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Bibliography on: Mesothelioma and Asbestos

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ESP: PubMed Auto Bibliography 08 Feb 2023 at 01:57 Created: 

Mesothelioma and Asbestos

Mesothelioma is a rare, but deadly form of cancer that is often (nearly always) associated with prior exposure to asbestos. The latency between exposure and disease onset is long, usually 20-50 years, making this a difficult cause-effect system to study.

Created with PubMed® Query: ( asbestos AND mesothelioma ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2023-02-05

Cunningham R, Jia S, Purohit K, et al (2023)

YAP/TAZ activation predicts clinical outcomes in mesothelioma and is conserved in in vitro model of driver mutations.

Clinical and translational medicine, 13(2):e1190.

The Hippo signalling pathway is dysregulated across a wide range of cancer types and, although driver mutations that directly affect the core Hippo components are rare, a handful is found within pleural mesothelioma (PM). PM is a deadly disease of the lining of the lung caused by asbestos exposure. By pooling the largest-scale clinical datasets publicly available, we here interrogate associations between the most prevalent driver mutations within PM and Hippo pathway disruption in patients, while assessing correlations with a variety of clinical markers. This analysis reveals a consistent worse outcome in patients exhibiting transcriptional markers of YAP/TAZ activation, pointing to the potential of leveraging Hippo pathway transcriptional activation status as a metric by which patients may be meaningfully stratified. Preclinical models recapitulating disease are transformative in order to develop new therapeutic strategies. We here establish an isogenic cell-line model of PM, which represents the most frequently mutated genes and which faithfully recapitulates the molecular features of clinical PM. This preclinical model is developed to probe the molecular basis by which the Hippo pathway and key driver mutations affect cancer initiation and progression. Implementing this approach, we reveal the role of NF2 as a mechanosensory component of the Hippo pathway in mesothelial cells. Cellular NF2 loss upon physiological stiffnesses analogous to the tumour niche drive YAP/TAZ-dependent anchorage-independent growth. Consequently, the development and characterisation of this cellular model provide a unique resource to obtain molecular insights into the disease and progress new drug discovery programs together with future stratification of PM patients.

RevDate: 2023-02-02

Slavik CE, Demers PA, Tamburic L, et al (2023)

Do patterns of past asbestos use and production reflect current geographic variations of cancer risk?: mesothelioma in Ontario and British Columbia, Canada.

Cancer causes & control : CCC [Epub ahead of print].

PURPOSE: Canada was a major global asbestos producer and consumer. Geographic patterns of Canadian asbestos use and mesothelioma, a highly fatal cancer linked to asbestos exposure, have not been previously reported. This study summarized key trends in mesothelioma incidence by geography and time in two Canadian provinces, Ontario and British Columbia (BC), and explored how past workforce characteristics and geographic trends in asbestos production and use may shape variations in regional rates of mesothelioma.

METHODS: We report trends in mesothelioma incidence (1993-2016) for Ontario and British Columbia using population-based incidence data that were age-standardized to the 2011 Canadian population. Historical records of asbestos production and use were analyzed to geo-locate industrial point sources of asbestos in Ontario and BC. The prevalence of occupations in regions with the highest and lowest rates of mesothelioma in Ontario and BC were calculated using labor force statistics from the 1981 Canadian Census.

RESULTS: Regional mesothelioma rates varied in both provinces over time; more census divisions in both Ontario and BC registered mesothelioma rates in the highest quintile of incidences during the period 2009 to 2016 than in any prior period examined. Certain occupations such as construction trades workers were more likely to be overrepresented in regions with high mesothelioma rates.

CONCLUSION: This work explored how studying asbestos exposure and mesothelioma incidence at small-scale geographies could direct cancer surveillance and research to more targeted areas. Findings indicated that regional variations in mesothelioma could signal important differences in past occupational and potentially environmental exposures.

RevDate: 2023-02-01

Endo I, Amatya VJ, Kushitani K, et al (2023)

miR-142-3p Suppresses Invasion and Adhesion of Mesothelioma Cells by Downregulating ITGAV.

Pathobiology : journal of immunopathology, molecular and cellular biology pii:000528670 [Epub ahead of print].

INTRODUCTION: Malignant mesothelioma is an aggressive cancer associated with asbestos exposure. Currently, the efficacy of therapeutics is limited in malignant mesothelioma, and developing more effective therapies is the need of the hour. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have attracted attention as therapeutic targets. To explore potential therapeutic targets, we focused on miR-142-3p expression, which was found to be significantly downregulated in mesothelioma cell lines in our previous study.

METHODS: Mesothelioma cell lines and tissues were validated for expression of miR-142-3p or integrin subunit alpha-V (ITGAV). We transfected mesothelioma cell lines with miR-142-3p mimic and ITGAV siRNA and analyzed their biological functions.

RESULTS: We found that miR-142-3p was significantly downregulated in mesothelioma tissues. Transfection with miR-142-3p mimic significantly suppressed cell proliferation, migration, and invasion. Bioinformatics analysis of potential targets of miR-142-3p identified ITGAV. Membrane ITGAV expression in mesothelioma cell lines was confirmed using immunocytochemistry. ITGAV was significantly upregulated in mesothelioma tissues. Moreover, transfection of miR-142-3p mimics into mesothelioma cell lines significantly suppressed ITGAV expression, indicating that miR-142-3p targets ITGAV. Next, ITGAV siRNA transfection into mesothelioma cell lines inhibited cell proliferation, migration, and invasion. Further investigation of cell adhesion mechanisms showed that the miR-142-3p/ITGAV axis specifically affects mesothelioma cell adhesion via vitronectin in the extracellular matrix.

CONCLUSION: This study proposed that the miR-142-3p/ITGAV axis is involved in tumor progression in malignant mesothelioma.

RevDate: 2023-01-31

Del Monaco A, Dimitriadis C, Xie S, et al (2023)

Workers in Australian prebake aluminium smelters: update on risk of mortality and cancer incidence in the Healthwise cohort.

Occupational and environmental medicine pii:oemed-2022-108605 [Epub ahead of print].

OBJECTIVES: To investigate mortality and the rates of incident cancer among a cohort of aluminium industry workers.

METHODS: Among 4507 male employees who worked in either of two Australian prebake smelters for at least 3 months, data linkage was undertaken with the Australian National Death Index and Australian Cancer Database. Standardised Mortality Ratios (SMRs) and Standardised Incidence Rates (SIRs) were estimated for the whole cohort and for: production; maintenance and office workers. SMRs and SIRs were calculated by time since first employment.

RESULTS: Among production workers, there was an excess risk of mortality from mesothelioma (SMR 2.8, 95% CI 1.3 to 5.2), lung (SMR 1.4, 95% CI 1.0 to 1.8), prostate (SMR 1.9, 95% CI 1.3 to 2.7) and liver cancer (SMR 2.0, 95% CI 1.1 to 3.4) and the SIR was also increased for overall respiratory cancers, specifically lung cancers. An excess risk of death from stomach cancer (SMR 2.9, 95% CI 1.2 to 6.1) and Alzheimer's disease (SMR 3.4, 95% CI 1.1 to 7.9) was seen among maintenance workers. The overall risk of death was similar to that of the Australian general population, as was mortality from cancers overall and non-malignant respiratory disease.

CONCLUSIONS: No excess risk of death from bladder cancer or non-malignant respiratory disease was found. Excess lung cancer mortality and incidence may be explained by smoking and excess mortality from mesothelioma may be explained by asbestos exposure. An excess risk of mortality from liver and prostate cancer has been shown in production workers and requires further investigation.

RevDate: 2023-01-27

Di Genova A, Mangiante L, Sexton-Oates A, et al (2022)

A molecular phenotypic map of malignant pleural mesothelioma.

GigaScience, 12:.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare understudied cancer associated with exposure to asbestos. So far, MPM patients have benefited marginally from the genomics medicine revolution due to the limited size or breadth of existing molecular studies. In the context of the MESOMICS project, we have performed the most comprehensive molecular characterization of MPM to date, with the underlying dataset made of the largest whole-genome sequencing series yet reported, together with transcriptome sequencing and methylation arrays for 120 MPM patients.

RESULTS: We first provide comprehensive quality controls for all samples, of both raw and processed data. Due to the difficulty in collecting specimens from such rare tumors, a part of the cohort does not include matched normal material. We provide a detailed analysis of data processing of these tumor-only samples, showing that all somatic alteration calls match very stringent criteria of precision and recall. Finally, integrating our data with previously published multiomic MPM datasets (n = 374 in total), we provide an extensive molecular phenotype map of MPM based on the multitask theory. The generated map can be interactively explored and interrogated on the UCSC TumorMap portal (

CONCLUSIONS: This new high-quality MPM multiomics dataset, together with the state-of-art bioinformatics and interactive visualization tools we provide, will support the development of precision medicine in MPM that is particularly challenging to implement in rare cancers due to limited molecular studies.

RevDate: 2023-01-25

Schelch K, Eder S, Zitta B, et al (2022)

YB-1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2.

Molecular oncology [Epub ahead of print].

Pleural mesothelioma (PM) is characterized by rapid growth, local invasion, and limited therapeutic options. The multifunctional oncoprotein Y-box-binding protein-1 (YB-1) is frequently overexpressed in cancer and its inhibition reduces aggressive behavior in multiple tumor types. Here, we investigated the effects of YB-1 on target gene regulation and PM cell behavior. Whereas siRNA-mediated YB-1 knockdown reduced cell motility, YB-1 overexpression resulted in scattering, increased migration, and intravasation in vitro. Furthermore, YB-1 stimulated PM cell spreading in zebrafish. Combined knockdown and inducible overexpression of YB-1 allowed bidirectional control and rescue of cell migration, the pattern of which was closely followed by the mRNA and protein levels of EGFR and the protein level of snail, whereas the mRNA levels of MMP1, EPHA5, and PARK2 showed partial regulation by YB-1. Finally, we identified snail as a critical regulator of YB-1-mediated cell motility in PM. This study provides insights into the mechanism underlying the aggressive nature of PM and highlights the important role of YB-1 in this cancer. In this context, we found that YB-1 closely regulates EGFR and snail, and, moreover, that YB-1-induced cell migration depends on snail.

RevDate: 2023-01-23

Romano M, Pinto P, Afonso R, et al (2023)

Pleural Mesothelioma: A Rapid Evolution of an Indolent Disease.

Cureus, 15(1):e33965.

Mesothelioma is a rare and insidious neoplasm and is characterized by its highly malignant and aggressive nature. The most common etiology is asbestos exposure, but there are some reports without known asbestos exposure and other factors leading to malignant pleural mesothelioma (MPM). Here, we present the case of a 58-year-old woman with pleuritic chest pain, dyspnea, and fever on presentation to the emergency department (ED), which caused several admissions to the ED in 20 days. The patient was then admitted to the internal medicine department with a diagnosis of community-acquired pneumonia with parapneumonic effusion. During hospitalization, a positron emission tomography (PET) scan, thoracic computed tomography (CT), and pleural biopsy were performed and a final diagnosis of malignant epithelioid pleural mesothelioma was made. Six weeks after the onset of symptoms, the patient presented with an exponential disease progression, dying two months after the diagnosis, despite the initiation of chemotherapy. MPM remains a diagnostic and therapeutic challenge with a very poor prognosis. However, studies show that mesothelioma patients who undergo treatment live at least twice as long as patients who do not receive treatment. This case report is particularly significant because, although it was epithelioid mesothelioma, multiple solid masses were noted on CT and the patient exhibited rapid disease progression, dying a few weeks after starting treatment.

RevDate: 2023-01-21

Magnani C, Mensi C, Binazzi A, et al (2023)

The Italian Experience in the Development of Mesothelioma Registries: A Pathway for Other Countries to Address the Negative Legacy of Asbestos.

International journal of environmental research and public health, 20(2): pii:ijerph20020936.

Asbestos (all forms, including chrysotile, crocidolite, amosite, tremolite, actinolite, and anthophyllite) is carcinogenic to humans and causally associated with mesothelioma and cancer of the lung, larynx, and ovary. It is one of the carcinogens most diffuse in the world, in workplaces, but also in the environment and is responsible for a very high global cancer burden. A large number of countries, mostly with high-income economies, has banned the use of asbestos which, however, is still widespread in low- and middle-income countries. It remains, thus, one of the most common occupational and environmental carcinogens worldwide. Italy issued an asbestos ban in 1992, following the dramatic observation of a large increase in mortality from mesothelioma and other asbestos-related diseases in exposed workers and also in subjects with non-occupational exposure. A mesothelioma registry was also organized and still monitors the occurrence of mesothelioma cases, conducting a case-by-case evaluation of asbestos exposure. In this report, we describe two Italian communities, Casale Monferrato and Broni, that faced an epidemic of mesothelioma resulting from the production of asbestos cement and the diffuse environmental exposure; we present the activity and results of the Italian mesothelioma registry (ReNaM), describe the risk-communication activities at the local and national level with a focus on international cooperation and also describe the interaction between mesothelioma registration and medical services specialized in mesothelioma diagnosis and treatment in an area at high risk of mesothelioma. Finally, we assess the potential application of the solutions and methods already developed in Italy in a city in Colombia with high mesothelioma incidence associated with the production of asbestos-cement materials and the presence of diffuse environmental asbestos pollution.

RevDate: 2023-01-18

Moline J, Patel K, AL Frank (2023)

Exposure to cosmetic talc and mesothelioma.

Journal of occupational medicine and toxicology (London, England), 18(1):1.

AIM: Mesothelioma is associated with asbestos exposure. In this case series, we present 166 cases of individuals who had substantial asbestos exposure to cosmetic talc products as well as some who had potential or documented additional exposures to other asbestos-containing products and who subsequently developed mesothelioma.

METHODS: Data were gathered for all subjects referred to an occupational and environmental medicine specialist as part of medicolegal review. Years of total cosmetic talcum powder usage was noted as well as the latency from the onset of talcum powder use to the mesothelioma diagnosis. Alternate asbestos exposure in addition to the exposure from cosmetic talc was categorized as none, possible, likely, and definite.

RESULTS: In 122 cases, the only known exposure to asbestos was from cosmetic talc. For 44 cases, potential or documented alternate exposures in addition to the cosmetic talc were described.

CONCLUSION: Cumulative exposure to asbestos leads to mesothelioma; for individuals with mixed exposures to asbestos, all exposures should be considered. Use of cosmetic talc is often overlooked as a source of asbestos exposure. All individuals with mesothelioma should have a comprehensive history of asbestos exposure, including cosmetic talc exposure.

RevDate: 2023-01-16

Piao ZH, Zhou XC, X Zhang (2022)

[Updates in the pathological diagnosis of Pleural Malignant Mesothelioma in the WHO classification of thoracic tumors (5(th) edition)].

Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases, 40(12):956-960.

The WHO Classification of Thoracic Tumors (5(th) edition) mainly has the following changes in the chapter of pleural malignant mesothelioma. (1) The concept of mesothelioma in situ and its diagnostic method have been established for the first time; (2) The tumour grading of pleural malignant mesothelioma was added, it was divided into low grade and high grade according to the cellular atypia, mitotic activity and presence of necrosis. (3) The morphological features of pleural malignant mesothelioma was classified into architectural pattern, cellular and stromal features, the correlation between histological features and prognosis was refined, and some of the controversial cellular types have been reclassified. In this review, we introduced the changes of related pathologic diagnosis, in the WHO Classification of Thoracic Tumors (5(th) edition) and discussed its clinical significance.

RevDate: 2023-01-13

Neff D, Padberg Sgier BC, Dietze H, et al (2022)

Unusually Aggressive Presentation of Malignant Peritoneal Mesothelioma: Two Case Reports.

Case reports in oncology, 15(3):1001-1008.

Malignant peritoneal mesothelioma is a rare disease. Patients mainly present with abdominal distension, pain, nausea, and weight loss with or without an exposure history of asbestos. Diagnosis may be difficult from a clinical and histopathologic perspective. Treatment options are surgery in early stages, radiotherapy and/or intraperitoneal or systemic therapy. Prognosis depends on TNM stage and histologic subtype with epithelioid subtype being the most favorable one but in general remains poor. We present a 59-year-old male (patient 1) and a 79-year-old female (patient 2) with progressive dyspnea. PET-CT of patient 1 revealed metastatic spread in the pleura and extensive peritoneal carcinomatosis. PET-CT of patient 2 displayed FDG-avid lymph nodes on both sides of the diaphragm, polyserositis, and FDG uptake along the peritoneum. Both patients were eventually diagnosed with malignant peritoneal mesothelioma. Patient 1 was treated with carboplatin and gemcitabine, and patient 2 received no systemic therapy. Even though the epithelioid subtype was found, both patients succumbed due to rapid tumor progression in a matter of a few weeks only. Presentation with polyserositis even in the absence of relevant asbestos exposure may represent malignant peritoneal mesothelioma if ascites is present, and rapid invasive diagnostic (excision biopsy) should be performed. These two unusual cases emphasize that even in epithelioid subtype, clinicians ought to be aware of possible rapid clinical deterioration, and timely diagnosis with initiation of therapy is crucial. Further research is necessary to better understand tumor biology, establish predictive markers, and develop new treatment options.

RevDate: 2023-01-13

Dusseault SK, Okobi OE, Thakral N, et al (2022)

Primary Peritoneal Mesothelioma: Diagnostic Challenges of This Lethal Imposter.

Case reports in gastroenterology, 16(3):588-594.

Primary Peritoneal Mesothelioma is a rapidly aggressive and rare neoplasm that arises from the lining of mesothelial cells of the peritoneum and spreads extensively within the confines of the abdominal cavity. The pathogenesis of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Characteristically, asbestos exposure has a strong relationship with mesothelioma of the pleura, but the peritoneal cavity is the second most commonly affected site. Additionally, in contrast to pleural mesothelioma, which has a male predominance (male-female ratio of between four and five to one), women comprise approximately one-half of all cases of malignant peritoneal mesothelioma. A thorough history of occupational/paraoccupational exposure along with histopathology is the key to timely diagnosis and treatment.

