) were calculated based on regional reference rates. Poisson regression analysis was used to study MM and lung cancer risk by latency, duration, and cumulative exposure.<br><br>RESULTS: Mortality was increased for all causes (SMR = 1.28; 95% confidence interval [CI] = 1.17-1.40), pleural cancer (SMR = 4.30; 95% CI = 1.58-9.37), asbestosis (SMR = 375.06; 95% CI = 262.68-519.23). An increase was also found for lung cancer (SMR = 1.14; 95% CI = 0.81-1.55) and peritoneal cancer (SMR = 3.25; 95% CI = 0.39-11.75). The risk of both pleural and peritoneal cancer mortality and of mesothelioma incidence increased with increasing cumulative exposure, duration, and latency. Poisson regression analyses showed an increase in mesothelioma risk with cumulative asbestos exposure and suggest a similar trend for lung cancer. Asbestosis mortality also increased with cumulative exposure.<br><br>CONCLUSIONS: Among Balangero chrysotile miners and millers, the occurrence of malignant and nonmalignant asbestos-related diseases was increased by exposure, with dose-response relation. The study confirms the carcinogenicity of chrysotile asbestos, in particular for pleural mesothelioma.}, }
@article {pmid31819191, year = {2019}, author = {Urso, L and Cavallari, I and Sharova, E and Ciccarese, F and Pasello, G and Ciminale, V}, title = {Metabolic rewiring and redox alterations in malignant pleural mesothelioma.}, journal = {British journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41416-019-0661-9}, pmid = {31819191}, issn = {1532-1827}, abstract = {Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in 18F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.}, }
@article {pmid31814459, year = {2019}, author = {Pfau, JC and McNew, T and Hanley, K and Swan, L and Black, B}, title = {Autoimmune markers for progression of Libby amphibole lamellar pleural thickening.}, journal = {Inhalation toxicology}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/08958378.2019.1699616}, pmid = {31814459}, issn = {1091-7691}, abstract = {Exposure to Libby Asbestiform Amphibole (LAA) is associated with asbestos-related diseases, including mesothelioma, pulmonary carcinoma, pleural fibrosis, and systemic autoimmune diseases. The pleural fibrosis can manifest as a rapidly progressing lamellar pleural thickening (LPT), which causes thoracic pain, dyspnea, and worsening pulmonary function tests (PFT). It is refractory to treatment and frequently fatal.Objective: Because of the immune dysfunction that has been described in the LAA-exposed population and the association of pleural manifestations with the presence of autoantibodies, this study tested whether specific immunological factors were associated with progressive LPT and whether they could be used as markers of progressive disease.Methods: Subjects were placed into three study groups defined as (1) progressive LPT, (2) stable LPT, (3) no LPT. Serum samples were tested for antinuclear autoantibodies, mesothelial cell autoantibodies, anti-plasminogen antibodies, IL1 beta, and IL17; which have all been shown to be elevated in mice and/or humans exposed to LAA.Results: Group 1 had significantly higher mean values for all of the autoantibodies, but not IL1 or IL-17, compared to the control Group 3. All three autoantibody tests had high specificity but low sensitivity, but ROC area-under-the-curve values for all three antibodies were over 0.7, statistically higher than a test with no value. When all LPT subjects were combined (Progressive plus Stable), no marker had predictive value for disease.Conclusion: The data support the hypothesis that progressive LPT is associated with immunological findings that may serve as an initial screen for progressive LPT.}, }
@article {pmid31812249, year = {2019}, author = {Consonni, D and De Matteis, S and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Impact of an asbestos cement factory on mesothelioma incidence in a community in Italy.}, journal = {Environmental research}, volume = {}, number = {}, pages = {108968}, doi = {10.1016/j.envres.2019.108968}, pmid = {31812249}, issn = {1096-0953}, abstract = {BACKGROUND: Broni is a small town (9000 inhabitants) in the province of Pavia, Lombardy, north-west Italy, where the second largest Italian asbestos cement factory (Fibronit) was in operation between 1932 and 1993. Based on Lombardy Mesothelioma Registry (RML) data (2000-2011), we previously showed a high impact of asbestos exposure on malignant mesothelioma (MM) incidence among Fibronit workers, their families, and people living in Broni and in the nearby town of Stradella (11,000 residents). Given the great concern of the community, we have recently updated the data regarding 5 more years (2012-2016).<br><br>METHODS: From the RML database we extracted subjects who ever worked in Fibronit, their family members, ever residents in Broni, and subjects living in Stradella and nearby towns at the time of diagnosis. For each type of exposure we calculated standardized incidence ratios (SIR = observed/expected cases).<br><br>RESULTS: In the period 2000-2016 we registered 56 cases (2.52 expected, SIR = 22.2), 49 men (41 pleural, 8 peritoneal MM), 7 women (5 pleural, 2 peritoneal MM) with past occupational exposure in Fibronit. Among subjects never occupationally exposed and never exposed to extra-occupational sources unrelated to Fibronit, we counted 39 cases (4.24 expected, SIR = 9.2), 10 men (all pleural MM), 29 women (28 pleural, 1 peritoneal MM) in Fibronit workers' families, 91 pleural mesothelioma cases (7.43 expected, SIR = 12.2, 31 men, 60 women), ever residents in Broni, and 25 pleural mesothelioma cases (3.05 expected, SIR = 8.2, 6 men, 19 women) living in Stradella at the time of diagnosis. The overall number of excess cases was about 194 (211 against 17.24 expected). In the remaining adjacent (No. 8) and surrounding (No. 17) municipalities (32,000 people) there were 7 cases (1 men, 6 women, 8.85 expected).<br><br>CONCLUSION: The mesothelioma burden related to the asbestos cement factory is still high on factory workers, their families, and residents in Broni and Stradella towns.}, }
@article {pmid31807495, year = {2019}, author = {Johnson, TG and Schelch, K and Mehta, S and Burgess, A and Reid, G}, title = {Corrigendum: Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {293}, pmid = {31807495}, issn = {2296-634X}, abstract = {[This corrects the article DOI: 10.3389/fcell.2019.00221.].}, }
@article {pmid31783178, year = {2019}, author = {Mian, I and Abdullaev, Z and Morrow, B and Kaplan, RN and Gao, S and Mettienen, M and Schrump, DS and Zgonc, V and Wei, JS and Khan, J and Pack, S and Hassan, R}, title = {Anaplastic lymphoma kinase (ALK) Gene Rearrangement in Children and Young Adults with Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtho.2019.11.011}, pmid = {31783178}, issn = {1556-1380}, abstract = {INTRODUCTION: Children and young adults diagnosed with malignant mesothelioma may have unique genetic characteristics. In this study, we evaluated for the presence of the anaplastic lymphoma kinase (ALK) translocations in these patients.<br><br>METHODS: In a prospective study of mesothelioma natural history (MNH) (ClinicalTrials.gov number NCT01950572) we assessed for the presence of the ALK translocation in patients less than 40 years old, irrespective of site of disease. The presence of this translocation was assessed via fluorescence in-situ hybridization (FISH). If positive, both immunohistochemistry (IHC) and RNA sequencing (RNASeq) were performed on the tumor specimen.<br><br>RESULTS: Between September 2013 and December 2018, 373 patients were enrolled on the MNH study of which 32 patients were <40 years old at the time of their mesothelioma diagnosis. 25 patients had peritoneal, 5 pleural, 1 pericardial and 1 had bi-compartmental mesothelioma. Presence of an ALK translocation by FISH was seen in 2 of the 32 (6%) mesothelioma patients. Both patients, a 14 year old female and a 27 year old male, had peritoneal mesothelioma and neither had history of asbestos exposure, prior radiation or predisposing germline mutations. Neither had detectable ALK expression by IHC. RNAseq revealed the presence of an STRN fusion partner in the female patient but failed to identify any fusion protein in the male patient.<br><br>CONCLUSIONS: Young patients with peritoneal mesothelioma should be evaluated for the presence of ALK translocations. Presence of this translocation should be assessed by FISH and these patients could potentially benefit from tyrosine kinase inhibitors targeting ALK.}, }
@article {pmid31766522, year = {2019}, author = {Martinotti, S and Patrone, M and Moccia, F and Ranzato, E}, title = {Targeting Calcium Signalling in Malignant Mesothelioma.}, journal = {Cancers}, volume = {11}, number = {12}, pages = {}, doi = {10.3390/cancers11121839}, pmid = {31766522}, issn = {2072-6694}, abstract = {Calcium ions (Ca2+) are central in cancer development and growth, serving as a major signaling system determining the cell's fate. Therefore, the investigation of the functional roles of ion channels in cancer development may identify novel approaches for determining tumor prognosis. Malignant mesothelioma is an aggressive cancer that develops from the serosal surface of the body, strictly related to asbestos exposure. The treatment of malignant mesothelioma is complex and the survival outcomes, rather than the overall survival data are, to date, disappointedly daunting. Nevertheless, conventional chemotherapy is almost ineffective. The alteration in the expression and/or activity of Ca2+ permeable ion channels seems to be characteristic of mesothelioma cells. In this review, we explore the involvement of the Ca2+toolkit in this disease. Moreover, the established sensitivity of some Ca2+channels to selective pharmacological modulators makes them interesting targets for mesothelioma cancer therapy.}, }
@article {pmid31755376, year = {2019}, author = {Celsi, F and Crovella, S and Moura, RR and Schneider, M and Vita, F and Finotto, L and Zabucchi, G and Zacchi, P and Borelli, V}, title = {Pleural mesothelioma and lung cancer: the role of asbestos exposure and genetic variants in selected iron metabolism and inflammation genes.}, journal = {Journal of toxicology and environmental health. Part A}, volume = {82}, number = {20}, pages = {1088-1102}, doi = {10.1080/15287394.2019.1694612}, pmid = {31755376}, issn = {1528-7394}, abstract = {Two of the major cancerous diseases associated with asbestos exposure are malignant pleural mesothelioma (MPM) and lung cancer (LC). In addition to asbestos exposure, genetic factors have been suggested to be associated with asbestos-related carcinogenesis and lung genotoxicity. While genetic factors involved in the susceptibility to MPM were reported, to date the influence of individual genetic variations on asbestos-related lung cancer risk is still poorly understood. Since inflammation and disruption of iron (Fe) homeostasis are hallmarks of asbestos exposure affecting the pulmonary tissue, this study aimed at investigating the association between Fe-metabolism and inflammasome gene variants and susceptibility to develop LC or MPM, by comparing an asbestos-exposed population affected by LC with an &quot;asbestos-resistant exposed population&quot;. A retrospective approach similar to our previous autopsy-based pilot study was employed in a novel cohort of autoptic samples, thus giving us the possibility to corroborate previous findings obtained on MPM by repeating the analysis in a novel cohort of autoptic samples. The protective role of HEPH coding SNP was further confirmed. In addition, the two non-coding SNPs, either in FTH1 or in TF, emerged to exert a similar protective role in a new cohort of LC exposed individuals from the same geographic area of MPM subjects. No association was found between NLRP1 and NLRP3 polymorphisms with susceptibility to develop MPM and LC. Further research into a specific MPM and LC &quot;genetic signature&quot; may be needed to broaden our knowledge of the genetic landscape attributed to result in MPM and LC.}, }
@article {pmid31743489, year = {2019}, author = {Cummings, KJ and Becich, MJ and Blackley, DJ and Deapen, D and Harrison, R and Hassan, R and Henley, SJ and Hesdorffer, M and Horton, DK and Mazurek, JM and Pass, HI and Taioli, E and Wu, XC and Zauderer, MG and Weissman, DN}, title = {Workshop summary: Potential usefulness and feasibility of a US National Mesothelioma Registry.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23062}, pmid = {31743489}, issn = {1097-0274}, support = {//Mesothelioma Applied Research Foundation/ ; CDC NIOSH 1-U19-OH009077//National Institute for Occupational Safety and Health (NIOSH)/ ; //Centers for Disease Control and Prevention (CDC)/ ; CDC NIOSH 1-U19-OH009077/OH/NIOSH CDC HHS/United States ; N/A/OH/NIOSH CDC HHS/United States ; N/A//Mesothelioma Applied Research Foundation/ ; }, abstract = {The burden and prognosis of malignant mesothelioma in the United States have remained largely unchanged for decades, with approximately 3200 new cases and 2400 deaths reported annually. To address care and research gaps contributing to poor outcomes, in March of 2019 the Mesothelioma Applied Research Foundation convened a workshop on the potential usefulness and feasibility of a national mesothelioma registry. The workshop included formal presentations by subject matter experts and a moderated group discussion. Workshop participants identified top priorities for a registry to be (a) connecting patients with high-quality care and clinical trials soon after diagnosis, and (b) making useful data and biospecimens available to researchers in a timely manner. Existing databases that capture mesothelioma cases are limited by factors such as delays in reporting, deidentification, and lack of exposure information critical to understanding as yet unrecognized causes of disease. National disease registries for amyotrophic lateral sclerosis (ALS) in the United States and for mesothelioma in other countries, provide examples of how a registry could be structured to meet the needs of patients and the scientific community. Small-scale pilot initiatives should be undertaken to validate methods for rapid case identification, develop procedures to facilitate patient access to guidelines-based standard care and investigational therapies, and explore approaches to data sharing with researchers. Ultimately, federal coordination and funding will be critical to the success of a National Mesothelioma Registry in improving mesothelioma outcomes and preventing future cases of this devastating disease.}, }
@article {pmid31732616, year = {2019}, author = {Eckert, RL and Kandasamy, S and Adhikary, G and Rorke, EA and Friedberg, JS and Mickle, MB and Alexander, HR}, title = {The YAP1 signaling inhibitors, verteporfin and CA3, suppress the mesothelioma cancer stem cell phenotype.}, journal = {Molecular cancer research : MCR}, volume = {}, number = {}, pages = {}, doi = {10.1158/1541-7786.MCR-19-0914}, pmid = {31732616}, issn = {1557-3125}, abstract = {Mesothelioma is an aggressive cancer that has a poor prognosis. Tumors develop in the mesothelial lining of the pleural and peritoneal cavities in response to asbestos exposure. Surgical debulking followed by chemotherapy is initially effective, but this treatment ultimately selects for resistant cells that form aggressive and therapy resistant recurrent tumors. Mesothelioma cancer stem cells (MCS cells) are a highly aggressive subpopulation present in these tumors that are responsible for tumor maintenance and drug resistance. In the present manuscript, we examine the impact of targeting YAP1/TAZ/TEAD signaling in MCS cells. YAP1, TAZ and TEADs are transcriptional mediators of the Hippo signaling cascade that activate gene expression to drive tumor formation. We show that two YAP1 signaling inhibitors, verteporfin and CA3, attenuate the MCS cell phenotype. Verteporfin or CA3 treatment reduces YAP1/TEAD level/activity to suppress MCS cell spheroid formation, matrigel invasion, migration and tumor formation. These agents also increase MCS cell apoptosis. Moreover, constitutively-active YAP1 expression antagonizes inhibitor action, suggesting that loss of YAP1/TAZ/TEAD signaling is required for response to verteporfin and CA3. These agents are active against mesothelioma cells derived from peritoneal (epithelioid) and patient-derived pleural (sarcomatoid) mesothelioma, suggesting that targeting YAP1/TEAD signaling may be a useful treatment strategy. Implications: These studies suggest that inhibition of YAP1 signaling may be a viable approach to treating mesothelioma.}, }
@article {pmid31727556, year = {2019}, author = {Lorentz, E and Despreaux, T and Quignette, A and Chinet, T and Descatha, A}, title = {[Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma].}, journal = {Revue des maladies respiratoires}, volume = {36}, number = {10}, pages = {1088-1095}, doi = {10.1016/j.rmr.2019.08.006}, pmid = {31727556}, issn = {1776-2588}, abstract = {INTRODUCTION: In the context of underreporting of occupational diseases, the aim was to study the validity of silica and asbestos job-exposure matrices in screening occupational exposure in the field of thoracic oncology.<br><br>METHODS: Fifty patients hospitalized with primitive lung cancer or mesothelioma in a university hospital center in the Hauts-de-Seine department of France were included between November 2016 and September 2017. For each patient 1/the job history was collected, from which data was entered single-blindly into the job-exposure matrices by a resident in occupational medicine, 2/a questionnaire (Q-SPLF) was completed similarly, and 3/the patients also had a consultation with a chief resident in occupational medicine, considered the gold standard. The main outcome was the diagnostic performance of the matrices. The Q-SPLF diagnostic performance was also studied.<br><br>RESULTS: The asbestos and silica matrices had sensitivities of 100%, specificities of respectively 76.1% and 87.8%, the positive likelihood ratios were at 4.19 [2.5-6] and 8.17 [3.8-10], and the negative likelihood ratios were at 0. The Q-SPLF diagnostic performance was comparable to that of the matrices.<br><br>CONCLUSIONS: The matrices and the questionnaire have a great diagnostic performance which seems interesting for a use as a screening tool for occupational exposures. These results have yet to be confirmed by large-scale studies.}, }
@article {pmid31720691, year = {2019}, author = {Alblin, M and Gustavsson, P}, title = {A silent epidemic: occupational exposure limits are insufficiently protecting individual worker health.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {}, number = {}, pages = {}, doi = {10.5271/sjweh.3864}, pmid = {31720691}, issn = {1795-990X}, abstract = {In an editorial in an earlier issue of this journal, Johanson &amp; Tinnerberg (1) expressed serious and well-founded concern over the large number of future occupational cancer cases that will result if exposures for a number of substances are not reduced below the so-called &quot;binding occupational exposure limit values&quot; (BOELV) issued by the EU (2). The balance between what is perceived as possible to comply with and the foreseeable health gain when setting BOELV is further discussed in a letter to the Editor by Cherrie (3). This debate raises several important aspects of how to protect workers from cancer as well as other potentially lethal diseases. Herewith, we discuss some of these aspects. One problem in setting OEL is that levels that are considered safe may not be seen as feasible when accounting for technological and societal aspects. The EU has recognized this problem by distinguishing between so-called &quot;indicative&quot; (health-based) and legally binding OEL (4). However, a BOELV that does not protect from a high risk for severe health effects is not adequate. Both Johanson &amp; Tinnerberg and Cherrie point to respirable crystalline silica (RCS) as an example: While the EU's Scientific Committee on Occupational Exposure Limits (SCOEL) recommended an OEL <0.05 (5) in order to protect workers reasonably well against negative health effects, the EU decided on a BOELV of 0.1 mg/m 3for RCS (2). The US Occupational Health and Safety administration (OSHA) has come to a different conclusion and decided on an OEL of 0.05 mg/m 3(6). The EU has presented an extensive risk assessment for RCS developed within the SHEcan project (7). We argue that a BOELV at 0.1 is insufficient and partly may be due to misinterpretations of the SHEcan report. The report estimates the future number of lung cancer cases attributable to occupational exposure to RCS in the EU up to 2069. Four scenarios are discussed: (i) a baseline scenario, essentially predicting future numbers of cases without further regulatory action, (ii) a BOELV of 0.2 mg/m3 with 99% compliance, (iii) a BOELV of 0.1 mg/m 3with 99% compliance, and (iv) a BOELV of 0.05 mg/m 3with 99% compliance. The estimations are based on an assumption of a latency period of 10-50 years from reduction of exposure until cancer risk drops. This assumption, in itself reasonable from present evidence, has the consequence that there is virtually no difference in projected annual future cases between the four scenarios for ≥40 years. The reduction in exposure in scenarios ii-iv comes into effect first only in the year 2050 (see figure 4.1 on p49 in ec.europa.eu/social/BlobServlet?docId=10161&amp;langId=en). An assumption of 99% compliance with the BOELV in scenarios ii-iv has a dramatically stronger effect on the projected number of cases than the OEL itself: Even if the OEL was doubled to 0.2 mg/m 3the number of attributable cancer registrations in 2060 would be reduced by 70% just from the assumption of almost full compliance. The additional number of attributable cancer registrations that are prevented when an OEL of 0.1 (scenario iii) is compared to an OEL of 0.05 (scenario iv) under an assumption of almost full compliance is comparatively small (7, p123). The reason for this strong effect of a 99% compliance is that exposure often will exceed the OEL. The report may lead to the misconception that an OEL of 0.05 mg/m 3has little benefit over an OEL of 0.1 mg/m 3, especially if the cases saved are expressed as lives saved per year over the entire 60-year period. For Sweden and other countries where OEL already have legal status, the introduction of BOELV would have no legal implications. The SHEcan report shows that occupational exposure to silica will cause in all 440 000 cancer cases between 2010 and 2069 in the EU if nothing further is done (scenario i). This number must be reduced even if it will take time until preventive measures have full effect. An analogy with asbestos is obvious: it is well known that reductions in the mesothelioma rate were seen first only many decades after asbestos was banned - yet no one would argue that it was not worth reducing asbestos exposure for this reason. The report assumes an annual 7% decrease in silica exposure levels until the period 2020-2029 even if no further regulatory action is taken. This is a very questionable assumption that went unconfirmed in a recent French report (8) that gave no evidence for reduced exposure to RCS in the French construction sector during the last decade. This indicates that even the very high number of 440 000 attributable cancer registrations is underestimated by the report, to which, in addition, should be added the number of chronic obstructive pulmonary disease and kidney disease cases, for which a much shorter latency period until risk drops is likely. The concepts &quot;maximum tolerable risk&quot; and &quot;acceptable risk&quot; have been developed for exposure to genotoxic carcinogens, for which no exposure level could be considered safe. A life-time extra number of four cases per 1000 exposed workers over a 40-year working life has been suggested as a maximum tolerable risk, and four cases per 100 000 exposed workers as an acceptable risk, both in Germany and in the Netherlands (9, 10). These figures can be transformed to the individual life-time risk of contracting cancer from the exposure as 4/1000, corresponding to 0.4% individual risk. While these limits are not absolute and can be discussed, it is of interest to apply them to the case of RCS. The risk associated with an OEL of 0.1 mg/m 3for RCS is associated with risks far higher than &quot;maximum tolerable&quot;, ie, 0,4%. The US OSHA estimated that exposing 1000 workers for 45 years at 0.1 mg/m3 would result in 33 extra lung cancer deaths as life-time risk, corresponding to an individual risk of 3.3% (6), exceeding the maximum tolerable risk nearly 10-fold. Since the EU Directive concerns cancer, the report did not consider other health effects, which is necessary for a general risk assessment. The US OSHA estimated there would be another 85 deaths from non-malignant lung disease (8.5%) and, roughly estimated, 39 deaths from renal disease (3.9%) that should be added to this toll. This adds up to an individual excess death risk of 15%, which by far clearly exceeds what is generally seen as the maximum tolerable risk of 0.4%! Still, this is a conservative estimate, which includes neither excess deaths from myocardial infarction that occur from 0.025 mg/m 3and up (11) nor excess autoimmune disease, eg, rheumatoid arthritis and other autoimmune diseases (12, 13). In support of Johanson &amp; Tinnerberg (1), we argue that the lifetime excess death risk for silica-exposed workers is totally incompatible with fundamental workers' rights of health and safety. This aspect, which must be safeguarded by the OSH society, will be even more important when working life is prolonged and when exposure conditions may be more diverse, ie, workers with high exposure and excessive risk may be too few to impact the disease burden in society but in that group the burden may still be extreme. In our view, the assumption of 99% compliance is unrealistic and it is necessary to lower the OEL. In addition, leaving the BOELV at 0.1 mg/m3 means this will continue for the future, a silent epidemic that is deeply unethical to ignore. References 1. Johanson G, Tinnerberg H. Binding occupational exposure limits for carcinogens in the EU - good or bad? Scand J Work Environ Health 2019 May;45(3):213-4. https://doi.org/10.5271/sjweh.3825. 2. Directive EU. (EU) 2019/130 of the European parliament and of the council of 16 January 2019. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32019L0130. 3. Cherrie JW. Binding occupational exposure limits for carcinogens in the EU - necessary but not sufficient to reduce risk. Scand J Work Environ Health 2019 Jul;45(4):423-4. https://doi.org/10.5271/sjweh.3836. 4. SCOEL. SCOEL's involvement in setting Occupational Exposure Limits: Webpage accessed 2019-10-23. Available from: http://ec.europa.eu/social/BlobServlet?docId=3879&amp;langId=en. 5. SCOEL. Recommendation from the Scientific Committee on Occupational Exposure Limits for Silica, Crystalline (respirable dust). SCOEL/SUM/94. November 2003. Available from: http://ec.europa.eu/social/BlobServlet?docId=3803&amp;langId=en. 6. OSHA. Occupational Exposure to Respriable Crystalline Silica. Federal Register/vol 81, no 58/Friday, March 25, 2016/ Rules and Regulations. Occupational Safety and Health, Department of Labour, Administration (Docket No. OSHA-2010-0034) RIN 1218/AB70. OSHA 2016. Available from: https://www.govinfo.gov/content/pkg/FR-2016-03-25/pdf/2016-04800.pdf. 7. Cherrie JW, Gorman Ng M, Searl A, Shafrir A, van Tongeren M et al. Health, socio-economic and environmental aspects of possible amendments to the EU Directive on the protection of workers from the risks related to exposure to carcinogens and mutagens at work. Respirable crystalline silica. IOM Research Project: P937/8, May 2011. Available from: https://ec.europa.eu/social/BlobServlet?docId=10161&amp;langId=en). 8. ANSES. Agence nationale de sécurité sanitaire alimentation, environnement, et du travail (ANSES). Dangers, expositions et risques relatifs à la silice cristalline. Avis de l'Anses Raports d'expertise collective (Saisine no 2015-SA-0236). Avril 2019. Èdition scientifique. ANSES English summary: Available from: https://www.anses.fr/en/content/exposure-crystalline-silica-poses-high-risks-worker-health 9. Federal Institute for Occupational safety and Health. The risk-based concept for carcinogenic substances developed by the Committee for Hazardous Substances. Federal Institute for Occupational safety and Health (BAuA), Dortmund, Germany, 2013. Available from: www.baua.de/dok/3581564 10. Health Council of the Netherlands. Guidelines for the calculation of occupational cancer risk values. Health Council of the Netherlands, 2012. Available from: www.healthcouncil.nl/documents/advisory-reports/2012/10/26/guideline-for-the-calculation-of-occupational-cancer-risk-values. 11. Liu Y, Zhou Y, Hnizdo E, Shi T, Steenland K, He X et al. Total and Cause-Specific Mortality Risk Associated With Low-Level Exposure to Crystalline Silica: A 44-Year Cohort Study From China. Am J Epidemiol 2017 Aug;186(4):481-90. https://doi.org/10.1093/aje/kwx124. 12. Stolt P, Källberg H, Lundberg I, Sjögren B, Klareskog L, Alfredsson L; EIRA study group. Silica exposure is associated with increased risk of developing rheumatoid arthritis: results from the Swedish EIRA study. Ann Rheum Dis 2005 Apr;64(4):582-6. https://doi.org/10.1136/ard.2004.022053. 13. Parks CG, Conrad K, Cooper GS. Occupational exposure to crystalline silica and autoimmune disease. Environ Health Perspect 1999 Oct;107 Suppl 5:793-802.}, }
@article {pmid31714372, year = {2019}, author = {Larson, TC and Williamson, L and Antao, VC}, title = {Follow-Up of the Libby, Montana Screening Cohort: A 17-Year Mortality Study.}, journal = {Journal of occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/JOM.0000000000001760}, pmid = {31714372}, issn = {1536-5948}, abstract = {OBJECTIVE: To evaluate mortality patterns among participants in a community-based screening program for asbestos-related disease.<br><br>METHODS: We calculated standardized mortality ratios (SMRs) and stratified results by exposure group (three occupational exposure groups, household contacts and residents without occupational asbestos exposure) and by radiographic abnormality presence.<br><br>RESULTS: All-cause mortality (15.8%; 1,429/8,043) was statistically lower than expected. Asbestosis was statistically elevated in all exposure groups. Lung cancer was moderately associated with vermiculite miner/miller employment. Mesothelioma was elevated in that same exposure group and among residents. Systemic autoimmune disease mortality was also elevated. Radiographic parenchymal abnormalities were associated with lung cancer mortality.<br><br>CONCLUSION: In addition to asbestos-related mortality in occupational exposure groups, this initial mortality follow-up of this cohort also shows elevated mortality for some asbestos-related causes in non-occupational exposure groups.}, }
@article {pmid31713586, year = {2019}, author = {Finkelstein, MM and Meisenkothen, C}, title = {Malignant Mesothelioma Among Employees of a Connecticut Factory That Manufactured Friction Materials Using Chrysotile Asbestos: An Update.}, journal = {Annals of work exposures and health}, volume = {}, number = {}, pages = {}, doi = {10.1093/annweh/wxz082}, pmid = {31713586}, issn = {2398-7316}, abstract = {There is an ongoing argument about the potency of chrysotile asbestos to cause malignant mesothelioma. Authors of chrysotile risk assessments have relied upon the results of an epidemiologic study, published in 1984, to state that there were no mesotheliomas found among workers at a Connecticut friction products plant. McDonald reported the first two cases in 1986. In 2010, we reported the work histories and pathologic reports of five individuals from the Connecticut plant who were diagnosed with mesothelioma. Despite this, a review of the health effects of chrysotile published in 2018 continued to state that there were no cases of mesothelioma from this plant. We report here two new cases that were diagnosed after the publication of our previous report, bringing the current total to nine cases. We also discuss the results of previously unpublished air sampling data from the plant. Chrysotile, mainly from Canada, was the only asbestos fiber type used until 1957 when some anthophyllite was added in making paper discs and bands. Beyond this original description of the anthophyllite usage from McDonald, there is a dearth of information about the amount of anthophyllite used in the plant, the frequency of its use, and the specific departments where it was used. For over 30 years in the published literature, this factory has alternatively been described as a 'chrysotile' or 'predominantly chrysotile' factory. While it is clear that some anthophyllite was used in the factory (in addition to 400 pounds of crocidolite in the laboratory), given the volume, frequency, and processes using chrysotile, it still seems satisfactory to describe this cohort as a predominantly, but not exclusively, chrysotile-exposed cohort.}, }
@article {pmid31701555, year = {2019}, author = {van Gerwen, M and Alpert, N and Flores, R and Taioli, E}, title = {An overview of existing mesothelioma registries worldwide, and the need for a US Registry.}, journal = {American journal of industrial medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajim.23069}, pmid = {31701555}, issn = {1097-0274}, abstract = {The association between asbestos exposure, mainly in occupational settings, and malignant mesothelioma has been well established; this has prompted several countries to establish mesothelioma epidemiologic surveillance programs often at the request of national agencies. This review compares currently existing mesothelioma registries worldwide to develop a concept model for a US real-time case capture mesothelioma registry. Five countries were identified with a mesothelioma specific registry, including Italy, France, UK, Australia, and South Korea. All, except the UK, used interviews to collect exposure data. Linkage with the national death index was available or was in future plans for all registries. The registries have limited information on treatment, quality of life, and other patient-centered outcomes such as symptoms and pain management. To thoroughly collect exposure data, &quot;real-time&quot; enrollment is preferable; to maximize the capture of mesothelioma cases, optimal coverage, and a simplified consent process are needed.}, }
@article {pmid31693951, year = {2020}, author = {Gwenzi, W}, title = {Occurrence, behaviour, and human exposure pathways and health risks of toxic geogenic contaminants in serpentinitic ultramafic geological environments (SUGEs): A medical geology perspective.}, journal = {The Science of the total environment}, volume = {700}, number = {}, pages = {134622}, doi = {10.1016/j.scitotenv.2019.134622}, pmid = {31693951}, issn = {1879-1026}, abstract = {Serpentinitic ultramafic geological environments (SUGEs) contain toxic geogenic contaminants (TGCs). Yet comprehensive reviews on the medical geology of SUGEs are still lacking. The current paper posits that TGCs occur widely in SUGEs, and pose human health risks. The objectives of the review are to: (1) highlight the nature, occurrence and behaviour of TGCs associated with SUGEs; (2) discuss the human intake pathways and health risks of TGCs; (4) identify the key risk factors predisposing human health to TGCs particularly in Africa; and (5) highlight key knowledge gaps and future research directions. TGCs of human health concern in SUGEs include chrysotile asbestos, toxic metals (Fe, Cr, Ni, Mn, Zn, Co), and rare earth elements. Human intake of TGCs occur via inhalation, and ingestion of contaminated drinking water, wild foods, medicinal plants, animal foods, and geophagic earths. Occupational exposure may occur in the mining, milling, sculpturing, engraving, and carving industries. African populations are particularly at high risk due to: (1) widespread consumption of wild foods, medicinal plants, untreated drinking water, and geophagic earths; (2) weak and poorly enforced environmental, occupational, and public health regulations; and (3) lack of human health surveillance systems. Human health risks of chrysotile include asbestosis, cancers, and mesothelioma. Toxic metals are redox active, thus generate reactive oxygen species causing oxidative stress. Dietary intake of iron and geophagy may increase the iron overload among native Africans who are genetically predisposed to such health risks. Synergistic interactions among TGCs particularly chrysotile and toxic metals may have adverse human health effects. The occurrence of SUGEs, coupled with the several risk factors in Africa, provides a unique and ideal setting for investigating the relationships between TGCs and human health risks. A conceptual framework for human health risk assessment and mitigation, and future research direction are highlighted.}, }
@article {pmid31690138, year = {2019}, author = {Boyles, MSP and Poland, CA and Raftis, J and Duffin, R}, title = {Assessment of the physicochemical properties of chrysotile-containing brake debris pertaining to toxicity.}, journal = {Inhalation toxicology}, volume = {31}, number = {8}, pages = {325-342}, doi = {10.1080/08958378.2019.1683103}, pmid = {31690138}, issn = {1091-7691}, abstract = {Grinding and drilling of chrysotile asbestos-containing brake pads during the 20th century led to release of chrysotile, resulting in varying levels of workplace exposures of mechanics. Despite exposures, excess risk of mesothelioma remains in doubt. Objectives: The toxicity of particulates is primarily derived through a combination of physicochemical properties and dose and as such this study aimed to determine properties of asbestos-containing brake debris (BD) which may influence pathogenicity and potential of mesothelioma. Materials and Methods: Chrysotile-containing brake pads were ground - to reflect occupational activities, aerosolized, and size-fractionated to isolate respirable fractions. Analysis of morphology, biodurability, surface charge, and interactions with macrophages were undertaken. Results: The respirable fraction of BD contained ∼15-17% free chrysotile fibers thereby constituting a small but relevant potential long fiber dose. Acellular biodurability studies showed rapid dissolution and fragmentation of chrysotile fibers that was consistent for pure chrysotile control and BD samples. Conclusions: The long, free, respirable chrysotile fibers were present in BD, yet were of low bio-durability; incubation in artificial lysosomal fluid led to destruction of free fibers.}, }
@article {pmid31684803, year = {2019}, author = {Waldron, T}, title = {ERA Merewether - And asbestos.}, journal = {Journal of medical biography}, volume = {}, number = {}, pages = {967772019883550}, doi = {10.1177/0967772019883550}, pmid = {31684803}, issn = {1758-1087}, abstract = {After a succession of posts and studying for the Bar, Edward Merewether joined the Medical Inspectorate of Factories in 1927. Not long thereafter he was asked to undertake a study of the effects of asbestos exposure on the lungs. His results showed that asbestos workers had a significant risk of developing pulmonary fibrosis and this resulted in the promulgation of regulations to limit exposure. Some years later, Merewether showed that asbestos workers also had a higher than expected risk of developing lung cancer, but on this occasion there was no further protective legislation, and the association was not generally accepted until some years later. Merewether's name is inextricably linked with the risks of asbestos exposure but after his death the importance of his efforts was often played down by those who wished to show that the government had not acted quickly enough, or vigorously enough to control the hazard. The contention of this paper is that these criticisms are not justified and that Merewether acted to the best of his ability, given the conditions and knowledge current at the time he was working.}, }
@article {pmid31682242, year = {2019}, author = {Świątkowska, B}, title = {[The occurrence of asbestos-related diseases among former employees of asbestos processing plants in Poland].}, journal = {Medycyna pracy}, volume = {70}, number = {6}, pages = {723-731}, doi = {10.13075/mp.5893.00890}, pmid = {31682242}, issn = {2353-1339}, abstract = {BACKGROUND: Despite the fact that asbestos is no longer used in production in Poland, there are still new cases of asbestos-related diseases among workers previously exposed to asbestos dust. This situation is related to the specificity of the biological activity of this mineral; the health consequences of asbestos can manifest not only during the exposure but also many years after exposure cessation. The aim of the analysis was to assess the occurrence of occupational diseases among people exposed to asbestos dust, who were examined under the Amiantus program.<br><br>MATERIAL AND METHODS: The research material consisted of the program cards filled by the doctors conducting the examinations as well as radiological images stored on the International Labour Organization form. The analysis covered 8049 people, including 37% of women surveyed in the years 2000-2017.<br><br>RESULTS: In the group of former employees of asbestos processing plants, the occupational disease was diagnosed in 1993 people (25%), including 584 women (19%). The most common was asbestosis (76% of occupational diseases) and pleural disease (17%). Malignant neoplasms accounted for 7% of all cases in this group. The analysis showed an increase in the incidence of respiratory system diseases along with the age of the surveyed persons, their seniority at asbestos processing plants and an increase in cumulative exposure. The chest radiographs revealed radiological changes among 75% of the examined cases, whereas the changes entitling to diagnose asbestosis, according to the criteria applicable in Poland, occurred in 23% of the workers. The adoption of international criteria would increase the incidence of asbestosis as an occupational disease by 19% in the study group.<br><br>CONCLUSIONS: The increase in the percentage of people with a diagnosed occupational disease provides evidence for the worsening health status of the former workers as well as a good detection of asbestos-related diseases among employees exposed to asbestos dust in the past. The results of the analysis indicate the need for undertaking a discussion in Poland on the implementation of international criteria for the diagnosis of asbestosis. Med Pr. 2019;70(6):723-31.}, }
@article {pmid31671889, year = {2019}, author = {Wörthmüller, J and Salicio, V and Oberson, A and Blum, W and Schwaller, B}, title = {Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin.}, journal = {International journal of molecular sciences}, volume = {20}, number = {21}, pages = {}, doi = {10.3390/ijms20215391}, pmid = {31671889}, issn = {1422-0067}, abstract = {Malignant mesothelioma (MM) is an aggressive asbestos-linked neoplasm, characterized by dysregulation of signaling pathways. Due to intrinsic or acquired chemoresistance, MM treatment options remain limited. Calretinin is a Ca2+-binding protein expressed during MM tumorigenesis that activates the FAK signaling pathway, promoting invasion and epithelial-to-mesenchymal transition. Constitutive calretinin downregulation decreases MM cells' growth and survival, and impairs tumor formation in vivo. In order to evaluate early molecular events occurring during calretinin downregulation, we generated a tightly controlled IPTG-inducible expression system to modulate calretinin levels in vitro. Calretinin downregulation significantly reduced viability and proliferation of MM cells, attenuated FAK signaling and reduced the invasive phenotype of surviving cells. Importantly, surviving cells showed a higher resistance to cisplatin due to increased Wnt signaling. This resistance was abrogated by the Wnt signaling pathway inhibitor 3289-8625. In various MM cell lines and regardless of calretinin expression levels, blocking of FAK signaling activated the Wnt signaling pathway and vice versa. Thus, blocking both pathways had the strongest impact on MM cell proliferation and survival. Chemoresistance mechanisms in MM cells have resulted in a failure of single-agent therapies. Targeting of multiple components of key signaling pathways, including Wnt signaling, might be the future method-of-choice to treat MM.}, }
@article {pmid31670764, year = {2019}, author = {Musk, AWB and Reid, A and Olsen, N and Hobbs, M and Armstrong, B and Franklin, P and Hui, J and Layman, L and Merler, E and Brims, F and Alfonso, H and Shilkin, K and Sodhi-Berry, N and de Klerk, N}, title = {The Wittenoom legacy.}, journal = {International journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/ije/dyz204}, pmid = {31670764}, issn = {1464-3685}, abstract = {The Wittenoom crocidolite (blue asbestos) mine and mill ceased operating in 1966. The impact of this industry on asbestos-related disease in Western Australia has been immense. Use of the employment records of the Australian Blue Asbestos Company and records of the Wittenoom township residents has permitted two cohorts of people with virtually exclusive exposure to crocidolite to be assembled and studied. Follow-up of these two cohorts has been conducted through data linkage with available hospital, mortality and cancer records. The evolution of asbestos-related disease has been recorded and, with the establishment of exposure measurements, quantitative exposure-response relationships have been estimated. There has been an ongoing epidemic of mortality from lung cancer and malignant mesothelioma and, less so, from asbestosis. Wittenoom crocidolite was used extensively in asbestos-cement products in Western Australia. As a result, the state has recorded a higher malignant-mesothelioma mortality rate than in any other Australian state and in any defined general population in the world. Thus, the legacy of Wittenoom has extended beyond the mine and the town, and is still evident more than 50 years after the closure of the mine.}, }
@article {pmid31670225, year = {2019}, author = {Cinausero, M and Rihawi, K and Cortiula, F and Follador, A and Fasola, G and Ardizzoni, A}, title = {Emerging therapies in malignant pleural mesothelioma.}, journal = {Critical reviews in oncology/hematology}, volume = {144}, number = {}, pages = {102815}, doi = {10.1016/j.critrevonc.2019.102815}, pmid = {31670225}, issn = {1879-0461}, abstract = {Malignant pleural mesothelioma (MPM) is a rare cancer of the pleural surfaces frequently related to asbestos exposure. It is characterized by a poor prognosis even for patients treated with trimodality therapy, including surgery, chemotherapy and radiotherapy. Moreover, the majority of patients are not candidates for surgery due to disease advanced stage or medical comorbidities. For these patients, the survival rate is even lower and few therapeutic options are currently available. Nevertheless, many interesting novel approaches are under investigation, among which immunotherapy represents one of the most promising emerging strategies. In this review, we will discuss the role of new therapeutic options, particularly immunotherapy, and present the results of the most important and promising clinical trials.}, }
@article {pmid31667596, year = {2019}, author = {Minami, K and Jimbo, N and Tanaka, Y and Hokka, D and Miyamoto, Y and Itoh, T and Maniwa, Y}, title = {Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00428-019-02674-x}, pmid = {31667596}, issn = {1432-2307}, abstract = {Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.}, }
@article {pmid31662422, year = {2019}, author = {Reynolds, CJ and Minelli, C and Darnton, A and Cullinan, P}, title = {Mesothelioma mortality in Great Britain: how much longer will dockyards dominate?.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {12}, pages = {908-912}, doi = {10.1136/oemed-2019-105878}, pmid = {31662422}, issn = {1470-7926}, abstract = {OBJECTIVES: We aimed to investigate whether there has been a geographic shift in the distribution of mesothelioma deaths in Great Britain given the decline of shipbuilding and progressive exposure regulation.<br><br>METHODS: We calculated age-adjusted mesothelioma mortality rates and estimated rate ratios for areas with and without a dockyard. We compared spatial autocorrelation statistics (Moran's I) for age-adjusted rates at local authority district level for 2002-2008 and 2009-2015. We measured the mean distance of the deceased's postcode to the nearest dockyard at district level and calculated the association of average distance to dockyard and district mesothelioma mortality using simple linear regression for men, for 2002-2008 and 2009-2015.<br><br>RESULTS: District age-adjusted male mortality rates fell during 2002-2015 for 80 of 348 districts (23%), rose for 267 (77%) and were unchanged for one district; having one or more dockyards in a district was associated with rates falling (OR=2.43, 95% CI 1.22 to 4.82, p=0.02). The mortality rate ratio for men in districts with a dockyard, compared with those without a dockyard was 1.41 (95% CI 1.35 to 1.48, p<0.05) for 2002-2008 and 1.18 (95% CI 1.13 to 1.23, p<0.05) for 2009-2015. Spatial autocorrelation (measured by Moran's I) decreased from 0.317 (95% CI 0.316 to 0.319, p=0.001) to 0.312 (95% CI 0.310 to 0.314, p=0.001) for men and the coefficient of the association between distance to dockyard and district level age-adjusted male mortality (per million population) from -0.16 (95% CI -0.21 to -0.10, p<0.01) to -0.13 (95% CI -0.18 to -0.07, p<0.01) for men, when comparing 2002-2008 with 2009-2015.<br><br>CONCLUSION: For most districts age-adjusted mesothelioma mortality rates increased through 2002-2015 but the relative contribution from districts with a dockyard fell. Dockyards remain strongly spatially associated with mesothelioma mortality but the strength of this association appears to be falling and mesothelioma deaths are becoming more dispersed.}, }
@article {pmid31655816, year = {2019}, author = {Fortin, M and Cabon, E and Berbis, J and Laroumagne, S and Guinde, J and Elharrar, X and Dutau, H and Astoul, P}, title = {Diagnostic Value of Computed Tomography Imaging Features in Malignant Pleural Mesothelioma.}, journal = {Respiration; international review of thoracic diseases}, volume = {}, number = {}, pages = {1-7}, doi = {10.1159/000503239}, pmid = {31655816}, issn = {1423-0356}, abstract = {BACKGROUND: Medical history, thoracentesis, and imaging features are usually the first steps in the investigation of a possible malignant pleural effusion (MPE). Unfortunately, the diagnostic yield of thoracentesis in this situation is suboptimal even if the procedure is repeated, especially in the context of malignant pleural mesothelioma (MPM). The next step for confirming the diagnosis, if clinically appropriate, is thoracoscopy, but not all patients are fit to undergo this procedure, so the diagnosis is then based on the medical history and imaging features only.<br><br>OBJECTIVES: Our objective was to evaluate the diagnostic value of the medical history and imaging features in MPM.<br><br>METHODS: We reviewed the imaging and medical charts of 92 patients with a final diagnosis of MPE included in our prospective medical thoracoscopy database. The clinical characteristics and imaging features of patients with primary MPE were compared with those of patients with secondary MPE.<br><br>RESULTS: Male sex (82 vs. 59%, p = 0.02), asbestos exposure (58 vs. 10%, p < 0.001), and mediastinal (68 vs. 33%, p = 0.04), diaphragmatic (75 vs. 31%, p = 0.001) and circumferential pleural thickening (55 vs. 19% p = 0.001) were significantly more frequent in MPM patients. In a multivariate linear regression model, only asbestos exposure (OR 11.2; 95% CI 3.4-36.9) and circumferential pleural thickening (OR 4.7; 95% CI 1.6-13.9) were significantly associated with a diagnosis of MPM.<br><br>CONCLUSION: In situations where it is impossible to obtain adequate pleural samples to differentiate MPM from a secondary pleural malignancy, the combination of circumferential pleural thickening and a history of asbestos exposure may be sufficient to make a clinical diagnosis.}, }
@article {pmid31648983, year = {2019}, author = {Alcala, N and Mangiante, L and Le-Stang, N and Gustafson, CE and Boyault, S and Damiola, F and Alcala, K and Brevet, M and Thivolet-Bejui, F and Blanc-Fournier, C and Le Rochais, JP and Planchard, G and Rousseau, N and Damotte, D and Pairon, JC and Copin, MC and Scherpereel, A and Wasielewski, E and Wicquart, L and Lacomme, S and Vignaud, JM and Ancelin, G and Girard, C and Sagan, C and Bonnetaud, C and Hofman, V and Hofman, P and Mouroux, J and Thomas de Montpreville, V and Clermont-Taranchon, E and Mazieres, J and Rouquette, I and Begueret, H and Blay, JY and Lantuejoul, S and Bueno, R and Caux, C and Girard, N and McKay, JD and Foll, M and Galateau-Salle, F and Fernandez-Cuesta, L}, title = {Redefining malignant pleural mesothelioma types as a continuum uncovers immune-vascular interactions.}, journal = {EBioMedicine}, volume = {48}, number = {}, pages = {191-202}, pmid = {31648983}, issn = {2352-3964}, abstract = {BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options.<br><br>METHODS: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples.<br><br>FINDINGS: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a &quot;hot&quot; bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a &quot;cold&quot; bad-prognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a &quot;VEGFR2+/VISTA+&quot; better-prognosis profile, with high expression of immune checkpoint VISTA and pro-angiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series.<br><br>INTERPRETATION: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response.}, }
@article {pmid31632972, year = {2019}, author = {Johnson, TG and Schelch, K and Mehta, S and Burgess, A and Reid, G}, title = {Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {221}, pmid = {31632972}, issn = {2296-634X}, abstract = {Lung cancers and malignant pleural mesothelioma (MPM) have some of the worst 5-year survival rates of all cancer types, primarily due to a lack of effective treatment options for most patients. Targeted therapies have shown some promise in thoracic cancers, although efficacy is limited only to patients harboring specific mutations or target expression. Although a number of actionable mutations have now been identified, a large population of thoracic cancer patients have no therapeutic options outside of first-line chemotherapy. It is therefore crucial to identify alternative targets that might lead to the development of new ways of treating patients diagnosed with these diseases. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) could serve as one such target. Recent studies also link this protein to many inherent behaviors of thoracic cancer cells such as proliferation, invasion, metastasis and involvement in cancer stem-like cells. Here, we review the regulation of YB-1 at the transcriptional, translational, post-translational and sub-cellular levels in thoracic cancer and discuss its potential use as a biomarker and therapeutic target.}, }
@article {pmid31624358, year = {2019}, author = {Nowak, AK and Forde, PM}, title = {Immunotherapy trials in mesothelioma - promising results, but don't stop here.}, journal = {Nature reviews. Clinical oncology}, volume = {16}, number = {12}, pages = {726-728}, doi = {10.1038/s41571-019-0291-4}, pmid = {31624358}, issn = {1759-4782}, }
@article {pmid31619883, year = {2019}, author = {Munot, MN and Utpat, KV and Desai, UD and Joshi, JM}, title = {Malignant Mesothelioma - Report of Two Cases with Different Presentations.}, journal = {Indian journal of occupational and environmental medicine}, volume = {23}, number = {2}, pages = {93-96}, pmid = {31619883}, issn = {0973-2284}, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm that stems from the mesothelial cells lining the visceral cavities, namely, the pleura, peritoneum, pericardium, and tunica vaginalis of the testes. MPM is the most common variant of these and constitutes up to 80% of all malignant mesotheliomas. It is usually associated with asbestos exposure and is a locally invasive neoplasm that spreads along pleura and can involve lungs with locoregional metastasis. Diagnosis remains challenging due to the latency between asbestos exposure and clinical presentation and the variable clinicoradiological manifestations. Meticulous history taking, high index of, suspicion and multimodality approach toward diagnosis are the keys to better prognosis. We hereby present two interesting cases of MPM with different presentations.}, }
@article {pmid31610664, year = {2019}, author = {Levý, M and Boublíková, L and Büchler, T and Šimša, J}, title = {Treatment of Malignant Peritoneal Mesothelioma.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {32}, number = {5}, pages = {333-337}, doi = {10.14735/amko2019333}, pmid = {31610664}, issn = {1802-5307}, abstract = {Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.}, }
