Hepatocellular Carcinoma Essay

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Hepatocellular carcinoma (HCC), the fifth most common cancer in men and seventh in women, is the end product of chronic liver disease that evolves over several decades [1]. The diverse etiologies of HCC, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcoholic diseases and obesity, often lead to cirrhosis, which is present in more than 80 to 90% of HCC patients [1]. Due to diverse etiological factors implicated in the development of HCC and its direct impact on the heterogeneity of the tumor which has limited treatment options, the overall survival is poor.

The origin of cancer is one fundamental question that is still hotly debated. In liver cancer, early observations of highly proliferative preneoplastic nodules or foci altered hepatocytes (FAH) in chemical hepatocarcinogenesis rodent models suggests that HCC arose from mature hepatocytes [2]. Moreover, similar lesions are frequently observed in human HCC samples [3]. Observations of oval cell activation and proliferation in response to injury when hepatocyte proliferation is inhibited in chemical hepatocarcinogensis models have led to the hypothesis that HCC can be derived from deregulated stem cells that become tumorigenic [2]. Current studies implicate that cancer stem cells (CSCs) are neoplastic cells that possess distinct survival mechanism and stem cell properties crucial for the maintenance and propagation of the tumor. The origins of CSCs are debatable; however, CSCs are hypothesized to be derived from tumor progenitor cells, stem cells, or a dedifferentiated cell that have acquired the CSC characteristics. Notably, recent studies in mice revealed that any cell type in the hepatic lineage can undergo oncogenic reprogramming into a CSC [4]. A ...

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...ost cirrhotic tissues contain FAHs, outstanding questions remains: are HcPCs also found in FAHs in cirrhotic tissues of non-HCC patients [1]? It is interesting to note that IL-6 plays two significant roles in the liver, (A) as a pro-inflammatory cytokine produced by Kupffer cells during acute phase response and (B) as a tumor promoter in damaged liver. Because IL-6 is elevated throughout the progression of HCC and its dual role; at what point does IL-6 become tumorigenic or metastatic? Notably, this study strengthens the use of IL-6 combined with AFP as biomarkers for early HCC detection. In fact, previous studies indicate that the IL-6 combined with AFP outperforms AFP or IL-6 alone in HCC detection [6]. While many questions remain, this study provided insights into the origin of HCCs and evidence for the long standing assumption that FAH are preneoplastic lesions.

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