English  |  正體中文  |  简体中文  |  Items with full text/Total items : 17326/19632 (88%)
Visitors : 3469976      Online Users : 31
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/23159

    標題: A novel cancer therapy by skin delivery of indoleamine 2,3-dioxygenase siRNA
    作者: Meng-ChiYen
    Chi-Chen Lin
    Yi-Ling Chen
    Shih-Shien Huang
    Chih-Peng Chang
    Huan-Yao Lei
    Ming-Derg Lai
    貢獻者: 老人服務事業管理系
    日期: 2009-01
    上傳時間: 2010-10-28 16:05:39 (UTC+8)
    摘要: Purpose: Indoleamine 2,3-dioxygenase (IDO), an enzyme that degrades tryptophan, is a negative immune regulatorym olecule of dendritic cells. IDO-expressing dendritic cells suppress Tcell responses and maybe immunosuppressive in vivo.We hypothesized that silencing the IDO expression in skin dendritic cells in vivo could elicit antitumor activityi n tumor-draining lymph nodes.
    Experimental Design: The efficiencyo f IDO-specific small interfering RNA (siRNA) was evaluated in vitro and in vivo. The therapeutic effect was evaluated in MBT-2 murine bladder tumor model and CT-26 colon tumor models.
    Results: IDO expression was down-regulated in CD11c-positive lymphocytes after IDO siRNA treatment. In vivo skin administration of IDO siRNA inhibited tumor growth and prolonged survival in both tumor models. The number of infiltrated Tcells and neutrophils increased at tumor sites, which are correlated with therapeutic efficacy.TheTcells may be mainly responsible for the immunologic rejection because the effect was abolished byd epletion of CD8-positiveT cells.
    Adoptive transfer of CD11c-positive dendritic cells from vaccinated mice delayed tumor progression. The cancer therapeutic effect was reproduciblyobservedwith another IDO siRNA targeting at different site, suggesting the effect was not due to off-target effect. In a neu-overexpressing MBT-2 tumor model, IDO siRNA enhanced the therapeutic efficacyo f Her2/Neu DNA vaccine. Down-regulation of IDO2, an IDO homologue, with siRNA also generated antitumor immunity
    in vivo.
    Conclusions: Antitumor immunityca n be effectively elicited by physical deliveryof siRNAs targeting immunoregulatoryg enes in skin dendritic cells in vivo, as shown byI DO and IDO2 in this report.
    Appears in Collections:[老人服務事業管理系] 期刊論文

    Files in This Item:

    File Description SizeFormat

    All items in CNU IR are protected by copyright, with all rights reserved.

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