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EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS IN ANIMAL MOD

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:
6346794
负责人:
Clinton Julian Grubbs
金额:
$34.13万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-08-01 至 2002-07-31

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中文摘要
翻译
正在使用雌性刘易斯大鼠研究各种化学预防剂减少或抑制卵巢癌的功效。 雌性刘易斯大鼠被皮下注射。在10和14日龄时给予0.8 mg N-亚硝基-(2-氧代丙基)胺(BOP)/kgBW。 在21天的断奶期后,雌性(30只/组)大鼠开始在研究期间通过饮食、注射或管饲接受CP剂。 研究持续约30周(直至大鼠约8月龄)。 待施用的剂量在六周范围探索测定之后确定。每种药剂施用两个剂量。 每周一次对动物称重并触诊卵巢肿块。 在研究结束时(约8个月)取出卵巢,并对病变进行组织学检查。记录肿瘤的发生率、多样性、组织学分类和位置。 待测试的测试试剂是:甲羟孕酮(在20日龄时注射,然后每两个月注射一次)、抗雌激素(TBN)、甲羟孕酮+抗雌激素、9-顺式-视黄酸、4 HPR和Apomine(SR-45023 A)(Symphar,Inc)。 对所有组进行编码,并由两名独立评分员以盲法对各组进行评分。 对所有数据进行适当的统计分析将确定各种药剂的增强或抑制作用的显著性。 正在研究的药物类别包括类维生素A、抗雌激素和卵巢特异性药物Apomine。
英文摘要
The efficacy of a variety of chemopreventive agents to reduce or inhibit ovarian cancer using female Lewis rats is being studied. Female Lewis rats are being injected s.c. with 0.8 mg N-nitroso-(2-oxopropyl)amine (BOP) /kgBW at 10 and 14 days of age. After the 21 day weaning period the female (30/group) rats begin receiving CP agents either in the diet, injected or by gavage for the duration of the study. The study runs approximately 30 weeks (until the rats are ~8 months old). The doses to be administered are determined following a six week rangefinding assay. Two doses per agent are administered. The animals are weighed and palpated for ovarian masses once per week. The ovaries are removed at the end of the study (~8 months) and histologically examined for lesions. The incidence, the multiplicity, the histological classification and locations of the tumors are recorded. The test agents to be tested are: Medroxyprogesterone (injected at 20 days of age then bimonthly), an antiestrogen (TBN), Medroxyprogesterone+Antiestrogen, 9-cis-retinoic acid, 4HPR, and Apomine (SR-45023A) (Symphar, Inc). All groups are coded and groups are scored in a blinded manner by two independent scorers. An appropriate statistical analysis on all data will determine significance of enhancing or inhibiting effects of the various agents. The classes of agent being studied include retinoids, antiestrogenic, and an ovarian specific drug Apomine.
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