A NEW ANTICANCER ANGOIGENESIS INHIBITOR FROM HUMAN URINE

抑制肿瘤血管生成（血管向肿瘤肿块生长）是一种新的、有前途的抗癌治疗方法。血管生成抑制剂，如从荷瘤小鼠尿液中纯化的血管抑制素，在啮齿类动物中具有有效的抗肿瘤活性。因此，我们提出从癌症患者尿液中纯化的血管生成抑制剂可能对人类具有有效的抗肿瘤活性。目的是直接从膀胱癌患者尿液中分离新的血管生成抑制剂SBD - 1。我们的初步结果表明，部分纯化的膀胱癌患者尿液选择性地抑制内皮细胞的生长。此外，这种抑制活性的色谱和过滤谱、蛋白酶敏感性以及抗体测试表明，它很可能属于一种新的抗血管生成蛋白。使用几种色谱技术的组合，我们打算快速分离这种抑制剂。此外，我们将在小鼠中测试其潜在的抗肿瘤活性，并确定其氨基酸序列。因此，该项目将分离出一种具有潜在抗肿瘤活性的新型血管生成抑制剂，作为实验室研究试剂和临床药物具有巨大的商业价值。建议的商业应用：对新的、更好的抗癌药物的需求是巨大的。此外，像我们这样的血管生成抑制剂可以用于治疗某些心血管疾病和黄斑变性。因此，我们提出要纯化的分子类型有一个巨大的、数十亿美元的市场。我们坚信，像我们这样的新型高效血管生成抑制剂将吸引合资伙伴，并将进行临床试验。同时，它可以作为实验室血管生成研究的试剂商业化。

Inhibition of tumor angiogenesis (the growth of blood vessels towards the tumor mass) is a new, promising approach to the anti-cancer therapy. Inhibitors of angiogenesis such as angiostatin purified from urine of tumor- bearing mice have a potent antineoplastic activity in rodents. Therefore, we propose that angiogenesis inhibitors purified from urine of cancer patients could have a potent antineoplastic activity in humans. The goal of this project is to isolate new angiogenesis inhibitor (SBD 1) directly from urine of patients with bladder carcinoma. Our preliminary results show that partially purified urine from patients with bladder carcinoma inhibits selectively the growth of endothelial cells. Moreover, the chromatographic and filtration profiles of this inhibitory activity, protease sensitivity as well as antibody testing indicate that most likely it belongs to a novel anti-angiogenic protein. Using several combinations of chromatographic techniques, we intend to rapidly isolate this inhibitor. Furthermore, we will test it for the potential anti-tumoral activity in mice, and determine its amino acid sequence. This project will therefore result in the isolation of a new angiogenesis inhibitor with potential anti-tumor activity, which can have a tremendous commercial importance both as a laboratory research reagent and as a clinical drug. PROPOSED COMMERCIAL APPLICATIONS: The need for new, better anticancer medicines is immense. Moreover, an angiogenesis inhibitor like ours could be used for the treatment of certain cardiovascular diseases and macular degeneration. Therefore, there is a large, multibillion dollar market for the type of molecule(s) that we propose to purify. We strongly believe that a novel efficient angiogenesis inhibitor like ours will attract joint venture partners and will be taken to clinical trials. Meanwhile, it can be commercialized as a reagent for laboratory research on angiogenesis.