...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular cancer therapeutics >Tasisulam sodium, an antitumor agent that inhibits mitotic progression and induces vascular normalization.
【24h】

Tasisulam sodium, an antitumor agent that inhibits mitotic progression and induces vascular normalization.

机译：Tasisulam钠，一种抗肿瘤药物，可抑制有丝分裂进程并诱导血管正常化。

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

LY573636-sodium (tasisulam) is a small molecule antitumor agent with a novel mechanism of action currently being investigated in a variety of human cancers. In vitro, tasisulam induced apoptosis via the intrinsic pathway, resulting in cytochrome c release and caspase-dependent cell death. Using high content cellular imaging and subpopulation analysis of a wide range of in vitro and in vivo cancer models, tasisulam increased the proportion of cells with 4N DNA content and phospho-histone H3 expression, leading to G(2)-M accumulation and subsequent apoptosis. Tasisulam also blocked VEGF, epidermal growth factor, and fibroblast growth factor-induced endothelial cell cord formation but did not block acute growth factor receptor signaling (unlike sunitinib, which blocks VEGF-driven angiogenesis at the receptor kinase level) or induce apoptosis in primary endothelial cells. Importantly, in vivo phenocopying of in vitro effects were observed in multiple human tumor xenografts. Tasisulam was as effective as sunitinib at inhibiting neovascularization in a Matrigel plug angiogenesis assay in vivo and also caused reversible, non G(2)-M-dependent growth arrest in primary endothelial cells. Tasisulam also induced vascular normalization in vivo. Interestingly, the combination of tasisulam and sunitinib significantly delayed growth of the Caki-1 renal cell carcinoma model, whereas neither agent was active alone. These data show that tasisulam has a unique, dual-faceted mechanism of action involving mitotic catastrophe and antiangiogenesis, a phenotype distinct from conventional chemotherapies and published anticancer agents.
机译：LY573636-钠（tasisulam）是一种小分子抗肿瘤药，目前正在多种人类癌症中进行研究，其作用机理新颖。在体外，tasisulam通过内在途径诱导凋亡，导致细胞色素c释放和caspase依赖性细胞死亡。 tasisulam使用高含量细胞成像和亚群分析对各种体外和体内癌症模型进行分析，tasisulam增加了具有4N DNA含量和磷酸化组蛋白H3表达的细胞比例，从而导致G（2）-M积累和随后的细胞凋亡。 Tasisulam还阻断VEGF，表皮生长因子和成纤维细胞生长因子诱导的内皮细胞线形成，但不阻断急性生长因子受体信号传导（与舒尼替尼不同，舒尼替尼在受体激酶水平上阻断VEGF驱动的血管生成）或诱导原代内皮细胞凋亡细胞。重要的是，在多种人类肿瘤异种移植物中观察到了体外作用的体内表型。 Tasisulam与舒尼替尼在体内Matrigel栓血管生成测定中抑制新血管形成一样有效，并且还引起原代内皮细胞中可逆的，非G（2）-M依赖性生长停滞。 Tasisulam还可以诱导体内血管正常化。有趣的是，tasisulam和舒尼替尼的组合显着延迟了Caki-1肾细胞癌模型的生长，而两种药物都不是单独有效的。这些数据表明，tasisulam具有独特的，双向作用机理，涉及有丝分裂灾难和抗血管生成，其表型不同于常规化学疗法和已发表的抗癌剂。

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