Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer.
Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer.
复制标题
DOI：
10.1038/onc.2010.594
复制
发表时间：
2011-04-28
期刊：
影响因子：
8
通讯作者：
Lemon, S. M.
中科院分区：
文献类型：
--
作者：
McGivern, D. R.;Lemon, S. M.
持续感染丙型肝炎病毒(丙型肝炎病毒)的人发生肝细胞癌是一个日益严重的世界性问题。目前的抗病毒治疗在许多慢性丙型肝炎患者中并不有效，更多地了解导致进展为肝癌的因素将是必要的，以设计新的方法来预防丙型肝炎相关的肝癌。缺乏慢性丙型肝炎病毒感染的小动物模型阻碍了对这些因素的了解。由于丙型肝炎病毒是一种RNA病毒，其遗传物质几乎没有整合到宿主基因组中的潜力，因此丙型肝炎病毒促进癌症的机制可能不同于其他病毒致癌模型。在持续感染丙型肝炎病毒的患者中，对感染的肝细胞的免疫反应导致的慢性炎症与进行性纤维化和肝硬变有关。肝硬变是肝细胞癌的一个独立于丙型肝炎病毒感染的重要危险因素，大多数与丙型肝炎病毒相关的肝细胞癌发生在肝硬变的背景下。然而，有相当一部分是在没有肝硬变的情况下出现的，这表明肝硬变不是癌症的先决条件。其他证据表明，可能涉及直接的、病毒特异性的机制。表达丙型肝炎病毒蛋白的转基因小鼠在转基因没有炎症或免疫识别的情况下会发生癌症。体外研究发现，丙型肝炎病毒编码的蛋白质与细胞周期调节蛋白和肿瘤抑制蛋白存在多种相互作用，这增加了丙型肝炎病毒可以破坏细胞增殖控制，或损害细胞对DNA损伤的反应的可能性。病毒特异性、宿主遗传、环境和免疫相关因素的组合可能决定慢性感染丙型肝炎患者进展为肝细胞癌的可能性。在这里，我们总结了目前关于病毒特异性机制的知识，这些机制可能有助于丙型肝炎相关的肝细胞癌。
The development of hepatocellular carcinoma (HCC) in persons who are persistently infected with hepatitis C virus (HCV) is a growing problem worldwide. Current antiviral therapies are not effective in many patients with chronic hepatitis C, and a greater understanding of the factors leading to progression to HCC will be necessary to design novel approaches to prevention of HCV-associated HCC. The lack of a small animal model of chronic HCV infection has hampered understanding of these factors. Since HCV is an RNA virus with little potential for integration of its genetic material into the host genome, the mechanisms underlying HCV promotion of cancer are likely to differ from other models of viral carcinogenesis. In patients persistently infected with HCV, chronic inflammation resulting from immune responses against infected hepatocytes is associated with progressive fibrosis and cirrhosis. Cirrhosis is an important risk factor for HCC independent of HCV infection, and a majority of HCV-associated HCC arises in the setting of cirrhosis. However, a significant minority arises in the absence of cirrhosis, indicating that cirrhosis is not a prerequisite for cancer. Other lines of evidence suggest that direct, virus-specific mechanisms may be involved. Transgenic mice expressing HCV proteins develop cancer in the absence of inflammation or immune recognition of the transgene. In vitro studies have revealed multiple interactions of HCV-encoded proteins with cell cycle regulators and tumor suppressor proteins, raising the possibility that HCV can disrupt control of cellular proliferation, or impair the cell's response to DNA damage. A combination of virus-specific, host genetic, environmental, and immune-related factors are likely to determine the progression to HCC in patients who are chronically infected with HCV. Here, we summarize current knowledge of the virus-specific mechanisms that may contribute to HCV-associated HCC.
登录
查看更多内容
影响因子：
5.4
作者：
Bigger, CB;Guerra, B;Lanford, RE
通讯作者：
Lanford, RE
影响因子：
--
作者：
Bartsch, H;Nair, J
通讯作者：
Nair, J
影响因子：
8
作者：
Botlagunta, M.;Vesuna, F.;Raman, V.
通讯作者：
Raman, V.
影响因子：
8
作者：
Chang, PC;Chi, CW;Lee, YHW
通讯作者：
Lee, YHW
影响因子：
11.2
作者：
Chao, Chi-Hong;Chen, Chun-Ming;Lee, Yan-Hwa Wu
通讯作者：
Lee, Yan-Hwa Wu