RevDate: 2023-01-12

Kurth L, Mazurek JM, DJ Blackley (2023)

Malignant mesothelioma among US Medicare beneficiaries: incidence, prevalence and therapy, 2016-2019.

Occupational and environmental medicine pii:oemed-2022-108706 [Epub ahead of print].

OBJECTIVES: Mesothelioma is a rare, aggressive cancer caused by exposure to asbestos fibres. Mesothelioma patients who receive trimodal therapy (chemotherapy, surgical resection and radiation) survive longer than those who receive two or fewer therapy modalities. This study analyses the 2016-2019 Medicare claims data to estimate the burden of malignant mesothelioma and describe therapy patterns (when available) among continuously enrolled fee-for-service (FFS; Medicare parts A and B) beneficiaries.

METHODS: We analysed claims and enrolment information from 42 529 117 FFS Medicare beneficiaries using three mesothelioma case definitions (broad, intermediate and narrow) with varying levels of diagnostic requirements. Results are presented as ranges of values for the three definitions.

RESULTS: Among FFS beneficiaries, 8213-19 036 beneficiaries with mesothelioma were identified depending on the case definition. The annual prevalence per 100 000 beneficiaries ranged from 8.8 in 2016 (narrow) to 31.3 in 2019 (broad) and annual incidence per 100 000 beneficiaries ranged from 4.5 in 2019 (narrow) to 12.6 in 2017 (broad). Depending on the mesothelioma case definition, 41.8%-81.5% had available therapy claim information indicating that 7.6%-11.3% received chemotherapy alone, 1.3%-1.5% received radiation alone, and 14.3%-27.0% underwent surgery only, with 4.6%-10.5% receiving all three therapy modalities.

CONCLUSIONS: Mesothelioma was a prevalent disease among FFS Medicare beneficiaries during 2016-2019, and a limited proportion of beneficiaries received all three therapy modalities. Medicare data build on findings from cancer registry data to enhance our understanding of the mesothelioma burden and therapy patterns.

RevDate: 2023-01-11

Caceres JD, AN Venkata (2023)

Asbestos-associated pulmonary disease.

Current opinion in pulmonary medicine [Epub ahead of print].

PURPOSE OF REVIEW: Exposure to asbestos can cause both benign and malignant, pulmonary and pleural diseases. In the current era of low asbestos exposure, it is critical to be aware of complications from asbestos exposure; as they often arise after decades of exposure, asbestos-related pulmonary complications include asbestosis, pleural plaques, diffuse pleural thickening, benign asbestos-related pleural effusions and malignant pleural mesothelioma.

RECENT FINDINGS: Multiple recent studies are featured in this review, including a study evaluating imaging characteristics of asbestos with other fibrotic lung diseases, a study that quantified pleural plaques on computed tomography imaging and its impact on pulmonary function, a study that examined the risk of lung cancer with pleural plaques among two large cohorts and a review of nonasbestos causes of malignant mesothelioma.

SUMMARY: Asbestos-related pulmonary and pleural diseases continue to cause significant morbidity and mortality. This review summarizes the current advances in this field and highlights areas that need additional research.

RevDate: 2023-01-09

Moscadelli A, Martini A, Angelini A, et al (2022)

[Mortality study in a cohort of entertainment workers].

Giornale italiano di medicina del lavoro ed ergonomia, 44(3):360-359.

Introduction. Malignant mesotheliomas have been observed in entertainment workers in the last decades. They have been evaluated as occupationally exposed to asbestos contained in tools used for fireproof and sound-absorbing purposes. Aim of the study. To evaluate the mortality of workers engaged in a Florentine theatre where a large quantity of asbestos was found in the '80s, put in place 20 years earlier. Methods. It is a cohort study on entertainment workers with follow-up period ranged from 1-1-1970 till 31-12-2018. Standardized Mortality Ratios (SMRs) and their 95% Confidence Intervals (95% IC) were calculated by gender and job ("manual workers" and "all other jobs"), using age and sex specific mortality rates of Tuscan population. Results. The cohort includes 826 workers (389 manual workers and 437 engaged in other jobs) engaged by the Florentine theatre between 01/01/1937 and 31/12/1990. Excesses of mortality for all causes are observed in manual workers, either males (301 cases; SMR 304,0; 95% IC 271,5-340,3) or females (86 cases; SMR 429,8; 95% IC 348,0-531,0). The group of the other workers presents deficits of mortality by all causes, cancers and cardiovascular diseases in both genders. One death for pleural cancer is observed in a manual worker. Discussion. The results are in line with previous observations in similar occupations. In the examined Florentine theatre the asbestos exposures were important only for the manual workers who worked in the technical rooms characterized by the presence of friable asbestos sprinkled and in a bad state of maintenance.

RevDate: 2023-01-08

Mutetwa B, Moyo D, D Brouwer (2022)

Prediction of Asbestos-Related Diseases (ARDs) and Chrysotile Asbestos Exposure Concentrations in Asbestos-Cement (AC) Manufacturing Factories in Zimbabwe.

International journal of environmental research and public health, 20(1): pii:ijerph20010058.

The use of historical asbestos measurement data in occupational exposure assessment is essential as it allows more quantitative analysis of possible exposure response relationships in asbestos-related disease (ARD) occurrence. The aim of this study was to predict possible ARDs, namely lung cancer, mesothelioma, gastrointestinal cancer, and asbestosis, in two chrysotile asbestos cement (AC) manufacturing factories. Prediction of ARDs was done using a specific designed job-exposure matrix for airborne chrysotile asbestos fibre concentrations obtained from the Harare and Bulawayo AC factories and through application of OSHA's linear dose effect model in which ARDs were estimated through extrapolation at 1, 10, 20, and 25 years of exposure. The results show that more cancer and asbestosis cases are likely to be experienced among those exposed before 2008 as exposure levels and subsequently cumulative exposure were generally much higher than those experienced after 2008. After a possible exposure period of 25 years, overall cancer cases predicted in the Harare factory were 325 cases per 100,000 workers, while for the Bulawayo factory, 347 cancer cases per 100,000 workers exposed may be experienced. Possible high numbers of ARDs are likely to be associated with specific tasks/job titles, e.g., saw cutting, kollergang, fettling table, ground hard waste, and possibly pipe-making operations, as cumulative exposures, though lower than reported in other studies, may present higher risk of health impairment. The study gives insights into possible ARDs, namely lung cancer, mesothelioma, gastrointestinal cancer, and asbestosis, that may be anticipated at various cumulative exposures over 1, 10, 20, and 25 years of exposure in AC manufacturing factories in Zimbabwe. Additionally, results from the study can also form a basis for more in-depth assessment of asbestos cancer morbidity studies in the AC manufacturing industries.

RevDate: 2023-01-08

Casalone E, Birolo G, Pardini B, et al (2022)

Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study.

Cancers, 15(1): pii:cancers15010125.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.

RevDate: 2023-01-05

Mankidy B, Sparkman J, Boddu S, et al (2022)

Simultaneous Use of Endobronchial and Endoscopic Ultrasound Guidance as Primary Tools in the Diagnosis of Malignant Pleural Mesothelioma.

Cureus, 14(12):e32110.

Malignant pleural mesothelioma (MPM) is related to exposure to asbestos. It is insidious in nature and is generally diagnosed at an advanced stage. MPM is aggressive and portends a poor prognosis. Definitive diagnosis is usually established by obtaining pathological samples of the pleura by medical or surgical thoracoscopy. However, these procedures are invasive and carry a risk of seeding of biopsy sites with tumors. We herein report an infrequently encountered case of simultaneous use of endobronchial ultrasound and endoscopic ultrasound-guided biopsy of malignant pleural mesothelioma in a 48-year-old female patient.

RevDate: 2022-12-23

Caraballo-Arias Y, Zunarelli C, Caffaro P, et al (2022)

Quantitative Assessment of Asbestos Fibers in Normal and Pathological Peritoneal Tissue-A Scoping Review.

Life (Basel, Switzerland), 12(12):.

Peritoneal tissue is the second most affected site by malignant mesothelioma linked to asbestos exposure. This scoping review aims to summarize the findings of the studies in which asbestos fibers in the peritoneum were quantified by electron microscopy, occasionally associated with spectroscopy, both in neoplastic and non-neoplastic tissue. The 9 studies selected comprised 62 cases, out of whom 100 samples were analyzed. Asbestos fibers were detected in 58 samples (58%). In addition, 28 cases had diagnosis of peritoneal mesothelioma. For 32 cases, a lung tumor sample was available: 28/32 samples analyzed presented asbestos fibers; 18/32 reported amphiboles with a range from not detected to 14.2 million fibers per gram of dry tissue (mfgdt); 18/32 reported chrysotile, with a range of 0 to 90 mfgdt. The studies were heterogeneous for type of samples, analytical technology, and circumstances of exposure to asbestos. To evaluate asbestos fibers in the peritoneum and to better understand the association between asbestos exposure and malignant peritoneal mesothelioma, it is desirable that the search for asbestos fibers becomes a routine process every time peritoneal tissue is accessible.

RevDate: 2022-12-23

Gardner M, Cross M, Reed S, et al (2022)

Pathogenic Potential of Respirable Spodumene Cleavage Fragments following Application of Regulatory Counting Criteria for Asbestiform Fibres.

International journal of environmental research and public health, 19(24): pii:ijerph192416649.

Health risks from exposure to lithium-bearing spodumene cleavage fragments are unknown. While asbestiform fibres can lead to fibrosis, mesothelioma and lung cancer, controversy remains whether non-asbestiform cleavage fragments, having equivalent dimensions, elicit similar pathologic responses. The mineralogy of respirable particles from two alpha (α)-spodumene concentrate grades (chemical and technical) were characterised using semi-quantitative X-ray diffraction (XRD). Particles were measured using scanning electron microscopy (SEM) and the dimensions (length [L], diameter [D], aspect ratio [AR]) applied to regulatory counting criteria for asbestiform fibres. Application of the current World Health Organization (WHO) and National Occupational Health and Safety Commission (NOHSC) counting criteria, L ˃ 5 µm, D ˂ 3 µm, AR ˃ 3:1, to 10 SEM images of each grade identified 47 countable particles in the chemical and 37 in the technical concentrate test samples. Of these particles, 17 and 16 in the chemical and technical test samples, respectively, satisfied the more rigorous, previously used Mines Safety and Inspection Regulations 1995 (Western Australia [WA]) criteria, L ˃ 5 µm and D ≤ 1 µm. The majority of the countable particles were consistent with α-spodumene cleavage fragments. These results suggest elongated α-spodumene particles may pose a health risk. It is recommended the precautionary principle be applied to respirable α-spodumene particles and the identification and control of dust hazards in spodumene extraction, handling and processing industries be implemented.

RevDate: 2022-12-23

Moro J, Sobrero S, Cartia CF, et al (2022)

Diagnostic and Therapeutic Challenges of Malignant Pleural Mesothelioma.

Diagnostics (Basel, Switzerland), 12(12): pii:diagnostics12123009.

Malignant pleural mesothelioma is a rare cancer characterized by a very poor prognosis. Exposure to asbestos is the leading cause of malignant pleural mesothelioma. The preinvasive lesions, the mesothelial hyperplasia and its possible evolution are the focus of the majority of the studies aiming to identify the treatable phase of the disease. The role of BAP-1 and MTAP in the diagnosis of mesothelioma in situ and in the prognosis of malignant pleural mesothelioma is the main topic of recent studies. The management of preinvasive lesions in mesothelioma is still unclear and many aspects are the subject of debate. The diagnosis, the disease staging and the accurate, comprehensive assessment of patients are three key instants for an appropriate management of patients/the disease.

RevDate: 2022-12-23

Rihs HP, Casjens S, Raiko I, et al (2022)

Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany.

Biology, 11(12): pii:biology11121826.

Malignant mesothelioma (MM) is a severe disease mostly caused by asbestos exposure. Today, one of the best available biomarkers is the soluble mesothelin-related protein (SMRP), also known as mesothelin. Recent studies have shown that mesothelin levels are influenced by individual genetic variability. This study aimed to investigate the influence of three mesothelin (MSLN) gene variants (SNPs) in the 5'-untranslated promoter region (5'-UTR), MSLN rs2235503 C > A, rs3764246 A > G, rs3764247 A > C, and one (rs1057147 G > A) in the 3'-untranslated region (3'-UTR) of the MSLN gene on plasma concentrations of mesothelin in 410 asbestos-exposed males without cancer and 43 males with prediagnostic MM (i.e., with MM diagnosed later on) from the prospective MoMar study, as well as 59 males with manifest MM from Germany. The mesothelin concentration differed significantly between the different groups (p < 0.0001), but not between the prediagnostic and manifest MM groups (p = 0.502). Five to eight mutations of the four SNP variants studied were associated with increased mesothelin concentrations (p = 0.001). The highest mesothelin concentrations were observed for homozygous variants of the three promotor SNPs in the 5'-UTR (p < 0.001), and the highest odds ratio for an elevated mesothelin concentration was observed for MSLN rs2235503 C > A. The four studied SNPs had a clear influence on the mesothelin concentration in plasma. Hence, the analysis of these SNPs may help to elucidate the diagnostic background of patients displaying increased mesothelin levels and might help to reduce false-positive results when using mesothelin for MM screening in high-risk groups.

RevDate: 2022-12-21

Chimed-Ochir O, Rath EM, Kubo T, et al (2022)

Must countries shoulder the burden of mesothelioma to ban asbestos? A global assessment.

BMJ global health, 7(12):.

INTRODUCTION: Mesothelioma is a key asbestos-related disease (ARD) but can be difficult to diagnose. Countries presumably ban asbestos to reduce future ARD burdens, but it is unknown if countries ban asbestos as a consequence of ARD burdens. We assessed if and to what extent mesothelioma burden has an impact on a country banning asbestos and obtaining targets for preventative strategies.

METHODS: We analysed the status of asbestos ban and mesothelioma burden during 1990-2019 in 198 countries. We assessed mesothelioma burden by age-adjusted mortality rates (MRs) estimated by the Global Burden of Disease Study (GBD) and mesothelioma identification by the WHO mortality database. For GBD-estimated mesothelioma MR, the pre-ban period in the asbestos-banned countries was compared with the 1990-2019 period in the not-banned countries. For mesothelioma identification, the 1990-2019 period was applied to both banned and not-banned countries.

RESULTS: The association of mesothelioma MR with ban status increased as the ban year approached. Logistic regression analyses showed that the odds of a country banning asbestos increased 14.1-fold (95% CI 5.3 to 37.9) for mesothelioma identification combined with a 26% (12% to 42%) increase per unit increase of mesothelioma MR (one death per million per year) during the period 1-5 year before ban (model p<0.0001).

CONCLUSION: Mesothelioma burden had an impact on, and together with its identification, explained the banning of asbestos in many countries. Asbestos-banned countries likely learnt lessons from their historical policies of using asbestos because mesothelioma burden and identification follow historical asbestos use. Prevention targets for ARD elimination should combine asbestos ban with mesothelioma identification.

RevDate: 2022-12-21

Luo Y, Akatsuka S, Motooka Y, et al (2022)

BRCA1 haploinsufficiency impairs iron metabolism to promote chrysotile-induced mesothelioma via ferroptosis-resistance.

Cancer science [Epub ahead of print].

Malignant mesothelioma (MM) is still a social burden associated with asbestos exposure. Local iron accumulation thereby represents the major pathogenesis, followed by oxidative DNA strand breaks and genomic alterations in the mesothelium. BRCA1 is a critical component of homologous recombination repair directed to DNA double-strand breaks. Whereas BRCA1 germline mutation is an established risk for breast/ovarian cancer, its role in MM development remains to be elucidated. Murine Brca1 mutant models thus far have not reproduced human phenotypes. However, a rat Brca1 mutant model (Mut; L63X/+) recently reproduced them at least partially. Here we describe the differential induction of MM in Brca1 mutant rats by intraperitoneal injection of chrysotile or crocidolite. Only Mut males injected with chrysotile revealed a promotional effect on mesothelial carcinogenesis in comparison to wild-type and/or females, with all the MMs Brca1-haploinsufficient. Array-based comparative genomic hybridization of MMs disclosed a greater extent of chromosomal deletions in Brca1 mutants, including Cdkn2a/2b accompanied by Tfr2 amplification, in comparison to wild-type tumors. Mutant MMs indicated iron metabolism dysregulation, such as increase in catalytic Fe(II) and Ki67-index as well as decrease in Fe(III) and ferritin expression. Simultaneously, mutant MMs revealed ferroptosis-resistance by upregulation of Slc7A11 and Gpx4. At an early carcinogenic stage of 4 weeks, induced Brca1 expression in mesothelial cells was significantly suppressed in chrysotile/Mut in comparison to crocidolite/Mut whereas significant preference to iron with decrease in Fe(III) has been already established. In conclusion, chrysotile exposure can be a higher risk for MM in BRCA1 mutant males, considering the rat results.

RevDate: 2022-12-16

Gazzano E, Petriglieri JR, Aldieri E, et al (2022)

Cytotoxicity of fibrous antigorite from New Caledonia.

Environmental research pii:S0013-9351(22)02373-8 [Epub ahead of print].

