AUTOANTIBODIES IN HEPATOCELLULAR CARCINOMA

描述：抗原驱动的自身免疫反应的概念是 抗核抗体(ANA)在肝细胞中应用的研究基础 癌(HCC)作为识别其他核蛋白的模型 参与致癌过程。肝细胞癌的独特特征是高 ANA频率(31%)和抗体反应的动态变化 从先兆慢性肝病状态向恶性转化。一个 编码丝氨酸-精氨酸(SR)选择性剪接因子HCc1的基因 家庭因这种方法而被孤立，它与 将在hc1转基因小鼠身上检测致癌作用。另一个基因 编码一种细胞周期相关核蛋白，在S和 被称为SG2NA(SG2核抗原)的G2将被分析其在细胞中的作用 涉及酵母突变的循环进展与互补研究。 该ts突变体缺乏CDC4，CDC4是一种酵母细胞周期蛋白，具有 与SG2NA相似的结构基序，是DNA复制和 中心体的分离，形成有丝分裂纺锤体的两极。 将继续进行研究，以确定参与 肿瘤发生学，特别强调使用抗体 在先兆疾病状态(慢性肝炎和肝脏)期间出现 肝硬变(CH/LC)和那些新出现的恶性病变。肝细胞癌提供优惠 分离参与核蛋白的独特机会 炎症状态，如CH/LC，与随后涉及的情况 恶毒。协作已经启动，并将继续与 日本肝病专家，有大约600名CH/LC患者 在长期的临床监测下。转化为肝癌的患者可能会 立即进行鉴定，并对这些患者进行血清和肝脏活检 学习。

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.