POTENTIAL CHEMOPREVENTIVE AGENTS

潜在的化学预防剂

• 批准号: 6312250
• 负责人: MICHAEL A. PEREIRA
• 金额: $ 3.64万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 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 2001-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6312250
• 关键词: adenoma; carcinogenesis inhibitor; carcinoma; chemical carcinogen; chemoprevention; colon neoplasms; combination chemotherapy; decarboxylase inhibitor; disease /disorder model; drug screening /evaluation; laboratory rat; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; nonsteroidal antiinflammatory agent; ornithine decarboxylase; oxidoreductase inhibitor; prostaglandin endoperoxide synthase; retinoids

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.

本研究的目的是利用氧化偶氮甲烷诱导的大鼠 结肠肿瘤模型来筛选潜在的化学预防剂。 这 模型在处理的F344雄性的结肠中诱导腺瘤和癌 大鼠 由此产生的肿瘤在组织学上与人类肿瘤相似 并且在大约50%的肿瘤中表现出Ki Ras突变 类似于人类。 我们将调查三名特工 化学预防活性（考克斯2抑制剂、类维生素A、ODC抑制剂）， 以及NSAIDS或ODC抑制剂与类维生素A的组合。 后一项研究是基于我们最近的发现， 类维生素A似乎是AOM肿瘤模型中的有效药剂。 应该 这些试剂中的任何一种或试剂的组合证明在这方面是有效的 模型，他们将先进的进一步临床前生物和 在临床开发之前进行毒理学研究。

项目成果

Altered expression of c-myc, p16 and p27 in rat colon tumors and its reversal by short-term treatment with chemopreventive agents.

• DOI: 10.1093/carcin/23.9.1447
• 发表时间: 2002-09
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: L. Tao;P. Kramer;Wei Wang;Siming Yang;R. Lubet;V. Steele;Michael A. Pereira

Modulation of DNA hypomethylation as a surrogate endpoint biomarker for chemoprevention of colon cancer.

DNA 低甲基化的调节作为结肠癌化学预防的替代终点生物标志物。

• DOI: 10.1002/mc.20003
• 发表时间: 2004
• 期刊: Molecular carcinogenesis
• 影响因子: 4.6
• 作者: Tao,Lianhui;Wang,Wei;Kramer,PaulaM;Lubet,RonaldA;Steele,VernonE;Pereira,MichaelA
• 通讯作者: Pereira,MichaelA