Wojtukiewicz M Z, Zacharski L R, Memoli V A, Kisiel W, Kudryk B J, Rousseau S M, Stump D C
Department of Medicine, Dartmouth Medical School.
Thromb Haemost. 1989 Dec 29;62(4):1062-6.
Systemic activation of the coagulation mechanism is known to exist in patients with colon cancer. The mechanism of such activation was investigated using immunohistochemical techniques applied to fresh frozen sections of resected primary colon cancer specimens. Tumor cells stained for tissue factor, factor V, and urokinase-type plasminogen activator. Perivascular and intercellular areas stained for fibrinogen and the "a" subunit of factor XIII. Staining was minimal or absent for protein C, protein S, plasminogen activator inhibitors 1-3, factor VII, factor X, and fibrin (the antigenic site on the amino-terminal portion of B beta chain that is exposed following thrombin cleavage of fibrinopeptide B was not detected). The lack of an intact thrombin-generating pathway in situ associated with viable colon cancer cells is consistent with the findings of others that coagulation activation in colon cancer may be triggered by a soluble tumor product that exerts its effect at sites distant from the tumor. These results may explain the absence of clinical responsiveness of colon cancer to antithrombotic drug therapy and may clarify therapeutic strategies for this common tumor.
已知结肠癌患者存在凝血机制的全身激活。利用免疫组织化学技术对切除的原发性结肠癌标本的新鲜冰冻切片进行研究,以探究这种激活的机制。肿瘤细胞对组织因子、因子V和尿激酶型纤溶酶原激活剂呈阳性染色。血管周围和细胞间区域对纤维蛋白原和因子XIII的“a”亚基呈阳性染色。蛋白C、蛋白S、纤溶酶原激活剂抑制剂1 - 3、因子VII、因子X和纤维蛋白(纤维蛋白肽B经凝血酶裂解后在Bβ链氨基末端部分暴露的抗原位点未检测到)的染色极少或无染色。与存活的结肠癌细胞相关的原位完整凝血酶生成途径的缺乏,与其他人的研究结果一致,即结肠癌中的凝血激活可能由一种可溶性肿瘤产物触发,该产物在远离肿瘤的部位发挥作用。这些结果可能解释了结肠癌对抗血栓药物治疗缺乏临床反应的原因,并可能阐明针对这种常见肿瘤的治疗策略。