EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD

化学预防剂在动物模型中的药效研究

• 批准号: 6346799
• 负责人: Clinton Julian Grubbs
• 金额: $ 36.65万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6346799
• 关键词: breast neoplasms; cancer prevention; carcinogenesis inhibitor; chemical carcinogenesis; chemoprevention; drug screening /evaluation; female; histopathology; laboratory rat; nonhuman therapy evaluation; oral administration; retinoate

Virgin, female Sprague-Dawley rats are being used to determine the efficacy of a series of combinations of chemopreventive agents to prevent mammary cancer. The animals are being fed a diet consisting of standard laboratory chow (e.g. Teklad 4% Rodent Chow). The carcinogen, N-methyl-N-nitrosourea (MNU), administered at about 120 days of age, is used to induce mammary tumors . An MTD for each combination of agents is established and the chemoprevention experiment shall proceed at 0.8 MTD and 0.4 MTD of each combination. Doses for both the rangefinding and the combination tests shall be approved by the Project Officer. The chemopreventive agents is administered starting 1 week prior to the first carcinogen dose and given to the end of the experiment. 9-cis Retinoic acid, Raloxifene, Celecoxib, Zileutin are being administered in the diet singly and in combination. Blood levels and food consumption are being determined for each agent (where practicable). The rats are sacrificed at the end of the experiment at 150 days after the carcinogen dose or when moribund. The number of mammary tumors per animal, and the percent of animals with tumors, and the mean tumor latency (mean time to first tumor) shall be recorded for each group. The mammary tumors shall be excised and a mean tumor weight established for each group. A histological diagnosis shall be made on each tumor.

处女，雌性Sprague-Dawley大鼠被用于确定一系列化学预防剂组合预防乳腺癌的功效。动物喂食由标准实验室饲料（例如Teklad 4%啮齿动物饲料）组成的饲料。致癌物N-甲基-N-亚硝基脲（MNU）在约120日龄时给药，用于诱导乳腺肿瘤。确定每种药物组合的MTD，并在每种组合的0.8 MTD和0.4 MTD下进行化学预防实验。范围确定试验和组合试验的剂量均须经项目官员批准。化学预防剂在第一次致癌剂给药前1周开始给药，直至实验结束。 9-顺式维甲酸、雷洛昔芬、塞来昔布、齐来昔布在饮食中单独或联合给药。正在测定每种药剂的血液水平和摄食量（如可行）。在致癌物剂量后150天实验结束时或濒死时处死大鼠。 应记录每组每只动物的乳腺肿瘤数量、肿瘤动物百分比和平均肿瘤潜伏期（至首次肿瘤的平均时间）。 应切除乳腺肿瘤，并确定每组的平均肿瘤重量。 应对每个肿瘤进行组织学诊断。

项目成果

Efficacy of 9-cis-retinoic acid and N-(4-hydroxyphenyl) retinamide alone and in combination in mammary cancer prevention.

9-顺式视黄酸和 N-(4-羟基苯基)视黄酰胺单独和联合使用在预防乳腺癌中的功效。

• 发表时间: 2004
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: Cope,MarkB;Steele,VernonE;Lubet,RonaldA;Eto,Isao;Juliana,MMargaret;Hill,DonaldL;Grubbs,ClintonJ
• 通讯作者: Grubbs,ClintonJ