原発性肝癌におけるビタミンB12結合蛋白に関する研究 ―異常B12結合蛋白の証明とその分析―
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概要
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Determinations of serum vitamin B12, transcobalamin and transcobalamin subfractions were made on 52 normal control sera and 101 patient sera with various hepatic diseases including hepatic malignancies, cirrhosis and hepatitis. Fractionation studies including the stepwise method, gel filtration and isoelectric focusing were performed. In selected cases of hepatocellular carcinoma with anomalous B12 binding protein in plasma, isolation and characterization of respective binding proteins were performed using affinity chromatography. Fractionation of transcobalamin subfractions on DEAEC column chromatography disclosed marked increases of cobalophilin in three cases of hepatoma, and increases in TC II in the remaining three cases of hepatoma. Among the latter, increased TC II showed peculiar properties in one case with hepatocellular carcinoma. This protein, a TC II-like novel hepatoma binder (TCNB), gave an apparent molecular weight of 60,000 dalton on gel filtration, pI values of 4.2-5.0 by electrofocusing, and data far more acidic than normal TC II. Radioimmuno-gel filtration disclosed that a cobalophilin-like hepatoma binder showed a reaction of identity with milk binder antiserum, whereas TCNB showed a reaction of non-identity using the same antiserum. TCNB was isolated in a pure state not only from the patient plasma but also from the tumor tissue obtained at the time of necropsy. TCNB degraded in the acidic solution and also had the capacity to deliver B12 to reticulocytes, both of these characteristics indicating the close similarlity to normal TC II in plasma. Furthermore, amino acid and cabohydrate analysis of purified TCNB disclosed its close correspondence to TC II except for the presence of cabohydrate moiety amounting 16%. TCNB was totally absent in normal and other patient sera, and in liver tissues of normal as well as other hepatoma tissues examined. The mechanisms for the presence of such anomalous B12 binding proteins in hepatoma sera are still obscure. However, decreased clearance of cobalophilin bound B12 in hepatoma cases may play a principal role, and the production of the protein by tumor tissue cannot be neglected. Further studies are in progress.
- 札幌医科大学の論文
- 1980-02-01
札幌医科大学 | 論文
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