INDUCTION AND SUPPRESSION OF ANGIOGENESIS

血管生成，即从预先存在的血管细胞形成新血管，是进行性肿瘤生长和转移所必需的。旨在抑制肿瘤血管生成的疗法在癌症治疗中具有很大的前景。我们已经提出（并在第一阶段提出证据），一个特定的最近表征的哺乳动物因子是一个很好的候选人的肿瘤血管生成的启动和进展的调节。II期的具体目的是：1）确定阻断该因子的血管生成活性是否抑制体内肿瘤生长和血管生成; 2）在开发标准化的离体和体内测定中使用该因子，以分别促进大规模筛选和随后的二次小规模筛选，以鉴定该因子的阻断剂作为候选抗癌剂; 3）该筛选方案的测试示范，以鉴定这样的候选抗癌剂。这些目标的实现将建立开发该因子作为可销售试剂以发现新型抗癌剂的有效性和可行性，并且还将鉴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，其医疗保健费用超过1000亿美元。实体瘤包括大多数癌症，折磨超过300万人，每年导致超过50万人死亡。抗血管生成抗癌剂的医疗保健市场非常重要，因为常规化疗选择耐药癌细胞，并对正常组织造成显著毒性。

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.