@article {pmid31609780, year = {2019}, author = {Moline, J and Bevilacqua, K and Alexandri, M and Gordon, RE}, title = {Mesothelioma Associated with the Use of Cosmetic Talc.}, journal = {Journal of occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/JOM.0000000000001723}, pmid = {31609780}, issn = {1536-5948}, abstract = {OBJECTIVE: To describe exposures to talcum powder leading to mesothelioma among 33 individuals as a non-occupational asbestos exposure.<br><br>METHODS: Cases were referred for medico-legal evaluation, and tissue digestions were performed in some cases. Tissue digestion for the six cases described was done according to standard methodology RESULTS:: Asbestos of the type found in talcum powder was found in all six cases evaluated.. Talcum powder usage was the only source of asbestos for all 33 cases.<br><br>CONCLUSIONS: Exposure to asbestos-contaminated talcum powders can cause mesothelioma. Clinicians should elicit a history of talcum powder usage in all patients presenting with mesothelioma.}, }
@article {pmid31596154, year = {2019}, author = {Ceresoli, GL and Rossi, A}, title = {Approved and emerging treatments of malignant pleural mesothelioma in elderly patients.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {12}, pages = {1179-1188}, doi = {10.1080/17476348.2019.1678386}, pmid = {31596154}, issn = {1747-6356}, abstract = {Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with asbestos exposure as the dominant etiologic agent. Owing to the long latent period following exposure, MPM is often diagnosed late in life. Despite this, elderly patients are under-represented in clinical trials. To date, data regarding the tolerability and efficacy of anticancer treatments for elderly patients affected by MPM are still lacking.Areas covered: The current state-of-the-art of approved treatments employed in the treatment of MPM elderly patients is reviewed and discussed, with a look to emerging therapies. A structured search of bibliographic databases for peer-reviewed research literature and of main meeting abstracts using a focused review question was undertaken.Expert opinion: Even though the median age of MPM patients enrolled in the most recent experimental trials is increasing, no specific analysis has been reported so far in the elderly. Moreover, no data are available for the 'oldest of the elderly' (>75 years). Treatment of elderly patients with MPM is one of the major challenges to the clinician. There is a clear need of large, well-conducted retrospective studies and above all of prospective investigations in this patient population, both in the first-and in the second-line setting.}, }
@article {pmid31594840, year = {2019}, author = {Kwak, K and Paek, D and Zoh, KE}, title = {Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {11}, pages = {861-871}, doi = {10.1136/oemed-2019-105735}, pmid = {31594840}, issn = {1470-7926}, abstract = {Asbestos exposure is associated with mesothelioma and cancer of the lung, larynx and ovary. However, the association between asbestos exposure and colorectal cancer is controversial despite several systematic reviews of the literature, including a number of meta-analyses. We performed a systematic review and meta-analysis to evaluate quantitatively the association between exposure to asbestos and colorectal cancer. We searched for articles on occupational asbestos exposure and colorectal cancer in PubMed, EMBASE and Web of Science published before April 2018. In total, 44 articles were selected and 46 cohort studies were analysed. The overall pooled risk estimates and corresponding 95% CIs of the association between occupational asbestos exposure and colorectal cancer were calculated using a random-effects model. Subgroup analyses and sensitivity tests were also performed. There was a significantly increased risk of colorectal cancer mortality among workers exposed to asbestos occupationally, with an overall pooled SMR of 1.16 (95% CI: 1.05 to 1.29). The pooled SMR for colorectal cancer was elevated in studies in which the asbestos-associated risk of lung cancer was also elevated (1.43; 95% CI: 1.30 to 1.56). This implies that the risk of colorectal cancer mortality increases as the level of asbestos exposure rises. A sensitivity analysis showed robust results and there was no publication bias. Although the effect size was small and the heterogeneity among studies was large, our findings indicate that occupational exposure to asbestos is a risk factor for colorectal cancer.}, }
@article {pmid31564247, year = {2019}, author = {Vimercati, L and Cavone, D and Caputi, A and Delfino, MC and De Maria, L and Ferri, GM and Serio, G}, title = {Malignant mesothelioma in construction workers: the Apulia regional mesothelioma register, Southern Italy.}, journal = {BMC research notes}, volume = {12}, number = {1}, pages = {636}, pmid = {31564247}, issn = {1756-0500}, abstract = {OBJECTIVE: Asbestos was widely used in construction in both a friable and a compact form until the 1990s, before its use was banned. Today, many of these materials are still in situ and represent a source of risk for construction workers. The objective of the study was to analyse the cases of mesothelioma arising among construction workers registered in the Apulia regional register of mesothelioma.<br><br>RESULTS: For the period 1993-2018, there were 178 male cases, and 10.2% of the cases were present in the regional register. The average age at diagnosis was 64.7 years. The site was pleural in 96.06% of cases, with a diagnosis of certainty in 86.5% of the total cases and 61.8% of cases with epithelial histology. The average latency is 43.9 years. In 75.2% of cases, the exposure began between 1941 and 1970, with an average duration of 24.3 years. The age at the start of exposure in 68.5% of cases is between 8 and 20 years. The ORs were 2.5 (C.I. 95% 1.01-6.17) for the epithelioid histotype and the high duration of exposure. The data underline the need for prevention and information on all activities involving construction workers in which asbestos-containing materials are still used.}, }
@article {pmid31557561, year = {2019}, author = {Takeda, M and Ohe, Y and Horinouchi, H and Hida, T and Shimizu, J and Seto, T and Nosaki, K and Kishimoto, T and Miyashita, I and Yamada, M and Kaneko, Y and Morimoto, C and Nakagawa, K}, title = {Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {137}, number = {}, pages = {64-70}, doi = {10.1016/j.lungcan.2019.09.010}, pmid = {31557561}, issn = {1872-8332}, abstract = {OBJECTIVES: CD26 is a transmembrane glycoprotein with dipeptidyl peptidase IV activity that is overexpressed in malignant pleural mesothelioma (MPM). We performed a phase I study to determine the maximum tolerated dose, pharmacokinetics, and antitumor activity of YS110, a monoclonal antibody to CD26, in Japanese patients with MPM intolerant of or refractory to prior standard therapies.<br><br>MATERIAL AND METHODS: The study was designed as an open-label, 3 + 3 dose-escalation, phase I trial. Patients were sequentially assigned to three dosing cohorts (2, 4, or 6 mg/kg). Each 6-week treatment cycle consisted of YS110 administration weekly for 5 weeks followed by a 1-week rest period. Treatment was continued until disease progression, death, or intolerable toxicity. Corticosteroid, antihistamine, and acetaminophen administration before each infusion was adopted to limit infusion-related reactions (IRRs).<br><br>RESULTS: Nine Japanese patients (seven men and two women, mean age of 62.2 years), three in each dosing cohort, were enrolled in the study. No patient developed a dose-limiting toxicity. Adverse events of grade 3 or 4 developed in seven patients, with the most common such event being a decreased lymphocyte count. Two patients had mild or moderate IRRs. The serum concentration of YS110 increased in a dose-dependent manner. Among seven patients evaluable for tumor response, four showed stable disease and one achieved a partial response.<br><br>CONCLUSIONS: YS110 showed promising antitumor efficacy and was generally well tolerated in Japanese patients with advanced MPM at doses of up to 6 mg/kg. YS110 will be tested at 6 mg/kg in a subsequent phase II study.}, }
@article {pmid31546009, year = {2019}, author = {Hinz, TK and Heasley, LE}, title = {Translating mesothelioma molecular genomics and dependencies into precision oncology-based therapies.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2019.09.014}, pmid = {31546009}, issn = {1096-3650}, abstract = {Malignant pleural mesothelioma (MPM) is a rare, yet lethal asbestos-induced cancer and despite marked efforts to reduce occupational exposure, the incidence has not yet significantly declined. Since 2003, combined treatment with a platinum-based agent and pemetrexed has been the first-line therapy and no effective or approved second-line treatments have emerged. The seemingly slow advance in developing new MPM treatments does not appear to be related to a low level of clinical and pre-clinical research activity. Rather, we suggest that a key hurdle in successfully translating basic discovery into novel MPM therapeutics is the underlying assumption that as a rare cancer, it will also be molecularly and genetically homogeneous. In fact, lung adenocarcinoma and melanoma only benefitted from precision oncology upon full appreciation of the high degree of molecular heterogeneity inherent in these cancers, especially regarding the diversity of oncogenic drivers. Herein, we consider the recent explosion of molecular and genetic information that has become available regarding MPM and suggest ways in which the unfolding landscape may guide identification of novel therapeutic vulnerabilities within subsets of MPM that can be targeted in a manner consistent with the tenets of precision oncology.}, }
@article {pmid31538797, year = {2019}, author = {Geyer, SJ}, title = {Malignant Mesothelioma and Its Nonasbestos Causes: Talcum Powder Does Not Create Occult Asbestos Exposure.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {143}, number = {12}, pages = {1439}, doi = {10.5858/arpa.2019-0388-LE}, pmid = {31538797}, issn = {1543-2165}, }
@article {pmid31534051, year = {2019}, author = {Hamaidia, M and Gazon, H and Hoyos, C and Hoffmann, GB and Louis, R and Duysinx, B and Willems, L}, title = {Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1-dependent mechanism.}, journal = {JCI insight}, volume = {4}, number = {18}, pages = {}, pmid = {31534051}, issn = {2379-3708}, abstract = {The roles of macrophages in orchestrating innate immunity through phagocytosis and T lymphocyte activation have been extensively investigated. Much less understood is the unexpected role of macrophages in direct tumor regression. Tumoricidal macrophages can indeed manifest cancer immunoediting activity in the absence of adaptive immunity. We investigated direct macrophage cytotoxicity in malignant pleural mesothelioma, a lethal cancer that develops from mesothelial cells of the pleural cavity after occupational asbestos exposure. In particular, we analyzed the cytotoxic activity of mouse RAW264.7 macrophages upon cell-cell contact with autologous AB1/AB12 mesothelioma cells. We show that macrophages killed mesothelioma cells by oxeiptosis via a mechanism involving enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27-specific (H3K27-specific) methyltransferase of the polycomb repressive complex 2 (PRC2). A selective inhibitor of EZH2 indeed impaired RAW264.7-directed cytotoxicity and concomitantly stimulated the PD-1 immune checkpoint. In the immunocompetent BALB/c model, RAW264.7 macrophages pretreated with the EZH2 inhibitor failed to control tumor growth of AB1 and AB12 mesothelioma cells. Blockade of PD-1 engagement restored macrophage-dependent antitumor activity. We conclude that macrophages can be directly cytotoxic for mesothelioma cells independent of phagocytosis. Inhibition of the PRC2 EZH2 methyltransferase reduces this activity because of PD-1 overexpression. Combination of PD-1 blockade and EZH2 inhibition restores macrophage cytotoxicity.}, }
@article {pmid31525810, year = {2019}, author = {Kim, RY and Sterman, DH and Haas, AR}, title = {Malignant Mesothelioma: Has Anything Changed?.}, journal = {Seminars in respiratory and critical care medicine}, volume = {40}, number = {3}, pages = {347-360}, doi = {10.1055/s-0039-1693406}, pmid = {31525810}, issn = {1098-9048}, abstract = {Malignant pleural mesothelioma is a rare cancer associated with asbestos exposure and portends a dismal prognosis. Its worldwide incidence has been increasing, and treatment options are currently suboptimal and noncurative. However, since the turn of the century, several encouraging steps have been made toward improving outcomes for mesothelioma patients. An increased understanding of disease pathophysiology has led to more accurate diagnosis and staging, and the establishment of the standard of care first-line pemetrexed/platin doublet chemotherapy regimen in 2003 initially revolutionized treatment. While significant debate remains regarding the preferred approach to surgical and radiation therapy in the context of multimodal therapy, recent breakthroughs in immunotherapy offer hope for another paradigm shift in the near future. This review will summarize the current clinical approach to diagnosis, staging, and treatment of malignant pleural mesothelioma.}, }
@article {pmid31511437, year = {2019}, author = {Huang, Q and Lan, YJ}, title = {Colorectal cancer and asbestos exposure-an overview.}, journal = {Industrial health}, volume = {}, number = {}, pages = {}, doi = {10.2486/indhealth.2018-0271}, pmid = {31511437}, issn = {1880-8026}, abstract = {The relationship between colorectal cancer and asbestos exposure has not been fully clarified. This study aimed to determine the associations between asbestos exposure and colorectal cancer. We performed a meta-analysis to quantitatively evaluate this association. A fixed effects model was used to summarize the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. We analyzed the dose-effect relationship using lung cancer Standardized mortality ratio (SMR) and the risk of mesothelioma as a percent (%) as exposure surrogates. A total of 47 cohort studies were included. We identified 28 incidence cohort studies from 17 separate papers and extracted colorectal cancer Standardized incidence ratio (SIR). Cancer mortality data were extracted from 19 separate cohorts among 13 papers. The overall colorectal cancer SMR for synthesis cohort was 1.07 (95% CI 1.02-1.12). Statistically significant excesses were observed in exposure to mixed asbestos (SMR/SIR=1.07), exposure to production (SMR/SIR=1.11), among asbestos cement workers (SMR/SIR=1.18) and asbestos textile workers (SMR/SIR=1.11). Additionally, we determined that the SMR for lung cancer increased with increased exposure to asbestos, as did the risk for colorectal cancer. This study confirms that colorectal cancer has a positive weak associations with asbestos exposure.}, }
@article {pmid31477126, year = {2019}, author = {Abdelgied, M and El-Gazzar, AM and Alexander, WT and Numano, T and Iigou, M and Naiki-Ito, A and Takase, H and Hirose, A and Taquahashi, Y and Kanno, J and Abdelhamid, M and Abdou, KA and Takahashi, S and Alexander, DB and Tsuda, H}, title = {Carcinogenic effect of potassium octatitanate (POT) fibers in the lung and pleura of male Fischer 344 rats after intrapulmonary administration.}, journal = {Particle and fibre toxicology}, volume = {16}, number = {1}, pages = {34}, doi = {10.1186/s12989-019-0316-2}, pmid = {31477126}, issn = {1743-8977}, abstract = {BACKGROUND: Potassium octatitanate fibers (K2O•8TiO2, POT fibers) are used as an asbestos substitute. Their physical characteristics suggest that respirable POT fibers are likely to be carcinogenic in the lung and pleura. However, previous 2-year inhalation studies reported that respired POT fibers had little or no carcinogenic potential. In the present study ten-week old male F344 rats were left untreated or were administered vehicle, 0.25 or 0.5 mg rutile-type nano TiO2 (r-nTiO2), 0.25 or 0.5 mg POT fibers, or 0.5 mg MWCNT-7 by intra-tracheal intra-pulmonary spraying (TIPS), and then observed for 2 years.<br><br>RESULTS: There were no differences between the r-nTiO2 and control groups. The incidence of bronchiolo-alveolar cell hyperplasia was significantly increased in the groups treated with 0.50 mg POT and 0.50 mg MWCNT-7. The overall incidence of lung tumors, however, was not increased in either the POT or MWCNT-7 treated groups. Notably, the carcinomas that developed in the POT and MWCNT-7 treated rats were accompanied by proliferative fibrous connective tissue while the carcinomas that developed in the untreated rats and the r-nTiO2 treated rats were not (carcinomas did not develop in the vehicle control rats). In addition, the carcinoma that developed in the rat treated with 0.25 mg POT was a squamous cell carcinoma, a tumor that develops spontaneously in about 1 per 1700 rats. The incidence of mesothelial cell hyperplasia was 4/17, 7/16, and 10/14 and the incidence of malignant mesothelioma was 3/17, 1/16, and 2/14 in the 0.25 mg POT, 0.5 mg POT, and MWCNT-7 treated groups, respectively. Neither mesothelial cell hyperplasia nor mesothelioma developed in control rats or the rats treated with r-nTiO2. Since the incidence of spontaneously occurring malignant mesothelioma in rats is extremely low, approximately 1 per 1000 animals (Japan Bioassay Research Center [JBRC] historical control data), the development of multiple malignant mesotheliomas in the POT and MWCNT-7 treated groups was biologically significant.<br><br>CONCLUSION: The incidence of pleural mesotheliomas in male F344 rats administered POT fibers and MWCNT-7 was significantly higher than the JBRC historical control data, indicating that the incidence of pleural mesothelioma in the groups administered POT fibers and MWCNT-7 fibers via the airway using TIPS was biologically significant. The incidence of type II epithelial cell hyperplasia and the histology of the carcinomas that developed in the POT treated rats also indicates that respirable POT fibers are highly likely to be carcinogenic in the lungs of male F344 rats.}, }
@article {pmid31475103, year = {2019}, author = {Cavallari, I and Urso, L and Sharova, E and Pasello, G and Ciminale, V}, title = {Liquid Biopsy in Malignant Pleural Mesothelioma: State of the Art, Pitfalls, and Perspectives.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {740}, doi = {10.3389/fonc.2019.00740}, pmid = {31475103}, issn = {2234-943X}, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to asbestos exposure. Although the risk factors for MPM are well-known, the majority of MPM patients are diagnosed at an advanced stage and have a very poor prognosis. Circulating biomarkers for early diagnosis remain to be identified, and the current standard for MPM diagnosis relies on pleural biopsies. Robust non-invasive tests for the screening of asbestos-exposed subjects are therefore an important unmet clinical need. This review provides a critical summary of recent liquid biopsy-based studies aimed at discovering novel blood-based circulating biomarkers for the early diagnosis and prognostic stratification of MPM patients.}, }
@article {pmid31470859, year = {2019}, author = {Vimercati, L and Cavone, D and Delfino, MC and De Maria, L and Caputi, A and Ferri, GM and Serio, G}, title = {Asbestos exposure and malignant mesothelioma of the tunica vaginalis testis: a systematic review and the experience of the Apulia (southern Italy) mesothelioma register.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {78}, doi = {10.1186/s12940-019-0512-4}, pmid = {31470859}, issn = {1476-069X}, abstract = {BACKGROUND: Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare disease with a poor prognosis. The diagnosis and management of these lesions are often difficult for pathologists, surgeons, oncologists and occupational physicians. A preoperative diagnosis of malignancy is rarely made, and there is no established effective therapy except orchidectomy.<br><br>METHODS: A systematic literature review was conducted among the articles published in the English literature on primary MMTVT. Moreover four cases from the Apulia mesothelioma register are reported here.<br><br>RESULTS: Two hundred eighty-nine cases of MMTVT have been reported from 1943 to 2018. Overall asbestos exposure has been investigated only for 58% of all cases reported in this review, while in 41.8% this data are not available. Noteworthy is the fact that in many reports there is not an anamnestic reconstruction of any asbestos exposure. A history of direct occupational, environmental or familial asbestos exposure is found in 27.6% of the cases. The four cases from the Apulia mesothelioma register are all with ascertained occupational exposure to asbestos.<br><br>CONCLUSIONS: The true incidence of asbestos exposure in MMTVT is underestimated because of insufficient information reported in older literature. To establish a broad consensus on the causal relationship between asbestos and MMTVT in the scientific community its necessary to analyze the same variables in the epidemiological studies. In general it should be recommended that a positive history of exposure to asbestos or to asbestos-containing materials are at risk for the development of a MMTVT and should be monitored.}, }
@article {pmid31467759, year = {2019}, author = {Hassan, D and Ligato, S}, title = {Localized Biphasic Malignant Peritoneal Mesothelioma with Rhabdoid Features Involving the Liver: Case Report and Review of the Literature.}, journal = {Case reports in pathology}, volume = {2019}, number = {}, pages = {2732674}, doi = {10.1155/2019/2732674}, pmid = {31467759}, issn = {2090-6781}, abstract = {Introduction: Localized malignant mesotheliomas, defined as sharply circumscribed tumors of the serosal membrane with the microscopic appearance of diffuse malignant mesothelioma, are rare tumors; their behavior and prognosis are uncertain. Intrahepatic mesotheliomas are postulated to arise from mesothelial cells of Glisson's capsule.<br><br>Case Presentation: A 69-year-old female with no history of asbestos exposure presented with a one-month history of increasing abdominal pain associated with constitutional symptoms. Computerized Tomography (CT) scan of the abdomen and pelvis revealed a sizable soft tissue mass within the right paracolic gutter, abutting the inferior hepatic margin, the lateral abdominal wall, and descending colon. Ultrasound-guided biopsy of the mass suggested a poorly differentiated hepatocellular carcinoma. There was no disease elsewhere on PET scan. Surgical resection of the mass was performed. Pathological assessment suggested the tumor to be arising from the liver with invasion of the liver, abdominal wall musculature, and the adventitial surface of the ascending colon. A final diagnosis of localized biphasic malignant peritoneal mesothelioma with rhabdoid features was rendered based on morphology and the result of immunohistochemical studies. The abdominal wall margin was positive. The patient progressed over the course of 6 months despite receiving adjuvant chemotherapy and immunotherapy with metastases and a decline in performance status and was transitioned to hospice.<br><br>Conclusion: Localized malignant peritoneal mesotheliomas are rare tumors that may present clinically as a liver mass and simulate primary hepatic or secondary tumors. Definitive diagnosis is obtained by surgical resection in most cases. The clinical outcome is variable with most cases having a poor outcome.}, }
@article {pmid31442913, year = {2019}, author = {Li, Z and Jiang, L and Chew, SH and Hirayama, T and Sekido, Y and Toyokuni, S}, title = {Carbonic anhydrase 9 confers resistance to ferroptosis/apoptosis in malignant mesothelioma under hypoxia.}, journal = {Redox biology}, volume = {26}, number = {}, pages = {101297}, pmid = {31442913}, issn = {2213-2317}, abstract = {Hypoxia and acidity provide microenvironment for selection under evolutionary pressure and proliferation in cancer cells. Carbonic anhydrases (CAs) are a superfamily of metalloenzymes present in all life kingdoms, equilibrating the reactions among CO2, bicarbonate and H+. CA9, a membrane-associated α-CA, has been a drug target for various cancers. Whereas iron is essential not only for cancer cells but also for all the lives on earth, little is known on the association among hypoxia, iron metabolism, extracellular acidity and redox regulation. Malignant mesothelioma (MM), an aggressive tumor with poor prognosis, is an intriguing model in that asbestos-associated pathogenesis includes excess iron environment during carcinogenesis. Re-analysis of rat asbestos-induced MM model revealed an inverse association between high CA9 expression and survival. Here we used human MMs to identify the molecular events surrounding CA9 from the viewpoint of iron metabolism. CA9 expression was significantly higher in MM cells than in MeT-5A mesothelial cells, which was further amplified under hypoxia (1%O2) with increased catalytic Fe(II). CA9 suppression by inhibitors (S4 and U104) decreased viability and migration of MM cells, accompanied by overexpression of TFRC, IREB1/2 and FPN1(SLC40A1) and by downregulation of FTH/FTL. This expressional pattern was similar to that of erastin-induced ferroptosis in the same cells. Furthermore, we observed mitochondrial fission and enhanced autophagy with increased catalytic Fe(II) in both mitochondria and lysosomes after CA9 inhibition, accompanied by increased peroxides, mitochondrial O2- and lipid peroxidation. The eventual cell death was significantly inhibited by deferoxamine, ferrostatin-1 and Z-VAD-FMK, suggesting a mixed cell death of ferroptosis and apoptosis. Therefore, CA9 plays a role in equilibrating among hypoxia, iron metabolism and redox regulation in MM cells.}, }
@article {pmid31428834, year = {2019}, author = {Keshava, HB and Tang, A and Siddiqui, HU and Raja, S and Raymond, DP and Bribriesco, A and Stevenson, J and Murthy, SC and Ahmad, U}, title = {Largely Unchanged Annual Incidence and Overall Survival of Pleural Mesothelioma in the USA.}, journal = {World journal of surgery}, volume = {43}, number = {12}, pages = {3239-3247}, pmid = {31428834}, issn = {1432-2323}, abstract = {BACKGROUND: Projections based on regulations curtailing asbestos use in the USA suggest that peak incidence of pleural mesothelioma would occur between 2000 and 2005 and then decline. We analyzed the National Cancer Database (NCDB) to assess current trends in disease incidence, patient demographics, cancer treatment, and survival.<br><br>METHODS: The NCDB was queried to identify patients diagnosed with pleural mesothelioma from 2004 through 2014. Clinical and pathologic characteristics, treatments, and survival were analyzed. Risk factors for death were identified by multivariable Cox regression.<br><br>RESULTS: A total of 20,988 patients with pleural mesothelioma were reported to the NCDB. The number of cases per year increased from 1783 to 1961, accounting for roughly 0.3% of all reported cancers each year. The proportion of elderly patients increased from 75 to 80%, but distribution by sex remained constant (20% female). The proportion of patients undergoing treatment increased from 34 to 54%. One-year survival increased from 37 to 47% and 3-year survival from 9 to 15% (p < 0.001). Factors associated with improved survival included younger age, female sex, epithelioid histology, treatment in an academic center, health insurance, higher income, and multimodality therapy.<br><br>CONCLUSIONS: The annual incidence of mesothelioma has not declined this century and remains stable. Reporting of histologic and clinical staging has improved. National trends suggest that survival is slowly increasing despite an aging cohort. Multimodal therapy and treatment at academic centers are modifiable risk factors associated with improved survival.}, }
@article {pmid31428586, year = {2019}, author = {Hoffmann, PR and Hoffmann, FW and Premeaux, TA and Fujita, T and Soprana, E and Panigada, M and Chew, GM and Richard, G and Hindocha, P and Menor, M and Khadka, VS and Deng, Y and Moise, L and Ndhlovu, LC and Siccardi, A and Weinberg, AD and De Groot, AS and Bertino, P}, title = {Multi-antigen Vaccination With Simultaneous Engagement of the OX40 Receptor Delays Malignant Mesothelioma Growth and Increases Survival in Animal Models.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {720}, doi = {10.3389/fonc.2019.00720}, pmid = {31428586}, issn = {2234-943X}, support = {G12 RR003061/RR/NCRR NIH HHS/United States ; U54 MD007584/MD/NIMHD NIH HHS/United States ; P20 GM103466/GM/NIGMS NIH HHS/United States ; P30 GM103341/GM/NIGMS NIH HHS/United States ; G12 MD007601/MD/NIMHD NIH HHS/United States ; P30 GM114737/GM/NIGMS NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; R13 CA150300/CA/NCI NIH HHS/United States ; R01 AI089999/AI/NIAID NIH HHS/United States ; }, abstract = {Malignant Mesothelioma (MM) is a rare and highly aggressive cancer that develops from mesothelial cells lining the pleura and other internal cavities, and is often associated with asbestos exposure. To date, no effective treatments have been made available for this pathology. Herein, we propose a novel immunotherapeutic approach based on a unique vaccine targeting a series of antigens that we found expressed in different MM tumors, but largely undetectable in normal tissues. This vaccine, that we term p-Tvax, is comprised of a series of immunogenic peptides presented by both MHC-I and -II to generate robust immune responses. The peptides were designed using in silico algorithms that discriminate between highly immunogenic T cell epitopes and other harmful epitopes, such as suppressive regulatory T cell epitopes and autoimmune epitopes. Vaccination of mice with p-Tvax led to antigen-specific immune responses that involved both CD8+ and CD4+ T cells, which exhibited cytolytic activity against MM cells in vitro. In mice carrying MM tumors, p-Tvax increased tumor infiltration of CD4+ T cells. Moreover, combining p-Tvax with an OX40 agonist led to decreased tumor growth and increased survival. Mice treated with this combination immunotherapy displayed higher numbers of tumor-infiltrating CD8+ and CD4+ T cells and reduced T regulatory cells in tumors. Collectively, these data suggest that the combination of p-Tvax with an OX40 agonist could be an effective strategy for MM treatment.}, }
@article {pmid31420427, year = {2019}, author = {Bousema, JE and van de Luijtgaarden, KM and Wilhelmus, S and Poelman, MM}, title = {Acute severe abdominal pain in a young woman caused by a well-differentiated papillary mesothelioma of the peritoneum.}, journal = {BMJ case reports}, volume = {12}, number = {8}, pages = {}, doi = {10.1136/bcr-2019-229769}, pmid = {31420427}, issn = {1757-790X}, abstract = {Acute abdominal pain is a common symptom in young women. We describe a patient with acute illness and severe lower abdominal pain. Laboratory tests were normal except for mildly deranged inflammatory markers. No abnormalities were reported on abdominal ultrasonography and MRI, whereas diagnostic laparoscopy revealed a tumour located dorsally from the uterus. We resected the tumour and pathology results showed a well-differentiated papillary mesothelioma of the peritoneum (WDPMP). Microscopy showed evidence of acute ischaemia in the resected lesion, which was likely the cause of the acute abdominal pain. WDPMP is a rare disease that arises from the serous membranes which does not seem to have a relation to asbestos exposure. Generally, WDPMP has a mild clinical course and good long-term prognosis.}, }
@article {pmid31419715, year = {2019}, author = {Consonni, D and Migliore, E and Barone-Adesi, F and Dallari, B and De Matteis, S and Oddone, E and Pesatori, AC and Riboldi, L and Mirabelli, D and Mensi, C}, title = {Gender differences in pleural mesothelioma occurrence in Lombardy and Piedmont, Italy.}, journal = {Environmental research}, volume = {177}, number = {}, pages = {108636}, doi = {10.1016/j.envres.2019.108636}, pmid = {31419715}, issn = {1096-0953}, abstract = {BACKGROUND: Higher mesothelioma rates in men (vs women) reflect more frequent and more intense asbestos exposure. We assessed the impact of exposure difference between genders on age-specific rates of pleural mesothelioma (PM) occurrence using data from two Italian regions.<br><br>METHODS: We used data from the Lombardy and Piedmont mesothelioma registries (period 2000-2016, age 45-74 years) to compare rates of PM in men and women and to estimate the rate advancement period (RAP).<br><br>RESULTS: Based on 3384 cases (2405 men, 979 women) in Lombardy and 2042 (1389 men, 653 women) in Piedmont, the rate ratio was 2.81 (90% confidence interval: 2.61-3.03) in Lombardy and 2.39 (2.17-2.62) in Piedmont. In both regions RAP ranged from 7 to 10 years (at age 45 and 63 in men, respectively).<br><br>CONCLUSION: Men showed more than twofold increased PM rates and reached the same incidence as women 7-10 years earlier. RAP can be a useful measure of exposure impact on premature disease occurrence.}, }
@article {pmid31416570, year = {2019}, author = {Betti, M and Aspesi, A and Sculco, M and Matullo, G and Magnani, C and Dianzani, I}, title = {Genetic predisposition for malignant mesothelioma: A concise review.}, journal = {Mutation research}, volume = {781}, number = {}, pages = {1-10}, doi = {10.1016/j.mrrev.2019.03.001}, pmid = {31416570}, issn = {1873-135X}, abstract = {Malignant mesothelioma (MM) is an aggressive cancer associated with asbestos exposure. Studies of familial malignant pleural mesothelioma (MPM) have suggested the existence of a genetic predisposition. Information on the role of genetic risk factors in the development of MM has been growing in the last years, and both low- and high-risk genetic factors have been identified, but genetic factors alone (without any exposure to asbestos or other mineral fibers) have never been shown to induce MM. Low-risk genetic factors have been identified in studies that systematically analyzed the whole genome. When considered alone these low-risk genetic factors carry a relative risk of MPM that is 10- to 15-fold lower than that carried by asbestos exposure; however, a large number of these factors in combination may increase the impact of asbestos exposure. High-risk genetic factors include truncating variants in the tumor suppressor BAP1 and in other tumor suppressor genes belonging to DNA repair pathways. Heterozygous germline variants in these genes may favor carcinogenesis if a second somatic variant occurs that impairs the wild-type allele. This impairment can cause genetic instability due to the suppression of a specific DNA repair pathway, and transformation. This genetic predisposition may have translational consequences, as it may predict patient response to drugs that induce tumor-specific synthetic lethality.}, }
@article {pmid31413184, year = {2019}, author = {Barone-Adesi, F and Ferrante, D and Chellini, E and Merler, E and Pavone, V and Silvestri, S and Miligi, L and Gorini, G and Bressan, V and Girardi, P and Ancona, L and Romeo, E and Luberto, F and Sala, O and Scarnato, C and Menegozzo, S and Oddone, E and Tunesi, S and Perticaroli, P and Pettinari, A and Cuccaro, F and Curti, S and Baldassarre, A and Cena, T and Angelini, A and Marinaccio, A and Mirabelli, D and Musti, M and Pirastu, R and Ranucci, A and Magnani, C and , }, title = {Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {9}, pages = {611-616}, doi = {10.1136/oemed-2019-105779}, pmid = {31413184}, issn = {1470-7926}, abstract = {OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis.<br><br>METHODS: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time.<br><br>RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer.<br><br>CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.}, }
@article {pmid31411568, year = {2019}, author = {Gudmundsson, G and Tomasson, K}, title = {[Asbestos and its effects on health of Icelanders - review].}, journal = {Laeknabladid}, volume = {105}, number = {7}, pages = {327-334}, doi = {10.17992/lbl.2019.0708.241}, pmid = {31411568}, issn = {1670-4959}, abstract = {Asbestos are crystallized silicate minerals that form fibers with different structures and characteristics. Asbestos fibers are very durable and can tolerate very high temperatures. Therefore it was common to use asbestos as a fire retardants, heat insulation and where high temperature is used. Asbestos has been banned in Iceland from 1983 but can still be found in large amounts in buildings, ships and hot water pipes. Large amounts of asbestos were imported in the years before the ban but diminished soon to almost nothing today. Needle or filamentous shaped dust is released when working with asbestos. It is this dust that is dangerous for health. The latent time from exposure to disease can be up to forty years. Asbestos reaches the lungs via inhalation and can cause asbestosis that is a form of lung fibrosis with slow progression. Asbestos can also cause benign pleural effusions, pleural plaques and diffuse pleural thickening. Asbestos is a carcinogen. Lung cancer is most common but asbestos is also a risk factor for cancers of other organs. Mesothelioma is most common in the pleura but can be seen in other membranes. The incidence of these tumors is high in Iceland and is still increasing among males. Of all the European countries mortality is highest in Iceland. It is important for physicians to include asbestos exposure in the differential diagnosis of lung diseases and when lung cancer is diagnosed.}, }
@article {pmid31411522, year = {2019}, author = {Jiang, Y and Mei, Z and Cao, H and Li, S and Xu, H and Qiu, H and Liu, Y}, title = {Meningeal metastasis of a malignant peritoneal mesothelioma: A case report and literature review.}, journal = {Cancer biology &amp; therapy}, volume = {20}, number = {12}, pages = {1409-1415}, pmid = {31411522}, issn = {1555-8576}, abstract = {Malignant peritoneal mesothelioma is a very rare tumor originating from the peritoneal serous mesothelium. Meningeal metastasis of malignant peritoneal is even more rare. Here, we reported a case of a 60-year-old female patient with a history of exposure to asbestos for 10 years who presented with massive peritoneal effusion followed by disorder of consciousness and symptoms of cranial nerve injury. The patient was diagnosed as peritoneal mesothelioma with meningeal metastasis through neurological symptoms, cytological finding of cerebrospinal fluid combined with cranial magnetic resonance imaging (MRI). The patient received systemic chemotherapy and total craniospinal irradiation. The follow up visits showed that the survival time of patient after diagnosis of meningeal metastasis from peritoneal mesothelioma was 5 months. To our knowledge, this is the first case of menigeal metastasis of peritoneal mesothelioma. We hope this particular case may be helpful in providing some experience to the treatment of peritoneal mesothelioma with meningeal metastasis.}, }
@article {pmid31406977, year = {2019}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {}, number = {}, pages = {}, doi = {10.1093/annonc/mdz217}, pmid = {31406977}, issn = {1569-8041}, }
@article {pmid31406207, year = {2019}, author = {Munson, PB and Hall, EM and Farina, NH and Pass, HI and Shukla, A}, title = {Exosomal miR-16-5p as a target for malignant mesothelioma.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {11688}, doi = {10.1038/s41598-019-48133-0}, pmid = {31406207}, issn = {2045-2322}, support = {R01 ES021110/ES/NIEHS NIH HHS/United States ; R21 ES028857/ES/NIEHS NIH HHS/United States ; W81XWH-13-PRCRP-IA//U.S. Department of Defense (United States Department of Defense)/ ; }, abstract = {Malignant mesothelioma (MM) is an asbestos-induced cancer arising on the mesothelial surface of organ cavities. MM is essentially incurable without a means of early diagnosis and no successful standard of care. These facts indicate a deep chasm of knowledge that needs to be filled. Our group recently delved into MM tumor biology from the perspective of exosome-contained microRNAs (miRNAs). We discovered that the most abundant miRNAs in MM cancer exosomes were tumor suppressors, particularly miR-16-5p. This observation lead us to hypothesize that MM cells preferentially secreted tumor-suppressor miRNAs via exosomes. Through separate avenues of potential therapeutic advance, we embarked on an innovative strategy to kill MM tumor cells. We employed small molecule inhibitors to block exosome secretion, thereby reducing miR-16-5p exosome loss and replenishing cellular miR-16-5p leading to reduced tumorigenic capacity and miR-16-5p target oncoproteins CCND1 and BCL2. Additionally, we force-fed MM tumor exosomes back to MM tumor cells, which led to cell death, and a reduction in the same oncoproteins. We recapitulated these results with direct transfection of miR-16-5p, confirmed that this is a cancer-cell specific effect, and elucidated a part of the miR-16-5p mechanism of exosome loading.}, }
@article {pmid31391078, year = {2019}, author = {Luberto, F and Ferrante, D and Silvestri, S and Angelini, A and Cuccaro, F and Nannavecchia, AM and Oddone, E and Vicentini, M and Barone-Adesi, F and Cena, T and Mirabelli, D and Mangone, L and Roncaglia, F and Sala, O and Menegozzo, S and Pirastu, R and Azzolina, D and Tunesi, S and Chellini, E and Miligi, L and Perticaroli, P and Pettinari, A and Bressan, V and Merler, E and Girardi, P and Bisceglia, L and Marinaccio, A and Massari, S and Magnani, C and , }, title = {Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.}, journal = {Environmental health : a global access science source}, volume = {18}, number = {1}, pages = {71}, doi = {10.1186/s12940-019-0510-6}, pmid = {31391078}, issn = {1476-069X}, support = {Current research 2012: asbestos project. Operative Unit 2//Istituto Superiore Sanità/International ; Piano Ricerca 2016-2018, &quot;Programma Speciale Amianto&quot;, Ricerca BRIC id 55//INAIL/International ; Piano Ricerca 2016-2018, &quot;Programma Speciale Amianto&quot;, Ricerca BRIC id 59//INAIL/International ; }, abstract = {BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos.<br><br>METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution.<br><br>RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%.<br><br>CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.}, }
@article {pmid31388672, year = {2019}, author = {Corti, A and Bonetti, J and Dominici, S and Piaggi, S and Fierabracci, V and Foddis, R and Pompella, A}, title = {Induction of gamma-glutamyltransferase activity and consequent prooxidant reactions in human macrophages exposed to crocidolite asbestos.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {}, number = {}, pages = {}, doi = {10.1093/toxsci/kfz175}, pmid = {31388672}, issn = {1096-0929}, abstract = {Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact react with macrophage-derived hydrogen peroxide in the so called Fenton reaction, giving rise to highly reactive and mutagenic hydroxyl radical. On the other hand, hydroxyl radical can as well originate after thiol-dependent reduction of iron, a process capable of starting its redox cycling. Previous studies showed that glutathione (GSH) is one such thiols, and that cellular gamma-glutamyltransferase (GGT) can efficiently potentiate GSH-dependent iron redox cycling and consequent oxidative stress. As GGT is expressed in macrophages and is released upon their activation, the present study was aimed at verifying the hypothesis that GSH/GGT-dependent redox reactions may participate in the oxidative stress following the activation of macrophages induced by crocidolite asbestos. Experiments in acellular systems confirmed that GGT-mediated metabolism of GSH can potentiate crocidolite-dependent production of superoxide anion, through the production of highly reactive dipeptide thiol cysteinyl-glycine. Cultured THP-1 macrophagic cells, as well as isolated monocytes obtained from healthy donors and differentiated to macrophages in vitro, were investigated as to their expression of GGT and the effects of exposure to crocidolite. The results show that crocidolite asbestos at sub-toxic concentrations (50-250 ng/1,000 cells) can upregulate GGT expression, which raises the possibility that macrophage-initiated, GSH/GGT-dependent prooxidant reactions may participate in the pathogenesis of tissue damage and inflammation consequent to crocidolite intoxication.}, }
@article {pmid31383968, year = {2019}, author = {Wronkiewicz, SK and Roggli, VL and Hinrichs, BH and Kendler, A and Butler, RA and Christensen, BC and Marsit, CJ and Nelson, HH and McClean, MD and Kelsey, KT and Langevin, SM}, title = {Chrysotile fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41379-019-0332-7}, pmid = {31383968}, issn = {1530-0285}, support = {R21DE027227//U.S. Department of Health &amp; Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; 2P30ES006096//U.S. Department of Health &amp; Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)/ ; }, abstract = {Asbestos describes a group of naturally occurring fibrous silicate mineral compounds that have been associated with a number of respiratory maladies, including mesothelioma and lung cancer. In addition, based primarily on epidemiologic studies, asbestos has been implicated as a risk factor for laryngeal and pharyngeal squamous cell carcinoma (SCC). The main objective of this work was to strengthen existing evidence via empirical demonstration of persistent asbestos fibers embedded in the tissue surrounding laryngeal and pharyngeal SCC, thus providing a more definitive biological link between exposure and disease. Six human papillomavirus (HPV)-negative laryngeal (n = 4) and pharyngeal (n = 2) SCC cases with a history working in an asbestos-exposed occupation were selected from a large population-based case-control study of head and neck cancer. A laryngeal SCC case with no history of occupational asbestos exposure was included as a control. Tissue cores were obtained from adjacent nonneoplastic tissue in tumor blocks from the initial primary tumor resection, and mineral fiber analysis was performed using a scanning electron microscope equipped with an energy dispersive X-ray analyzer (EDXA). Chrysotile asbestos fiber bundles were identified in 3/6 of evaluated cases with a history of occupational asbestos exposure. All three cases had tumors originating in the larynx. In addition, a wollastonite fiber of unclear significance was identified one of the HPV-negative pharyngeal SCC cases. No mineral fibers were identified in adjacent tissue of the case without occupational exposure. The presence of asbestos fibers in the epithelial tissue surrounding laryngeal SCC in cases with a history of occupational asbestos exposure adds a key line of physical evidence implicating asbestos as an etiologic factor.}, }
@article {pmid31380709, year = {2019}, author = {Jacobs, NFB and Towle, KM and Finley, BL and Gaffney, SH}, title = {An updated evaluation of potential health hazards associated with exposures to asbestos-containing drywall accessory products.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {5}, pages = {430-444}, doi = {10.1080/10408444.2019.1639612}, pmid = {31380709}, issn = {1547-6898}, abstract = {Following a previously published (2012) evaluation of the potential health hazards related to the use of asbestos-containing drywall accessory products, additional information regarding asbestos exposures during the use of accessory products, as well as studies of chrysotile asbestos risk as a function of exposure, have been published in the peer-reviewed literature. The purpose of this analysis is to update the original evaluation with this new information. It was previously estimated that a professional drywaller performing joint compound-associated tasks could have a lifetime cumulative chrysotile exposure of 12-26 f/cc-year. Using conservative assumptions regarding airborne asbestos levels during different drywalling tasks, task duration, and job tenure, we found that a range of 4.3-36.3 f/cc-year is a plausible estimate of a career drywaller's cumulative asbestos exposure from historical joint compound use. The estimated range for bystander exposures would be below (sometimes significantly below) this range depending on the frequency and duration of work near drywallers. Further, the estimated drywaller and bystander total fiber exposures were well below a recently published &quot;no-observed adverse effect level, best estimate&quot; for predominately chrysotile exposures of 89-168 f/cc-year for lung cancer and 208-415 f/cc-year for mesothelioma. We also determined that, even if the chrysotile or possibly talc ingredients in the drywall products had contained asbestiform tremolite, the cumulative tremolite exposures would have been well below a recently published tremolite no-effect level of 0.5-2.6 f/cc-year. Based on our calculations, typical drywall work using asbestos-containing drywall accessory products is not expected to increase the risk of asbestos-related lung cancer or mesothelioma. These conclusions are consistent with the lack of epidemiological evidence that drywall work resulted in an increased incidence of asbestos-related disease in the drywall trades.}, }
@article {pmid31380702, year = {2019}, author = {Marsh, GM and Ierardi, AM and Benson, SM and Finley, BL}, title = {Occupational exposures to cosmetic talc and risk of mesothelioma: an updated pooled cohort and statistical power analysis with consideration of latency period.}, journal = {Inhalation toxicology}, volume = {31}, number = {6}, pages = {213-223}, doi = {10.1080/08958378.2019.1645768}, pmid = {31380702}, issn = {1091-7691}, abstract = {Objectives: We previously published a pooled statistical power analysis of mesothelioma incidence in the Italian, Norwegian, Austrian, and French cosmetic talc miner and miller cohorts. Soon thereafter, updates to the Italian and Norwegian cohorts were published, providing an additional 14,322 person-years of observation. In this study, we provide an updated power analysis using the newly available information. Methods: We pooled the current results regarding pleural cancer/mesothelioma mortality or incidence in four cosmetic talc miner and miller cohorts in Italy, Norway, Austria, and France. We used the expected numbers of cases as reported by the authors and the power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities. Results: There was a pooled total of 113,344 person-years in the cohorts. Although 3.0 pleural cancers/mesotheliomas were expected, there were no reported pleural cancer or mesothelioma cases in any cohort. Our pooled analysis was associated with 79 and 62% power to detect a 3.0-fold and 2.5-fold or greater increase in pleural cancer/mesothelioma, respectively. These favorable power characteristics were effectively maintained when restricting the pooled cohort to workers with a latency period of 30 or more years (observation time from first employment). Conclusions: The epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that exposure to cosmetic talc is associated with the development of pleural cancer/mesothelioma.}, }
@article {pmid31376434, year = {2019}, author = {Butnor, KJ and Pavlisko, EN and Sporn, TA and Roggli, VL}, title = {Mesothelioma of the tunica vaginalis testis.}, journal = {Human pathology}, volume = {92}, number = {}, pages = {48-58}, doi = {10.1016/j.humpath.2019.07.009}, pmid = {31376434}, issn = {1532-8392}, abstract = {Malignant mesothelioma (MM) arising from the serosal membranes of the tunica vaginalis testis (TVT) is rare. Most examples in the published medical literature are individual case reports. This study presents the clinicopathological findings of mesothelioma of the TVT in one of the largest series to date. Individuals with mesothelioma of the TVT were identified from a database of more than 4000 mesothelioma cases, and their clinicopathological features were recorded. Eighteen men with MM and 2 with well-differentiated papillary mesothelioma of the TVT were identified, which represented 0.6% of males with mesothelioma in study population. The median age at diagnosis was 72 years (range, 32-85 years). A neoplasm was not suspected preoperatively in 12 of the 17 (71%) men whose clinical presentation was known, 7 of whom presented with hydrocele and 5 with inguinal hernia. The other 5 had a clinically recognized mass. Seven of the men underwent herniorrhaphy; 7, radical orchiectomy; 3, hydrocelectomy; and 3, paratesticular mass biopsy or excision as the initial diagnostic procedure. Twelve of the MM cases were epithelioid and 6 were biphasic. Among the 6 men with MM who had ≥6 months of follow-up, 1 was alive with no evidence of disease at 6 months, and 5 were known to have died of disease 8-74 months (median = 31.5 months) following diagnosis. Three men with MM had received either chemotherapy or radiation therapy. Of the 2 men initially diagnosed with well-differentiated papillary mesothelioma, 1 was alive without evidence of disease 5 years after diagnosis, while the other had findings more compatible with MM with peritoneal involvement 2 years following initial diagnosis. In 15 of the 18 cases of MM (83%), there was documented occupational or paraoccupational exposure to asbestos, the average duration of which was 33 years (range, 2-46 years). Information regarding the presence or absence of pleural plaques was available in 5 of the MM cases, and pleural plaques had been found in 4. Lung tissue was not available for fiber analysis in any of the cases. One additional case originally diagnosed at another institution as MM of the TVT was reclassified as adenocarcinoma following performance of additional immunohistochemical testing. TVT is a rare site of MM, the diagnosis of which is often unsuspected preoperatively. Like its counterparts at other serosal sites, MM of the TVT is an aggressive tumor with a poor prognosis that evidence would suggest is etiologically associated with asbestos in at least some cases.}, }
@article {pmid31375830, year = {2019}, author = {Sorahan, TM}, title = {Cancer incidence in UK electricity generation and transmission workers, 1973-2015.}, journal = {Occupational medicine (Oxford, England)}, volume = {69}, number = {5}, pages = {342-351}, doi = {10.1093/occmed/kqz082}, pmid = {31375830}, issn = {1471-8405}, abstract = {BACKGROUND: Long-term health outcomes in cohorts of workers from the electricity supply industry have been studied.<br><br>AIMS: The aim of the study was to examine updated cancer incidence findings among a cohort of UK electricity generation and transmission workers.<br><br>METHODS: Cancer morbidity experienced by 81 616 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-2015. All employees had worked for at least 6 months with some employment between 1973 and 1982. Standardized registration ratios (SRRs) were calculated based on national rates.<br><br>RESULTS: Overall cancer morbidity was slightly below expectation in males. Significant excesses were found in male workers for mesothelioma (observed [Obs] 763, SRR 326), skin cancer (non-melanoma) (Obs 5616, SRR 106), and prostate cancer (Obs 4298, SRR 106), and in female workers for cancer of the small intestine (Obs 13, SRR 220), nasal cancer (Obs 11, SRR 407), and breast cancer (Obs 758, SRR 110). More detailed analyses showed important contrasts, particularly for mesothelioma, lung cancer, skin cancer, prostate cancer and breast cancer.<br><br>CONCLUSIONS: A clear occupational excess of mesothelioma was not matched by a corresponding excess of asbestos-induced lung cancer. Confident interpretation of the excesses of cancers of the nasal cavities and small intestine is not possible, although occupational exposures received in this industry may well not be involved. An excess of skin cancer in transmission workers may be associated with outdoor working.}, }
@article {pmid31375770, year = {2019}, author = {Churg, A and Galateau-Salle, F and Roden, AC and Attanoos, R and von der Thusen, JH and Tsao, MS and Chang, N and De Perrot, M and Dacic, S}, title = {Malignant mesothelioma in situ: morphologic features and clinical outcome.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41379-019-0347-0}, pmid = {31375770}, issn = {1530-0285}, abstract = {The existence of an in situ phase of malignant mesothelioma has long been postulated but until recently has been impossible to prove. Here we describe ten patients with mesothelioma in situ, defined by a single layer of surface mesothelial cells showing loss of BAP1 nuclear immunostaining, no evidence of tumor by imaging and/or by direct examination of the pleura/peritoneum, and no invasive mesothelioma developing for at least 1 year. Nine cases were pleural and one peritoneal. Most patients were biopsied for repeated effusions of unknown etiology; in two patients mesothelioma in situ was found incidentally in lung cancer resections. In addition to surface mesothelium with BAP1 loss, one case had a surface papillary proliferation with BAP1 loss, and two cases had a small (few millimeter) nodule with BAP1 loss. CDKN2A was deleted by FISH in one of eight cases. Methylthioadenosine phosphorylase showed partial loss in the surface mesothelium by immunohistochemistry in three cases. Invasive malignant mesothelioma developed in seven patients with time between biopsy and invasive disease from 12 to 92 (median 60) months. Invasive mesothelioma has not developed in the other three patients at 12, 57, and 120 months, but the latter patient, who has pleural plaques, still has repeated pleural effusions, probably representing a so-called &quot;benign asbestos effusion.&quot; We conclude that mesothelioma in situ, as diagnosed using the criteria outlined above, is associated with a high risk of developing invasive mesothelioma, but typically over a relatively protracted time, so that curable interventions maybe possible.}, }
