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This book is devoted to the state of the art, pitfalls and perspectives in the diagnosis and treatment of mesothelioma - a peculiar malignant tumour arising from mesothelial cells that line the pleura, the pericardium and the peritoneum. Mesothelioma is known for its strong association with asbestos exposure, difficult surgical treatment and dismal prognosis. However, recent years have yielded significant discoveries on, for example, germline mutations in BAP1 gene coding BRCA1-associated protein 1, the pathogenetic role of inflammation, and innovative treatment approaches such as immune checkpoint inhibitors. The volume is intended to summarise classic views and innovations in the pathogenetic concepts, diagnostics, treatment and scientific studies of mesothelioma, resulting in a comprehensive reference work as well as a source of ideas for relevant clinical and basic research.

Mesothelioma.

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"Mesothelioma is a type of cancer in which tumors form in the tissue that lines the lungs, heart, stomach, and other organs. While mesothelioma is relatively rare, it represents a serious health crisis as the disease is aggressive and often fatal. This book includes five chapters that detail the treatment and prognosis of the disease as well as the factors that put a person at risk for developing mesothelioma. Chapter One describes the most promising emerging immunotherapy combinations for the treatment of malignant pleural mesothelioma, discussing the biological rational underlying their development as well as the issues surrounding their clinical development. Chapter Two provides an overview of malignant mesothelioma, describing the history of its diagnosis and treatment as well as the role that asbestos exposure and other factors play in its development. Chapter Three revises the role of the main inflammatory and immunological markers as prognostic indicators in malignant pleural mesothelioma and discusses the surgical effects on immune response against cancer. Chapter Four explores the main cancer markers utilized for mesothelioma diagnosis as well as the new developments in the field. Lastly, Chapter Five examines the various surgical options available for removing pleural tumors"--

Mesothelioma.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

This book is devoted to the state of the art, pitfalls and perspectives in the diagnosis and treatment of mesothelioma - a peculiar malignant tumour arising from mesothelial cells that line the pleura, the pericardium and the peritoneum. Mesothelioma is known for its strong association with asbestos exposure, difficult surgical treatment and dismal prognosis. However, recent years have yielded significant discoveries on, for example, germline mutations in BAP1 gene coding BRCA1-associated protein 1, the pathogenetic role of inflammation, and innovative treatment approaches such as immune checkpoint inhibitors. The volume is intended to summarise classic views and innovations in the pathogenetic concepts, diagnostics, treatment and scientific studies of mesothelioma, resulting in a comprehensive reference work as well as a source of ideas for relevant clinical and basic research.

Mesothelioma.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

This book is devoted to the state of the art, pitfalls and perspectives in the diagnosis and treatment of mesothelioma - a peculiar malignant tumour arising from mesothelial cells that line the pleura, the pericardium and the peritoneum. Mesothelioma is known for its strong association with asbestos exposure, difficult surgical treatment and dismal prognosis. However, recent years have yielded significant discoveries on, for example, germline mutations in BAP1 gene coding BRCA1-associated protein 1, the pathogenetic role of inflammation, and innovative treatment approaches such as immune checkpoint inhibitors. The volume is intended to summarise classic views and innovations in the pathogenetic concepts, diagnostics, treatment and scientific studies of mesothelioma, resulting in a comprehensive reference work as well as a source of ideas for relevant clinical and basic research.

Mesothelioma.

