...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cancer research: The official organ of the American Association for Cancer Research, Inc >Coactivated platelet-derived growth factor receptor {alpha} and epidermal growth factor receptor are potential therapeutic targets in intimal sarcoma.
【24h】

Coactivated platelet-derived growth factor receptor {alpha} and epidermal growth factor receptor are potential therapeutic targets in intimal sarcoma.

机译：共激活的血小板衍生的生长因子受体和表皮生长因子受体是内膜肉瘤的潜在治疗靶标。

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

Intimal sarcoma (IS) is a rare, malignant, and aggressive tumor that shows a relentless course with a concomitant low survival rate and for which no effective treatment is available. In this study, 21 cases of large arterial blood vessel IS were analyzed by immunohistochemistry and fluorescence in situ hybridization and selectively by karyotyping, array comparative genomic hybridization, sequencing, phospho-kinase antibody arrays, and Western immunoblotting in search for novel diagnostic markers and potential molecular therapeutic targets. Ex vivo immunoassays were applied to test the sensitivity of IS primary tumor cells to the receptor tyrosine kinase (RTK) inhibitors imatinib and dasatinib. We showed that amplification of platelet-derived growth factor receptor alpha (PDGFRA) is a common finding in IS, which should be considered as a molecular hallmark of this entity. This amplification is consistently associated with PDGFRA activation. Furthermore, the tumors reveal persistent activation of the epidermal growth factor receptor (EGFR), concurrent to PDGFRA activation. Activated PDGFRA and EGFR frequently coexist with amplification and overexpression of the MDM2 oncogene. Ex vivo immunoassays on primary IS cells from one case showed the potency of dasatinib to inhibit PDGFRA and downstream signaling pathways. Our findings provide a rationale for investigating therapies that target PDGFRA, EGFR, or MDM2 in IS. Given the clonal heterogeneity of this tumor type and the potential cross-talk between the PDGFRA and EGFR signaling pathways, targeting multiple RTKs and aberrant downstream effectors might be required to improve the therapeutic outcome for patients with this disease.
机译：内膜肉瘤（IS）是一种罕见，恶性和侵袭性肿瘤，显示出无情的病程，伴随着较低的存活率，并且尚无有效的治疗方法。在这项研究中，通过免疫组织化学和荧光原位杂交并通过核型分析，阵列比较基因组杂交，测序，磷酸激酶抗体阵列和Western免疫印迹来分析21例大动脉血管IS，以寻找新的诊断标志物和潜力分子治疗靶标。应用离体免疫测定来测试IS原发性肿瘤细胞对受体酪氨酸激酶（RTK）抑制剂伊马替尼和达沙替尼的敏感性。我们表明，血小板衍生的生长因子受体α（PDGFRA）的扩增是IS中的常见发现，应将其视为该实体的分子标志。该扩增始终与PDGFRA激活相关。此外，肿瘤揭示了表皮生长因子受体（EGFR）的持续激活，同时又激活了PDGFRA。活化的PDGFRA和EGFR通常与MDM2癌基因的扩增和过表达共存。一例原发性IS细胞的离体免疫测定显示达沙替尼抑制PDGFRA和下游信号通路的效力。我们的发现为研究针对IS中PDGFRA，EGFR或MDM2的疗法提供了理论依据。考虑到这种肿瘤类型的克隆异质性以及PDGFRA和EGFR信号通路之间潜在的相互影响，可能需要靶向多个RTK和异常下游效应子来改善该病患者的治疗效果。

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