AUTOANTIBODIES IN HEPATOCELLULAR CARCINOMA

描述：抗原驱动的自身免疫反应的概念是 本研究的基础上，使用抗核抗体（ANA）在肝细胞 癌（HCC）作为一种模型，以确定其他核蛋白， 参与致癌作用。 关于HCC的独特特征是高 ANA的频率（31%）和抗体应答的动态变化， 从前驱慢性肝病状态转变为恶性。 一 编码丝氨酸-精氨酸（SR）可变剪接因子HCC 1的cDNA 家庭一直与这种方法隔离，其关系， 将在HCC 1转基因小鼠中检查致癌作用。 另一个cDNA 编码在S中最大表达的细胞周期相关核蛋白， G2，称为SG 2NA（SG 2核抗原），将分析其在细胞中的作用。 涉及酵母突变体的互补研究的循环进展。 这种ts突变体缺乏CDC 4，CDC 4是一种酵母细胞周期蛋白， 与SG 2NA相似的结构基序，是DNA复制所必需的， 中心体的分离形成有丝分裂纺锤体的两极。 研究将继续确定其他蛋白质参与 肿瘤发生，特别强调使用抗体， 在前驱疾病状态（慢性肝炎和肝病）期间存在 肝硬化CH/LC）和那些新发恶性肿瘤。 HCC提供 这是一个分离核蛋白的独特机会， 炎症性疾病，如CH/LC，从那些参与随后的 恶性肿瘤 合作已经启动，并将继续与 日本的肝病学家拥有约600例CH/LC患者队列 长期临床监测。 转化为HCC的患者可能 立即识别并获得这些血清和肝脏活检 问题研究

DESCRIPTION: The concept of antigen-driven autoimmune responses is the basis of this study to use antinuclear antibodies (ANAs) in hepatocellular carcinoma (HCC) as a model to identify other nuclear proteins which could be participating in carcinogenesis. Unique features about HCC are the high frequency (31%) of ANAs and dynamic changes in antibody responses during transformation from precursor chronic liver disease states to malignancy. A cDNA encoding alternative splicing factor HCC1 of the serine-arginine (SR) family has been isolated with this approach, and its relationship with carcinogenesis will be examined in HCC1 transgenic mice. Another cDNA encoding a cell cycle-related nuclear protein maximally expressed in S and G2, called SG2NA (SG2 nuclear antigen) will be analyzed for its role in cell cycle progression with complementation studies involving a yeast mutant. This ts mutant is deficient in CDC4, a yeast cell cycle protein which has similar structural motifs as SG2NA and is required for DNA replication and separation of the centrosome to form the poles of the mitotic spindle. Studies will be continued to identify other proteins involved in tumorigenesis with special emphasis devoted to using antibodies which are present during the precursor disease states (chronic hepatitis and liver cirrhosis CH/LC) and those which appear de novo with malignancy. HCC offers a unique opportunity for separating nuclear proteins involved in inflammatory conditions such as CH/LC from those involved in subsequent malignancy. Collaboration has been initiated and will be continued with hepatologists in Japan who have a cohort of about 600 patients with CH/LC under long-term clinical surveillance. Patients converting to HCC can be immediately identified and serum and liver biopsies obtained for these studies.