Can they be of a congenital nature?
The hepatic cholangiocarcinoma is one of the form of extremely rare cancer and most dangerous, however I would like to know the precise causes and especially if this pathology is related to a transmissible gene.
As you mentioned, cholangiocellular carcinoma (CCC) is rare but increasing worldwide.
Liver tissue is composed of several types of cells and importantly, hepatocytes and cholangiocyes have the identical progenitor cells. That is why TGF-beta signal-induced inflammation and fibrosis and alcoholic cirrhosis or NASH in the clinical settings would promote not only hepatic cell-derived cancer (HCC) but also cholangiocellular carcinoma (CCC). Indeed, according to the pathological classifications of the heaptic tumors, not a few patients develop the mixed type of HCC and CCC with significant fibrosis.
In the perspective from genetic alterations, tissue-specific disruption of the tumor suppressor genes such as NF2, SMAD4 andPTEN contributes to the development of CCC. Furthermore, It has been recently reported that hyper-activation of the Notch signaling pathway leads to a dysregulation of the oncogenic cyclinE and subsequent genetic instability, which results in the incidence of CCC. Inhibition of Notch intra-cellular domain (NICD) activity in CCC blocks tumor cell proliferation and induces apoptosis in vitro and in vivo; loss of Notch 1 expression led to a reduction in HES1 and cyclin E expression, while p53, p27, and p21 were strongly induced and cell-cycle would be arrested (apoptosis or senescence).
Article Cholangiocarcinoma can originate from hepatocytes in mice
Article A Critical Role for Notch Signaling in the Formation of Chol...
Liver cirhosis due to alcohol and hepatitis C is a risk factor, besides the classical schlerosing cholangitis
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