Exposure to asbestos and asbestos-like minerals has been related to the development of severe lung diseases, including cancer and malignant mesothelioma (MM). A high incidence of non-occupational MM was observed in New Caledonia (France) in people living in proximity of serpentinite outcrops, containing chrysotile and fibrous antigorite. Antigorite is a magnesium silicate, which shares with chrysotile asbestos the chemical formula. To achieve information on antigorite toxicity, we investigated the physico-minero-chemical features relevant for toxicity and cellular effects elicited on murine macrophages (MH-S) and alveolar epithelial cells (A549) of three fibrous antigorites (f-Atg) collected in a Caledonian nickel lateritic ore and subjected to supergene alteration. Field Atg were milled to obtain samples suitable for toxicological studies with a similar particle size distribution. UICC chrysotile (Ctl) and a non-fibrous antigorite (nf-Atg) were used as reference minerals. A high variability in toxicity was observed depending on shape, chemical alteration, and surface reactivity. The antigorites shared with Ctl a similar surface area (16.3, 12.1, 20.3, 13.4, and 15.6 m[2]/g for f-Atg1, 2, 3, nf-Atg, and Ctl). f-Atg showed different level of pedogenetic weathering (Ni depletion f-Atg1 ≪ f-Atg2 and 3) and contained about 50% of elongated mineral particles, some of which exhibited high aspect ratios (AR > 10 μm, 20%, 26%, 31% for f-Atg1, 2, and 3, respectively). The minerals differed in bio-accessible iron at pH 4.5 (f-Atg1 ≪ f-Atg3, < f-Atg2, nf-Atg < Ctl), and surface reactivity (ROS release in solution, f-Atg1 ≪ f-Atg2, 3, nf-Atg, and Ctl). f-Atg2 and f-Atg3 induced oxidative stress and pro-inflammatory responses, while the less altered, poorly reactive sample (f-Atg1) induced negligible effects, as well nf-Atg. The slow dissolution kinetics observed in simulated body fluids may signal a high biopersistence. Overall, our work revealed a significative cellular toxicity of f-Atg that correlates with fibrous habit and surface reactivity.

RevDate: 2022-12-15

Klotz LV, Hoffmann H, Shah R, et al (2022)

Multimodal therapy of epithelioid pleural mesothelioma: improved survival by changing the surgical treatment approach.

Translational lung cancer research, 11(11):2230-2242.

BACKGROUND: The exact role and type of surgery for malignant pleural mesothelioma (MPM) remains controversial. This study aimed at analyzing a 20-year single center perioperative experience in MPM surgery at our high-volume thoracic surgery center and comparing the overall survival after trimodal extrapleural pneumonectomy (EPP) and extended pleurectomy and decortication combined with hyperthermic intrathoracic chemoperfusion (EPD/HITOC) and adjuvant chemotherapy with that after chemotherapy (CTx) alone.

METHODS: Patients with epithelioid MPM treated with neoadjuvant chemotherapy, EPP and adjuvant radiotherapy within a trimodal concept or EPD/HITOC in combination with adjuvant chemotherapy between 2001 and 2018 were included in this retrospective analysis. Surgical cohorts were compared to patients treated with standard chemotherapy.

RESULTS: Overall, 182 patients (69 EPP, 57 EPD/HITOC, 56 CTx) were analyzed. Due to occupational exposure to asbestos for most of the patients, 154 patients (84.6%) were male. The patients in the surgical cohorts were significantly younger than those in the CTx cohort. There was no significant difference between the proportion of patient age and side. The median overall survival of the EPD/HITOC cohort with 38.1 months was significantly longer than that of the EPP and CTx cohorts (24.0 and 15.8 months). Better survival was significantly associated with an ECOG 0 performance status, age below 70 years, and negative lymph node status. In the multivariate analysis, EPD/HITOC was significantly associated with improved overall survival. Perioperative morbidity was lower in the EPD/HITOC group than in the EPP cohort.

CONCLUSIONS: EPD/HITOC is feasible and safe for localized epithelioid pleural mesothelioma. Changing the surgical approach to a less radical lung-sparing technique may improve overall survival compared to trimodal EPP.

RevDate: 2022-12-12

Guglielmucci F, Bonafede M, Azzolina D, et al (2022)

Preliminary validation of a brief PROM assessing psychological distress in patients with malignant mesothelioma: The mesothelioma psychological distress tool-Patients.

Frontiers in psychology, 13:974982.

OBJECTIVE: Psychological suffering in malignant mesothelioma (MM) differs from that in other cancers because of its occupational etiology, and we aimed to develop specific patient-reported outcome measures to assess it.

METHODS: We used a multi-method prospective observational multicentric study (N = 149), and a preliminary questionnaire validation was performed through a Bayesian approach.

RESULTS: Item analysis showed a good internal consistency and reliability (Cronbach alpha = 0.79 [95% CI = 0.74-0.93]. Twenty of the 41 initial items were selected as posterior 95% highest density interval factor loading standardized effect size fell outside of the region of practical equivalence. Bayesian exploratory factor analysis showed a two-factor structure: (1) Trauma-related reactions (TR, 13 items) and (2) Claim for justice (CJ, 7 items), confirmed by the Bayesian confirmatory factor analysis. Latent factors were poorly correlated (Posterior median: 0.13; 95% CI = -0.079 to 0.323). The 90% root mean square error of approximation posterior median was 0.04 [90% CI = 0.03-0.58]; the 90% chi-square posterior median was 242 [90% CI = 209-287].

CONCLUSION: Psychological suffering in MM patients implies negative cognitive, emotional, and somatic reactions related to the traumatic impact of the disease and the need to obtain justice through economic compensation. Our findings provide preliminary evidence that the Mesothelioma Psychological Distress Tool-Patients could be a promising and reliable instrument to assess MM patients' psychological distress.

RevDate: 2022-12-11

Munson P, A Shukla (2022)

Potential Roles of Exosomes in the Development and Detection of Malignant Mesothelioma: An Update.

International journal of molecular sciences, 23(23): pii:ijms232315438.

Malignant mesothelioma (MM) is a devastating cancer of mesothelial cells, caused by asbestos exposure. Limited knowledge regarding the detection of asbestos exposure and the early diagnosis of MM, as well as a lack of successful treatment options for this deadly cancer, project an immediate need to understand the mechanism(s) of MM development. With the recent discovery of nano-vesicles, namely exosomes, and their enormous potential to contain signature molecules representative of different diseases, as well as to communicate with distant targets, we were encouraged to explore their role(s) in MM biology. In this review, we summarize what we know so far about exosomes and MM based on our own studies and on published literature from other groups in the field. We expect that the information contained in this review will help advance the field of MM forward by revealing the mechanisms of MM development and survival. Based on this knowledge, future therapeutic strategies for MM can potentially be developed. We also hope that the outcome of our studies presented here may help in the detection of MM.

RevDate: 2022-12-11

Huh DA, Chae WR, Choi YH, et al (2022)

Disease Latency according to Asbestos Exposure Characteristics among Malignant Mesothelioma and Asbestos-Related Lung Cancer Cases in South Korea.

International journal of environmental research and public health, 19(23): pii:ijerph192315934.

Korea was one of the major consumers of asbestos in the late 1900s, and asbestos-related disease patients have been reported continuously to date, owing to long disease latency. Several studies have been conducted to predict the future incidence of malignant mesothelioma and lung cancer in Korea, but little is understood about the latency time. Therefore, the aim of this study is to estimate the latency period of malignant mesothelioma and asbestos-related lung cancer in Korea and its determinants. We obtained information from the Environmental Health Centers for Asbestos in Korea on the history of asbestos exposure and demographic characteristics of 1933 patients with malignant mesothelioma and asbestos-related lung cancer. In our study, the latency periods for malignant mesothelioma and lung cancer were 33.7 and 40.1 years, respectively. Regardless of the disease type, those with a history of exposure related to the production of asbestos-containing products or asbestos factories had the shortest latency period. In addition, we observed that those who worked in or lived near asbestos mines tended to have a relatively long disease latency. Smoking was associated with shorter latency, but no linear relationship between the lifetime smoking amount (expressed in pack years) and latent time was observed. In addition, the age of initial exposure showed a negative linear association with the latency period for mesothelioma and lung cancer.

RevDate: 2022-12-07

Ferrari L, Iodice S, Cantone L, et al (2022)

Identification of a new potential plasmatic biomarker panel for the diagnosis of malignant pleural mesothelioma.

La Medicina del lavoro, 113(6):e2022052.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare highly aggressive tumor strongly associated with asbestos exposure and characterized by poor prognosis. Currently, diagnosis is based on invasive techniques, thus there is a need of identifying non-invasive biomarkers for early detection of the disease among asbestos-exposed subjects. In the present study, we measured the plasmatic concentrations of Mesothelin, Fibulin-3, and HMGB1 protein biomarkers, and of hsa-miR-30e-3p and hsa-miR-103a-3p Extracellular-Vesicles- embedded micro RNAs (EV-miRNAs). We tested the ability of these biomarkers to discriminate between MPM and PAE subjects alone and in combination.

METHODS: the study was conducted on a population of 26 patients with MPM and 54 healthy subjects with previous asbestos exposure (PAE). Mesothelin, Fibulin-3, and HMGB1 protein biomarkers were measured by the enzyme-linked immunosorbent assay (ELISA) technique; the levels of hsa-miR-30e-3p and hsa-miR-103a-3p EV-miRNAs was assessed by quantitative real-time PCR (qPCR).

RESULTS: the most discriminating single biomarker resulted to be Fibulin-3 (AUC 0.94 CI 95% 0.88-1.0; Sensitivity 88%; Specificity 87%). After investigating the different possible combinations, the best performance was obtained by the three protein biomarkers Mesothelin, Fibulin-3, and HMGB1 (AUC 0.99 CI 95% 0.97-1.0; Sensitivity 96%; Specificity 93%).

CONCLUSIONS: the results obtained contribute to identifying new potential non-invasive biomarkers for the early diagnosis of MPM in high-risk asbestos-exposed subjects. Further studies are needed to validate the evidence obtained, in order to assess the reliability of the proposed biomarker panel.

RevDate: 2022-12-06
CmpDate: 2022-12-06

Graham PT, Nowak AK, Cornwall SMJ, et al (2022)

The STING agonist, DMXAA, reduces tumor vessels and enhances mesothelioma tumor antigen presentation yet blunts cytotoxic T cell function in a murine model.

Frontiers in immunology, 13:969678.

We assessed the murine Stimulator of Interferon Genes (STING) agonist, DMXAA, for anti-mesothelioma potential using the AE17-sOVA model that expresses ovalbumin (OVA) as a neo tumor antigen. Dose response experiments alongside testing different routes of administration identified a safe effective treatment regimen that induced 100% cures in mice with small or large tumors. Three doses of 25mg/kg DMXAA given intra-tumorally every 9 days induced tumor regression and long-term survival (>5 months). Re-challenge experiments showed that tumor-free mice developed protective memory. MTT and propidium-iodide assays showed that DMXAA exerted direct cytotoxic effects at doses >1mg/ml on the murine AE17 and AB1 mesothelioma cell lines. In-vivo studies using a CFSE-based in-vivo proliferation assay showed that DMXAA improved tumor-antigen presentation in tumor-draining lymph nodes, evidenced by OVA-specific OT-1 T cells undergoing more divisions. An in-vivo cytotoxic T lymphocyte (CTL) assay showed that DMXAA blunted the lytic quality of CTLs recognizing the dominant (SIINFEKL) and a subdominant (KVVRFDKL) OVA epitopes. DMXAA reduced tumor vessel size in-vivo and although the proportion of T cells infiltrating tumors reduced, the proportion of tumor-specific T cells increased. These data show careful dosing and treatment protocols reduce mesothelioma cell viability and modulate tumor vessels such that tumor-antigen specific CTLs access the tumor site. However, attempts to enhance DMXAA-induced anti-tumor responses by combination with an agonist anti-CD40 antibody or IL-2 reduced efficacy. These proof-of-concept data suggest that mesothelioma patients could benefit from treatment with a STING agonist, but combination with immunotherapy should be cautiously undertaken.

RevDate: 2022-12-06

Patel JP, Brook MS, Kah M, et al (2022)

Global geological occurrence and character of the carcinogenic zeolite mineral, erionite: A review.

Frontiers in chemistry, 10:1066565.

As with the six regulated asbestos minerals (chrysotile, amosite, crocidolite, anthophyllite, tremolite, and actinolite), the zeolite mineral, erionite, can exhibit a fibrous morphology. When fibrous erionite is aerosolized and inhaled, it has been linked to cases of lung cancers, such as malignant mesothelioma. Importantly, fibrous erionite appears to be more carcinogenic than the six regulated asbestos minerals. The first health issues regarding erionite exposure were reported in Cappadocia (Turkey), and more recently, occupational exposure issues have emerged in the United States. Erionite is now classified as a Group 1 carcinogen. Thus, identifying the geological occurrence of erionite is a prudent step in determining possible exposure pathways, but a global review of the geological occurrence of erionite is currently lacking. Here, we provide a review of the >100 global locations where erionite has been reported, including: 1) geological setting of host rocks; 2) paragenetic sequence of erionite formation, including associated zeolite minerals; 3) fiber morphological properties and erionite mineral series (i.e., Ca, K, Na); and 4) a brief overview of the techniques that have been used to identify and characterize erionite. Accordingly, erionite has been found to commonly occur within two major rock types: felsic and mafic. Within felsic rocks (in particular, tuffaceous layers within lacustrine paleoenvironments), erionite is disseminated through the layer as a cementing matrix. In contrast, within mafic (i.e., basaltic) rocks, erionite is typically found within vesicles. Nevertheless, aside from detailed studies in Italy and the United States, there is a paucity of specific information on erionite geological provenance or fiber morphology. The latter issue is a significant drawback given its impact on erionite toxicity. Future erionite studies should aim to provide more detailed information, including variables such as rock type and lithological properties, quantitative geochemistry, and fiber morphology.

RevDate: 2022-11-29
CmpDate: 2022-11-29

Handra CM, Chirila M, Smarandescu RA, et al (2022)

Near Missed Case of Occupational Pleural Malignant Mesothelioma, a Case Report and Latest Therapeutic Options.

International journal of environmental research and public health, 19(22): pii:ijerph192214763.

Asbestos use started to be gradually banned in Europe from 1991 onwards, and there are currently strict occupational exposure limits for asbestos. However, malignant mesothelioma has a long latency time (in some cases up to 50-60 years), so the risks related to asbestos exposure should not be forgotten. Considering the increased risk of lung cancer following the inhalation of asbestos fibers, lifetime health monitoring should be considered in people occupationally exposed to asbestos, with an emphasis on the respiratory system. An assessment of their occupational history should be performed rigorously, especially in the areas with a history of asbestos production/use, as this is a key element for an early diagnosis and appropriate treatment. This case report presents a near-missed case of occupational pleural malignant mesothelioma. The latency time between the first asbestos exposure and the diagnosis of occupational pleural malignant mesothelioma was 49 years. The accurate diagnosis was made two years after the first symptoms appeared.

RevDate: 2022-11-25

Keam S, MacKinnon KM, D'Alonzo RA, et al (2022)

Effects of Photon Radiation on DNA Damage, Cell Proliferation, Cell Survival, and Apoptosis of Murine and Human Mesothelioma Cell Lines.

Advances in radiation oncology, 7(6):101013.

PURPOSE: To characterize the cellular responses of murine and human mesothelioma cell lines to different doses of photon radiation with a long-term aim of optimizing a clinically relevant in vivo model in which to study the interaction of radiation therapy and immunotherapy combinations.

METHODS AND MATERIALS: Two murine mesothelioma cell lines (AB1 and AE17) and 3 human cell lines (BYE, MC, and JU) were used in the study. Cells were treated with increasing doses of photon radiation. DNA damage, DNA repair, cell proliferation, and apoptosis at different time points after irradiation were quantified by flow cytometry, and cell survival probability was examined using clonogenic survival assay.

RESULTS: DNA damage increased with escalating dose in all cell lines. Evident G2/M arrest and reduced cell proliferation were observed after irradiation with 8 Gy. DNA repair was uniformly less efficient at higher compared with lower radiation-fraction doses. The apoptosis dose response varied between cell lines, with greater apoptosis observed at 16 Gy with human BYE and murine AB1 cell lines but less for other studied cell lines, regardless of dose and time. The α/β ratio from the cell survival fraction of human mesothelioma cell lines was smaller than from murine ones, suggesting human cell lines in our study were more sensitive to a change of dose per fraction than were murine mesothelioma cell lines. However, in all studied cell lines, colony formation was completely inhibited at 8 Gy.

CONCLUSIONS: A threshold dose of 8 Gy appeared to be appropriate for hypofractionated radiation therapy. However, the radiation therapy doses between 4 and 8 Gy remain to be systematically analyzed. These observations provide an accurate picture of the in vitro response of mesothelioma cell lines to photon irradiation and characterize the heterogeneity between human and murine cell lines. This information may guide in vivo experiments and the strengths and limitations of extrapolation from murine experimentation to potential human translation.

RevDate: 2022-11-25

Yabuuchi Y, Hiroshima K, Oshima H, et al (2022)

Usefulness of malignant pleural effusion for early cytological diagnosis of mesothelioma in situ: A case report.

Oncology letters, 24(6):440.

Mesothelioma in situ (MIS) is defined as a preinvasive mesothelioma that forms a single layer of mild atypical mesothelial cells lining on the serosa surface of pleura. The atypical mesothelial cells present loss of BRCA-1 associated protein-1 (BAP-1) and/or methylthioadenosine phosphorylase as examined by immunohistochemistry (IHC) and/or homozygous deletion of cyclin-dependent kinase inhibitor 2A/p16 as examined by fluorescence in situ hybridization. It is difficult to diagnose because of the unremarkable clinical findings except for pleural effusion. The present report describes a case in which MIS was diagnosed at the time of sampling due to the presence of clearly malignant mesothelial cells in the pleural fluid. In 2016, a 74-year-old man with a history of past exposure to asbestos was admitted to Ibaraki Higashi National Hospital (Tokai-mura, Japan) with dyspnea. Chest CT indicated only right pleural effusion. Malignant mesothelial cells were suspected in a cell block made using pleural effusion; therefore, right pleural biopsy was performed. Pathologically, there was proliferation of mesothelial cells with mild atypia that formed a single-flat layer on the pleural surface; however, there was no invasion. Furthermore, IHC revealed loss of BAP-1 in cells from the biopsied pleura and pleural effusion. MIS was suspected at the time; however, the patient arbitrarily quit his medical check-ups. After 44 months, the patient was readmitted to our hospital complaining of dyspnea. CT indicated a large right pleural mass. A specimen of the mass obtained via CT-guided needle biopsy revealed malignant mesothelioma. The patient continued to deteriorate and eventually died. This case indicated that pleural effusion could be used to demonstrate overtly malignant mesothelial cells and diagnose MIS at the time of sampling. To the best of our knowledge, this is first report of MIS with overtly malignant mesothelial cells in pleural effusion. Pleural effusion may serve an important role in MIS diagnosis.

