Spatial and Temporal Regulation of Angiogenesis

血管生成的时空调节

• 批准号: 7174561
• 负责人: HAROLD FISHER DVORAK
• 金额: $ 2.15万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-13 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7174561
• 关键词: angiogenesis; blood vessels; clinical research; metastasis; neoplasm /cancer blood supply; thrombospondins; vascular endothelial growth factors

DESCRIPTION (provided by applicant) Angiogenesis is a key step in the progression of neoplasia from benign lesions to life-threatening disease. The central theme of this project is that the integration of knowledge from the molecular, cellular and tissue morphological levels will lead to a detailed understanding of the spatial and temporal regulation of angiogenesis in neonatal, normal adult and tumor settings. Subproject 1 will characterize blood vessels in normal or neoplastic tissue that form in the presence of various cytokines and inhibitors either alone or in combination. This project will also compare the gene expression of endothelium from neonatal, adult and VEGF-A overexpressing tissue. Subproject 2 seeks to characterize VEGF-A-mediated signaling pathways downstream of KDR/Flk-1 and Flt-1 and evaluate the role of these pathways in normal and tumor-induced angiogenesis. Subproject 3 will define the role of PlGF for vascularization of normal skin as well as during inflammation, carcinogenesis, experimental tumor growth, metastasis and angiogenesis. Subproject 4 seeks to characterize the multiprotein complex that functions as a receptor for thrombospondin-1 (TSP-1) on endothelial cells and determine the signaling pathways that mediate TSP-1-induced apoptosis. Core A (Administrative Support) will oversee and coordinate the scientific, fiscal and regulatory operations of the program. Core B (Morphology Support) will provide expertise in electron microscopy, in situ hybridization and confocal microscopy to the program. Core C (Cell Biology Support) will prepare and supply various types of well-characterized and standardized endothelial cells. Core D (Genomics Support) will perform the gene profiling studies and will provide bioinformatics support for data analysis and mining. Taken together, the scientific interactions, collaborations and exchange of reagents and expertise afforded by this Program Project will lead to a comprehensive understanding of the molecular, cellular and morphological basis of angiogenesis.

描述（由申请人提供） 血管生成是良性病变进展为肿瘤的关键步骤 到危及生命的疾病。该项目的中心主题是 分子、细胞和组织形态学知识的整合 水平将导致对空间和时间的详细理解 新生儿、正常成人和肿瘤环境中血管生成的调节。 子项目 1 将描述正常或肿瘤组织中的血管特征 在单独或在多种细胞因子和抑制剂存在下形成 组合。该项目还将比较基因表达 来自新生儿、成人和 VEGF-A 过表达组织的内皮细胞。子项目2 寻求表征 VEGF-A 介导的下游信号通路 KDR/Flk-1 和 Flt-1 并评估这些途径在正常和 肿瘤诱导的血管生成。子项目 3 将定义 PlGF 的作用： 正常皮肤的血管化以及炎症、癌变过程中， 实验性肿瘤生长、转移和血管生成。子项目 4 旨在 表征作为受体的多蛋白复合物 内皮细胞上的血小板反应蛋白-1 (TSP-1) 并确定信号传导 介导 TSP-1 诱导细胞凋亡的途径。核心A（行政 支持）将监督和协调科学、财政和监管 程序的操作。核心 B（形态支持）将提供专业知识 在电子显微镜、原位杂交和共聚焦显微镜中 程序。 Core C（细胞生物学支持）将准备并提供各种类型 具有良好特征和标准化的内皮细胞。核心 D（基因组学 支持）将进行基因分析研究并提供 生物信息学支持数据分析和挖掘。综合起来， 科学互动、合作以及试剂和专业知识的交流 该计划提供的项目将导致全面了解 血管生成的分子、细胞和形态学基础。