@article {pmid31372931, year = {2019}, author = {Itano, H and Takeda, T and Yamada, T and Koide, M and Kobayashi, T}, title = {Heterologous sarcomatoid pleural mesothelioma with osteosarcomatous differentiation: a report of autopsy case that accomplished trimodality therapy and review of the literature.}, journal = {General thoracic and cardiovascular surgery}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11748-019-01182-8}, pmid = {31372931}, issn = {1863-6713}, abstract = {Heterologous mesothelioma is a very rare subtype of sarcomatoid mesothelioma characterized by the presence of malignant heterologous elements. A 69-year-old man with a strong history of asbestos exposure presented with a 5-cm mass in his chest wall, destroying the right 5th rib and spreading along the parietal pleura, on a CT. Biopsy revealed heterologous mesothelioma with osteosarcomatous elements, following which left extrapleural pneumonectomy was performed with combined resection of pericardium, hemidiaphragm, and 4th, 5th, and 6th costal segments. A small cytokeratin-positive epithelioid component in the resected tumor definitively confirmed the diagnosis. Post-operative chemotherapy and intensity-modulated radiotherapy were undertaken. After 12-month disease-free period post treatment, rapid intraperitoneal recurrence resulted in death. Autopsy revealed no tumors in the left thorax. We present here a case of heterologous osteosarcomatous pleural mesothelioma that followed a unique clinical course after trimodality therapy. In addition, literature of 54 cases of the similar heterologous mesothelioma was reviewed.}, }
@article {pmid31366157, year = {2019}, author = {Gogou, E and Hatzoglou, C and Zarogiannis, SG and Malli, F and Jagirdar, RM and Gourgoulianis, KI}, title = {Mesothelioma Mortality Rates in Greece for the Period 2005-2015 Is Increased Compared to Previous Decades.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {55}, number = {8}, pages = {}, doi = {10.3390/medicina55080419}, pmid = {31366157}, issn = {1648-9144}, abstract = {Background and Objective: To present summary statistics regarding malignant mesothelioma (MM) mortality in Greece during the period 2005-2015 and compare it with previous decades, along with gender, age and geographical area analysis. Materials and Methods: The Hellenic Statistical Authority provided the data, which included all deaths for the period 1983 to 2015 that mentioned MM as the death cause in the corresponding death certificate. MM mortality rates have been calculated with respect to gender, age, and geographical location in Greece. Furthermore, a comparison analysis was made among three eleven consecutive year periods, in order to assess potential changes in the mortality rates. Results: The MM mortality rate has significantly increased during the period 2005-2015 both in males and females compared to earlier decades. The maximum number of MM deaths has shifted to an older age group of 70-80 years during the 2005-2015 period as compared to that of 1983-2004 in both genders. Additionally, MM mortality rates have significantly increased in all geographical areas except for the Epirus Prefecture. Conclusions: Our results demonstrate an increased MM mortality rate in Greece for the decade 2005-2015 as compared to the two previous decades. This increase is possibly due to the fact that the peak in asbestos production and use in Greece was in mid 1990s, while the asbestos ban came in effect in 2005. Based on these findings the MM epidemic in Greece has not yet peaked, therefore it is important to implement screening strategies for early MM detection.}, }
@article {pmid31360386, year = {2019}, author = {Borrelli, E and Babcock, Z and Kogut, S}, title = {Costs of medical care for mesothelioma.}, journal = {Rare tumors}, volume = {11}, number = {}, pages = {2036361319863498}, doi = {10.1177/2036361319863498}, pmid = {31360386}, issn = {2036-3605}, abstract = {Malignant mesothelioma is a rare and devastating form of cancer with an increasing economic burden. We sought to describe the direct cost burden of mesothelioma to the US health system. A systematic literature review was performed to locate published estimates of the medical cost of mesothelioma. In addition, we performed an analysis of hospital discharge data from the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. We also reviewed publicly available legal settlements. We found that published estimates of the cost of medical care for mesothelioma are sparse, and differ with respect to nation, timeframe, and types of cost included. For the year 2014 in the United States, we estimated a mean cost per mesothelioma hospitalization of US$24,124 (95% confidence interval: US$20,819-US$28,983) and a total cost for hospital care of US$44,214,835. In conclusion, we found that reports describing the direct medical cost of care for mesothelioma in the United States are lacking, yet the per-patient cost of care is substantial, as evidenced by analyses of inpatient care and legal settlements.}, }
@article {pmid31355511, year = {2019}, author = {Lee, MJ and Kuehne, N and Hueniken, K and Liang, S and Rai, S and Sorotsky, H and Herman, M and Shepshelovich, D and Bruce, J and Liang, M and Patel, D and Cheng, D and Chen, Z and Eng, L and Brown, MC and Cho, J and Leighl, NB and de Perrot, M and Reisman, D and Xu, W and Bradbury, PA and Liu, G}, title = {Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis.}, journal = {Molecular carcinogenesis}, volume = {58}, number = {11}, pages = {1960-1973}, doi = {10.1002/mc.23088}, pmid = {31355511}, issn = {1098-2744}, support = {//Posluns Family Foundation/ ; //Princess Margaret Cancer Centre Alan Brown Chair in Molecular Genomics/ ; //Comprehensive Research Experience for Medical Students Research Scholar Program, University of Toronto/ ; }, abstract = {Brahma (BRM), of the SWI/SNF complex, has two 6 to 7 bp insertion promoter polymorphisms (BRM-741/BRM-1321) that cause epigenetic BRM suppression, and are associated with risk of multiple cancers. BRM polymorphisms were genotyped in malignant pleural mesothelioma (MPM) cases and asbestos-exposed controls. Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between BRM-741/BRM-1321 and risk in patients with MPM, a differential effect by smoking status was observed (P-interaction < .001), where homozygous variants were protective (aOR of 0.18-0.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7-4.4). While there was no association between BRM polymorphisms and OS in ever-smokers, the aHR of carrying homozygous-variants of BRM-741, BRM-1321 or both were 4.0 to 8.6 in never-smokers when compared to wild-type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA-affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never-smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever-smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.}, }
@article {pmid31355131, year = {2019}, author = {Di Somma, S and Iannuzzi, CA and Passaro, C and Forte, IM and Iannone, R and Gigantino, V and Indovina, P and Botti, G and Giordano, A and Formisano, P and Portella, G and Malfitano, AM and Pentimalli, F}, title = {The Oncolytic Virus dl922-947 Triggers Immunogenic Cell Death in Mesothelioma and Reduces Xenograft Growth.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {564}, doi = {10.3389/fonc.2019.00564}, pmid = {31355131}, issn = {2234-943X}, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with asbestos exposure that urgently requires effective therapeutic strategies. Current treatments are unable to increase significantly patient survival, which is often limited to <1 year from diagnosis. Virotherapy, based on the use of oncolytic viruses that exert anti-cancer effects by direct cell lysis and through the induction of anti-tumor immune response, represents an alternative therapeutic option for rare tumors with limited life expectancy. In this study, we propose the use of the adenovirus dl922-947, engineered to allow selective replication in cancer cells, to counteract MPM. Methods: We performed a thorough preclinical assessment of dl922-947 effects in a set of MPM cell lines and xenografts. Cytotoxicity of dl922-947 alone and in combination assays was evaluated by sulforhodamine B assay. Cell cycle, calreticulin expression, and high mobility group box protein 1 (HMGB1) secretion were determined by flow cytometry, whereas ATP content was determined by a luminescence-based bioassay. The modulation of angiogenic factors in MPM-infected cells was evaluated through ELISA. Results: We found that dl922-947 infection exhibits cytotoxic effects in MPM cell lines, affecting cell viability, cell cycle progression, and regulating main hallmarks of immunogenic cell death inducing calreticulin surface exposure, HMGB1 and ATP release. Our results also suggest that dl922-947 may affect angiogenic signals by regulation of VEGF-A and IL-8 secretion. Furthermore, dl922-947 shows anti-tumor efficacy in murine xenograft models reducing tumor growth and enhancing survival. Finally, the combination with cisplatin potentiated the cytotoxic effect of dl922-947. Conclusions: Overall our data identify virotherapy, based on the use of dl922-947, as a new possible therapeutic strategy against MPM, which could be used alone, in combination with standard chemotherapy drugs, as shown here, or other approaches also aimed at enhancing the antitumoral immune response elicited by the virus.}, }
@article {pmid31336692, year = {2019}, author = {Krówczyńska, M and Wilk, E}, title = {Environmental and Occupational Exposure to Asbestos as a Result of Consumption and Use in Poland.}, journal = {International journal of environmental research and public health}, volume = {16}, number = {14}, pages = {}, doi = {10.3390/ijerph16142611}, pmid = {31336692}, issn = {1660-4601}, abstract = {Asbestos is harmful to human health; exposure to asbestos causes a wide range of asbestos-related diseases.<br><br>AIM: Malignant mesothelioma (MM) is unique to occupational and environmental asbestos exposure.<br><br>METHODS: Environmental asbestos exposure was examined in relation to asbestos use and manufacturing, the quantity of the asbestos-containing products still in use, the concentrations of asbestos fibres in the air and the number of MM cases diagnosed each year per county.<br><br>RESULTS: The correlation coefficient of the measurements of the asbestos fibre concentrations in the air and the quantity of asbestos-cement products in use is high and amounts to 0.68. Meanwhile, the correlation coefficient of the measurements of asbestos fibre concentrations in air and MM morbidity rate resulting from environmental exposure calculated for particular counties in provinces is low and amounts to 0.37. The highest MM morbidity rate was observed for Małopolskie and Śląskie, a typical industrial area of Poland.<br><br>CONCLUSIONS: There are MM cases which are still attributable to occupational asbestos exposure, although MM cases resulting from environmental exposure to asbestos have an increased MM risk. Poland is among those countries with a low MM incidence rate, which seems to be an underestimation of environmental asbestos exposure. As long as asbestos-cement products are used in the environment, actions should be undertaken to protect public health.}, }
@article {pmid31328588, year = {2019}, author = {Korchevskiy, A and Rasmuson, JO and Rasmuson, EJ}, title = {Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality.}, journal = {Inhalation toxicology}, volume = {31}, number = {5}, pages = {180-191}, doi = {10.1080/08958378.2019.1640320}, pmid = {31328588}, issn = {1091-7691}, abstract = {Context: The potency of various mineral fiber types to produce mesothelioma was previously evaluated for numerous cohorts, but the differences in potencies for distinct fiber types have yet to be explained. Objective: To develop an empirical model that would reconstruct mesothelioma potency factors for various types of fiber based on their chemical composition and dimensionality. Methods: Typical chemical composition and dimensionality metrics (aspect ratios) were obtained and combined with mesothelioma potency factors estimated by Hodgson and Darnton method for Quebec chrysotile, South Africa amosite, South Africa and Australian crocidolite, Russian anthophyllite, Libby amphiboles, and Turkey erionite. The forward stepwise log-log regression method was utilized to determine the best combination of input parameters. Results: Mesothelioma potency factors (RM) for selected cohorts were effectively reconstructed utilizing the median aspect ratio of fibers and equivalent fractions of SiO2, total Fe oxides or total equivalent Fe3+ as Fe2O3, and MgO. Modeled potency factors increase as the aspect ratio, SiO2, and total Fe oxide (or Fe2O3) content grow, and as the MgO content diminishes. Correlation coefficients up to 0.999, p < 0.01, were achieved. The models also yield reasonable estimates of mesothelioma potencies for other fiber types, including Bolivian crocidolite, Russian chrysotile, fluoro-edenite, and others. Conclusion: In spite of the empirical approach, the proposed models provide a starting point for targeted studies of mesothelioma mechanisms by elucidating significant contributing physicochemical factors. The models have an exploratory and preliminary character but can potentially be useful to introduce quantitative structure-activity relationship approaches for the toxicology of fibrous minerals.}, }
@article {pmid31314677, year = {2019}, author = {Henley, SJ and Peipins, LA and Rim, SH and Larson, TC and Miller, JW}, title = {Geographic Co-Occurrence of Mesothelioma and Ovarian Cancer Incidence.}, journal = {Journal of women's health (2002)}, volume = {}, number = {}, pages = {}, doi = {10.1089/jwh.2019.7752}, pmid = {31314677}, issn = {1931-843X}, abstract = {Background: Asbestos is an established cause of several cancers, including mesothelioma and ovarian cancer. Incidence of mesothelioma, the sentinel asbestos-associated cancer, varies by state, likely reflecting different levels of asbestos exposure. We hypothesized that states with high mesothelioma incidence may also have high ovarian cancer incidence. Materials and Methods: Using data from the Centers for Disease Control and Prevention National Program for Cancer Registries and the National Cancer Institute Surveillance, Epidemiology, and End Results Program, we examined the geographic co-occurrence of mesothelioma and ovarian cancer incidence rates by U.S. state for 2003-2015. Results: By state, mesothelioma incidence ranged from 0.5 to 1.3 cases per 100,000 persons and ovarian cancer incidence ranged from 9 to 12 cases per 100,000 females. When states were grouped by quartile of mesothelioma incidence, the average ovarian cancer incidence rate was 10% higher in states with the highest mesothelioma incidence than in states with the lowest mesothelioma incidence. Ovarian cancer incidence tended to be higher in states with high mesothelioma incidence (Pearson correlation r = 0.54; p < 0.0001). Conclusions: Data from state cancer registries show ovarian cancer incidence was positively correlated with mesothelioma incidence, suggesting asbestos may be a common exposure. The potential for asbestos exposure has declined since the 1970s because fewer products contain asbestos; however, some products, materials, and buildings may still release asbestos and thousands of workers may be exposed. Ensuring that people are protected from exposure to asbestos in their workplaces, homes, schools, and communities may reduce the risk of several cancers.}, }
@article {pmid31295974, year = {2019}, author = {Zona, A and Iavarone, I and Buzzoni, C and Conti, S and Santoro, M and Fazzo, L and Pasetto, R and Pirastu, R and Bruno, C and Ancona, C and Bianchi, F and Forastiere, F and Manno, V and Minelli, G and Minerba, A and Minichilli, F and Stoppa, G and Pierini, A and Ricci, P and Scondotto, S and Bisceglia, L and Cernigliaro, A and Ranzi, A and Comba, P and ,  and ,  and , }, title = {[SENTIERI: Epidemiological Study of Residents in National Priority Contaminated Sites. Fifth Report].}, journal = {Epidemiologia e prevenzione}, volume = {43}, number = {2-3 Suppl 1}, pages = {1-208}, doi = {10.19191/EP19.2-3.S1.032}, pmid = {31295974}, issn = {1120-9763}, abstract = {INTRODUCTION AND OBJECTIVES: This volume provides an update of the health status of the populations living in the National Priority Contaminated Sites (NPCSs) included in the SENTIERI Project. This update is part of an epidemiological surveillance programme carried out in NPCSs, promoted by the Italian Ministry of Health as a further step of a project started in 2006, when the health status of residents in contaminated sites was first addressed within the National Strategic Program &quot;Environment and Health&quot;. The Report focuses on five health outcomes: mortality, cancer incidence, hospital discharges, congenital anomalies, and children, adolescents and young adults' health. A key element of SENTIERI project is the a priori evaluation of the epidemiological evidence of a causal association between the considered cause of disease and the exposure. When an a priori evidence is identified, it is given a greater importance in the comment of the study findings.<br><br>METHODS: The present update of the SENTIERI Project concerns 45 NPCSs including in all 319 Italian Municipalities (out of over 8,000 Municipalities), with an overall population of 5,900,000 inhabitants at the 2011 Italian Census. Standardized Mortality Ratios (SMRs) and Standardized Hospitalization Ratios (SHRs), referring to a time window of 2006-2013, were computed for all the 45 NPCSs, using as a reference the corresponding mortality and hospitalization rates of the Regions where each NCPS is located. Standardized Incidence Ratios (SIRs) were computed by the Italian Association of Cancer Registries (AIRTUM) for the 22 NPCSs served by a Cancer Registry. AIRTUM covers about 56% of Italy, with partly different time-windows. SIRs have been estimated using as reference population the 4 macroareas in which Italy is divided (North-West, North-East, Centre, South). Prevalence of congenital anomalies was computed for 15 NPCSs.<br><br>RESULTS: An all-cause excess of 5,267 and 6,725 deaths was observed, respectively, in men and women; the cancer death excess was of 3,375 in men and 1,910 in women. It was estimated an excess of cancer incidence of 1,220 case in men and 1,425 in women over a five-year time window. With regard to the diseases with an a priori environmental aetiological validity, an excess for malignant mesothelioma, lung, colon, and gastric cancer, and for non-malignant respiratory diseases was observed. Cancer excess mainly affected NPCSs with presence of chemical and petrochemical plants, oil refineries, and dumping hazardous wastes. An excess of non-malignant respiratory disease was also detected in NPCSs in which steel industries and thermoelectric plants were present. An excess of mesothelioma was observed in NPCSs characterized by presence of asbestos and fluoro-edenite; it was also observed where the presence of asbestos was not reported in the legislative national decrees which define the NPCS areas. It is worth noting that, even if the presence of asbestos is not reported in many NPCSs legislative decrees, petrochemical plants and steel industries, for instance, are often characterized by the presence of a large amount of this mineral that, in the past, was extensively used as an insulating material. For the first time, the present Report includes a focus on the health status of children and adolescents (1,160,000 subjects, aged 0-19 years), and young adults (660,000 subjects, aged 20-29 years). Among infants (0-1 year), an excess of 7,000 hospitalizations was observed, 2,000 of which due to conditions of perinatal origin. In the age class 0-14, an excess of 22,000 hospitalizations for all causes was observed; 4,000 of them were due to acute respiratory diseases, and 2,000 to asthma. Data on cancer incidence for subjects aged 0-24 years were derived from general population cancer registries for twenty NPCSs, and from children cancer registries (age group: 0-19 years) for six NPCSs; 666 cases where diagnosed in the age group 0-24 years, corresponding to an excess of 9%. The main contributions to this excess are from soft tissue sarcomas in children (aged 0-14 years), acute myeloid leukaemia in children (aged 0-14 years) and in the age group 0-29 years, non-Hodgkin lymphoma and testicular cancer in young adults (aged 20-29 years). In seven out of 15 NPCSs, an excess prevalence rate of overall congenital anomalies at birth was observed. Congenital anomalies excesses included the following sites: genital organs, heart, limbs, nervous system, digestive system, and urinary system.<br><br>CONCLUSIONS: The main findings of SENTIERI Project have been the detection of excesses for the diseases which showed an a priori epidemiological evidence of a causal association with the environmental exposures specific for each considered NPCS. These observations are valuable within public health, because they contribute to priority health promotion activities. Looking ahead, the health benefits of an improved environmental quality might be appreciated in terms of reduction of the occurrence of adverse health effects attributable to each Site major pollutant agents. Due to the methodological approach of the present study, it was not possible to adjust for several confounding factors reported to be risk factors for the studied diseases (e.g., smoking, alcohol consumption, obesity). Even if excesses of mortality, hospitalization, cancer incidence, and prevalence of congenital anomalies were found in several NPCSs, the study design and the multifactorial aetiology of the considered diseases do not permit, for all of them, to draw conclusions in terms of causal links with environmental contamination. Moreover, it must be taken into consideration that economic factors and the availability of health services may also play a relevant role in a diseases outcome. A few observations regarding some methodological limitations of SENTIERI Project should be made. There is not a uniform environmental characterisation of the studied NPCSs in term of quality and detection of the pollutants, because this information is present in different databases which at present are not adequately connected. Moreover, the recognition of a contaminated site as a National Priority Site is based on soil and groundwater pollution, and the available information on air quality is currently sparse and not homogenous. Another limitation, in term of statistical power, is the small population size of many NPCSs and the low frequency of several health outcomes. A special caution must be paid in data interpretation when considering the correspondence between the contaminated areas and the municipality boundaries, as they do not always coincide perfectly: in some cases, a small municipality with a large industrial site, while in other settings only a part of the municipality is exposed to the sources of pollution. Furthermore, all available health information systems are currently accessible at municipality level. The real breakthrough is essentially comprised of the development and fostering of a networking system involving all local health authorities and regional environmental protection agencies operating in the areas under study. The possibility to integrate the geographic approach of SENTIERI Project with a set of ad hoc analytic epidemiological investigations, such as residential cohort studies, case control studies, children health surveys, biomonitoring surveys, and with socioepidemiological studies, might greatly contribute to the identification of health priorities for environmental remediation activities. Finally, as discussed in the last section of the report, there is a need to adopt, in each NPCS, a two-way oriented communication plan involving public health authorities, scientific community, and resident population, taking into account that the history, the cultural frame and the network of relationships specific of each local context play a major role in the risk perception perspective.}, }
@article {pmid31290725, year = {2019}, author = {Mumma, MT and Sirko, JL and Boice, JD and Blot, WJ}, title = {Mesothelioma mortality within two radiation monitored occupational cohorts.}, journal = {International journal of radiation biology}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/09553002.2019.1642540}, pmid = {31290725}, issn = {1362-3095}, abstract = {Purpose: The risk of mesothelioma, including cancers of the pleura and peritoneum, was examined within two large cohorts of workers monitored for exposure to ionizing radiation. Methods and materials: Mortality was assessed among 253,632 workers routinely monitored for external radiation, including 30,724 industrial radiographers (IR) at shipyards, 142,583 workers at nuclear power plants (NPP), and 83,441 IR who had not worked at an NPP or shipyard. Follow-up was from 1969 through 2011. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were computed; observed numbers of deaths from mesothelioma (including cancers of the pleura and peritoneum) and asbestosis were compared with numbers expected based on age-, sex-, and calendar year-specific national mortality rates. Job history and quantitative asbestos exposure data were unavailable, but work at a shipyard was taken as a surrogate for the likelihood of exposure. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mesothelioma in relation to estimated cumulative radiation exposure to the lung. Results: The mean duration of follow-up was 25.3 years (max 42 years). The mean cumulative lung dose was 28.6 mGy (7.3% > 250 mGy). Nearly 20% of the workers had died by 2011. A total of 421 mesothelioma deaths were found (75% occurring after 1999) with increased SMRs among workers monitored in shipyards (SMR 9.97; 95% CI 8.50-11.63) and for NPP workers (SMR 5.55; 95% CI 4.88-6.29), but not for IR who had not worked in shipyards (SMR 1.15; 95% CI 0.53-2.19). Likewise, deaths from asbestosis (n = 189) were also increased for shipyard and NPP workers (SMR = 18.1 and 9.2, respectively), but not among workers who never worked at a shipyard or NPP (SMR = 0.70; n = 1). Radiation dose to the lung was not associated with a statistically meaningful dose-response trend for mesothelioma in the combined cohorts (HR at 100 mGy = 1.10; 95% CI 0.96-1.27; p = .18), nor was mesothelioma risk associated with radiation exposure among IR who had not worked in a shipyard and assumed minimally exposed to asbestos. Conclusions: An elevated rate of death from mesothelioma was observed in two radiation-exposed occupational groups with potential for asbestos exposure. The increased risk of death from asbestosis, combined with little evidence of a rising trend in mesothelioma mortality with increasing radiation exposure, suggests that the mesothelioma (and asbestosis) excess in these workers was due to asbestos exposure in shipyards and power plants and not to occupational low-dose radiation.}, }
@article {pmid31289611, year = {2019}, author = {Williams, M and Cheng, YY and Kirschner, MB and Sarun, KH and Schelch, K and Winata, P and McCaughan, B and Kao, S and Van Zandwijk, N and Reid, G}, title = {Transcriptional suppression of the miR-15/16 family by c-Myc in malignant pleural mesothelioma.}, journal = {Oncotarget}, volume = {10}, number = {41}, pages = {4125-4138}, doi = {10.18632/oncotarget.27010}, pmid = {31289611}, issn = {1949-2553}, abstract = {MicroRNA downregulation is frequent in malignant pleural mesothelioma (MPM), but the mechanisms responsible for loss of miR-15/16 and miR-193a are yet to be elucidated and were investigated in this study. Copy Number Variation (CNV) of microRNA-coding genes was analyzed in MPM cells by digital droplet PCR (ddPCR) and revealed heterozygous loss of miR-193a and miR-15a/16-1, but no change in miR-15b/16-2. Epigenetic control of microRNA expression was inferred following decitabine and Trichostatin A (TSA) treatment which did not substantially affect microRNA expression. Knockdown of c-Myc expression led to upregulation of SMC4, miR-15b and 16, and to a lesser extent DLEU2 and miR-15a, whereas c-Myc overexpression repressed microRNA expression. Chromatin immunoprecipitation (ChIP) assays confirmed the interaction of c-Myc with the DLEU2 and SMC4 promoters. Tumor microRNA expression was determined in samples from MPM patients, with samples of pleura from cardiac surgery patients used as controls. In tumor samples, a strong correlation was observed between the expression of miR-15b and 16 (R2=0.793), but not miR-15a and 16. Our data suggest that in MPM, the downregulation of miR-15/16 is due to transcriptional repression by c-Myc, primarily via control of the miR-15b/16-2 locus, while miR-193a-3p loss is due to genomic deletion.}, }
@article {pmid31289169, year = {2019}, author = {Taylor, L and Cooper, D and Aujayeb, A}, title = {Malignant deciduoid mesothelioma: a rare variant of epithelioid mesothelioma.}, journal = {BMJ case reports}, volume = {12}, number = {7}, pages = {}, doi = {10.1136/bcr-2019-229945}, pmid = {31289169}, issn = {1757-790X}, abstract = {We describe a case of a deciduoid mesothelioma, a rare variant of epithelioid mesothelioma, which is associated with a very poor prognosis. A review of the relevant literature is also included. The patient was a man with probable asbestos exposure and presented with classic features of pleural malignancy. Diagnosis was reached with close correlation between clinical, radiological and pathological findings.}, }
@article {pmid31285358, year = {2019}, author = {Consonni, D and Calvi, C and De Matteis, S and Mirabelli, D and Landi, MT and Caporaso, NE and Peters, S and Vermeulen, R and Kromhout, H and Dallari, B and Pesatori, AC and Riboldi, L and Mensi, C}, title = {Peritoneal mesothelioma and asbestos exposure: a population-based case-control study in Lombardy, Italy.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {8}, pages = {545-553}, doi = {10.1136/oemed-2019-105826}, pmid = {31285358}, issn = {1470-7926}, abstract = {OBJECTIVES: Asbestos is the main risk factor for peritoneal mesothelioma (PeM). However, due to its rarity, PeM has rarely been investigated in community-based studies. We examined the association between asbestos exposure and PeM risk in a general population in Lombardy, Italy.<br><br>METHODS: From the regional mesothelioma registry, we selected PeM cases diagnosed in 2000-2015. Population controls (matched by area, gender and age) came from two case-control studies in Lombardy on lung cancer (2002-2004) and pleural mesothelioma (2014). Assessment of exposure to asbestos was performed through a quantitative job-exposure matrix (SYN-JEM) and expert evaluation based on a standardised questionnaire. We calculated period-specific and gender-specific OR and 90% CI using conditional logistic regression adjusted for age, province of residence and education.<br><br>RESULTS: We selected 68 cases and 2116 controls (2000-2007) and 159 cases and 205 controls (2008-2015). The ORs for ever asbestos exposure (expert-based, 2008-2015 only) were 5.78 (90% CI 3.03 to 11.0) in men and 8.00 (2.56 to 25.0) in women; the ORs for definite occupational exposure were 12.3 (5.62 to 26.7) in men and 14.3 (3.16 to 65.0) in women. The ORs for ever versus never occupational asbestos exposure based on SYN-JEM (both periods) were 2.05 (90% CI 1.39 to 3.01) in men and 1.62 (0.79 to 3.27) in women. In men, clear positive associations were found for duration, cumulative exposure (OR 1.33 (1.19 to 1.48) per fibres/mL-years) and latency.<br><br>CONCLUSIONS: Using two different methods of exposure assessment we provided evidence of a clear association between asbestos exposure and PeM risk in the general population.}, }
@article {pmid31283845, year = {2019}, author = {Carbone, M and Adusumilli, PS and Alexander, HR and Baas, P and Bardelli, F and Bononi, A and Bueno, R and Felley-Bosco, E and Galateau-Salle, F and Jablons, D and Mansfield, AS and Minaai, M and de Perrot, M and Pesavento, P and Rusch, V and Severson, DT and Taioli, E and Tsao, A and Woodard, G and Yang, H and Zauderer, MG and Pass, HI}, title = {Mesothelioma: Scientific clues for prevention, diagnosis, and therapy.}, journal = {CA: a cancer journal for clinicians}, volume = {69}, number = {5}, pages = {402-429}, doi = {10.3322/caac.21572}, pmid = {31283845}, issn = {1542-4863}, support = {1R01CA198138-01/CA/NCI NIH HHS/United States ; //V Foundation for Cancer Research/ ; //University of Hawaii Foundation through donations from Honeywell International, Inc., Riviera United-4-a Cure, and Maurice and Joanna Sullivan Family Foundation/ ; W81XWH-16-1-0344//U.S. Department of Defense/ ; W81XWH-16-1-0441//U.S. Department of Defense/ ; 1U01CA214195-01/CA/NCI NIH HHS/United States ; }, abstract = {Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.}, }
@article {pmid31280996, year = {2019}, author = {Tsao, A and Nakano, T and Nowak, AK and Popat, S and Scagliotti, GV and Heymach, J}, title = {Targeting angiogenesis for patients with unresectable malignant pleural mesothelioma.}, journal = {Seminars in oncology}, volume = {46}, number = {2}, pages = {145-154}, doi = {10.1053/j.seminoncol.2019.06.001}, pmid = {31280996}, issn = {1532-8708}, mesh = {Asbestos/toxicity ; Bevacizumab/therapeutic use ; Carcinogenesis/*drug effects/genetics ; Humans ; Indoles/therapeutic use ; Lung Neoplasms/*drug therapy/genetics/pathology ; Mesothelioma/*drug therapy/genetics/pathology ; Neovascularization, Pathologic/*drug therapy/genetics/pathology ; Pleural Neoplasms/*drug therapy/genetics/pathology ; Quinazolines/therapeutic use ; }, abstract = {Malignant pleural mesothelioma (MPM) is a global health issue, the principal cause of which is exposure to asbestos. The prevalence is anticipated to rise over the next 2 decades, particularly in developing countries, due to the 30-50-year latency period between exposure to asbestos and carcinogenic development. Unresectable MPM has a poor prognosis and limited treatment options and, as such, there is a broad range of therapeutic targets of interest, including angiogenesis, immune checkpoints, mesothelin, as well as chemotherapeutic agents. Recently, the results of several randomized trials in the first-line setting combining antiangiogenic agents with chemotherapy have been reported. This review examines the scientific rationale for targeting angiogenesis in the treatment of unresectable MPM and analyzes recent clinical results with antiangiogenic agents in development (bevacizumab, nintedanib, and cediranib) for the management of MPM.}, }
@article {pmid31273181, year = {2019}, author = {Terakawa, H and Gabata, R and Haba, Y and Takada, S and Sakamoto, K and Sasaki, M}, title = {[A Case of Peritoneal Mesothelioma Diagnosed by Ileus].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {6}, pages = {1081-1083}, pmid = {31273181}, issn = {0385-0684}, mesh = {Aged ; *Asbestos ; Humans ; *Ileus/etiology ; Male ; *Mesothelioma/complications ; *Peritoneal Neoplasms/complications ; }, abstract = {The present case involved a man aged about 70 years. He visited our hospital with the main complaint of abdominal pain. We diagnosed him with intestinal obstruction, and we decided to perform surgery. White knot sections were spread inside the abdominal cavity, and the small intestine appeared as a single block. This block was resected and examined for peritoneal mesothelioma. Peritoneal mesothelioma is thought to have incubation period of 20-25 years after exposure to asbestos, and the number of affected patients will increase in the future. In some cases, peritoneal mesothelioma occurs only in the peritoneum; therefore, diagnosis often becomes difficult. Once intestinal obstruction occurs, administering chemotherapy is difficult. Therefore, early diagnosis is thought to be very important.}, }
@article {pmid31269586, year = {2019}, author = {Liu, XH and Wu, H and Huang, YF and Zhang, GY and Xu, MH}, title = {[Clinical characteristics of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis: a report of 6 cases].}, journal = {Zhonghua yi xue za zhi}, volume = {99}, number = {24}, pages = {1893-1897}, doi = {10.3760/cma.j.issn.0376-2491.2019.24.011}, pmid = {31269586}, issn = {0376-2491}, mesh = {Adult ; Aged ; Humans ; Male ; *Mesothelioma ; Middle Aged ; *Peritoneal Neoplasms ; *Peritonitis, Tuberculous ; Retrospective Studies ; }, abstract = {Objective: To reduce the misdiagnosis rate of ascites and improve the diagnosis rate of malignant peritoneal mesothelioma. Methods: From May 2008 to May 2018, in Xiangya Hospital of Central South University,the clinical data of malignant peritoneal mesothelioma misdiagnosed as tuberculous peritonitis were retrospectively analyzed. Results: (1) Among the 6 patients, they were male; the age of onset was 42-70 (52±9.57) years old, and there was no history of asbestos exposure. (2) All cases with abdominal pain or abdominal distension were there and the course of disease was more than 1 month to more than 2 years. (3) In all patients,the nature of ascites was exudate; ADA was higher than normal value and below 45 U/L; LDH value in ascites was higher than 200 U/L (83.3%); mesothelioma was considered in ascites cytology in 1 case. (4) Laparoscopic biopsy was performed in 2 cases and B-ultrasound guided biopsy in 4 cases; Among them, malignant peritoneal mesothelioma diagnosed by pathology. (5) In Immunohistochemical positive markers, MC was the most sensitive (100%), followed by CR (67%), CK-Pan (67%), Ki-67 (67%) and EMA (67%). (6) Two patients received treatment with operation, abdominal hyperthermic perfusion and postoperative systemic chemotherapy. Conclusions: (1) Malignant peritoneal mesothelioma should be considered in middle-aged and aged male patients with unexplained ascites and early laparoscopy or laparotomy for diagnosis. (2) ADA and LDH level in ascites are significant in differentiating tuberculous peritonitis from malignant peritoneal mesothelioma. (3) Immunohistochemical positive marker MC may be a potential specific marker for malignant mesothelioma. (4) The survival time of patients is improved by comprehensive treatment such as operation and chemotherapy.}, }
@article {pmid31267149, year = {2019}, author = {Jiménez-Ramírez, C and Casjens, S and Juárez-Pérez, CA and Raiko, I and Del Razo, LM and Taeger, D and Calderón-Aranda, ES and Rihs, HP and Acosta-Saavedra, LC and Weber, DG and Cabello-López, A and Pesch, B and Ochoa-Vázquez, MD and Burek, K and Torre-Bouscoulet, L and Pérez-Padilla, JR and García-Bazan, EM and Brüning, T and Johnen, G and Aguilar-Madrid, G}, title = {Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {197}, number = {5}, pages = {641-649}, pmid = {31267149}, issn = {1432-1750}, abstract = {PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM.<br><br>METHOD: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016.<br><br>RESULTS: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively.<br><br>CONCLUSIONS: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.}, }
@article {pmid31265162, year = {2019}, author = {Numano, T and Higuchi, H and Alexander, DB and Alexander, WT and Abdelgied, M and El-Gazzar, AM and Saleh, D and Takase, H and Hirose, A and Naiki-Ito, A and Suzuki, S and Takahashi, S and Tsuda, H}, title = {MWCNT-7 administered to the lung by intratracheal instillation induces development of pleural mesothelioma in F344 rats.}, journal = {Cancer science}, volume = {110}, number = {8}, pages = {2485-2492}, doi = {10.1111/cas.14121}, pmid = {31265162}, issn = {1349-7006}, support = {//5th Term Long-Range Research Initiative (2017) by Japan Chemical Industry Association/ ; H22-kagaku-ippan-005//Ministry of Health, Labour and Welfare/ ; H22-kagaku-shitei-004//Ministry of Health, Labour and Welfare/ ; H25-kagaku-ippan-004//Ministry of Health, Labour and Welfare/ ; H27-kagaku-shitei-004//Ministry of Health, Labour and Welfare/ ; H28-kagaku-ippan-004//Ministry of Health, Labour and Welfare/ ; //Egyptian Cultural Affairs and Missions Sector/ ; }, mesh = {Animals ; Asbestos, Crocidolite/adverse effects ; Injections, Intraperitoneal/methods ; Lung/*drug effects ; Lung Neoplasms/*chemically induced/pathology ; Male ; Mesothelioma/*chemically induced/pathology ; Nanotubes, Carbon/*adverse effects ; Pleural Neoplasms/*chemically induced/pathology ; Rats ; Rats, Inbred F344 ; Trachea/drug effects/pathology ; }, abstract = {Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 μg/mL MWCNT-7 or 0.250 μg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups.}, }
@article {pmid31262194, year = {2019}, author = {Guazzelli, A and Meysami, P and Bakker, E and Bonanni, E and Demonacos, C and Krstic-Demonacos, M and Mutti, L}, title = {What can independent research for mesothelioma achieve to treat this orphan disease?.}, journal = {Expert opinion on investigational drugs}, volume = {28}, number = {8}, pages = {719-732}, doi = {10.1080/13543784.2019.1638363}, pmid = {31262194}, issn = {1744-7658}, mesh = {Animals ; Antineoplastic Agents/*administration &amp; dosage/pharmacology ; Drug Repositioning ; Humans ; Immunotherapy/methods ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Molecular Docking Simulation ; Molecular Targeted Therapy ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Rare Diseases/drug therapy/pathology ; Survival Rate ; }, abstract = {Introduction: Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis, as current therapies are ineffective. Despite the increased understanding of the molecular biology of mesothelioma, there is still a lack of drugs that dramatically enhance patient survival. Area Covered: This review discusses recent and complete clinical trials supported by the NIH, other U.S. Federal agencies, universities and organizations found on clinicaltrials.gov. Firstly, chemotherapy-based trials are described, followed by immunotherapy and multitargeted therapy. Then we introduce drug repositioning and the use of drug docking as tools to find new interesting molecules. Finally, we highlight potential molecular pathways that may play a role in mesothelioma biology and therapy. Expert Opinion: Numerous biases are present in the clinical trials due to a restricted number of cases, inappropriate endpoints and inaccurate stratification of patients which delay the finding of a treatment for MPM. The most crucial issue of independent research for MPM is the lack of more substantive funding to translate these findings to the clinical setting. However, this approach is not necessarily scientific given the low mutational load of mesothelioma relative to other cancers, and therefore patients need a more solid rationale to have a good chance of successful treatment.}, }
@article {pmid31260913, year = {2019}, author = {Pyana Kitenge, J and Kapinga Kayembe, D and Tshibangu Muamba, M and Kachil Rubing, H and De Vos, B and Van Bouwel, J and Nemery, B}, title = {Malignant mesothelioma in Sub-Saharan Africa: A case report from Lubumbashi, DR Congo.}, journal = {Environmental research}, volume = {176}, number = {}, pages = {108556}, doi = {10.1016/j.envres.2019.108556}, pmid = {31260913}, issn = {1096-0953}, abstract = {Although asbestos has been used throughout Africa in the past decades, no reports of asbestos-related malignant mesothelioma are available from sub-Saharan Africa, except from South Africa and Zimbabwe. We present a case of a 39-year-old man who died from a histologically proven malignant mesothelioma of the peritoneum in Lubumbashi, DR Congo. No occupational exposure to asbestos could be found in his history. In view of his young age, we speculated that he had been exposed to asbestos as a child, which was highly plausible because he had grown up in one of the numerous mining estates of the region. The houses of these estates were often built with asbestos-containing materials, notably roofs made of corrugated asbestos-cement. The possibility of past domestic or environmental exposure to asbestos was substantiated by the identification of chrysotile and crocidolite fibres in samples of asbestos-cement collected from the home where the patient had lived as a child. To our knowledge, this is the first report of malignant mesothelioma from a country in the Central African region. We expect that heightened awareness and improved diagnosis will lead to the detection of more asbestos-related diseases in Africa.}, }
@article {pmid31260832, year = {2019}, author = {Tsao, MS and Carbone, M and Galateau-Salle, F and Moreira, AL and Nicholson, AG and Roden, AC and Adjei, AA and Aubry, MC and Fennell, DA and Gomez, D and Harpole, D and Hesdorffer, M and Hirsch, FR and Liu, G and Malik, S and Nowak, A and Peikert, T and Salgia, R and Szlosarek, P and Taioli, E and Yang, H and Tsao, A and Mansfield, AS}, title = {Pathologic Considerations and Standardization in Mesothelioma Clinical Trials.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {10}, pages = {1704-1717}, doi = {10.1016/j.jtho.2019.06.020}, pmid = {31260832}, issn = {1556-1380}, abstract = {The accurate diagnosis of mesothelioma is critical for the appropriate clinical management of this cancer. Many issues complicate making the diagnosis of mesothelioma including the presence of reactive mesothelial cells in benign pleural effusions, the heterogeneity of mesothelioma histopathology, the relatively high incidence of other epithelial malignancies that metastasize to the pleura, and primary sarcomas that arise within the pleura. Given the rapidly evolving field of molecular profiling and the need for translational correlates in mesothelioma clinical trials, the National Cancer Institute (NCI)-International Association for the Study of Lung Cancer-Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting was convened in March 2017 to develop a consensus on standard pathology guidelines for future NCI-sponsored clinical trials in mesothelioma. This consensus statement covers recommendations for specimen handling, pathologic classification and diagnosis, biobanking, and tissue correlative studies.}, }
@article {pmid31239765, year = {2019}, author = {Ospina, D and Villegas, VE and Rodríguez-Leguizamón, G and Rondón-Lagos, M}, title = {Analyzing biological and molecular characteristics and genomic damage induced by exposure to asbestos.}, journal = {Cancer management and research}, volume = {11}, number = {}, pages = {4997-5012}, doi = {10.2147/CMAR.S205723}, pmid = {31239765}, issn = {1179-1322}, abstract = {Asbestos is one of the most important occupational carcinogens. Currently, about 125 million people worldwide are exposed to asbestos in the workplace. According to global estimates, at least 107,000 people die each year from lung cancer, mesothelioma, and asbestosis as a result of occupational exposure to asbestos. The high pathogenicity of this material is currently known, being associated with the development of pulmonary diseases, of which lung cancer is the main cause of death due to exposure to this mineral. Pulmonary diseases related to asbestos are a common clinical problem and a major health concern worldwide. Extensive research has identified many important pathogenic mechanisms; however, the precise molecular mechanisms involved, and the generated genomic damage that lead to the development of these diseases, are not completely understood. The modes of action that underlie this type of disease seem to differ depending on the type of fiber, lung clearance, and genetics. This evidences the need to increase our knowledge about these effects on human health. This review focuses on the characteristics of asbestos and the cellular and genomic damage generated in humans via exposure.}, }
@article {pmid31237454, year = {2019}, author = {Ledda, C and Caltabiano, R and Vella, F and Matera, S and Marconi, A and Loreto, C and Rapisarda, V}, title = {Fibulin-3 as biomarker of malignant mesothelioma.}, journal = {Biomarkers in medicine}, volume = {13}, number = {10}, pages = {875-886}, doi = {10.2217/bmm-2018-0285}, pmid = {31237454}, issn = {1752-0371}, abstract = {Many malignant diseases are associated with past asbestos exposure; the most lethal and strictly related to previous fiber exposure being malignant mesothelioma (MM). Effective preventive protocols may include sensitive and specific biomarkers. The role of Fb-3 has been recently investigated for MM early detection, but its role is still under debate. After an independent search for scientific literature, nine studies were included for a systematic review. Human Fb-3 levels seem to be able to separate healthy people with previous exposure to asbestiform fibers from MM patients. Fb-3 blood levels can distinguish MM effusions from other malignant and benign effusions. Furthers investigations on more significant groups of patients are desirable to validate and assess the validity of combining Fb-3 with other biomarkers.}, }
@article {pmid31229775, year = {2019}, author = {Ramos-Bonilla, JP and Cely-García, MF and Giraldo, M and Comba, P and Terracini, B and Pasetto, R and Marsili, D and Ascoli, V and Lysaniuk, B and Rodríguez, MC and Mazzeo, A and Panqueva, RDPL and Baldión, M and Cañón, D and García-Herreros, LG and Pinzón, B and Hernández, LJ and Silva, YA}, title = {An asbestos contaminated town in the vicinity of an asbestos-cement facility: The case study of Sibaté, Colombia.}, journal = {Environmental research}, volume = {176}, number = {}, pages = {108464}, doi = {10.1016/j.envres.2019.04.031}, pmid = {31229775}, issn = {1096-0953}, abstract = {INTRODUCTION: The asbestos industry began operations in Colombia in 1942, with an asbestos-cement facility located in the municipality of Sibaté. In recent years residents from Sibaté have been complaining about what they consider is an unusually large number of people diagnosed with asbestos-related diseases in the town. A study to analyze the situation of Sibaté started in 2015, to verify if the number of asbestos related diseases being diagnosed were higher than expected, and to identify potential asbestos exposure sources in the town.<br><br>METHODS: A health and socioeconomic survey was implemented door-to-door to identify potential asbestos-related diseases. Several self-reported mesothelioma cases were identified, and for confirmation purposes, copies of the medical record with the histopathology report were obtained. A panel of six physicians analyzed the medical records. Information of validated cases was used to estimate the male and female age-adjusted incidence rate for Sibaté. Based on reports of the existence of potential asbestos-contaminated landfills, topographic maps, a digital elevation model, and current satellite images were crossed using a geographic information system to identify potential landfilled areas, and soils samples were collected in some of these areas.<br><br>RESULTS: A total of 355 surveys were completed, and 29 self-reported mesothelioma cases were identified. Twenty-five of these cases have been persons who had lived at some moment of their lives in Sibaté. It was possible to obtain copies of the medical diagnosis for 17 cases. Of these, the panel of physicians classified 15 cases as certain pleural mesothelioma, one as probable, and one as not mesothelioma. Based on this information, the estimated age-adjusted incidence rate of mesothelioma in Sibaté was 3.1 × 105 persons-year for males and 1.6 × 105 persons-year for females. These rates are high in comparison to those reported in other cities, regions, and countries of the world. Using geographic information systems, landfilled zones in the urban area of Sibaté were identified, on top of which a school and different sports facilities were built. The analysis of four soil samples collected in landfilled zones, confirmed the existence of an underground layer of friable and non-friable asbestos.<br><br>CONCLUSION: The collected evidence suggests the presence of a malignant pleural mesothelioma cluster in Sibaté.}, }
@article {pmid31225962, year = {2019}, author = {Marsili, D and Canepa, A and Mossone, N and Comba, P}, title = {Environmental Health Education for Asbestos-Contaminated Communities in Italy: The Casale Monferrato Case Study.}, journal = {Annals of global health}, volume = {85}, number = {1}, pages = {}, doi = {10.5334/aogh.2491}, pmid = {31225962}, issn = {2214-9996}, abstract = {BACKGROUND: Environmental health education contributes towards increasing awareness of communities to prevent exposure to hazardous substances. Casale Monferrato, the operating site for the Eternit asbestos-cement factory from 1907 to 1986, is a prioritized asbestos-contaminated site for remediation in Italy. The area is prone to severe asbestos-related diseases. About 50 cases of mesothelioma are diagnosed in Casale Monferrato annually; mesothelioma has been shown to be caused by occupational, environmental and domestic asbestos exposure.<br><br>OBJECTIVES: The goal of this paper is to analyze the Casale Monferrato case study in terms of youth engagement in environmental health education initiatives on asbestos risk and health impact. The paper aims at underlining the lessons learned in order to share the success of this initiative with other communities living in asbestos-contaminated sites in different countries.<br><br>METHODS: Peer education methodology has been used through the Asbestos Classroom to involve teachers, students and other local stakeholders in training activities, in selection of the contents for educational materials and interactive tools, as well as in choosing the presentation process for the aforementioned knowledge sharing instruments.<br><br>FINDINGS: From November 2014 to June 2018, 185 high school students and teachers were trained through the Asbestos Classroom. Through December 2018, they trained 3,241 classroom visitors. The Classroom relies on an inclusive participative process in which young people play a key role in the network of relationships within their community.<br><br>CONCLUSIONS: The paper corroborates the importance of engaging the educational system in communication efforts aimed at fostering collective awareness on environmental risk and health-related impacts for communities living in industrially contaminated sites. Considering the global dimension of the asbestos contamination and disease burden, this experience might be of relevance both in countries that banned asbestos and in those where asbestos is not yet prohibited.}, }
@article {pmid31211722, year = {2019}, author = {Metintas, M and Ak, G and Metintas, S and Yildirim, H and Dündar, E and Rahman, N}, title = {Prospective Study of the Utility of Computed Tomography Triage of Pleural Biopsy Strategies in Patients With Pleural Diseases.}, journal = {Journal of bronchology &amp; interventional pulmonology}, volume = {26}, number = {3}, pages = {210-218}, doi = {10.1097/LBR.0000000000000559}, pmid = {31211722}, issn = {1948-8270}, abstract = {BACKGROUND: This study aimed to prospectively evaluate the efficacy and reliability of a diagnostic workup, triaging pleural biopsy method according to baseline computerized tomography (CT) findings in the diagnosis of pleural diseases.<br><br>METHODS: Patients with pleural pathology were divided into 3 arms according to findings on CT scan images. Arm A: patients with pleural thickening/lesion in addition to pleural effusion. These patients underwent CT scan-guided Abrams' needle pleural biopsy. Arm B: patients with pleural effusion alone or suspected benign asbestos pleurisy. This group underwent medical thoracoscopy (MT). Arm C: patients with only pleural thickening. This group underwent ultrasonography-guided cutting needle pleural biopsy. MT was planned in patients who did not have a specific diagnosis in the CT scan-guided Abrams' needle pleural biopsy group. When patients with a histopathologic diagnosis of fibrinous pleuritis after MT were assessed in terms of the risk factors for malignant pleural diseases, we offered a further invasive procedure.<br><br>RESULTS: A total of 164 patients were enrolled in the study. Diagnostic sensitivity after the initial procedure was 90.2% in Arm A, 93.3% in Arm B, 95.2% in Arm C, and 92.4% in the entire workup. The negative predictive value of the entire workup was 90.4% for malignant pleural mesothelioma, 97.1% for metastatic malignant pleural diseases, and 100% for tuberculous pleurisy. Five cases who had a diagnosis of fibrinous pleuritis after MT were detected to have risk factors, 4 of which (80%) indicated malignant disease. Complication rates were low and acceptable.<br><br>CONCLUSION: Use of CT scans to triage an appropriate pleural biopsy method is associated with high diagnostic success. We recommend that the proposed diagnostic workup in this study may be used as a diagnostic algorithm for pleural diseases that require a histopathologic analysis. Determination of risk factors predicting malignant disease in patients where fibrinous pleuritis is reported after MT would be useful for clinical practice.}, }