RevDate: 2022-11-23

Walter M, Schenkeveld WDC, Tomatis M, et al (2022)

The Potential Contribution of Hexavalent Chromium to the Carcinogenicity of Chrysotile Asbestos.

Chemical research in toxicology [Epub ahead of print].

Chrysotile asbestos is a carcinogenic mineral that has abundantly been used in industrial and consumer applications. The carcinogenicity of the fibers is partly governed by reactive Fe surface sites that catalyze the generation of highly toxic hydroxyl radicals (HO[•]) from extracellular hydrogen peroxide (H2O2). Chrysotile also contains Cr, typically in the low mass permille range. In this study, we examined the leaching of Cr from fibers at the physiological lung pH of 7.4 in the presence and absence of H2O2. Furthermore, we investigated the potential of cells from typical asbestos-burdened tissues and cancers to take up Cr leached from chrysotile in PCR expression, immunoblot, and cellular Cr uptake experiments. Finally, the contribution of Cr to fiber-mediated H2O2 decomposition and HO[•] generation was studied. Chromium readily dissolved from chrysotile fibers in its genotoxic and carcinogenic hexavalent redox state upon oxidation by H2O2. Lung epithelial, mesothelial, lung carcinoma, and mesothelioma cells expressed membrane-bound Cr(VI) transporters and accumulated Cr up to 10-fold relative to the Cr(VI) concentration in the spiked medium. Conversely, anion transporter inhibitors decreased cellular Cr(VI) uptake up to 45-fold. Finally, chromium associated with chrysotile neither decomposed H2O2 nor contributed to fiber-mediated HO[•] generation. Altogether, our results support the hypothesis that Cr may leach from inhaled chrysotile in its hexavalent state and subsequently accumulate in cells of typically asbestos-burdened tissues, which could contribute to the carcinogenicity of chrysotile fibers. However, unlike Fe, Cr did not significantly contribute to the adverse radical production of chrysotile.

RevDate: 2022-11-18

Chang F, Keam S, Hoang TS, et al (2022)

Immune marker expression of irradiated mesothelioma cell lines.

Frontiers in oncology, 12:1020493.

BACKGROUND: Though immune checkpoint inhibition has recently shown encouraging clinical efficacy in mesothelioma, most patients do not respond. Combining immune checkpoint inhibition with radiotherapy presents an attractive option for improving treatment responses owing to the various immunomodulatory effects of radiation on tumors. However, the ideal dosing and scheduling of combined treatment remains elusive, as it is poorly studied in mesothelioma. The present study characterizes the dose- and time-dependent changes to expression of various immune markers and cytokines important to antitumor responses following irradiation of mesothelioma cell lines.

METHODS: Two murine (AB1, AE17) and two human (BYE, JU77) mesothelioma cell lines were treated with titrated gamma-radiation doses (1-8 Gy) and the expression of MHC class-I, MHC class-II and PD-L1 was measured over a series of post-irradiation timepoints (1-72 hours) by flow cytometry. Levels of cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-β, IFN-γ, TNF-α, and GM-CSF were measured by multiplex immunoassay in murine cell lines following 8 Gy radiation.

RESULTS: Following irradiation, a dose-dependent upregulation of MHC-I and PD-L1 was observed on three of the four cell lines studied to varying extents. For all cell lines, the increase in marker expression was most pronounced 72 hours after radiation. At this timepoint, increases in levels of cytokines IFN-β, MCP-1 and IL-6 were observed following irradiation with 8 Gy in AB1 but not AE17, reflecting patterns in marker expression.

CONCLUSIONS: Overall, this study establishes the dose- and time-dependent changes in immune marker expression of commonly studied mesothelioma cell lines following radiation and will inform future study into optimal dosing and scheduling of combined radiotherapy and immune checkpoint inhibition for mesothelioma.

RevDate: 2022-11-17
CmpDate: 2022-11-14

Crovella S, Moura RR, Brandão L, et al (2022)

Variant Enrichment Analysis to Explore Pathways Disruption in a Necropsy Series of Asbestos-Exposed Shipyard Workers.

International journal of molecular sciences, 23(21):.

The variant enrichment analysis (VEA), a recently developed bioinformatic workflow, has been shown to be a valuable tool for whole-exome sequencing data analysis, allowing finding differences between the number of genetic variants in a given pathway compared to a reference dataset. In a previous study, using VEA, we identified different pathway signatures associated with the development of pulmonary toxicities in mesothelioma patients treated with radical hemithoracic radiation therapy. Here, we used VEA to discover novel pathways altered in individuals exposed to asbestos who developed or not asbestos-related diseases (lung cancer or mesothelioma). A population-based autopsy study was designed in which asbestos exposure was evaluated and quantitated by investigating objective signs of exposure. We selected patients with similar exposure to asbestos. Formalin-fixed paraffin-embedded (FFPE) tissues were used as a source of DNA and whole-exome sequencing analysis was performed, running VEA to identify potentially disrupted pathways in individuals who developed thoracic cancers induced by asbestos exposure. By using VEA analysis, we confirmed the involvement of pathways considered as the main culprits for asbestos-induced carcinogenesis: oxidative stress and chromosome instability. Furthermore, we identified protective genetic assets preserving genome stability and susceptibility assets predisposing to a worst outcome.

RevDate: 2022-11-17
CmpDate: 2022-11-14

Paajanen J, Bueno R, A De Rienzo (2022)

The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma.

International journal of molecular sciences, 23(21):.

Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20-40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.

RevDate: 2022-11-17
CmpDate: 2022-11-14

Vorster T, Mthombeni J, teWaterNaude J, et al (2022)

The Association between the Histological Subtypes of Mesothelioma and Asbestos Exposure Characteristics.

International journal of environmental research and public health, 19(21):.

Asbestos mining operations have left South Africa with a legacy of asbestos contamination and asbestos-related diseases continue to be a problem. The large-scale mining of three types of asbestos presents a unique opportunity to study malignant mesothelioma of the pleura (mesothelioma) in South Africa. This study aimed to describe the demographics of deceased individuals diagnosed with mesothelioma and explore any associations between the histological morphology of mesothelioma and asbestos characteristics. We reviewed the records of all deceased miners and ex-miners from the Pathology Automation System (PATHAUT) database of the National Institute of Occupational Health (NIOH) that were histologically diagnosed with mesothelioma in the period from January 2006-December 2016 (11 years). The study population does not include all cases of mesothelioma in South Africa but rather those that reached the compensation system. Crocidolite asbestos fibres were identified in the majority of mesothelioma cases (n = 140; 53.4%). The epithelioid subtype was most commonly present in both occupational and environmental cases. Cases with the sarcomatous subtype were older at death and fewer female cases were diagnosed with this subtype. No relationship between mesothelioma subtype and asbestos type or asbestos burden or fibre size was established.

RevDate: 2022-11-10

Azzolina D, Consonni D, Ferrante D, et al (2022)

Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.

Thorax pii:thorax-2021-217862 [Epub ahead of print].

INTRODUCTION: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy.

METHOD: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE).

RESULT: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE.

CONCLUSION: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.

RevDate: 2022-11-10

Kadariya Y, Sementino E, Shrestha U, et al (2022)

Inflammation as a chemoprevention target in asbestos-induced malignant mesothelioma.

Carcinogenesis pii:6820973 [Epub ahead of print].

Malignant mesothelioma (MM) is an incurable cancer of the serosal lining that is often caused by exposure to asbestos. Therefore, novel agents for the prevention and treatment of this disease are urgently needed. Asbestos induces the release of pro-inflammatory cytokines such as IL-1β and IL-6, which play a role in MM development. IL-6 is a component of the JAK-STAT3 pathway that contributes to inflammation-associated tumorigenesis. Glycoprotein 130 (gp130), the signal transducer of this signaling axis, is an attractive drug target because of its role in promoting neoplasia via the activation of downstream STAT3 signaling. The anticancer drug, SC144, inhibits the interaction of gp130 with the IL-6 receptor (IL6R), effectively blunting signaling from this inflammatory axis. To test whether the inflammation-related release of IL-6 plays a role in the formation of MM, we evaluated the ability of SC144 to inhibit asbestos-induced carcinogenesis in a mouse model. The ability of sulindac and anakinra, an IL6R antagonist/positive control, to inhibit MM formation in this model were tested in parallel. Asbestos-exposed Nf2 +/-;Cdkn2a +/- mice treated with SC144, sulindac, or anakinra showed significantly prolonged survival compared to asbestos-exposed vehicle-treated mice. STAT3 activity was markedly decreased in MM specimens from SC144-treated mice. Furthermore, SC144 inhibited STAT3 activation by IL-6 in cultured normal mesothelial cells, and in vitro treatment of MM cells with SC144 markedly decreased the expression of STAT3 target genes. The emerging availability of newer, more potent SC144 analogs showing improved pharmacokinetic properties holds promise for future trials, benefitting individuals at high risk of this disease.

RevDate: 2022-11-10
CmpDate: 2022-11-10

Fassio F, Bussa M, Oddone E, et al (2022)

Health status of petrochemical workers: a narrative review.

Giornale italiano di medicina del lavoro ed ergonomia, 44(1):51-58.

Professional exposure to benzene has been extensively investigated by occupational medicine, leading to strict regulation of exposure threshold values. However, the petrochemical industry utilizes many chemical substances, whose exposure, without effective control and mitigation actions, could influence the health status over time. The aim of this narrative review is to describe health status of petrochemical workers related to occupational exposures, inquiring literature from 1980 to present. We used the PubMed and Web of Science search engines. As regards non-neoplastic diseases, despite heterogeneous prevalence estimates, we could say that standardized mortality rate (SMR) for hypertension, hypercholesterolemia and diabetes does not increase overall, compared to reference populations; a possible explanation may be the "healthy worker effect". Attention should be paid to color disperception and respiratory symptoms, due to toxic or irritating substances exposure. Studies concerning neoplastic pathology have mainly investigated mortality outcomes, finding no increase in cancer, except for melanoma or other skin cancers and leukemia. As regards the former, however, it is not excluded that other risk factors may contribute (e.g. UV rays in offshore workers), while for leukemia, only the most recent studies have analyzed various subtypes of hematopoietic tumors, highlighting a possible risk for the development of myelodysplastic syndrome. The risk of pleural mesothelioma was also increased, likely due to asbestos exposures, while the risk of death from prostate cancer remains controversial.

RevDate: 2022-11-04

Ge T, Phung AL, Jhala G, et al (2022)

Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a JAK1/JAK2 inhibitor.

Clinical & translational immunology, 11(11):e1425.

OBJECTIVES: Immune checkpoint inhibitors have achieved clinical success in cancer treatment, but this treatment causes immune-related adverse events, including type 1 diabetes (T1D). Our aim was to test whether a JAK1/JAK2 inhibitor, effective at treating spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice, can prevent diabetes secondary to PD-L1 blockade.

METHODS: Anti-PD-L1 antibody was injected into NOD mice to induce diabetes, and JAK1/JAK2 inhibitor LN3103801 was administered by oral gavage to prevent diabetes. Flow cytometry was used to study T cells and beta cells. Mesothelioma cells were inoculated into BALB/c mice to induce a transplantable tumour model.

RESULTS: Anti-PD-L1-induced diabetes was associated with increased immune cell infiltration in the islets and upregulated MHC class I on islet cells. Anti-PD-L1 administration significantly increased islet T cell proliferation and islet-specific CD8[+] T cell numbers in peripheral lymphoid organs. JAK1/JAK2 inhibitor treatment blocked IFNγ-mediated MHC class I upregulation on beta cells and T cell proliferation mediated by cytokines that use the common γ chain receptor. As a result, anti-PD-L1-induced diabetes was prevented by JAK1/JAK2 inhibitor administered before or after checkpoint inhibitor therapy. Diabetes was also reversed when the JAK1/JAK2 inhibitor was administered after the onset of anti-PD-L1-induced hyperglycaemia. Furthermore, JAK1/JAK2 inhibitor intervention after checkpoint inhibitors did not reverse or abrogate the antitumour effects in a transplantable tumour model.

CONCLUSION: A JAK1/JAK2 inhibitor can prevent and reverse anti-PD-L1-induced diabetes by blocking IFNγ and γc cytokine activities. Our study provides preclinical validation of JAK1/JAK2 inhibitor use in checkpoint inhibitor-induced diabetes.

RevDate: 2022-11-04

Caporali S, Butera A, I Amelio (2022)

BAP1 in cancer: epigenetic stability and genome integrity.

Discover. Oncology, 13(1):117.

Mutations in BAP1 have been identified in a hereditary cancer predisposition syndrome and in sporadic tumours. Individuals carrying familiar BAP1 monoallelic mutations display hypersusceptibility to exposure-associated cancers, such as asbestos-driven mesothelioma, thus BAP1 status has been postulated to participate in gene-environment interaction. Intriguingly, BAP1 functions display also a high degree of tissue dependency, associated to a peculiar cancer spectrum and cell types of specific functions. Mechanistically, BAP1 functions as an ubiquitin carboxy-terminal hydrolase (UCH) and controls regulatory ubiquitination of histones as well as degradative ubiquitination of a range of protein substrates. In this article we provide an overview of the most relevant findings on BAP1, underpinning its tissue specific tumour suppressor function. We also discuss the importance of its epigenetic role versus the control of protein stability in the regulation of genomic integrity.

RevDate: 2022-11-30

Allione A, Viberti C, Cotellessa I, et al (2022)

Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohort.

International journal of cancer [Epub ahead of print].

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.

RevDate: 2022-10-29

Lam SK, Yan S, Lam JS, et al (2022)

Disturbance of the Warburg effect by dichloroacetate and niclosamide suppresses the growth of different sub-types of malignant pleural mesothelioma in vitro and in vivo.

Frontiers in pharmacology, 13:1020343.

Background: Inhalation of asbestos fibers is the most common cause of malignant pleural mesothelioma (MPM). In 2004, the United States Food and Drug Administration approved a combination of cisplatin with pemetrexed to treat unresectable MPM. Nonetheless novel treatment is urgently needed. The objective of this study is to report the combination effect of dichloroacetate (DCA) or niclosamide (Nic) Nic in MPM. Materials and methods: The effect of a combination of DCA and Nic was studied using a panel of MPM cell lines (H28, MSTO-211H, H226, H2052, and H2452). Cell viability was monitored by MTT assay. Glycolysis, oxidative phosphorylation, glucose, glycogen, pyruvate, lactate, citrate, succinate and ATP levels were determined by corresponding ELISA. Apoptosis, mitochondrial transmembrane potential, cell cycle analysis, hydrogen peroxide and superoxide were investigated by flow cytometry. Cell migration and colony formation were investigated by transwell migration and colony formation assays respectively. The in vivo effect was confirmed using 211H and H226 nude mice xenograft models. Results and conclusion: Cell viability was reduced. Disturbance of glycolysis and/or oxidative phosphorylation resulted in downregulation of glycogen, citrate and succinate. DCA and/or Nic increased apoptosis, mitochondrial transmembrane depolarization, G2/M arrest and reactive oxygen species. Moreover, DCA and/or Nic suppressed cell migration and colony formation. Furthermore, a better initial tumor suppressive effect was induced by the DCA/Nic combination compared with either drug alone in both 211H and H226 xenograft models. In H226 xenografts, DCA/Nic increased median survival of mice compared with single treatment. Single drug and/or a combination disturbed the Warburg effect and activated apoptosis, and inhibition of migration and proliferation in vivo. In conclusion, dichloroacetate and/or niclosamide showed a tumor suppressive effect in MPM in vitro and in vivo, partially mediated by disturbance of glycolysis/oxidative phosphorylation, apoptosis, ROS production, G2/M arrest, and suppression of migration and proliferation.

RevDate: 2022-10-30
CmpDate: 2022-10-28

Chernova T, Grosso S, Sun XM, et al (2022)

Extracellular Vesicles Isolated from Malignant Mesothelioma Cancer-Associated Fibroblasts Induce Pro-Oncogenic Changes in Healthy Mesothelial Cells.

International journal of molecular sciences, 23(20):.

Malignant mesothelioma is an aggressive tumour of the pleura (MPM) or peritoneum with a clinical presentation at an advanced stage of the disease. Current therapies only marginally improve survival and there is an urgent need to identify new treatments. Carcinoma-associated fibroblasts (CAFs) represent the main component of a vast stroma within MPM and play an important role in the tumour microenvironment. The influence of CAFs on cancer progression, aggressiveness and metastasis is well understood; however, the role of CAF-derived extracellular vesicles (CAF-EVs) in the promotion of tumour development and invasiveness is underexplored. We purified CAF-EVs from MPM-associated cells and healthy dermal human fibroblasts and examined their effect on cell proliferation and motility. The data show that exposure of healthy mesothelial cells to EVs derived from CAFs, but not from normal dermal human fibroblasts (NDHF) resulted in activating pro-oncogenic signalling pathways and increased proliferation and motility. Consistent with its role in suppressing Yes-Associated Protein (YAP) activation (which in MPM is a result of Hippo pathway inactivation), treatment with Simvastatin ameliorated the pro-oncogenic effects instigated by CAF-EVs by mechanisms involving both a reduction in EV number and changes in EV cargo. Collectively, these data determine the significance of CAF-derived EVs in mesothelioma development and progression and suggest new targets in cancer therapy.

RevDate: 2022-11-16
CmpDate: 2022-10-27

Mangone L, Storchi C, Pinto C, et al (2022)

Incidence of malignant mesothelioma and asbestos exposure in the Emilia-Romagna region, Italy.

