...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Phenotypic knockout of VEGF-R2 and Tie-2 with an intradiabody reduces tumor growth and angiogenesis in vivo
【24h】

Phenotypic knockout of VEGF-R2 and Tie-2 with an intradiabody reduces tumor growth and angiogenesis in vivo

机译：用双抗体表型敲除VEGF-R2和Tie-2可减少体内肿瘤的生长和血管生成

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

The endothelial cell receptor-tyrosine kinases, VEGF receptor 2 (VEGF-R2) and Tie-2, and their ligands, vascular endothelial growth factor (VEGF) and angiopoietins 1 and 2, respectively, play key roles in tumor angiogenesis. Several studies suggest that the VEGF receptor pathway and the Tie-2 pathway are independent and essential mediators of angiogenesis, leading to the hypothesis that simultaneous interference with both pathways should result in additive effects on tumor growth. In this study, a human melanoma xenograft model (M21) was used to analyze the effects of simultaneous intradiabody depletion of vascular endothelial growth receptor-R2 arid Tie-2 on tumor angiogenesis and tumor xenograft growth. The intradiabodies were expressed from recom-binant adenovirus delivered through subtumoral injection. Blockade of both VEGF-R2 and Tie-2 pathways simultaneously or the VEGF receptor pathway alone resulted in a significant inhibition of tumor growth and tumor angiogenesis (92.2% and 74.4%, respectively). In addition, immunohistochemical staining of intradiabody-treated tumors demonstrated a decreased number of tumor-associated blood vessels versus control treatment. Previous studies with intrabodies had demonstrated that the Tie-2 receptor pathway was essential for tumor growth. The simultaneous blockade of the VEGF and Tie-2 pathways resulted in effective inhibition of tumor growth and demonstrated the potential of simultaneous targeting of multiple pathways as a therapeutic strategy.
机译：内皮细胞受体酪氨酸激酶，VEGF受体2（VEGF-R2）和Tie-2，及其配体，血管内皮生长因子（VEGF）和血管生成素1和2在肿瘤血管生成中起关键作用。多项研究表明，VEGF受体途径和Tie-2途径是血管生成的独立且必不可少的介质，从而导致了这样一个假设，即同时干扰这两种途径应导致对肿瘤生长的累加效应。在这项研究中，人类黑素瘤异种移植模型（M21）用于分析血管内内皮生长受体R2和Tie-2的双抗体同时消耗对肿瘤血管生成和异种移植物生长的影响。腹膜内抗体由通过肿瘤下注射递送的重组腺病毒表达。同时阻断VEGF-R2和Tie-2途径或单独阻断VEGF受体途径导致对肿瘤生长和肿瘤血管生成的显着抑制（分别为92.2％和74.4％）。此外，与对照组相比，双抗体治疗的肿瘤的免疫组织化学染色显示肿瘤相关血管的数量减少。先前对体内抗体的研究表明，Tie-2受体途径对于肿瘤生长至关重要。 VEGF和Tie-2途径的同时阻断导致肿瘤生长的有效抑制，并证明了同时靶向多种途径作为治疗策略的潜力。

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