國家衛生研究院 NHRI:Item 3990099045/8885
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 861738      線上人數 : 733
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋
    主頁 ‧ 登入 ‧ 上傳 ‧ 說明 ‧ 關於NHRI ‧ 管理 到手機版


    請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/8885


    題名: Inhibition of pancreatic cancer by a kinase inhibitor by targeting mutiple signaling pathways
    作者: Hung, WC;Chen, HM;Tsai, CH
    貢獻者: National Institute of Cancer Research
    摘要: Introduction: Foretinib is a multiple kinase inhibitor undergoing different phase clinical trials and exhibits potent inhibitory effect on hepatocyte growth factor (HGF) receptor c-MET and vascular endothelialgrowth factor receptor-2 (VEGFR-2) and TIE-2. Aims: In this study, we investigated the effect of Foretinib on lymphatic endothelial cells (LECs) in vitro and lymphangiogenesis in vivo. Materials & methods: MTT assay was used to evaluate cell proliferation. Westrn blotting was done to study apoptotic cell death and the activation status of different signaling pathways. Xenograft and orthotopic animal models were used to investigate the anti-cancer effect of Foretinib on pancreatic cancer. Immunohistochemical satining was performed to assess the parameters of cell proliferation, angiogenesis and lymphangiogenesis. Results: Foretinib inhibited basal- and HGF-induced c-MET activity at low concentrations. However, Foretinib only suppressed the proliferation of pancreatic cancer cells at high concentration reflecting the intrinsic chemoresistance of pancreatic cancer cells. Foretinib inhibited VEGFA, VEGF-C and Angiopoetin-2 (ANG-2)-stimulated tube formation and sprouting of LECs and triggered apoptotic cell death of LECs. At molecular level, Foretinib attenuated growth factor-induced VEGFR-2, VEGFR-3 and TIE-2 activation in LECs. In xenograft animal study, Foretinib suppressed tumor growth and reduced proliferation, angiogenesis and lymphangiogenesis. In orthotopic animal study, Foretinib inhibited angiogenesis and lymphangiogenesis more significantly and exhibited low detrimental effect on experimental animals. Conclusion: Our results suggested that Foretinib simultaneously targets cancer cells and LECs to inhibit pancreatic tumor growth and demonstrated for the first time that Foretinib suppresses angiogenesis and lymphangiogenesis by blocking multiple signaling.
    日期: 2015-06
    關聯: Pancreatology. 2015 Jun;15(3, Suppl.):S35-S36.
    Link to: http://dx.doi.org/10.1016/j.pan.2015.05.154
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1424-3903&DestApp=IC2JCR
    顯示於類別:[洪文俊] 會議論文/會議摘要

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    SDO1424390315002513.pdf48KbAdobe PDF551檢視/開啟


    在NHRI中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