La Medicina del lavoro, 113(5):e2022047.

BACKGROUND: The aim of this study is to describe the incidence of malignant mesothelioma (MM) and asbestos exposure in an Italian region in the period 1996-June 2021.

METHODS: The study included cases with microscopic confirmation and those with instrumental confirmation. For each case, information on sex, age, tumour site, morphology and date of diagnosis was collected, along with details of exposure to asbestos.

RESULTS: 3,097 cases of MM (2,233 males and 864 females) were registered: 90.8% with microscopic confirmation. A total of 2,840 cases involved the pleura (92%), 230 cases the peritoneum (7%), and a small number of cases the pericardium and testis (9 and 18, respectively). Most cases (78.0%) occurred after 65 years of age, while only 1.5% concerned individuals with age < 45 years. The standardized incidence rate for the entire period (adjusted to the 2000 Italian standard population and calculated per 100,000 person-years) was equal to 3.9 in males and 1.4 in females, and the trend showed an increase with age in both sexes. Concerning asbestos exposure, 79.7% of cases were exposed (86.7% males and 60.1% females). In 70.3%, exposure was occupational (83.4% males and 33.2% females), while 20.7% of females and 0.8% of males had familial exposure. Building construction, rolling stock manufacture/repair and metalworking were the most prevalent economic activities associated with occupational exposure.

CONCLUSIONS: This study offers an overview of MM in an Italian region characterized by high incidence and high exposure due to its particular production activities.

RevDate: 2022-10-25

Quigley N, Lang-Lazdunski L, Boily-Daoust C, et al (2022)

An unusual isolated anterior mediastinal lesion.

Respirology case reports, 10(11):e01059.

Malignant pleural mesothelioma (MPM) is an infrequent tumour of poor prognosis with a strong association with asbestos exposure. Pleural effusion or thickening is the most common radiological finding. Thoracoscopic biopsy is the diagnostic modality of choice. In our report, we present the case of a career welder who consulted with vocal cord palsy and an atypical anterior mediastinal lesion. An EBUS-TBNA-guided biopsy and a thorough cytological assessment led to an unexpected diagnosis of epithelioid MPM. A localized anterior mediastinal lesion is an extremely infrequent presentation of MPM that deserves clinical recognition.

RevDate: 2022-10-19
CmpDate: 2022-10-18

Jiménez-Ramírez C, Gilbert Weber D, Aguilar-Madrid G, et al (2022)

Assessment of miR-103a-3p in leukocytes-No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis.

PloS one, 17(10):e0275936.

Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney U test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants ≤60 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.

RevDate: 2022-10-19
CmpDate: 2022-10-17

Gesmundo I, Pedrolli F, Vitale N, et al (2022)

Antagonist of Growth Hormone-Releasing Hormone Potentiates the Antitumor Effect of Pemetrexed and Cisplatin in Pleural Mesothelioma.

International journal of molecular sciences, 23(19):.

Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display strong antitumor effects in many experimental cancers, including lung cancer and mesothelioma. Here, we aimed to determine whether GHRH antagonist MIA-690 potentiates the antitumor effect of cisplatin and pemetrexed in PM. In vitro, MIA-690, in combination with cisplatin and pemetrexed, synergistically reduced cell viability, restrained cell proliferation and enhanced apoptosis, compared with drugs alone. In vivo, the same combination resulted in a strong growth inhibition of MSTO-211H xenografts, decreased tumor cell proliferation and increased apoptosis. Mechanistically, MIA-690, particularly with chemotherapeutic drugs, inhibited proliferative and oncogenic pathways, such as MAPK ERK1/2 and cMyc, and downregulated cyclin D1 and B1 mRNAs. Inflammatory pathways such as NF-kB and STAT3 were also reduced, as well as oxidative, angiogenic and tumorigenic markers (iNOS, COX-2, MMP2, MMP9 and HMGB1) and growth factors (VEGF and IGF-1). Overall, these findings strongly suggest that GHRH antagonists of MIA class, such as MIA-690, could increase the efficacy of standard therapy in PM.

RevDate: 2022-10-17

Johnson B, Zhuang L, Rath EM, et al (2022)

Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response.

Cancers, 14(19):.

Malignant pleural mesothelioma (MPM) is a deadly thoracic malignancy and existing treatment options are limited. Chemotherapy remains the most widely used first-line treatment regimen for patients with unresectable MPM, but is hampered by drug resistance issues. The current study demonstrated a modest enhancement of MPM cell sensitivity to chemotherapy drug treatment following microRNA (miRNA) transfection in MPM cell lines, albeit not for all tested miRNAs. This effect was more pronounced for FAK (PND-1186) small molecule inhibitor treatment; consistent with previously published data. We previously established that MPM response to survivin (YM155) small molecule inhibitor treatment is unrelated to basal survivin expression. Here, we showed that MPM response to YM155 treatment is enhanced following miRNA transfection of YM155-resistant MPM cells. We determined that YM155-resistant MPM cells secrete a higher level of exosomes in comparison to YM155-sensitive MPM cells. Despite this, an exosome inhibitor (GW4896) did not enhance MPM cell sensitivity to YM155. Additionally, our study showed no evidence of a correlation between the mRNA expression of inhibitor of apoptosis (IAP) gene family members and MPM cell sensitivity to YM155. However, two drug transporter genes, ABCA6 and ABCA10, were upregulated in the MPM cell lines and correlated with poor sensitivity to YM155.

RevDate: 2022-12-06
CmpDate: 2022-12-06

Hariharan A, Qi W, Rehrauer H, et al (2022)

Heterogeneous RNA editing and influence of ADAR2 on mesothelioma chemoresistance and the tumor microenvironment.

Molecular oncology, 16(22):3949-3974.

We previously observed increased levels of adenosine-deaminase-acting-on-dsRNA (Adar)-dependent RNA editing during mesothelioma development in mice exposed to asbestos. The aim of this study was to characterize and assess the role of ADAR-dependent RNA editing in mesothelioma. We found that tumors and mesothelioma primary cultures have higher ADAR-mediated RNA editing compared to mesothelial cells. Unsupervised clustering of editing in different genomic regions revealed heterogeneity between tumor samples as well as mesothelioma primary cultures. ADAR2 expression levels are higher in BRCA1-associated protein 1 wild-type tumors, with corresponding changes in RNA editing in transcripts and 3'UTR. ADAR2 knockdown and rescue models indicated a role in cell proliferation, altered cell cycle, increased sensitivity to antifolate treatment, and type-1 interferon signaling upregulation, leading to changes in the microenvironment in vivo. Our data indicate that RNA editing contributes to mesothelioma heterogeneity and highlights an important role of ADAR2 not only in growth regulation in mesothelioma but also in chemotherapy response, in addition to regulating inflammatory response downstream of sensing nucleic acid structures.

RevDate: 2022-10-27
CmpDate: 2022-10-27

Gualtieri AF (2023)

Journey to the centre of the lung. The perspective of a mineralogist on the carcinogenic effects of mineral fibres in the lungs.

Journal of hazardous materials, 442:130077.

This work reviews the bio-chemical mechanisms leading to adverse effects produced when mineral fibres are inhaled and transported in the lungs from the perspective of a mineralogist. The behaviour of three known carcinogenic mineral fibres (crocidolite, chrysotile, and fibrous-asbestiform erionite) during their journey through the upper respiratory tract, the deep respiratory tract and the pleural cavity is discussed. These three fibres have been selected as they are the most socially and economically relevant mineral fibres representative of the classes of chain silicates (amphiboles), layer silicates (serpentine), and framework silicates (zeolites), respectively. Comparison of the behaviour of these fibres is made according to their specific crystal-chemical assemblages and properties. Known biological and subsequent pathologic effects which lead and contribute to carcinogenesis are critically reviewed under the mineralogical perspective and in relation to recent progress in this multidisciplinary field of research. Special attention is given to the understanding of the cause-effect relationships for lung cancer and malignant mesothelioma. Comparison with interstitial pulmonary fibrosis, or "asbestosis", will also be made here. This overview highlights open issues, data gaps, and conflicts in the literature for these topics, especially as regards relative potencies of the three mineral fibres under consideration for lung cancer and mesothelioma. Finally, an attempt is made to identify future research lines suitable for a general comprehensive model of the carcinogenicity of mineral fibres.

RevDate: 2022-10-04

Kazi M, Vispute T, Shah P, et al (2022)

Localized gastric mesothelioma with nodal metastasis-an exceptionally rare entity.

Indian journal of surgical oncology, 13(3):612-615.

Localized mesothelioma is a rare disease with very few reports of presentation in visceral organs. We report a case of localized gastric mesothelioma with lymph node metastasis in a 32-year-old man without asbestos exposure. A failed attempt at resection was made before presentation at another center. He was given perioperative chemotherapy that was followed by a D2 radical subtotal gastrectomy and hyperthermic intraperitoneal chemotherapy. Histopathology showed epithelioid mesothelioma with nodal metastasis but without visceral peritoneal involvement. Cytoreductive surgery and regional chemotherapy are standard in diffuse mesothelioma. Management of localized mesothelioma is anecdotal; however aggressive surgery plays a central role with selective use of perioperative chemotherapy.

RevDate: 2022-10-04
CmpDate: 2022-10-04

Cimen F, Agackiran Y, Düzgün S, et al (2022)

Factors affecting the life expectancy in malignant pleural mesothelioma: Our 10 years of studies and experience.

Medicine, 101(39):e30711.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. In our study, we aimed to investigate the specific clinical, laboratory, and radiological features of the tumor and the prognostic effect of SUVmax (maximum standardized uptake values) according to PET/CT (positron emission tomography). Demographic, therapeutic, clinical, and survival information of patients diagnosed with histologically-validated pleural mesothelioma in our hospital between January 2010 to December 2019 will be retrospectively scanned from the hospital records. A total of 116 patients, 61 men (52.6%), and 55 women (47.4%), were analyzed. Thirty five patients (30.2%) were over the age of 65. Percentage of patients over 65 years of age, neutrophil count, and PET SUV Max values, asbestos exposure and pleural thickening rate were significantly higher in the deceased patients' group than in the living patients' group (P = .042, P = .039, P = .002, P = .004, P = .037). T stage (tumor stage), N stage (lymph nodes stage), metastasis stage, and Grade distribution were significantly higher in the deceased patients' group than in the living patients' group (P < .000, P < .000, P = .003, P < .000). The rates of chemotherapy and surgical treatment, right lung location, and epithelioid pathology were significantly lower in the deceased patients' group compared to the living patients' group (P = .016, P = .030, P = .018, P = .008). The mean follow-up time was 13 months. Key determinants of survival in MPM include age, male gender, neutrophil increase, pleural thickening, high PET SUV max values, stage, histological type, asbestos exposure, and treatment regimen.

RevDate: 2022-10-06
CmpDate: 2022-10-03

Wang X, Katz S, Miura J, et al (2022)

A single-center retrospective cohort study of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma.

PloS one, 17(9):e0275187.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare variant of malignant mesothelioma, representing 10-15% of malignant mesothelioma cases. The preferred therapeutic approach is cytoreductive surgery (CRS) accompanied by hyperthermic intraperitoneal chemotherapy (HIPEC); the role of systemic chemotherapy is not well established. While some limited retrospective studies report worse outcomes with neoadjuvant chemotherapy, our institution has favored the use of neoadjuvant chemotherapy for symptom relief and surgical optimization. The aim of our study was to assess the outcomes of patients receiving neoadjuvant chemotherapy, compared to those receiving adjuvant or no perioperative chemotherapy.

PATIENTS AND METHODS: We conducted a single-center retrospective cohort study of treatment-naïve, non-papillary DMPM patients seen at our institution between 1/1/2009 and 9/1/2019. We explored the effect of type of systemic therapy on clinical outcomes and estimated median overall survival (mOS) using Kaplan-Meier curves. Hazard ratios (HR) calculated by Cox proportional hazard model were used to estimate effect of the exposures on overall survival.

RESULTS: 47 patients were identified with DMPM (median age at diagnosis 61.2 years, 76.6% epithelioid histology, 74.5% white race, 55.3% known asbestos exposure). CRS was performed in 53.2% of patients (25/47); 76.0% of surgical patients received HIPEC (19/25). The majority received systemic chemotherapy (37/47, 78.7%); among patients receiving both CRS and chemotherapy, neoadjuvant chemotherapy was more common than adjuvant chemotherapy (12 neoadjuvant, 8 adjuvant). Overall mOS was 84.1 months. Among neoadjuvant patients, 10/12 underwent surgery, and 2 were lost to follow-up; the majority (9/10) had clinically stable or improved disease during the pre-operative period. There were numerical more issues with chemotherapy with the adjuvant patients (4/8: 2 switches in platinum agent, 2 patients stopped therapy) than with the neoadjuvant patients (2/10: 1 switch in platinum agent, 1 delay due to peri-procedural symptoms). Neoadjuvant chemotherapy was not associated with worse mOS compared to adjuvant chemotherapy (mOS NR vs 95.1 mo, HR 0.89, 95% CI 0.18-4.5, p = 0.89).

CONCLUSIONS: When used preferentially, the use of neoadjuvant chemotherapy in DMPM patients was not associated with worse outcomes compared to adjuvant chemotherapy. It was well-tolerated and did not prevent surgical intervention.

RevDate: 2022-10-17
CmpDate: 2022-10-17

Han Y, Zhang T, Chen H, et al (2022)

Global magnitude and temporal trend of mesothelioma burden along with the contribution of occupational asbestos exposure in 204 countries and territories from 1990 to 2019: Results from the Global Burden of Disease Study 2019.

Critical reviews in oncology/hematology, 179:103821.

Understanding the burden of mesothelioma with the contribution of occupational asbestos exposure globally provides essential foundations for cancer control, policy decisions and resource allocation. Globally, 34,511 incident cases, 29,251 deaths and 668,104 disability-adjusted life years (DALYs) of mesothelioma were estimated in 2019. The age-standardized rates of incidence, mortality and DALYs all showed a slightly declining trend over the past 30 years, but the latest absolute number of mesothelioma burden almost doubled since 1990. The burden rate decreased among the population aged under 70 years, but increased among the population aged over 80 years, especially in the High socio-demographic index (SDI) region. The burden rate of mesothelioma attributable to asbestos exposure was positively associated with SDI at the national level. This study depicted a continuous increase in mesothelioma burden globally over the past 30 years. Controlling occupational asbestos exposure will reduce the mesothelioma burden, especially for higher SDI regions.

RevDate: 2022-11-08
CmpDate: 2022-11-08

Golka K, Böthig R, Weistenhöfer W, et al (2022)

[Occupation-related cancer in urology-Current knowledge including environmental medical aspects].

Urologie (Heidelberg, Germany), 61(11):1198-1207.

Occupation-related cancers are of considerable importance, which is not yet adequately recognized in the field of urology. The three numerically most significant entities are tumors of the urinary tract caused by carcinogenic aromatic amines or polycyclic aromatic hydrocarbons, renal cell cancer after high exposure to the solvent trichloroethylene, and mesotheliomas of the tunica vaginalis of the testis after exposure to asbestos; however, these can only be recognized as occupation-related if an occupational history regarding the hazard relevant to the organ bearing the tumor is documented from the beginning of employment, e.g. by a questionnaire. This is because the relevant exposures generally date back several decades. With the exception of high exposure to trichloroethylene, the substances mentioned can also environmentally trigger the same tumors. In the context of environmental risk factors, it is of considerable importance that smoking is now considered to be a trigger for some 50% of all bladder cancers in men and women; however, smoking cessation results in a reduction in smoking-related cancer risk of over 30% after only 3-4 years. Work and commuting accidents, which are considered occupational risks, can lead to urological sequelae. For example, increased tumors of the bladder can occur after spinal cord injury lasting longer than 10 years.

RevDate: 2022-09-28

Algranti E, Santana VS, Campos F, et al (2022)

Analysis of Mortality from Asbestos-Related Diseases in Brazil Using Multiple Health Information Systems, 1996-2017.

Safety and health at work, 13(3):302-307.

BACKGROUND: In Brazil, asbestos was intensively used from the 1960s until its ban in 2017. Mesothelioma, asbestosis, and pleural plaques are typical asbestos-related diseases (ARD-T). To create an ARD-T national database, death records from 1996-2017 were retrieved from several health information systems (HIS).

METHODS: All national HIS containing coded diagnoses (ICD-10) and death information were obtained. Linkage was performed to create a single database of ARD-T death records, either as underlying or contributory causes, in adults aged 30 years and older.

RESULTS: A total of 3,057 ARD-T death records were found, 2,405 (76.4%) of which being malignant mesotheliomas (MM). Pleural MM (n = 1,006; 41.8%) and unspecified MM (n = 792; 32.9%) prevailed. Male to female MM ratio (M:F) was 1.4:1, and higher ratios were found for non-malignant ARD-T: 3.5:1 for asbestosis and 2.4:1 for pleural plaques. Male crude annual mesothelioma mortality (CMmm x1,000,000) was 0.98 in 1996 and 2.26 in 2017, a 131.1% increment, while for females it was 1.04 and 1.25, a 20.2% increase, correspondingly. The small number of deaths with asbestosis and pleural plaques records precluded conclusive interpretations.

CONCLUSIONS: Even with the linkage of several HIS, ARD-T in death records remained in low numbers. MM mortality in men was higher and showed a rapid increase and, along with non-malignant ARD-T, higher M:F ratios suggested a predominant pattern of work-related exposure. The monitoring of workplace and environmental asbestos exposure needs to be improved, as well as the workers surveillance, following the recent Brazilian ban.

RevDate: 2022-09-28

Tedesco J, Jaradeh M, WT Vigneswaran (2022)

Malignant Pleural Mesothelioma: Current Understanding of the Immune Microenvironment and Treatments of a Rare Disease.

Cancers, 14(18):.