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Le mésothéliome malin est un cancer rare, généralement causé par une exposition à l’asbeste et affectant les membranes séreuses des cavités pleurales et péritonéales. A l’heure actuelle, les stratégies thérapeutiques restent peu efficaces, engendrant son mauvais pronostic. Les similitudes entre les fibres d’amiante et les nanotubes de carbone (CNT), notamment leur capacité à induire le mésothéliome, rendent l’utilisation de ce matériau préoccupante pour la santé publique. Des recherches expérimentales sont donc nécessaires pour mieux comprendre les mécanismes pathogéniques menant au mésothéliome induit par les fibres d’amiante et les nanotubes de carbone. Notre projet a pour but de caractériser les réponses immunosuppressives lors du développement di mésothéliome chez le rat traité aux CNT. Il est maintenant connu que des cellules immunosuppressive sont présentes dans le microenvironnement tumoral ; elles inhibent l’immunité innée et adaptative, déstabilisent la surveillance immunitaire et empêchent les réponses immunitaires anti-tumorales. Nous déterminons en particulier si les réponses cancérigènes précoces aux CNT Mitsui-7 (CNT-7) sont associées à l’accumulation de macrophages immunosuppresseurs. Nous utilisons un modèle péritonéal chez le rat Wistar qui permet d’exposer directement les cellules mésothéliales aux CNT ou à l’asbeste, et de prélever facilement des échantillons de la cavité séreuse afin d’évaluer les réponses macrophagiques durant le processus cancérigène. Nous avons confirmé que les macrophages CD11b/c high et his48int présents dans le microenvironnement du mésothéliome induit par les CNT-7 et triés par FACS ont la capacité d’inhiber l’activation polyclonale des lymphocytes T in vitro. Ces macrophages suppresseurs sont déjà présents, grâce à une prolifération locale, lors de la réponse précoce aux CNT cancérigènes ou à l’asbeste (jour 1 à 30) , bien avant le développement du mésothéliome (6 mois). Ces cellules accumulées de manière précoces n’ont pas été observés chez la souris, résistante au mésothéliome induit par les CNT-7. L’analyse de l’expression des gènes immunosuppresseurs (RT-qPCR) a révélé que les macrophages péritonéaux de rats traités aux CNT (jour 1 à 30) expriment fortement les médiateurs immunosuppresseurs IL-10 et Arginase-1, comparativement aux macrophages péritonéaux naïfs ou aux macrophages obtenus après traitement à la silice, une particule n’induisant pas le mésothéliome. Dès lors nos données indiquent que les nanotubes cancérigènes possèdent la capacité d’induire une accumulation préférentielle, rapide et soutenue de macrophages immunosuppresseurs avant que le mésothéliome ne soit établi. Cette accumulation de macrophages immunosuppresseurs lors du développement du mésothéliome supporte l’utilisation des réponses immunosuppressives pour détecter les nanomatériaux mésothéliomagéniques. MM is a rare cancer caused by asbestos exposure affecting the serous membrane of pleural and peritoneal cavities. MM remains a highly refractory cancer to existing therapeutic strategies. The asbestos-like toxicity of engineered carbon nanotubes (CNT). Notably their capacity to induce malignant mesothelioma (MM), is a serious cause of concern for public health. Intensive research efforts are therefore needed to better understand the pathomechanisms of CNT-induced MM. The present project deals with immunosuppression during the mesothelial response to CNT in rats. There is growing evidence that tumors harbor immunosuppressive cells that inhibit both innate and adaptive immunity, subverting immune surveillance and preventing efficient natural or therapeutic anti-tumor immune responses. We aim to determine if the carcinogenic response to Mitsio-7 CNT (CNT-7) is associated with accumulation of immunosuppressive macrophages. We used a Wistar rat peritoneum model which allows directly exposing mesothelial cells to CNT or asbestos, and easily sampling the mesothelial cavity for monitoring macrophage responses during the carcinogenic process. We show that FACS-sorted CD11b/c high and His48int macrophages present in CNT-7 induced mesothelioma microenvironment suppress polyclonal activation of T lymphocytes in vitro. The inhibitory macrophages are already present during the early response to carcinogenic CNT or asbestos (day 1 to 30), well before the establishment of mesothelioma (6 months). Immunosuppressive peritoneal macrophages were not observed in mice, which are resistant to mesothelioma development upon CNT-7. RTqPCR revealed that peritoneal macrophages purified from CNT-treated rats (day 1-30) highly expressed the immunosuppressive mediators IL-10 and Arginase-1 in comparison to naïve peritoneal macrophages or macrophages obtained after silica, a particle that does not induce mesothelioma. Altogether, our data demonstrate that carcinogenic CNT possess the intrinsic capacity to induce a preferential, rapid and sustained accumulation of immunosuppressive macrophages before mesothelioma is established. These data provide new insight into the possible contribution of immunosuppression in the early pathogenic processes of CNT-induced mesothelioma.

Macrophages --- Mesothelioma