@article {pmid31207975, year = {2019}, author = {Catino, A and de Gennaro, G and Di Gilio, A and Facchini, L and Galetta, D and Palmisani, J and Porcelli, F and Varesano, N}, title = {Breath Analysis: A Systematic Review of Volatile Organic Compounds (VOCs) in Diagnostic and Therapeutic Management of Pleural Mesothelioma.}, journal = {Cancers}, volume = {11}, number = {6}, pages = {}, doi = {10.3390/cancers11060831}, pmid = {31207975}, issn = {2072-6694}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm related to asbestos exposure and with high mortality rate. The management of patients with MPM is complex and controversial, particularly with regard to early diagnosis. In the last few years, breath analysis has been greatly implemented with this aim. In this review the strengths of breath analysis and preliminary results in searching breath biomarkers of MPM are highlighted and discussed, respectively. Through a systematic electronic literature search, collecting papers published from 2000 until December 2018, fifteen relevant scientific papers were selected. All papers considered were prospective, comparative, observational case-control studies although every single one pilot and based on a relatively small number of samples. The identification of diagnostic VOCs pattern, through breath sample characterization and the statistical data treatment, allows to obtain a strategic information for clinical diagnostics. To date the collected data provide just preliminary information and, despite the promising results and diagnostic accuracy, conclusions cannot be generalized due to the limited number of individuals included in each cohort study. Furthermore none of studies was externally validated, although validation process is a necessary step towards clinical implementation. Breathomics-based biomarker approach should be further explored to confirm and validate preliminary findings and to evaluate its potential role in monitoring the therapeutic response.}, }
@article {pmid31205069, year = {2019}, author = {Alchami, FS and Attanoos, RL and Gibbs, A and Morgan, F and Jasani, B}, title = {Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts.}, journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM}, volume = {}, number = {}, pages = {}, doi = {10.1097/PAI.0000000000000779}, pmid = {31205069}, issn = {1533-4058}, abstract = {BACKGROUND: Simian virus 40 (SV40)-contaminated polio vaccine was accidentally administered to about one-third of the UK population receiving polio vaccines between 1956 and 1962. SV40 was subsequently demonstrated to be a carcinogenic virus in experimental and animal models. Since then, the SV40 oncogenic protein large T antigen (SV40 Tag) has been shown to cause malignant transformation of asbestos-treated human pleural mesothelial cells and malignant pleural mesotheliomas in asbestos-exposed SV40 Tag transgenic mice. The present study was designed to investigate the possible association of SV40 Tag with human malignant pleural mesothelioma samples from birth cohorts of the UK population exposed to combined peak levels of asbestos and SV40-contaminated polio vaccines.<br><br>MATERIALS AND METHODS: Tumor and background lung tissue microarrays prepared from archival surgical specimens of 139 pleural mesothelioma cases, collected over a period of 8 years (1998 to 2005), were analyzed. These represented birth cohorts overlapping with the period 1950 to 1960, exposed to a high level of both asbestos and SV40-contaminated live polio vaccines. SV40 Tag mRNA expression was investigated using a highly sensitive and specific SV40 Tag RNA in situ hybridization detection method on the basis of the novel RNAscope technology.<br><br>RESULTS: SV40 Tag RNA was not detected in any of the 127 evaluable tumor cases, despite appropriate results obtained for the external positive and negative controls included.<br><br>CONCLUSION: The complete absence of SV40 Tag mRNA in this large series of cases contradicts experimental evidence suggestive of SV40 link with asbestos-exposed malignant pleural mesotheliomas in the UK population. Alternative explanations of the negative findings are discussed to exclude possible confounding factors.}, }
@article {pmid31200818, year = {2019}, author = {Tsim, S and Paterson, S and Cartwright, D and Fong, CJ and Alexander, L and Kelly, C and Holme, J and Evison, M and Blyth, KG}, title = {Baseline predictors of negative and incomplete pleural cytology in patients with suspected pleural malignancy - Data supporting 'Direct to LAT' in selected groups.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {133}, number = {}, pages = {123-129}, doi = {10.1016/j.lungcan.2019.05.017}, pmid = {31200818}, issn = {1872-8332}, abstract = {OBJECTIVES: Negative effusion cytology is more common in certain forms of Malignant Pleural Effusion (MPE) and results in pathway delay. Local Anaesthetic Thoracoscopy (LAT) is extremely sensitive and safe but cannot be offered to all. A stratified pathway, including 'Direct to LAT' in selected cases could enhance patient experience but requires reliable baseline predictors of unhelpful cytology, including both negative (no malignant cells) and incomplete results (malignant cells identified but predictive markers failed), since pleural biopsies will be required in the latter for optimal management. This retrospective analysis of a prospective multi-centre study, sought to identify baseline features for pathway rationalization.<br><br>MATERIALS AND METHODS: 363/638 (57%) of patients recruited to the DIAPHRAGM study (ISRCTN10079972) were included. Prospective data, including final diagnoses, asbestos exposure and fluid cytology results were supplemented by retrospective Computed Tomography (CT) and predictive marker reports. Independent predictors of negative and incomplete cytology were determined by multivariable logistic regression. Contingency tables were used to assess diagnostic value of cytology in associated phenotypes.<br><br>RESULTS: 238/363 (66%) patients were diagnosed with MPE (18 tumour types). Fluid cytology was negative in 151/238 (63%) and independently associated with asbestos-exposure (Odds Ratio (OR) 5.34) and a malignant CT (OR 2.25). When both features were recorded the sensitivity and negative predictive value of fluid cytology were 19% (95% CI 11-30%) and 9% (95% CI 4-20%)), respectively. Cytology was incomplete in 34/238 (14%), i.e. 47% of positive cytology cases) but was not associated with any baseline feature. ORs for incomplete cytology in Ovarian, Breast, Renal and Lung Cancer were 83, 22, 21 and 9, respectively.<br><br>CONCLUSION: Negative cytology is extremely likely in patients with asbestos exposure and a malignant CT report. A 'Direct-to-LAT' approach may be appropriate in this setting. No baseline predictors of incomplete cytology were identified.}, }
@article {pmid31192957, year = {2019}, author = {Zan, X and Wang, Y and Shi, J and Zhao, L and Zhao, Y and Liu, R and Zhou, Y and Wan, Y and , }, title = {Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy.}, journal = {Medicine}, volume = {98}, number = {24}, pages = {e16028}, doi = {10.1097/MD.0000000000016028}, pmid = {31192957}, issn = {1536-5964}, mesh = {Biomarkers, Tumor/metabolism ; Humans ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; *Meta-Analysis as Topic ; Pleural Neoplasms/*metabolism ; *Systematic Reviews as Topic ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM.<br><br>METHODS: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers.<br><br>RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication.<br><br>CONCLUSION: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM.<br><br>ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews.<br><br>PROSPERO REGISTRATION NUMBER: CRD42019125880.}, }
@article {pmid31179006, year = {2019}, author = {Taylor, BH and Warnock, C and Tod, A}, title = {Communication of a mesothelioma diagnosis: developing recommendations to improve the patient experience.}, journal = {BMJ open respiratory research}, volume = {6}, number = {1}, pages = {e000413}, doi = {10.1136/bmjresp-2019-000413}, pmid = {31179006}, issn = {2052-4439}, abstract = {Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer linked to asbestos exposure and inhalation. As with other cancers, receiving a diagnosis of MPM is challenging and distressing. Particular challenges are associated with communicating a diagnosis of MPM, including explaining the disease and its prognosis, treatment options and legal and financial implications. Receiving A Diagnosis Of Mesothelioma (RADIO Meso) aimed to understand the experience of communicating a diagnosis of MPM from the perspective of patients, family carers and health professionals.<br><br>Methods: This qualitative study comprised 31 individual interviews with patients, family carers and health professionals. This was followed by two group interviews (n=42) and an electronic consultation exercise (n=39).<br><br>Results: This study provides unique insight into the mesothelioma diagnostic experience of patients, family carers and health professionals. Key findings include the importance of regarding diagnosis as a process, and provision of continuity and consistency. The clinical nurse specialist and effective multidisciplinary team working provided vital contributions to successful mesothelioma diagnostic communication. Facilitators to diagnostic communication included honesty and timeliness in communication, partnership working and maintaining a patient-centred approach. Challenges to enhancing mesothelioma diagnosis communication included accessing ongoing training, ensuring a suitable clinical environment and being able to allocate appropriate time.<br><br>Conclusion: The RADIO Meso study highlights factors that influence the communication of a diagnosis of MPM from the perspectives of individual patients and family carers. These findings provide the basis for a set of recommendations that can be used by health professionals to improve the MPM diagnostic experience.}, }
@article {pmid31171576, year = {2019}, author = {Takada, K and Fujimoto, N and Ozeki, T and Nishimura, J and Miyamoto, Y and Asano, M and Fuchimoto, Y and Wada, S and Ozaki, S and Igawa, T and Sonobe, H and Kishimoto, T}, title = {Small intestinal intussusception in an adult.}, journal = {Journal of clinical pathology}, volume = {72}, number = {7}, pages = {510}, doi = {10.1136/jclinpath-2017-204973}, pmid = {31171576}, issn = {1472-4146}, mesh = {Aged ; Autopsy ; Cell Proliferation ; Fatal Outcome ; Humans ; Intestine, Small/diagnostic imaging/pathology ; Intussusception/*diagnostic imaging/pathology ; Male ; Mesothelioma/*diagnostic imaging/pathology ; }, }
@article {pmid31169558, year = {2019}, author = {Louw, A and Badiei, A and Creaney, J and Chai, MS and Lee, YCG}, title = {Advances in pathological diagnosis of mesothelioma: what pulmonologists should know.}, journal = {Current opinion in pulmonary medicine}, volume = {25}, number = {4}, pages = {354-361}, doi = {10.1097/MCP.0000000000000578}, pmid = {31169558}, issn = {1531-6971}, abstract = {PURPOSE OF REVIEW: Malignant pleural mesothelioma (MPM) is a universally fatal illness with a rising incidence, particularly in developing countries. The diagnosis can be challenging and require repeated investigations with implications for the patient and healthcare system.<br><br>RECENT FINDINGS: Distinguishing between benign/reactive and malignant mesothelial proliferations can be challenging. Cytological diagnosis of MPM from pleural fluid is as reliable as histological analysis of tissue biopsies in epithelioid MPM - an approach endorsed by the International Academy of Cytology. Identification of BRCA1-associated protein 1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations in MPM have led to the development of new ancillary tests that can streamline the diagnostic pathway. The prognostic values of these molecules are being investigated. Clinicians should be aware of the recently described BAP1 tumor predisposition syndrome and offer genetic investigations in potential patients. Routine use of prophylactic radiotherapy in MPM patients after pleural interventions has been disproved in a randomized trial.<br><br>SUMMARY: Diagnosis of epithelioid MPM can be established on pleural fluid analysis in most patients. The use of BAP1 immunostaining and CDKN2A/p16 fluorescence in-situ hybridization are particularly useful in distinguishing benign from malignant mesothelial proliferations. Clinicians should ensure these investigations are available in the pathological assessment of cases to minimize invasive investigations and the associated risks.}, }
@article {pmid31166112, year = {2019}, author = {Santos Seoane, SM and Yano Escudero, R and Arenas García, V}, title = {An unexpected cause of dysphagia: pleural mesothelioma.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {111}, number = {6}, pages = {494-495}, doi = {10.17235/reed.2019.6024/2018}, pmid = {31166112}, issn = {1130-0108}, abstract = {Malignant mesothelioma usually originates from the pleura or peritoneum, and has a poor prognosis. The incidence of this type of tumor is increasing worldwide, which is probably a result of occupational or environmental exposure to asbestos. In 90% dyspnea, chest pain or a combination of both are usually the initial symptoms. Dysphagia only occurs in 1.4% and is very rare as the initial symptom. We present the case of a middle-aged patient, in whom the initial symptom was dysphagia, so an endoscopy was performed. This showed extrinsic compression of the esophagus that was demonstrated when performing the chest X-ray, in which it was revealed a posterior mediastinal mass surrounding the esophagus concentrically without mucosal invasion.}, }
@article {pmid31158563, year = {2019}, author = {Konen, T and Johnson, JE and Lindgren, P and Williams, A}, title = {Cancer incidence and mortality associated with non-occupational and low dose exposure to Libby vermiculite in Minnesota.}, journal = {Environmental research}, volume = {175}, number = {}, pages = {449-456}, doi = {10.1016/j.envres.2019.04.004}, pmid = {31158563}, issn = {1096-0953}, abstract = {BACKGROUND: A vermiculite processing plant in a Minneapolis, Minnesota neighborhood utilized asbestos-containing ore from Libby, Montana from the late 1930's until 1989. Multiple pathways of exposure to Libby asbestos were characterized in a cohort of over 6000 plant workers and residents living near the plant.<br><br>OBJECTIVE: We conducted a cohort linkage study to assess the impact of cumulative low dose exposure and the role of occupational history on asbestos-related mortality and cancer morbidity among cohort members residing near a vermiculite plant.<br><br>METHODS: Cohort members alive in 1988 (n = 5848) were linked to the Minnesota Cancer Surveillance System to identify incident cases of mesothelioma, lung cancer, and all-cancer diagnosed from 1988 to 2010. Proportional incidence ratios (PIRs) were calculated for mesothelioma and lung cancer. Vital status and cause of death were ascertained from Minnesota vital records and the National Death Index (1988-2011). Mortality rates of the cohort (2001-2011) for asbestos-related outcomes were compared to the Minnesota population to estimate standardized mortality ratios (SMRs) and stratified by gender, exposure, and occupational history categories.<br><br>RESULTS: We identified seven cases of mesothelioma, with elevated incidence only in females (PIR = 11.76, 95% CI: 3.17, 30.12). Lung cancer was elevated in both genders: PIR = 1.54 (95% CI: 1.19, 2.0) in males and 1.62 (95% CI: 1.21, 2.12) in females. We found elevated mortality from COPD, lung cancer, and mesothelioma among females (SMR for mesothelioma in females = 18.97, CI: 3.91, 55.45), among the 546 deaths identified. All four deaths from mesothelioma occurred in the >75th percentile of exposure (>0.0156 fiber/cc x months). The SMR for lung cancer and all respiratory cancer was elevated even after controlling for occupation.<br><br>CONCLUSIONS: Community exposure to Libby amphibole asbestos from a vermiculite processing plant is associated with increased risk of COPD, lung cancer and mesothelioma incidence and mortality, most notably among females, and is likely to remain a public health issue for years to come.}, }
@article {pmid31138176, year = {2019}, author = {Kettunen, E and Savukoski, S and Salmenkivi, K and Böhling, T and Vanhala, E and Kuosma, E and Anttila, S and Wolff, H}, title = {CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {507}, doi = {10.1186/s12885-019-5652-y}, pmid = {31138176}, issn = {1471-2407}, support = {115372//Terveyden Tutkimuksen Toimikunta/ ; 109003//Työsuojelurahasto/ ; }, mesh = {Aged ; Asbestos/*adverse effects ; Chromosomes, Human/genetics ; Cyclin-Dependent Kinase Inhibitor p16/*genetics/*metabolism ; *DNA Copy Number Variations ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/chemically induced/genetics/*metabolism ; Male ; Mesothelioma/chemically induced/genetics/*metabolism ; Middle Aged ; Stromal Cells/metabolism ; Tissue Array Analysis ; }, abstract = {BACKGROUND: Deletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protein, p16, in relation to MPM patient's asbestos exposure is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier been shown to accumulate in lung cancer in relation to asbestos exposure but their status in MPM is unclear.<br><br>METHODS: We studied DNA copy numbers for CDKN2A using fluorescence in situ hybridization (FISH) and p16 expression by immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 and 19p13 by FISH.<br><br>RESULTS: We were unable to detect an association between p16 expression and pulmonary asbestos fiber count in MPM tumor cells. However, significantly more MPM patients with high pulmonary asbestos fiber count (> 1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure (≤ 0.5 million f/g) (51.4% vs 16.7%; p = 0.035, Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells associated with a high pulmonary asbestos fiber count (p = 0.044, Fisher's Exact test, two-tailed). In contrast to our earlier findings in asbestos associated lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in MPM although single cases with variable copy numbers on those regions were seen.<br><br>CONCLUSIONS: We found two instances where the gene locus CDKN2A or its corresponding protein expression, is associated with high asbestos exposure levels. This suggests that there may be biological differences between the mesotheliomas with high pulmonary asbestos fiber count and those with low fiber count.}, }
@article {pmid31132706, year = {2019}, author = {Colombino, E and Capella, S and Casalinuovo, F and Racco, R and Pruiti, F and Volante, M and Di Marco Lo Presti, V and Belluso, E and Capucchio, MT}, title = {Malignant peritoneal mesothelioma in a boar who lived in Calabria (Italy): Wild animal as sentinel system of human health.}, journal = {The Science of the total environment}, volume = {683}, number = {}, pages = {267-274}, doi = {10.1016/j.scitotenv.2019.05.254}, pmid = {31132706}, issn = {1879-1026}, mesh = {Animals ; Asbestos/analysis ; Asbestosis/epidemiology/veterinary ; Environmental Exposure/*statistics &amp; numerical data ; Environmental Monitoring/*methods ; Environmental Pollutants/analysis ; Humans ; Italy ; Lung Neoplasms/epidemiology/*veterinary ; Mesothelioma/epidemiology/*veterinary ; Swine ; }, abstract = {Mesothelioma is a tumor of the serosal membranes described both in human and veterinary medicine. While in humans the relationship between mesothelioma and exposure to asbestos and some other asbestiform minerals is well known, in animals it is still difficult to establish. In this paper a case of malignant peritoneal mesothelioma probably related to asbestos exposure in a wild boar is described. At post-mortem evaluation the peritoneum, diaphragm and serosal surface of liver and kidneys showed isolated to coalescent multiple nodular lesions. Samples from diaphragm, liver and lung were collected to perform microbiological and histological investigations. To assess the presence of asbestos and/or other asbestiform minerals, SEM-EDS investigations were performed on organs and soil samples collected from the area where the wild boar lived. Microbiological investigations were negative for Mycobacterium species. Gross and histological examination were compatible with a biphasic mesothelioma, with nodules composed of epithelioid and sarcomatoid elements with high pleomorphism. Immunohistochemistry revealed only multifocal scattered positivity for WT-1 and D2-40. Asbestos fibres were detected in all samples (organs and soil) by SEM-EDS, demonstrating a potential relationship between the neoplasia and the exposure to naturally occurring asbestos (NOA). In conclusion, the results of the present study are further confirmation that wild animals, such as the boar, are suitable sentinels to indicate the risk of environmental exposure to asbestos for human populations.}, }
@article {pmid31120100, year = {2019}, author = {Kamiya, H and Peters, S and Sodhi-Berry, N and Reid, A and Gordon, L and de Klerk, N and Brims, F and Musk, AW and Franklin, P}, title = {Validation of an Asbestos Job-Exposure Matrix (AsbJEM) in Australia: Exposure-Response Relationships for Malignant Mesothelioma.}, journal = {Annals of work exposures and health}, volume = {63}, number = {7}, pages = {719-728}, doi = {10.1093/annweh/wxz038}, pmid = {31120100}, issn = {2398-7316}, abstract = {OBJECTIVES: An asbestos job-exposure matrix (AsbJEM) has been developed to systematically and cost-effectively evaluate occupational exposures in population-based studies. The primary aim of this study was to examine the accuracy of the AsbJEM in determining exposure-response relationships between asbestos exposure estimates and malignant mesothelioma (MM) incidence (indirect validation). The secondary aim was to investigate whether the assumptions used in the development of the original AsbJEM provided accurate asbestos exposure estimates.<br><br>METHODS: The study population consisted of participants in an annual health surveillance program, who had at least 3-month occupational asbestos exposure. Calculated asbestos exposure indices included cumulative asbestos exposure and the average exposure intensity, estimated using the AsbJEM and duration of employment. Asbestos and MM exposure-response relationships were compared between the original AsbJEM and its variations based on manipulations of the intensity, duration and frequency of exposure. Twenty-four exposure estimates were calculated for both cumulative asbestos exposure and the average exposure intensity using three exposure intensities (50th, 75th and 90th percentile of the range of mode exposure), four peak durations (15, 30, 60 and 120 min) and two patterns of peak frequency (original and doubled). Cox proportional hazards models were used to describe the associations between MM incidence and each of the cumulative and average intensity estimates.<br><br>RESULTS: Data were collected from 1602 male participants. Of these, 40 developed MM during the study period. There were significant associations between MM incidence and both cumulative and average exposure intensity for all estimates. The strongest association, based on the regression-coefficient from the models, was found for the 50th percentile of mode exposure, 15-min peak duration and the doubled frequency of peak exposure. Using these assumptions, the hazard ratios for mesothelioma were 1 (reference), 1.91, 3.24 and 5.37 for the quartiles of cumulative asbestos exposure and 1 (reference), 1.84, 2.31 and 4.40 for the quartiles of the average exposure intensity, respectively.<br><br>CONCLUSION: The well-known positive exposure-response relationship between MM incidence and both estimated cumulative asbestos exposure and average exposure intensity was confirmed. The strongest relationship was found when the frequency of peak exposure in the AsbJEM was doubled from the originally published estimates.}, }
@article {pmid31119375, year = {2019}, author = {Galani, V and Varouktsi, A and Papadatos, SS and Mitselou, A and Sainis, I and Constantopoulos, S and Dalavanga, Y}, title = {The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment.}, journal = {Cancer chemotherapy and pharmacology}, volume = {84}, number = {2}, pages = {241-253}, doi = {10.1007/s00280-019-03878-3}, pmid = {31119375}, issn = {1432-0843}, abstract = {Malignant mesothelioma (MM) is a highly aggressive tumor that is strongly related to asbestos fiber exposure. The tumorigenesis procedure in MM is complex, and many pathogenetic mechanisms including chronic inflammation, deregulation of cell death, and the genomic copy-number losses and gains may contribute to carcinogenesis. MM cells are resistant to TRAIL-mediated apoptosis due to defects in extrinsic apoptotic pathway. CAPS, a regulator of cell cycle and death, may contribute to the MM development as well. BAP1 is the most frequently inactivated gene in MPM; BAP1 deficiency triggers malignant transformation via disruption of DNA repair, transcription regulation, cell metabolism, apoptosis, and ferroptosis. In addition, bcl-2 family proteins as well as abnormal activation of PI3 K/Akt/mTOR pathway and deregulation of the Wnt signaling pathway may result in MM tumorigenesis. Finally, the Hippo pathway plays a critical role in MPM development. Mutations of NF2 and LATS lead to YAP activation in MPM. Thus, inhibition of YAP activity by YAP inhibitors could be a potentially promising treatment option for MM. In conclusion, extensive genetic alterations exist in mesotheliomas associated with the signaling of apoptotic HM cells death. The comprehension of these pathways may contribute to enhancing survival via developing new effective therapeutic strategies.}, }
@article {pmid31110054, year = {2019}, author = {Waqar, AB and Menzies, D and Casey, M and Doran, M}, title = {Paraneoplastic phenomenon in mesothelioma.}, journal = {Thorax}, volume = {74}, number = {7}, pages = {719-720}, doi = {10.1136/thoraxjnl-2019-213176}, pmid = {31110054}, issn = {1468-3296}, abstract = {A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy.}, }
@article {pmid31107974, year = {2020}, author = {Milosevic, V and Kopecka, J and Salaroglio, IC and Libener, R and Napoli, F and Izzo, S and Orecchia, S and Ananthanarayanan, P and Bironzo, P and Grosso, F and Tabbò, F and Comunanza, V and Alexa-Stratulat, T and Bussolino, F and Righi, L and Novello, S and Scagliotti, GV and Riganti, C}, title = {Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.}, journal = {International journal of cancer}, volume = {146}, number = {1}, pages = {192-207}, doi = {10.1002/ijc.32419}, pmid = {31107974}, issn = {1097-0215}, support = {IG21408//Associazione Italiana per la Ricerca sul Cancro/ ; ERAWEB Action 2//ERANET- Erasmus Mundus/ ; TOPMESO//ERA-Net Transcan-2-JTC 2017/ ; 2016-2443//Fondazione Cassa di Risparmio di Torino/ ; //Fondazione Franco e Marilisa Caligara for Multidisciplinary Sciences/ ; GR-2011-02348356//Ministero della Salute/ ; FABR2017//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; Intramural Grant 2015//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; Intramural Grant 2016//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; Intramural Grant 2017//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; RBFR12SOQ1//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; //Trialect Inc.-Global Medical Education Program/ ; CCM2012//Italian Mesothelioma Network/ ; MESOLINE//Azienda Ospedaliera &quot;SS. Antonio e Biagio e Cesare Arrigo&quot;/ ; }, abstract = {Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM-initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness-related pathways determine chemoresistance. Moreover, there are no predictive markers of IC-associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness-related pathways. We generated MPM IC from primary MPM samples and compared the gene expression and chemo-sensitivity profile of IC and differentiated/adherent cells (AC) of the same patient. Compared to AC, IC had upregulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed. ABCB5-knocked-out (KO) IC clones were resensitized to the drugs in vitro and in patient-derived xenografts. ABCB5 was transcriptionally activated by the Wnt/GSK3β/β-catenin/c-myc axis that also increased IL-8 and IL-1β production. IL-8 and IL-1β-KO IC clones reduced the c-myc-driven transcription of ABCB5 and reacquired chemosensitivity. ABCB5-KO clones had lower IL-8 and IL-1β secretion, and c-myc transcriptional activity, suggesting that either Wnt/GSK3β/β-catenin and IL-8/IL-1β signaling drive c-myc-mediated transcription of ABCB5. ABCB5 correlated with lower time-to-progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first-line chemotherapy in MPM patients.}, }
@article {pmid31103412, year = {2019}, author = {Scagliotti, GV and Gaafar, R and Nowak, AK and Nakano, T and van Meerbeeck, J and Popat, S and Vogelzang, NJ and Grosso, F and Aboelhassan, R and Jakopovic, M and Ceresoli, GL and Taylor, P and Orlandi, F and Fennell, DA and Novello, S and Scherpereel, A and Kuribayashi, K and Cedres, S and Sørensen, JB and Pavlakis, N and Reck, M and Velema, D and von Wangenheim, U and Kim, M and Barrueco, J and Tsao, AS}, title = {Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial.}, journal = {The Lancet. Respiratory medicine}, volume = {7}, number = {7}, pages = {569-580}, doi = {10.1016/S2213-2600(19)30139-0}, pmid = {31103412}, issn = {2213-2619}, abstract = {BACKGROUND: Nintedanib targets VEGF receptors 1-3, PDGF receptors α and β, FGF receptors 1-3, and Src and Abl kinases, which are all implicated in malignant pleural mesothelioma pathogenesis. Here, we report the final results of the phase 3 part of the LUME-Meso trial, which aimed to investigate the efficacy and safety of pemetrexed plus cisplatin combined with nintedanib or placebo in unresectable malignant pleural mesothelioma.<br><br>METHODS: This double-blind, randomised, placebo-controlled phase 3 trial was done at 120 academic medical centres and community clinics in 27 countries across the world. Chemotherapy-naive adults (aged ≥18 years) with unresectable epithelioid malignant pleural mesothelioma and ECOG performance status 0-1 were randomly assigned 1:1 via an independently verified random number-generating system to receive up to six 21-day cycles of pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on day 1, then nintedanib (200 mg twice daily) or matched placebo on days 2-21. Patients without disease progression after six cycles received nintedanib or placebo maintenance on days 1-21 of each cycle. The primary endpoint was progression-free survival (investigator-assessed according to mRECIST) in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of their assigned study drug. This study is registered with ClinicalTrials.gov, number NCT01907100.<br><br>FINDINGS: Between April 14, 2016, and Jan 5, 2018, 541 patients were screened and 458 were randomly assigned to either the nintedanib group (n=229) or the placebo group (n=229). Median treatment duration was 5·3 months (IQR 2·8-7·3) in the nintedanib group and 5·1 months (2·7-7·8) in the placebo group. After 250 events, progression-free survival was not different between the nintedanib group (median 6·8 months [95% CI 6·1-7·0]) and the placebo group (7·0 months [6·7-7·2]; HR 1·01 [95% CI 0·79-1·30], p=0·91). The most frequently reported grade 3 or worse adverse event in both treatment groups was neutropenia (73 [32%] in the nintedanib group vs 54 [24%] in the placebo group). Serious adverse events were reported in 99 (44%) patients in the nintedanib group and 89 (39%) patients in the placebo group. The only serious adverse event occurring in at least 5% of patients in either group was pulmonary embolism (13 [6%] vs seven [3%]).<br><br>INTERPRETATION: The primary progression-free survival endpoint of the phase 3 part of LUME-Meso was not met and phase 2 findings were not confirmed. No unexpected safety findings were reported.<br><br>FUNDING: Boehringer Ingelheim.}, }
@article {pmid31097089, year = {2019}, author = {MacRae, RM and Ashton, M and Lauk, O and Wilson, W and O'Rourke, N and Simone, CB and Rimner, A}, title = {The role of radiation treatment in pleural mesothelioma: Highlights of the 14th International Conference of the International mesothelioma interest group.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {132}, number = {}, pages = {24-27}, doi = {10.1016/j.lungcan.2019.03.023}, pmid = {31097089}, issn = {1872-8332}, abstract = {Radiation remains an important component of mesothelioma treatment in 2018. Its use as a treatment modality continues to evolve as the technology for planning and delivery continues to improve. Use of radiation to improve local control in the involved hemithorax has been a common adjuvant treatment post extrapleural pneumonectomy for many years. Modern treatment options with advanced planning techniques including protons and intensity modulated radiation therapy lead to new potential options for treatment post lung-sparing surgery or in the unresectable setting. Presentations and discussions on the implementation of these strategies for palliation, treatment of oligometastatic recurrence or unresectable disease were the focus of a session dedicated to the role of radiation therapy at the 14th International Conference of the International Mesothelioma Interest Group and are reviewed in this article. Preclinical data to better understand how to integrate radiation and the delivery of novel systemic therapy approached like check point inhibitors are also presented.}, }
@article {pmid31095409, year = {2019}, author = {Rosner, D and Markowitz, G and Chowkwanyun, M}, title = {&quot;Nondetected&quot;: The Politics of Measurement of Asbestos in Talc, 1971-1976.}, journal = {American journal of public health}, volume = {109}, number = {7}, pages = {969-974}, doi = {10.2105/AJPH.2019.305085}, pmid = {31095409}, issn = {1541-0048}, abstract = {The recent lawsuits against Johnson &amp; Johnson have raised the issue of what and when talcum powder manufacturers knew about the presence of asbestos in their products and what they did or did not do to protect the public. Low-level exposure to asbestos in talc is said to result in either mesothelioma or ovarian cancer. Johnson &amp; Johnson has claimed that there was &quot;no detectable asbestos&quot; in their products and that any possible incidental presence was too small to act as a carcinogen. But what exactly does &quot;nondetected&quot; mean? Here, we examine the historical development of the argument that asbestos in talcum powder was &quot;nondetected.&quot; We use a unique set of historical documents from the early 1970s, when low-level pollution of talc with asbestos consumed the cosmetics industry. We trace the debate over the Food and Drug Administration's efforts to guarantee that talc was up to 99.99% free of chrysotile and 99.9% free of amphibole asbestos. Cosmetic talc powder manufacturers, through their trade association, pressed for a less stringent methodology and adopted the term &quot;nondetected&quot; rather than &quot;asbestos-free&quot; as a term of art.}, }
@article {pmid31092657, year = {2019}, author = {de Boer, NL and van Kooten, JP and Burger, JWA and Verhoef, C and Aerts, JGJV and Madsen, EVE}, title = {Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial.}, journal = {BMJ open}, volume = {9}, number = {5}, pages = {e026779}, 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.<br><br>METHODS AND ANALYSIS: The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma.<br><br>INTERVENTION: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.<br><br>ETHICS AND DISSEMINATION: Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.<br><br>TRIAL REGISTRATION NUMBER: NTR7060. EudraCT: 2017-000897-12; Pre-Results.}, }
@article {pmid31087402, year = {2019}, author = {Loomis, D and Richardson, DB and Elliott, L}, title = {Quantitative relationships of exposure to chrysotile asbestos and mesothelioma mortality.}, journal = {American journal of industrial medicine}, volume = {62}, number = {6}, pages = {471-477}, 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.<br><br>METHODS: Quantitative relationships of mortality from mesothelioma and pleural cancer were investigated in an established cohort of 5397 asbestos textile manufacturing workers in North Carolina, USA. Eligible workers were those employed between 1950 and 1973 with mortality follow-up through 2003. Individual exposure to chrysotile fibres was estimated on the basis of 3420 air samples covering the entire study period linked to work history records. Exposure coefficients adjusted for age, race, and time-related covariates were estimated by Poisson regression.<br><br>RESULTS: Positive, statistically significant associations were observed between mortality from all pleural cancer (including mesothelioma) and time since first exposure (TSFE) to asbestos (rate ratio [RR], 1.19; 95% confidence interval [CI], 1.06-1.34 per year), duration of exposure, and cumulative asbestos fibre exposure (RR, 1.15; 95% CI, 1.04-1.28 per 100 f-years/mL; 10-year lag). Analyses of the shape of exposure-response functions suggested a linear relationship with TSFE and a less-than-linear relationship with cumulative exposure. Restricting the analysis to years when mesothelioma was coded as a unique cause of death yielded stronger but less precise associations.<br><br>CONCLUSIONS: These observations support with quantitative data the conclusion that chrysotile causes mesothelioma and encourage exposure-response analyses of mesothelioma in other cohorts exposed to chrysotile.}, }
@article {pmid31078776, year = {2019}, author = {Salaroglio, IC and Kopecka, J and Napoli, F and Pradotto, M and Maletta, F and Costardi, L and Gagliasso, M and Milosevic, V and Ananthanarayanan, P and Bironzo, P and Tabbò, F and Cartia, CF and Passone, E and Comunanza, V and Ardissone, F and Ruffini, E and Bussolino, F and Righi, L and Novello, S and Di Maio, M and Papotti, M and Scagliotti, GV and Riganti, C}, title = {Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {8}, pages = {1458-1471}, doi = {10.1016/j.jtho.2019.03.029}, pmid = {31078776}, issn = {1556-1380}, abstract = {INTRODUCTION: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified.<br><br>METHODS: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome.<br><br>RESULTS: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4+) programmed death 1-positive (PD-1+) (>5.2%) and CD8+PD-1+ (6.4%) cells, CD4+ lymphocyte activating 3-positive (LAG-3+) (>2.8%) and CD8+LAG-3+ (>2.8%) cells, CD4+ T cell immunoglobulin and mucin domain 3-positive (TIM-3+) (>2.5%), and CD8+TIM-3+ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1+/LAG-3+/TIM-3+ CD4+ tumor-infiltrating lymphocytes correlated with overall survival.<br><br>CONCLUSIONS: A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome.}, }
@article {pmid31078166, year = {2019}, author = {Labrèche, F and Kim, J and Song, C and Pahwa, M and Ge, CB and Arrandale, VH and McLeod, CB and Peters, CE and Lavoué, J and Davies, HW and Nicol, AM and Demers, PA}, title = {The current burden of cancer attributable to occupational exposures in Canada.}, journal = {Preventive medicine}, volume = {122}, number = {}, pages = {128-139}, doi = {10.1016/j.ypmed.2019.03.016}, pmid = {31078166}, issn = {1096-0260}, support = {//CIHR/Canada ; }, abstract = {Exposure to occupational carcinogens is often overlooked as a contributor to the burden of cancer. To estimate the proportion of cancer cases attributable to occupational exposure in Canada in 2011, exposure prevalence and levels of 44 carcinogens were informed by data from the Canadian carcinogen exposure surveillance project (CAREX Canada). These were used with Canadian Census (between 1961 and 2011) and Labour Force Survey (annual surveys between 1976 and 2013) data to estimate the number of workers ever exposed to occupational carcinogens. Risk estimates of the association between each carcinogen and cancer site were selected mainly from published literature reviews. Population attributable risks were estimated using Levin's equation and applied to the 2011 cancer statistics from the Canadian Cancer Registry. It is estimated that 15.5 million Canadians alive in 2011 were exposed, during at least one year between 1961 and 2001, to at least one carcinogen in the workplace. Overall, we estimated that in 2011, between 3.9% (95% CI: 3.1%-8.1%) and 4.2% (95% CI: 3.3%-8.7%) of all incident cases of cancer were due to occupational exposure, corresponding to lower and upper numbers of 7700-21,800 cases. Five of the cancer sites - mesothelioma, non-melanoma skin cancer, lung, female breast, and urinary bladder - account for a total of 7600 to 21,200 cancers attributable to occupational exposures such as solar radiation, asbestos, diesel engine exhaust, crystalline silica, and night shift work. Our study highlights cancer sites and occupational exposures that need recognition and efforts by all stakeholders to avoid preventable cancers in the future.}, }
@article {pmid31068670, year = {2019}, author = {Fitzgerald, RC and Rhodes, JM}, title = {Ingested asbestos in filtered beer, in addition to occupational exposure, as a causative factor in oesophageal adenocarcinoma.}, journal = {British journal of cancer}, volume = {120}, number = {12}, pages = {1099-1104}, doi = {10.1038/s41416-019-0467-9}, pmid = {31068670}, issn = {1532-1827}, abstract = {Oesophageal adenocarcinoma has become much more common over the past 50 years, particularly in Britain, with an unexplained male to female ratio of > 4:1. Given the use of asbestos filtration in commercial brewing and reports of its unregulated use in British public houses in the 1970's to clear draught beer &quot;slops&quot;, we have assessed the hypothesis that ingested asbestos could be a causative factor for this increased incidence. Importantly, occupational asbestos exposure increases the risk of adenocarcinoma but not squamous cell carcinoma of the oesophagus. The presence of asbestos fibres was consistently reported in filtered beverages including beers in the 1970s and asbestos bodies have been found in gastrointestinal tissue, particularly oesophageal tissue, at autopsy. There is no reported association between the intake of alcohol and oesophageal adenocarcinoma but studies would mostly have missed exposure from draught beer before 1980. Oesophageal adenocarcinoma has some molecular similarities to pleural mesothelioma, a condition that is largely due to inhalation of asbestos fibres, including predominant loss of tumour suppressor genes rather than an increase of classical oncogenic drivers. Trends in incidence of oesophageal adenocarcinoma and mesothelioma are similar, rising rapidly over the past 50 years but now plateauing. Asbestos ingestion, either from beer consumed before around 1980, or from occupational exposure, seems a plausible causative factor for oesophageal adenocarcinoma. If this is indeed the case, its incidence should fall back to a low baseline by around 2050.}, }
@article {pmid31057996, year = {2019}, author = {Barsky, AR and Cengel, KA and Katz, SI and Sterman, DH and Simone, CB}, title = {First-ever Abscopal Effect after Palliative Radiotherapy and Immuno-gene Therapy for Malignant Pleural Mesothelioma.}, journal = {Cureus}, volume = {11}, number = {2}, pages = {e4102}, 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 = {26}, number = {18}, pages = {18708-18718}, doi = {10.1007/s11356-019-04978-6}, pmid = {31055741}, issn = {1614-7499}, support = {No. 41472046//National Natural Fund Project of China/ ; No. 41602033//National Natural Youth Fund Project of China/ ; No. YF17-Y12//the Fund Project of Sichuan Medical Law Research Center/ ; No. 2017LZXNYD-J24//Collaborative Fund of Luzhou Government and Southwest Medical University/ ; }, mesh = {Animals ; Asbestos, Serpentine/chemistry/*toxicity ; China ; Heme Oxygenase-1/metabolism ; Lipid Peroxidation/drug effects ; Lung/*drug effects/metabolism ; Lung Injury/*chemically induced/metabolism ; Male ; Oxidative Stress/*drug effects ; Particle Size ; Rats ; Rats, Wistar ; }, abstract = {Chrysotile accounts for some 90% to 95% of all the asbestos used worldwide. Scientific evidences have shown that asbestos (including chrysotile) exposure is associated with increased rates of lung cancer, asbestosis, and mesothelioma. However, molecular mechanisms underlying the toxicity effects of chrysotile are not clear. This study evaluated the oxidative stress in chronic lung toxicity caused by the intratracheal instillation (IT) of four kinds China representative chrysotile once a month for 12 months in Wistar rats. These results indicated that chrysotile exposure led to an obvious increase in lung mass and slowed the growth of body mass. Inflammation and fibrosis were observed by hematoxylin-eosin (HE) staining. Exposure to chrysotile significantly increased the accumulation of reactive oxygen species (ROS) and the level of lipid peroxidation and decreased antioxidant capacity in lung tissues. Furthermore, 1-6-month chrysotile exposure activated heme oxygenase-1 (HO-1) and heat shock protein 70 (HSP70) expression, whereas 12-month exposure caused significant decreases of two-factor expression levels in XK and MN groups when compared to negative control group. Therefore, our results suggested that chronic chrysotile pulmonary injury in Wistar rats is triggered by oxidative damage. Meanwhile, the oxidative damage of MN and XK was stronger than that of SSX and AKS, and the difference of oxidative damage in four chrysotile could have been brought by its properties, morphology, chemical composition, and particle size. With all the above mentioned in view, we hope that the revealed data in the experiment could contribute to the progress of further researches on the toxicity and mechanism of chrysotile.}, }
@article {pmid31046484, year = {2019}, author = {Nowak, AK and McDonnell, A and Cook, A}, title = {Immune checkpoint inhibition for the treatment of mesothelioma.}, journal = {Expert opinion on biological therapy}, volume = {19}, number = {7}, pages = {697-706}, doi = {10.1080/14712598.2019.1606209}, pmid = {31046484}, issn = {1744-7682}, abstract = {INTRODUCTION: Combination chemotherapy is currently standard care for advanced mesothelioma. Checkpoint blockade is a promising new treatment.<br><br>AREAS COVERED: This review covers clinical use and biomarkers of checkpoint blockade. Medline search used keywords 'mesothelioma' combined with 'checkpoint blockade' OR 'PD-L1' OR 'PD1' OR 'anti-CTLA4'; the search terms AND 'clinical trial' or AND 'biomarker*' were added. Handsearching covered abstracts from relevant meetings from 2016 to 2018 and reference lists. Data informed a narrative review.<br><br>EXPERT OPINION: Single agent anti-CTLA4 blockade is inactive in mesothelioma. Single agent PD-1 blockade as second or subsequent treatment gives 20-29% partial responses; no randomized comparisons against placebo or chemotherapy are available. Biomarkers of response have been difficult to identify. There is no consensus as to whether tumor PD-L1 expression predicts outcomes. Combination checkpoint inhibitors (CTLA4 and PD1 blockade) provide a small incremental increase in response rates and progression-free survival. Chemoimmunotherapy is the next frontier.}, }
@article {pmid31046142, year = {2019}, author = {Macedo, RF and Cerqueira, EMFP and Algranti, E and Silva, D and De Capitani, EM}, title = {High frequency and severity of pleural changes in former workers exposed to anthophyllite associated with other contaminating amphibole asbestos in Brazil.}, journal = {American journal of industrial medicine}, volume = {62}, number = {6}, pages = {503-510}, doi = {10.1002/ajim.22977}, pmid = {31046142}, issn = {1097-0274}, abstract = {OBJECTIVE: To evaluate the frequency and severity of pleuropulmonary alterations in anthophyllite-exposed former workers in Itapira, São Paulo, Brazil. The amphibole anthophyllite, a magnesium-iron silicate, had its mining, marketing, and use forbidden in Brazil in 1995.<br><br>METHODS: Former workers were followed from 1999 to 2011. All completed chest X-ray interpreted using the International Labour Office (ILO) classification. High-resolution computed tomography was used at the final evaluation. Spirometry assessed forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC throughout the follow-up period. Samples from the mined ore were analyzed by X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS).<br><br>RESULTS: XRD and SEM-EDS confirmed the presence in ore of anthophyllite at a concentration of 75%, in addition to tremolite and other amphiboles in lower concentrations. Twenty-eight subjects were evaluated. Median time of exposure was 3 years (minimum = 1; maximum = 18; interquartile interval = 1-4). Twenty cases of pleural abnormalities were diagnosed in 26 evaluated (77%). The average latency time was 25.6 ± 7.4 years. Two individuals (7.7%) showed progressive worsening of diffuse pleural thickening (DPT) and exhibited an annual FVC decrease of 85 mL and 150 mL, respectively.<br><br>CONCLUSION: This small sample showed a very high index of nonmalignant pleural abnormalities in anthophyllite-exposed workers compared with workers exposed to other kinds of fibers. Rapidly progressive DPT, defined by the severity of pleural compromise, was possibly secondary to the presence of other amphibole types in the inhaled dust. No significant loss of FVC was found in the studied group as a whole. No cases of asbestosis, lung carcinoma, and mesothelioma were diagnosed in this cohort.}, }
@article {pmid31038674, year = {2019}, author = {Oey, H and Daniels, M and Relan, V and Chee, TM and Davidson, MR and Yang, IA and Ellis, JJ and Fong, KM and Krause, L and Bowman, RV}, title = {Whole-genome sequencing of human malignant mesothelioma tumours and cell lines.}, journal = {Carcinogenesis}, volume = {40}, number = {6}, pages = {724-734}, doi = {10.1093/carcin/bgz066}, pmid = {31038674}, issn = {1460-2180}, 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.<br><br>METHODS: National Bureau of Statistics data for MPeM municipal mortality (ICD-10, Code C45.1) were analyzed in the time-window 2003-2014: mortality standardized rates (reference Italian population, census 2011), temporal trends of the annual national rates, Standardized Mortality Ratios and a municipal clustering analysis were performed.<br><br>RESULTS: 747 deaths for MPeM were recorded (0.10/100,000): 464 in men (0.14/100,000) and in 283 women (0.07/100,000). No significant MPeM mortality temporal trend was found. Seventeen municipalities showed excesses of mortality for MPeM in at least one gender and/or overall population. Four clusters in male population, and one in women were identified.<br><br>CONCLUSIONS: The study identifies some areas where remediation activities and/or health care actions may be warranted.}, }
@article {pmid31023248, year = {2019}, author = {Nagamatsu, Y and Oze, I and Aoe, K and Hotta, K and Kato, K and Nakagawa, J and Hara, K and Kishimoto, T and Fujimoto, N}, title = {Physician requests by patients with malignant pleural mesothelioma in Japan.}, journal = {BMC cancer}, volume = {19}, number = {1}, pages = {383}, doi = {10.1186/s12885-019-5591-7}, pmid = {31023248}, issn = {1471-2407}, mesh = {Adult ; Aged ; Asbestos/*toxicity ; Environmental Exposure ; Female ; Humans ; Japan/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology/pathology ; Male ; Mesothelioma/chemically induced/*epidemiology/pathology ; Middle Aged ; Palliative Care ; Physicians ; Pleural Neoplasms/chemically induced/*epidemiology/pathology ; Quality of Life ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed.<br><br>METHODS: This cross-sectional survey was part of a larger study (N = 133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content.<br><br>RESULTS: Responses (N = 217) from MPM patients (N = 73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients.<br><br>CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.}, }
@article {pmid31022494, year = {2019}, author = {Christofidou-Solomidou, M and Pietrofesa, RA and Park, K and Albelda, SM and Serve, KM and Keil, DE and Pfau, JC}, title = {Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice.}, journal = {Toxicology and applied pharmacology}, volume = {375}, number = {}, pages = {81-93}, doi = {10.1016/j.taap.2019.04.018}, pmid = {31022494}, issn = {1096-0333}, support = {R21 CA178654/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R03 CA180548/CA/NCI NIH HHS/United States ; R01 CA133470/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice.<br><br>METHODS: Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry.<br><br>RESULTS: LA exposure induced a significant increase (p < 0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p < 0.0001) elevated post LA exposure, and were significantly (p < 0.0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells.<br><br>CONCLUSIONS: LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases.<br><br>SUMMARY: Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.}, }
@article {pmid30993422, year = {2019}, author = {Boffetta, P and Donato, F and Pira, E and Luu, HN and La Vecchia, C}, title = {Risk of mesothelioma after cessation of asbestos exposure: a systematic review and meta-regression.}, journal = {International archives of occupational and environmental health}, volume = {92}, number = {7}, pages = {949-957}, pmid = {30993422}, issn = {1432-1246}, abstract = {PURPOSE: A 'risk reversal' has been observed for several human carcinogens following cessation of exposure, but it is unclear whether it also exists for asbestos-related mesothelioma.<br><br>METHODS: We conducted a systematic review of the literature and identified nine studies that reported information on risk of mesothelioma after cessation of asbestos exposure, and performed a meta-regression based on random effects models. As comparison we analyzed results on lung cancer risk from four of these studies.<br><br>RESULTS: A total of six risk estimates from five studies were included in the meta-analysis. The summary relative risk (RR) of mesothelioma for 10-year interval since cessation of exposure was 1.02 [95% confidence interval (CI) 0.87-1.19; p-heterogeneity 0.01]. The corresponding RR of lung cancer was 0.91 (95% CI 0.84-0.98).<br><br>CONCLUSIONS: This analysis provides evidence that the risk of mesothelioma does not decrease after cessation of asbestos exposure, while lung cancer risk does.}, }
@article {pmid30968843, year = {2019}, author = {Fedrigotti, A and Riccadonna, A and Riccadonna, D}, title = {&quot;Candido's List&quot;: the workers of Collotta Cis &amp; Figli at Molina di Ledro in Trento Province, Italy. A tale of magnesia, asbestos and work.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {90-93}, doi = {10.4415/ANN_19_01_16}, pmid = {30968843}, issn = {2384-8553}, mesh = {Asbestos, Amosite/*adverse effects/history ; Environmental Restoration and Remediation ; Female ; History, 19th Century ; Humans ; Italy ; Magnesium/adverse effects ; Magnesium Oxide/adverse effects ; Male ; Mesothelioma/*epidemiology/etiology/history ; Occupational Diseases/etiology/history ; Occupational Exposure ; Pleural Neoplasms/*epidemiology/etiology/history ; }, abstract = {The study entitled &quot;Candido's List&quot; (La Lista di Candido) is not the work of the three authors alone. A good part of the community is entitled to feel itself coauthor, each for his/her own part, of a research project that has succeeded in blending a variety of different ingredients: history, entrepreneurship, the industrialization of the Trento Province with all its high and low points, personal life stories, medicine, genius, work, women's emancipation, the past but also the present and future. The research comprises an eloquent collection of memories and a variety of iconographic materials; it has now become a book and a travelling exhibition containing the accounts of the people who worked at the Collotta-Cis factory in Molina di Ledro. It starts with the brilliance of Pier Antonio Cassoni, who in 1816 deposited the first patent in the world for the extraction of magnesium carbonate, and closes with the decontamination of the factory site in the late 1980s. A needful section has been set aside for the painful facts relating to the processing of asbestos fibre; a final space, midway between an artistic reading and an interpretation for the future, has seen the involvement of the Circolo Fotoamatori di Ledro, with a photographic itinerary enabling the reader to &quot;virtually' enter the remaining worksites and listen to these spaces &quot;tell&quot; their stories after years of silence. A story in black and white, where the two tones are also messages for reading a complex story, one that it is important to remember.}, }
@article {pmid30968842, year = {2019}, author = {Parolari, G}, title = {An outbreak of cancer and asbestosis among former amosite-exposed subjects in Ledro Valley, Italy. From discovery to environmental cleanup.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {80-89}, doi = {10.4415/ANN_19_01_15}, pmid = {30968842}, issn = {2384-8553}, mesh = {Adolescent ; Adult ; Aged ; Asbestos ; Asbestos, Amosite/*adverse effects ; Asbestosis/*epidemiology/mortality ; Child ; Disease Outbreaks ; Environmental Restoration and Remediation/*methods ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/epidemiology/etiology/mortality ; Male ; Mesothelioma/epidemiology/etiology/mortality ; Middle Aged ; Neoplasms/chemically induced/*epidemiology/mortality ; Occupational Exposure/statistics &amp; numerical data ; Young Adult ; }, abstract = {Here are reviewed the studies conducted on asbestos-amosite pollution and its effects on the health of workers exposed from 1928 to 1973 at the Collotta-Cis factory of Ledro, Italy. The methods adopted to conduct the initial research, involving the population itself and the local administrations are described. The data summarized include: epidemiological studies of mortality carried out in 1977-85 and updated in 2009; results of the investigations carried out throughout the 1980s on the health consequences on workers, their families and residents near the factory; process of environmental cleanup from asbestos of the industrial area, completed in 1989, and the pollution risk assessment in the whole Ledro Valley. Although this was a small community of about 400 workers, these studies show that exposure to asbestos is responsible for the death of 81 people (22 mesotheliomas, 21 asbestosis, 38 malignant tumors of the lung, digestive system, ovary), for 1400 years of life lost, and for about 100 invalidity pensions, as recognized to former workers by INAIL.}, }
