Therapeutic modulation with thrombospondin-1

血小板反应蛋白-1 的治疗调节

• 批准号: 6790522
• 负责人: Chalet Tan
• 金额: $ 3.55万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-14 至 2005-04-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6790522
• 关键词: angiogenesis; disease /disorder model; gene expression; gene therapy; glioma; laboratory mouse; neoplasm /cancer therapy; nerve stem cell; nonhuman therapy evaluation; postdoctoral investigator; stem cell transplantation; thrombospondins

DESCRIPTION (provided by applicant): Thrombospondin-1 (TSP-1), an endogenous angiogenisis inhibitor, is normally secreted by many cell types. Tumors of various origins, including glioblastomas, have been found to down-regulate thrombospondin-1 (TSP-1) expression. We have previously shown that overexpression of TSP-1 in human glioblastoma cells reduces their tumorigenicity in immunocompromised mice, apparently due to inhibition of angiogenesis. We propose to extend our tumorigenicity studies by determining whether induced expression of TSP-1 in a pre-existing brain tumor will result in arrest or reversal of tumor growth in subcutaneous and intracranial glioma models. Additionally, we plan to investigate if mini-TSP-1 proteins containing solely type 1 repeats will have anti-angiogenic activities comparable to full length TSP-1. We will ultimately use neural progenitor cells as a therapeutic tool to deliver TSP-1 or mini-TSP-1 in an intracranial glioma model. With this approach steady and efficacious levels of TSP-1 or mini-TSP-1 will be ideally achievable at the tumor sites. Experimental success in this treatment modality will be readily adaptable to a clinical situation, and could lead to new and highly effective treatment for glioblastomas and other types of cancer.

描述（由申请人提供）：内源性血管生成抑制剂的血小板传播-1（TSP-1）通常由许多细胞类型分泌。已经发现包括胶质母细胞瘤在内的各种起源的肿瘤下调了血小板传播1（TSP-1）的表达。我们先前已经表明，在人胶质母细胞瘤细胞中TSP-1的过表达显然是由于抑制了血管生成的抑制作用。我们建议通过确定在现有的脑肿瘤中诱导TSP-1表达的表达来扩展肿瘤性研究，这将导致皮下和颅内神经胶质瘤模型中肿瘤生长的停滞或逆转。此外，我们计划调查是否仅包含1型重复的Mini-TSP-1蛋白具有与全长TSP-1相当的抗血管生成活性。我们最终将使用神经祖细胞作为治疗工具，以在颅内神经胶质瘤模型中传递TSP-1或Mini-TSP-1。通过这种方法，在肿瘤部位，可以实现稳定有效的TSP-1或Mini-TSP-1。这种治疗方式的实验成功将很容易适应临床状况，并可能导致对胶质母细胞瘤和其他类型的癌症的新的高效治疗。