...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>British Journal of Cancer >Chemotherapy-induced dynamic gene expression changes in vivo are prognostic in ovarian cancer
【24h】

Chemotherapy-induced dynamic gene expression changes in vivo are prognostic in ovarian cancer

机译：体内化学疗法诱导的动态基因表达变化可预测卵巢癌的预后

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background: The response of ovarian cancer patients to carboplatin and paclitaxel is variable, necessitating identification of biomarkers that can reliably predict drug sensitivity and resistance. In this study, we sought to identify dynamically controlled genes and pathways associated with drug response and its time dependence.Methods: Gene expression was assessed for 14 days post-treatment with carboplatin or carboplatin–paclitaxel in xenografts from two ovarian cancer models: platinum-sensitive serous adenocarcinoma-derived OV1002 and a mixed clear cell/endometrioid carcinoma-derived HOX424 with reduced sensitivity to platinum.Results: Tumour volume reduction was observed in both xenografts, but more dominantly in OV1002. Upregulated genes in OV1002 were involved in DNA repair, cell cycle and apoptosis, whereas downregulated genes were involved in oxygen-consuming metabolic processes and apoptosis control. Carboplatin–paclitaxel triggered a more comprehensive response than carboplatin only in both xenografts. In HOX424, apoptosis and cell cycle were upregulated, whereas Wnt signalling was inhibited. Genes downregulated after day 7 from both xenografts were predictive of overall survival. Overrepresented pathways were also predictive of outcome.Conclusions: Late expressed genes are prognostic in ovarian tumours in a dynamic manner. This longitudinal gene expression study further elucidates chemotherapy response in two models, stressing the importance of delayed biomarker detection and guiding optimal timing of biopsies.
机译：背景：卵巢癌患者对卡铂和紫杉醇的反应是可变的，因此有必要鉴定能够可靠地预测药物敏感性和耐药性的生物标志物。在这项研究中，我们试图确定与药物反应及其时间依赖性相关的动态控制基因和途径。方法：在两种卵巢癌模型的异种移植物中，用卡铂或卡铂-紫杉醇治疗后14天评估基因表达。敏感的浆液性腺癌衍生的OV1002和混合的透明细胞/子宫内膜样癌衍生的HOX424，对铂的敏感性降低。结果：两种异种移植物中均观察到肿瘤体积减少，但在OV1002中更为明显。 OV1002中的上调基因与DNA修复，细胞周期和细胞凋亡有关，而下调的基因与耗氧的代谢过程和细胞凋亡控制有关。仅在两种异种移植物中，卡铂-紫杉醇比卡铂引起更全面的反应。在HOX424中，凋亡和细胞周期被上调，而Wnt信号被抑制。两种异种移植物在第7天后下调的基因可预测总体存活率。结论：晚期表达的基因可以动态预测卵巢肿瘤的预后。这项纵向基因表达研究进一步阐明了两种模型的化疗反应，强调了延迟生物标志物检测的重要性并指导了活检的最佳时机。

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