BIOLOGY OF SOLID TUMOR GROWTH AND IMMUNE REJECTION

实体瘤生长和免疫排斥的生物学

• 批准号: 3168150
• 负责人: HAROLD FISHER DVORAK
• 金额: $ 14.9万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-02-01 至 1988-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3168150
• 关键词: Hodgkin's disease; anticoagulants; autoradiography; biliary tract neoplasm; breast neoplasms; chemoattractants; electron microscopy; fibrin; fibrinolytic agents; host neoplasm interaction; immunochemistry; immunofluorescence technique; immunopathology; leukocytes; macrophage; malignant ascites; mathematical model; migration inhibition factor; neoplasm /cancer blood supply; neoplasm /cancer immunology; neoplasm /cancer pharmacology; neoplasm /cancer remission /regression; neoplasm /cancer transplantation; neoplastic cell; neoplastic growth; radiation detector; radiotracer; tissue /cell culture

The goal of this research has been to evaluate the role of fibrin deposition and turnover in the biology of tumor growth, particularly with reference to tumor stroma formation. In the past year we have completed initial studies concerning the quantitation of fibrinogen influx and fibrin deposition and turnover in two well-characterized guinea pig carcinomas, line 1 and line 10 bile duct tumors. Earlier immunofluorescence studies revealed fibrin deposits in both tumors (line 1 much greater than line 10). In accord with these data, trace-labeled guinea pig fibrinogen (GPF) accumulated in both tumors in amounts that matched or exceeded plasma fibrinogen levels. However, line 1 tumor GPF content was four times that of line 10 tumors and 11 to 33 times that of normal subcutaneous tissue. The great bulk of accumulated GPF was in the form of cross linked (transglutaminated) fibrin. Because initial influx of fibrinogen into tumors and clotting were identical for both tumors, the large differences in GPF accumulation (line 1 greater than line 10) apparently reflect differences in fibrinolysis. Other studies have been concerned with the nature and importance of tumor-associated procoagulants to tumor fibrin deposition. Several tumor procoagulant activities have been identified in both the intrinsic and extrinsic coagulation pathways, as well as provision of a surface for prothrombinase generation, the penultimate step in the common coagulation pathway and one essential for clotting to proceed to completion. However, our studies in the past year have shown that tumor-associated procoagulants may be very much less important than had been thought earlier. We found that increased microvascular permeability alone is sufficient to induce equivalant extravascular coagulation in several normal tissues. The results indicate that saturating levels of procoagulant are present even in normal tissues in association with normal connective tissue cells. Therefore, the level of microvascular permeability becomes the rate limiting step in extravascular coagulation for solid tumors and also for a broad spectrum of inflammatory reactions. (A)

这项研究的目的是评估纤维蛋白的作用 肿瘤生长生物学中的沉积和周转，特别是 参考肿瘤基质形成。 在过去的一年里我们完成了 关于纤维蛋白原流入和纤维蛋白定量的初步研究 两种特征明确的豚鼠癌的沉积和周转， 1 线和 10 线胆管肿瘤。 早期免疫荧光研究 显示两个肿瘤中都有纤维蛋白沉积（第 1 行比第 1 行大得多） 10）。 根据这些数据，痕量标记的豚鼠纤维蛋白原 (GPF) 两个肿瘤中累积的量与血浆相当或超过 纤维蛋白原水平。 然而，1号线肿瘤GPF含量是其四倍 10 系肿瘤的体积是正常皮下组织的 11 至 33 倍。 大部分累积的 GPF 是以交联的形式存在的。 （转谷氨酰胺）纤维蛋白。 因为纤维蛋白原最初流入 两种肿瘤的肿瘤和凝血均相同，但差异很大 在 GPF 累积中（第 1 行大于第 10 行）显然反映了 纤溶作用的差异。 其他研究关注的是 肿瘤相关促凝血剂导致肿瘤纤维蛋白沉积。 几个肿瘤 促凝血活性已在内在和 外源性凝血途径，以及提供表面 凝血酶原的产生，普通凝血的倒数第二步 途径，也是凝血完成所必需的途径。 然而， 我们过去一年的研究表明，肿瘤相关促凝血剂 可能没有之前想象的那么重要。 我们发现 仅增加微血管通透性就足以诱导 几种正常组织中的等效血管外凝血。 这 结果表明，即使在 与正常结缔组织细胞相关的正常组织。 因此，微血管通透性的水平变为速率 实体瘤血管外凝血的限制步骤 广泛的炎症反应。 （一个）