...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>AIDS Research and Human Retroviruses >HIV infection accelerates gastrointestinal tumor outgrowth in NSG-HuPBL mice
【24h】

HIV infection accelerates gastrointestinal tumor outgrowth in NSG-HuPBL mice

机译：HIV感染会加速NSG-HuPBL小鼠胃肠道肿瘤的生长

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

HIV infection is a risk factor for the tumorigenesis including non-AIDS-defining cancers such as those of the gastrointestinal tract. However, the mechanisms underlying such cancer outgrowth are still unknown. Furthermore, combined HIV/cancer studies are difficult to evaluate using primate models or in the clinical patient setting. To understand the mechanisms of tumor outgrowth in the context of HIV infection, we adopted a humanized mouse model permissive to infection and cancer as well as an in vivo humanized mouse challenge with colon cancer in the context of HIV infection. Immunodeficient NOD SCID IL-2R-/- mice were immunologically reconstituted by adoptive transfer of 107 HIV-negative donor peripheral blood leukocytes and challenged with 106 HCT116 human colon cancer cells. A group of mice was treated with antiretroviral therapy. Tumor microenvironment and epithelial tissues in the context of HIV infection were analyzed using immunohistochemistry. We demonstrate that HIV-infected humanized mice develop significantly larger tumors than uninfected mice (p0.05). Epithelial cell proliferation in HIV-infected mice is significantly enhanced in comparison to proliferation in uninfected mice (p0.01). Moreover, the activation of β-catenin, an important step in intestinal epithelial cell proliferation and tumorigenesis, is elevated in the tumors of HIV-infected mice (p0.0001). Importantly, antiretroviral therapy reverses these pathological processes independently of CD4+ T cell return. These findings model the ability of HIV infection to result in tumor outgrowth that is evident in HIV-positive patients and lend insight into previously unrecognized mechanisms that may underlie this pathology.
机译：HIV感染是肿瘤发生的危险因素，包括非爱滋病定义的癌症，例如胃肠道癌。然而，这种癌变的潜在机制仍是未知的。此外，很难使用灵长类动物模型或在临床患者中评估艾滋病毒/癌症的综合研究。为了了解在HIV感染情况下肿瘤生长的机制，我们采用了允许感染和癌症的人源化小鼠模型，并在HIV感染情况下采用了结肠癌的体内人源化小鼠攻击。通过过继转移107个HIV阴性供体外周血白细胞免疫重建免疫缺陷的NOD SCID IL-2R-/-小鼠，并用106个HCT116人结肠癌细胞攻击。一组小鼠接受了抗逆转录病毒治疗。使用免疫组织化学分析了HIV感染情况下的肿瘤微环境和上皮组织。我们证明，HIV感染的人源化小鼠比未感染的小鼠发展出明显更大的肿瘤（p <0.05）。与未感染的小鼠相比，HIV感染的小鼠的上皮细胞增殖显着增强（p <0.01）。此外，在感染了HIV的小鼠的肿瘤中，β-catenin的激活（肠道上皮细胞增殖和肿瘤发生的重要步骤）被提高（p <0.0001）。重要的是，抗逆转录病毒疗法可逆转这些病理过程，而与CD4 + T细胞的返回无关。这些发现模拟了HIV感染导致肿瘤过度生长的能力，这在HIV阳性患者中很明显，并且有助于了解可能是这种病理学基础的先前未被认识的机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号