@article {pmid30968841, year = {2019}, author = {Marsili, D and Magnani, C and Canepa, A and Bruno, C and Luberto, F and Caputo, A and Fazzo, L and Zona, A and Comba, P}, title = {Communication and health education in communities experiencing asbestos risk and health impacts in Italy.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {55}, number = {1}, pages = {70-79}, doi = {10.4415/ANN_19_01_14}, pmid = {30968841}, issn = {2384-8553}, mesh = {Asbestos/*adverse effects ; Asbestosis/*epidemiology/prevention &amp; control ; Communication ; Environmental Exposure ; Health Education/*statistics &amp; numerical data ; Humans ; Incidence ; Italy/epidemiology ; Neoplasms/epidemiology/etiology ; Occupational Exposure ; Public Health Surveillance ; }, abstract = {INTRODUCTION: Numerous municipalities in Italy currently experience asbestos health impact, in particular excesses of pleural mesothelioma incidence and mortality. This paper presents an integrated analysis of epidemiological studies and communication actions in affected municipalities to highlight how communication has been implemented depending on health impact evidence and involvement of local stakeholders.<br><br>METHODOLOGY: Four case studies are identified concerning industrial and natural sources of asbestos exposure having different diseases burden. This integrated analysis benefited from multidisciplinary skills.<br><br>DISCUSSION: Evidence of different stakeholders engagement is presented to emphasize their role in the communication process. Similarities and differences among case studies allowed us to identify lessons-learned to be transferred in other asbestos contaminated sites.<br><br>CONCLUSIONS: The adoption of communication strategies and practices, since the very early evidence of asbestos health impact, represents a relevant contribution for epidemiological and health surveillance, particularly for those communities where asbestos health impact has only been recently reported.}, }
@article {pmid30946862, year = {2019}, author = {Finkelstein, MM}, title = {A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.}, journal = {Toxicology and applied pharmacology}, volume = {371}, number = {}, pages = {1-2}, doi = {10.1016/j.taap.2019.03.023}, pmid = {30946862}, issn = {1096-0333}, abstract = {Dr. Garabrant presented a paper concerning a comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans at the Elongate Mineral Particles Conference in Charlottesville, Virginia in 2017. I was a participant at the Conference. Following Dr. Garabrant's talk, I rose in question period to point out that he had not considered information about the occurrence of mesothelioma in several cohorts that was published after the studies that he cited. These additional data were still not addressed in the paper published in your Journal. I believe that your readers would be interested in these, so this letter is written to draw the additional data to their attention.}, }
@article {pmid30944991, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {A survey of patient and caregiver experience with malignant pleural mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {12}, pages = {4675-4686}, pmid = {30944991}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Caregivers/*psychology ; Decision Making ; Female ; Grief ; Health Personnel/*psychology ; Humans ; Lung Neoplasms/*psychology/*therapy ; Male ; Mesothelioma/*psychology/*therapy ; Middle Aged ; Palliative Care/methods ; Physician-Patient Relations ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer with poor prognosis. As there is little information on the lived experience of MPM, our aim was to document the experience of MPM patients and their caregivers.<br><br>METHODS: Surveys for MPM patients and caregivers were developed from previous interviews with patients, caregivers, and health professionals, about treatments and decision-making. Participants were recruited from two hospitals, government compensation body, and support groups.<br><br>RESULTS: Survey responses were received from 78 MPM patients and 106 caregivers from January to September 2014.<br><br>PATIENTS: 85% male, median age 69 years, median time since diagnosis 15 months. Caregivers: median age 68, 91% female, 90% spouse of MPM patient, 95% bereaved. Most participants felt informed about treatment options but only 69% thought all treatment options were discussed. Chemotherapy was discussed most frequently (92-95%); ~80% had sufficient information for decision-making. Decision regarding chemotherapy was made by patient considering doctor's opinion (24%), doctor and patient equally (18%), and doctor (17%). Participants 'agreed'/'strongly agreed' that they made the right decision about chemotherapy (patients 81%, caregivers 60%), but 5% and 16%, respectively, regretted the decision. Most participants received 'sufficient' support (71%). A quarter reported seeing cancer nurse specialists. Palliative care referral: 31% patients, 85% caregivers. Caregivers would have liked to talk to someone by themselves (41%), more time with doctors (30%), psychological support (29%), and clearer information (31%). Bereaved caregivers requested grief counselling (39%) and post-death consultation with specialists (23-25%).<br><br>CONCLUSIONS: Satisfaction with treatment was high, but participants identified need for improved communication and quality information, discussion about all treatments, end-of-life assistance, and caregiver support after the patient's death.}, }
@article {pmid30941506, year = {2019}, author = {Lococo, F and Di Stefano, T and Rapicetta, C and Piro, R and Gelli, MC and Muratore, F and Ricchetti, T and Taddei, S and Zizzo, M and Cesario, A and Facciolongo, N and Paci, M}, title = {Thoracic Hyper-IgG4-Related Disease Mimicking Malignant Pleural Mesothelioma.}, journal = {Lung}, volume = {197}, number = {3}, pages = {387-390}, 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}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Compensation and Redress/legislation &amp; jurisprudence ; Environmental Exposure/*adverse effects/legislation &amp; jurisprudence ; Fatal Outcome ; Humans ; India ; Lung Neoplasms/chemically induced/*diagnosis/mortality ; Male ; Mesothelioma/chemically induced/*diagnosis/mortality ; Occupational Exposure/*adverse effects/legislation &amp; jurisprudence ; Pleural Neoplasms/chemically induced/*diagnosis/mortality ; Workers' Compensation/legislation &amp; jurisprudence ; }, abstract = {India is the largest consumer of asbestos in the world. There is no report from India of mesothelioma related to asbestos. The case is a 42-year-old man who died of pleural mesothelioma. He was exposed to asbestos domestically and from the environment since birth. Two of his close family members worked in a factory that used asbestos. The living quarter of the family was within the premises of the factory. Asbestos waste was strewn on the grounds surrounding the quarters. After decades of legal battles by workers and families exposed to asbestos, Indian courts have ordered remedial measures and compensation to people, who are exposed to asbestos at work and the environment. Mesothelioma, currently in epidemic proportions in the west where asbestos production was banned in the 1990s, could rise to alarming levels in the next decades in India if the legal remedial measures are not implemented soon.}, }
@article {pmid30928905, year = {2019}, author = {Reid, A and Franklin, P and Berry, G and Peters, S and Sodhi-Berry, N and Brims, F and Musk, AW and de Klerk, NH}, title = {Response to letter by Farioli et al.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {5}, pages = {356}, doi = {10.1136/oemed-2019-105740}, pmid = {30928905}, issn = {1470-7926}, mesh = {Adult ; Asbestos, Crocidolite ; Child ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30927363, year = {2019}, author = {Koutros, S and Lubin, JH and Graubard, BI and Blair, A and Stewart, PA and Beane Freeman, LE and Silverman, DT}, title = {Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile.}, journal = {American journal of epidemiology}, volume = {188}, number = {8}, pages = {1484-1492}, 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 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.}, }
@article {pmid30927189, year = {2019}, author = {Kennedy, JM}, title = {The forensic significance of pseudomesotheliomatous adenocarcinoma of the lung.}, journal = {Forensic science, medicine, and pathology}, volume = {15}, number = {3}, pages = {458-462}, doi = {10.1007/s12024-019-00110-9}, pmid = {30927189}, issn = {1556-2891}, mesh = {Adenocarcinoma/metabolism/*pathology ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Lung/*pathology ; Lung Neoplasms/metabolism/*pathology ; Mesothelioma ; }, 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.<br><br>OBJECTIVE: To discuss scientific and socio-economic issues and conflicts of interest and to summarize epidemiological data of asbestos health effects in LA.<br><br>DISCUSSION: Recent data on chrysotile strengthened the evidence of its carcinogenicity and showed an excessive risk of lung cancer at cumulative exposure levels as low as 1.5 fibre-years/ml. Technology for substitution is available for all asbestos-containing products and ceasing asbestos production and manufacturing will not result in unemployment and loss of income, except for the mining industry. The flawed arguments used by the industry to maintain its market, both to the public and in courtrooms, strongly relies on the lack of local evidence of the ill effects and on the invisibility of asbestos-related diseases in LA, due to the limited number of studies and the exposed workers' difficulty accessing health services. The few epidemiological studies available show clear evidence of clusters of mesothelioma in municipalities with a history of asbestos consumption and a forecasted rise in its incidence in Argentina and Brazil for the next decade. In Brazil, non-governmental organizations of asbestos workers were pivotal to counterbalance misinformation and inequities, ending recently in a Supreme Court decision backing an asbestos ban. In parallel, continuous efforts should be made to stimulate the growth of competent and ethical researchers to convey adequate information to the scientific community and to the general public.}, }
@article {pmid30917938, year = {2019}, author = {Linton, A and Blinman, P and Kao, S and van Zandwijk, N}, title = {Patterns of care and survival of older patients with malignant pleural mesothelioma.}, journal = {Journal of geriatric oncology}, volume = {10}, number = {4}, pages = {573-576}, doi = {10.1016/j.jgo.2019.02.013}, pmid = {30917938}, issn = {1879-4076}, abstract = {OBJECTIVE: Malignant pleural mesothelioma (MPM) is a cancer that primarily affects older adults. However this patient population is frequently under-represented in clinical studies. Therefore, we studied the impact of advancing age on treatment utilisation and clinical outcomes in an extensive series of minimally selected MPM patients.<br><br>MATERIALS AND METHODS: Patients with MPM receiving compensation from the New South Wales (NSW) Dust Diseases Authority (2002-2009) were assessed. They were categorised by age (<70 years, 70-80 years or > 80 years) and chi-square testing was used to assess the relationship between clinical and demographic variables, age, treatment and overall survival (OS).<br><br>RESULTS: We identified 910 patients; 41% were aged <70 years, 40% were aged 70-80 years, and 19% were aged >80 years old. Median OS decreased with increasing age: 13.5 months in <70 years, 9.5 months in 70-80 years and 7.1 months in >80 years as did chemotherapy use (66%, 35% and 8% respectively). Radical surgical intervention, adjuvant, and palliative radiotherapy were less frequently used with advanced age. A Kaplan Meier analysis revealed that there was a significant survival advantage (p < .001) for patients <70 and 70-80 years receiving chemotherapy (16.8 vs 7.0 months; 13.9 vs 5.8 months respectively), but not for patients >80 years.<br><br>CONCLUSION: Advancing age group of NSW patients with MPM was associated with reduced treatment utilisation and a decline in OS. Prospective studies are warranted to verify if current treatment guidelines are relevant for the older adults with MPM.}, }
@article {pmid30915902, year = {2019}, author = {Grosso, F and Croce, A and Libener, R and Mariani, N and Pastormerlo, M and Maconi, A and Rinaudo, C}, title = {Asbestos fiber identification in liver from cholangiocarcinoma patients living in an asbestos polluted area: a preliminary study.}, journal = {Tumori}, volume = {105}, number = {5}, pages = {404-410}, doi = {10.1177/0300891619839305}, pmid = {30915902}, issn = {2038-2529}, mesh = {Asbestos/isolation &amp; purification/*toxicity ; Bile Duct Neoplasms/chemically induced/*diagnostic imaging/pathology ; Cholangiocarcinoma/chemically induced/*diagnostic imaging/pathology ; Environmental Pollutants/isolation &amp; purification/toxicity ; Female ; Humans ; Italy ; Liver/*diagnostic imaging/drug effects/pathology ; Male ; Mesothelioma/chemically induced ; Microscopy, Electron, Scanning ; Occupational Exposure ; }, abstract = {PURPOSE: To assess whether asbestos fibers may be observed in liver tissue of patients with cholangiocarcinoma (CC) with environmental or working asbestos exposure.<br><br>METHODS: Detection of fibers was performed directly on histologic sections of liver from 7 patients with CC using optical microscope and variable pressure scanning electron microscopy equipped with energy-dispersive spectroscopy (VP-SEM/EDS). All patients were from Casale Monferrato, Italy, a highly asbestos-polluted town. Due to ethical constraints, observers were blinded to patients' clinical features.<br><br>RESULTS: Fibers/bundles of fibers of chrysotile were detected in 5 out of 7 patients (71%). The boundary between healthy and neoplastic tissue or the fibrocollagen tissue produced by the neoplasia were identified as areas of fiber incorporation.<br><br>CONCLUSIONS: This study is the first report about the detection of chrysotile asbestos fibers in the liver of patients with CC. Further studies on larger cohorts are needed to corroborate our preliminary findings.}, }
@article {pmid30915265, year = {2019}, author = {Robalino Gonzaga, ES and Guzman Rojas, P and Vanar, V}, title = {Malignant Peritoneal Mesothelioma Mimicking Recurrent Diverticulitis.}, journal = {Cureus}, volume = {11}, number = {1}, pages = {e3906}, 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}, mesh = {Adult ; Humans ; Lung Neoplasms/*diagnosis/pathology/surgery ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Orchiectomy ; Positron Emission Tomography Computed Tomography ; Scrotum/diagnostic imaging/*pathology/surgery ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Testis/diagnostic imaging/*pathology/surgery ; Treatment Outcome ; Ultrasonography ; }, abstract = {Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare tumor. It is seen in elderly patients, with painless scrotal swelling being the most common presentation. The exact etiology is unknown; a few risk factors have been suggested. Here, we present an uncommon case of MM of TV without any known predisposing factors. We also discuss the possible risk factors, clinical presentation, pathological features and the difficulties in diagnosis, and management of this rare malignancy.}, }
@article {pmid30893058, year = {2019}, author = {Levpuscek, K and Goricar, K and Kovac, V and Dolzan, V and Franko, A}, title = {The influence of genetic variability of DNA repair mechanisms on the risk of malignant mesothelioma.}, journal = {Radiology and oncology}, volume = {53}, number = {2}, pages = {206-212}, 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 = {Corrigendum: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {492}, doi = {10.1093/carcin/bgz037}, pmid = {30892588}, issn = {1460-2180}, }
@article {pmid30891101, year = {2019}, author = {Wang, Y and Jiang, Z and Yan, J and Ying, S}, title = {HMGB1 as a Potential Biomarker and Therapeutic Target for Malignant Mesothelioma.}, journal = {Disease markers}, volume = {2019}, number = {}, pages = {4183157}, doi = {10.1155/2019/4183157}, pmid = {30891101}, issn = {1875-8630}, mesh = {Animals ; Biomarkers, Tumor/*genetics/metabolism ; Gene Expression Regulation, Neoplastic ; HMGB1 Protein/*genetics/metabolism ; Humans ; Lung Neoplasms/drug therapy/*genetics/metabolism/pathology ; Mesothelioma/drug therapy/*genetics/metabolism/pathology ; }, abstract = {Malignant mesothelioma (MM) is a rare, aggressive, and highly lethal cancer that is substantially induced by exposure to asbestos fibers. High-mobility group box 1 (HMGB1) is an intriguing proinflammatory molecule involved in MM. In this review, we describe the possible crucial roles of HMGB1 in carcinogenic mechanisms based on in vivo and in vitro experimental evidence and outline the clinical findings of epidemiological investigations regarding the possible roles of HMGB1 as a biomarker for MM. We conclude that novel strategies targeting HMGB1 may suppress MM cells and interfere with asbestos-induced inflammation.}, }
@article {pmid30888083, year = {2019}, author = {Hino, O and Abe, M and Han, B and Yan, Y}, title = {In commemoration of the 2018 Mataro Nagayo Prize: A road to early diagnosis and monitoring of asbestos-related mesothelioma.}, journal = {Cancer science}, volume = {110}, number = {5}, pages = {1518-1524}, doi = {10.1111/cas.14001}, pmid = {30888083}, issn = {1349-7006}, support = {S1311011//Foundation of Strategic Research Projects in Private Universities of the NEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan)/ ; S1511008L//Foundation of Strategic Research Projects in Private Universities of the NEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan)/ ; //Institute for Environmental and Gender-Specific Medicine of Juntendo University Urayasu Hospital/ ; //Shizuoka Medical Research Center for Disaster of Juntendo University Shizuoka Hospital/ ; 221S0001//Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Animals ; Asbestos/*adverse effects ; Awards and Prizes ; Biomarkers, Tumor/blood ; Disease Management ; Early Detection of Cancer/*methods ; Humans ; Japan ; Lung Neoplasms/blood/chemically induced/*diagnosis/*surgery ; Mesothelioma/blood/chemically induced/*diagnosis/*surgery ; Occupational Diseases/chemically induced/diagnosis/surgery ; Oncogene Proteins/*blood ; }, abstract = {Primarily caused by exposure to asbestos, mesothelioma is a typical occupational disease. The latency of mesothelioma is as long as 20-40 years, and the cancer initially progresses mainly along the surfaces of pleura or peritoneum without forming masses. As symptoms do not develop until late stages, it has been challenging to diagnose this disease in its early stages and to carry out complete surgical removal. In responding to Japan's asbestos crisis in the mid-2000s, we have developed and improved ERC/MSLN-based serum and radiological markers and pioneered the use of an N-ERC ELISA kit for screening populations at risk for asbestos exposure. In the present article, we review our research toward early diagnosis of asbestos-related mesothelioma before symptoms develop and share our clinical experience of screening, diagnosing and monitoring of this disease. This paper is dedicated to the author (Dr Okio Hino) to commemorate the honor bestowed upon him as the recipient of the Mataro Nagayo Prize in 2018.}, }
@article {pmid30886321, year = {2019}, author = {Jeffery, E and Lee, YCG and Newton, RU and Lyons-Wall, P and McVeigh, J and Nowak, AK and Cheah, HM and Nguyen, B and Fitzgerald, DB and Creaney, J and Straker, L and Peddle-McIntyre, CJ}, title = {Body composition and nutritional status in malignant pleural mesothelioma: implications for activity levels and quality of life.}, journal = {European journal of clinical nutrition}, volume = {73}, number = {10}, pages = {1412-1421}, doi = {10.1038/s41430-019-0418-9}, pmid = {30886321}, issn = {1476-5640}, abstract = {BACKGROUND/OBJECTIVES: Malignant pleural mesothelioma (MPM) is an incurable cancer and optimizing daily physical activity and quality of life are key goals of patient management. Little is known about the prevalence of pre-sarcopenia and malnutrition in MPM or their associations with patient outcomes. This study aimed to determine the prevalence of pre-sarcopenia and malnutrition in MPM and investigate if activity levels and quality of life differed according to body composition and nutritional status.<br><br>SUBJECTS/METHODS: Patients with a diagnosis of MPM were recruited. Pre-sarcopenia was defined as low appendicular skeletal muscle mass (≤ 7.26 kg/m2 for men and ≤ 5.45 kg/m2 for women), measured by dual energy X-ray absorptiometry. Malnutrition was defined as a rating of B or C on the Patient-Generated Subjective Global Assessment. Outcome measures included objective activity levels (Actigraph GT3X) and health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy General).<br><br>RESULTS: Sixty-one people participated (79% male, median age 69 [IQR 62-74] years and median BMI 25.8 [IQR 24.3-28.4] kg/m2). Fifty-four percent were pre-sarcopenic and 38% were malnourished. Percent of time spent in light activity/day was lower in participants with pre-sarcopenia compared with non-sarcopenic participants (median 25.4 [IQR 19.8-32.1]% vs. 32.3 [27.1-35.6]%; p = 0.008). Participants with malnutrition had poorer HRQoL than well-nourished participants (mean 69.0 (16.3) vs. 84.4 (13.3); p < 0.001).<br><br>CONCLUSION: Participants with MPM had high rates of pre-sarcopenia and malnutrition. Pre-sarcopenia was associated with poorer activity levels, whilst malnutrition was associated with poorer quality of life. Interventions that aim to address reduced muscle mass and weight loss, should be tested in MPM to assess their impact on patient outcomes.}, }
@article {pmid30885349, year = {2019}, author = {Ahmadzada, T and Lee, K and Clarke, C and Cooper, WA and Linton, A and McCaughan, B and Asher, R and Clarke, S and Reid, G and Kao, S}, title = {High BIN1 expression has a favorable prognosis in malignant pleural mesothelioma and is associated with tumor infiltrating lymphocytes.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {130}, number = {}, pages = {35-41}, doi = {10.1016/j.lungcan.2019.02.005}, pmid = {30885349}, issn = {1872-8332}, abstract = {OBJECTIVES: A number of key immune regulators show prognostic value in malignant pleural mesothelioma (MPM), but the association between Bridging integrator 1 (BIN1), indoleamine 2,3 dioxygenase 1 (IDO1) and patient outcome has not been investigated. We aimed to determine the expression of BIN1 and IDO1, their association with other markers and impact on overall survival (OS) in MPM.<br><br>MATERIALS AND METHODS: The expression of BIN1, IDO1, CD3, CD20 and CD68 were evaluated by immunohistochemistry in 67 patients who underwent pleurectomy/decortication. Survival analyses were performed using the Kaplan Meier method and significant biomarkers were entered into a Cox Regression multivariate model, accounting for known prognostic factors such as age, gender, histological subtype, PD-L1 expression and neutrophil-to-lymphocyte ratio.<br><br>RESULTS: Immune markers were variably expressed in tumor cells, ranging from 0% to 100% for BIN1 (median: 89%), and 0% to 77.5% for IDO1 (median: 0%). Expression of markers of tumor-infiltrating lymphocytes (TILs) and macrophages ranged from 0% to more than 50%. BIN1 expression was high in 35 patients (51%) and was associated with increased OS (median: 12 vs 6 months for high and low BIN1 respectively,p = 0.03). Multivariate analysis showed BIN1 remained an independent prognostic indicator (HR 0.39; 95% CI: 0.18-0.82, p = 0.01). The majority of patients had immune inflamed tumors (77%) and there was a significant association between TILs and BIN1 (p = 0 < 0.01), PD-L1 (p=0.04) and CD68+ macrophages in the tumor (p < 0.01). There were no significant associations between PD-L1 and BIN1 or IDO1.<br><br>CONCLUSION: High BIN1 expression is a favorable prognostic biomarker and is associated with TILs in MPM.}, }
@article {pmid30882147, year = {2019}, author = {Nakai, T and Matsumoto, Y and Sasada, S and Tanaka, M and Tsuchida, T and Ohe, Y and Motoi, N}, title = {Cryobiopsy during flex-rigid pleuroscopy: an emerging alternative biopsy method in malignant pleural mesothelioma. A comparative study of pathology.}, journal = {Japanese journal of clinical oncology}, volume = {49}, number = {6}, pages = {559-566}, doi = {10.1093/jjco/hyz032}, pmid = {30882147}, issn = {1465-3621}, mesh = {Aged ; Biopsy/instrumentation/methods ; Female ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Mesothelioma/*diagnosis ; Middle Aged ; Pleural Neoplasms/*diagnosis ; Thoracoscopy/*instrumentation/*methods ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is rarely an asbestos-related cancer with a poor prognosis that is difficult to distinguish from some benign conditions by using conventional biopsy techniques. The purpose of this study was to evaluate the utility of a novel biopsy technique using a cryoprobe during flex-rigid pleuroscopy for diagnosing MPM.<br><br>METHODS: Consecutive patients who underwent pleural cryobiopsy during flex-rigid pleuroscopy from June through November 2017 to diagnose the cause of pleural effusion were collected. From these, cases ultimately diagnosed as MPM were selected. Pleural biopsies were performed by using conventional instruments followed by a cryoprobe. The obtained samples were histologically examined and compared with regard to the quality (sample size, tissue depth, and crush rate), immunohistochemical (IHC) staining, and p16 by fluorescence in situ hybridization (FISH).<br><br>RESULTS: In total, five patients ultimately diagnosed as MPM were enrolled. The sample collected was significantly larger for cryobiopsy than conventional biopsy (18.9 mm2 vs. 6.7 mm2, P < 0.001). Full-thickness biopsies were achieved in four cases by using cryobiopsy compared with one case by conventional biopsy. Moreover, the crush rate was significantly less for cryobiopsy than conventional biopsy (9% vs. 35%, P < 0.001). The results of IHC staining and p16 by FISH were similar between biopsy techniques. Cryobiopsy successfully led to accurate diagnosis of MPM in all cases, whereas conventional biopsy was diagnostic in one case. No severe complications developed after either biopsy technique.<br><br>CONCLUSION: Cryobiopsy during flex-rigid pleuroscopy is a feasible and convenient biopsy technique that supports precise diagnosis of MPM.}, }
@article {pmid30879467, year = {2019}, author = {Miyata, T and Fujiwara, Y and Nishijima, K and Futagami, F and Nakamura, T and Takamura, H}, title = {Localized multiple malignant epithelioid peritoneal mesotheliomas arising from the hepatoduodenal ligament and diaphragm: a case report.}, journal = {Journal of medical case reports}, volume = {13}, number = {1}, pages = {66}, doi = {10.1186/s13256-019-2008-9}, pmid = {30879467}, issn = {1752-1947}, mesh = {Female ; Humans ; Liver Neoplasms/diagnostic imaging/*pathology/secondary/surgery ; Lung Neoplasms/diagnostic imaging/*pathology/surgery ; Mesothelioma/diagnostic imaging/*pathology/surgery ; Middle Aged ; Muscle Neoplasms/*pathology ; Neoplasm Invasiveness ; Peritoneal Neoplasms/diagnostic imaging/*pathology/secondary/surgery ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma is a rare aggressive tumor of the peritoneum. We report a rare case of resection of multiple localized malignant peritoneal mesotheliomas.<br><br>CASE PRESENTATION: A 55-year-old Japanese woman was admitted to our hospital because liver tumors were detected by abdominal ultrasonography during a screening examination. Blood examination findings, including tumor makers, were within normal ranges. She had no evidence of exposure to asbestos. Computed tomography showed four hypervascular, round liver tumors, one in the lateral liver segment adjacent to the hepatic hilus, and the other three on the liver surface. Computed tomography angiography revealed that the tumor in the lateral segment had strong enhancement and was fed from the left gastric artery. In contrast, the other tumors showed no enhancement, and were fed from the right inferior phrenic artery. Abnormal accumulation was identified in the four tumors only with 18F-fluorodeoxyglucose positron emission tomography. It was very difficult to obtain a definitive preoperative diagnosis, but surgical resection was performed because we considered potential malignancy. Laparotomy revealed the principal site of the tumor in the lateral segment was on the hepatoduodenal ligament, and all other tumors were on the diaphragm. A left lobectomy and partial diaphragmatic resection were performed. The final pathological diagnosis was multiple malignant epithelioid mesotheliomas. Our patient has had no recurrence for 20 months postoperatively.<br><br>CONCLUSIONS: In general, malignant peritoneal mesotheliomas are classified as diffuse tumors, which are often unresectable and have a poor prognosis. However, early diagnosis and treatment, particularly with the localized type, as in our patient, could lead to long-term survival of the patient. We recommend that multiple malignant epithelioid mesotheliomas be included in the differential diagnosis for patients with subcapsular hepatic tumors.}, }
@article {pmid30874891, year = {2019}, author = {Hutter, HP and Waldhoer, T and Müller, K and Hackl, M and Weitensfelder, L and Heinzl, H}, title = {Cancer incidence in an Austrian alpine valley 1983-2012 : A descriptive study.}, journal = {Wiener klinische Wochenschrift}, volume = {131}, number = {9-10}, pages = {200-204}, doi = {10.1007/s00508-019-1476-7}, pmid = {30874891}, issn = {1613-7671}, mesh = {Asbestos/adverse effects ; Austria/epidemiology ; Hexachlorobenzene/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Neoplasms/*epidemiology ; }, abstract = {After one of Austria's largest environmental scandals in 2014, which involved the release of hexachlorobenzene (HCB) in the Carinthian valley Görtschitztal, concerns about increased cancer rates have arísen in the affected local population. A descriptive study was conducted to examine the cancer incidence rates between 1983 and 2012. Data from the affected area (Görtschitztal, district St. Veit) were compared to data from the neighboring area within the same district and Carinthia excluding St. Veit, considering incidence rates of liver, lung, kidney, thyroid cancer and mesothelioma. Prostate cancer and carcinoma in situ were both included and excluded from overall cancer incidents in order to prevent potential bias due to screening programs. Considering the observed variability at an overall level, no conspicuous differences in cancer incidences could be found (Carinthia: 495, St. Veit West: 408, St. Veit East: 572 cases per 100,000 person-years in 2012). For some cancer types, e. g. liver, thyroid cancer and mesothelioma, the affected region showed a higher increase in rates than the neighboring area or Carinthia overall; however, these increased rates date back to a time prior to the HCB exposure, suggesting other carcinogenic influences, such as asbestos exposure from antecedent years.}, }
@article {pmid30873891, year = {2019}, author = {Poland, CA and Duffin, R}, title = {The toxicology of chrysotile-containing brake debris: implications for mesothelioma.}, journal = {Critical reviews in toxicology}, volume = {49}, number = {1}, pages = {11-35}, doi = {10.1080/10408444.2019.1568385}, pmid = {30873891}, issn = {1547-6898}, abstract = {The global use of &quot;asbestos&quot; in various commercial products has led to a wide range and pervasive legacy of disease. One such use of chrysotile asbestos was brake pads and was utilized commonly in automobiles and heavy vehicles. The result of incorporation of chrysotile into brake pads is associated with the exposure of mechanics fitting and servicing vehicles to liberated chrysotile fibers. Despite the proven exposure, the relative risk of malignant mesothelioma (MM) in this occupational population is broadly seen as low. The toxicity of particulates, including fibers such as chrysotile, is driven by a combination of dose and physicochemical properties. As such, it is plausible that chrysotile released from brake pads may have undergone modification, thereby altering the pathogenicity profile. The impact of high sheer stress causing shortening of long fibers, heat modification, binding of resin matrix to the fiber surface on the relative toxicity of brake debris with regards to MM is considered. It is apparent that released chrysotile can undergo significant modification, reducing the long fiber dose although not all modifications may lead to reduced toxicity.}, }
@article {pmid30873867, year = {2019}, author = {Baqui, AA and Boire, NA and Baqui, TT and Etwaru, DJ}, title = {Malignant Mesothelioma of the Tunica Vaginalis Testis-A Malignancy Associated With Asbestos Exposure and Trauma: A Case Report and Literature Review.}, journal = {Journal of investigative medicine high impact case reports}, volume = {7}, number = {}, pages = {2324709619827335}, 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 = {61}, number = {5}, pages = {410-416}, 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.<br><br>METHODS: We calculated standardized mortality ratios (SMRs) for several causes of death stratified by latency, cumulative exposure, and time since last exposure (TSLE).<br><br>RESULTS: Latency: we observed a peak and then a decrease in SMR for lung, pleural, and peritoneal cancer. Cumulative Exposure: We observed a peak and then a decrease in SMR for lung and pleural cancer, not for peritoneal cancer. TSLE: Pleural cancer SMR peaked at 20 to 29 years, then decreased, peritoneal cancer SMR reached a plateau after 20 years and lung cancer mortality was in excess in each class.<br><br>CONCLUSIONS: We found different patterns in mortality in the main asbestos-related tumors.}, }
@article {pmid30863440, year = {2019}, author = {Liang, Y and Zheng, G and Yin, W and Song, H and Li, C and Tian, L and Yang, D}, title = {Significance of EGFR and PTEN Expression and PLR and NLR for Predicting the Prognosis of Epithelioid Malignant Peritoneal Mesothelioma.}, journal = {Gastroenterology research and practice}, volume = {2019}, number = {}, pages = {7103915}, 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).<br><br>Methods: 33 patients of pathologically diagnosed epithelioid MPeM tissues were analyzed using immunohistochemistry to detect EGFR and PTEN; the PLR and NLR were determined by using a routine blood test. We analyzed the relationships of these markers to age, sex, asbestos exposure, elevated platelet count, ascites, and clinical stage.<br><br>Results: EGFR and PTEN expressions were positive in 22 (66.67%) and 7 (21.21%) epithelioid MPeM patients, respectively. However, these two markers as well as PLR and NLR were not significantly associated with age, sex, asbestos exposure, elevated platelet counts, ascites, and clinical stage (P > 0.05). The correlation between EGFR and PTEN was negative (r = -0.577, P < 0.001), but the correlation between NLR and PLR was positive (r = 0.456, P = 0.008). The median survival of all patients was 6 months. In univariate analysis, PTEN (P < 0.001), PLR (P = 0.014), and NLR (P = 0.015) affected the overall survival. Multivariate analysis revealed that PTEN and PLR were validated as predictive for overall survival of epithelioid MPeM (HR = 0.070, P = 0.001, and HR = 3.379, P = 0.007, respectively).<br><br>Conclusion: On the basis of these results, it is suggested that PTEN and PLR are risk factors for the prognosis of epithelioid MPeM, which may be targets for selective therapies and improve the outcomes of patients with epithelioid MPeM.}, }
@article {pmid30863365, year = {2019}, author = {Baird, AM and Easty, D and Jarzabek, M and Shiels, L and Soltermann, A and Klebe, S and Raeppel, S and MacDonagh, L and Wu, C and Griggs, K and Kirschner, MB and Stanfill, B and Nonaka, D and Goparaju, CM and Murer, B and Fennell, DA and O'Donnell, DM and Barr, MP and Mutti, L and Reid, G and Finn, S and Cuffe, S and Pass, HI and Opitz, I and Byrne, AT and O'Byrne, KJ and Gray, SG}, title = {When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {89}, 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, &quot;A Comparison of Asbestos Fiber Potency and Elongate Mineral Particle (EMP) Potency for Mesothelioma in Humans&quot;).}, journal = {Toxicology and applied pharmacology}, volume = {370}, number = {}, pages = {131-132}, doi = {10.1016/j.taap.2019.03.002}, pmid = {30851279}, issn = {1096-0333}, }
@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 {pmid30815702, year = {2019}, author = {Pasetto, R and Zona, A and Fazzo, L and Binazzi, A and Bruno, C and Pirastu, R and Comba, P and Marinaccio, A}, title = {Proportion of mesothelioma attributable to living in industrially contaminated areas in Italy.}, journal = {Scandinavian journal of work, environment &amp; health}, volume = {45}, number = {5}, pages = {444-449}, doi = {10.5271/sjweh.3809}, pmid = {30815702}, issn = {1795-990X}, abstract = {Objectives The aim of this study was to estimate the attributable proportion (AP) of mesothelioma resulting from living in or close to major Italian industrially contaminated areas. Methods For populations living close to 39 sites of &quot;national priority for remediation&quot;, incident mesothelioma cases were extracted from the Italian National Mesothelioma Registry (ReNaM) in the period 2000‒2011. Each site was classified in one of seven asbestos risk groups (RG) on the basis of the type of industrial plants. RG were ranked by the a priori evidence on asbestos risk. The AP for each RG was calculated as the meta-analytic estimate of AP of sites of the same group by gender and age class (0-64, 65-74, ≥75 years). The sex ratio (men/women) was computed for each RG. Results Among men, the AP by age class had the same gradient in each RG, with the highest values in the age class 0-64 years and the lowest in the ≥75 class; in the age class 0-64 years, the AP was positive in each RG, >90% in the presence of asbestos cement factories and harbors with shipyards. Among women, the overall AP decreased by RG, with negative values in the last two ranked RG; the AP by age class was variable without a definite gradient. The sex ratio was close to one only in the RG &quot;only asbestos-cement factories&quot;; the highest value (9.6) was observed in the age class 0-64 years in the RG &quot;harbors with shipyard&quot;. Conclusions The integration of a geographic- and case-based approach provides valuable insights into occupational and environmental determinants of mesothelioma risk in industrially contaminated sites.}, }
@article {pmid30809599, year = {2018}, author = {Biersack, B}, title = {Relations between approved platinum drugs and non-coding RNAs in mesothelioma.}, journal = {Non-coding RNA research}, volume = {3}, number = {4}, pages = {161-173}, 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 = {76}, number = {5}, pages = {355}, doi = {10.1136/oemed-2018-105637}, pmid = {30804167}, issn = {1470-7926}, mesh = {Adult ; Asbestos, Crocidolite ; Child ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@article {pmid30804166, year = {2019}, author = {Dalsgaard, SB and Würtz, ET and Hansen, J and Røe, OD and Omland, Ø}, title = {Environmental asbestos exposure in childhood and risk of mesothelioma later in life: a long-term follow-up register-based cohort study.}, journal = {Occupational and environmental medicine}, volume = {76}, number = {6}, pages = {407-413}, doi = {10.1136/oemed-2018-105392}, pmid = {30804166}, issn = {1470-7926}, abstract = {OBJECTIVE: To examine the risk of malignant mesothelioma (MM) in former pupils who attended primary school near an asbestos cement plant.<br><br>METHODS: A cohort of 12 111 former pupils, born 1940-1970, was established from individual historical records from four primary schools located at a distance of 100-750 m in the prevailing wind direction from an asbestos cement plant operating from 1928 to 1984 in Aalborg, Denmark. The school cohort and a comparison cohort consisting of 108 987 gender and 5-year frequency-matched subjects were followed up (2015) for MM in the Danish Cancer Registry. Using Cox regression, HRs were estimated for the incidence of MM. Adjustments for occupational and familial asbestos exposure were made with a job exposure matrix. An SIR analysis including latency periods testing the cancer incidence rate was performed with the comparison cohort as the reference rate.<br><br>RESULTS: The median person-years of follow-up were 62.5 years in the school cohort and 62.2 years in the comparison cohort. There were 32 males and 6 females of the former pupils who developed MM during the follow-up: HRmale 7.01 (95% CI 4.24 to 11.57), HRfemale 7.43 (95% CI 2.50 to 22.13). Those who attended school 250 m north of the plant had the highest HR for MM, 10.65 (95% Cl 5.82 to 19.48). No significant trend between school distance and risk of MM was established (p=0.35).<br><br>CONCLUSION: Our results suggest that boys and girls who attended schools and lived in the neighbourhood of an asbestos cement plant later in life have a significantly increased risk of MM.}, }
@article {pmid30804152, year = {2019}, author = {Kim, M and Kim, HS}, title = {Clinicopathological Characteristics of Well-differentiated Papillary Mesothelioma of The Peritoneum: A Single-institutional Experience of 12 Cases.}, journal = {In vivo (Athens, Greece)}, volume = {33}, number = {2}, pages = {633-642}, doi = {10.21873/invivo.11521}, pmid = {30804152}, issn = {1791-7549}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Mesothelioma/epidemiology/*pathology ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology/*pathology ; Patient Selection ; Peritoneal Neoplasms/epidemiology/*pathology ; Peritoneum/pathology ; Pleural Neoplasms/epidemiology/*pathology ; }, abstract = {BACKGROUND/AIM: Well-differentiated papillary mesothelioma (WDPM) is histologically characterized by papillary architecture with fibrovascular cores, lined by bland mesothelial cells. We recently experienced a case of WDPM associated with multiple peritoneal inclusion cysts, which prompted us to initiate a comprehensive review of previously diagnosed WDPM cases.<br><br>MATERIALS AND METHODS: The clinicopathological characteristics and immunophenotype of 12 cases of peritoneal WDPM were investigated using a review of electronic medical records, pathological examination, and immunostaining.<br><br>RESULTS: The patients' ages ranged from 23 to 75 years. No patient had endometriosis or a previous history of asbestos exposure. Ten tumors were detected incidentally during surgery for other causes. Most tumors appeared as a small, single nodule on the peritoneal surface, but in three cases, WDPM presented as multiple lesions. All but one patient had no symptoms. All the patients examined are still well without postoperative recurrence. Histologically, all cases demonstrated typical papillary architecture with fibrovascular cores. The mesothelial cells lining the papillae consisted mostly of single row of cells, although areas of proliferation to multiple layers were observed in a few cases. Their nuclei appeared bland, but two cases exhibited mild nuclear atypia and prominent nucleoli. Immunostaining revealed that the mesothelial cells were positive for D2-40, cytokeratin 5/6, cytokeratin 7, and Wilms' tumor 1.<br><br>CONCLUSION: We herein demonstrated the clinicopathological characteristics of peritoneal WDPMs. WDPM has distinct pathological features. Although all cases we examined were uneventful after surgery, further surveillance is recommended since the biological behavior of WDPM is still uncertain.}, }
@article {pmid30776941, year = {2019}, author = {Wang, F and Chen, Y and Wang, Y and Yin, Y and Qu, G and Song, M and Wang, H}, title = {Ultra-long silver nanowires induced mitotic abnormalities and cytokinetic failure in A549 cells.}, journal = {Nanotoxicology}, volume = {13}, number = {4}, pages = {543-557}, doi = {10.1080/17435390.2019.1571645}, pmid = {30776941}, issn = {1743-5404}, 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}, mesh = {Apoptosis/drug effects ; Biopsy ; CD146 Antigen/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Endocytosis/drug effects ; Gold/chemistry ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Mesothelioma/*drug therapy/pathology ; Metal Nanoparticles/*chemistry ; Pemetrexed/pharmacology/*therapeutic use ; Pleural Neoplasms/*drug therapy/pathology ; Reactive Oxygen Species/metabolism ; }, abstract = {Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.<br><br>Methods: MPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).<br><br>Results: GNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.<br><br>Conclusion: GNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.}, }
@article {pmid30773744, year = {2019}, author = {Yoshida, GJ}, title = {Beyond Stanton and Pott hypothesis; carbon nanotubes-induced malignant mesothelioma as a disease of gene loss.}, journal = {Journal of occupational health}, volume = {61}, number = {2}, pages = {203-205}, doi = {10.1002/1348-9585.12019}, pmid = {30773744}, issn = {1348-9585}, mesh = {Animals ; Asbestos/adverse effects ; Genes, p16 ; Humans ; Lung Neoplasms/*chemically induced/*genetics ; Mesothelioma/*chemically induced/*genetics ; Mice ; Nanotubes, Carbon/*adverse effects ; Occupational Exposure/adverse effects ; }, }
@article {pmid30770142, year = {2019}, author = {Douglas, T and Van den Borre, L}, title = {Asbestos neglect: Why asbestos exposure deserves greater policy attention.}, journal = {Health policy (Amsterdam, Netherlands)}, volume = {123}, number = {5}, pages = {516-519}, doi = {10.1016/j.healthpol.2019.02.001}, pmid = {30770142}, issn = {1872-6054}, 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}, mesh = {Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Cell Proliferation/drug effects ; Drug Carriers/chemistry ; Drug Delivery Systems ; Histone Deacetylase Inhibitors/chemistry/*pharmacology ; Humans ; Hydrogen-Ion Concentration ; Nanoparticles/*chemistry ; Neoplasms/*drug therapy/pathology ; Polymerization ; }, abstract = {Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.}, }
@article {pmid30754975, year = {2018}, author = {Pelclová, D}, title = {Diagnostics and acknowledgement of occupational diseases - topics and challenges in the Czech Republic.}, journal = {Casopis lekaru ceskych}, volume = {157}, number = {8}, pages = {396-399}, pmid = {30754975}, issn = {0008-7335}, mesh = {*Asbestos/adverse effects ; *Asthma/diagnosis/etiology ; Czech Republic ; Humans ; *Mesothelioma/diagnosis/etiology ; *Occupational Diseases/diagnosis/therapy ; }, abstract = {The causes of occupational diseases are changing, thats why a regular update of Czech List of Occupational Diseases is needed. New compensable occupational diseases, such as cancer of the larynx and ovarian cancer due to asbestos, and chronic obstructive pulmonary diseases due to black coal dust were included in the last two updates of the Czech List. The need of an early examination at the Centers of Occupational Diseases is stressed in this article, especially before a surgery or other treatment of epicondylitis and carpal tunnel syndrome. These treatments may suppress the diagnostic hallmarks requested for acknowledgements of these disorders. Extrinsic allergic alveolitis, allergic rhinitis and bronchial asthma are underdiagnosed, and isocyanates belong among the key factors. Only about 10 % patients with mesotheliomas due to asbestos are compensated. The latency in cancers due to asbestos may reach more than 50 years.}, }
@article {pmid30744695, year = {2019}, author = {Weber, DG and Brik, A and Casjens, S and Burek, K and Lehnert, M and Pesch, B and Taeger, D and Brüning, T and Johnen, G and , }, title = {Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study.}, journal = {BMC research notes}, volume = {12}, number = {1}, pages = {77}, doi = {10.1186/s13104-019-4113-7}, pmid = {30744695}, issn = {1756-0500}, mesh = {Adult ; Asbestosis/blood ; Biomarkers, Tumor/*blood ; Case-Control Studies ; Circulating MicroRNA/*blood ; Early Detection of Cancer/*standards ; Humans ; Lung Neoplasms/blood/*diagnosis ; Male ; Mesothelioma/blood/*diagnosis ; MicroRNAs/*blood ; Middle Aged ; Prodromal Symptoms ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case-control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease.<br><br>RESULTS: Using prediagnostic plasma samples collected in median 8.9 months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.}, }
@article {pmid30741658, year = {2019}, author = {García-Ibáñez, J and Cayuelas-Rubio, C and Durán-Rivera, A and Mitjana-Biosca, S and Monzó-Cataluña, A and Sánchez Ballester, F and Ramos de Campos, M and Ramos de Campos, M and López-Alcina, E}, title = {[Report of two cases of malignant mesothelioma of the tunica vaginalis.].}, journal = {Archivos espanoles de urologia}, volume = {72}, number = {1}, pages = {85-88}, pmid = {30741658}, issn = {0004-0614}, mesh = {Aged ; Humans ; *Lung Neoplasms ; Male ; *Mesothelioma/diagnosis ; *Testicular Hydrocele ; *Testicular Neoplasms/diagnosis ; }, abstract = {OBJECTIVE: Paratesticular mesothelioma isan infrequent tumor and only 250 cases have been published.It originates in the scrotal tunica vaginalis. It represents0.3-1.4% of mesotheliomas and it predominates inpatients with history of asbestos exposure and old age. Itsdiagnosis is usually casual. Our objective is to present thecases that occurred in our service with malignant paratesticularmesothelioma and to carry out a review of the currentliterature on this pathology.<br><br>METHODS: We report two cases diagnosed with malignantparatesticular mesothelioma that happened in the lasttwo years.<br><br>RESULT: The first case was a 73-year-old male with asymptomatichydrocele. The second was a 57-year-oldmale who had testicular pain and hydrocele. Both werediagnosed of mesothelioma after hydrocelectomy. The firsttreatment was radical orchiectomy in both cases. The firstpatient did not need more treatments. The second patientpresented pulmonary nodules, lymphadenopathy and localrelapse, which was treated with chemotherapy and localresection.<br><br>CONCLUSION: Paratesticular mesothelioma is an infrequenttumor. Scrotal mass associated with hydrocele is thetypical form of presentation. Surgical treatment consists ofradical orchiectomy. They have poor prognosis because inmost cases there is rapid local and dissemination.}, }
@article {pmid30719319, year = {2019}, author = {Guo, X and Watanabe, J and Takahashi, K and Hayashi, T and Kurose, N and Sasaguri, Y and Uramoto, H and Iwagaki, H and Nabeshima, K and Yamada, S}, title = {Localized malignant pleural mesothelioma arising in the interlobar fissure: a unique surgical case masquerading clinicopathologically as primary lung adenocarcinoma.}, journal = {SAGE open medical case reports}, volume = {7}, number = {}, pages = {2050313X18824802}, 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}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asbestos/adverse effects ; Cytoreduction Surgical Procedures/mortality ; Female ; Finland ; Humans ; Hyperthermia, Induced ; Lung Neoplasms/*drug therapy/mortality/*surgery ; Male ; Mesothelioma/*drug therapy/mortality/*surgery ; Middle Aged ; Peritoneal Neoplasms/*drug therapy/mortality/*surgery ; Prognosis ; Retrospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland.<br><br>MATERIALS AND METHODS: The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure.<br><br>RESULTS: Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009).<br><br>CONCLUSION: Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.}, }
@article {pmid30706690, year = {2019}, author = {Rojas, L and Cardona, AF and Trejo-Rosales, R and Zatarain-Barrón, ZL and Ramírez-Tirado, LA and Ruiz-Patiño, A and Campos Gómez, S and Corrales, L and Oblitas, G and Bacon, L and Martín, C and de Lima, VCC and Freitas, HC and Mas, L and Vargas, C and Carranza, H and Otero, J and Pérez, MA and González, L and Chirinos, L and Granados, ST and Rodriguez, J and Báez, R and Remolina Bonilla, YA and Núñez Cerrillo, G and Archila, P and Cuello, M and Karachaliou, N and Rosell, R and Arrieta, O and , }, title = {Characteristics and long-term outcomes of advanced pleural mesothelioma in Latin America (MeSO-CLICaP).}, journal = {Thoracic cancer}, volume = {10}, number = {3}, pages = {508-518}, 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.<br><br>METHODS: The MeSO-CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first-line chemotherapy among Latin American patients.<br><br>RESULTS: The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first-line platinum-based chemotherapy. The overall response rate to first-line chemotherapy was 40.4%, progression-free survival to first-line treatment was 5.7 months (95% CI 4.9-6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0-20.5), and multivariate analysis found that stage (P = 0.013), and pleurodesis (P = 0.048), were independent prognostic factors for first-line overall survival. The model to predict response to first-line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non-responders.<br><br>CONCLUSION: This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes.}, }
@article {pmid30706505, year = {2019}, author = {Sun, H}, title = {North-south gradient of mesothelioma and asbestos consumption-production in the United States-Progresses since the 1st asbestos partial ban in 1973.}, journal = {American journal of industrial medicine}, volume = {62}, number = {4}, pages = {337-346}, doi = {10.1002/ajim.22955}, pmid = {30706505}, issn = {1097-0274}, abstract = {BACKGROUND: Temporal trends and broad geographical distributions of asbestos use and the incidence of malignant mesothelioma (MM) in the US still need to be studied.<br><br>METHODS: Data on asbestos consumption and production between 1900 and 2015 and MM mortality and incidence rates between 1975 and 2015 in the US were examined. Spatial distributions of MM mortality and incidence rates and their association with climate zone were analyzed.<br><br>RESULTS: Decline of MM incidence and mortality rates in the US occurred about 20 years after the peak of asbestos consumption-production in 1973. There are apparent north-south (N-S) gradients in MM mortality and incidence rates in the US.<br><br>CONCLUSION: Recent decline of MM incidence and mortality rates in the US may be associated with reduced US asbestos consumption. N-S MM gradients between 1999 and 2015 were likely related to larger asbestos requirements in building materials in the northern states.}, }
@article {pmid30702033, year = {2019}, author = {Germine, M and Puffer, JH}, title = {Analytical transmission electron microscopy of amosite asbestos from South Africa.}, journal = {Archives of environmental &amp; occupational health}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/19338244.2018.1556201}, pmid = {30702033}, issn = {2154-4700}, 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}, support = {G0600475//Medical Research Council/United Kingdom ; }, abstract = {Introduction: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand.<br><br>Methods and analysis: MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months.<br><br>Ethics and dissemination: This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy.<br><br>Trial registration: NCT03412357.}, }
@article {pmid30686559, year = {2019}, author = {Neviere, Z and Berthet, P and Polycarpe, F and Dubos-Arvis, C and Dô, P and Gervais, R}, title = {[Malignant mesothelioma and constitutional BAP1 gene mutations].}, journal = {Revue des maladies respiratoires}, volume = {36}, number = {2}, pages = {241-248}, doi = {10.1016/j.rmr.2017.11.014}, pmid = {30686559}, issn = {1776-2588}, mesh = {Aftercare/methods ; Genetic Counseling ; Genetic Predisposition to Disease ; Genetic Testing ; Humans ; Lung Neoplasms/diagnosis/epidemiology/*genetics/*therapy ; Medical Oncology/methods ; Mesothelioma/diagnosis/epidemiology/*genetics/*therapy ; *Mutation ; Referral and Consultation ; Tumor Suppressor Proteins/*genetics/physiology ; Ubiquitin Thiolesterase/*genetics/physiology ; }, abstract = {Malignant mesothelioma is a rare tumour, usually the result of asbestos exposure. Several cases of familial aggregation have been reported and recently shown to be associated with constitutional mutations of the BAP1 gene. BAP1 is a deubiquitinating enzyme implicated in several different cellular mechanisms such as the repair or differentiation of DNA. About a half of malignant mesotheliomas present a somatic, bi-allelic inactivation of BAP1, demonstrated by nuclear extinction on histochemistry. Constitutional alterations of BAP1 are extremely rare. Present in the heterozygous state they are transmitted as an autosomal dominant. They are associated with a risk of developing other tumours such as uveal and cutaneous melanomas, benign melanocytic tumours (melanocytic BAP1-mutated atypical intradermal tumour or MBAITS) and clear cell renal carcinomas. The causal link between mesothelioma and germinal mutations of BAP1 has still not been clearly identified. At present there is, in France, no consensus on recommendations for the management of patients with these mutations. This article is a synthesis of the literature on the functions of the BAP1 gene, the tumour risks related to its alteration and the follow up of patients bearing a constitutional mutation.}, }
