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road to stemness in hepatocellular carcinoma

World Journal of Gastroenterology 2017年第37期23卷 6750-6776页

作者： Teresita NJ Flores-Téllez Saúl Villa-Trevino Carolina Pina-Vázquez Departam ento de Biología Celular Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAV-IPN) Av.IPN No.2508 Col

Carcinogenic process has been proposed to relay on the capacity to induce local tissue damage and proliferative repair. Liver has a great regeneration capacity and currently, most studies point towards the dominant role of hepatocytes in regeneration at all levels of liver damage. The most frequent liver cancer is hepatocellular carcinoma(HCC). Historical findings originally led to the idea that the cell of origin of HCC might be a progenitor cell. However, current linage tracing studies put the progenitor hypothesis of HCC origin into question. In agreement with their dominant role in liver regeneration, mature hepatocytes are emerging as the cell of origin of HCC, although, the specific hepatocyte subpopulation of origin is yet to be determined. The relationship between the cancer cell of origin(CCO) and cancer-propagating cells, known as hepatic cancer stem cell(HCSC) is unknown. It has been challenging to identify the definitive phenotypic marker of HCSC, probably due to the existence of different cancer stem cells(CSC) subpopulations with different functions within HCC. There is a dynamic interconversion among different CSCs, and between CSC and non-CSCs. Because of that, CSC-state is currently defined as a description of a highly adaptable and dynamic intrinsic property of tumor cells, instead of a static subpopulation of a tumor. Altered conditions could trigger the gain of stemness, some of them include: EMT-MET, epigenetics, microenvironment and selective stimulus such as chemotherapy. This CSC heterogeneity and dynamism makes them out reach from therapeutic protocols directed to a single target. A further avenue of research in this line will be to uncover mechanisms that trigger this interconversion of cell populations within tumors and target it.

关键词： cancer stem cell Liver progenitor cell Liver stem progenitor cell Stemness Plasticity cancer cell of origin cancer stem cells subpopulations

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Selecting an Appropriate Experimental Animal Model for Cholangiocarcinoma Research

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Journal of Clinical and Translational Hepatology 2022年第4期10卷 700-710页

作者： Man Li Xueli Zhou Wei Wang Baoan Ji Yu Shao Qianyu Du Jinghao Yao Yan Yang Department of Medical Oncology The First Affiliated Hospital of Bengbu Medical CollegeBengbuAnhuiChina Depart-ment of cancer Biology Mayo ClinicJacksonvilleFloridaUSA

Cholangiocarcinoma(CCA)is a highly aggressive biliary tree malignancy with intrahepatic and extra-hepatic sub-types that differ in molecular pathogeneses,epidemiology,clinical manifestations,treatment,and *** over-all prognosis and patient survival remains poor because of lack of early diagnosis and effective ***-cal in vivo studies have become increasingly paramount as they are helpful not only for the study of the fundamental molecular mechanisms of CCA but also for developing novel and effective therapeutic approaches of this fatal *** advancements in cell and molecular biology have made it possible to mimic the pathogenicity of human CCA in chemical-mechanical,infection-induced inflammatory,implantation,and genetically engineered animal *** review is intended to help investigators understand the particular strengths and weaknesses of the currently used in vivo animal models of human CCA and their related mod-eling techniques to aid in the selection of the one that is the best for their research needs.

关键词： Cholangiocarcinoma Heterogeneity Animal model Genetically engineered model cancer cell of origin

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