PRECLINICAL EVALUATION OF INTERMEDIATE ENDPOINTS

中间终点的临床前评估

• 批准号: 2600140
• 负责人: Martin Lipkin
• 金额: $ 29.39万
• 依托单位: STRANG CANCER PREVENTION CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-30 至 1999-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2600140
• 关键词: biomarker; breast neoplasms; cell proliferation; cellular oncology; colon neoplasms; computer assisted diagnosis; computer program /software; dietary calcium; dietary lipid; histopathology; laboratory mouse; nutrition related neoplasm /cancer; nutrition related tag; pancreas neoplasms; pathogenic diet; physiologic stressor; preneoplastic state; prostate neoplasms; prostate preneoplastic state; vitamin D deficiency

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.

乳腺、前列腺、胰腺的早期替代生物标志物的验证， 和结肠肿瘤。 它有 已经确定西式压力饮食可以增加细胞 增殖，改变凋亡，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的发育异常变化 而不进行致癌物处理（Newmark等人，JNCI 82：491，1990，Risio等 例如，Cancer Res. 56：4910，1996和Yang等人Cancer Res 56：4644， 1996年）。 此外，小鼠乳腺导管上皮也被诱导， 当喂食类似的西方应激饮食时变得增生（Khan等人， Carcinogenesis 15：2645，1994）。 西方的压力饮食是高脂肪的， 与AIN-76 A饮食相比，钙和维生素D低。 这个项目 正在制定诱导细胞增殖的定量标准， 计算机辅助细胞图像分析和组织化学染色 乳腺、前列腺、胰腺和结肠导管上皮细胞的方法 在营养应激条件下。 在喂食应激饮食的小鼠中， 乳腺、前列腺、胰腺和结肠上皮细胞正在被测量。 特别是倍性、核形态测量和增殖性 正在使用软件算法测量单元的状态。