Malignant pleural mesothelioma is a rare disease with an annual incidence of around 3000 cases a year in the United States. Most cases are caused by asbestos exposure, with a latency period of up to 40 years. Pleural mesothelioma is an aggressive disease process with overall survival of roughly 6-12 months after the time of diagnosis. It is divided into three subtypes: epithelioid, mixed type, and sarcomatoid type, with the epithelioid subtype having the best overall survival. Often, the treatment is multimodality with surgery, chemotherapy, and radiation. The survival benefit is improved but remains marginal. New treatment options involving targeted immune therapies appear to offer some promise. The tumor microenvironment is the ecosystem within the tumor that interacts and influences the host immune system. Understanding this complex interaction and how the host immune system is involved in the progression of the disease process is important to define and guide potential treatment options for this devastating and rare disease.

RevDate: 2022-09-28
CmpDate: 2022-09-19

Hoang NTD, Hassan G, Suehiro T, et al (2022)

BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation.

BMC cancer, 22(1):984.

BACKGROUND: Malignant mesothelioma (MM) is an aggressive mesothelial cell cancer type linked mainly to asbestos inhalation. MM characterizes by rapid progression and resistance to standard therapeutic modalities such as surgery, chemotherapy, and radiotherapy. Our previous studies have suggested that tumor cell-derived connective tissue growth factor (CTGF) regulates the proliferation of MM cells as well as the tumor growth in mouse xenograft models.

METHODS: In this study, we knock downed the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) and CTGF in MM cells and investigated the relationship between both and their impact on the cell cycle and cell proliferation.

RESULTS: The knockdown of CTGF or BAMBI reduced MM cell proliferation. In contrast to CTGF knockdown which decreased BAMBI, knockdown of BAMBI increased CTGF levels. Knockdown of either BAMBI or CTGF reduced expression of the cell cycle regulators; cyclin D3, cyclin-dependent kinase (CDK)2, and CDK4. Further, in silico analysis revealed that higher BAMBI expression was associated with shorter overall survival rates among MM patients.

CONCLUSIONS: Our findings suggest that BAMBI is regulated by CTGF promoting mesothelioma growth by driving cell cycle progression. Therefore, the crosstalk between BAMBI and CTGF may be an effective therapeutic target for MM treatment.

RevDate: 2022-09-13

Shi H, Rath EM, Lin RCY, et al (2022)

3-Dimensional mesothelioma spheroids provide closer to natural pathophysiological tumor microenvironment for drug response studies.

Frontiers in oncology, 12:973576.

Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics in vivo conditions and pathological conditions such as cancer. In comparison to biospecimens taken from in vivo tissue, the details of gene expression of 3D culture models are largely undefined, especially in mesothelioma - an aggressive cancer with very limited effective treatment options. In this study, we examined the veracity of the 3D mesothelioma cell culture model to study cell-to-cell interaction, gene expression and drug response from 3D cell culture, and compared them to 2D cell and tumor samples. We confirmed via SEM analysis that 3D cells grown using the spheroid methods expressed highly interconnected cell-to-cell junctions. The 3D spheroids were revealed to be an improved mini-tumor model as indicated by the TEM visualization of cell junctions and microvilli, features not seen in the 2D models. Growing 3D cell models using decellularized lung scaffold provided a platform for cell growth and infiltration for all cell types including primary cell lines. The most time-effective method was growing cells in spheroids using low-adhesive U-bottom plates. However, not every cell type grew into a 3D model using the the other methods of hanging drop or poly-HEMA. Cells grown in 3D showed more resistance to chemotherapeutic drugs, exhibiting reduced apoptosis. 3D cells stained with H&E showed cell-to-cell interactions and internal architecture that better represent that of in vivo patient tumors when compared to 2D cells. IHC staining revealed increased protein expression in 3D spheroids compared to 2D culture. Lastly, cells grown in 3D showed very different microRNA expression when compared to that of 2D counterparts. In conclusion, 3D cell models, regardless of which method is used. Showed a more realistic tumor microenvironment for architecture, gene expression and drug response, when compared to 2D cell models, and thus are superior preclinical cancer models.

RevDate: 2022-09-13

Trassl L, GT Stathopoulos (2022)

KRAS Pathway Alterations in Malignant Pleural Mesothelioma: An Underestimated Player.

Cancers, 14(17):.

Malignant pleural mesothelioma (MPM) is a rare, incurable cancer of the mesothelial cells lining the lungs and the chest wall that is mainly caused by asbestos inhalation. The molecular mechanisms of mesothelial carcinogenesis are still unclear despite comprehensive studies of the mutational landscape of MPM, and the most frequently mutated genes BAP1, NF2, CDKN2A, TP53, and TSC1 cannot cause MPM in mice in a standalone fashion. Although KRAS pathway alterations were sporadically detected in older studies employing targeted sequencing, they have been largely undetected by next generation sequencing. We recently identified KRAS mutations and copy number alterations in a significant proportion of MPM patients. Here, we review and analyze multiple human datasets and the published literature to show that, in addition to KRAS, multiple other genes of the KRAS pathway are perturbed in a significant proportion of patients with MPM.

RevDate: 2022-09-13

Ranzato E, Bonsignore G, S Martinotti (2022)

ER Stress Response and Induction of Apoptosis in Malignant Pleural Mesothelioma: The Achilles Heel Targeted by the Anticancer Ruthenium Drug BOLD-100.

Cancers, 14(17):.

Malignant mesothelioma is a rare cancer arising from the serosal surfaces of the body, mainly from the pleural layer. This cancer is strongly related to asbestos exposure and shows a very inauspicious prognosis, because there are scarce therapeutic options for this rare disease. Thus, there is an urgent need to develop novel therapeutic approaches to treat this form of cancer. To explore the biology of malignant pleural mesothelioma (MPM), we previously observed that MPM cell lines show high expression of the GRP78 protein, which is a chaperone protein and the master regulator of the unfolded protein response (UPR) that resides in the endoplasmic reticulum (ER). Based on our previous studies showing the importance of GRP78 in MPM, we observed that BOLD-100, a specific modulator of GRP78 and the UPR, shows cytotoxicity against MPM cells. Our studies demonstrated that BOLD-100 increases ROS production and Ca[2+] release from the ER, leading to ER stress activation and, ultimately, to cell death. Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM.

RevDate: 2022-09-13
CmpDate: 2022-09-12

Pietrofesa RA, Chatterjee S, Kadariya Y, et al (2022)

Synthetic Secoisolariciresinol Diglucoside (LGM2605) Prevents Asbestos-Induced Inflammation and Genotoxic Cell Damage in Human Mesothelial Cells.

International journal of molecular sciences, 23(17):.

Although alveolar macrophages play a critical role in malignant transformation of mesothelial cells following asbestos exposure, inflammatory and oxidative processes continue to occur in the mesothelial cells lining the pleura that may contribute to the carcinogenic process. Malignant transformation of mesothelial cells following asbestos exposure occurs over several decades; however, amelioration of DNA damage, inflammation, and cell injury may impede the carcinogenic process. We have shown in an in vitro model of asbestos-induced macrophage activation that synthetic secoisolariciresinol diglucoside (LGM2605), given preventively, reduced inflammatory cascades and oxidative/nitrosative cell damage. Therefore, it was hypothesized that LGM2605 could also be effective in reducing asbestos-induced activation and the damage of pleural mesothelial cells. LGM2605 treatment (50 µM) of huma n pleural mesothelial cells was initiated 4 h prior to exposure to asbestos (crocidolite, 20 µg/cm[2]). Supernatant and cells were evaluated at 0, 2, 4, and 8 h post asbestos exposure for reactive oxygen species (ROS) generation, DNA damage (oxidized guanine), inflammasome activation (caspase-1 activity) and associated pro-inflammatory cytokine release (IL-1β, IL-18, IL-6, TNFα, and HMGB1), and markers of oxidative stress (malondialdehyde (MDA) and 8-iso-prostaglandin F2a (8-iso-PGF2α). Asbestos induced a time-dependent ROS increase that was significantly (p < 0.0001) reduced (29.4%) by LGM2605 treatment. LGM2605 pretreatment also reduced levels of asbestos-induced DNA damage by 73.6% ± 1.0%. Although levels of inflammasome-activated cytokines, IL-1β and IL-18, reached 29.2 pg/mL ± 0.7 pg/mL and 43.9 pg/mL ± 0.8 pg/mL, respectively, LGM2605 treatment significantly (p < 0.0001) reduced cytokine levels comparable to baseline (non-asbestos exposed) values (3.8 pg/mL ± 0.2 pg/mL and 5.4 pg/mL ± 0.2 pg/mL, respectively). Furthermore, levels of IL-6 and TNFα in asbestos-exposed mesothelial cells were high (289.1 pg/mL ± 2.9 pg/mL and 511.3 pg/mL ± 10.2 pg/mL, respectively), while remaining undetectable with LGM2605 pretreatment. HMGB1 (a key inflammatory mediator and initiator of malignant transformation) release was reduced 75.3% ± 0.4% by LGM2605. Levels of MDA and 8-iso-PGF2α, markers of oxidative cell injury, were significantly (p < 0.001) reduced by 80.5% ± 0.1% and 76.6% ± 0.3%, respectively. LGM2605, given preventively, reduced ROS generation, DNA damage, and inflammasome-activated cytokine release and key inflammatory mediators implicated in asbestos-induced malignant transformation of normal mesothelial cells.

RevDate: 2022-11-16
CmpDate: 2022-10-21

Mai HL, Deshayes S, Nguyen TV, et al (2022)

IL-7 is expressed in malignant mesothelioma and has a prognostic value.

Molecular oncology, 16(20):3606-3619.

Malignant pleural mesothelioma (MPM) is an aggressive cancer mainly related to asbestos exposure. Despite recent therapeutic advances, notably immunotherapies, the benefit remains limited and restricted to a small percentage of patients. Thus, a better understanding of the disease is needed to identify new therapeutic strategies. Recently, interleukin 7 receptor (IL-7R) has been described as being expressed by MPM cells and associated with poorer patient survival. Thus, the aim of this work was to study the IL-7R/IL-7 pathway in MPM using patient samples. We found that, although more than 40% of MPM cells expressed IL-7R, IL-7 had no effect on their intracellular signaling. Accordingly, the addition of IL-7 to the culture medium did not affect MPM cell growth. Using The Cancer Genome Atlas (TCGA) database, we showed that high IL7 gene expression in MPM tumors was associated with a higher overall patient survival and an induction of genes involved in the immune response. In pleural effusions (PEs), we found that IL-7 concentration was not a good diagnostic biomarker. However, we observed that high IL-7 levels in PEs were associated with shorter survival of MPM patients, but not of lung cancer patients. The prognostic value of IL-7 was also conserved when only patients with epithelioid mesothelioma, the most common histological type of MPM, were analyzed. Taken together, our study suggests that, although the IL-7R/IL-7 signaling pathway is not functional in MPM cells, IL-7 expression in PEs may have prognostic value in MPM patients.

RevDate: 2022-09-07
CmpDate: 2022-08-31

Kenchetty PK, Balasundaram S, K Rao (2022)

An uncommon aetiology for a common clinical problem: Primary pericardial mesothelioma.

The National medical journal of India, 35(1):14-16.

Mesothelioma is a tumour arising from the mesothelial cells lining the pleura, pericardium, peritoneum, or the tunica vaginalis of testes. Primary pericardial mesothelioma is a rare tumour that can have varied manifestations and survival in patients with malignant pericardial tumours is generally dismal. The role of asbestos in pericardial mesotheliomas is less well established compared to that in pleural or peritoneal mesotheliomas. The prognosis is generally poor with the treatment options available. We present a middle-aged man with large pericardial effusion secondary to primary pericardial mesothelioma with no previous exposure to asbestos.

RevDate: 2022-08-31

Kerosky ZP, Powell CR, PC Lindholm (2022)

Malignant Peritoneal Mesothelioma Presenting with High Protein, High Serum-Ascites Albumin Gradient.

Cureus, 14(7):e27286.

Mesothelioma is a difficult-to-detect neoplasm that rarely develops in the peritoneum. In patients with unexplained ascites, pleural fluid analysis and ultrasonography is often the first step to achieving a diagnosis. This case report shares a unique presentation in which a patient who presented with unexplained ascites, was initially thought to have cirrhosis but was later found to have malignant peritoneal mesothelioma after cross-sectional imaging and tissue acquisition. This case illustrates the importance of a high clinical index of suspicion for mesothelioma given its variety of clinical presentations, as well as the utility of early cross-sectional imaging in such cases.

RevDate: 2022-08-30
CmpDate: 2022-08-29

Setlai BP, Mkhize-Kwitshana ZL, Mehrotra R, et al (2022)

Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma.

International journal of molecular sciences, 23(16):.

Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome-epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed.

RevDate: 2022-12-06
CmpDate: 2022-08-25

Gregório PHP, Terra RM, Lima LP, et al (2022)

Mesothelioma in a developing country: a retrospective analysis of the diagnostic process.

Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia, 48(5):e20220064.

OBJECTIVE: To evaluate the process of diagnosing patients with malignant pleural mesothelioma (MPM) at a tertiary care hospital.

METHODS: This was a retrospective study involving patients referred to a tertiary-care cancer center in Brazil between 2009 and 2020. The diagnostic process was divided into four steps: onset of symptoms, referral to a specialist visit, histopathological diagnosis, and beginning of treatment. The intervals between each phase and the factors for delays were evaluated. Data including clinical status, radiological examinations, staging, treatment modalities, and survival outcomes were collected.

RESULTS: During the study period, 66 patients (mean age = 64 years) were diagnosed with MPM and underwent treatment. Only 27 (41%) of the patients had knowledge of prior exposure to asbestos. The median number of months (IQR) between the onset of symptoms and the first specialist visit, between the specialist visit and histopathological characterization, and between definite diagnosis and beginning of treatment was, respectively, 6.5 (2.0-11.4), 1.5 (0.6-2.1), and 1.7 (1.2-3.4). The knowledge of prior asbestos exposure was associated with a shorter time to referral to a specialist (median: 214 vs. 120 days; p = 0.04). A substantial number of nondiagnostic procedures and false-negative biopsy results (the majority of which involved the use of Cope needle biopsy) were found to be decisive factors for the length of waiting time. The mean overall survival was 11.9 months.

CONCLUSIONS: The unfamiliarity of health professionals with MPM and the patient's lack of knowledge of prior asbestos exposure were the major factors to cause a long time interval between the onset of symptoms and beginning of treatment. An overall survival shorter than 1 year is likely to have been due to the aforementioned delays.

RevDate: 2022-08-26
CmpDate: 2022-08-23

Muti P, Sacconi A, Pulito C, et al (2022)

Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial.

Journal of experimental & clinical cancer research : CR, 41(1):255.

BACKGROUND: Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set.

METHODS: In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model.

RESULTS: We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants.

CONCLUSIONS: We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma.

TRIAL REGISTRATION:, NCT02076672 . Registered 03/03/2014.

RevDate: 2022-08-19

Jiang Z, Chen J, Chen J, et al (2022)

Mortality due to respiratory system disease and lung cancer among female workers exposed to chrysotile in Eastern China: A cross-sectional study.

Frontiers in oncology, 12:928839.

Female workers in the asbestos processing industry of Eastern China are at high risk of developing multiple types of cancer, and more data are urgently needed to better understand and address this issue. Death certificate data were selected from an asbestos processing city in China from 2005 to 2006. Information was investigated using the relatives of those individuals who had died as sources of information. Individuals were classified into one of three asbestos exposure levels. Standardized mortality ratio and 95% confidence interval were calculated. A total of 2,964 individual deaths were identified from 2005 to 2006; of these, 21.4% were occupationally exposed to asbestos. The main cause of death was circulatory system diseases (21.2%). The proportion of individuals with respiratory system diseases increased by age among each exposure subgroup (P trend < 0.01). Among females, a significant trend was observed between increased asbestos exposure and mortality due to respiratory system diseases and lung cancer. Our study indicated that asbestos exposure was associated with excess mortality from lung cancer and respiratory diseases, particularly among female workers in an asbestos processing area in Eastern China.

RevDate: 2022-11-09
CmpDate: 2022-10-04

Silvestri S, Ciapini C, A Innocenti (2022)

Past Asbestos Exposure in Rolling Stock Manufacturing in the Absence of Environmental Monitoring: An Original Method.

Journal of occupational and environmental medicine, 64(10):e635-e640.

OBJECTIVE: The aim of this study is the reconstruction of asbestos exposure in absence of environmental monitoring data, to use the results in a cohort study of railway rolling stock workers.

METHODS: To reconstruct past exposures, the production data (number of rolling stock and asbestos content) and working methods were reconstructed with former employees and company documentation, literature data, and author expertise.

RESULTS: The result of the work is a job/exposure matrix from 1956 to 1979, when sprayed asbestos was used as insulator of the metal bodies. Annual exposure estimate varies from 0.08 to 4.9 fb/mL depending on the specific jobs. Thirty-one mesotheliomas with occupational exposure, one with environmental and one with family exposures, were identified.

CONCLUSIONS: The originality of the study consists on the use of company production data to establish frequency duration of asbestos exposure.

RevDate: 2022-09-21

Chun CP, Song LX, Zhang HP, et al (2022)

Malignant peritoneal mesothelioma.

The American journal of the medical sciences pii:S0002-9629(22)00332-9 [Epub ahead of print].

Malignant peritoneal mesothelioma (MPM) is a rare, life-threatening malignant tumor. We present a report of a rare case of a 67-year-old male patient with MPM and severe abdominal pain, bloating, and bloody ascites as manifestations. The diagnosis was confirmed by cytology of ascites aspiration fluid and further verified by laparoscopic exploratory biopsy. The characteristics of signs and clinical manifestations in this case are less common. As everyone knows, asbestos exposure is usually associated with pleural mesothelioma, but only 6%-10% of malignant mesothelioma cases originate from the peritoneum, which is far less than pleural mesothelioma. Generally, its non-specificity provides a huge challenge to medical professionals in its diagnosis, and this is also the main reason for delayed diagnosis. Patients should be vigilant, even though no clear risk factor is observed.

