POTENTIAL CHEMOPREVENTIVE AGENTS

本研究的目的是利用偶氮甲烷诱导的大鼠 结肠癌模型筛选潜在的化学预防药物。这 模型治疗后F344雄性大鼠结肠腺瘤和癌 老鼠。由此产生的肿瘤在组织上看起来与人类肿瘤相似。 此外，在大约50%的肿瘤中显示出Ki-RAS突变 与人类相似。我们将检查三个单独的特工是否 化学预防活性(COX-2抑制剂、维甲酸、ODC抑制剂) 以及非甾体抗炎药或ODC抑制剂与维甲酸的组合。 后一项研究是基于我们最近的发现，即一些 在AOM肿瘤模型中，维甲酸似乎是有效的药物。应该 这些药剂中的任何一种或药剂的组合在这方面都被证明是有效的 模型它们将被推进到进一步的临床前生物学和 在临床开发之前的毒理学研究。

The objective of this study is to employ the Azoxymethane induced rat colon tumor model to screen for potential chemopreventive agents. This model induces adenomas and carcinomas in the colons of treated F344 male rats. The resulting tumors appear histologically similar to human tumors and furthermore exhibit Ki Ras mutations in approximately 50% of tumors similarly to humans. We will examine three individual agents for their chemopreventive activity (Cox 2 inhibitor, retinoid, ODC inhibitor) as well as combinations of agents NSAIDS or ODC inhibitor plus retinoids. The latter studies are based on our recent findings that some of the retinoids appear to be effective agents in the AOM tumor model. Should any of these agents or combinations of agents prove efficaceous in this model they will be advanced for further preclinical biological and toxicologic studies prior to their development in the clinic.