Altered Fibrinogen Metabolism in Experimental Tumor-bearer

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  • 担癌体におけるフィブリノーゲン代謝異常に関する実験的研究
  • タンガンタイ ニ オケル フィブリノーゲン タイシャ イジョウ ニ カンスル

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It is well known that various changes have been induced by tumor-host interactions. Patients with advanced cancer often have bleeding or thrombosis. An alteration in fibrinogen metabolism may be associated with malignant tumors. In recent years, patients with malignant tumors have often shown hypercoagulability and hypofibrinolysis. This study was carried out in order to investigate fibrinogen metabolism related to tumor growth.<BR>In the first experiment, to investigate the fibrinogen metabolism of tumor-bearing animals, Yoshida Sarcoma (1×106cells) was inoculated subcutaneously in the backs of Donryu rats. Controls received subcutaneous injections of turpentine or physiological saline. The level of plasma fibrinogen tended to increase with tumor growth until the 15th day after tumor inoculation when it fell as cahexia developed. The incorporation of 14C-Leucine into plasma fibrinogen also was increased on the 8th day but significantly decreased on the 15th day after inoculation. The level of fibrinogen in the circulation represents, at least to some extent, a balance between production and destruction. Moreover, from the evidence of the shortened survival of radioactive: fibrinogen in tumor-bearing animals, fibrinogen turnover appears to be accelerated. Therefore, the author examined the alterations in fibrinogen metabolism in tumor-bearing rats. The experimental results showed that the blood levels of soluble fibrin monomer complex and of cryofibrinogen were elevated in rats with Yoshida Sarcoma. In addition to paracoagulation, the fibrinolytic system including plasmin and activator were thought to play an important role in fibrinogen metabolism. The results showed that high concentrations of fibrin or fibrinogen degradation products in the serum and high plasminogen activator activity were present in tumor-bearing rats, especially on the 15th day after inoculation. The citrated plasma was fractionated by means of Lysine-Sepharose affinity chromatography and used to determine the inhibitor, activator, plasminogen and plasmin activities. The results obtained in this experiment showed that increased plasmin and decreased plasminogen activities were present in rats with advanced tumors.<BR>In the second experiment, the mechanism of the altered fibrinogen metabolism in rats was investigated. The tissue extract as well as toxohormone was prepared according to Nakahara's method, and the effects of toxohormone on fibrinogen metabolism in vivo and on thromboplastic activity in vitro were examined. The toxohormone injected intraperitoneally caused elevation of plasma fibrinogen levels and increased incorporation of 14C-Leucine into the plasma fibrinogen fraction in healthy rats. An elevated level of altered fibrinogen was noted in the circulation of rats injected with toxohormone intraperitoneally. Toxhormone also had higher thromboplastic activity than normal tissue extract.

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