國家衛生研究院 NHRI:Item 3990099045/5769
English  |  正體中文  |  简体中文  |  全文笔数/总笔数 : 12145/12927 (94%)
造访人次 : 858535      在线人数 : 560
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜寻范围 查询小技巧：
  • 您可在西文检索词汇前后加上"双引号"，以获取较精准的检索结果
  • 若欲以作者姓名搜寻，建议至进阶搜寻限定作者字段，可获得较完整数据
    •  进阶搜寻
    主页 ‧ 登入 ‧ 上传 ‧ 说明 ‧ 关于NHRI ‧ 管理 到手机版


    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/5769


    题名: Loss of ASS1 expression in myxofibrosarcoma via promoter hypermethylation: Prognostic and potential therapeutic implications
    作者: Li, CF;Chen, LT;Wang, YH;Shiue, YL;Huang, HY
    贡献者: National Institute of Cancer Research
    摘要: Background: Argininosuccinate synthase 1 (ASS1), catalyzing the penultimate step of the arginine biosynthetic pathway, is commonly downregulated in human cancers. Taking advantage of this deregulated cellular metabolism, pegylated arginine deiminase (ADI-PEG20) has emerged as a novel target therapy that renders ASS1-deficient cancer cells particularly susceptible to arginine deprivation. We herein address ASS1 expression status and its downregulating mechanism, prognostic value, and therapeutic relevance in myxofibrosarcoma (MFS).Design: Immunoexpression of ASS1 protein was evaluated on tissue microarrays of primary MFS, yielding 90 cases with assessable results for correlation with clincopathological variables and patient survival. Methylation status of ASS1 gene promoter was examined by methylation-specific PCR (MSP). Compared with CCD966SK dermal fibroblasts, three MFS cell lines (OH931, NMFH-1, NMFH-2) were analyzed for protein and mRNA levels of ASS1 by immunoblotting and quantitative RT-PCR assays, respectively. XTT assay was performed to evaluate the susceptibility to ADI-PEG20 treatment in three MFS cell lines vs. CCD966SK fibroblasts. Results: ASS1 deficiency was identified in 40 cases and significantly associated with increment in FNCLCC grade (p=0.005), AJCC stage (p=0.007), and mitotic activity (p=0.030), with remarkable tumor necrosis (p=0.046), and univariately with inferior metastasis-free survival (MeFS, p=0.0052) and disease-specific survival (DSS, p=0.0035). In multivariate comparisons, ASS1 deficiency independently predicted both MeFS (p=0.0213, risk ratio [RR] =4.237) and DSS (p=0.0230, RR=10.416), along with higher FNCLCC grades. In the first batch subjected to MSP, hypermethylation of ASS1 promoter was identified in 6 of 10 cases and associated with loss of ASS1 immunoexpression (p=0.004). Compared to fibroblasts, the endogenous ASS1 mRNA expression was remarkably downregulated in all 3 MFS cell lines (0-, 0.004-, and 0.055-folds), concordant with the hypermethylation of their ASS1 promoters and deficiency in protein expression. In contrast to no susceptibility seen in CCD966SK fibroblasts, ADI-PEG20 at a low concentration (0.1ug/ml) could remarkably attenuate cell viability of 3 MFS cell lines. Conclusions: Epigenetic promoter methylation may lead to ASS1 deficiency in a significant subset of MFS, which not only confers tumor aggressiveness but also represents a novel target for arginine deprivation therapy.
    日期: 2011-02
    關聯: Modern Pathology. 2011 Feb;24(Suppl. 1):17A-18A.
    Link to: http://dx.doi.org/10.1038/modpathol.2011.14
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0893-3952&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000287282300060
    显示于类别:[陳立宗] 會議論文/會議摘要

    文件中的档案:

    档案 大小格式浏览次数
    ISI000287282300060.pdf802KbAdobe PDF433检视/开启


    在NHRI中所有的数据项都受到原著作权保护.

    TAIR相关文章

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