AUTOANTIBODIES IN HEPATOCELLULAR CARCINOMA

抗核抗体（ANA）存在于超过30%的患者中， 肝细胞癌（HCC），但很少有人知道的意义， 这一观察结果或核自身抗原的身份。 的目的 这项研究计划是表征分子结构， 作为靶标的核抗原和核仁抗原的生物学功能 肝癌自身抗体，并启动一项前瞻性研究， ANA滴度和特异性变化的相关性， 在部分肝硬化和慢性肝炎患者中观察到 谁发展了HCC。 这是与信州大学的研究人员合作的成果 日本松本的一家医院收集了大量来自 HCC患者，并且正在随访一个大型患者队列， 与病毒性肝炎相关的慢性肝病。 初步研究 已经表明与HCC相关的三种核仁抗原， RNA加工和与细胞定型相关的核仁蛋白 DNA合成和细胞增殖。 待检验的假设是 ANA是对参与生长的细胞内蛋白质的免疫反应， 和增殖过程相关的致癌作用， 可以作为探针来鉴定这些蛋白质及其同源物 功能协调发展的 将使用自身抗体来探测cDNA表达文库 并分析分离的cDNA克隆以表征编码的蛋白质。 HCC中ANA应答的动态性质将在 病毒性肝炎相关肝硬化患者的前瞻性研究 慢性肝炎在日本 据了解，其中一些患者 将发生HCC，并将定期获得血清， 检查ANA阴性转为ANA阳性状态， ANA滴度增加和ANA特异性变化。 患者 显示这些变化将有广泛的诊断程序， 确定自身抗体的改变是否是早期 致癌作用 如果某些与细胞生长相关的调节途径 在致癌作用中受到干扰，这些成分的鉴定 可以通过使用自身抗体来实现途径。

Antinuclear antibodies (ANAs) are present in more than 30% of patients with hepatocellular carcinoma (HCC) but little is known of the significance of this observation or the identity of the nuclear autoantigens. The aims of this research proposal are to characterize the molecular structure and biological function of the nuclear and nucleolar antigens which are targets of autoantibodies in HCC and to initiate a prospective study to determine the relevance of changing ANA titers and specificities, a phenomenon which was observed in some patients with liver cirrhosis and chronic hepatitis who developed HCC. This is a collaborative effort with investigators at Shinshu University Hospital in Matsumoto, Japan who have a large collection of sera from patients with HCC and who are following a large cohort of patients with chronic liver disease associated with viral hepatitis. Initial studies have already shown that three nucleolar antigens associated with HCC are RNA processing and a nucleolar protein associated with cellular commitment to DNA synthesis and cell proliferation. The hypothesis to be examined is that ANAs are immune responses to intracellular proteins involved in growth and proliferative processes associated with carcinogenesis and that ANAs could be used as probes to identify these proteins and their cognate functions. Autoantibodies will be used to probe cDNA expression libraries and isolated cDNA clones will be analyzed to characterize encoded proteins. The dynamic nature of ANA responses in HCC will be investigated in a prospective study of patients with viral hepatitis-related liver cirrhosis and chronic hepatitis in Japan. It is known that some of these patients will develop HCC and sera will be obtained at regular intervals and examined for conversion from ANA-negative to ANA-positive status, for increases in ANA titers and for changes in ANA specificities. Patients showing these changes will have extensive diagnostic procedures to determine if the autoantibody alterations are reporters of early carcinogenesis. If certain regulatory pathways associated with cell growth are perturbed in carcinogenesis, identification of components of these pathways might be achieved by using autoantibodies.