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Mesothelioma is a rare aggressive cancer that develops from the mesothelium. Recent molecular analyses have defined four different types of mesothelioma based on gene expression and two major molecularly-defined groups based on prognosis. In this volume, potential mechanisms causing this heterogeneity are explored. The different chapters include heterogeneity learned from experimental animal models in NF2/Hippo pathway signaling, stem cell signaling pathways, the tumor microenvironment, and micro RNA secretome. Novel aspects deserving attention such as the implication of long, non-coding RNA in disease heterogeneity are described. The volume also includes the description of tools useful to address some specific questions such as an assessment of the copy number variations of two tumor suppressors frequently mutated in mesothelioma or an investigation of Macrophage Inhibition Factor signaling in mesothelioma.

NF2 signaling pathway --- tumor microenvironment --- mesothelioma --- experimental mesothelioma models

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Le mésothéliome pleural malin (MPM) est un cancer rare qui affecte les cellules mésothéliales de la plèvre. Actuellement, les traitements conventionnels tels que la chirurgie, la radiothérapie et la chimiothérapie sont peu efficaces et ne permettent d’allonger la durée de vie des patients que de quelques mois. Capables de phagocytose, les éosinophiles sont des acteurs de l’immunité innée impliqués dans les infections parasitaires. Leur implication dans les cancers dépend de l’environnement immunologique de la tumeur. Dans le mésothéliome pleural malin, des observations cliniques et au laboratoire montrent que des patients caractérisés par une hyperéosinophilie répondent faiblement à la chimiothérapie. 
Les objectifs de ce travail consistent d’une part à caractériser l’effet de la chimiothérapie sur les différentes lignées cellulaires humaines de MPM, et d’autre part à comprendre l’effet des éosinophiles sur la résistance à la chimiothérapie. Les résultats ont montré que la chimiothérapie standard (cisplatine + pemetrexed) altère l'activité métabolique, provoque l'arrêt du cycle cellulaire et induit l'apoptose des cellules MPM. Le surnageant isolé de cultures d’éosinophiles diminue l’apoptose des cellules de MPM en présence de chimiothérapie. L'interleukine-5, une interleukine impliquée dans l'activation des éosinophiles, affecte également l’apoptose selon le sous-type histologique de MPM. L'imagerie confocale indique que les granules produits par les éosinophiles interagissent avec les cellules de MPM en culture.
Ce travail démontre donc que les éosinophiles altèrent la sensibilité des cellules humaines de MPM à la chimiothérapie. Malignant pleural mesothelioma (MPM) is a rare cancer that affects mesothelial cells of the pleura. Currently, conventional treatments such as surgery, radiotherapy and chemotherapy are inefficient and only enable to extend patient’s survival of a few months. Eosinophils are phagocytic cells involved in innate immunity against parasitic infections. Their involvement in cancer depends on the immune microenvironment of the tumour. In MPM, clinical evidence indicates that patients characterized by hypereosinophilia respond weakly to conventional chemotherapy.
The goals of this study are, on one hand, to study the effect of chemotherapy on different human MPM cell lines, and on the other hand, to investiguate the effect of eosinophils on chemoresistance. Results show that the standard chemotherapy (cisplatin + pemetrexed) reduces metabolic activity, induces cell cycle arrest and increase apoptosis of MPM cells. Cell culture supernatants isolated from eosinophils decreases apoptosis of MPM cells in presence of chemotherapy. Interleukin-5, an interleukin associated to eosinophil activation, also affects apoptosis depending on the histological subtype of MPM. Confocal microscopy shows that granules produced by eosinophils interact with MPM cells in culture.
These data thus demonstrate eosinophils modify sensitivity of human MPM cells to chemotherapy.

mésothéliome --- chimiothérapie --- chimiorésistance --- mesothelioma --- chemotherapy --- chemoresistance --- Sciences de la santé humaine > Oncologie

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This book covers different aspects of the rare neoplasms – malignant mesothelioma and pseudomyxoma peritonei. The monograph includes up-to-date information on etiology, pathogenesis and diagnostics of malignant mesothelioma and pseudomyxoma peritonei, as well as detailed description of surgical and combined treatment of patients with these diseases. The book comprises a large illustrative material presented by schemes and original micrographs that represent pathological and immunohistochemical specific features of these malignancies, demonstrate the stages of surgical operations and hyperthermic intraperitoneal chemotherapy, and show the results of experimental studies. The book includes validated discussion on etiology and pathogenesis of malignant mesothelioma and pseudomyxoma peritonei, differential diagnosis and treatment of these diseases. The scope is really extensive and involves, for instance, a description of the technique of cytoreductive surgeries and regimens of intraperitoneal hyperthermic chemoperfusion, whereas a particular section discusses experimental ground for optimal regimens of hyperthermia, local chemotherapy and adoptive immunotherapy by cytokine induced killers. The final section presents the most recent data about perspective approaches for immunotherapy of malignant mesothelioma and pseudomyxoma peritonei with cell based technologies and target drugs including inhibitors of immune checkpoints. The co-authors of the book are leading specialists in this area, surgeons and scientists who present the results of their research along with the analysis of the state-of-the-art of this problem. The book is designed for a wide audience of students and professors of medical universities and schools, specialists of research and diagnostic centers, practical oncologists and immunologists, as well as doctors of different medical areas. .

Mesothelioma. --- Surgical oncology. --- Oncology. --- Psychology, clinical. --- Surgical Oncology. --- Cancer Research. --- Clinical Psychology. --- Tumors --- Cancer --- Oncologic surgery --- Oncological surgery --- Surgical oncology --- Excision --- Treatment --- Cancer research. --- Clinical psychology. --- Psychiatry --- Psychology, Applied --- Psychological tests --- Cancer research