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Dimensions of hepatocellular carcinoma phenotypic diversity

World Journal of Gastroenterology 2018年第40期24卷 4536-4547页

作者： Romain Désert natalia nieto Orlando Musso Institut NuMeCan Université de Rennes 1 Institut national de la recherche agronomique (INRA) Institut national de la santé et de la recherche médicale (INSERM) Department of Pathology Department of Medicine (Gastroenterology and Hepatology) University of Illinois at Chicago

Hepatocellular carcinoma(HCC) is the 3^(rd) leading cause of cancer-related death worldwide. More than 80% of HCCs arise within chronic liver disease resulting from viral hepatitis, alcohol, hemochromatosis, obesity and metabolic syndrome or genotoxins. Projections based on Western lifestyle and its metabolic consequences anticipate a further increase in incidence, despite recent breakthroughs in the management of viral hepatitis. HCCs display high heterogeneity of molecular phenotypes, which challenges clinical management. However, emerging molecular classifications of HCCs have not yet formed a unified corpus translatable to the clinical practice. Thus, patient management is currently based upon tumor number, size, vascular invasion, performance status and functional liver reserve. Nonetheless, an impressive body of molecular evidence emerged within the last 20 years and is becoming increasingly available to medical practitioners and researchers in the form of repositories. Therefore, the aim this work is to review molecular data underlying HCC classifications and to organize this corpus into the major dimensions explaining HCC phenotypic diversity. Major efforts have been recently made worldwide toward a unifying "clinically-friendly" molecular landscape. As a result, a consensus emerges on three major dimensions explaining the HCC heterogeneity. In the first dimension, tumor cell proliferation and differentiation enabled allocation of HCCs to two major classes presenting profoundly different clinical aggressiveness. In the second dimension, HCC microenvironment and tumor immunity underlie recent therapeutic breakthroughs prolonging patients' survival. In the third dimension,metabolic reprogramming, with the recent emergence of subclass-specific metabolic profiles, may lead to adaptive and combined therapeutic approaches. Therefore, here we review recent molecular evidence, their impact on tumor histopathological features and clinical behavior and highlight the r

关键词： Liver metabolism Liver zonation Hepatocellular carcinoma classification Wnt/β-catenin TP53 Tumor microenvironment Inflammation Tumor immunity Hepatocyte proliferation Hepatocyte differentiation

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Tauroursodeoxycholic acid:more than just a neuroprotective bile conjugate

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Neural Regeneration Research 2017年第1期12卷 62-63页

作者： Lorenzo Romero-Ramírez Manuel nieto-Sampedro natalia Yanguas-Casás Hospital Nacional de Paraplejicos SESCAMToledoSpain Instituto Cajal CSICMadridSpain

Neurological diseases and the neuroinflammatory response：Neurological diseases are usually accompanied by dramatic changes in the tissue homeostasis,inducing a neuroinflammatory environment that leads to the progress... 详细信息

关键词： Tauroursodeoxycholic acid more than just a neuroprotective bile conjugate TGF CNS

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