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Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis.

机译:肝细胞癌:乙型肝炎和丙型肝炎病毒蛋白在肝癌发生中的作用。

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摘要

Hepatocellular carcinoma (HCC) is the most important primary hepatic cancer, being a common cancer type worldwide. Many aetiological factors have been related with HCC development, such as cirrhosis, hepatitis viruses and alcohol. Chronic infection with hepatitis B (HBV) and C viruses (HCV) often results in cirrhosis and enhances the probability of developing HCC. The underlying mechanisms that lead to malignant transformation of infected cells, however, remain unclear. HBV is a DNA virus that integrates into the host genome, and this integration is believed, in part, to be carcinogenic. Besides, the virus encodes a 17 kDa protein, HBx, which is known to be a causative agent in the formation of HCC. On the contrary, HCV is a RNA virus that does not integrate into the host genome but likely induces HCC through host protein interactions or via the inflammatory response to the virus. Products encoded in the HCV genome interfere with and disturb intracellular signal transduction. Some HCV proteins, such asthe core protein, NS3 and NS5A, have seen to have a regulatory effect on cellular promoters, to interact with a number of cellular proteins, and to be involved in programmed-cell death modulation under certain conditions. The identification of these proteins functions in HCC development and the subsequent development of strategies to inhibit protein-protein interactions may be the first step towards reducing the chronicity and/or of the carcinogenicity of these two viruses.
机译:肝细胞癌(HCC)是最重要的原发性肝癌,是全世界常见的癌症类型。许多病因与肝癌的发生有关,例如肝硬化,肝炎病毒和酒精。乙型肝炎(HBV)和丙型肝炎病毒(HCV)的慢性感染通常会导致肝硬化,并增加发生HCC的可能性。然而,导致感染细胞恶变的潜在机制尚不清楚。 HBV是一种整合入宿主基因组的DNA病毒,这种整合被认为部分具有致癌性。此外,该病毒编码一种17 kDa的蛋白HBx,它是导致HCC形成的致病因子。相反,HCV是一种RNA病毒,它不会整合到宿主基因组中,而是可能通过宿主蛋白相互作用或对病毒的炎症反应诱导HCC。 HCV基因组中编码的产物干扰并干扰细胞内信号转导。已经看到某些HCV蛋白,例如核心蛋白NS3和NS5A,对细胞启动子具有调节作用,可与多种细胞蛋白相互作用,并在某些条件下参与程序性细胞死亡调节。这些蛋白的鉴定在HCC的发展中起作用,随后抑制蛋白-蛋白相互作用的策略的发展可能是降低这两种病毒的慢性和/或致癌性的第一步。

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