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 ro...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.展开更多
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 prognosis.Th...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 prognosis.The over-all prognosis and patient survival remains poor because of lack of early diagnosis and effective treatments.Preclini-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 cancer.Recent 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 models.This 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.展开更多
文摘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.
基金This work was supported by the Outstanding Young Talents Program in Higher Education Institutions of Anhui Province(No.gxfx2017066)the 512 Talent Cultivation Plan of Bengbu Medical College(No.by51202208)+2 种基金the internal grants from both Distinguished Young Scholars Science Foundation(No.2019byyfyjq02)General New Technology Project(No.2020144)of the First Affiliated Hospital of Bengbu Medical CollegeBaoan Ji is supported by the NCI-funded Mayo Clinic SPORE in Hepatobiliary Cancer(P50 CA210964).
文摘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 prognosis.The over-all prognosis and patient survival remains poor because of lack of early diagnosis and effective treatments.Preclini-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 cancer.Recent 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 models.This 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.