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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists
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Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists

机译：使用雌激素受体拮抗剂预防和治疗小鼠宫颈癌

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The majority of human cervical cancers are associated with the high-risk human papillomavirus (HPV) types. In mouse models for HPV-associated cancers, estrogen is required for the development of cervical and vaginal cancers. The estrogen receptor a (ERα) also is required in mice for these cancers to arise. These data are consistent with the observation in women that long-term use of oral contraceptives or multiple pregnancies significantly increases the risk for cervical cancer in HPV-positive women. In the present study, we examined whether drugs that interfere with the function of ERa are effective in treating and/or preventing cervical cancer in mice. We provide evidence that a complete ER antagonist, ICI 182,780 (ICI). as well as a selective ER modulator, raloxifene, efficiently clear cancer and its precursor lesions in both the cervix and the vagina. Furthermore, ICI was capable of preventing the onset of cancers in mice bearing precursor lesions. These findings point to the potential value of ER antagonists in controlling gynecological disease in the lower reproductive tracts in women.
机译：大多数人宫颈癌与高危型人乳头瘤病毒（HPV）类型有关。在与HPV相关的癌症的小鼠模型中，雌激素是宫颈癌和阴道癌发展所必需的。引起这些癌症的小鼠也需要雌激素受体α（ERα）。这些数据与女性观察到的结论一致，即长期使用口服避孕药或多次怀孕会大大增加HPV阳性女性患宫颈癌的风险。在本研究中，我们检查了干扰ERa功能的药物是否有效治疗和/或预防小鼠宫颈癌。我们提供了一个完整的ER拮抗剂ICI 182,780（ICI）的证据。以及选择性的ER调节剂雷洛昔芬可有效清除子宫颈和阴道中的癌症及其前体病变。此外，ICI能够预防患有前体病变的小鼠中癌症的发作。这些发现表明ER拮抗剂在控制女性下生殖道的妇科疾病中的潜在价值。

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