Invasion and Angiogenesis in Malignant Gliomas

恶性胶质瘤的侵袭和血管生成

• 批准号: 7048559
• 负责人: DAVID ZAGZAG
• 金额: $ 27.06万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048559
• 关键词: analog; angiogenesis; antineoplastic antibiotics; cell line; cell migration; collagenase; drug screening /evaluation; enzyme activity; focal adhesion kinase; glioma; green fluorescent proteins; hypoxia inducible factor 1; immunocytochemistry; in situ hybridization; integrins; laboratory mouse; mitogen activated protein kinase; molecular oncology; neoplasm /cancer chemotherapy; neoplasm /cancer invasiveness; neoplastic process; phosphorylation; protein structure function; transfection; vascular endothelial growth factors

DESCRIPTION (provided by applicant): There is a dire need for novel therapy for brain tumors. Diffuse glioma cell invasion into surrounding brain tissue and angiogenesis are fundamental features of gliomas that have not been successfully addressed by conventional therapy to control tumor growth in brain tumor patients. Current aggressive local treatments such as surgery, radiotherapy and chemotherapy are effective at controlling the localized mass of tumor cells in the brain. This success is only temporary, because tumor cells that have already invaded into the surrounding brain and serve as seeds by which the tumor re-grows. The process by which these tumor cells invade into the brain is not well understood. New treatment approaches that are capable to control these invading tumor cells can have a dramatic impact on patient outcome. We have developed assays in vitro and in vivo that allow us to study invading glioma and endothelial cells. Our long-term goal remains to interfere with tumor invasion and angiogenesis to diminish tumor growth. To this end we propose i) to determine mechanisms involved in the migration of both endothelial and glioma cells; and ii) to investigate the mechanism and therapeutic potential of two geldanamycin analogues on glioma in vitro and in vivo. Our proposal seeks to take advantage of new molecular biologic techniques to improve our understanding of this process. Collectively, the proposed experiments will analyze the cellular and molecular pathways necessary for tumor invasion and angiogenesis. Results from these experiments will lead to future strategies designed to inhibit specific molecular components implicated in these critical processes.

描述（由申请人提供）：目前迫切需要新的脑肿瘤治疗方法。弥漫性胶质瘤细胞侵入周围脑组织和血管生成是胶质瘤的基本特征，传统治疗方法无法成功地控制脑肿瘤患者的肿瘤生长。目前积极的局部治疗，如手术、放疗和化疗，对控制脑内肿瘤细胞的局部肿块是有效的。这种成功只是暂时的，因为肿瘤细胞已经侵入了周围的大脑，并作为肿瘤重新生长的种子。这些肿瘤细胞侵入大脑的过程尚不清楚。能够控制这些入侵肿瘤细胞的新治疗方法可以对患者的预后产生巨大影响。我们已经开发了体外和体内的试验，使我们能够研究入侵的胶质瘤和内皮细胞。