EFFICACY OF CHEMOPREVENTIVE AGENTS IN ANIMAL MODELS

这项研究主要考察了化学保护剂对 肿瘤终点和更有限数量的潜在替代物 这些药物对其调节的终点生物标记物。端点 包括：a)各种细胞周期调节蛋白，即细胞周期蛋白和 它们相关的激活酶。例如，细胞周期蛋白D1B)的DNA测量 合成(BUDR或PCNA)；C)端粒酶。这些终端可提供 对自己进行了定量分析。这些标记在 各种上皮性癌症。因此，制定出各种 与此特定模型中的这些端点相关的参数应该 事实证明，它适用于多种肿瘤。另一个目标 这些研究中的一项是雇佣代理人，从10周开始 在开始对小鼠进行紫外线照射后。 这项研究的目标是： 1)采用SKH无毛小鼠模型检测三种病原体 在紧接之前开始化学预防治疗 在药物治疗后或治疗后10周。这些 吲哚美辛、DFMO和一种稍后命名的化合物都将 在饲料中给药；2)使用两种有效药剂； 确定它们是否可以调节潜能的表达 生物标志物(如细胞周期蛋白(如增殖细胞核抗原)、细胞周期蛋白水平和 端粒酶活性)。

This study examines the effects of chemopreventives primarily on tumor endpoints and a more limited number of potential surrogate endpoint biomarkers for their modulation by these agents. Endpoints include: A) Various cell cycle regulated proteins i.e. cyclins and their related kinases. e.g. Cyclin D1 B) Measures of DNA synthesis(BudR or PCNA); C) Telomerase . These endpoints lend themselves to quantitative analysis. These markers are altered in a variety of epithelial cancers. Therefore working out various parameters related to these endpoints in this specific model should prove applicable for a wide variety of tumors. One further objective of these studies is to employ agents beginning up to 10 weeks following the beginning of the administration of UV to the mice. The objectives of this study are: 1) To employ the SKH hairless mouse model to examine three agents starting chemopreventive treatment either immediately prior to following or 10 weeks following treatment with the agents. These agents Indomethacin, DFMO and a compound to be named later will all be administered in feed and 2) To employ two effective agent and to determine whether they can modulate expression of potential biomarkers (e.g. cell cycle proteins (e.g. PCNA),cyclin levels and telomerase activity).