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双链RNA依赖性蛋白激酶在慢性肝炎和分化型肝细胞癌肝细胞中的异常表达。

Aberrant expression of double-stranded RNA-dependent protein kinase in hepatocytes of chronic hepatitis and differentiated hepatocellular carcinoma.

作者信息

Shimada A, Shiota G, Miyata H, Kamahora T, Kawasaki H, Shiraki K, Hino S, Terada T

机构信息

Department of Virology, Faculty of Medicine, Tottori University, Yonago, Japan.

出版信息

Cancer Res. 1998 Oct 1;58(19):4434-8.

PMID:9766675
Abstract

We immunohistochemically analyzed the expression of double-stranded RNA-dependent protein kinase (PKR) using a monoclonal antibody, 71/10. Test samples included 64 human liver biopsies and 25 liver sections of rats inoculated with diethylnitrosamine. The PKR signals in human fatty livers and normal rat livers were minimum. Scoring signal intensity from 0-4, the average scores of chronic active (14 cases) and chronic persistent (6 cases) hepatitis associated with hepatitis virus C (HCV) were 2.8 and 2.0, respectively (P = 0.038). The stained cells were significantly more abundant in the periportal than centrilobular regions for both chronic active and persistent hepatitis (P < 0.001 each). The average score of liver cirrhosis associated with HCV was 1.9. Those scores of well-, moderately, and poorly differentiated hepatocellular carcinomas associated with HCV were 3.4, 2.1, and 0.3, respectively (P < 0.001 for each pair). Those scores of well- and poorly differentiated carcinomas associated with hepatitis virus B were 2.3 and 0.0, respectively (P < 0.001). The average score of rat carcinomas induced by diethylnitrosamine was 1.9. Morphologically, nuclei of the vast majority of PKR-positive cells looked not apoptotic. The ratio of PKR-positive cells to apoptotic cells by terminal transferase-mediated dUTP nick end labeling method was approximately 20 in hepatitis, and over 100 in well-differentiated carcinoma.

摘要

我们使用单克隆抗体71/10对双链RNA依赖性蛋白激酶(PKR)的表达进行了免疫组织化学分析。测试样本包括64例人类肝脏活检组织和25例接种二乙基亚硝胺的大鼠肝脏切片。人类脂肪肝和正常大鼠肝脏中的PKR信号最低。以0至4分对信号强度进行评分,丙型肝炎病毒(HCV)相关的慢性活动性肝炎(14例)和慢性持续性肝炎(6例)的平均评分分别为2.8和2.0(P = 0.038)。对于慢性活动性肝炎和慢性持续性肝炎,门静脉周围区域的染色细胞明显比小叶中心区域丰富(两者P均<0.001)。HCV相关肝硬化的平均评分为1.9。HCV相关的高分化、中分化和低分化肝细胞癌的评分分别为3.4、2.1和0.3(每对P < 0.001)。乙型肝炎病毒相关的高分化和低分化癌的评分分别为2.3和0.0(P < 0.001)。二乙基亚硝胺诱导的大鼠癌的平均评分为1.9。形态学上,绝大多数PKR阳性细胞的细胞核看起来没有凋亡。通过末端转移酶介导的dUTP缺口末端标记法检测,PKR阳性细胞与凋亡细胞的比例在肝炎中约为20,在高分化癌中超过100。

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