INDUCTION AND SUPPRESSION OF ANGIOGENESIS

血管生成的诱导和抑制

• 批准号: 6513232
• 负责人: JEFFREY A GREENSPAN
• 金额: $ 31.37万
• 依托单位: MUNIN CORPORATION
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-18 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6513232
• 关键词: angiogenesis; angiogenesis inhibitors; antineoplastics; cell line; cell migration; chemoattractants; combinatorial chemistry; drug screening /evaluation; monoclonal antibody; neoplasm /cancer blood supply; protein structure function; transfection; vascular endothelium

Angiogenesis, formation of new blood vessels from cells of preexisting vessels, is essential for progressive tumor growth and metastasis. Therapies aimed at inhibiting tumor angiogenesis hold great promise in cancer treatment. We have proposed (and presented evidence in Phase I) that a specific recently characterized mammalian factor is an excellent candidate for a regulator of the initiation and progression of tumor angiogenesis. The specific aims of Phase II are: 1) the determination of whether blocking the angiogenic activity of this factor inhibits tumor growth and angiogenesis in vivo; 2) the use of this factor in the development of standardized ex vivo and in vivo assays to facilitate, respectively, large-scale screening and subsequent secondary small-scale screening to identify blockers of this factor as candidate anti-cancer agents; 3) the test-demonstration of this screening protocol to identify such candidate anti-cancer agents. Fulfillment of these aims would establish the validity and feasibility of developing this factor as a marketable reagent to discover novel anti-cancer agents, and also would identify potential anti-cancer agents that block the angiogenic activity of this factor. PROPOSED COMMERCIAL APPLICATION: Cancer is the second leading cause of mortality in the U.S., and its health care costs are well over $100 billion. Solid tumors comprise the majority of cancers, afflict over 3 million people, and cause over a half million deaths annually. The health care market for anti-angiogenesis anti-cancer agents is very significant because conventional chemotherapy selects for resistant cancer cells, and causes significant toxicity to normal tissue.

血管生成，即从现有血管细胞形成新血管，对于肿瘤的进行性生长和转移至关重要。旨在抑制肿瘤血管生成的疗法在癌症治疗中具有广阔的前景。我们提出（并在第一阶段提供了证据），最近表征的特定哺乳动物因子是肿瘤血管生成起始和进展调节剂的极好候选者。 II期的具体目标是：1）确定阻断该因子的血管生成活性是否会抑制体内肿瘤生长和血管生成； 2) 使用该因子开发标准化的离体和体内测定，以分别促进大规模筛选和随后的二次小规模筛选，以确定该因子的阻断剂作为候选抗癌剂； 3) 该筛选方案的测试演示，以确定此类候选抗癌药物。这些目标的实现将确立将该因子开发为可销售试剂以发现新型抗癌剂的有效性和可行性，并且还将确定阻断该因子的血管生成活性的潜在抗癌剂。拟议的商业应用：癌症是美国第二大死亡原因，其医疗保健费用远远超过 1000 亿美元。实体瘤占癌症的大多数，每年影响超过 300 万人，并导致超过 50 万人死亡。抗血管生成抗癌药物的医疗保健市场非常重要，因为传统化疗会选择耐药癌细胞，并对正常组织造成显着毒性。