RevDate: 2022-08-12
CmpDate: 2022-08-09

Shobana M, Balasraswathi VR, Radhika R, et al (2022)

Classification and Detection of Mesothelioma Cancer Using Feature Selection-Enabled Machine Learning Technique.

BioMed research international, 2022:9900668.

Cancer of the mesothelium, sometimes referred to as malignant mesothelioma (MM), is an extremely uncommon form of the illness that almost always results in death. Chemotherapy, surgery, radiation therapy, and immunotherapy are all potential treatments for multiple myeloma; however, the majority of patients are identified with the disease at an advanced stage, at which time it is resistant to these therapies. After obtaining a diagnosis of advanced multiple myeloma, the average length of time that a person lives is one year after hearing this news. There is a substantial link between asbestos exposure and mesothelioma (MM). Using an approach that enables feature selection and machine learning, this article proposes a classification and detection method for mesothelioma cancer. The CFS correlation-based feature selection approach is first used in the feature selection process. It acts as a filter, selecting just the traits that are relevant to the categorization. The accuracy of the categorization model is improved as a direct consequence of this. After that, classification is carried out with the help of naive Bayes, fuzzy SVM, and the ID3 algorithm. Various metrics have been utilized during the process of measuring the effectiveness of machine learning strategies. It has been discovered that the choice of features has a substantial influence on the accuracy of the categorization.

RevDate: 2022-09-05
CmpDate: 2022-08-09

Røe OD, Creaney J, BAP1 Study Group (2022)

Response to "Revisiting 'BAP1ness' in Malignant Pleural Mesothelioma".

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 17(8):e69-e70.

RevDate: 2022-09-05
CmpDate: 2022-08-09

Yang H, Gaudino G, Bardelli F, et al (2022)

Does the Amount of Asbestos Exposure Influence Prognosis?.

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 17(8):949-952.

RevDate: 2022-08-02

Tachibana M, Nozawa M, Kamimura K, et al (2022)

Synchronous Jejunal Sarcomatoid Carcinoma and Incidentally Associated Localized Peritoneal Malignant Mesothelioma.

Cureus, 14(6):e26270.

Sarcomatoid carcinoma (SCA) of the small bowel is a rare aggressive variant of small intestinal cancer accompanying a poor prognosis. The tumor primarily affects middle-aged and elderly patients. We report herein a 67-year-old Japanese male who manifested anemia. He had a history of asbestos exposure 30 years earlier. An abdominal computed tomography (CT) scan showed a 6.5-cm aneurysmal, dilated mass of the small intestine. Capsule endoscopy revealed a large circumferential hemorrhagic ulcerative lesion in the jejunum. Biopsy indicated sarcomatoid carcinoma, and partial resection of the small bowel and adjacent transverse colon and omentum was performed. In addition to the T3N0M0 jejunal giant sarcomatoid carcinoma (SCA), a 3-mm small localized peritoneal (omental) malignant mesothelioma (LMM) was also incidentally included. Synchronous presentation of small intestinal and mesothelial malignancies is extremely rare, and the avoidance of incorrect clinical staging is critically important. Surgical resection is still considered the best first-line therapy, because of a poor response to chemotherapy and radiotherapy. Dual-color fluorescent in situ hybridization (FISH) for p16/CDKN2A and chromosome 9 indicated homologous deletion of p16/CDKN2A in SCA and a normal pattern in LMM. Methylthioadenosine phosphorylase (MTAP) was negative in SCA but positive in LMM. Both tumors consistently expressed BRCA1-associated protein 1 (BAP1). Tumor necrosis factor receptor-associated factor 7 (TRAF7) was suppressed, and neural cell adhesion molecule L1 precursor (NCAML1/L1CAM) was agitated in both tumors. Diffuse and strong expression of programmed death-ligand 1 (PD-L1) and the association of tumor-infiltrating lymphocytes in SCA may indicate a potential for PD-L1-targeted immunotherapy for treating this type of aggressive cancer. PD-L1 was focally expressed in LMM. The postoperative course was uneventful for two years.

RevDate: 2022-08-23
CmpDate: 2022-08-23

Parvathaneni V, Chilamakuri R, Kulkarni NS, et al (2022)

Repurposing clofazimine for malignant pleural mesothelioma treatment - In-vitro assessment of efficacy and mechanism of action.

Life sciences, 306:120843.

AIMS: Malignant pleural mesothelioma (MPM) is a rare cancer of lungs' pleural cavity, with minimally effective therapies available. Thus, there exists a necessity for drug repurposing which is an attractive strategy for drug development in MPM. Repurposing of an old FDA-approved anti-leprotic drug, Clofazimine (CFZ), presents an outstanding opportunity to explore its efficacy in treating MPM.

MAIN METHODS: Cytotoxicity, scratch assay, and clonogenic assays were employed to determine CFZ's ability to inhibit cell viability, cell migration, and colony growth. 3D Spheroid cell culture studies were performed to identify tumor growth inhibition potential of CFZ in MSTO-211H cell line. Gene expression analysis was performed using RT-qPCR assays to determine the CFZ's effect of key genes. Western blot studies were performed to determine CFZ's ability to induce apoptosis its effect to induce autophagy marker.

KEY FINDINGS: CFZ showed significant cytotoxicity against both immortalized and primary patient-derived cell lines with IC50 values ranging from 3.4 μM (MSTO-211H) to 7.1 μM (HAY). CFZ significantly impaired MPM cell cloning efficiency, migration, and tumor spheroid formation. 3D Spheroid model showed that CFZ resulted in reduction in spheroid volume. RT-qPCR data showed downregulation of genes β-catenin, BCL-9, and PRDX1; and upregulation of apoptosis markers such as PARP, Cleaved caspase 3, and AXIN2. Additionally, immunoblot analysis showed that CFZ down-regulates the expression of β-catenin (apoptosis induction) and up-regulates p62, LC3B protein II (autophagy inhibition).

SIGNIFICANCE: It can be concluded that CFZ could be a promising molecule to repurpose for MPM treatment which needs numerous efforts from further studies.

RevDate: 2022-08-30
CmpDate: 2022-08-04

Dubois F, Bazille C, Levallet J, et al (2022)

Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP.

Targeted oncology, 17(4):407-431.

Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a ban of using asbestos in many countries, the incidence of malignant pleural mesothelioma failed to decline worldwide. While little progress has been made in malignant pleural mesothelioma diagnosis, bevacizumab at first, then followed by double immunotherapy (nivolumab plus ipilumumab), were all shown to improve survival in large phase III randomized trials. The morphological analysis of the histological subtyping remains the primary indicator for therapeutic decision making at an advanced disease stage, while a platinum-based chemotherapy regimen combined with pemetrexed, either with or without bevacizumab, is still the main treatment option. Consequently, malignant pleural mesothelioma still represents a significant health concern owing to poor median survival (12-18 months). Given this context, both diagnosis and therapy improvements require better knowledge of the molecular mechanisms underlying malignant pleural mesothelioma's carcinogenesis and progression. Hence, the Hippo pathway in malignant pleural mesothelioma initiation and progression has recently received increasing attention, as the aberrant expression of its core components may be closely related to patient prognosis. The purpose of this review was to provide a critical analysis of our current knowledge on these topics, the main focus being on the available evidence concerning the role of each Hippo pathway's member as a promising biomarker, enabling detection of the disease at earlier stages and thus improving prognosis.

RevDate: 2022-07-31

Sculco M, La Vecchia M, Aspesi A, et al (2022)

Diagnostics of BAP1-Tumor Predisposition Syndrome by a Multitesting Approach: A Ten-Year-Long Experience.

Diagnostics (Basel, Switzerland), 12(7):.

Germline mutations in the tumor suppressor gene BRCA1-associated protein-1 (BAP1) lead to BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by high susceptibility to several tumor types, chiefly melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma. Here, we present the results of our ten-year experience in the molecular diagnosis of BAP1-TPDS, along with a clinical update and cascade genetic testing of previously reported BAP1-TPDS patients and their relatives. Specifically, we sequenced germline DNA samples from 101 individuals with suspected BAP1-TPDS and validated pathogenic variants (PVs) by assessing BAP1 somatic loss in matching tumor specimens. Overall, we identified seven patients (7/101, 6.9%) carrying six different germline BAP1 PVs, including one novel variant. Consistently, cascade testing revealed a total of seven BAP1 PV carriers. In addition, we explored the mutational burden of BAP1-TPDS tumors by targeted next-generation sequencing. Lastly, we found that certain tumors present in PV carriers retain a wild-type BAP1 allele, suggesting a sporadic origin of these tumors or a functional role of heterozygous BAP1 in neoplastic development. Altogether, our findings have important clinical implications for therapeutic response of BAP1-TPDS patients.

RevDate: 2022-08-10
CmpDate: 2022-07-28

Pandey SK, Machlof-Cohen R, Santhanam M, et al (2022)

Silencing VDAC1 to Treat Mesothelioma Cancer: Tumor Reprograming and Altering Tumor Hallmarks.

Biomolecules, 12(7):.

Mesothelioma, an aggressive cancer with a poor prognosis, is linked to asbestos exposure. However, carbon nanotubes found in materials we are exposed to daily can cause mesothelioma cancer. Cancer cells reprogram their metabolism to support increased biosynthetic and energy demands required for their growth and motility. Here, we examined the effects of silencing the expression of the voltage-dependent anion channel 1 (VDAC1), controlling the metabolic and energetic crosstalk between mitochondria and the rest of the cell. We demonstrate that VDAC1 is overexpressed in mesothelioma patients; its levels increase with disease stage and are associated with low survival rates. Silencing VDAC1 expression using a specific siRNA identifying both mouse and human VDAC1 (si-m/hVDAC1-B) inhibits cell proliferation of mesothelioma cancer cells. Treatment of xenografts of human-derived H226 cells or mouse-derived AB1 cells with si-m/hVDAC1-B inhibited tumor growth and caused metabolism reprogramming, as reflected in the decreased expression of metabolism-related proteins, including glycolytic and tricarboxylic acid (-)cycle enzymes and the ATP-synthesizing enzyme. In addition, tumors depleted of VDAC1 showed altered microenvironments and inflammation, both associated with cancer progression. Finally, tumor VDAC1 silencing also eliminated cancer stem cells and induced cell differentiation to normal-like cells. The results show that silencing VDAC1 expression leads to reprogrammed metabolism and to multiple effects from tumor growth inhibition to modulation of the tumor microenvironment and inflammation, inducing differentiation of malignant cells. Thus, silencing VDAC1 is a potential therapeutic approach to treating mesothelioma.

RevDate: 2022-07-27

Di Marzio N, Ananthanarayanan P, Guex AG, et al (2022)

Sound-based assembly of a microcapillary network in a saturn-like tumor model for drug testing.

Materials today. Bio, 16:100357.

The tumor microenvironment (TME), consisting of extracellular matrix, proteins, stromal cells, and a vascular system, is reported to have a key role in cancer progression and prognosis. Thereby, the interaction between the vascular network and tumor mass is an important feature of the TME since the anticancer agents which are delivered to the TME can trigger the vascular response and influence the therapeutic outcome of the treatment. To identify and develop new therapeutic strategies, 3D in vitro models that recapitulate the complexity of the TME are urgently needed. Among them, vascularized tumor models are a promising approach, allowing to target tumor angiogenesis and reduce tumor growth. By using sound patterning, cells can be condensed locally into highly reproducible patterns through the action of mild hydrodynamic forces. Here, we use a soundwave-driven cell assembly approach to create a ring-shaped microcapillary network in fibrin hydrogel. Then, we generate a 3D vascularized tumor model by combining a tumor heterotypic spheroid, consisting of fibroblasts and Malignant Pleural Mesothelioma (MPM) cells, with the surrounding vascular ring. Based on its shape, we name it Saturn-like vascularized Tumor Model (STM). The growth of the microcapillary network is monitored over time by fluorescence imaging. The area covered by the microcapillary network, and its continuous increase in presence of the heterotypic tumor spheroid was monitored. Interestingly, this effect is enhanced when treating the STM with the anticancer agent Cisplatin. Overall, we show the use of sound patterning as a fast and cell-friendly approach to spatially organize and condense cells, to generate a 3D in vitro platform from which simple readouts of drug tests can be extracted by image analysis, with the potential to provide a model system for tailored tumor therapy.

RevDate: 2022-07-28
CmpDate: 2022-07-27

Urban M, Pelclová D, Urban P, et al (2022)

Asbestos danger in central Europe is not yet over - the situation in the Czech Republic.

Central European journal of public health, 30(2):67-73.

OBJECTIVES: In the Czech Republic, asbestos has been classified as a known human carcinogen since 1984. The use of asbestos-containing products was limited to scenarios where the use of other materials was not possible. Since 1997, the manufacture of asbestos materials has been forbidden, and in 1999, the import, manufacture and distribution of all types of asbestos fibres was legally banned by Act No. 157/1998 Coll. Although the use of asbestos is forbidden, the risk of exposure still exists given the ongoing demolition and reconstruction of buildings in which asbestos has been used. In addition, a novel risk has arisen through the quarrying of asbestos-containing aggregates and their subsequent use. The aim of this paper was to describe and evaluate asbestos in terms of history, legislation, current risk of occupational exposure and its health consequences in the Czech Republic over the last three decades.

METHODS: This retrospective descriptive study used the collected data on occupational exposure and occupational diseases. The counts of workers occupationally exposed to asbestos were obtained from the Registry of Work Categorization; the numbers and structure of occupational diseases caused by asbestos were taken from the Czech National Registry of Occupational Diseases. Data on the total number of mesothelioma cases recorded in the Czech National Cancer Registry was provided by the Institute of Health Information and Statistics of the Czech Republic.

RESULTS: A total of 13,112 subjects were registered as occupationally exposed to asbestos during the period 2001-2020. A total of 687 cases of asbestos-related occupational diseases were reported in the period 1991-2020 in the Czech Republic, comprising 178 cases of asbestosis, 250 cases of pleural hyalinosis, 168 cases of pleural or peritoneal mesothelioma, 90 cases of lung cancer, and one case of laryngeal cancer. The data from the Czech National Cancer Registry, available for a shorter period (1991-2018), reveal 1,389 cases of mesothelioma, of which only ~11% were recognised as occupational, despite the fact that the occupational causality of mesotheliomas is estimated to be up to 90% of mesotheliomas. Moreover, the latency of mesotheliomas since the last occupational exposure reached up to 50 years and this trend is still slightly increasing, unlike asbestosis, where a high cumulative dose of inhaled asbestos is needed. The real proportion of occupational lung cancers may obviously be even higher, especially in smokers, where occupational causes including asbestos are not suspected by most physicians.

CONCLUSION: Czech data on asbestos-related occupational diseases, especially cancers, are grossly underestimated, which is most apparent through the low proportion of mesotheliomas diagnosed as occupational. Asbestos materials in older buildings remained in situ and may represent a danger during reconstruction works. The current source of exposure appears to be quarrying of asbestos-containing aggregate and its subsequent use. Awareness of the professional community is therefore crucial, not only for the possibility of compensating those affected, but also for the early detection of the diseases through the dispensary of exposed persons.

RevDate: 2022-07-26

Mazzoni E, Bononi I, Rotondo JC, et al (2022)

Sera from Patients with Malignant Pleural Mesothelioma Tested Positive for IgG Antibodies against SV40 Large T Antigen: The Viral Oncoprotein.

Journal of oncology, 2022:7249912.

Malignant pleural mesothelioma (MPM), a fatal tumor, is mainly linked to the asbestos exposure. It has been reported that together with the inhalation of asbestos fibers, other factors are involved in the MPM onset, including simian virus 40 (SV40). SV40, a polyomavirus with oncogenic potential, induces (i) in vitro the mesenchymal cell transformation, whereas (ii) in vivo the MPM onset in experimental animals. The association between MPM and SV40 in humans remains to be elucidated. Sera (n = 415) from MPM-affected patients (MPM cohort 1; n = 152) and healthy subjects (HSs, n = 263) were investigated for their immunoglobulin G (IgG) against simian virus 40 large tumor antigen (Tag), which is the transforming protein. Sera were investigated with an indirect enzyme-linked immunosorbent assay (ELISA) using two synthetic peptides from SV40 Tag protein. SV40 Tag protein was evaluated by immunohistochemical (IHC) staining on MPM samples (MPM cohort 2; n = 20). Formalin-fixed and paraffin-embedded (FFPE) samples were obtained from MPM patients unrelated to MPM serum donors. The proportion of sera, from MPM patients, showing antibodies against SV40 Tag (34%) was significantly higher compared to HSs (20%) (odds ratio 2.049, CI 95% 1.32-3.224; p=0.0026). Immunohistochemical staining (IHS) assays showed SV40 Tag expression in 8/20, 40% of MPM specimens. These results indicate that SV40 is linked to a large fraction of MPM. It is worth noting that the prevalence of SV40 Tag antibodies detected in sera from cohort 1 of MPM patients is similar to the prevalence of SV40 Tag found to be expressed in FFPE tissues from MPM cohort 2.

RevDate: 2022-08-19
CmpDate: 2022-08-19

Thives LP, Ghisi E, Thives Júnior JJ, et al (2022)

Is asbestos still a problem in the world? A current review.

Journal of environmental management, 319:115716.

