RELATION OF HEPATITIS C VIRUS - HEPATOCELLULAR CARCINOMA

丙型肝炎病毒与肝细胞癌的关系

• 批准号: 3199158
• 负责人: MICHAEL A GERBER
• 金额: $ 16.83万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-03-15 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3199158
• 关键词: athymic mouse; cell line; genetically modified animals; hepatitis C virus; histopathology; human subject; immunocytochemistry; in situ hybridization; liver cells; molecular cloning; molecular oncology; neoplastic cell; nucleic acid probes; nucleic acid sequence; oncogenic virus; polymerase chain reaction; preneoplastic state; transfection; virus RNA; virus cytopathogenic effect; virus genetics

Multiple lines of evidence indicate that chronic infection with hepatitis B virus (HBV) is causally related to hepatocellular carcinoma (HCC). Furthermore, there is increasing evidence that the recently identified hepatitis C virus (HCV) also plays a role in the development of HCC. A high percentage of the HBV-positive or HBV-negative patients with HCC is seropositive for anti-HCV antibodies indicating previous or current HCV infection. Premalignant cytologic changes of hepatocytes have been observed in patients with chronic hepatitis C. In recent studies using the polymerase chain reaction (PCR) we detected HCV RNA sequences in liver and tumor tissues from patients with HCC. These observations support the hypothesis that HCV may persist in hepatocytes as they progress from preneoplasia to neoplasia. It is the long term goal of our research to elucidate whether this RNA virus or subgenomic viral sequences, particularly in combination with HBV or other events such as p53 alterations, mediate malignant transformation. In this application we propose to determine by sensitive and specific techniques (PCR, ribonuclease protection assay, and in situ hybridization) the presence of HCV RNA sequences in non-neoplastic liver tissue, preneoplastic liver tissue, and tumor tissue of patients with or without chronic HCV and/or HBV infection. Next, we will investigate whether different levels or specific sequences of HCV are associated with defined preneoplastic and neoplastic liver lesions. These viral sequences will be cloned and sequenced and their oncogenic potential will be determined by transfection or retrovirus mediated gene transfer and transformation studies of several non-tumorigenic cell lines such as human fetal hepatocytes, immortalized transgenic mouse hepatocytes (FMH202) and HBV genome transfected cells. It is expected that these molecular studies in correlation with the histopathologic progression from normal hepatocytes to HCC will provide new insights into the pathogenesis of human HCC.

多行证据表明，长期感染 丙型肝炎病毒（HBV）与肝细胞癌有关 （HCC）。 此外，有越来越多的证据表明 确定的乙型肝炎病毒（HCV）也在发展中起作用 hcc。 HBV阳性或HBV阴性患者的比例很高 与HCC有关抗HCV抗体的血清阳性，表明先前或 当前的HCV感染。 肝细胞的细胞学细胞学变化 在慢性丙型肝炎患者中已经观察到。 使用聚合酶链反应（PCR）的研究我们检测到HCV RNA HCC患者的肝脏和肿瘤组织中的序列。 这些 观察结果支持HCV可能持续在肝细胞中的假设 随着它们从肿瘤发展到肿瘤。 这是长期的 我们研究的目标是阐明该RNA病毒还是亚基因组 病毒序列，特别是与HBV或其他事件结合 例如p53改变，介导恶性转化。 在此应用中，我们建议通过敏感和特定 技术（PCR，核糖核酸酶保护分析和原位 杂交）非塑性肝脏中HCV RNA序列的存在 组织，肿瘤肝组织和患者的肿瘤组织 没有慢性HCV和/或HBV感染。 接下来，我们将调查 HCV的不同级别还是特定序列是关联的 具有定义的前肿瘤和肿瘤病变。 这些病毒 序列将被克隆和测序，其致癌电位 将通过转染或逆转录病毒介导的基因转移确定 以及几个非肿瘤细胞系（例如）的转化研究，例如 人胎儿肝细胞，永生的转基因小鼠肝细胞 （FMH202）和HBV基因组转染的细胞。 预计这些 与组织病理学进程相关的分子研究 从正常的肝细胞到HCC将为您提供新的见解 人HCC的发病机理。