BIOLOGY OF THE VASCULATURE OF HUMAN PRIMARY BRAIN TUMORS

人类原发性脑肿瘤脉管系统的生物学

• 批准号: 3100605
• 负责人: DENNIS R GROOTHUIS
• 金额: $ 15万
• 依托单位: EVANSTON HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-27 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3100605
• 关键词: brain neoplasms; neoplasm /cancer blood supply; neoplasm /cancer pharmacology

This is a Feasibility Grant application for a Brain Tumor Research Center from Northwestern University and its affiliated hospitals. Despite substantially increased knowledge about the biological behavior of malignant primary brain tumors and significant improvements in early diagnosis, survival of patients with brain tumors has not improved. This is the first application from a team of investigators that has been carefully assembled to bring clinical and basic research strengths to the study and treatment of brain tumors at Northwestern University. Additional faculty recruitments are now occurring and more are planned over the three year period of this feasibility grant, which, when completed, will bring the research and clinical complement of the team to a point it can conduct extensive collaborative basic and clinical research and can successfully compete for a full Program Project Grant application in three years. The central theme of this application is angiogenesis and its functional consequences. Angiogenesis is an obligate consequence of primary brain tumor growth, and yet the function of the new vessels may be nearly normal or wildly abnormal, particularly with regard to the one vessel property that most affects brain tumor therapy, i.e., permeability. The four projects in this application will focus on the two polar aspects of angiogenesis, the factors controlling initiation, and, at the other pole, vessel behavior and responses to therapy in fully developed tumors. These projects will attempt to bring these very basic and applied poles together. Project 1 will focus on the altered properties of brain tumor blood vessels by measuring blood- to-tissue transport in malignant gliomas, oligodendrogliomas, and medulloblastomas, and responses to common therapy. This is a topic about which almost no quantitative information exists in humans, and yet which must ultimately form the basis for understanding delivery of any diagnostic or therapeutic substance to brain tumors. Project 2 is designed to explore the mechanisms of angiogenesis inhibition, focusing on the role of copper dependent enzymes in growth factor-protease interactions. Project 3 intends to develop novel in vivo methods for measuring the development of angiogenesis and the effects of therapy. These new methods will add to our knowledge base about the vasculature of brain tumors, allow us to predict the behavior of brain tumor vessels, and serve as the basis for modeling drug delivery to brain tumors. Project 4 hypothesizes that proteolytic enzyme production in gliomas can be related to the aberrant expression of proto-oncogenes, and will study proto-oncogene products, secondary cellular messengers, and proteolytic enzymes, and determine if these can be related to angiogenesis and capillary function. No therapeutic studies are included in this application, but therapeutic trials of angiogenesis inhibitors are currently being designed and will become an integral part of this program within the first year.

这是脑肿瘤研究的可行性拨款申请 中心由西北大学及其附属医院组成。 尽管对生物行为的了解大大增加 恶性原发性脑肿瘤和早期显着改善 确诊后，脑肿瘤患者的生存率并没有改善。 这是研究小组提出的第一份申请 精心集结，将临床和基础研究优势 西北大学脑肿瘤的研究和治疗。 目前正在招聘更多教师，并计划进行更多招聘 在该可行性拨款的三年期间，当 完成后，将带来团队的研究和临床补充 在一定程度上它可以进行广泛的基础和临床协作 研究并可以成功竞争完整的计划项目补助金 三年内申请。 该应用程序的中心主题是 血管生成及其功能后果。 血管生成是 原发性脑肿瘤生长的必然结果，但其功能 新血管的数量可能几乎正常或极不正常，特别是 关于对脑肿瘤影响最大的一种血管特性 治疗，即渗透性。 本申请中的四个项目将 重点关注血管生成的两个极端方面，即控制因素 启动，而在另一极，船舶行为和响应 治疗完全发育的肿瘤。 这些项目将试图带来 这些非常基本和应用的极点放在一起。 项目1将重点关注 通过测量血液来改变脑肿瘤血管的特性 恶性胶质瘤、少突神经胶质瘤和组织运输 髓母细胞瘤以及对常见治疗的反应。 这是一个话题 关于人类几乎不存在任何定量信息，但是 最终必须构成理解任何交付的基础 脑肿瘤的诊断或治疗物质。 项目2是 旨在探索血管生成抑制机制，重点关注 生长因子蛋白酶中铜依赖性酶的作用 互动。 项目3旨在开发新颖的体内方法 测量血管生成的发展和治疗效果。 这些新方法将增加我们关于脉管系统的知识库 脑肿瘤，让我们能够预测脑肿瘤的行为 血管，并作为药物向大脑输送建模的基础 肿瘤。 项目 4 假设蛋白水解酶的产生 神经胶质瘤可能与原癌基因的异常表达有关， 并将研究原癌基因产物、次级细胞信使、 和蛋白水解酶，并确定这些是否与 血管生成和毛细血管功能。 尚无治疗研究 包括在本申请中，但血管生成的治疗试验 抑制剂目前正在设计中，并将成为不可或缺的一部分 该计划的第一年。