INDUCTION AND SUPPRESSION OF ANGIOGENESIS

血管生成，即由原有血管细胞形成的新血管，是肿瘤生长和转移的必要条件。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I期研究中提供了证据），最近发现的一种特定的哺乳动物因子是肿瘤血管生成起始和进展的一种极好的调节因子。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能抑制体内肿瘤生长和血管生成；2)利用该因子开发标准化的离体和体内试验，分别促进大规模筛选和随后的二次小规模筛选，以确定该因子的阻滞剂作为候选抗癌药物；3)筛选方案的试验论证，以确定这些候选抗癌药物。这些目标的实现将确立开发该因子作为一种市场试剂的有效性和可行性，以发现新的抗癌药物，也将确定潜在的抗癌药物，阻断该因子的血管生成活性。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，每年折磨300多万人，造成50多万人死亡。抗血管生成抗癌药物的保健市场非常重要，因为常规化疗选择耐药的癌细胞，并对正常组织产生明显的毒性。

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.