...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Gene Therapy and Molecular Biology >Reversal of MDR1/P-glycoprotein associated drugresistance in human Hepatoblastoma
【24h】

Reversal of MDR1/P-glycoprotein associated drugresistance in human Hepatoblastoma

机译：逆转人肝母细胞瘤中MDR1 / P-糖蛋白相关的耐药性

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

摘要

Despite impressive improvements of treatment results in children suffering from hepatoblastoma (HB), advanced tumor stages still provide unsolved problems for treating physicians. A major factor for this phenomenon is the phenotype of drug resistance. The mechanism related to the Multidrug Resistance Gene 1 (MDR1) and its product P-glycoprotein (P-gp) has been identified in experimental studies as major factor contributing to drug resistance in HB. P-gp is an ATP dependant membrane channel, which pumps cytotoxic agents out of the tumor cells. Modulation of P-gp using atoxic chemosensitizers improved treatment results in several tumor types. There is a correlation between MDR1 gene expression levels and the amount of applied chemotherapy courses in resected HB. Relapses and metastases show the highest expression followed by primary tumors after neoadjuvant chemotherapy. Lowest expression levels are found in tumors that were not pre-treated before surgery. We also observed significant treatment improvements of chemosensitizers compared to respective mono-therapies both, in cell lines and in xenotransplanted HB. In cell cultures, cell viabilities decreased significantly without an increase of MDR1 gene expression levels. In xenotransplanted HB, tumor growth and serum alpha-fetoprotein levels were decreased significantly. Again, there were no effects of chemosensitizers on MDR1/P-gp expression levels. Our data underlinethe hypothesis that chemosensitizers may represent a promising tool for the treatment of advanced types of HB.
机译：尽管患肝母细胞瘤（HB）的儿童的治疗效果有了显着改善，但晚期肿瘤阶段仍为医师治疗提供了未解决的问题。这种现象的主要因素是耐药性的表型。在实验研究中已确定与多重耐药基因1（MDR1）及其产物P-糖蛋白（P-gp）有关的机制是导致HB耐药的主要因素。 P-gp是ATP依赖的膜通道，可将细胞毒剂泵出肿瘤细胞。使用无毒化学增敏剂调节P-gp可改善几种肿瘤类型的治疗效果。在切除的HB中，MDR1基因表达水平与所用化学疗法的疗程之间存在相关性。在新辅助化疗后，复发和转移显示出最高的表达，其次是原发肿瘤。在未经手术治疗的肿瘤中发现最低的表达水平。与细胞系和异种移植HB中的单一疗法相比，我们还观察到了化学增敏剂的显着治疗改善。在细胞培养中，细胞活力显着下降，而MDR1基因表达水平没有增加。在异种移植的HB中，肿瘤生长和血清甲胎蛋白水平显着降低。同样，化学增敏剂对MDR1 / P-gp表达水平没有影响。我们的数据强调了以下假设：化学增敏剂可能代表了一种用于治疗晚期HB的有前途的工具。

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