Clinical Gastroenterology and Hepatology
Intrahepatic Cholangiocarcinoma Progression: Prognostic Factors and Basic Mechanisms
Section snippets
Biomarkers Correlated With Poor Outcome and Progression in Human Intrahepatic Cholangiocarcinoma
Macroscopically, intrahepatic cholangiocarcinoma, also known as peripheral cholangiocarcinoma, has been subclassified into mass-forming, periductular-infiltrating, mass-forming plus periductular-infiltrating, and intraductal papillary types.5, 6, 7 Of these, mass-forming and mass-forming plus periductular infiltrating intrahepatic cholangiocarcinomas are the most common types, with the mass-forming plus periductular infiltrating type showing the poorest survival outcome.5, 7 In comparison,
Preclinical Animal Models of Intrahepatic Cholangiocarcinogenesis and Tumor Progression Recapitulating Key Features of the Human Disease
Animal models that recapitulate key cellular, molecular, and clinical features of human intrahepatic cholangiocarcinoma progression are highly desirable, because such models would not only facilitate studies aimed at elucidating mechanisms of cholangiocarcinoma cell growth, invasion, and metastasis, but also because they could serve as valuable preclinical platforms for testing new molecular strategies for cholangiocarcinoma therapy. Table 2 lists established rodent models of intrahepatic
Role of Tumor Stroma in Intrahepatic Cholangiocarcinoma Progression
It is well-recognized that unlike hepatocellular carcinoma, intrahepatic cholangiocarcinoma typically exhibits an excessive desmoplastic reaction characterized by abundant extracellular matrix (ECM) proteins and cancer- associated fibroblasts (CAFs) predominately expressing a myofibroblast-like phenotype.58, 59 As exemplified in Figure 3A and B, intrahepatic cholangiocarcinoma is most often characterized by nests of cytokeratin 19–positive malignant ductal carcinoma cells typically surrounded
Concluding Remarks
Significant progress has been made during the past several years in defining cellular interactions and molecular pathways associated with the pathogenesis of intrahepatic cholangiocarcinoma and, as highlighted in this review, leading to the identification of various select molecular markers having potential as either prognostic indicators and/or therapeutic targets for this lethal cancer. However, translation of these findings into effective clinical strategies for the treatment of advanced
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Cancer-associated fibroblasts in intrahepatic cholangiocarcinoma progression and therapeutic resistance
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2022, Advances in Cancer ResearchCitation Excerpt :Low to no Postn expression had also been reported for select benign liver diseases and hepatocellular carcinoma (Utispan et al., 2010). Furthermore, Postn was not detected by Western blotting at 21 days after bile duct ligation in cholestatic rat liver with a periportal bile ductular reaction (Sirica et al., 2009). Sugiyama et al. (2016), however, demonstrated positive α-SMA expression together with Postn enhancement in the fine fibrotic septa around proliferating bile ducts/ductules emanating from the hepatic portal areas of wild-type mice induced by cholestatic injury produced by dietary administered 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC).
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by National Institutes of Health Grants R01 CA 83650 and R01 CA 39225 (A.E.S).