STUDIES OF FIBRIN DEPOSITION IN CANCER

癌症中纤维蛋白沉积的研究

• 批准号: 3165765
• 负责人: FREDERICK R. RICKLES
• 金额: $ 14.81万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3165765
• 关键词: anticoagulants; chemical structure function; complementary DNA; cytotoxicity; disease /disorder model; fibrin; fibrinolysis; human subject; human therapy evaluation; immune complex; immunoregulation; laboratory mouse; macrophage; membrane activity; metastasis; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunology; neoplasm /cancer invasiveness; neoplastic cell; radioimmunoassay; tissue /cell culture; vascular endothelium; warfarin

Local and systemic activation of blood coagulation appears to be a common and an important host response to growing tumors. The pathogenesis of this process and the importance of the resultant fibrin deposition to tumor growth remains uncertain. Tumor cells, tumor-associated macrophages and tumor-associated endothelial cells contain proteins with potent procoagulant activities (PCAs) and fibrin deposition has been observed histologically on the surface of both tumor cells and stromal elements within tumors in situ. It is the objective of this project to examine this association in more detail and, using specific probes, to define the importance of the 2 main types of PCAs in the pathogenesis of fibrin deposition in human cancer. Utilizing specific monoclonal antibodies (mAbs) and cDNA probes specific for the PCAs, cell surface antigens and immunoregulatory molecules, we will examine the interactions between the 2 principal tumor-associated PCAs, cancer procoagulant (CP) and tissue factor (TF), inflammatory cell and vascular cell infiltration and fibrin deposition in human tumors. We will characterize the PCAs from homogeneous cell populations isolated from primary and metastatic tumors in these models, utilizing traditional biochemical methods and specific immunologic and functional probes. The long-term goals for this research are to: 1) provide a better understanding of the mechanism(s) for fibrin deposition in cancer; 2) develop strategies for the specific inhibition of cell mediated fibrin deposition; 3) demonstrate inhibition of metastasis formation by inhibiting cell-mediated clotting.

血液凝固的局部和全身激活似乎是 一种常见的重要的宿主对肿瘤生长的反应。 的 这一过程的发病机制和结果的重要性， 纤维蛋白沉积对肿瘤生长的影响仍不确定。 肿瘤细胞， 肿瘤相关巨噬细胞和肿瘤相关内皮细胞 含有具有强效促凝血活性（PCA）的蛋白质， 在组织学上观察到纤维蛋白沉积在表面上 肿瘤细胞和肿瘤内基质成分在原位。 本项目的目的是研究这种关联， 更详细，并使用特定的探针，以确定重要性 纤维蛋白原的发病机制中的2种主要类型的PCA 在人类癌症中的沉积。 利用特异性单克隆抗体（mAb）和cDNA探针 对PCA、细胞表面抗原和免疫调节因子具有特异性， 分子，我们将研究2个主要分子之间的相互作用。 肿瘤相关PCA、癌症促凝剂（CP）和组织因子 (TF)炎性细胞和血管细胞浸润和纤维蛋白 在人类肿瘤中的沉积。 我们将描述PCA的特征， 从原发性和转移性肿瘤中分离的同质细胞群 利用传统的生物化学方法， 和特异性免疫和功能探针。 长期 本研究的目的是：1）提供更好的理解 癌症中纤维蛋白沉积的机制; 2）发展 特异性抑制细胞介导的纤维蛋白的策略 沉积; 3）证实通过以下抑制转移形成： 抑制细胞介导的凝血。