Epidemiology of Mesothelioma

Moolgavkar, Suresh H.; Chang, Ellen T.; Mezei, Gábor; Mowat, Fionna

doi:10.1007/978-3-319-53560-9_3

Cited by 12 publications

(5 citation statements)

References 170 publications

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“…Otherwise, for modeling purposes, chrysotile would have to be assigned a mesothelioma potency value near zero, and not 0.0009, as we assumed. However, the developed models further confirm that chrysotile asbestos is about two orders of magnitude or less potent for mesothelioma, than typical amphibole asbestos on a fiber-by-fiber basis (Moolgavkar et al 2017).…”

Section: Uncertainties and Limitationsmentioning

confidence: 68%

“…Asbestos toxicological mechanisms and fiber-type cancer potencies remain one of the most controversial topics of modern epidemiology, toxicology, and industrial hygiene (Mossman et al 2011;Moolgavkar et al 2017). IARC recognizes all asbestos mineral types as human carcinogens, and it is clear that apparently all asbestos mineral types can increase risk of lung cancer (IARC 2012).…”

Section: Introductionmentioning

confidence: 99%

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Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality

Korchevskiy¹,

Rasmuson²,

Rasmuson³

2019

Inhalation Toxicology

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Context: The potency of various mineral fiber types to produce mesothelioma was previously evaluated for numerous cohorts, but the differences in potencies for distinct fiber types have yet to be explained. Objective: To develop an empirical model that would reconstruct mesothelioma potency factors for various types of fiber based on their chemical composition and dimensionality. Methods: Typical chemical composition and dimensionality metrics (aspect ratios) were obtained and combined with mesothelioma potency factors estimated by Hodgson and Darnton method for Quebec chrysotile, South Africa amosite, South Africa and Australian crocidolite, Russian anthophyllite, Libby amphiboles, and Turkey erionite. The forward stepwise log-log regression method was utilized to determine the best combination of input parameters. Results: Mesothelioma potency factors (R M) for selected cohorts were effectively reconstructed utilizing the median aspect ratio of fibers and equivalent fractions of SiO 2 , total Fe oxides or total equivalent Fe 3þ as Fe 2 O 3 , and MgO. Modeled potency factors increase as the aspect ratio, SiO 2 , and total Fe oxide (or Fe 2 O 3) content grow, and as the MgO content diminishes. Correlation coefficients up to 0.999, p < 0.01, were achieved. The models also yield reasonable estimates of mesothelioma potencies for other fiber types, including Bolivian crocidolite, Russian chrysotile, fluoro-edenite, and others. Conclusion: In spite of the empirical approach, the proposed models provide a starting point for targeted studies of mesothelioma mechanisms by elucidating significant contributing physicochemical factors. The models have an exploratory and preliminary character but can potentially be useful to introduce quantitative structure-activity relationship approaches for the toxicology of fibrous minerals.

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Section: Uncertainties and Limitationsmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality

Korchevskiy¹,

Rasmuson²,

Rasmuson³

2019

Inhalation Toxicology

View full text Add to dashboard Cite

show abstract

“…Besides asbestos inhalation, associations with ionizing radiation, such as mantle radiation for Hodgkin's lymphoma or a germline mutation of the BRCA 1-associated protein (BAP1), are known risk factors [3]. An increase in the incidence of PM cases without a concomitant increase in asbestos exposure suggests that genetic predisposing factors may play a crucial role, and idiopathic/spontaneous cases are thought to account for a significant percentage of cases [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers

Sorino,

Mondoni,

Marchetti

et al. 2023

JCM

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Pleural mesothelioma (PM) is a type of cancer that is highly related to exposure to asbestos fibers. It shows aggressive behavior, and the current therapeutic approaches are usually insufficient to change the poor prognosis. Moreover, apart from staging and histological classification, there are no validated predictors of its response to treatment or its long-term outcomes. Numerous studies have investigated minimally invasive biomarkers in pleural fluid or blood to aid in earlier diagnosis and prognostic assessment of PM. The most studied marker in pleural effusion is mesothelin, which exhibits good specificity but low sensitivity, especially for non-epithelioid PM. Other biomarkers found in pleural fluid include fibulin-3, hyaluronan, microRNAs, and CYFRA-21.1, which have lower diagnostic capabilities but provide prognostic information and have potential roles as therapeutic targets. Serum is the most investigated matrix for biomarkers of PM. Several serum biomarkers in PM have been studied, with mesothelin, osteopontin, and fibulin-3 being the most often tested. A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker in patients with suspected mesothelioma. With different serum and pleural fluid cut-offs, it provides useful information on the diagnosis, prognosis, follow-up, and response to therapy in epithelioid PM. Panels combining different markers and proteomics technologies show promise in terms of improving clinical performance in the diagnosis and monitoring of mesothelioma patients. However, there is still no evidence that early detection can improve the treatment outcomes of PM patients.

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“…Diffuse malignant mesothelioma (DMM), a cancer that originates from mesothelial cells lining the pleural, pericardial, and abdominal cavities including the testis, is mainly caused by asbestos exposure. 1 The annual incidence of DMM varies between countries and is estimated to be 0.8 – 2.9 per 100’000 people. Depending on the stage and the modality of treatment, median survival is between 12 and 22 months, making DMM one of the prognostically most discouraging human malignancies.…”

Section: Introductionmentioning

confidence: 99%

The “don't eat me” signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma

et al. 2017

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Diffuse malignant mesothelioma (DMM) is one of the prognostically most discouraging cancers with median survivals of only 12–22 months. Due to its insidious onset and delayed detection, DMM is often at an advanced stage at diagnosis and is considered incurable. Combined chemo- and radiotherapy followed by surgery only marginally affect outcome at the cost of significant morbidity. Because of the long time period between exposure to asbestos and disease onset, the incidence of DMM is still rising and predicted to peak around 2020. Novel markers for the reliable diagnosis of DMM in body cavity effusion specimens as well as more effective, targeted therapies are urgently needed. Here, we show that the “don't eat me” signalling molecule CD47, which inhibits phagocytosis by binding to signal regulatory protein α on macrophages, is overexpressed in DMM cells. A two-marker panel of high CD47 expression and BRCA1-associated protein 1 (BAP-1) deficiency had a sensitivity of 78% and specificity of 100% in discriminating DMM tumour cells from reactive mesothelial cells in effusions, which is superior to the currently used four-marker combination of BAP-1, glucose transporter type 1, epithelial membrane antigen and desmin. In addition, blocking CD47 inhibited growth and promoted phagocytosis of DMM cell lines by macrophages in vitro. Furthermore, DMM tumours in surgical specimens from patients as well as in a mouse DMM model expressed high levels of CD47 and were heavily infiltrated by macrophages. Our study demonstrates that CD47 is an accurate novel diagnostic DMM biomarker and that blocking CD47 may represent a promising therapeutic strategy for DMM.

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Epidemiology of Mesothelioma

Cited by 12 publications

References 170 publications

Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality

Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality

Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers

The “don't eat me” signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma

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