Di Bisceglie A M
Liver Diseases Section, National Institutes of Health, Bethesda, Maryland.
Med Clin North Am. 1989 Jul;73(4):985-97. doi: 10.1016/s0025-7125(16)30649-6.
Hepatocellular carcinoma is a very common tumor worldwide and is associated with high mortality rates. Evidence that the development of hepatocellular carcinoma is related to chronic HBV infection has accumulated from epidemiologic studies, information from animal and cell culture models, and molecular biologic evidence that HBV components can be found within hepatocellular carcinoma tissue. Integration of HBV DNA within host liver cell chromosomes may be a crucial step in the development of hepatocellular carcinoma. Integration is associated with disruption of both structure and function of DNA at the site of integration. The study of individual examples of HBV DNA integration in hepatocellular carcinoma tissue illustrates possible mechanisms of hepatocarcinogenesis by HBV. In many cases, activation of various growth factors has been found in association with HBV DNA integration including IGF II, oncogenes such as c-myc, and novel growth factors such as the retinoic acid receptor. A clearer understanding of the mechanisms involved may allow for possible therapeutic interventions in the future, or perhaps even the prevention of hepatocellular carcinoma.
肝细胞癌是全球范围内非常常见的肿瘤，且死亡率很高。流行病学研究、动物和细胞培养模型的信息以及在肝细胞癌组织中可发现乙肝病毒成分的分子生物学证据，都已积累表明肝细胞癌的发生与慢性乙肝病毒感染有关。乙肝病毒DNA整合到宿主肝细胞染色体中可能是肝细胞癌发生发展的关键步骤。整合与整合位点处DNA的结构和功能破坏有关。对肝细胞癌组织中乙肝病毒DNA整合的个别实例研究，阐明了乙肝病毒导致肝癌发生的可能机制。在许多情况下，已发现各种生长因子的激活与乙肝病毒DNA整合有关，包括胰岛素样生长因子II、癌基因如c-myc，以及新型生长因子如视黄酸受体。对其中涉及机制的更清晰理解，可能为未来的治疗干预甚至肝细胞癌的预防提供可能。
