Taketa K, Shimamura J, Ueda M, Shimada Y, Kosaka K
Health Research Center, Kagawa University, Takamatsu, Japan.
Cancer Res. 1988 Jan 15;48(2):467-74.
Activities of key carbohydrate-metabolizing enzymes in biopsied human tissues of hepatocellular carcinoma and related conditions were determined by established methods. Among the enzymes analyzed, fetal-type liver enzymes (low-Km hexokinase, glucose 6-phosphate dehydrogenase, and pyruvate kinase-M2) showed increased activities, and adult-type liver enzymes [glucose 6-phosphatase, fructose 1,6-bisphosphatase, high-Km hexokinase (or glucokinase), and pyruvate kinase-L] showed decreased activities, resulting in undifferentiated enzyme patterns not only in fetal livers and hepatocellular carcinomas but also in livers of acute and chronic hepatitis and liver cirrhosis with or without tumors. Hepatocellular carcinomas showed a general tendency of having greater enzyme deviations than hepatitic and cirrhotic livers. The extent of the enzyme deviation in hepatocellular carcinomas varied considerably from one enzyme to another for each tumor tissue as compared with that in the benign liver diseases. Thus, the phenotypic heterogeneity was important for discriminating between the neoplastic and inflammatory changes in differentiation markers. The enzyme patterns of tumors and their corresponding host cirrhotic livers were unrelated, suggesting that the cirrhotic liver has a significance as preneoplastic state only in terms of having a high incidence of evolving hepatocellular carcinoma.
采用既定方法测定了肝细胞癌及相关病症活检人体组织中关键碳水化合物代谢酶的活性。在所分析的酶中,胎儿型肝脏酶(低 Km 己糖激酶、葡萄糖 6 - 磷酸脱氢酶和丙酮酸激酶 - M2)活性增加,而成人型肝脏酶[葡萄糖 6 - 磷酸酶、果糖 1,6 - 二磷酸酶、高 Km 己糖激酶(或葡萄糖激酶)和丙酮酸激酶 - L]活性降低,不仅在胎儿肝脏和肝细胞癌中,而且在伴有或不伴有肿瘤的急性和慢性肝炎及肝硬化肝脏中均导致未分化的酶模式。肝细胞癌相较于肝炎和肝硬化肝脏,通常具有更大的酶偏差趋势。与良性肝脏疾病相比,每个肿瘤组织中不同酶之间的酶偏差程度差异很大。因此,表型异质性对于区分肿瘤性和炎症性变化的分化标志物很重要。肿瘤及其相应宿主肝硬化肝脏的酶模式无关,这表明肝硬化肝脏仅在发生肝细胞癌的高发病率方面具有癌前状态的意义。