Cholangiocarcinoma: Recent progress. Part 2: Molecular pathology and treatment

Abstract

Part 2 of this review discusses DNA damage in biliary epithelial cells in the development of cholangiocarcinoma, alterations in cell kinetics of biliary epithelial cells, biliary epithelial mitoinhibition, and apoptosis that includes the role of Bcl-2 , transforming growth factor-β , telomerase activities and deregulation of Ras and p53 , cancer-associated antigens in cholangiocarcinoma, precancerous lesions, stroma formation and angiogenesis, cancer invasion, cell-cell and cell-matrix interactions, and the mechanism of evasion from immune surveillance. These discussions are followed briefly by treatments such as photodynamic therapy, and surgical approaches comparing resection and liver transplantation.

Cholangiocarcinoma: Molecular targeting strategies for chemoprevention and therapy

“…It is beyond the scope of this review to provide a detailed analysis of each of these factors and their relationship to the molecular pathogenesis of cholangiocarcinoma. However, the reader is referred to the several recent reviews 7,[42][43][44][45][46][47] for an updated analysis of the molecular pathological features of cholangiocarcinoma. This section instead highlights such factors as tumor location, subtype, and grade, which have been found to be associated with variations in the frequencies of expression of selected molecular alterations and which need to be considered when assessing outcome and in devising molecular therapeutic strategies for cholangiocarcinoma.…”

Cyclooxygenase-2 Is Involved in the Up-Regulation of Matrix Metalloproteinase-9 in Cholangiocarcinoma Induced by Tumor Necrosis Factor-α

“…Cholangiocarcinoma (CC) arising from the intrahepatic, hilar, and extrahepatic bile ducts shows a dismal prognosis even after a complete surgical resection, [1][2][3] and the early invasion and metastasis of CC limit the efficacy of surgery. There have been many reports regarding the pathological factors that relate to the prognosis of CC patients, such as the TNM stage, and papillary phenotype and histological grade of the CC.…”

“…There have been many reports regarding the pathological factors that relate to the prognosis of CC patients, such as the TNM stage, and papillary phenotype and histological grade of the CC. [1][2][3][4][5][6] Recently, much attention has been given to the endogenous factors within malignant tumors, which are directly or indirectly responsible for tumor progression. [7][8][9][10] Among them, matrix metalloproteinase (MMP), cyclooxygenase (COX), and prostaglandin E2 (PGE2) are representative endogenous factors.…”

“…[22][23][24] As for the CCs, long-standing inflammation, injury, and reparative biliary epithelial proliferation, such as primary sclerosing cholangitis (PSC) and hepatolithiasis, 20,21,24 are reported to be background conditions. 1,20,21,24,25 The tumor microenvironment is primarily orchestrated by cytokines that play an indispensable role during tumor progression. 22,23,26 Tumor necrosis factor (TNF)-␣, a proinflammatory cytokine, seems to belong to such cytokines and is also an important endogenous tumor promoter.…”

Comparative molecular analysis of loss of heterozygosity in adenocarcinoma in bile duct brushings and corresponding surgical pathology specimens

“…In addition, biliary and pancreatic neoplasms often are discovered late; therefore, cumulative genetic changes may result in clonal diversity within a monoclonal tumor. 11,12 Because the biliary brushing procedure preferentially samples the ductal epithelium, the specimens may contain in situ and superficially invasive carcinoma cells but not the cellular population present in the more deeply invasive areas of the neoplasm with divergent and complex clones.…”