...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Sorafenib selectively depletes human glioblastoma tumor-initiating cells from primary cultures
【24h】

Sorafenib selectively depletes human glioblastoma tumor-initiating cells from primary cultures

机译：索拉非尼选择性地消耗原代培养物中的人类胶质母细胞瘤肿瘤起始细胞

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

Glioblastomas are grade IV brain tumors characterized by high aggressiveness and invasiveness, giving patients a poor prognosis. We investigated the effects of the multi-kinase inhibitor sorafenib on six cultures isolated from human glioblastomas and maintained in tumor initiating cells-enriching conditions. These cell subpopulations are thought to be responsible for tumor recurrence and radio- and chemo-resistance, representing the perfect target for glioblastoma therapy. Sorafenib reduces proliferation of glioblastoma cultures, and this effect depends, at least in part, on the inhibition of PI3K/Akt and MAPK pathways, both involved in gliomagenesis. Sorafenib significantly induces apoptosis/cell death via downregulation of the survival factor Mcl-1. We provide evidence that sorafenib has a selective action on glioblastoma stem cells, causing enrichment of cultures in differentiated cells, downregulation of the expression of stemness markers required to maintain malignancy (nestin, Olig2 and Sox2) and reducing cell clonogenic ability in vitro and tumorigenic potential in vivo. The selectivity of sorafenib effects on glioblastoma stem cells is confirmed by the lower sensitivity of glioblastoma cultures after differentiation as compared with the undifferentiated counterpart. Since current GBM therapy enriches the tumor in cancer stem cells, the evidence of a selective action of sorafenib on these cells is therapeutically relevant, even if, so far, results from first phase II clinical trials did not demonstrate its efficacy. ? 2013 Landes Bioscience.
机译：胶质母细胞瘤是具有高度侵袭性和侵袭性的IV级脑肿瘤，患者预后较差。我们研究了多激酶抑制剂索拉非尼对从人胶质母细胞瘤分离并维持在肿瘤起始细胞富集条件下的六种培养物的影响。这些细胞亚群被认为是导致肿瘤复发以及抗放射和化学耐药的原因，是胶质母细胞瘤治疗的理想靶点。索拉非尼减少了胶质母细胞瘤培养物的增殖，这种作用至少部分取决于对PI3K / Akt和MAPK通路的抑制，两者均与胶质瘤的发生有关。索拉非尼通过下调生存因子Mcl-1来显着诱导凋亡/细胞死亡。我们提供的证据表明，索拉非尼对胶质母细胞瘤干细胞具有选择性作用，导致分化细胞中的培养物富集，维持恶性肿瘤所需的干性标志物（nestin，Olig2和Sox2）的表达下调，并在体外降低了细胞克隆能力和致瘤性体内。索拉非尼对胶质母细胞瘤干细胞的选择性的选择性通过与未分化的胶质母细胞瘤培养物相比分化后较低的敏感性得以证实。由于目前的GBM治疗使癌症干细胞中的肿瘤富集，因此索拉非尼对这些细胞的选择性作用的证据在治疗上具有相关性，即使到目前为止，第二阶段临床试验的结果仍未证明其功效。 ？ 2013 Landes生物科学。

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