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Dr. Michele Carbone's Scientific Publications

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Published in Ca: A Cancer Journal for Clinicians, online version on July 9, 2019

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-associated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested.  The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapties are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.
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BAP1 regulates different mechanisms of cell death

BAP1 regulates different mechanisms of cell death

Cell Death & Disease, volume 9, Article number: 1151 (2018)

The ubiquitin carboxyl terminal BAP1 is a member of deubiquitinating enzymes superfamily, which are responsible for coordinating ubiquitin-signaling processes through the removal of ubiquitin from protein substrates. Studies of families with high incidence of mesothelioma led to the discovery that all affected family members carried heterozygous BAP1 mutations (BAP1+/−), a condition that was named “the BAP1 cancer syndrome”.

 

Since the initial discovery in 2011, over 100 families have been identified worldwide affected by the BAP1 cancer syndrome.

 

Authors: El Bachir Affar, Michele Carbone

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A Subset of Mesotheliomas With Improved Survival Occurring in Carriers of BAP1 and Other Germline Mutations

A Subset of Mesotheliomas With Improved Survival Occurring in Carriers of BAP1 and Other Germline Mutations

ABSTRACT

We hypothesized that four criteria could help identify malignant mesotheliomas (MMs) most likely linked to germline mutations of BAP1 or of other genes: family history of MM, BAP1-associated cancers, or multiple malignancies; or age younger than 50 years old.

 Authors: Sandra Pastorino, Yoshie Yoshikawa, Harvey I. Pass, Mitsuru Emi, Masaki Nasu, Ian Nasu, Ian Pagano, Yasutaka Takinishi, Ryuji Yamamoto, Michael Manaai, Tomoko Hashimoto-Tamaoki, Masaki Ohmuraya, Keisuke  Goto, Chandra Goparaju, Kavita Y. Sarin, Mika Tanji, Angela Bononi, Andrea Napolitano, Giovanni Gaudino, Mary Hesdorffer, and Michele Carbone.

 





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Consensus report of the 8 and 9th Weinman Symposia on Gene xEnvironment Interaction: novel opportunities for precision medicine in carcinogenesis

Consensus report of the 8 and 9th Weinman Symposia on Gene xEnvironment Interaction: novel opportunities for precision medicine in carcinogenesis

For the past 10 years, the Virginia  & Barry Weinman Foundation, in conjunction with the University of Hawaii Cancer Center, has sponsored an annual meeting of top researchers from around the world. This publication in Cell Death & Differentiation (6 August 2018) is a consensus report about the role of genes and environment in carcinogenesis.

 

 

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Oncogene Short Communication:

Oncogene Short Communication:

Inhibition of the spindle assembly checkpoint kinase Mps-1 as a novel therapeutic strategy in malignant mesothelioma

CFI-402257 is a promising novel therapeutic agent to improve the efficacy of the current chemotherapeutic regimens for MM patients.
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