@article {pmid30685089, year = {2019}, author = {Abayasiriwardana, KS and Wood, MK and Prêle, CM and Birnie, KA and Robinson, BW and Laurent, GJ and McAnulty, RJ and Mutsaers, SE}, title = {Inhibition of collagen production delays malignant mesothelioma tumor growth in a murine model.}, journal = {Biochemical and biophysical research communications}, volume = {510}, number = {2}, pages = {198-204}, doi = {10.1016/j.bbrc.2019.01.057}, pmid = {30685089}, issn = {1090-2104}, support = {/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Collagen/antagonists &amp; inhibitors/*biosynthesis ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Female ; Humans ; Inflammation ; Lung Neoplasms/*metabolism/pathology ; Mesothelioma/*metabolism/pathology ; Mice ; Mice, Inbred CBA ; Pleural Neoplasms/*metabolism/pathology ; Thiazolidines/pharmacology ; Transforming Growth Factor beta/metabolism ; }, abstract = {Malignant mesothelioma is an aggressive fibrous tumor, predominantly of the pleura, with a very poor prognosis. Cell-matrix interactions are recognized important determinants of tumor growth and invasiveness but the role of the extracellular matrix in mesothelioma is unknown. Mesothelioma cells synthesize collagen as well as transforming growth factor-beta (TGF-β), a key regulator of collagen production. This study examined the effect of inhibiting collagen production on mesothelioma cell proliferation in vitro and tumor growth in vivo. Collagen production by mesothelioma cells was inhibited by incubating cells in vitro with the proline analogue thiaproline (thiazolidine-4-carboxylic acid) or by oral administration of thiaproline in a murine tumor model. Cell cytotoxicity was measured using neutral red uptake and lactate dehydrogenase assays. Proliferation was measured by tritiated thymidine incorporation, and inflammatory cell influx, proliferation, apoptosis and angiogenesis in tumors examined by immunohistochemical labelling. Tumor size was determined by tumor weight and collagen production was measured by HPLC. Thiaproline at non-toxic doses significantly reduced basal and TGF-β-induced collagen production by over 50% and cell proliferation by over 65%. In vivo thiaproline administration inhibited tumor growth at 10 days, decreasing the median tumor weight by 80%. The mean concentration of collagen was 50% lower in the thiaproline-treated tumors compared with the controls. There were no significant differences in vasculature or inflammatory cell infiltration but apoptosis was increased in thiaproline treated tumors at day 10. In conclusion, these observations strongly support a role for collagen in mesothelioma growth and establish the potential for inhibitors of collagen synthesis in mesothelioma treatment.}, }
@article {pmid30684047, year = {2019}, author = {Warby, A and Dhillon, HM and Kao, S and Vardy, JL}, title = {Managing malignant pleural mesothelioma: experience and perceptions of health care professionals caring for people with mesothelioma.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {27}, number = {9}, pages = {3509-3519}, doi = {10.1007/s00520-019-4648-0}, pmid = {30684047}, issn = {1433-7339}, support = {n/a//New South Wales Workers' Compensation Dust Disease Board/ ; }, mesh = {Adult ; Aged ; *Attitude of Health Personnel ; Caregivers/*psychology ; Communication ; Female ; Humans ; Lung Neoplasms/pathology/*therapy ; Male ; Medical Oncology ; Mesothelioma/pathology/*therapy ; Middle Aged ; Palliative Care/methods ; Pleural Neoplasms/pathology/*therapy ; Practice Patterns, Physicians'/*statistics &amp; numerical data ; Referral and Consultation ; Refusal to Treat/*statistics &amp; numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor prognosis and heavy symptom burden. Here, we investigate health professionals' attitudes to management and decision-making in people with MPM.<br><br>METHODS: Survey questions were based on previous interviews with health professionals, MPM patients, and caregivers. Surveys were sent to specialist doctors and nurses who treat MPM.<br><br>RESULTS: Surveys were completed by 107 doctors and 19 nurses from January-September 2014. Most doctors were respiratory physicians (50%) or medical oncologists (35%). Overall, 90% of doctors estimated > 10% of eligible MPM patients did not receive chemotherapy; 43% estimated the rate was > 20%. Doctors believed clinical barriers to chemotherapy were clinician nihilism (70%); non-referral to medical oncology (49%); and lack of specialists in rural/regional areas (44%). Nurses perceived barriers as follows: delayed diagnosis (74%); non-referral to medical oncology (63%); lack of clinician knowledge (58%). Patient-related barriers were negative perception of chemotherapy (83%) and belief survival benefit not worthwhile (63%). Doctors' preference in decision-making was for the patient to make the decision while strongly considering the doctor's opinion (33%); equally with the doctor (29%); and using knowledge gained (23%). Nurses described their roles as providing patient support (100%); information (95%); intermediary (74%); and link to palliative care (74%). Overall, 95% believed they enabled better resource allocation and provided patients with holistic care (95%); clearer communication (89%); more time (89%); additional information (89%); timely referrals (89%).<br><br>CONCLUSIONS: Caring for patients with MPM is challenging and complex. Health care professionals believe under-utilisation of chemotherapy is occurring, primarily due to clinician nihilism and lack of medical oncology referral.}, }
@article {pmid30663400, year = {2018}, author = {Wang, QQ and Zheng, GQ and Yang, DL and Liang, YF and Yin, WJ and Su, SS}, title = {Pretreatment Controlling Nutritional Status Score and Lactate Dehydrogenase as Predictive Markers of Survival in Patients with Malignant Peritoneal Mesothelioma.}, journal = {Nutrition and cancer}, volume = {70}, number = {8}, pages = {1264-1274}, doi = {10.1080/01635581.2018.1560481}, pmid = {30663400}, issn = {1532-7914}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/administration &amp; dosage/therapeutic use ; Asbestos/toxicity ; Biomarkers, Tumor/blood ; Female ; Humans ; L-Lactate Dehydrogenase/*blood ; Male ; Mesothelioma/drug therapy/*mortality/surgery ; Middle Aged ; Nutritional Status/*physiology ; Peritoneal Neoplasms/drug therapy/*mortality/surgery ; Prognosis ; ROC Curve ; }, abstract = {OBJECTIVE: To investigate the relationships between the Controlling Nutritional Status (CONUT) score and ascites fluid lactate dehydrogenase (LDH) level, and prognosis in patients with malignant peritoneal mesothelioma (MPeM).<br><br>METHODS: A total of 125 patients with MPeM were selected for the study using a pathological screening method. Once the diagnosis is established, before the treatment their clinical characteristics and nutritional evaluations were recorded including CONUT score and ascites LDH level. The associations between CONUT, ascites LDH, and other clinicopathological features including body mass index, asbestos exposure, pathological type, and treatment method were analyzed. Prognostic parameters predicting overall survival (OS) were analyzed by Cox regression.<br><br>RESULTS: High CONUT score, high ascites LDH level were positively associated with poor prognosis in patients with MPeM according to univariate analyses (P < 0.001, P < 0.001, respectively), and CONUT score and ascites LDH were independent predictors of a poor prognosis according to multivariate analysis. When the CONUT score is greater than 3 and the ascites LHD is greater than 474 IU/l, it indicates a poor prognosis.<br><br>CONCLUSIONS: CONUT score and ascites LDH are important factors influencing the prognosis of MPeM patients and should thus be considered in clinical applications.}, }
@article {pmid30659154, year = {2019}, author = {Villanova, T and Gesmundo, I and Audrito, V and Vitale, N and Silvagno, F and Musuraca, C and Righi, L and Libener, R and Riganti, C and Bironzo, P and Deaglio, S and Papotti, M and Cai, R and Sha, W and Ghigo, E and Schally, AV and Granata, R}, title = {Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {6}, pages = {2226-2231}, doi = {10.1073/pnas.1818865116}, pmid = {30659154}, issn = {1091-6490}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Disease Models, Animal ; Gene Expression ; Growth Hormone-Releasing Hormone/*antagonists &amp; inhibitors/genetics/metabolism ; Humans ; Lung Neoplasms/drug therapy/*metabolism/*pathology ; Mesothelioma/drug therapy/*metabolism/*pathology ; Mice ; Mitochondria/drug effects/metabolism ; Pleural Neoplasms/drug therapy/*metabolism/*pathology ; Receptors, Neuropeptide/genetics/metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with exposure to asbestos, with poor prognosis and no effective therapies. The strong inhibitory activities of growth hormone-releasing hormone (GHRH) antagonists have been demonstrated in different experimental human cancers, including lung cancer; however, their role in MPM remains unknown. We assessed the effects of the GHRH antagonists MIA-602 and MIA-690 in vitro in MPM cell lines and in primary MPM cells, and in vivo in MPM xenografts. GHRH, GHRH receptor, and its main splice variant SV1 were found in all the MPM cell types examined. In vitro, MIA-602 and MIA-690 reduced survival and proliferation in both MPM cell lines and primary cells and showed synergistic inhibitory activity with the chemotherapy drug pemetrexed. In MPM cells, GHRH antagonists also regulated activity and expression of apoptotic molecules, inhibited cell migration, and reduced the expression of matrix metalloproteinases. These effects were accompanied by impairment of mitochondrial activity and increased production of reactive oxygen species. In vivo, s.c. administration of MIA-602 and MIA-690 at the dose of 5 μg/d for 4 wk strongly inhibited the growth of MPM xenografts in mice, along with reduction of tumor insulin-like growth factor-I and vascular endothelial growth factor. Overall, these results suggest that treatment with GHRH antagonists, alone or in association with chemotherapy, may offer an approach for the treatment of MPM.}, }
@article {pmid30651596, year = {2019}, author = {Sépult, C and Bellefroid, M and Rocks, N and Donati, K and Gérard, C and Gilles, C and Ludwig, A and Duysinx, B and Noël, A and Cataldo, D}, title = {ADAM10 mediates malignant pleural mesothelioma invasiveness.}, journal = {Oncogene}, volume = {38}, number = {18}, pages = {3521-3534}, doi = {10.1038/s41388-018-0669-2}, pmid = {30651596}, issn = {1476-5594}, mesh = {ADAM10 Protein/*genetics ; Amyloid Precursor Protein Secretases/*genetics ; Animals ; Cadherins/genetics ; Cell Line, Tumor ; Cell Movement/*genetics ; Disease Progression ; Down-Regulation/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Lung Neoplasms/*genetics/*pathology ; Male ; Membrane Proteins/*genetics ; Mesothelioma/*genetics/*pathology ; Mice ; Mice, Inbred BALB C ; Pleural Neoplasms/*genetics/*pathology ; }, abstract = {Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options and treatment efficiency. Even if the latency period between asbestos exposure, the main risk factor, and mesothelioma development is very long, the local invasion of mesothelioma is very rapid leading to a mean survival of one year after diagnosis. ADAM10 (A Disintegrin And Metalloprotease) sheddase targets membrane-bound substrates and its overexpression is associated with progression in several cancers. However, nothing is known about ADAM10 implication in MPM. In this study, we demonstrated higher ADAM10 expression levels in human MPM as compared to control pleural samples and in human MPM cell line. This ADAM10 overexpression was also observed in murine MPM samples. Two mouse mesothelioma cell lines were used in this study including one primary cell line obtained by repeated asbestos fibre injections. We show, in vitro, that ADAM10 targeting through shRNA and pharmacological (GI254023X) approaches reduced drastically mesothelioma cell migration and invasion, as well as for human mesothelioma cells treated with siRNA targeting ADAM10. Moreover, ADAM10 downregulation in murine mesothelioma cells significantly impairs MPM progression in vivo after intrapleural cell injection. We also demonstrate that ADAM10 sheddase downregulation decreases the production of a soluble N-cadherin fragment through membrane N-cadherin, which stimulated mesothelioma cell migration. Taken together, we demonstrate that ADAM10 is overexpressed in MPM and takes part to MPM progression through the generation of N-cadherin fragment that stimulates mesothelioma cell migration. ADAM10 inhibition is worth considering as a therapeutic perspective in mesothelioma context.}, }
@article {pmid30648431, year = {2019}, author = {Harris, EJA and Musk, A and de Klerk, N and Reid, A and Franklin, P and Brims, FJH}, title = {Diagnosis of asbestos-related lung diseases.}, journal = {Expert review of respiratory medicine}, volume = {13}, number = {3}, pages = {241-249}, doi = {10.1080/17476348.2019.1568875}, pmid = {30648431}, issn = {1747-6356}, 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}, mesh = {Computational Biology/methods ; Female ; Health Records, Personal ; Humans ; *Machine Learning ; Male ; Mesothelioma/*diagnosis ; Regression Analysis ; }, abstract = {BACKGROUND: Mesothelioma is a lung cancer that kills thousands of people worldwide annually, especially those with exposure to asbestos. Diagnosis of mesothelioma in patients often requires time-consuming imaging techniques and biopsies. Machine learning can provide for a more effective, cheaper, and faster patient diagnosis and feature selection from clinical data in patient records.<br><br>METHODS AND FINDINGS: We analyzed a dataset of health records of 324 patients having mesothelioma symptoms from Turkey. The patients had prior asbestos exposure and displayed symptoms consistent with mesothelioma. We compared probabilistic neural network, perceptron-based neural network, random forest, one rule, and decision tree classifiers to predict diagnosis of the patient records. We measured classifiers' performance through standard confusion matrix scores such as Matthews correlation coefficient (MCC). Random forest outperformed all models tried, obtaining MCC = +0.37 on the complete imbalanced dataset and MCC = +0.64 on the under-sampled balanced dataset. We then employed random forest feature selection to identify the two most relevant dataset traits associated with mesothelioma: lung side and platelet count. These two risk factors resulted so predictive, that decision tree focusing on them achieved the second top accuracy on the complete dataset diagnosis prediction (MCC = +0.28), outperforming all other methods and even decision tree itself applied to all features.<br><br>CONCLUSIONS: Our results show that machine learning can predict diagnoses of patients having mesothelioma symptoms with high accuracy, sensitivity, and specificity, in few minutes. Additionally, random forest can efficiently select the most important features of this clinical dataset (lung side and platelet count) in few seconds. The importance of pleural plaques in lung sides and blood platelets in mesothelioma diagnosis indicates that physicians should focus on these two features when reading records of patients with mesothelioma symptoms. Moreover, doctors can exploit our machinery to predict patient diagnosis when only lung side and platelet data are available.}, }
@article {pmid30623323, year = {2019}, author = {Taghizadeh, F and Jafari, AJ and Gholami, M and Kermani, M and Arfaeinia, H and Mohammadi, S and Dowlati, M and Shahsavani, A}, title = {Monitoring of airborne asbestos fibers in an urban ambient air of Shahryar City, Iran: levels, spatial distribution, seasonal variations, and health risk assessment.}, journal = {Environmental science and pollution research international}, volume = {26}, number = {7}, pages = {6450-6459}, doi = {10.1007/s11356-018-4029-0}, pmid = {30623323}, issn = {1614-7499}, support = {31563//Environmental and occupational health center/ ; }, mesh = {Air Pollutants/*analysis ; Air Pollution/statistics &amp; numerical data ; Asbestos/*analysis ; Cities ; Environmental Exposure/*statistics &amp; numerical data ; Environmental Monitoring ; Humans ; Iran/epidemiology ; Lung Neoplasms/epidemiology ; Mesothelioma/epidemiology ; Microscopy, Phase-Contrast ; Risk Assessment ; Seasons ; }, abstract = {Asbestos, as with other pollutants in the air, has adverse effects on the health of human beings and animals. Today, the relationship between presence of asbestos fibers in the air breathed by humans and developing serious diseases such as lung cancer (asbestosis) and mesothelioma has been proven. This study was designed and conducted within the time period of August 2017 and June 2018 to determine the concentration of asbestos fiber in the ambient air of Shahryar City and to evaluate their health effects for the general population of the city. For this purpose, samples were taken from four points, and overall 32 air samples were taken along the year. The samples were then analyzed by the phase contrast microscopy (PCM) method. Also, to investigate the type of asbestos and for more accurate counting of fibers, SEM analysis was utilized. Finally, based on the EPA IRIS method, the health effects resulting from asbestos risks were also evaluated. The results of this study indicated that the mean annual concentration of asbestos fiber in the ambient air of Shahryar City was obtained as 0.0019 f/ml PCM and 0.0072 f/ml SEM. Furthermore, the most polluted point was S1 point (0.0119 -0.0026 f/ml, PCM), while the lowest concentration was related to S4 point (0.001 f/ml PCM-0.0021 f/ml SEM). The mean annual risk resulting from airborne asbestos fiber in the ambient air of Shahryar City for all samples was obtained as 1.72 × 10-6 to 2.2 × 10-4, which was higher than the recommended risk range in some points.}, }
@article {pmid30622932, year = {2018}, author = {Lo Russo, G and Tessari, A and Capece, M and Galli, G and de Braud, F and Garassino, MC and Palmieri, D}, title = {MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {650}, 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 = {110}, number = {3}, pages = {1076-1084}, doi = {10.1111/cas.13930}, pmid = {30618090}, issn = {1349-7006}, support = {15H04774//Japan Society for the Promotion of Science KAKENHI/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Crocidolite/adverse effects ; Asbestos, Serpentine/adverse effects ; Cohort Studies ; Humans ; Japan/epidemiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; Occupational Diseases/*epidemiology/*etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/epidemiology/etiology ; }, abstract = {Occupational asbestos exposure occurs in many workplaces and is a well-known cause of mesothelioma and lung cancer. However, the association between nonoccupational asbestos exposure and those diseases is not clearly described. The aim of this study was to investigate cause-specific mortality among the residents of Amagasaki, a city in Japan with many asbestos factories, and evaluate the potential excess mortality due to established and suspected asbestos-related diseases. The study population consisted of 143 929 residents in Amagasaki City before 1975 until 2002, aged 40 years or older on January 1, 2002. Follow-up was carried out from 2002 to 2015. Standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated by sex, using the mortality rate of the Japanese population as reference. A total of 38 546 deaths (including 303 from mesothelioma and 2683 from lung cancer) were observed. The SMRs in the long-term residents' cohort were as follows: death due to all causes, 1.12 (95% CI, 1.10-1.13) in men and 1.07 (95% CI, 1.06-1.09) in women; lung cancer, 1.28 (95% CI, 1.23-1.34) in men and 1.23 (95% CI, 1.14-1.32) in women; and mesothelioma, 6.75 (95% CI, 5.83-7.78) in men and 14.99 (95% CI, 12.34-18.06) in women. These SMRs were significantly higher than expected. The increased SMR of mesothelioma suggests the impact of occupational asbestos exposure among men and nonoccupational asbestos exposure among women in the long-term residents' cohort. In addition, the high level of excess mortality from mesothelioma has persisted, despite the mixture of crocidolite and chrysotile no longer being used for three or four decades.}, }
@article {pmid30609805, year = {2019}, author = {Turini, S and Bergandi, L and Gazzano, E and Prato, M and Aldieri, E}, title = {Epithelial to Mesenchymal Transition in Human Mesothelial Cells Exposed to Asbestos Fibers: Role of TGF-β as Mediator of Malignant Mesothelioma Development or Metastasis via EMT Event.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, doi = {10.3390/ijms20010150}, pmid = {30609805}, issn = {1422-0067}, mesh = {Antibodies/immunology ; Asbestos, Serpentine/*toxicity ; Cadherins/genetics/metabolism ; Cell Line ; Down-Regulation/drug effects ; Epithelial Cells/cytology/drug effects/metabolism ; Epithelial-Mesenchymal Transition/*drug effects ; Fibronectins/genetics/metabolism ; Humans ; Lung Neoplasms/chemically induced/pathology ; Matrix Metalloproteinase 2/genetics/metabolism ; Mesothelioma/chemically induced/pathology ; Smad Proteins/genetics/metabolism ; Snail Family Transcription Factors/genetics/metabolism ; Transforming Growth Factor beta/immunology/*metabolism ; Up-Regulation/drug effects ; Vimentin/genetics/metabolism ; Zinc Finger E-box-Binding Homeobox 1/genetics/metabolism ; beta Catenin/genetics/metabolism ; }, abstract = {Asbestos exposure increases the risk of asbestosis and malignant mesothelioma (MM). Both fibrosis and cancer have been correlated with the Epithelial to Mesenchymal Transition (EMT)-an event involved in fibrotic development and cancer progression. During EMT, epithelial cells acquire a mesenchymal phenotype by modulating some proteins. Different factors can induce EMT, but Transforming Growth Factor β (TGF-β) plays a crucial role in promoting EMT. In this work, we verified if EMT could be associated with MM development. We explored EMT in human mesothelial cells (MeT-5A) exposed to chrysotile asbestos: we demonstrated that asbestos induces EMT in MeT-5A cells by downregulating epithelial markers E-cadherin, β-catenin, and occludin, and contemporarily, by upregulating mesenchymal markers fibronectin, α-SMA, and vimentin, thus promoting EMT. In these cells, this mechanism is mediated by increased TGF-β secretion, which in turn downregulates E-cadherin and increases fibronectin. These events are reverted in the presence of TGF-β antibody, via a Small Mother Against Decapentaplegic (SMAD)-dependent pathway and its downstream effectors, such as Zinc finger protein SNAI1 (SNAIL-1), Twist-related protein (Twist), and Zinc Finger E-Box Binding Homeobox 1 (ZEB-1), which downregulate the E-cadherin gene. Since SNAIL-1, Twist, and ZEB-1 have been shown to be overexpressed in MM, these genes could be considered possible predictive or diagnostic markers of MM development.}, }
@article {pmid30603603, year = {2019}, author = {Shehata, M and Zaid, F and Ottaviano, P and Shweihat, Y and Munn, N}, title = {Case report: Steroid responsive mesothelioma-related pleural effusion.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {131-135}, 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}, mesh = {*Cancer Vaccines ; Humans ; Immunologic Factors/*therapeutic use ; Immunotherapy/*methods ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Precision Medicine/methods ; }, abstract = {INTRODUCTION: Immunotherapy has long been considered a potential therapy for malignant mesothelioma and is currently being pursued as such. Some of the early phase clinical trials involving immunomodulators have demonstrated encouraging results and numerous clinical trials are underway to further investigate this treatment approach in various treatment settings and larger patient cohorts. Areas covered: This review summarizes the current and emerging clinical evidence for checkpoint blockade and other immunotherapeutic strategies in mesothelioma. The mesothelioma tumor immune microenvironment and mutational landscape are also discussed, including their impact on treatment strategies. We also provide an evaluation of the current evidence for neoantigen targeted personalized immunotherapy. Expert opinion: Immune checkpoint inhibitors work by unleashing the host immune response against probable neoantigens. Despite impressive activity in a small subset of patients and the potential for prolonged responses, most patients experience treatment failure. Neoantigen vaccines provide a potential complementary therapeutic strategy by increasing the immunogenic antigen load, which can lead to an increased tumor specific immune response. Further research is needed explore this treatment option in mesothelioma and technological advances are required to translate this concept into clinical practice.}, }
@article {pmid30594459, year = {2019}, author = {McGehee, E and Gerber, DE and Reisch, J and Dowell, JE}, title = {Treatment and Outcomes of Primary Pericardial Mesothelioma: A Contemporary Review of 103 Published Cases.}, journal = {Clinical lung cancer}, volume = {20}, number = {2}, pages = {e152-e157}, doi = {10.1016/j.cllc.2018.11.008}, pmid = {30594459}, issn = {1938-0690}, support = {K24 CA201543/CA/NCI NIH HHS/United States ; UL1 TR001105/TR/NCATS NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Asbestos/adverse effects ; Environmental Exposure/adverse effects ; Heart Neoplasms/mortality/*therapy ; Humans ; Neoplasms, Mesothelial/mortality/*therapy ; Pemetrexed/*therapeutic use ; Pericardium ; Platinum/*therapeutic use ; Risk Factors ; Survival Analysis ; Treatment Outcome ; }, abstract = {Primary pericardial mesothelioma (PPM) is a rare cancer for which there is no consensus on treatment. We evaluated and summarized a large contemporary population of published PPM cases to characterize risk factors, treatment patterns, and clinical outcomes. Using Ovid and PubMed, literature published from 2000 through 2016 was searched using the terms &quot;primary pericardial mesothelioma,&quot; &quot;pericardial mesothelioma,&quot; and &quot;malignant pericardial mesothelioma.&quot; We identified 6 case series and 84 case reports for a total of 103 PPM cases published from 2000 through 2016. The median age at diagnosis was 55 years, and the median overall survival was 6 months. In univariate analyses of clinical characteristics including gender, asbestos exposure, tobacco use, prior radiation exposure, histologic subtype, and metastasis and/or mediastinal spread, only the presence of metastasis and/or mediastinal spread was a significant predictor of decreased survival (P = .015). Surgery did not provide a statistically significant survival benefit (P = .12). A survival benefit was noted in those who received chemotherapy (median survival, 13 months vs. 0.5 months, P = .002), specifically chemotherapy with a platinum agent with or without pemetrexed. In multivariate analysis, only the receipt of chemotherapy was associated with improved survival. PPM remains a rare and poorly understood malignancy with unclear etiology and a poor prognosis. In this retrospective systematic review, a survival benefit was seen in patients who received chemotherapy.}, }
@article {pmid30594195, year = {2018}, author = {Merlo, DF and Bruzzone, M and Bruzzi, P and Garrone, E and Puntoni, R and Maiorana, L and Ceppi, M}, title = {Mortality among workers exposed to asbestos at the shipyard of Genoa, Italy: a 55 years follow-up.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {94}, 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.<br><br>METHODS: We conducted a historical prospective cohort mortality study aimed at estimating mortality from specific causes, the temporal changes of pleural and lung cancer mortality, and the attributable fraction (AF) of lung cancer deaths following asbestos exposure. The study included 3984 shipyard workers employed at the shipyard of Genoa, Italy, between 1960 and 1981 and followed up to December 2014. Standardized Mortality Ratios (SMR) and their 95% confidence intervals (95%CI) were computed.<br><br>RESULTS: Overall deaths recorded were 3331 (83.6%). Excess mortality was observed for all cancers (SMR = 127, 95%CI:120-134), pleural mesothelioma (575, 469-697), cancers of the larynx (183, 134-244) and of the lung (154, 139-170), and for respiratory tract diseases (127, 114-141), including asbestosis (2277, 1525-3270). Ninety out of 399 deaths (22.6%) from lung cancer were attributed to asbestos exposure. The estimated lung cancer AF was 49.3% in workers with the highest SMR for pleural cancer. Median latency times for pleural and lung cancer were 42.8 years (minimum latency: 9.3 years) and 38.7 years (minimum latency: 6 years). The peak of mesothelioma incidence, expected in Italy in the period 2015-2024, was confirmed.<br><br>CONCLUSIONS: The long follow-up period of our study allowed the detection of a substantial disease burden following asbestos exposure. These findings support the urgent need for the prevention of asbestos related diseases through the implementation of asbestos ban worldwide, including those countries where asbestos is still mined, manufactured and used.}, }
@article {pmid30567579, year = {2018}, author = {Xu, R and Barg, FK and Emmett, EA and Wiebe, DJ and Hwang, WT}, title = {Association between mesothelioma and non-occupational asbestos exposure: systematic review and meta-analysis.}, journal = {Environmental health : a global access science source}, volume = {17}, number = {1}, pages = {90}, 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.<br><br>OBJECTIVE: To estimate the association between mesothelioma and non-occupational asbestos exposure, and evaluate control recruitment and exposure measurement methods.<br><br>METHODS: A systematic literature review was conducted to identify case-control (CC) and cohort studies that examined the association between mesothelioma and non-occupational exposure to asbestos, including neighborhood, domestic, and household exposure. Meta-analysis was performed to estimate a summary relative risk estimate (SRRE) and 95% confidence interval using random-effects models. Subgroup analyses were also conducted by exposure type, gender, region, and fiber type.<br><br>RESULTS: Twenty CC and 7 cohort studies were selected. Controls in CC studies were selected from the general population (55%), hospital records (18%), cancer registry (23%) and a combination of population and hospital records (5%). Multiple methods were used to measure neighborhood exposure (e.g., linear distance and direction of residence from an asbestos factory), domestic (e.g., whether living with an asbestos worker) and household exposure (e.g., whether involved in asbestos-containing home improvement projects). Primary meta-analyses suggested a SRRE of mesothelioma of 5.33 (95%CI: 2.53, 11.23) from neighborhood exposure, 4.31 (95%CI, 2.58, 7.20) from domestic exposure, and 2.41 (95%CI, 1.30, 4.48) from household exposure with large I2 statistics ranging from 83-99%.<br><br>CONCLUSIONS: Non-occupational asbestos exposure is significantly associated with an elevated risk of mesothelioma. Funnel plots indicated a potential of publication bias. Some SRREs should be interpreted with cautions because of high between-studies heterogeneity.}, }
@article {pmid30563645, year = {2018}, author = {Rogers, AJ}, title = {Exposures estimates of the Wittenoom mining workforce and town residents - Implications associated with risk estimation for persons exposed to asbestiform riebeckite.}, journal = {Toxicology and applied pharmacology}, volume = {361}, number = {}, pages = {168-170}, doi = {10.1016/j.taap.2018.06.032}, pmid = {30563645}, issn = {1096-0333}, mesh = {Adult ; Asbestos/analysis ; Asbestos, Crocidolite/analysis/*toxicity ; Australia/epidemiology ; Child ; Dust/analysis ; Environmental Exposure/*statistics &amp; numerical data ; Female ; Humans ; Industry ; Inhalation Exposure/*analysis ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; *Mining ; Occupational Exposure/*statistics &amp; numerical data ; Risk Assessment ; Workforce ; }, abstract = {The mining of crocidolite at Wittenoom from 1943 to 1966 is infamous due to the adverse health outcomes in the mining and milling workforce and the non-mining residents and families. Proportional latency risk analysis provided estimates that 6% of the mine workforce along with 1.9% of women and 1.1% of children residents who were environmentally exposed, have or will die from mesothelioma. The absence of environmental exposure data relevant to the period restricts the extrapolation of these historical risk outcomes being applied to the low level exposures from natural contaminant crocidolite and other amphibole fibres experienced in contemporary mining practices in the Pilbara region.}, }
@article {pmid30561515, year = {2019}, author = {Oddone, E and Terracini, B and Mirabelli, D and Mensi, C and Consonni, D and Barone-Adesi, F}, title = {Comment on: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {488-489}, doi = {10.1093/carcin/bgy179}, pmid = {30561515}, issn = {1460-2180}, }
@article {pmid30558734, year = {2019}, author = {Kai, Y and Tsutani, Y and Ito, M and Mimura, T and Miyata, Y and Okada, M}, title = {Metachronous Lung Cancer After Pleurectomy/Decortication.}, journal = {The Annals of thoracic surgery}, volume = {107}, number = {1}, pages = {e1-e3}, doi = {10.1016/j.athoracsur.2018.05.087}, pmid = {30558734}, issn = {1552-6259}, abstract = {Pleurectomy/decortication is a surgical procedure for malignant pleural mesothelioma (MPM) and has been proposed as an alternative to extrapleural pneumonectomy. We report a second primary lung cancer developing after pleurectomy/decortication for MPM. A 59-year-old man was diagnosed with MPM on the right side and underwent pleurectomy/decortication. Follow-up computed tomography detected a nodule in the right upper lobe that was diagnosed as adenocarcinoma by wedge resection. Lung cancer and MPM are associated with asbestos exposure. However, predicting lung cancer after treatment for MPM is difficult. Careful follow-up of the spared lung is necessary for detecting second primary lung cancer or MPM recurrence.}, }
@article {pmid30557225, year = {2019}, author = {Schnatter, AR and Wojcik, NC and Jorgensen, G}, title = {Mortality Update of a Cohort of Canadian Petroleum Workers.}, journal = {Journal of occupational and environmental medicine}, volume = {61}, number = {3}, pages = {225-238}, 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.<br><br>METHODS: Standardized mortality ratios were generated for all-cause and specific cause mortality.<br><br>RESULTS: All cause and all cancer mortality were favorable compared with the general Canadian population. Cancers of previous interest were largely consistent with expectation. There is a continuing excess of mesothelioma, which is of similar magnitude as the previous update, although based on larger numbers. This excess is mostly attributable to men who died in their 50s and 60s and who worked in the refining sector.<br><br>CONCLUSION: Most causes of death show mortality rates lower than the Canadian general population. Given the excess of mesothelioma observed, this study supports ongoing vigilance in asbestos exposure control programs, as refineries continue to remove asbestos from their facilities.}, }
@article {pmid30545133, year = {2018}, author = {Wörthmüller, J and Oberson, A and Salicio, V and Blum, W and Schwaller, B}, title = {Calretinin Functions in Malignant Mesothelioma Cells Cannot Be Replaced by the Closely Related Ca2+-Binding Proteins Calbindin-D28k and Parvalbumin.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, doi = {10.3390/ijms19124015}, pmid = {30545133}, issn = {1422-0067}, support = {130680, 139226, 147697/1//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {Calbindin 1/*metabolism ; Calbindin 2/*metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Clone Cells ; Down-Regulation ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Focal Adhesions/metabolism ; Green Fluorescent Proteins/metabolism ; Humans ; Lentivirus/metabolism ; Lung Neoplasms/*metabolism ; Mesothelioma/*metabolism ; Parvalbumins/*metabolism ; Phenotype ; }, abstract = {Calretinin (CR; CALB2) belonging to the family of EF-hand Ca2+-binding proteins (CaBP) is widely used as a positive marker for the identification of human malignant mesothelioma (MM) and functionally was suggested to play a critical role during carcinogenesis of this highly aggressive asbestos-associated neoplasm. Increasing evidence suggests that CR not only acts as a prototypical Ca2+ buffer protein, i.e., limiting the amplitude of Ca2+ signals but also as a Ca2+ sensor. No studies have yet investigated whether other closely related CaBPs might serve as substitutes for CR's functions(s) in MM cells. Genetically modified MM cell lines with medium (MSTO-211H and ZL5) or low (SPC111) endogenous CR expression levels were generated that overexpress either CR's closest homologue calbindin-D28k (CB) or parvalbumin (PV), the latter considered as a &quot;pure&quot; Ca2+ buffer protein. After lentiviral shCALB2-mediated CR downregulation, in both MSTO-211H and ZL5 cells expressing CB or PV, the CR deficiency-mediated increase in cell death was not prevented by CB or PV. With respect to proliferation and cell morphology of SPC111 cells, CB was able to substitute for CR, but not for CR's other functions to promote cell migration or invasion. In conclusion, CR has a likely unique role in MM that cannot be substituted by &quot;similar&quot; CaBPs.}, }
@article {pmid30534997, year = {2019}, author = {Boffetta, P and Righi, L and Ciocan, C and Pelucchi, C and La Vecchia, C and Romano, C and Papotti, M and Pira, E}, title = {Reply to letters to the editor by Brentisci et al. and Consonni and Mensi.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {2}, pages = {341}, doi = {10.1093/annonc/mdy523}, pmid = {30534997}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30533375, year = {2019}, author = {Yamazoe, M and Tomioka, H and Kamada, T and Kaneko, M and Katsuyama, E}, title = {Simultaneous presence of lung adenocarcinoma and malignant pleural mesothelioma: A case report.}, journal = {Respiratory medicine case reports}, volume = {26}, number = {}, pages = {45-49}, pmid = {30533375}, issn = {2213-0071}, abstract = {The co-presence of malignant pleural mesothelioma (MPM) and lung cancer is rare. We report a 70-year-old male with exposure to asbestos. Chest computed tomography revealed a right mediastinal mass combined with an enlarged ipsilateral lymph node and left pleural effusion. Transbronchial lung biopsy revealed lung adenocarcinoma. Thoracoscopic examination revealed multiple left pleural nodules, leading to the diagnosis of MPM. Despite aggressive anticancer drug therapy, he expired due to disease progression 2.5 years after diagnosis. Autopsy confirmed an epithelioid MPM in the left pleura. MPM comorbidity in patients diagnosed with lung cancer should be considered, especially in those exposed to asbestos.}, }
@article {pmid30530573, year = {2018}, author = {Lee, LJ and Lin, CK and Pan, CH and Cheng, Y and Chang, YY and Liou, SH and Wang, JD}, title = {Clustering of malignant pleural mesothelioma in asbestos factories: a subgroup analysis in a 29-year follow-up study to identify high-risk industries in Taiwan.}, journal = {BMJ open}, volume = {8}, number = {12}, pages = {e021063}, doi = {10.1136/bmjopen-2017-021063}, pmid = {30530573}, issn = {2044-6055}, mesh = {Asbestos/*adverse effects ; Cluster Analysis ; Cohort Studies ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Manufacturing and Industrial Facilities/*statistics &amp; numerical data ; Mesothelioma/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology ; Retrospective Studies ; Risk ; Taiwan ; }, abstract = {OBJECTIVE: Exposure to asbestos is the major cause for malignant pleural mesothelioma (MPM), but the causal link of individual cases is difficult to establish for lack of exposure information and long disease latency.<br><br>METHODS: We established a retrospective cohort of workers employed in asbestos industries during the period of 1950-1989 and the occurrence of MPM during the period of 1980-2009 was examined with the Taiwan Cancer Registry. Estimated rate ratios (eRRs) were computed for each factory where any case of MPM was diagnosed by assuming Poisson distribution with a minimal latency of 20 years.<br><br>RESULTS: A total of 18 MPM (17 males, 1 female) in eight factories were found. The incidence rate of MPM for the eight factories was 18.0 per million, ranging from 6.2 per million (military factory) to 268.2 per million (asbestos cement). We observed significantly increased risks for MPM in asbestos cement, thermal insulation and shipbuilding industries, with eRR (genders combined) of 113.6, 87.5 and 15.8, respectively. The sensitivity analyses considering latency showed similar findings in latency ≥30 years, and the shipbuilding industry presented a significant eRR given a latency ≥40 years. The gender-specific eRR showed similar results in men, but high eRR of 729.6 was observed in an asbestos cement factory where a female MPM was diagnosed.<br><br>CONCLUSIONS: This nationwide study in Taiwan comprehensively shows that different asbestos manufacturing processes, including asbestos cement, thermal insulation and shipbuilding industries, were at significantly increased risks for MPM. We recommend to establish a medical screening programme for workers previously exposed to asbestos to identify MPM and other asbestos-related diseases at an earlier stage.}, }
@article {pmid30527173, year = {2018}, author = {Serio, G and Vimercati, L and Pennella, A and Gentile, M and Cavone, D and Buonadonna, AL and Scattone, A and Fortarezza, F and De Palma, A and Marzullo, A}, title = {Genomic changes of chromosomes 8p23.1 and 1q21: Novel mutations in malignant mesothelioma.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {126}, number = {}, pages = {106-111}, doi = {10.1016/j.lungcan.2018.10.012}, pmid = {30527173}, issn = {1872-8332}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1/*genetics ; Chromosomes, Human, Pair 8/*genetics ; Comparative Genomic Hybridization ; Female ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; *Mutation ; Ubiquitin-Conjugating Enzymes/genetics ; }, abstract = {INTRODUCTION: Malignant mesothelioma is an aggressive malignancy of the thoracic cavity caused by prior asbestos exposure. In the peritoneum the mesothelioma is an extremely rare condition. In the present preliminary study, high-resolution array-comparative genomic hybridization (a-CGH) was performed to identify genetic imbalances in a series of malignant peritoneal mesothelioma cases.<br><br>MATERIALS AND METHODS: Between 1990 and 2008, among the cases recorded in the Apulia Mesothelioma Register, we found 22 peritoneal mesothelioma cases. CGH-array was performed on samples from all patients.<br><br>RESULTS: The CGH-array analysis revealed multiple chromosomal imbalances. Interestingly, deletion at 8p23.1 was observed in 12 cases. Furthermore, another novel deletion at 1q21 was present in 11. Often, 1q21 and 8p23.1 losses were present in the same patient (7 cases). Losses of BAP1 and CDKN2A loci were not detected.<br><br>DISCUSSION: The region at 8p23.1 contains the beta-defensin gene cluster (DEF) and 1q21 contains ubiquitin conjugating enzyme E2 (UBE2Q1). We hypotesized that the loss of function of ubiquitination, as well as of the defensins, could play an important role in the initial development and subsequent progression of mesothelioma.}, }
@article {pmid30518402, year = {2018}, author = {Chee, J and Watson, MW and Chopra, A and Nguyen, B and Cook, AM and Creaney, J and Lesterhuis, WJ and Robinson, BW and Lee, YCG and Nowak, AK and Lake, RA and McDonnell, AM}, title = {Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {864}, pmid = {30518402}, issn = {1756-0500}, support = {CA150787//U.S. Department of Defense/ ; }, mesh = {Aged ; Aged, 80 and over ; Humans ; Lung Neoplasms/blood/*immunology ; Mesothelioma/blood/*immunology ; Middle Aged ; Pleural Effusion/blood/*immunology ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Cell Surface/*metabolism ; T-Lymphocytes/*immunology ; }, abstract = {OBJECTIVE: Pleural effusion (PE) is a common feature of malignant pleural mesothelioma. These effusions typically contain lymphocytes and malignant cells. We postulated that the PE would be a source of lymphocytes for analysis of tumor immune milieu. The aim of this study was to compare the phenotype and T cell receptor usage of pleural effusion T cells with paired concurrently drawn peripheral blood lymphocytes. We used multi-parameter flow cytometry and high-throughput T cell receptor sequencing to analyse peripheral blood and pleural effusion mononuclear cells.<br><br>RESULTS: Both CD8+ and CD4+ T cells from effusion showed increased expression of T cell inhibitory receptors PD-1, LAG-3 and Tim-3 compared to blood. Comprehensive T cell receptor sequencing on one of the patients showed a discordant distribution of clonotypes in the antigen-experienced (PD-1+) compartment between effusion and blood, suggesting an enrichment of antigen specific clonotypes in the effusion, with potential as an immunological response biomarker.}, }
@article {pmid30506035, year = {2018}, author = {Okita, R and Nojima, Y and Saisho, S and Shimizu, K and Shirai, R and Kanomata, N and Oka, M and Nakata, M}, title = {Deciduoid type malignant pleural mesothelioma: a case report.}, journal = {AME case reports}, volume = {2}, number = {}, pages = {43}, pmid = {30506035}, issn = {2523-1995}, abstract = {Here, we report a patient with deciduoid type malignant pleural mesothelioma (MPM), which rapidly progressed. A 55-year-old man who might have been exposed to asbestos a few decades ago had severe back pain. The chest X-ray scanning and computed tomography (CT) revealed pleural thickness on his right thoracic space, without the presence of a lung mass. A pleural biopsy was performed and the patient was histologically diagnosed with deciduoid type MPM. Although he received two cycles of chemotherapy, his disease rapidly progressed and he died within two months of the diagnosis of deciduoid type MPM.}, }
@article {pmid30501113, year = {2018}, author = {Izquierdo-Sánchez, V and Muñiz-Hernández, S and Vázquez-Becerra, H and Pacheco-Yepez, J and Romero-Piña, ME and Arrieta, O and Medina, LA}, title = {Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft.}, journal = {Molecules (Basel, Switzerland)}, volume = {23}, number = {12}, pages = {}, 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/ ; }, mesh = {Animals ; Antibodies, Monoclonal, Humanized/*pharmacokinetics ; Cell Line, Tumor ; Fluorodeoxyglucose F18/chemistry ; Gallium Radioisotopes/*pharmacokinetics ; Humans ; Imaging, Three-Dimensional ; Liver/metabolism ; Lung Neoplasms/diagnostic imaging/*metabolism ; Male ; Mesothelioma/diagnostic imaging/*metabolism ; Mice, Nude ; Pleural Neoplasms/diagnostic imaging/*metabolism ; Positron Emission Tomography Computed Tomography ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon ; *Xenograft Model Antitumor Assays ; }, abstract = {Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.}, }
@article {pmid30513236, year = {2018}, author = {Till, JE and Beck, HL and Boice, JD and Mohler, HJ and Mumma, MT and Aanenson, JW and Grogan, HA}, title = {Asbestos Exposure and Mesothelioma Mortality among Atomic Veterans.}, journal = {International journal of radiation biology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/09553002.2018.1551641}, pmid = {30513236}, issn = {1362-3095}, abstract = {BACKGROUND: During the Cold War the United States (U.S.) conducted 230 above-ground atmospheric nuclear weapons tests between 1945 and 1962 at the Nevada Test Site and the Pacific Proving Grounds. These tests involved over 250,000 military personnel. Asbestos was used on the naval vessels for insulation in the boiler room, engine room, and other areas. This is the first quantitative assessment of asbestos-related mesothelioma, including cancers of the pleura and peritoneum, among military personnel who participated in above-ground nuclear weapons testing.<br><br>METHODS: Approximately 114,000 atomic veterans were selected for an epidemiological study because they were in one of eight series of weapons tests that were associated with somewhat higher personnel exposures than the other tests and because they have been previously studied. We were able to categorize specific jobs into potential for asbestos exposure based on a detailed database of the military activities of the atomic veterans, developed using historical records provided by the Defense Threat Reduction Agency. Standardized mortality ratios (SMR) were calculated by service, rank(officer/enlisted) and ratings (occupation code and work location aboard ship) after 65 years of follow-up… Results: Mesothelioma deaths were significantly increased overall (SMR 1.56; 95% CI 1.32-1.82; n= 153). This increase was seen only among those serving in the Pacific Proving Ground (SMR 1.97; 95% CI 1.65-2.34; n= 134), enlisted men (SMR 1.81; 95% CI 1.53-2.13; n= 145) and the 70,309 navy personnel (SMR 2.15; 95% CI 1.80-2.56; n= 130). No increased mortality rates were seen among the other services: army (SMR 0.45), air force (SMR 0.85) or marines (SMR 0.75). Job categories with the highest potential for asbestos exposure (machinist's mates, boiler technicians, water tender, pipe fitters, and fireman) had an of SMR 6.47. Job categories with lower potential (SMR =1.35) or no potential (SMR =1.28) for asbestos exposure had non-significantly elevated mesothelioma mortality.<br><br>CONCLUSIONS: Although jobs with high potential for exposure to asbestos products were held by only 20% of the enlisted naval population, sailors with these jobs (machinist's mate, pipe fitter, boiler technician, water tender and fireman) experienced 55% of mesothelioma deaths. The significantly higher mortality rate overall was explained by asbestos exposure among enlisted naval personnel in this low-dose radiation exposed cohort.}, }
@article {pmid30500290, year = {2019}, author = {Regragui, M and Guebessi, NB}, title = {Primary Malignant Deciduoid Mesothelioma: A Challenging Diagnosis.}, journal = {Archives of pathology &amp; laboratory medicine}, volume = {143}, number = {4}, pages = {531-533}, doi = {10.5858/arpa.2017-0461-RS}, pmid = {30500290}, issn = {1543-2165}, abstract = {Primary malignant deciduoid mesothelioma is a rare subtype of epithelioid mesothelioma that was first described in the peritoneum in young women without a history of asbestos exposure. It was thought to be a distinct clinicopathologic entity with ominous prognosis; recent studies have better characterized this entity. On morphology, primary malignant deciduoid mesothelioma is characterized by cytomorphologic features resembling decidualized tissue. Pleomorphism is variable. The immunoprofile is similar to other epithelioid mesotheliomas. The prognosis is the same as other epithelioid mesotheliomas and seems to depend on histological grade.}, }
@article {pmid30489434, year = {2019}, author = {Dournes, G and Dubois, A and Benlala, I and Lacourt, A and Paris, C and Gislard, A and Clin, B and Pairon, JC and Baldacci, F and Laurent, F}, title = {3-Dimensional Quantification of Composite Pleural Plaque Volume in Patients Exposed to Asbestos Using High-resolution Computed Tomography: A Validation Study.}, journal = {Journal of thoracic imaging}, volume = {34}, number = {5}, pages = {320-325}, doi = {10.1097/RTI.0000000000000377}, pmid = {30489434}, issn = {1536-0237}, abstract = {RATIONALE: As pleural plaque has been reported as a risk factor in the occurrence of lung cancer and mesothelioma, a reproducible and precise method of measurement of pleural plaque volume (PPV) is needed to further describe these relationships. The aim of the study was to assess the reproducibility of a 3-dimensional computed tomography (3D-CT) volumetric analysis of PPV in patients with occupational exposure to asbestos.<br><br>MATERIAL AND METHODS: A total of 28 patients were retrospectively randomly selected from the multicenter APEXS (Asbestos Post Exposure Survey) study, which was held between 2003 and 2005. All patients underwent a 3D-CT scan. Two readers specialized in chest radiology completed the 3D semiautomated quantification of lung volume using dedicated software. They also had to categorize the visual extent of pleural plaque in terms of thickness and circumference. Reproducibility of the continuous PPV variable was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Reproducibility of categorical variables was assessed using the κ test.<br><br>RESULTS: Intraobserver reproducibility of PPV was almost perfect (ICC=0.98 [95% interval: 0.97-0.99]), and interobserver reproducibility was very good (ICC=0.93 [0.88-0.97]). At Bland-Altman analysis, the mean differences were 0.1 (limit of agreement: -11.0 to 11.2) and 3.7 cc (-17.8 to 25.2), respectively. Visual analysis of both plaque in terms of thickness and circumference were fair to moderate, with κ values ranging from 0.30 to 0.60.<br><br>CONCLUSIONS: 3D semiautomatic quantification of PPV is feasible and reproducible using CT in patients with occupational exposure to asbestos. PPV measurement may be useful to correlate with other asbestos-related disease outcomes and prognosis.}, }
@article {pmid30479777, year = {2018}, author = {Park, S and Park, J and Lee, E and Eom, H and Shin, MY and Kim, J and Kang, D and Lee, S}, title = {Ovarian cancer in a former asbestos textile factory worker: a case report.}, journal = {Annals of occupational and environmental medicine}, volume = {30}, number = {}, pages = {65}, pmid = {30479777}, issn = {2052-4374}, abstract = {Background: The International Agency for Research on Cancer (IARC) defined that asbestos is a group 1 substance that causes lung cancer, mesothelioma (pleura and peritoneum), laryngeal cancer, and ovarian cancer in humans. Many studies on lung cancer, and mesothelioma caused by asbestos exposure have been conducted, but there was no case report of ovarian cancer due to asbestos exposure in Korea. We describe a case of ovarian cancer caused by asbestos exposure in a worker who worked at an asbestos textile factory for 3 years and 7 months in the late 1970s.<br><br>Case presentation: A 57-year-old woman visited the hospital because she had difficulty urinating. Ovarian cancer was suspected in radiologic examination, and exploratory laparotomy was performed. She was diagnosed with epithelial ovarian cancer. The patient did not undergo postoperative chemotherapy and recovered. She joined the asbestos factory in March 1976 and engaged in asbestos textile twisting and spinning for 1 year, 2 years and 7 months respectively. In addition, she lived near the asbestos factory for more than 20 years. There was no other specificity or family history.<br><br>Conclusion: Considering the patient's occupational and environmental history, it is estimated that she had been exposed to asbestos significantly, so we determined that ovarian cancer in the patient is highly correlated with the occupational exposure of asbestos and environmental exposure is a possible cause as well. Social devices are needed to prevent further exposure to asbestos. It is also necessary to recognize that ovarian cancer can occur in workers who have previously been exposed to asbestos, and the education and social compensation for those workers are needed.}, }
@article {pmid30479770, year = {2019}, author = {Tlotleng, N and Sidwell Wilson, K and Naicker, N and Koegelenberg, CF and Rees, D and Phillips, JI}, title = {The significance of non-occupational asbestos exposure in women with mesothelioma.}, journal = {Respirology case reports}, volume = {7}, number = {1}, pages = {e00386}, pmid = {30479770}, issn = {2051-3380}, abstract = {Malignant mesothelioma is a rare and aggressive pleural or peritoneal tumour almost always caused by exposure to asbestos fibres. Exposure to asbestos can cause malignant mesothelioma 30-40 years after exposure. A description of sources of exposure is important for prevention and possible financial compensation. Three women with cases of histologically confirmed malignant mesothelioma diagnosed from non-occupational asbestos exposure are described. Patients were contacted for an interview to assess their exposure history to asbestos. All three cases had mixed exposure histories related to secondary, environmental contamination, and domestic exposure. This case series highlight how ubiquitous asbestos is in the environment and how diverse the exposures may be. It is anticipated that a significant number of cases of non-occupational mesothelioma will be seen in many countries for several decades given the extent of asbestos containing materials.}, }
