ROLE OF TRANSFORMING GROWTH FACTOR ALPHA IN HEPATOCARCINOGENESIS

转化生长因子α（TGF-α）以高水平表达 在人肝细胞癌（HCC）中，它可能是一种机制的一部分， B型肝炎病毒（HBV）通过其引起HCC。 研究继续在 TGF-α在肝癌发病中的作用分析。 先前 该实验室的工作表明，在人乳腺癌中TGF-α表达水平较高， 大多数人HCC中TGF-α基因的上调， 用B型肝炎病毒转染后的肝母细胞瘤细胞系 （HBV）。 虽然有一些关于TGF-α在HCC中的研究已经发表，但没有一项研究 检查肝脏中TGF-α的表达，或者 干扰素α（IFN-α）疗法治疗 慢性B型肝炎对肝脏TGF-α表达的影响。 串行 对35名参与了研究的患者的肝活检进行了评价， 重组人干扰素-α治疗糖尿病的随机对照试验 治疗慢性B型肝炎。 获得经皮肝活检 在进入试验前和试验后一年， 用抗TGF-α单克隆抗体在抗生物素蛋白-生物素-过氧化物酶- 复杂系统 TGF-α在每个切片中的表达是 盲法评价（关于治疗组和活检顺序） 并进行了数字评分。 TGF-β 1表达无显著性差异（P> 0.05）。 13名接受治疗的患者在治疗前后的α表达 每天接受IFN-α，13例隔日接受IFN-α，9例隔日接受IFN-α， 没有治疗。 持续清除HBV-DNA和DNA聚合酶活性 26例治疗患者中有8例发生（"应答者"）; 18例其他患者中有1例发生（"应答者"）。 患者为"无应答者"。"TGF-α在IFN-α之前表达 治疗应答者的疗效显著高于无应答者; IFN-α治疗后，TGF-α表达显著降低， 与无应答者和未治疗的对照组相比。

Transforming growth factor alpha (TGF-alpha) is expressed at high levels in human hepatocellular carcinoma (HCC); it may be part of a mechanism by which hepatitis B virus (HBV) causes HCC. Research has continued in the analysis of the role of TGF-alpha in the etiology of HCC. Previous work in this laboratory has shown high levels of TGF-alpha expression in most human HCCs, and an up-regulation of the TGF-alpha gene in a hepatoblastoma cell line after transfection with the hepatitis B virus (HBV). Although a few studies have been published on TGF-alpha in HCC, none have examined TGF-alpha expression in liver over the course of time, or the effect of interferon alpha (IFN-alpha) therapy for the treatment of chronic hepatitis B on the expression of TGF-alpha in the liver. Serial liver biopsies were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-alpha for the treatment of chronic hepatitis B. Percutaneous liver biopsies obtained before and one year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-alpha in an avidin-biotin-peroxidase- complex system. The expression of TGF-alpha in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF- alpha expression before or after therapy between 13 patients receiving daily IFN-alpha, 13 receiving alternate day IFN-alpha, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients ("responders"); the 18 other patients were "non-responders." Expression of TGF-alpha before IFN-alpha therapy was significantly higher in responders than in nonresponders; after IFN-alpha therapy, TGF-alpha expression decreased significantly among responders compared to nonresponders and untreated controls.