PRECLINICAL EVALUATION OF INTERMEDIATE ENDPOINTS

乳房、前列腺、胰腺早期替代生物标志物的验证 和喂食营养压力饮食的动物的结肠瘤。它有 已经确定西式压力饮食可以增加细胞 增殖、改变细胞凋亡、改变细胞角蛋白表达、调节 酸性粘蛋白，并诱导小鼠结肠上皮细胞发育异常 未经致癌物治疗(Newmark et All.，JNCI 82：491,1990，Risio et 等，癌症研究56：4910,1996，杨等。癌症资源56：4644， 1996年)。此外，小鼠乳腺导管上皮细胞也被诱导 当喂食类似的西方压力饮食时，会变得增生性(Khan等人， 癌变15：2645,1994)。西方的压力饮食是高脂肪的， 与AIN-76A饮食相比，钙和维生素D含量较低。这个项目 正在制定量化诱导细胞增殖的标准 和其他SEB通过计算机辅助细胞图像分析和组织化学 方法乳房、前列腺、胰腺和结肠导管上皮细胞 在营养压力条件下。在饲喂应激饮食的小鼠中 乳房、前列腺、胰腺和结肠上皮细胞正在被测量。 特别是倍性、核形态计量学和增殖性的改变 正在使用软件算法测量细胞的状态。

Validation of Early Surrogate Biomarkers of Breast, Prostate, Pancreas, and Colon Neoplasia in Animals Fed a Nutritional Stress diet. It has already been established that Western-style stress diets can increase cell proliferation, alter apoptosis, alter cytokeratin expression, modulate acidic mucins, and induce dysplastic changes in colon epithelia in mice without carcinogen treatment (Newmark et all., JNCI 82:491, 1990, Risio et al., Cancer Res. 56:4910, 1996, and Yang, et al. Cancer Res 56:4644, 1996). in addition mouse mammary ductal epithelium is also induced to become hyperplastic when fed similar Western stress diets (Khan et al., Carcinogenesis 15:2645, 1994). The Western-stress diet is high in fat, and low in calcium and vitamin D compared to AIN-76A diet. This project is developing criteria for the quantitation of induced cell proliferation and other SEB by computer-assisted cell image analysis and histochemical methods in breast, prostate, pancreas, and colon ductal epithelial cells under nutritional stress conditions. In mice fed stress diets SEBs in breast, prostate, pancreas and colon epithelial cells are being measured. Specifically alterations in ploidy, nuclear morphometry, and proliferative status of cells using software algorithms are being measured.