@article {pmid30475941, year = {2019}, author = {Consonni, D and Mensi, C}, title = {Comment on the paper 'Boffetta et al. Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy. Ann Oncol 2018; 29(2): 484-489'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {30}, number = {2}, pages = {340-341}, doi = {10.1093/annonc/mdy521}, pmid = {30475941}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30451473, year = {2018}, author = {Krówczyńska, M and Wilk, E and Pabjanek, P and Olędzka, G}, title = {Pleural mesothelioma in Poland: Spatial analysis of malignant mesothelioma prevalence in the period 1999-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.667}, pmid = {30451473}, issn = {1970-7096}, mesh = {Air Pollutants/analysis ; Asbestos/*analysis ; Female ; Humans ; Incidence ; Inhalation Exposure/analysis ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Pleural Neoplasms/*chemically induced/*epidemiology ; Poland/epidemiology ; Prevalence ; Spatial Analysis ; }, abstract = {Malignant mesothelioma (MM), a rare and very deadly tumour, can be due to asbestos exposure. To better understand the cause of incidence of MM, spatial autocorrelation analysis with reference to the quantity of asbestos-cement products in use and the localisation of former asbestos manufacturing plants was applied. Geostatistical analysis shows that strong spatial clustering of MM incidence (referring to the general population as well as females and males separately) during the period 1999-2013 in the administrative units of Poland (provinces and counties). Incidence hotspots were found to be concentrated primarily in southern Poland but also seen in the county of Szczecin, which stands out in local autocorrelation analysis in north-western Poland. High incidence rates were discovered, in particular with reference to counties around former plants manufacturing asbestos-containing products, mainly asbestos-cement manufacturers. The highest frequency of MM incidence rate was found in within a 55 km radius of plants in or near the towns Trzebinia, Ogrodzieniec and Szczucin in the South, where asbestos-cement products had been manufactured for close to 40 years. Areas with significantly high incidence rates were also discovered in the provinces of Śląskie, Małopolskie and Świętokrzyskie in southern Poland.}, }
@article {pmid30451463, year = {2018}, author = {Krówczyńska, M and Wilk, E}, title = {Spatial analysis of asbestos exposure and occupational health care in Poland during the period 2004-2013.}, journal = {Geospatial health}, volume = {13}, number = {2}, pages = {}, doi = {10.4081/gh.2018.689}, pmid = {30451463}, issn = {1970-7096}, mesh = {Air Pollutants, Occupational/adverse effects/*analysis ; Asbestos/*adverse effects/analysis ; Asbestosis/epidemiology ; Humans ; Inhalation Exposure/adverse effects/*analysis ; Lung Neoplasms/chemically induced/epidemiology ; Manufacturing Industry ; Mesothelioma/chemically induced/epidemiology ; Mineral Fibers ; Occupational Exposure/adverse effects/*analysis ; Occupational Health/*statistics &amp; numerical data ; Poland/epidemiology ; Smoking/epidemiology ; *Spatial Analysis ; Time Factors ; }, abstract = {Asbestos is carcinogenic to humans and exposure to this substance can cause a wide range of diseases. In Poland 1997, a statutory ban was introduced on the production, use and marketing of products containing asbestos. The National Programme for Asbestos Abatement for 2009-2032 includes scheduled activities considering asbestos exposure assessment and health protection. As there are several data sources for asbestos exposure in Poland, which are not linked, the aim of this study was to gather and order them developing a PostgreSQL database, an open-source, objectrelational system. The data gathered combines the following information: the quantity of asbestos-cement products in use, details of asbestos manufacturing plants, the results of the measurements of asbestos fibre concentrations in the air and cases of asbestos-related diseases. The relational database was then used to develop a spatial analysis of asbestos monitoring and exposure in Poland to demonstrate the current state of realisation of the National Asbestos Abatement Programme in the country for 2009-2032 with the use of geoinformation techniques. The use of a database on health aspects of occupational and environmental asbestos exposure was also proposed in Asbestos, Asbestosis, and Cancer: Helsinki Criteria update 2014.}, }
@article {pmid30450291, year = {2018}, author = {Broeckx, G and Pauwels, P}, title = {Malignant peritoneal mesothelioma: a review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {537-542}, pmid = {30450291}, issn = {2218-6751}, abstract = {Malignant peritoneal mesothelioma (MPM) is a very rare malignancy of the peritoneum and has a poor prognosis. Of all mesotheliomas, pleural mesothelioma is more common than MPM. In comparison to pleural mesothelioma, the link with asbestos exposure is weaker (33-50% vs. >80%), but it is still the best-defined risk factor. MPM spreads predominantly expansive rather than infiltrative and symptoms are related to tumor spread within the abdominal cavity. Often, MPM is encountered incidentally by diagnostic imaging or by surgery. Computed tomography scan is widely accepted as a first line modality in diagnostic imaging. In diagnostic histopathology, MPM presents some challenges. Firstly, adequate clinical information is of utmost importance to consider the possibility of the diagnosis of MPM. Furthermore, a few morphological subtypes and variants exist. The most sensitive immunohistochemical markers are calretinin (100%), WT1 (94%) and CK5/6 (89%). The malignant character of immunohistochemically demonstrated mesothelial cells is not always obvious. This paradigm somewhat changed with the advent of immunohistochemical demonstration of BAP1 (BRCA-1 associated protein 1). Loss of BAP1 expression supports a diagnosis of malignancy. The gold standard in treatment remains cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Targetable molecular pathways in MPM are being identified. An exciting finding was the demonstration of ALK rearrangements in a small subset of patients with MPM and it is hoped for that at least this small subgroup of patients could benefit from treatment with ALK inhibitors. First-generation tyrosine kinase inhibitors against epidermal growth factor receptor (EGFR) did not show any significant activity in MPM. In contrast, nintedanib, an angiokinase inhibitor, improved progression-free survival and bevacizumab, a humanized anti-VEGF antibody increased overall survival in patients with MPM, when administered in combination with cisplatin and pemetrexed. Ongoing immunotherapy trials will offer a possible new treatment.}, }
@article {pmid30450290, year = {2018}, author = {Brusselmans, L and Arnouts, L and Millevert, C and Vandersnickt, J and van Meerbeeck, JP and Lamote, K}, title = {Breath analysis as a diagnostic and screening tool for malignant pleural mesothelioma: a systematic review.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {520-536}, pmid = {30450290}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma (MPM) is a tumour related to a historical exposure to asbestos fibres. Currently, the definite diagnosis is made only by the histological examination of a biopsy obtained through an invasive thoracoscopy. However, diagnosis is made too late for curative treatment because of non-specific symptoms mainly appearing at advanced stage disease. Hence, due to its biologic aggressiveness and the late diagnosis, survival rate is low and the patients' outcome poor. In addition, radiological imaging, like computed tomographic scans, and blood biomarkers are found not to be sensitive enough to be used as an early diagnostic tool. Detection in an early stage is assumed to improve the patients' outcome but is hampered due to non-specific and late symptomology. Hence, there is a need for a new screening and diagnostic test which could improve the patients' outcome. Despite extensive research has focused on blood biomarkers, not a single has been shown clinically useful, and therefore research recently shifted to &quot;breathomics&quot; techniques to recognize specific volatile organic compounds (VOCs) in the breath of the patient as potential non-invasive biomarkers for disease. In this review, we summarize the acquired knowledge about using breath analysis for diagnosing and monitoring MPM and asbestos-related disorders (ARD). Gas chromatography-mass spectrometry (GC-MS), the gold standard of breath analysis, appears to be the method with the highest accuracy (97%) to differentiate MPM patients from at risk asbestos-exposed subjects. There have already been found some interesting biomarkers that are significantly elevated in asbestosis (NO, 8-isoprostane, leukotriene B4, α-Pinene…) and MPM (cyclohexane) patients. Regrettably, the different techniques and the plethora of studies suffer some limitations. Most studies are pilot studies with the inclusion of a limited number of patients. Nevertheless, given the promising results and easy sampling methods, we can conclude that breath analysis may become a useful tool in the future to screen for MPM, but further research is warranted.}, }
@article {pmid30450289, year = {2018}, author = {Nuyts, V and Nawrot, T and Nemery, B and Nackaerts, K}, title = {Hotspots of malignant pleural mesothelioma in Western Europe.}, journal = {Translational lung cancer research}, volume = {7}, number = {5}, pages = {516-519}, pmid = {30450289}, issn = {2218-6751}, abstract = {Malignant pleural mesothelioma, a highly invasive tumour, has been epidemiologically linked to an occupational or environmental exposure to asbestos. Although asbestos has been widely used in diverse industrial applications and in construction, some industrial sectors have been affected much more than others. The objective of this review was to describe the existence of clusters of malignant pleural mesothelioma in Western European countries, based on epidemiological studies published between 2000 and 2015. MEDLINE (PubMed) and Embase were searched for relevant studies on spatial clustering of mesothelioma in Western European countries. Eventually, 16 different studies published between 2000 and 2015 were selected for a comprehensive analysis. Relevant studies on spatial clustering of mesothelioma were found for Belgium, the Netherlands, the United Kingdom, Germany, France, Spain, Italy and Denmark. Clustering of pleural mesothelioma was found mainly around shipyards (16 studies) and asbestos cement industries (10 studies). Although malignant pleural mesothelioma may be found throughout Western Europe, the present study indicates specific areas with higher past and also probable future incidence.}, }
@article {pmid30446780, year = {2018}, author = {Feder, IS and Jülich, M and Tannapfel, A and Tischoff, I}, title = {[The German Mesothelioma Register : Current pathological diagnostics and services].}, journal = {Der Pathologe}, volume = {39}, number = {Suppl 2}, pages = {241-246}, doi = {10.1007/s00292-018-0509-8}, pmid = {30446780}, issn = {1432-1963}, mesh = {*Asbestos ; Germany ; Humans ; Lung ; *Lung Neoplasms ; *Mesothelioma ; *Occupational Exposure ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, abstract = {BACKGROUND: In Germany, asbestos-related diseases (asbestosis, lung cancer, mesothelioma) are recognised and compensated occupational diseases. The histologic diagnosis of mesothelioma is sometimes a challenge; additional immunohistochemical and molecular methods are needed. With lung dust analysis, the current asbestos fibre burden of the lung is measured (biomonitoring). Identification of grade I asbestosis (minimal asbestosis) requires directed histological examinations with up to 400-fold magnification, additional iron staining and possibly in connection with a lung dust analysis.<br><br>OBJECTIVES: Demonstration of current pathologic diagnostics in association with mesothelioma and lung dust analysis.<br><br>MATERIALS AND METHODS: Analysis of routine data from the German Mesothelioma Register.<br><br>RESULTS: Contrary to reactive mesothelial hyperplasia, malignant mesotheliomas have a nuclear BAP1 loss-of-expression in up to 66% of cases. For differential diagnosis between reactive versus malignant, a p16-FISH test may be helpful. BAP1 loss-of-expression and p16-deletion are independent markers. Evaluation of the dataset of the German Mesothelioma Register of patients with repeated tissue sampling proves the detection of asbestos fibres at the same level even after 40 years. The asbestos fibre burden in the human lung remains stable over this long period of time. In the electron microscopic analysis, white asbestos was predominantly found.<br><br>CONCLUSIONS: The well-known and industrially appreciated characteristics of asbestos fibres (in ancient ἄσβεστος asbestos &quot;imperishable&quot;) as biopersistent have also been experimentally confirmed in human lungs.}, }
@article {pmid30426024, year = {2018}, author = {Kumagai-Takei, N and Nishimura, Y and Matsuzaki, H and Lee, S and Yoshitome, K and Otsuki, T}, title = {Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8+ T Cell Line following Long-Term Exposure to Asbestos Fibers.}, journal = {Journal of immunology research}, volume = {2018}, number = {}, pages = {4391731}, pmid = {30426024}, issn = {2314-7156}, mesh = {Asbestos/adverse effects ; Asbestos, Serpentine/adverse effects ; CD8-Positive T-Lymphocytes/*immunology ; Cell Degranulation ; Cell Line ; Environmental Exposure/adverse effects ; Granzymes/metabolism ; Humans ; Interferon-gamma/*metabolism ; Lung Neoplasms/immunology/*metabolism ; Lymphocyte Activation ; Mesothelioma/immunology/*metabolism ; 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}, mesh = {Animals ; Combined Modality Therapy/*methods/standards/trends ; Humans ; Lung Neoplasms/mortality/*therapy ; Mesothelioma/mortality/*therapy ; Pleura/pathology ; Rare Diseases/therapy ; Treatment Outcome ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which the lung is removed en bloc, and pleurectomy/decortication, in which the lung stays in situ. Chemotherapy usually consists of a platinum-based chemotherapy, such as cisplatin, often combined with a folate antimetabolite, such as pemetrexed. More recently, immunotherapy has emerged as a possible therapeutic strategy for MPM. Evidence suggests that single-modality treatments are not an effective therapeutic approach for MPM. Therefore, researchers have started to explore different multimodality treatment approaches, in which often combinations of surgery, chemotherapy, immunotherapy, and RT are investigated. There is still no definitive answer to the question of which multimodality treatment combinations are most effective in improving the poor prognosis of MPM. Research into the effects of trimodality treatment approaches have found that radical approaches such as EPP and hemithoracic RT post-EPP are less effective than was previously assumed. In general, there are still a great number of unanswered questions and unknown factors regarding the ideal treatment approach for MPM. Hopefully, more research into multimodality therapy will provide insight into which combination of treatment modalities is most effective.}, }
@article {pmid30408567, year = {2019}, author = {Guarrera, S and Viberti, C and Cugliari, G and Allione, A and Casalone, E and Betti, M and Ferrante, D and Aspesi, A and Casadio, C and Grosso, F and Libener, R and Piccolini, E and Mirabelli, D and Dianzani, I and Magnani, C and Matullo, G}, title = {Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {3}, pages = {527-539}, doi = {10.1016/j.jtho.2018.10.163}, pmid = {30408567}, issn = {1556-1380}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive tumor strongly associated with asbestos exposure. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive early diagnostic tests to monitor asbestos-exposed people.<br><br>METHODS: We used a genome-wide methylation array to identify, in asbestos-exposed subjects, novel blood DNA methylation markers of MPM in 163 MPM cases and 137 cancer-free controls (82 MPM cases and 68 controls, training set; replication in 81 MPM cases and 69 controls, test set) sampled from the same areas.<br><br>RESULTS: Evidence of differential methylation between MPM cases and controls was found (more than 800 cytosine-guanine dinucleotide sites, false discovery rate p value (pfdr) < 0.05), mainly in immune system-related genes. Considering the top differentially methylated signals, seven single- cytosine-guanine dinucleotides and five genomic regions of coordinated methylation replicated with similar effect size in the test set (pfdr < 0.05). The top hypomethylated single-CpG (cases versus controls effect size less than -0.15, pfdr < 0.05 in both the training and test sets) was detected in FOXK1 (Forkhead-box K1) gene, an interactor of BAP1 which was found mutated in MPM tissue and as germline mutation in familial MPM. In the test set, comparison of receiver operating characteristic curves and the area under the curve (AUC) of two models, including or excluding methylation, showed a significant increase in case/control discrimination when considering DNA methylation together with asbestos exposure (AUC = 0.81 versus AUC = 0.89, DeLong's test p = 0.0013).<br><br>CONCLUSIONS: We identified signatures of differential methylation in DNA from whole blood between asbestos exposed MPM cases and controls. Our results provide the rationale to further investigate, in prospective studies, the potential use of blood DNA methylation profiles for the identification of early changes related to the MPM carcinogenic process.}, }
@article {pmid30401981, year = {2019}, author = {Matsushita, A and Sato, T and Mukai, S and Fujishita, T and Mishiro-Sato, E and Okuda, M and Aoki, M and Hasegawa, Y and Sekido, Y}, title = {TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation.}, journal = {Oncogene}, volume = {38}, number = {11}, pages = {1966-1978}, doi = {10.1038/s41388-018-0417-7}, pmid = {30401981}, issn = {1476-5594}, support = {25090053//Japan Society for the Promotion of Science (JSPS)/International ; 16H04706//Japan Society for the Promotion of Science (JSPS)/International ; 17K19628//Japan Society for the Promotion of Science (JSPS)/International ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*genetics ; Cytokines/*genetics/metabolism ; Epithelium/metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics/metabolism ; Lung Neoplasms/*genetics/metabolism/pathology ; Mesothelioma/*genetics/metabolism/pathology ; Mice ; Mice, Nude ; Protein-Serine-Threonine Kinases/*genetics/metabolism ; Signal Transduction/genetics ; Transcription Factors/*genetics/metabolism ; Transcriptional Activation ; }, abstract = {Malignant mesothelioma (MM) constitutes a very aggressive tumor that is caused by asbestos exposure after long latency. The NF2 tumor suppressor gene is mutated in 40-50% of MM; moreover, one of its downstream signaling cascades, the Hippo signaling pathway, is also frequently inactivated in MM cells. Although the YAP transcriptional coactivator, which is regulated by the Hippo pathway, can function as a pro-oncogenic protein, the role of TAZ, a paralog of YAP, in MM cells has not yet been clarified. Here, we show that TAZ is expressed and underphosphorylated (activated) in the majority of MM cells compared to immortalized mesothelial cells. ShRNA-mediated TAZ knockdown highly suppressed cell proliferation, anchorage-independent growth, cell motility, and invasion in MM cells harboring activated TAZ. Conversely, transduction of an activated form of TAZ in immortalized mesothelial cells enhanced these in vitro phenotypes and conferred tumorigenicity in vivo. Microarray analysis determined that activated TAZ most significantly enhanced the transcription of genes related to &quot;cytokine-cytokine receptor interaction.&quot; Among selected cytokines, we found that IL-1 signaling activation plays a major role in proliferation in TAZ-activated MM cells. Both IL1B knockdown and an IL-1 receptor antagonist significantly suppressed malignant phenotypes of immortalized mesothelial cells and MM cells with activated TAZ. Overall, these results indicate an oncogenic role for TAZ in MMs via transcriptional induction of distinct pro-oncogenic genes including cytokines. Among these, IL-1 signaling appears as one of the most important cascades, thus potentially serving as a target pathway in MM cells harboring Hippo pathway inactivation.}, }
@article {pmid30376426, year = {2018}, author = {Pastorino, S and Yoshikawa, Y and Pass, HI and Emi, M and Nasu, M and Pagano, I and Takinishi, Y and Yamamoto, R and Minaai, M and Hashimoto-Tamaoki, T and Ohmuraya, M and Goto, K and Goparaju, C and Sarin, KY and Tanji, M and Bononi, A and Napolitano, A and Gaudino, G and Hesdorffer, M and Yang, H and Carbone, M}, title = {A Subset of Mesotheliomas With Improved Survival Occurring in Carriers of BAP1 and Other Germline Mutations.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {}, number = {}, pages = {JCO2018790352}, doi = {10.1200/JCO.2018.79.0352}, pmid = {30376426}, issn = {1527-7755}, support = {R01 CA198138/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: We hypothesized that four criteria could help identify malignant mesotheliomas (MMs) most likely linked to germline mutations of BAP1 or of other genes: family history of MM, BAP1-associated cancers, or multiple malignancies; or age younger than 50 years.<br><br>PATIENTS AND METHODS: Over the course of 7 years, 79 patients with MM met the four criteria; 22 of the 79 (28%) reported possible asbestos exposure. They were screened for germline BAP1 mutations by Sanger sequencing and by targeted next-generation sequencing (tNGS) for germline mutations in 55 additional cancer-linked genes. Deleterious mutations detected by tNGS were validated by Sanger sequencing.<br><br>RESULTS: Of the 79 patients, 43 (16 probands and 27 relatives) had deleterious germline BAP1 mutations. The median age at diagnosis was 54 years and median survival was 5 years. Among the remaining 36 patients with no BAP1 mutation, median age at diagnosis was 45 years, median survival was 9 years, and 12 had deleterious mutations of additional genes linked to cancer. When compared with patients with MMs in the SEER cohort, median age at diagnosis (72 years), median survival for all MM stages (8 months), and stage I (11 months) were significantly different from the 79 patients with MM in the current study (P < .0001).<br><br>CONCLUSION: We provide criteria that help identify a subset of patients with MM who had significantly improved survival. Most of these patients were not aware of asbestos exposure and carried either pathogenic germline mutations of BAP1 or of additional genes linked to cancer, some of which may have targeted-therapy options. These patients and their relatives are susceptible to development of additional cancers; therefore, genetic counseling and cancer screening should be considered.}, }
@article {pmid30375909, year = {2019}, author = {Laaksonen, S and Ilonen, I and Kuosma, E and Sutinen, E and Wolff, H and Vehmas, T and Husgafvel-Pursiainen, K and Salo, JA and Koli, K and Räsänen, J and Myllärniemi, M}, title = {Malignant pleural mesothelioma in Finland: regional and gender variation.}, journal = {Acta oncologica (Stockholm, Sweden)}, volume = {58}, number = {1}, pages = {38-44}, doi = {10.1080/0284186X.2018.1532599}, pmid = {30375909}, issn = {1651-226X}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Finland/epidemiology ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Registries ; Sex Distribution ; }, abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare occupational cancer with a poor prognosis. Even with a multimodality treatment approach, the treatment outcomes remain unsatisfactory. The use of asbestos has been banned in most developed countries, but MPM continues to be a significant occupational disease also in these countries. Aim of this study is to identify modern epidemiology and assess equality in care.<br><br>METHODS: Our study cohort consists of 1010 patients diagnosed with MPM in Finland during 2000-2012. The data were collected from the Finnish Cancer Registry, the National Workers' Compensation Center Registry and the National Registry of Causes of Death, Statistics Finland.<br><br>RESULTS: Women were diagnosed a mean of 4.5 years later than males (p = .001), but survival did not differ (overall median survival 9.7 months). A workers' compensation claim was more common in males (OR 11.0 [95% CI 7.5-16.2]) and in regions with a major asbestos industry (OR 1.7 [95% CI 1.3-2.2]). One-year and three-year survivals did not differ regionally. Patients without chemotherapy treatment had an inferior survival (RR 1.8 [95% CI 1.5-2.0]). The initial survival benefit gained with pemetrexed was diluted at 51 months.<br><br>CONCLUSIONS: MPM is a disease with a poor prognosis, although chemotherapy appears to improve survival time. Significant gender and regional variation exists among patients, with notable differences in diagnostic and treatment practices. Long-term outcomes with pemetrexed remain indeterminate.<br><br>IMPACT: Emphasize centralized consult services for the diagnosis, treatment and support that patients receive for MPM, facilitating equal outcomes and compensation.}, }
@article {pmid30370748, year = {2018}, author = {Algranti, E and Giannasi, F and Sousa Santana, V}, title = {[The fight for the asbestos ban in Brazil and the 2nd International seminar &quot;Brazil without asbestos&quot;].}, journal = {Epidemiologia e prevenzione}, volume = {42}, number = {5-6}, pages = {388-390}, doi = {10.19191/EP18.5-6.P388.115}, pmid = {30370748}, issn = {1120-9763}, mesh = {*Asbestos/toxicity ; Asbestosis/*prevention &amp; control ; Brazil ; Congresses as Topic ; Construction Materials/standards/statistics &amp; numerical data ; Environmental Policy/*legislation &amp; jurisprudence ; *Environmental Pollutants/toxicity ; Environmental Pollution/legislation &amp; jurisprudence/*prevention &amp; control ; Flame Retardants/toxicity ; Humans ; Mesothelioma/etiology/prevention &amp; control ; Occupational Health/legislation &amp; jurisprudence ; Pleural Neoplasms/etiology/prevention &amp; control ; }, }
@article {pmid30370160, year = {2018}, author = {Plato, N and Martinsen, JI and Kjaerheim, K and Kyyronen, P and Sparen, P and Weiderpass, E}, title = {Mesothelioma in Sweden: Dose-Response Analysis for Exposure to 29 Potential Occupational Carcinogenic Agents.}, journal = {Safety and health at work}, volume = {9}, number = {3}, pages = {290-295}, pmid = {30370160}, issn = {2093-7911}, abstract = {Background: There is little information on the dose-response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma.<br><br>Methods: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961-2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratios and 95% confidence intervals.<br><br>Results: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25-2.0 fb/ml but also a clear dose-response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix.<br><br>Conclusion: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.}, }
@article {pmid30366103, year = {2019}, author = {Harris, EJA and Kao, S and McCaughan, B and Nakano, T and Kondo, N and Hyland, R and Nowak, AK and de Klerk, NH and Brims, FJH}, title = {Prediction modelling using routine clinical parameters to stratify survival in Malignant Pleural Mesothelioma patients undergoing cytoreductive surgery.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {288-293}, doi = {10.1016/j.jtho.2018.10.005}, pmid = {30366103}, issn = {1556-1380}, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.<br><br>METHODS: Data were collected from subjects undergoing cytoreductive surgery for MPM from specialist centers in Hyõgo, Japan, and Sydney, Australia, between 1991 and 2016. The CART model was applied using the combination of clinical variables to stratify subjects into risk groups (1 through 4); survival characteristics were then compared.<br><br>RESULTS: Two hundred eighty-nine cases were included (205 from Australia, 84 from Japan). Overall median survival was 34.6 (interquartile range: 17.5-56.1) months; median age was 63.0 (interquartile range: 57.0-67.8) years, and 83.0% (n = 240) were male. There were no clinically meaningful differences between the two cohorts. Survival across the four risk groups was significantly different (p < 0.0001); the model stratified survival well with a Harrell's concordance statistic of 0.62 (95% confidence interval: 0.57-0.66) at 36 months. The group with the longest survival (median, 82.5 months) had: no weight loss, hemoglobin > 153 g/L and serum albumin > 43 g/L at time of referral to the surgical center.<br><br>CONCLUSIONS: Using routinely available clinical variables, the CART model was able to stratify surgical patients into risk groups with statistically different survival characteristics with fair to good performance. Presence of weight loss, anemia, and low albumin should confer caution when considering surgical therapy for MPM.}, }
@article {pmid30362690, year = {2018}, author = {Trenti, E and Palermo, SM and D'Elia, C and Comploj, E and Pycha, A and Carella, R and Pycha, A}, title = {Malignant mesothelioma of tunica vaginalis testis: Report of a very rare case with review of the literature.}, journal = {Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica}, volume = {90}, number = {3}, pages = {212-214}, doi = {10.4081/aiua.2018.3.212}, pmid = {30362690}, issn = {1124-3562}, mesh = {Adult ; Follow-Up Studies ; Frozen Sections ; Humans ; Lung Neoplasms/*diagnosis/pathology/surgery ; Lymph Node Excision ; Male ; Mesothelioma/*diagnosis/pathology/surgery ; Prognosis ; Testicular Hydrocele/*surgery ; Testicular Neoplasms/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: Mesothelioma of the tunica vaginalis testis is a extremely rare tumor and represents 0.3 to 0.5% of all malignant mesotheliomas. Exposure to asbestos often precedes illness. Because of its low incidence and nonspecific clinical presentation, it is mostly diagnosed accidentally during surgery for other reasons and the prognosis is usually poor. We present a case of a patient with a mesothelioma of tunica vaginalis testis, diagnosed secondarily during hydrocele surgery, with long-term survival after radical surgery.<br><br>MATERIALS AND METHODS: a 40 years old patient was admitted to our department for routine surgery of a left hydrocele. During the operation a frozen section analysis was requested because of the unusual nodular thickening of the tunica vaginalis: the examination revealed a diffuse malignant mesothelioma with epithelioid structure and tubular-papillary proliferation. Therefore a left hemi-scrotectomy with left inguinal lymph node dissection was performed.<br><br>RESULTS: The definitive histology confirmed the previous report of diffuse malignant mesothelioma with angio-invasion but normal testicle findings and negative lymph nodes. No metastases were found on the CT-scan. For the first 2 years a CT was repeated every 4 months, for other 3 years every 6 months and then yearly. Six years after surgery the patient is classified as no evidence of disease.<br><br>CONCLUSIONS: malignant mesothelioma of the tunica vaginalis testis is a rare entity, often initially thought to be a hydrocele or an epididymal cyst. An aggressive approach with hemiscrotectomy with or without inguinal and retroperitoneal lymphadenectomy can reduce the risk of recurrence.}, }
@article {pmid30362153, year = {2019}, author = {Matboli, M and Shafei, AE and Ali, MA and Gaber, AI and Galal, A and Tarek, O and Marei, M and Khairy, E and El-Khazragy, N and Anber, N and Abdel-Rahman, O}, title = {Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma.}, journal = {Journal of cellular biochemistry}, volume = {120}, number = {3}, pages = {3203-3211}, doi = {10.1002/jcb.27586}, pmid = {30362153}, issn = {1097-4644}, 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.<br><br>METHODS: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A (ARSA) gene expression with their epigenetic regulators microRNA (miR-2053) and long noncoding RNA (lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed.<br><br>RESULTS: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM.<br><br>CONCLUSION: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.}, }
@article {pmid30357666, year = {2018}, author = {Pascotto, E and Gianoncelli, A and Calligaro, C and Marcuzzo, T and Melato, M and Rizzardi, C and Pascolo, L}, title = {Ferruginous bodies resolved by synchrotron XRF in a dog with peritoneal malignant mesothelioma.}, journal = {Environmental science and pollution research international}, volume = {25}, number = {35}, pages = {35707-35714}, pmid = {30357666}, issn = {1614-7499}, mesh = {Animals ; Asbestos/toxicity ; Dogs ; Environmental Exposure/*adverse effects ; Immunohistochemistry ; Iron/analysis ; Lung/pathology ; Lung Neoplasms/diagnostic imaging/*pathology ; Male ; Mesothelioma/diagnostic imaging/*pathology ; Peritoneal Neoplasms/diagnostic imaging/*pathology ; Silicon/analysis ; Spectrometry, X-Ray Emission ; Synchrotrons ; }, abstract = {Mesothelioma is a malignant tumor mainly correlated to occupational asbestos exposure. Rare reports describe its occurrence also in animals, mainly linked to asbestos in the environment. Asbestos exposure is demonstrated by the appearance of characteristic histological hallmarks: asbestos containing ferruginous bodies that are iron-based structures forming around fibers and also other dust particles. Here we present a clinical case of a suspect of mesothelioma in the peritoneum of a dog with parallel histological observation of ferruginous bodies. To possibly correlate the dog tumor to environmental exposure, we performed X-ray fluorescence (XRF) analyses at two different synchrotrons to resolve the ferruginous bodies' composition. While the histological examination diagnoses a tubulo-papillary mesothelioma, the XRF analyses show that ferruginous bodies contain Si particles, resembling formations of exogenous origin; however, the morphology is unlikely that of asbestos fibers. We speculate that the peritoneal mesothelioma of this dog could be related to environmental exposure to non-asbestos material.}, }
@article {pmid30357324, year = {2019}, author = {Dragani, TA and Colombo, F and Pavlisko, EN and Roggli, VL}, title = {Response to comments on 'Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure' by Farioli et al. and Oddone et al.}, journal = {Carcinogenesis}, volume = {40}, number = {3}, pages = {490-491}, doi = {10.1093/carcin/bgy145}, pmid = {30357324}, issn = {1460-2180}, }
@article {pmid30349836, year = {2018}, author = {Ibrahim, AM and Al-Akchar, M and Obaidi, Z and Al-Johany, H}, title = {Malignant Peritoneal Mesothelioma: A Rare Cause of Ascites.}, journal = {Journal of investigative medicine high impact case reports}, volume = {6}, number = {}, pages = {2324709618807506}, pmid = {30349836}, issn = {2324-7096}, abstract = {Malignant peritoneal mesothelioma (MPM) is a rare diagnosis that presents with difficulties in diagnosis and management. This article reports a case of an 88-year-old male who presented with a 2-week history of abdominal distention and bloating. He worked at an insulation production factory between the ages of 23 and 25 years with presumed asbestos exposure. On the computed tomography scan of the abdomen/pelvis, the patient was found to have diffuse omental, peritoneal, and mesenteric nodularity with moderate to large ascites. Omental biopsy revealed MPM. The overall prognosis of MPM remains poor, with a median survival time of 12 months at the time of diagnosis. Treatment modalities offered in the United States include chemotherapy alone, cytoreductive surgery alone, or cytoreductive surgery/chemotherapy combination.}, }
@article {pmid30349716, year = {2018}, author = {Grosso, F and Roveta, A and Gallizzi, G and Belletti, M}, title = {Management of recurrent pleural mesothelioma: Successful rechallenge with nintedanib in combination with chemotherapy.}, journal = {Clinical case reports}, volume = {6}, number = {10}, pages = {2000-2004}, pmid = {30349716}, issn = {2050-0904}, abstract = {Malignant pleural mesothelioma (MPM) is a rare neoplasm, generally caused by asbestos exposure. This case details how a patient treated with nintedanib during the LUME-Meso study was rechallenged with nintedanib. The findings highlight the benefit of nintedanib rechallenge and the potential use of continuous anti-angiogenic therapy in MPM treatment.}, }
@article {pmid30349644, year = {2018}, author = {Adhikary, G and Grun, D and Alexander, HR and Friedberg, JS and Xu, W and Keillor, JW and Kandasamy, S and Eckert, RL}, title = {Transglutaminase is a mesothelioma cancer stem cell survival protein that is required for tumor formation.}, journal = {Oncotarget}, volume = {9}, number = {77}, pages = {34495-34505}, pmid = {30349644}, issn = {1949-2553}, support = {R01 CA184027/CA/NCI NIH HHS/United States ; R01 CA211909/CA/NCI NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; }, abstract = {Mesothelioma is a rare cancer of the mesothelial cell layer of the pleura, peritoneum, pericardium and tunica vaginalis. It is typically caused by asbestos, notoriously resistant to chemotherapy and generally considered incurable with a poor life expectancy. Transglutaminase 2 (TG2), a GTP binding regulatory protein, is an important cancer stem cell survival and therapy resistance factor. We show that TG2 is highly expressed in human mesothelioma tumors and in mesothelioma cancer stem cells (MCS cells). TG2 knockdown or TG2 inhibitor treatment reduces MCS cell spheroid formation, matrigel invasion, migration and tumor formation. Time to tumor first appearance is doubled in TG2 knockout cells as compared to wild-type. In addition, TG2 loss is associated with reduced expression of stemness, and epithelial mesenchymal transition markers, and enhanced apoptosis. These studies indicate that TG2 is an important MCS cell survival protein and suggest that TG2 may serve as a mesothelioma cancer stem cell therapy target.}, }
@article {pmid30338612, year = {2018}, author = {Betti, M and Aspesi, A and Ferrante, D and Sculco, M and Righi, L and Mirabelli, D and Napoli, F and Rondón-Lagos, M and Casalone, E and Vignolo Lutati, F and Ogliara, P and Bironzo, P and Gironi, CL and Savoia, P and Maffè, A and Ungari, S and Grosso, F and Libener, R and Boldorini, R and Valiante, M and Pasini, B and Matullo, G and Scagliotti, G and Magnani, C and Dianzani, I}, title = {Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes.}, journal = {Genes, chromosomes &amp; cancer}, volume = {57}, number = {11}, pages = {573-583}, doi = {10.1002/gcc.22670}, pmid = {30338612}, issn = {1098-2264}, support = {IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; 2015 IG 17464//Associazione Italiana per la Ricerca sul Cancro/International ; //Istituto Superiore di Sanità (Progetto Amianto)/International ; //Italian Institute for Genomic Medicine/International ; //Ministry of Health - Italy/International ; //Regione Piemonte/International ; GR-2011-02348356//Young Researcher/International ; 2011-02348356//Young Researcher/International ; //INAIL Bric program 2016-2018/International ; }, mesh = {Adult ; Asbestos/*adverse effects ; Cohort Studies ; DNA Repair/genetics ; Environmental Exposure/*analysis ; Female ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/*genetics ; Humans ; Italy ; Male ; Mesothelioma/epidemiology/*genetics ; Middle Aged ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, abstract = {Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1-TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1-TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5-year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer-predisposing genes. We report here a new pathogenic germline variant in BAP1: c.783 + 2 T > C. The prevalence of pathogenic germline variants in BAP1 was 7.7% among patients with familial MPM (3/39). Patients with pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes showed lower cumulative asbestos exposure than patients without germline variants in 94 cancer-predisposing genes (P = .00002). This suggests an interaction between genetic risk factors and asbestos in the development of mesothelioma.}, }
@article {pmid30321262, year = {2018}, author = {Brentisci, C and Gangemi, M and Migliore, E and Mirabelli, D and Stura, A}, title = {Comment on 'Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy'.}, journal = {Annals of oncology : official journal of the European Society for Medical Oncology}, volume = {29}, number = {12}, pages = {2395-2396}, doi = {10.1093/annonc/mdy463}, pmid = {30321262}, issn = {1569-8041}, mesh = {*Asbestos ; Humans ; Italy ; *Lung Neoplasms ; *Mesothelioma ; Textiles ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase ; }, }
@article {pmid30319235, year = {2018}, author = {Jargin, SV}, title = {Asbestos and Mesothelioma: A Comment.}, journal = {Indian journal of occupational and environmental medicine}, volume = {22}, number = {2}, pages = {113-114}, pmid = {30319235}, issn = {0973-2284}, }
@article {pmid30317900, year = {2018}, author = {Duke, KS and Thompson, EA and Ihrie, MD and Taylor-Just, AJ and Ash, EA and Shipkowski, KA and Hall, JR and Tokarz, DA and Cesta, MF and Hubbs, AF and Porter, DW and Sargent, LM and Bonner, JC}, title = {Role of p53 in the chronic pulmonary immune response to tangled or rod-like multi-walled carbon nanotubes.}, journal = {Nanotoxicology}, volume = {12}, number = {9}, pages = {975-991}, 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 ; }, mesh = {Animals ; Dose-Response Relationship, Drug ; Granuloma, Respiratory Tract/*chemically induced/genetics/immunology ; Inhalation Exposure ; Lung/*drug effects/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nanotubes, Carbon/*chemistry/*toxicity ; Surface Properties ; Tertiary Lymphoid Structures/*chemically induced/genetics/immunology ; Tumor Suppressor Protein p53/genetics/*physiology ; }, abstract = {The fiber-like shape of multi-walled carbon nanotubes (MWCNTs) is reminiscent of asbestos, suggesting they pose similar health hazards when inhaled, including pulmonary fibrosis and mesothelioma. Mice deficient in the tumor suppressor p53 are susceptible to carcinogenesis. However, the chronic pathologic effect of MWCNTs delivered to the lungs of p53 heterozygous (p53+/-) mice has not been investigated. We hypothesized that p53+/- mice would be susceptible to lung tumor development after exposure to either tangled (t-) or rod-like (r-) MWCNTs. Wild-type (p53+/+) or p53+/- mice were exposed to MWCNTs (1 mg/kg) via oropharyngeal aspiration weekly over four consecutive weeks and evaluated for cellular and pathologic outcomes 11-months post-initial exposure. No lung or pleural tumors were observed in p53+/+ or p53+/- mice exposed to either t- or rMWCNTs. In comparison to tMWCNTs, the rMWCNTs induced the formation of larger granulomas, a greater number of lymphoid aggregates and greater epithelial cell hyperplasia in terminal bronchioles in both p53+/- and p53+/+ mice. A constitutively larger area of CD45R+/CD3+ lymphoid tissue was observed in p53+/- mice compared to p53+/+ mice. Importantly, p53+/- mice had larger granulomas induced by rMWCNTs as compared to p53+/+ mice. These findings indicate that a combination of p53 deficiency and physicochemical characteristics including nanotube geometry are factors in susceptibility to MWCNT-induced lymphoid infiltration and granuloma formation.}, }
@article {pmid30316650, year = {2018}, author = {Fournel, L and Janet-Vendroux, A and Canny-Hamelin, E and Mansuet-Lupo, A and Guinet, C and Bobbio, A and Damotte, D and Alifano, M}, title = {[Malignant pleural mesothelioma: The role of surgery].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {5}, pages = {351-358}, doi = {10.1016/j.pneumo.2018.09.006}, pmid = {30316650}, issn = {1776-2561}, mesh = {Chemotherapy, Adjuvant ; Combined Modality Therapy ; Humans ; Lung Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Mesothelioma/diagnosis/drug therapy/radiotherapy/*surgery ; Pleural Neoplasms/diagnosis/drug therapy/radiotherapy/*surgery ; Pneumonectomy ; Radiotherapy, Adjuvant ; Thoracic Surgical Procedures/*methods ; Thoracoscopy ; Treatment Outcome ; }, abstract = {INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease, whose incidence is increasing. Asbestos is the primary causal agent.<br><br>STATE OF KNOWLEDGE: Knowledge about MPM has evolved. Thoracoscopy is essential for diagnosis of MPM. It allows performing pleural biopsies, to study the extent of the disease and to relieve dyspnea. The pathological diagnosis is also better codified with immunohistochemistry and with analysis by expert of Mesopath group. Curative surgical treatments are pleurectomy decortication and extended pneumonectomy in combination with chemotherapy and/or radiotherapy. Those heavy treatments improve survival in highly selected patients. For the other patients, supportive measures will be considered to reduce pain and dyspnea.<br><br>PROSPECT: Radical surgical treatment is only offered in therapeutic trials or multimodal treatment. Its place is not formally established. New therapies associated to surgical treatment are being studied.<br><br>CONCLUSIONS: Surgical management of MPM has to be operated in specialized teams where the survival benefit and quality of life is discussed case by case.}, }
@article {pmid30316012, year = {2019}, author = {Mansfield, AS and Peikert, T and Smadbeck, JB and Udell, JBM and Garcia-Rivera, E and Elsbernd, L and Erskine, CL and Van Keulen, VP and Kosari, F and Murphy, SJ and Ren, H and Serla, VV and Schaefer Klein, JL and Karagouga, G and Harris, FR and Sosa, C and Johnson, SH and Nevala, W and Markovic, SN and Bungum, AO and Edell, ES and Dong, H and Cheville, JC and Aubry, MC and Jen, J and Vasmatzis, G}, title = {Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma.}, journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, volume = {14}, number = {2}, pages = {276-287}, 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.<br><br>METHODS: We used mate-pair (n = 22), RNA (n = 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome.<br><br>RESULTS: We observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival.<br><br>CONCLUSIONS: Our findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies.}, }
@article {pmid30312759, year = {2019}, author = {Toyokuni, S}, title = {Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention.}, journal = {Free radical biology &amp; medicine}, volume = {133}, number = {}, pages = {206-215}, doi = {10.1016/j.freeradbiomed.2018.10.401}, pmid = {30312759}, issn = {1873-4596}, abstract = {Cancer is the primary cause of human mortality in most countries. This tendency has increased as various medical therapeutics have advanced, which suggests that we cannot escape carcinogenesis, although the final outcome may be modified by exposomes and statistics. Cancer is classified by its cellular differentiation. Mesothelial cells are distinct in that they line somatic cavities, facilitating the smooth movement of organs, but are not exposed to the external environment. Malignant mesothelioma, or simply mesothelioma, develops either in the pleural, peritoneal or pericardial cavities, or in the tunica vaginalis testes. Mesothelioma has been a relatively rare cancer but is socially important due to its association with asbestos exposure, caused by modern industrial development. The major pathogenic mechanisms include oxidative stress either via catalytic reactions against the asbestos surface or frustrated phagocytosis of macrophages, and specific adsorption of hemoglobin and histones by asbestos fibers in the presence of phagocytic activity of mesothelial cells. Multiwall carbon nanotubes of ~50 nm-diameter, additionally adsorbing transferrin, are similarly carcinogenic to mesothelial cells in rodents and were thus classified as Group 2B carcinogens. Genetic alterations found in human and rat mesothelioma notably contain changes found in other excess iron-induced carcinogenesis models. Phlebotomy and iron chelation therapies have been successful in the prevention of mesothelioma in rats. Alternatively, loading of oxidative stress by non-thermal plasma to mesothelioma cells causes ferroptosis. Therefore, carcinogenesis by foreign fibrous inorganic materials may overlap the uncovered molecular mechanisms of birth of life and its evolution.}, }
@article {pmid30309369, year = {2018}, author = {Smeele, P and d'Almeida, SM and Meiller, C and Chéné, AL and Liddell, C and Cellerin, L and Montagne, F and Deshayes, S and Benziane, S and Copin, MC and Hofman, P and Le Pimpec-Barthes, F and Porte, H and Scherpereel, A and Grégoire, M and Jean, D and Blanquart, C}, title = {Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis.}, journal = {Molecular cancer}, volume = {17}, number = {1}, pages = {148}, pmid = {30309369}, issn = {1476-4598}, mesh = {Biomarkers, Tumor ; Brain-Derived Neurotrophic Factor/*blood/genetics ; Gene Expression ; Humans ; Lung Neoplasms/*blood/genetics/mortality/*pathology ; Mesothelioma/*blood/genetics/mortality/*pathology ; Neovascularization, Pathologic/*blood ; Pleural Effusion, Malignant/genetics/metabolism ; Pleural Neoplasms/*blood/genetics/mortality/*pathology ; Prognosis ; RNA, Messenger/genetics ; ROC Curve ; }, abstract = {Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.}, }
@article {pmid30309285, year = {2018}, author = {Funahashi, S and Okazaki, Y and Nishiyama, T and Ohyoshi, H and Yasui, H and Nishida, K and Matsui, S and Toyokuni, S}, title = {Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice.}, journal = {Free radical research}, volume = {52}, number = {9}, pages = {1030-1039}, doi = {10.1080/10715762.2018.1514604}, pmid = {30309285}, issn = {1029-2470}, mesh = {Animals ; Asbestos, Crocidolite/*toxicity ; Carcinogenesis/drug effects/*genetics ; Cation Transport Proteins/*genetics ; Epithelial Cells ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Iron ; Lung Neoplasms/chemically induced/*genetics/pathology ; Mesothelioma/chemically induced/*genetics/pathology ; Mice ; Mice, Transgenic ; }, abstract = {Exposure to asbestos fiber is central to mesothelial carcinogenesis, for which iron overload in or near mesothelial cells is a key pathogenic mechanism. Alternatively, iron chelation therapy with deferasirox or regular phlebotomy was significantly preventive against crocidolite-induced mesothelial carcinogenesis in rats. However, the role of iron transporters during asbestos-induced carcinogenesis remains elusive. Here, we studied the role of divalent metal transporter 1 (DMT1; Slc11a2), which is a Fe(II) transporter, that is present not only on the apical plasma membrane of duodenal cells but also on the lysosomal membrane of every cell, in crocidolite-induced mesothelial carcinogenesis using DMT1 transgenic (DMT1Tg) mice. DMT1Tg mice show mucosal block of iron absorption without cancer susceptibility under normal diet. We unexpectedly found that superoxide production was significantly decreased upon stimulation with crocidolite both in neutrophils and macrophages of DMT1Tg mice, and the macrophage surface revealed higher iron content 1 h after contact with crocidolite. Intraperitoneal injection of 3 mg crocidolite ultimately induced malignant mesothelioma in ∼50% of both wild-type and DMT1Tg mice (23/47 and 14/28, respectively); this effect was marginally (p = 0.069) delayed in DMT1Tg mice, promoting survival. The promotional effect of nitrilotriacetic acid was limited, and the liver showed significantly higher iron content both in DMT1Tg mice and after crocidolite exposure. The results indicate that global DMT1 overexpression causes decreased superoxide generation upon stimulation in inflammatory cells, which presumably delayed the promotional stage of crocidolite-induced mesothelial carcinogenesis. DMT1Tg mice with low-stamina inflammatory cells may be helpful to evaluate the involvement of inflammation in various pathologies.}, }
@article {pmid30301262, year = {2018}, author = {Sarun, KH and Lee, K and Williams, M and Wright, CM and Clarke, CJ and Cheng, NC and Takahashi, K and Cheng, YY}, title = {Genomic Deletion of BAP1 and CDKN2A Are Useful Markers for Quality Control of Malignant Pleural Mesothelioma (MPM) Primary Cultures.}, journal = {International journal of molecular sciences}, volume = {19}, number = {10}, pages = {}, pmid = {30301262}, issn = {1422-0067}, mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics/*standards ; Cell Line, Tumor ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18/*genetics ; Gene Deletion ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; 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 &amp; jurisprudence ; *Truth Disclosure ; United States ; }, }
@article {pmid30293912, year = {2018}, author = {Mlika, M and Lamzirbi, O and Limam, M and Mejri, N and Ben Saad, S and Chaouch, N and Ben Miled, K and Marghli, A and Mezni, F}, title = {[Clinical and pathological profile of the pleural malignant mesothelioma: A retrospective study about 30 cases].}, journal = {Revue de pneumologie clinique}, volume = {74}, number = {6}, pages = {427-435}, doi = {10.1016/j.pneumo.2018.06.004}, pmid = {30293912}, issn = {1776-2561}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Incidence ; Lung Neoplasms/diagnosis/*epidemiology/pathology ; Male ; Mesothelioma/diagnosis/*epidemiology/pathology ; Middle Aged ; Pleural Neoplasms/diagnosis/*epidemiology/pathology ; Retrospective Studies ; Tunisia/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: The malignant pleural mesothelioma (MPM) is a rare tumour usually associated to asbestos exposure. The delay between the exposure and the occurrence of the cancer can reach 40 years. This caused the pick of incidence described in many countries including Tunisia. The diagnosis is suspected based on clinical features but positive diagnosis is microscopic. Our aim was to describe the clinical and microscopic features of MPM through a single institution experience.<br><br>PATIENTS AND METHODS: We conducted a retrospective study about 30 MPM diagnosed over a 20-year-period (1995-2015). We included only patients with complete records including clinical, radiologic and microscopic features. All the microscopic diagnoses were reviewed by 2 pathologists. A mean of 12 slides per case was reviewed. The diagnosis was based on the 2015 WHO classification.<br><br>RESULTS: The mean age of the patients was 61 years, average 22 to 80 years. The sex ratio was 6,5. An asbetose exposition was reported in 21 cases. The most frequent symptoms was chest pain reported in 25 cases. Physical exam was normal in 9 cases. It revealed pleural syndorm in most patients (60 %). Imaging findings consisted mainly in diffuse pleural thickening in 17 cases. Twelve tumours were classified as stage I, 3 stage II, 14 stage III et 1 stage IV. Pleural biopsy was performed using needle in 18 cases, through thoracoscopy in 16 cases, thoracotomy in 3 cases and allowed the diagnosis in respectively 7 cases/18, 16 cases/16 and 3 cases/3. A lymph node biopsy was performed through mediastinoscopy in one case and yelded the diagnosis. The diagnosis was performed on surgical specimen in 2 patients: one bullectomy and one right upper lobectomy. The microscopic exam concluded to an EM in 17 cases, sarcomatoid mesothelioma (SM) in 4 cases and biphasic mesothelioma (BM) in 9 cases. Pan-cytokeratin antibody was used in all cases in association with 2 antibodies with positive diagnostic value and 2 antibodies with negative diagnostic value. It was repeated in 15 cases and the most used antibodies were the anti-calretinin and the TTF1. This was due to the lack of fixation in one case and in order to reach a quality criteria in the other cases. Surgical resection was possible in 2 patients. 15 patients were lost of view after a mean follow-up period of 3 months. Thirteen patients died before or during the follow-up.<br><br>CONCLUSION: This work was about a Tunisian experience in the diagnosis and management of MPM. The major limits faced were the incomplete databases, the small number of patients included. Microsocpic positive diagnosis necessitates a degree of expertise and every laboratory has to determine the most valuable antibodies through its experience in order to optimize the diagnosis and to reduce the delay of diagnosis.}, }