Asbestos has been used by automobile, construction, manufacturing, power, and chemical industries for many years due to its particular properties, i.e. high tensile strength, non-flammable, thermal and electrical resistance and stability, and chemical resistance. However, such a mineral causes harmful effects to human health, including different types of cancer (e.g., mesothelioma). As a result, the use of asbestos has been banned since the 1980s in many countries. Nonetheless, asbestos is still part of the daily life of the population as asbestos-containing materials (ACMs) are still present in many buildings constructed and renovated before the 1990s. This work aims to present a current literature review about asbestos. The literature review was composed mainly of research articles published in international journals from the medical and engineering disciplines to provide an overview of asbestos use effects reported in interdisciplinary areas. The literature review comprised asbestos characteristics and its relationship to the risks of human exposure, countries where asbestos use is permitted or banned, reducing asbestos in the built environment, and environmental impact due to use and disposal of asbestos. The main findings were that ACMs are still responsible for severe human diseases, particularly in areas where there is a lack of coordinated asbestos management plans, reduced awareness about asbestos health risks, or even a delay in the implementation of asbestos-ban. Such issues may be more prevailing in developing countries. The current research in many countries contemplates several methodologies and techniques to process ACMs into inert and recyclable materials. The identification and coordinated management of ACM hazardous waste is a significant challenge to be faced by countries, and its inadequate disposal causes severe risk of exposure to asbestos fibres. Based on this work, it was concluded that banning asbestos is indicated in all countries in the world.

RevDate: 2022-07-22

Kumar N, Natrayan L, Kasirajan G, et al (2022)

Development of Novel Bio-mulberry-Reinforced Polyacrylonitrile (PAN) Fibre Organic Brake Friction Composite Materials.

Bioinorganic chemistry and applications, 2022:6426763.

Natural fibre reinforcement is used in important sectors such as medical, aerospace, automobile, and many other fields. Many articles have reported that natural fibre has the potential to replace synthetic fibres. Natural fibre reinforcement has given good results as a brake friction material. It has already been proven that asbestos causes lung cancer and mesothelioma in brakes. Many people died from the effects of asbestos. According to the World Health Organization's trending brake report, this material leads to serious health issues. This work is going on for the replacement of these materials. Mulberry fibre is a unique material, and PAN fibre is combined with mulberry fibre and used as a brake reinforcement material to replace Kevlar fibre. The brake pads were fabricated with the various wt% of mulberry fibres and PAN fibre [3-12%] with an equal ratio and aramid fibre [3-6%] in the hydraulic hind brake moulding machine. The mechanical, chemical, physical, tribological, and thermal properties were evaluated. MF-2 [6 wt%] mulberry-PAN-fibre-based brake pad composites have shown better results for ultimate shear strength and proof stress, tensile strength, compressive strength, and impact energy.

RevDate: 2022-10-06
CmpDate: 2022-09-22

Price B (2022)

Projection of future numbers of mesothelioma cases in the US and the increasing prevalence of background cases: an update based on SEER data for 1975 through 2018.

Critical reviews in toxicology, 52(4):317-324.

Historically, mesothelioma, which is almost exclusively a cancer of the pleura or peritoneum, has been referred to as a sentinel disease for asbestos exposure meaning that the disease is an epidemiologic marker for asbestos. This description of mesothelioma often has been misinterpreted to mean that the only risk factor for mesothelioma is asbestos. In addition to a few risk factors other than asbestos, in the US, background mesotheliomas, i.e. mesothelioma cases that are a consequence of spontaneous tumor formation, are the most prevalent number of cases after asbestos-associated cases.[1] My analysis of SEER data for 1973 through 2005 published in 2009 projected that around 2040 virtually all mesothelioma cases in the US will be background cases. The update here, which is based on the most current SEER data, 1975 through 2018, and the same methods used in 2009 shows that the pattern of mesothelioma incidence is unchanged. Further, in general agreement with the analysis published in 2009, after 2040 virtually all mesothelioma cases, currently estimated to be approximately 1600 per year, will be background cases.

RevDate: 2022-08-10
CmpDate: 2022-07-19

Henshall C, Dawson P, Rahman N, et al (2022)

Understanding clinical decision-making in mesothelioma care: a mixed methods study.

BMJ open respiratory research, 9(1):.

INTRODUCTION: Malignant pleural mesothelioma is a rare, incurable cancer arising from previous asbestos exposure; patients have a poor prognosis, with a median survival rate of 8-14 months. Variation in mesothelioma clinical decision-making remains common with a lack of multidisciplinary knowledge sharing, leading to inconsistencies in treatment decisions. The study aimed to explore which factors impacted on clinicians' decision-making in mesothelioma care, with a view to optimising the mesothelioma care pathway.

METHODS: This mixed methods study consisted of documentary analysis of local and national guidelines, policies or documents pertaining to mesothelioma care pathways, secondary analysis of mesothelioma patient data, and interviews with clinicians attending lung cancer and/or mesothelioma-specific multidisciplinary team meetings. The study took place at three National Health Service trusts in England. Documentations relating to patients' treatment pathways were collated and reviewed qualitatively. Records of patients with mesothelioma were extracted from hospital patient records and data collected on diagnosis date, treatment, mortality rates, survival postdiagnosis, age and clinical care team. Data were statistically analysed. Interviews with clinicians explored influences on clinical decision-making, including challenges or barriers involved. Data were thematically analysed. The Strengthening the Reporting of Observational Studies in Epidemiology reporting checklist was used.

RESULTS: There were differences in the structure and delivery of mesothelioma treatment and care between trusts. Four main themes were identified: 'collaboration and communication', 'evidence base and knowledge', 'role of the clinician' and 'role of the patient'. Two cross-cutting themes relating to the role of the mesothelioma nurse specialist and the impact of COVID-19 were identified.

DISCUSSION: There is a need to review the structure of mesothelioma multidisciplinary team meetings to ensure patients are reviewed by clinicians with appropriate knowledge, expertise and understanding of how, why and when decisions should be made. There is a need for expert clinicians in mesothelioma care to promote an up-to-date evidence and knowledge base within the wider multidisciplinary team.

RevDate: 2022-07-16

Ma GY, Shi S, Wang P, et al (2022)

Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion.

Biomedical reports, 17(2):66.

The diagnostic value of the 9P21 gene determined using fluorescence in situ hybridization (FISH) combined with BRCA1-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) expression detection by immunohistochemistry, was investigated in serous effusion samples of malignant mesothelioma. A total of 70 serous disease samples with serous effusion were collected from June 2017 to June 2020. Following biopsy specimen pathological diagnosis, samples were divided into malignant mesothelioma and benign mesothelioma. Differential expression of BAP1 and MTAP genes were identified in mesothelioma and mesenchymal hyperplasia. The 9P21 gene fragment was lost in mesothelioma. The positive rates of FISH, BAP1 and MTAP in biopsy specimens were 98.00, 94.00 and 90.00%. The specificity of the three were 96.00, 85.71 and 77.27%, the sensitivity were 90.00, 95.92 and 93.75%, and the positive rate of the combined detection of the three was 93.33%. The positive rate of serous fluid samples detected by the three methods (9P21 FISH probe combined with BAP1 and MTAP expression detected immunohistochemically) was 96.00, 92.00 and 88.00%, the specificity were 90.00, 77.27 and 71.43%, the sensitivity was 96.00, 93.75 and 89.80%, and the positive rate of the three combined detections was 91.33%. It was demonstrated that there was a high consistency between serous fluid samples and biopsy samples. According to clinicopathological analysis, sex, age, lesion site, Ki67 had little association with the occurrence and development of malignant mesothelioma, while asbestos exposure history was closely associated to the occurrence of mesothelioma. A high level of BAP1 gene was positively associated with the prognosis of mesothelioma, while a high level of MTAP gene was negatively associated with the prognosis of mesothelioma (P<0.05). Therefore, 9P21 FISH probe combined with BAP1 and MTAP can be used as a new method for the detection of malignant mesothelioma, and provide an important basis for the early diagnosis of mesothelioma.

RevDate: 2022-07-16

Janssens E, Schillebeeckx E, Zwijsen K, et al (2022)

External Validation of a Breath-Based Prediction Model for Malignant Pleural Mesothelioma.

Cancers, 14(13):.

During the past decade, volatile organic compounds (VOCs) in exhaled breath have emerged as promising biomarkers for malignant pleural mesothelioma (MPM). However, as these biomarkers lack external validation, no breath test for MPM has been implemented in clinical practice. To address this issue, we performed the first external validation of a VOC-based prediction model for MPM. The external validation cohort was prospectively recruited, consisting of 47 MPM patients and 76 asbestos-exposed (AEx) controls. The predictive performance of the previously developed model was assessed by determining the degree of agreement between the predicted and actual outcome of the participants (patient/control). Additionally, to optimise the performance, the model was updated by refitting it to the validation cohort. External validation revealed a poor performance of the original model as the accuracy was estimated at only 41%, indicating poor generalisability. However, subsequent updating of the model improved the differentiation between MPM patients and AEx controls significantly (73% accuracy, 92% sensitivity, and 92% negative predictive value), substantiating the validity of the original predictors. This updated model will be more generalisable to the target population and exhibits key characteristics of a potential screening test for MPM, which could significantly impact MPM management.

RevDate: 2022-07-16

Song Y, Baxter SS, Dai L, et al (2022)

Mesothelioma Mouse Models with Mixed Genomic States of Chromosome and Microsatellite Instability.

Cancers, 14(13):.

Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g., asbestos). Genomic studies have revealed that the most frequent genetic lesions in human MMe are mutations in tumor suppressor genes. Several genetically engineered mouse models have been generated by introducing the same genetic lesions found in human MMe. However, most of these models require specialized breeding facilities and long-term exposure of mice to asbestos for MMe development. Thus, an alternative model with high tumor penetrance without asbestos is urgently needed. We characterized an orthotopic model using MMe cells derived from Cdkn2a[+/-];Nf2[+/-] mice chronically injected with asbestos. These MMe cells were tumorigenic upon intraperitoneal injection. Moreover, MMe cells showed mixed chromosome and microsatellite instability, supporting the notion that genomic instability is relevant in MMe pathogenesis. In addition, microsatellite markers were detectable in the plasma of tumor-bearing mice, indicating a potential use for early cancer detection and monitoring the effects of interventions. This orthotopic model with rapid development of MMe without asbestos exposure represents genomic instability and specific molecular targets for therapeutic or preventive interventions to enable preclinical proof of concept for the intervention in an immunocompetent setting.

RevDate: 2022-07-16

Tanaka T, Asakura S, Hisamatsu K, et al (2022)

Thrombocytopenia as an Immune-Related Adverse Event in Malignant Pleural Mesothelioma: A Case Report.

JTO clinical and research reports, 3(7):100351.

A 69-year-old man presented with a pulmonary opacity at a regular medical check-up. He had been exposed to asbestos in a chemical fiber manufacturing setting. Result of positron emission tomography with computed tomography (CT) revealed fluorodeoxyglucose accumulations along the right pleura in areas with multiple nodules and irregular pleural thickening. On the basis of analysis of a CT-guided needle biopsy result, he had been diagnosed with having epithelioid malignant pleural mesothelioma. He received neoadjuvant chemotherapy, and subsequently, a pleurectomy and decortication. After 6 months, malignant pleural mesothelioma recurred with multiple tumors in the pleural cavity. Nivolumab was administered as salvage immunotherapy. A CT scan result revealed marked tumor reduction; however, his platelet count was low (8000/μL), and he was diagnosed with having nivolumab-induced immune thrombocytopenia. Oral prednisone and thrombopoietin receptor agonist were delivered, and the platelet count improved; therefore, a sustained cycle of nivolumab was resumed. This case revealed that nivolumab could be readministered for continued antitumor effects, with careful management of immune-related adverse events.

RevDate: 2022-07-16

Kuryk L, Rodella G, Staniszewska M, et al (2022)

Novel Insights Into Mesothelioma Therapy: Emerging Avenues and Future Prospects.

Frontiers in oncology, 12:916839.

Malignant mesothelioma is a rare and aggressive cancer that develops in the thin layer surrounding the mesothelium and is mainly caused by asbestos exposure. Despite improvements in patient prognosis with conventional cancer treatments, such as surgery, chemotherapy, and radiotherapy, there are still no curative treatment modalities for advanced disease. In recent years, new therapeutic avenues have been explored. Improved understanding of the mechanisms underlying the dynamic tumor interaction with the immune system has led to the development of immunotherapeutic approaches. Numerous recent clinical trials have shown a desire to develop more effective treatments that can be used to fight against the disease. Immune checkpoint inhibitors, oncolytic adenoviruses, and their combination represent a promising strategy that can be used to synergistically overcome immunosuppression in the mesothelioma tumor microenvironment. This review provides a synthesized overview of the current state of knowledge on new therapeutic options for mesothelioma with a focus on the results of clinical trials conducted in the field.

RevDate: 2022-09-06
CmpDate: 2022-08-24

Fennell DA, Dulloo S, J Harber (2022)

Immunotherapy approaches for malignant pleural mesothelioma.

Nature reviews. Clinical oncology, 19(9):573-584.

Over the past decade, immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. In mesothelioma, a rare cancer with a dismal prognosis generally caused by exposure to asbestos, treatment with single or dual ICIs results in robust improvements in overall survival over previous standard-of-care therapies, both in the first-line and relapsed disease settings. Predictive biological features that underpin response to ICIs remain poorly understood; however, insights into the immune microenvironment and genomic landscape of mesothelioma as well as into their association with response or acquired resistance to ICIs are emerging. Several studies of rational combinations involving ICIs with either another ICI or a different agent are ongoing, with emerging evidence of synergistic antitumour activity. Non-ICI-based immunotherapies, such as peptide-based vaccines and mesothelin-targeted chimeric antigen receptor T cells, have demonstrated promising efficacy. Moreover, results from pivotal trials of dendritic cell vaccines and viral cytokine delivery, among others, are eagerly awaited. In this Review, we comprehensively summarize the key steps in the development of immunotherapies for mesothelioma, focusing on strategies that have led to randomized clinical evaluation and emerging predictors of response. We then forecast the future treatment opportunities that could arise from ongoing research.

RevDate: 2022-07-28
CmpDate: 2022-06-28

Locher BN, Barresi F, Kuhn BK, et al (2022)

Occupations and geographical distribution of mesothelioma in Switzerland 1989-2018 - record linkage of an asbestos-exposed population with the Swiss National Cohort.

Swiss medical weekly, 152:w30164 pii:Swiss Med Wkly. 2022;152:w30164.

OBJECTIVE: We investigated the possibility of linking the data of the Swiss Laboratory for Particle Analysis (Silag), a valuable but incomplete data source in the field of asbestos-related diseases, to the Swiss National Cohort (SNC). With the resulting comprehensive dataset, we intended to provide a source for further research in the field. We also conducted preliminary analyses of data focusing on occupations and regional distribution of malignant pleural mesothelioma cases.

METHODS: Data of asbestos-exposed individuals available from the Silag were anonymously linked with the SNC by means of deterministic record linkage. From this linkage, data on occupation classified according to the international standard classification of occupations (ISCO) as well as the canton of residence in Switzerland could be retrieved.

RESULTS: Of 838 eligible individuals from the Silag data, 788 (94.0%) could be linked to the SNC database, including 476 mesothelioma cases. In 340 cases of the latter, data on occupation and industries were available. Although the majority of them were blue-collar workers, a significant proportion (n = 44, 12.9%) had executive professions. The Canton of residence in 1990 was established in 430 of subjects with mesothelioma. A cluster could be identified in eastern Switzerland, especially in the canton of Glarus.

CONCLUSIONS: It was possible to link the datasets to a large extent thereby creating a data source for further research. Of note, the linkage provided data on occupation of a selection of mesothelioma cases in Switzerland.

RevDate: 2022-07-16

Nagamatsu Y, Sakyo Y, Barroga E, et al (2022)

Depression and Complicated Grief, and Associated Factors, of Bereaved Family Members of Patients Who Died of Malignant Pleural Mesothelioma in Japan.

Journal of clinical medicine, 11(12):.

OBJECTIVES: we investigated the prevalence and associated factors of depression and complicated grief (CG) among bereaved family members of malignant pleural mesothelioma (MPM) patients in Japan.

METHODS: Bereaved family members of MPM patients (n = 72) were surveyed. The Japanese version of the Patient Health Questionnaire-9 (PHQ-9) and the Japanese version of the Brief Grief Questionnaire (BGQ) were used to assess depression and complicated grief (CG), respectively. Socio-economic factors, anger toward asbestos, care satisfaction, achievement of good death, and quality of end-of-life care were assessed in relation to depression and CG.

RESULTS: In the family members of MPM patients, the frequencies of depression and CG were 19.4% and 15.3%, respectively. The bereaved family members who were not compensated by the asbestos-related health-damage relief system (p = 0.018) and who felt the financial impacts of the patient's MPM on the family (p = 0.006) had a higher likelihood of depression. The bereaved family members who were not satisfied with the care given when the patient became critical (p = 0.034), who were not compensated by the asbestos-related health-damage relief system (p = 0.020), who felt the financial impact of the patient's MPM on the family (p = 0.016), and whose deceased relative underwent surgery (p = 0.030) had a higher likelihood of CG.

CONCLUSIONS: For bereaved family members of MPM patients, routine screening for depression and CG and the provision of grief care are suggested. In addition, for family members of MPM patients, financial support, including the promotion of the asbestos-related health-damage relief system, and improved care for patients who undergo surgery and when patients become critical, are recommended.

RevDate: 2022-07-16

Bellini A, Mazzarra S, Sterrantino S, et al (2022)

Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review.

Journal of clinical medicine, 11(12):.

Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumour with poor prognosis. To date, a multimodality treatment, including chemotherapy and surgery, with or without radiotherapy, is the gold standard therapy for selected patients with epithelioid and early-stage MPM. In this setting, the goal of surgery is to achieve the macroscopic complete resection, obtained by either extrapleural pneumonectomy or pleurectomy/decortication. Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for the recurrence of MPM after the multimodal approach, and the role of surgery in this context is still controversial. By using electronic databases, studies that included recurrent MPM patients who underwent a second surgery were identified. The endpoints included were: a pattern of recurrence, post-recurrence survival (PRS), and the type of second surgery. When available, factors predicting better PRS and perioperative mortality and morbidity were collected. This systematic review offers an overview of the results that are currently obtained in patients undergoing a second surgery for relapsed MPM, with the aim to provide a comprehensive view on this subject that explores if a second surgery leads to an improvement in survival.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )