Spatial and Temporal Regulation of Angiogenesis

血管生成的时空调节

• 批准号: 7074844
• 负责人: HAROLD FISHER DVORAK
• 金额: $ 168.92万
• 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 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7074844
• 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） 血管生成是从良性病变中肿瘤发展的关键步骤 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 调节新生儿，正常成人和肿瘤环境中的血管生成。 第1个副标理1将表征正常或肿瘤组织中的血管 在存在各种细胞因子和抑制剂的情况下形成 组合。该项目还将比较 来自新生儿，成人和VEGF-A过表达组织的内皮。子标记2 试图表征vegf-a介导的信号通路 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。 subproject 3将定义PLGF的作用 正常皮肤以及炎症，癌变的血管化， 实验性肿瘤生长，转移和血管生成。第4个试图 表征功能充当受体的多蛋白复合物 内皮细胞上的血小板传播1（TSP-1）并确定信号传导 介导TSP-1诱导凋亡的途径。核心A（管理 支持）将监督和协调科学，财政和监管 该程序的操作。核心B（形态支持）将提供专业知识 在电子显微镜中，原位杂交和共聚焦显微镜与 程序。核心C（细胞生物学支持）将准备和提供各种类型 良好的和标准化的内皮细胞。核心D（基因组学 支持）将执行基因分析研究，并将提供 生物信息学支持数据分析和采矿。总的来说， 科学互动，合作和试剂和专业知识的交流 该计划项目提供的将导致对 血管生成的分子，细胞和形态基础。