@article {pmid30293239, year = {2018}, author = {van Gerwen, M and Wolf, A and Liu, B and Flores, R and Taioli, E}, title = {Short-term outcomes of pleurectomy decortication and extrapleural pneumonectomy in mesothelioma.}, journal = {Journal of surgical oncology}, volume = {118}, number = {7}, pages = {1178-1187}, doi = {10.1002/jso.25260}, pmid = {30293239}, issn = {1096-9098}, support = {NCI CCSG P30 CA196521//National Cancer Institute/ ; }, mesh = {Aged ; Arrhythmias, Cardiac/epidemiology ; Databases, Factual ; Female ; *Hospital Mortality ; Humans ; Male ; Mesothelioma/mortality/*surgery ; Middle Aged ; New York/epidemiology ; Pleura/*surgery ; Pleural Neoplasms/mortality/*surgery ; Pneumonectomy/*adverse effects ; Postoperative Complications ; Propensity Score ; }, abstract = {BACKGROUND/OBJECTIVES: We evaluated postoperative mortality and complications after extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) to better understand their effectiveness in malignant pleural mesothelioma (MPM).<br><br>METHODS: A meta-analysis was done to evaluate 30-day mortality and postoperative complications. In addition, in-patients data of 500 eligible patients with MPM who underwent EPP or P/D was extracted from the New York Statewide Planning and Research Cooperative System (SPARCS). Multivariate analyses and propensity matching were used to compare in-hospital mortality and postoperative complications in EPP vs P/D.<br><br>RESULTS: The meta-analysis showed a statistically significant difference in 30-day mortality (5% [95% CI: 4-6] vs P/D 2% [95% CI: 1-3]), proportion of complications (46% [95% CI: 36-56] vs 24% [95% CI: 15-34]) and postoperative arrhythmias (20% [95% CI: 12-31] vs 5% [95% CI: 2-8]) for EPP vs P/D. In-hospital mortality (OR adj : 2.6; 95% CI: 0.86-7.75) and postoperative complications (OR adj : 1.1; 95% CI: 0.68-1.86) were not different in EPP compared with P/D while supraventricular arrhythmia was significantly more frequent after EPP vs P/D (OR adj : 5.2; 95% CI: 2.34-11.33).<br><br>CONCLUSIONS: Postoperative mortality, postoperative complications, and particularly supraventricular arrhythmia are less frequent after P/D vs EPP. P/D, a less invasive surgery, may provide a better option when technically feasible for patients with MPM.}, }
@article {pmid30288361, year = {2018}, author = {Fear, VS and Tilsed, C and Chee, J and Forbes, CA and Casey, T and Solin, JN and Lansley, SM and Lesterhuis, WJ and Dick, IM and Nowak, AK and Robinson, BW and Lake, RA and Fisher, SA}, title = {Combination immune checkpoint blockade as an effective therapy for mesothelioma.}, journal = {Oncoimmunology}, volume = {7}, number = {10}, pages = {e1494111}, pmid = {30288361}, issn = {2162-4011}, abstract = {Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma and is now being applied to other cancers, including mesothelioma. However, the efficacy of ICPB and which immune checkpoint combinations constitute the best therapeutic option for mesothelioma have yet to be fully elucidated. Here, we used our well characterised mesothelioma tumour model to investigate the efficacy of different ICBP treatments to generate effective therapy for mesothelioma. We show that tumour resident regulatory T cell co-express high levels of CTLA-4, OX40 and GITR relative to T effector subsets and that these receptors are co-expressed on a large proportion of cells. Targeting any of CTLA-4, OX40 or GITR individually generated effective responses against mesothelioma. Furthermore, the combination of αCTLA-4 and αOX40 was synergistic, with an increase in complete tumour regressions from 20% to 80%. Other combinations did not synergise to enhance treatment outcomes. Finally, an early pattern in T cell response was predictive of response, with activation status and ICP receptor 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}, mesh = {Angiogenesis Inhibitors/*administration &amp; dosage/pharmacology ; Animals ; Antineoplastic Agents/*administration &amp; dosage/pharmacology ; Apoptosis Inducing Factor/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Curcumin/*administration &amp; dosage/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung Neoplasms/blood supply/*drug therapy/metabolism ; Mesothelioma/blood supply/*drug therapy/metabolism ; Mice ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays ; }, 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}, mesh = {Consensus ; Humans ; Lung Neoplasms/pathology/*therapy ; Mesothelioma/pathology/*therapy ; National Cancer Institute (U.S.) ; United States ; }, 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}, mesh = {Adenocarcinoma/complications/*diagnosis/epidemiology ; Aged ; Aged, 80 and over ; *Cytodiagnosis ; Female ; Humans ; Lung Neoplasms/complications/*diagnosis/epidemiology ; Male ; Mesothelioma/complications/*diagnosis/epidemiology ; Middle Aged ; Neoplasms/complications/*diagnosis/epidemiology ; Pleural Effusion, Malignant/*diagnosis/epidemiology/etiology ; Prospective Studies ; Sensitivity and Specificity ; Thoracentesis ; United Kingdom/epidemiology ; }, 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}, mesh = {Biomarkers, Tumor/*analysis ; Biopsy ; Humans ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/pathology ; Mesothelioma/*diagnosis/pathology ; Neoplasm Grading ; Pleural Neoplasms/*diagnosis/pathology ; Prognosis ; }, 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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 {pmid30256306, year = {2018}, author = {Tomasallo, CD and Christensen, KY and Raymond, M and Creswell, PD and Anderson, HA and Meiman, JG}, title = {An Occupational Legacy: Malignant Mesothelioma Incidence and Mortality in Wisconsin.}, journal = {Journal of occupational and environmental medicine}, volume = {60}, number = {12}, pages = {1143-1149}, doi = {10.1097/JOM.0000000000001461}, pmid = {30256306}, issn = {1536-5948}, support = {U60 OH010898/OH/NIOSH CDC HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asbestos ; Case-Control Studies ; Construction Industry/statistics &amp; numerical data ; Death Certificates ; Extraction and Processing Industry/statistics &amp; numerical data ; Female ; Humans ; Incidence ; Industry/*statistics &amp; numerical data ; Lung Neoplasms/*epidemiology/mortality ; Male ; Manufacturing Industry/statistics &amp; numerical data ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Occupational Diseases/*epidemiology/mortality ; Occupational Exposure/*statistics &amp; numerical data ; Peritoneal Neoplasms/*epidemiology/mortality ; Pleural Neoplasms/*epidemiology/mortality ; Registries ; Schools ; Teaching/statistics &amp; numerical data ; Wisconsin/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: The aim of the study was to describe mesothelioma occurrence in Wisconsin from 1997 to 2013 by usual industry and occupation (I&amp;O), including occupations generally considered low risk.<br><br>METHODS: Population-based rates and standardized incidence and mortality ratios were calculated. Two case-control analyses were designed to compare mesothelioma incidence and mortality in specific I&amp;O groups with occurrence of (1) brain and central nervous system cancers and (2) other causes of death, using logistic regression.<br><br>RESULTS: Mesothelioma incidence and mortality were elevated in Wisconsin (SIRadj = 1.20 [1.13 to 1.28]; SMRadj = 1.30 [1.22 to 1.38]). Certain industry (construction, manufacturing) and occupation (construction and extraction) groups were associated with increased odds of mesothelioma, with some evidence of increased risk among teachers.<br><br>CONCLUSIONS: Forty years after the Occupational and Safety Health Act, mesothelioma incidence and mortality remain elevated in Wisconsin, with increased risk continuing for certain I&amp;O groups.}, }
@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}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Calbindin 2/*blood ; Case-Control Studies ; Cohort Studies ; Female ; GPI-Linked Proteins/*blood ; Humans ; Incidence ; Lung Neoplasms/*blood/chemically induced/diagnosis ; Male ; Mesothelioma/*blood/chemically induced/diagnosis ; Middle Aged ; Occupational Exposure/*adverse effects ; Prognosis ; Prospective Studies ; }, 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 = {4}, number = {}, pages = {1-15}, pmid = {30241199}, issn = {2378-9506}, support = {P30 ES023515/ES/NIEHS NIH HHS/United States ; }, mesh = {Age Factors ; Female ; Humans ; International Classification of Diseases/*standards ; Mesothelioma/*mortality ; Mortality ; }, 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 {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 {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}, mesh = {*Asbestos ; Female ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@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}, mesh = {*Asbestos ; Female ; Humans ; *Lung Neoplasms ; *Mesothelioma ; }, }
@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}, mesh = {Adolescent ; Adult ; Cohort Studies ; Female ; Humans ; Lung Neoplasms/*etiology/pathology ; Male ; Mesothelioma/*etiology/pathology ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*etiology/pathology ; Prospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: We aimed to explore the effect of occupation on familial risk of pleural mesothelioma in a nationwide cohort study design.<br><br>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.<br><br>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).<br><br>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}, mesh = {Carcinogens/*toxicity ; Female ; France/epidemiology ; Humans ; Male ; Neoplasms/*chemically induced/epidemiology ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking.<br><br>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.<br><br>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.<br><br>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%).<br><br>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}, mesh = {Adolescent ; Adult ; Age Distribution ; Asbestos, Crocidolite/*toxicity ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Infant ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Proportional Hazards Models ; Sex Distribution ; Western Australia/epidemiology ; Young Adult ; }, 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.<br><br>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.<br><br>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.<br><br>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 {pmid30156102, year = {2018}, author = {Felley-Bosco, E and MacFarlane, M}, title = {Asbestos: Modern Insights for Toxicology in the Era of Engineered Nanomaterials.}, journal = {Chemical research in toxicology}, volume = {31}, number = {10}, pages = {994-1008}, doi = {10.1021/acs.chemrestox.8b00146}, pmid = {30156102}, issn = {1520-5010}, support = {MC_U132685863//Medical Research Council/United Kingdom ; }, mesh = {Air Pollutants/toxicity ; Asbestos/*toxicity ; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; Female ; Humans ; Lung Neoplasms/*etiology/mortality ; Male ; Mesothelioma/*etiology/mortality ; Mutation ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; Nanostructures/*chemistry ; Survival Rate ; Tumor Suppressor Protein p53/genetics/metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {Asbestos fibers are naturally occurring silicates that have been extensively used in the past, including house construction, but because of their toxicity, their use has been banned in 63 countries. Despite this, more than one million metric tons of asbestos are still consumed annually in countries where asbestos use has not been banned. Asbestos-related disease incidence is still increasing in several countries, including those countries that banned the use of asbestos more than 30 years ago. We highlight here recent knowledge obtained in experimental models about the mechanisms leading to tumor development following asbestos exposure, including genetic and epigenetic changes. Importantly, the landscape of alterations observed experimentally in tumor samples is consistent with alterations observed in clinical tumor samples; therefore, studies performed on early/precancer stages should help inform secondary prevention, which remains crucial in the absence of an efficient primary prevention. Knowledge gathered on asbestos should also help address future challenges, especially in view of the increased production of new materials that may behave similarly to asbestos fibers.}, }
@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}, mesh = {Aged ; Asbestos/*adverse effects ; Asbestosis ; Europe ; Female ; Humans ; Laryngeal Neoplasms ; Lung Neoplasms ; Male ; Mesothelioma ; Middle Aged ; Occupational Diseases/*chemically induced ; Occupational Exposure ; Ovarian Neoplasms ; Republic of Korea ; }, 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.<br><br>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.<br><br>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.<br><br>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 = {2019}, 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 = {40}, number = {3}, pages = {487}, 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}, mesh = {Animals ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis/toxicity ; Humans ; Lung Neoplasms/chemically induced/epidemiology ; Mesothelioma/chemically induced/epidemiology ; Microscopy, Electron, Transmission ; Mineral Fibers/*analysis/toxicity ; Minerals/*analysis/toxicity ; Occupational Exposure ; Particle Size ; Particulate Matter/*analysis/toxicity ; }, 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 &quot;Ambient Asbestos Fiber Concentrations and Long-Term Trends in Pleural Mesothelioma Incidence Between Urban and Rural Areas in the United States (1973-2012)&quot; 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 {pmid30126335, year = {2018}, author = {Egilman, D and Bird, T and Wilson, R}, title = {Use of Anti-Warnings to Falsely Reassure Downstream Users: An Asbestos Example.}, journal = {New solutions : a journal of environmental and occupational health policy : NS}, volume = {28}, number = {3}, pages = {515-538}, doi = {10.1177/1048291118794198}, pmid = {30126335}, issn = {1541-3772}, mesh = {Air Pollutants, Occupational/*adverse effects ; Asbestos/*adverse effects ; Asbestos, Serpentine/adverse effects ; *Communication ; Humans ; Industry/*organization &amp; administration ; Mesothelioma/chemically induced ; Occupational Exposure/*adverse effects ; Safety ; Uncertainty ; }, abstract = {Product warnings are theoretically designed to reduce injuries associated with occupational, environmental, or consumer product exposures. Unfortunately, in an effort to protect sales, some companies have produced media and information to falsely reassure their customers about the risks associated with their products. These tactics have been termed &quot;anti-warnings.&quot; We reviewed corporate documents uncovered in litigation alongside other historical publications to ascertain the types of anti-warnings used by Union Carbide Corporation (UCC) regarding their asbestos products. Our review finds that UCC went to great lengths to confuse their customers and make their particular asbestos product-which contained short-fiber, chrysotile asbestos-look safe. We discuss three primary communications methods UCC used: industry-produced publications, sales force direct communication with customers, and public speeches. These examples provide further insight into how corporations encourage uncertainty about the risks associated with their products. Understanding anti-warning methods is critical for the implementation of future policies that protect consumer, worker, and environmental health.}, }
@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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Female ; Humans ; Mesothelioma/*genetics/*pathology ; Middle Aged ; Mutation ; Peritoneal Neoplasms/*genetics/*pathology ; Von Hippel-Lindau Tumor Suppressor Protein/*genetics ; }, 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}, pmid = {30113886}, issn = {1527-7755}, support = {T35 DK062719/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Genetic Predisposition to Disease/genetics ; Germ-Line Mutation/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/*genetics ; Male ; Mesothelioma/*genetics ; Middle Aged ; Young Adult ; }, 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).<br><br>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.<br><br>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).<br><br>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}, mesh = {Carcinoma, Verrucous/*genetics ; Germ-Line Mutation/*genetics ; Humans ; Lung Neoplasms/*genetics ; Mesothelioma/*genetics ; Mouth Neoplasms/*genetics ; PTEN Phosphohydrolase/*genetics ; Rare Diseases ; }, 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.<br><br>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.<br><br>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 &amp; 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.<br><br>AIM: Malignant mesothelioma (MM) is unique for asbestos exposure.<br><br>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.<br><br>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.<br><br>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}, mesh = {Asbestos/*adverse effects ; Humans ; Incidence ; Lung Neoplasms/epidemiology/etiology/physiopathology ; *Medicine in the Arts ; Mesothelioma/epidemiology/etiology/physiopathology ; *Motion Pictures ; Occupational Exposure/*adverse effects ; Pleural Neoplasms/*epidemiology/etiology/physiopathology ; United States/epidemiology ; }, }
@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}, mesh = {Air Pollutants, Occupational/*toxicity ; Aluminum Silicates/toxicity ; Asbestos/*toxicity ; Asbestos, Amosite/toxicity ; Asbestos, Amphibole/toxicity ; Asbestos, Crocidolite/toxicity ; Asbestos, Serpentine/toxicity ; Carcinogens/*toxicity ; Cohort Studies ; Humans ; Iron/toxicity ; Lung Neoplasms/etiology/*mortality ; Mesothelioma/etiology/*mortality ; Minerals/*toxicity ; Mining ; Occupational Exposure ; Particle Size ; Particulate Matter/*toxicity ; Silicates/toxicity ; Talc/toxicity ; }, 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}, mesh = {Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Child ; Child, Preschool ; Environmental Exposure/*adverse effects ; Female ; *Forecasting ; Humans ; Incidence ; Infant ; Infant, Newborn ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Pleural Neoplasms/chemically induced/*epidemiology ; Regression Analysis ; Sex Distribution ; Taiwan/epidemiology ; Young Adult ; }, 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.<br><br>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.<br><br>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.<br><br>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 {pmid30049702, year = {2018}, author = {Lin, RT and Soeberg, MJ and Chien, LC and Fisher, S and Takala, J and Lemen, R and Driscoll, T and Takahashi, K}, title = {Bibliometric analysis of gaps in research on asbestos-related diseases: declining emphasis on public health over 26 years.}, journal = {BMJ open}, volume = {8}, number = {7}, pages = {e022806}, pmid = {30049702}, issn = {2044-6055}, mesh = {Asbestos/*adverse effects ; Asbestosis/*etiology ; Bibliometrics ; Biomedical Research/*trends ; China ; Finland ; Humans ; Italy ; Mesothelioma/*etiology ; Netherlands ; Public Health/trends ; }, abstract = {OBJECTIVES: The global burden of asbestos-related diseases (ARDs) is significant, and most of the world's population live in countries where asbestos use continues. We examined the gaps between ARD research and suggestions of WHO and the International Labour Organization on prevention.<br><br>METHODS: From the Web of Science, we collected data on all articles published during 1991-2016 and identified a subset of ARD-related articles. We classified articles into three research areas-laboratory, clinical and public health-and examined their time trends. For all and the top 11 countries publishing ARD-related articles, we calculated the proportions of all ARD-related articles that were in each of the three areas, the average rates of ARD-related articles over all articles, and the average annual per cent changes of rates.<br><br>RESULTS: ARD-related articles (n=14 284) accounted for 1.3‰ of all articles in 1991, but this had declined to 0.8‰ by 2016. Among the three research areas, the clinical area accounted for the largest proportion (65.0%), followed by laboratory (26.5%) and public health (24.9%). The public health area declined faster than the other areas, at -5.7% per year. Discrepancies were also observed among the top 11 countries regarding emphasis on public health research, with Finland and Italy having higher, and China and the Netherlands lower, emphases.<br><br>CONCLUSIONS: There is declining emphasis on the public health area in the ARD-related literature. Under the ongoing global situation of ARD, primary prevention will remain key for some time, warranting efforts to rectify the current trend in ARD-related research.}, }
@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}, mesh = {Aged ; Asbestos/*adverse effects ; Belgium/epidemiology ; Cohort Studies ; *Databases, Factual ; Female ; Humans ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/*epidemiology/mortality ; Middle Aged ; Registries/*statistics &amp; numerical data ; Survival Analysis ; Survivors ; }, 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).<br><br>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.<br><br>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%.<br><br>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.<br><br>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}, mesh = {Animals ; *Antineoplastic Agents/administration &amp; dosage/therapeutic use ; Cell Line, Tumor ; *Cisplatin/administration &amp; dosage/therapeutic use ; *Drug Carriers ; *Hyaluronic Acid ; Lung Neoplasms/*drug therapy ; Male ; Mesothelioma/*drug therapy ; Neoplasm Recurrence, Local/drug therapy ; *Pemetrexed/administration &amp; dosage/therapeutic use ; Pleural Neoplasms/*drug therapy ; Rats ; Rats, Inbred F344 ; }, 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}, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Asbestos/toxicity ; Carcinogenesis ; Carcinogens/*toxicity ; Cell Transformation, Neoplastic/drug effects ; Chromosomes/drug effects ; DNA/drug effects ; Humans ; Minerals/*toxicity ; }, 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 &amp; health}, volume = {45}, number = {1}, pages = {82-89}, doi = {10.5271/sjweh.3756}, pmid = {30025147}, issn = {1795-990X}, mesh = {Asbestos/*toxicity ; Carcinogens/*toxicity ; Denmark/epidemiology ; Environmental Exposure/*adverse effects ; Female ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Mesothelioma/*epidemiology ; Registries ; Risk Assessment ; }, 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 &quot;hotspot&quot; 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.<br><br>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).<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Female ; Germ-Line Mutation/*genetics ; Humans ; Laparoscopy ; Lung Neoplasms/diagnostic imaging/*genetics/pathology ; Male ; Mesothelioma/diagnostic imaging/*genetics/pathology ; Middle Aged ; Pedigree ; Peritoneal Neoplasms/diagnostic imaging/*genetics/pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, 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}, mesh = {Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/*mortality ; Male ; Mesothelioma/*epidemiology/*mortality ; Pleural Neoplasms/*epidemiology/*mortality ; *Population Surveillance ; Prognosis ; Survival Rate ; }, abstract = {BACKGROUND: Malignant mesothelioma (MM) is causally linked to asbestos exposure with an estimated etiological fraction of 80% or more.<br><br>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.<br><br>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.<br><br>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}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Asbestos/*analysis/*toxicity ; Environmental Exposure/*adverse effects ; Female ; Humans ; Lung Neoplasms/*chemically induced/*diagnosis ; Male ; Mesothelioma/*chemically induced/*diagnosis ; Middle Aged ; Occupational Exposure/*adverse effects ; }, 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}, support = {Z01 BC010816-01//Intramural NIH HHS/United States ; }, mesh = {Humans ; *Lung Neoplasms ; *Mesothelioma ; }, 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}, mesh = {Asbestos/*toxicity ; Belgium ; Female ; Humans ; Lung Neoplasms/chemically induced/epidemiology/*genetics ; Male ; Mesothelioma/chemically induced/epidemiology/*genetics ; Middle Aged ; Mutation ; Prevalence ; RNA-Binding Proteins/genetics ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, 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 ; }, mesh = {Animals ; Asbestos/*toxicity ; Carcinogens/*toxicity ; Disease Models, Animal ; Humans ; Lung Diseases/chemically induced ; Nanostructures/toxicity ; Nanotechnology ; Nanotubes, Carbon/*toxicity ; Occupational Exposure/adverse effects ; }, 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 &quot;fiber pathogenicity paradigm&quot; 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}, mesh = {Air Pollutants, Occupational ; Asbestos/*analysis ; Humans ; Lung/*chemistry ; Lung Neoplasms ; Mesothelioma ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mineral Fibers/analysis ; Minerals/*analysis ; Particle Size ; Particulate Matter/*analysis ; }, 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}, mesh = {B7-H1 Antigen/*genetics/metabolism ; Benzamides/pharmacology/therapeutic use ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; DNA Methylation/drug effects ; Decitabine/*pharmacology/therapeutic use ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Epigenesis, Genetic/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Histone Deacetylase Inhibitors/*pharmacology/therapeutic use ; Humans ; Hydroxamic Acids/pharmacology/therapeutic use ; Immunotherapy ; Killer Cells, Natural/cytology/drug effects ; Lung Neoplasms/drug therapy/*genetics/metabolism ; Male ; Mesothelioma/drug therapy/*genetics/metabolism ; T-Lymphocytes, Regulatory/cytology/drug effects ; Valproic Acid/*pharmacology/therapeutic use ; Vorinostat/*pharmacology/therapeutic use ; }, 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.<br><br>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.<br><br>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}, mesh = {Animals ; Cytokines ; Dose-Response Relationship, Drug ; Humans ; Inflammasomes/*drug effects ; Inhalation Exposure/*adverse effects ; Mineral Fibers/*toxicity ; NLR Family, Pyrin Domain-Containing 3 Protein/*genetics ; Particulate Matter/*toxicity ; Risk Assessment ; }, 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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Air Pollutants, Occupational ; Ceramics/*toxicity ; Humans ; Inhalation Exposure ; Mineral Fibers/*toxicity ; Occupational Diseases ; Occupational Exposure ; Respiratory Tract Diseases/chemically induced/pathology ; }, 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 {pmid29873855, year = {2018}, author = {Angelico, G and Ieni, A and Caltabiano, R and Zeppa, P and Tuccari, G}, title = {Aquaporin-1 expression in fluoro-edenite-induced mesothelioma effusions: An approach by cell-block procedure.}, journal = {Cytopathology : official journal of the British Society for Clinical Cytology}, volume = {29}, number = {5}, pages = {455-460}, doi = {10.1111/cyt.12583}, pmid = {29873855}, issn = {1365-2303}, mesh = {Aged ; Aged, 80 and over ; Aquaporin 1/*metabolism ; Asbestos, Amphibole/*toxicity ; Biomarkers, Tumor/*metabolism ; Cohort Studies ; Cytodiagnosis ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*chemically induced/*diagnosis/mortality ; Male ; Mesothelioma/*chemically induced/*diagnosis/mortality ; Middle Aged ; Pleural Effusion, Malignant/*chemically induced/*diagnosis/mortality ; Prognosis ; }, abstract = {OBJECTIVE: Aquaporin 1 (AQP-1) is a water channel protein found in cell membranes, whose expression has been considered an independent favourable prognostic factor in pleural malignant mesothelioma (MM). The aim of this study was to evaluate the expression of AQP-1 and its prognostic value in a series of pleural MM effusions, from a geographical area with high concentrations of fluoro-edenite (FE).<br><br>METHODS: We selected 25 MM cases from Biancavilla (Italy), an area with high environmental concentrations of FE. Cytological samples, cell-blocks (CB), clinical and follow-up data were available for all cases. Immunohistochemistry for calretinin, CK5/6, WT1, CK7 and TTF1 was used on CB sections to confirm the cytological diagnosis of MM. Immunohistochemistry for AQP-1 was performed and high expression was defined when ≥50% of tumour cells showed linear and circumferential membranous staining.<br><br>RESULTS: The cohort included 16 men and nine women (median age: 67.5 years; range: 49-88 years). The median survival was 14 months (range 1.5-60 months), with a significant value (P = 0.006). All cases have been histologically confirmed and classified as epithelioid (16 cases), biphasic (seven cases) and sarcomatoid (two cases). AQP-1 high expression has been observed in 16 cases. Comparing AQP-1 high expression to the survival of corresponding patients, a significant association with a slight increased overall survival of 12 months has been demonstrated. Nine patients with a AQP-1 score less than 50% showed a shorter median overall survival (7 months).<br><br>CONCLUSIONS: AQP-1 high expression is detectable on cytological samples of FE-induced MM with a prognostic value.}, }
@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.<br><br>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.<br><br>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).<br><br>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}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration &amp; dosage ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Male ; Mesothelioma/*drug therapy/pathology ; Middle Aged ; Nivolumab/administration &amp; dosage ; Pemetrexed/administration &amp; dosage ; Pleural Neoplasms/*drug therapy/pathology ; Prognosis ; Prospective Studies ; *Research Design ; Survival Rate ; Young Adult ; }, 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).<br><br>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.<br><br>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 &amp; 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 &amp; 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 &amp; inhibitors ; Programmed Cell Death 1 Receptor/antagonists &amp; 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.<br><br>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.<br><br>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).<br><br>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 &amp; 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).<br><br>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}, mesh = {Adult ; Aged ; Asbestos/adverse effects ; Cohort Studies ; Denmark/epidemiology ; Employment ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms/epidemiology/etiology ; Humans ; Incidence ; Lip Neoplasms/epidemiology/etiology ; Lung Neoplasms/epidemiology/etiology ; Male ; Mesothelioma/epidemiology/etiology ; Middle Aged ; Neoplasms/*epidemiology/etiology ; Occupational Diseases/*epidemiology/etiology ; Occupational Exposure/*adverse effects ; *Occupations ; Respiratory Tract Neoplasms/epidemiology/etiology ; Sex Factors ; *Ships ; Ultraviolet Rays/adverse effects ; Urogenital Neoplasms/epidemiology/etiology ; }, 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.<br><br>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.<br><br>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.<br><br>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 {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 {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}, mesh = {Aged ; Aged, 80 and over ; Asbestos/*toxicity ; Asbestosis/*etiology/mortality ; Environmental Exposure ; Environmental Monitoring ; Environmental Pollutants/*toxicity ; Female ; Geography, Medical ; Geological Phenomena ; Hospitalization/statistics &amp; numerical data ; Humans ; Incidence ; Italy ; Male ; Mesothelioma/etiology/mortality ; Mineral Fibers/toxicity ; Ovarian Neoplasms/mortality ; Population Surveillance ; Respiratory Tract Neoplasms/etiology/mortality ; }, abstract = {OBJECTIVES: to estimate the health impact of asbestos fibres naturally occurring in Mount Pollino area (Basilicata Region, Southern Italy).<br><br>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.<br><br>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.<br><br>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 {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 {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 &amp; control ; Cost of Illness ; Global Health/*statistics &amp; numerical data ; Humans ; Mesothelioma/diagnosis/*epidemiology/etiology/prevention &amp; 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}, mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Humans ; Lung Neoplasms/diagnostic imaging/drug therapy/*pathology ; Mesothelioma/diagnostic imaging/drug therapy/*pathology ; Pleural Neoplasms/diagnostic imaging/drug therapy/*pathology ; *Response Evaluation Criteria in Solid Tumors ; Survival Rate ; Tomography, X-Ray Computed/methods ; Treatment Outcome ; }, 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.<br><br>METHODS: The current de facto standard for the assessment of mesothelioma tumor response, &quot;modified RECIST&quot; (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 &quot;modified RECIST 1.1 for mesothelioma&quot; 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.<br><br>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.<br><br>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 ; }, mesh = {Asbestos/toxicity ; Computer Simulation ; Humans ; Inhalation Exposure/*adverse effects ; Minerals/*toxicity ; Occupational Exposure ; Particle Size ; Particulate Matter/*toxicity ; Respiratory Tract Diseases/*chemically induced ; Risk Assessment ; }, 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 &amp; 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}, mesh = {Animals ; Asbestos, Serpentine/*adverse effects/chemistry/toxicity ; Asbestosis/epidemiology/*etiology ; Humans ; Lung Neoplasms/*chemically induced/epidemiology ; Mesothelioma/*chemically induced/epidemiology ; *Mining ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; }, 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.<br><br>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.<br><br>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 &amp; 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 = {2019}, 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 = {105}, number = {4}, pages = {304-311}, doi = {10.1177/0300891618765538}, pmid = {29714657}, issn = {2038-2529}, mesh = {Asbestos/adverse effects ; Autopsy/methods ; Humans ; Immunohistochemistry/methods ; Lung Neoplasms/*diagnosis ; Mesothelioma/*diagnosis ; Pleural Diseases/*diagnosis ; Pleural Effusion/diagnosis ; Pleural Neoplasms/*diagnosis ; }, 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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Aged ; Databases, Factual ; Female ; Hospitals, University ; Humans ; Lung Neoplasms/diagnosis/*mortality/*therapy ; Male ; Mesothelioma/diagnosis/*mortality/*therapy ; Middle Aged ; Neoplasm Staging ; Pleural Neoplasms/diagnosis/*mortality/*therapy ; Prognosis ; Survival Analysis ; Taiwan/epidemiology ; }, 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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).<br><br>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).<br><br>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.<br><br>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.<br><br>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.<br><br>CONCLUSIONS: Our results demonstrate septin 7 not only serving as a &quot;cytoskeletal&quot; 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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Asbestos/adverse effects ; Denmark/epidemiology ; Humans ; *Lung Neoplasms/diagnosis/epidemiology/etiology/therapy ; *Mesothelioma/diagnosis/epidemiology/etiology/therapy ; Occupational Exposure/adverse effects ; *Pleural Neoplasms/diagnosis/epidemiology/etiology/therapy ; Prognosis ; Workers' Compensation ; }, 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 &amp; derivatives/pharmacology ; DNA (Cytosine-5-)-Methyltransferase 1/antagonists &amp; 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 = {2019}, 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 &amp; occupational health}, volume = {74}, number = {1-2}, pages = {76-84}, doi = {10.1080/19338244.2018.1467873}, pmid = {29677456}, issn = {2154-4700}, mesh = {Asbestos/*toxicity ; *Environmental Exposure ; Female ; Humans ; Incidence ; Lung Neoplasms/*chemically induced/epidemiology ; Male ; Mesothelioma/*chemically induced/epidemiology ; Mineral Fibers/*toxicity ; *Occupational Exposure ; Rural Population ; Zeolites/*toxicity ; }, 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 {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/ ; }, mesh = {Antineoplastic Agents, Immunological/adverse effects/economics/*therapeutic use ; Clinical Trials, Phase III as Topic ; Cost-Benefit Analysis ; Double-Blind Method ; Drug Costs ; Female ; Humans ; Male ; Mesothelioma/*drug therapy/economics/immunology/pathology ; Multicenter Studies as Topic ; *Neoplasm Recurrence, Local ; Nivolumab/adverse effects/economics/*therapeutic use ; Peritoneal Neoplasms/*drug therapy/economics/immunology/pathology ; Pleural Neoplasms/*drug therapy/economics/immunology/pathology ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; Progression-Free Survival ; Quality of Life ; Randomized Controlled Trials as Topic ; Time Factors ; Treatment Outcome ; United Kingdom ; }, 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.<br><br>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).<br><br>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.<br><br>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 ; }, mesh = {Administration, Oral ; Animals ; Asbestos/administration &amp; dosage/*toxicity ; Blood Proteins/drug effects/*metabolism ; Carcinogens/administration &amp; dosage/*toxicity ; Exosomes/drug effects/*metabolism ; Mice ; Mice, Inbred C57BL ; Proteomics ; Respiratory Aspiration ; }, 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}, mesh = {Cell Line, Tumor ; Cell Movement/drug effects/genetics ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Down-Regulation/drug effects ; *Drug Repositioning ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Inhibitory Concentration 50 ; Mesothelioma/*drug therapy/genetics/pathology ; Pyrvinium Compounds/pharmacology/*therapeutic use ; RNA, Messenger/genetics/metabolism ; Spheroids, Cellular/drug effects/metabolism/pathology ; Time Factors ; Wnt Signaling Pathway/drug effects/genetics ; beta Catenin/metabolism ; }, 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}, mesh = {Aged ; Aged, 80 and over ; Asbestos/adverse effects ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; DNA Copy Number Variations ; Environmental Exposure/adverse effects ; Female ; Humans ; Lung Neoplasms/*genetics/pathology ; Male ; Mesothelioma/*genetics/pathology ; Middle Aged ; Mutation/*genetics ; Neurofibromin 2/*genetics ; Pleural Effusion, Malignant/*genetics/pathology ; Tumor Cells, Cultured ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; }, 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Adult ; Aged ; Asbestos, Amphibole/*analysis/toxicity ; *Automobiles ; Humans ; Limit of Detection ; Lung/*chemistry ; Maintenance ; Mesothelioma/*etiology ; Middle Aged ; Occupational Diseases/*etiology ; Occupational Exposure/adverse effects/analysis/*statistics &amp; numerical data ; Peritoneal Neoplasms/*etiology ; Pleural Neoplasms/*etiology ; Regression Analysis ; }, 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.<br><br>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.<br><br>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).<br><br>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.<br><br>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).<br><br>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.<br><br>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}, mesh = {Construction Industry ; Forestry ; Humans ; Inhalation Exposure/analysis ; Montana ; National Institute for Occupational Safety and Health, U.S. ; Occupational Exposure/*analysis/prevention &amp; control ; Particulate Matter/analysis ; Silicon Dioxide/*analysis ; South Dakota ; United States ; Wyoming ; Zeolites/*analysis ; }, 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}, mesh = {Adaptation, Psychological ; Asbestos/*adverse effects ; Depression/psychology ; Female ; Humans ; Lung Neoplasms/epidemiology/*psychology ; Male ; Mesothelioma/epidemiology/*psychology ; Occupational Exposure/*adverse effects ; Quality of Life ; Social Support ; *Stress, Psychological ; }, 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.<br><br>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.<br><br>RESULTS: We identified 12 papers that investigated the psychological distress and care needs of mesothelioma patients, and nine papers for asbestos-exposed subjects.<br><br>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}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, }
@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.<br><br>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.<br><br>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).<br><br>DISCUSSION: ECE is a semi-objective, perfusion-based biomarker of PM, measurable in minimal pleural thickening. Further studies are warranted.}, }
@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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Air Pollutants, Occupational/*toxicity ; Animals ; Environmental Monitoring ; Humans ; Mineral Fibers/*toxicity ; Occupational Diseases/*epidemiology ; Occupational Exposure/adverse effects/analysis ; }, 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 &amp; 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 &amp; 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 ; }, mesh = {Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Asbestos, Amphibole/analysis ; Asbestos, Serpentine/analysis ; Carcinogens, Environmental/*adverse effects ; Environmental Exposure/*standards ; Female ; Humans ; Lung Neoplasms/etiology/*mortality ; Male ; Mesothelioma/etiology/*mortality ; Middle Aged ; Regression Analysis ; Risk Assessment ; Risk Factors ; United Kingdom/epidemiology ; }, 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.<br><br>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.<br><br>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.<br><br>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 &quot;An innovative mesothelioma treatment based on mir-16 mimic loaded EGFR targeted minicells (TargomiRs)&quot;.}, 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}, support = {R01 CA160715/CA/NCI NIH HHS/United States ; R01 CA198138/CA/NCI NIH HHS/United States ; U01 CA214195/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Immunotherapy/*methods/trends ; Lung Neoplasms/*therapy ; Mesothelioma/*therapy ; }, 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}, mesh = {Antigens, Neoplasm/genetics ; Asbestos/chemistry/*toxicity ; Asbestos, Crocidolite/administration &amp; dosage/toxicity ; Asbestos, Serpentine/administration &amp; dosage/toxicity ; Carbonic Anhydrase IX/genetics ; Cell Line ; DNA Methylation/*drug effects ; Dose-Response Relationship, Drug ; Epithelial Cells/drug effects ; Humans ; Lung Neoplasms/chemically induced/genetics ; Mesothelioma/chemically induced/genetics ; Real-Time Polymerase Chain Reaction ; Transcriptome/*drug effects ; }, 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.<br><br>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.<br><br>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).<br><br>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 &quot;epidemic&quot; of MPM with about half of the inhabitants dying for the disease. However, no results for a &quot;Cappadocia&quot; 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.<br><br>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.<br><br>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.<br><br>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 ; Transcription Factors ; *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 &amp; dosage ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/drug therapy/*pathology ; Lymphocytes/*pathology ; Male ; Mesothelioma/drug therapy/*pathology ; Middle Aged ; Neutrophils/*pathology ; Pemetrexed/administration &amp; 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).<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; laboratory medicine}, volume = {142}, number = {6}, pages = {753-760}, doi = {10.5858/arpa.2017-0365-RA}, pmid = {29480760}, issn = {1543-2165}, mesh = {Asbestos, Serpentine/adverse effects ; Europe ; Female ; Germ-Line Mutation ; Humans ; Lung Neoplasms/chemically induced/*etiology/genetics/pathology ; Male ; Mesothelioma/chemically induced/*etiology/genetics/pathology ; Nanotubes, Carbon/adverse effects ; North America ; Peritoneal Neoplasms/chemically induced/*etiology/genetics/pathology ; Pleural Neoplasms/chemically induced/*etiology/genetics/pathology ; Tumor Suppressor Proteins/*genetics ; Ubiquitin Thiolesterase/*genetics ; Zeolites/adverse effects ; }, abstract = {CONTEXT: - Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma.<br><br>OBJECTIVE: - To provide a review of non-asbestos causes for malignant mesothelioma.<br><br>DATA SOURCES: - Review of relevant published literature via PubMed and other search engines.<br><br>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 &amp; control ; Australia/epidemiology ; Female ; *Health Policy ; Humans ; Lung Neoplasms/*chemically induced/*epidemiology ; Male ; Mesothelioma/*chemically induced/*epidemiology ; Middle Aged ; Occupational Exposure/adverse effects/*legislation &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; 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 &amp; dosage/adverse effects ; Cisplatin/administration &amp; dosage/adverse effects ; Combined Modality Therapy ; Humans ; Immunotherapy/*methods ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Pemetrexed/administration &amp; 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.<br><br>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 &quot;IFCT MAPS-2&quot;, recently presented during the 2017 ASCO meeting, confirmed the value of ICI in MPM patients in cases of chemotherapy failure.<br><br>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.<br><br>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).<br><br>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.<br><br>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.<br><br>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}, mesh = {Adult ; Aged ; Area Under Curve ; Asbestos/toxicity ; Biomarkers, Tumor/blood ; Environmental Exposure ; Female ; Humans ; Lung Neoplasms/*diagnosis/genetics/pathology ; Male ; Mesothelioma/*diagnosis/genetics/pathology ; MicroRNAs/*blood/genetics/metabolism ; Middle Aged ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Smoking ; }, 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]).<br><br>PATIENTS &amp; 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.<br><br>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.<br><br>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 &amp; 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}, mesh = {Asbestos/*adverse effects ; Humans ; *Inhalation Exposure ; Lung Diseases/diagnosis/etiology ; Mass Screening ; Risk Factors ; }, 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 &amp; purification/*pharmacology ; Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Drug Synergism ; Female ; Humans ; In Vitro Techniques ; Lectins/isolation &amp; purification/*pharmacology ; Male ; Mesothelioma/*pathology ; Mice, Inbred BALB C ; Mice, Nude ; Ovum/*chemistry ; Pemetrexed/administration &amp; dosage ; Rana catesbeiana ; Ribonucleases/isolation &amp; 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 &quot;don't eat me&quot; 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 &quot;don't eat me&quot; 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}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, }
@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}, mesh = {Animals ; Asbestos, Amphibole/*toxicity ; Asbestos, Crocidolite/*toxicity ; Calcium Compounds/*toxicity ; Female ; Inflammation/chemically induced ; Lung/*drug effects/immunology/pathology ; Mice ; Mice, Inbred C57BL ; Silicates/*toxicity ; Transcriptome/*drug effects ; Zeolites/*toxicity ; }, 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 &quot;The asbestos fibre burden in human lungs: new insights into the chrysotile debate&quot;.}, 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 &quot;The asbestos fibre burden in human lungs: new insights into the chrysotile debate&quot;.}, 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 &quot;The asbestos fibre burden in human lungs: new insights into the chrysotile debate&quot;.}, 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}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asbestos/*adverse effects ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; Occupational Exposure/*adverse effects/statistics &amp; numerical data ; Registries ; Risk Factors ; Sex Factors ; }, 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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Aged ; Aged, 80 and over ; Apoptosis Regulatory Proteins/*genetics/metabolism ; Asbestos/*toxicity ; Body Burden ; Female ; Genetic Variation ; Humans ; Italy ; Lung/drug effects/*pathology ; Lung Neoplasms/*genetics/metabolism ; Male ; Mesothelioma/*genetics/metabolism ; Middle Aged ; Occupational Exposure/*adverse effects ; }, 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.<br><br>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.<br><br>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).<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Aged, 80 and over ; Asbestos, Crocidolite/isolation &amp; purification/*toxicity ; Asbestos, Serpentine/isolation &amp; purification/*toxicity ; Female ; Gallbladder/*chemistry/pathology ; Humans ; Lung Neoplasms/*mortality/pathology ; Mesothelioma/*mortality/pathology ; Occupational Exposure/*adverse effects ; }, 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}, mesh = {Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Bortezomib/*pharmacology ; Cell Line, Tumor ; Epithelium/pathology ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; Proteasome Endopeptidase Complex/*metabolism ; Proteasome Inhibitors/*pharmacology ; Ubiquitinated Proteins/metabolism ; }, 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 &amp; 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 &amp; medicine}, volume = {115}, number = {}, pages = {266-277}, doi = {10.1016/j.freeradbiomed.2017.12.008}, pmid = {29229551}, issn = {1873-4596}, mesh = {Acetylcysteine/pharmacology ; Androstadienes/*pharmacology ; Antineoplastic Agents/*pharmacology ; Aromatase Inhibitors/*pharmacology ; Asbestos/adverse effects ; Cell Death ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclic AMP/metabolism ; Environmental Exposure/adverse effects ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Mesothelioma/*drug therapy ; Oxidative Stress ; Pleural Neoplasms/*drug therapy ; Reactive Oxygen Species/metabolism ; Receptors, Estrogen ; Receptors, G-Protein-Coupled ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Treatment Outcome ; }, 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.<br><br>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).<br><br>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.<br><br>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.<br><br>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}, mesh = {Adult ; Aged ; Asbestos/*adverse effects ; Biomarkers, Tumor/analysis ; Cohort Studies ; Female ; Humans ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/etiology ; Male ; Mesothelioma/*epidemiology/etiology ; Middle Aged ; Occupational Exposure/adverse effects ; Peritoneal Neoplasms/*epidemiology/etiology ; Pleural Neoplasms/*epidemiology/etiology ; Textile Industry ; Tumor Suppressor Proteins/*biosynthesis ; Ubiquitin Thiolesterase/*biosynthesis ; }, 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.<br><br>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.<br><br>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.<br><br>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 &amp; 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 &amp; jurisprudence ; Humans ; *Inhalation Exposure ; Lung Neoplasms/chemically induced/economics ; Mesothelioma/chemically induced/economics ; *Occupational Exposure ; *Workers' Compensation/economics/legislation &amp; 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 = {}, 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 &amp; control ; Male ; Mesothelioma/blood/*chemically induced/pathology/*prevention &amp; 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.<br><br>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: &quot;Letter to the Editor&quot; regarding content of &quot;Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States&quot; 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 &amp; numerical data ; Humans ; Incidence ; Lung Neoplasms/chemically induced ; Mesothelioma/chemically induced ; Occupational Exposure/statistics &amp; 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 &amp; dosage/*analysis/therapeutic use ; Cell Line, Tumor ; *Drug Delivery Systems ; Humans ; Lung Neoplasms/*drug therapy ; Mesothelioma/*drug therapy ; MicroRNAs/administration &amp; 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.<br><br>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 &amp; 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 &quot;Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States&quot; 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}, doi = {10.5694/mja17.00397}, 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 &amp; 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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Animals ; Cell Movement/physiology ; DNA Methylation ; Gene Knockdown Techniques ; Heterografts ; Humans ; Lung Neoplasms/genetics/*metabolism/pathology ; Mesothelioma/genetics/*metabolism/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs/antagonists &amp; inhibitors/biosynthesis/genetics/*metabolism ; Neoplasm Invasiveness ; Pleural Neoplasms/genetics/*metabolism/pathology ; Promoter Regions, Genetic ; Transfection ; Y-Box-Binding Protein 1/genetics/*metabolism ; }, 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.<br><br>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.<br><br>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.<br><br>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}, mesh = {Animals ; *Asbestos ; Humans ; Inflammation ; *Lung Neoplasms ; *Mesothelioma ; Mice ; *Nanotubes, Carbon ; }, 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}, mesh = {Adult ; Age Factors ; Aged ; Asbestosis/diagnosis/epidemiology ; Clinical Competence ; *Environmental Exposure ; Female ; *General Practitioners ; *Health Knowledge, Attitudes, Practice ; Humans ; Incidence ; Italy/epidemiology ; Lung Neoplasms/*epidemiology/mortality ; Male ; Mesothelioma/diagnosis/*epidemiology/mortality ; Middle Aged ; Pleural Neoplasms/*epidemiology/mortality ; Registries ; }, 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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; numerical data ; Registries/*statistics &amp; 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.<br><br>OBJECTIVES: This study evaluated the impact of the extension of the network on MR sensitivity and timeliness.<br><br>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.<br><br>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).<br><br>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 = {2531-6745}, 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.<br><br>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.<br><br>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%).<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; jurisprudence/*prevention &amp; 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 &amp; control ; Environmental Monitoring ; Female ; Humans ; Incidence ; Lung Neoplasms/chemically induced/*epidemiology ; Male ; Mesothelioma/chemically induced/*epidemiology ; Middle Aged ; *Population Surveillance ; Risk ; Rural Population/statistics &amp; 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 &quot;from case to the field&quot; 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}, mesh = {*Asbestos ; Humans ; *Lung Neoplasms ; *Mesothelioma ; *Pleural Neoplasms ; }, }
@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.<br><br>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.<br><br>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).<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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 (&quot;luto&quot;) that resulted in a declining epidemic of malignant mesothelioma.<br><br>OBJECTIVES: We aimed to evaluate whether other sources of asbestos exposure exist following &quot;luto&quot; abandonment.<br><br>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 &quot;luto,&quot; in the 1980s-1990s, mainly to evaluate alveolitis. Those belonging to individuals of the same age range were used for further comparison.<br><br>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 &quot;luto&quot; 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.<br><br>CONCLUSION: &quot;Luto&quot; 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 =