Invasion and Angiogenesis in Malignant Gliomas

描述（由申请人提供）：迫切需要用于脑肿瘤的新疗法。弥漫性神经胶质瘤细胞侵入周围脑组织和血管生成是神经胶质瘤的基本特征，其尚未通过常规疗法成功地解决以控制脑肿瘤患者中的肿瘤生长。目前积极的局部治疗，如手术，放疗和化疗是有效的控制肿瘤细胞在大脑中的局部质量。这种成功只是暂时的，因为肿瘤细胞已经侵入周围的大脑，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试验，使我们能够研究入侵的胶质瘤和内皮细胞。 我们的长期目标仍然是干扰肿瘤侵袭和血管生成，以减少肿瘤生长。为此，我们建议i）确定参与内皮细胞和胶质瘤细胞迁移的机制; ii）研究两种格尔德霉素类似物在体外和体内对胶质瘤的机制和治疗潜力。 我们的建议旨在利用新的分子生物学技术来提高我们对这一过程的理解。总的来说，拟议的实验将分析肿瘤侵袭和血管生成所需的细胞和分子途径。这些实验的结果将导致未来的策略，旨在抑制这些关键过程中涉及的特定分子组分。

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.