國家衛生研究院 NHRI:Item 3990099045/2082
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    题名: Pathogenesis and mechanism of disease progression from hemophagocytic lymphohistiocytosis to Epstein-Barr virus-associated T-cell lymphoma: Nuclear factor-kappa B pathway as a potential therapeutic target
    作者: Chuang, HC;Lay, JD;Hsieh, WC;Su, IJ
    贡献者: Division of Clinical Research;National Institute of Cancer Research
    摘要: Epstein-Barr virus (EBV) can infect T lymphocytes and manifests as hemophagocytic lymphohistiocytosis (HLH), a distinct entity of hemophagocytic syndrome (HPS) characterized by fever, hepatosplenomegaly, cytopenia, hypercytokinemia, and systemic macrophage activation with hemophagocytosis. In a substantial percentage of HLH patients, the disease may relapse or progress to T-cell lymphoma in months to years. In the present review, the authors summarize the previous studies on the pathogenesis of HLH and the potential mechanism for the progression of disease from HLH to T-cell lymphoma. The infection of T cells by EBV could activate T cells to secrete proinflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), which subsequently activate macrophages. EBV latent membrane protein-1 (LMP-1) is the viral product responsible for the activation of the TNF receptor (TNFR) associated factors/nuclear factor-kappa B (NF-kappa B)/ERK pathway to enhance cytokine secretion mediated through the suppression of the SAP/SH2D1A gene. The activation of NF-kappa B will confer resistance to TNF-alpha-induced apoptosis on EBV-infected T cells through the down-regulation of TNFR-1. Consistent with in vitro observations, EBV-associated T or natural killer/T-cell lymphoma showed constitutive activation of NF-kappa B, explaining its drug resistance, hypercytokinemia, and poor prognosis. Therefore, similar to other inflammation-associated cancers, HLH provides a unique model to study the mechanism of disease progression from a benign virus-infected disorder (HLH) to T-cell lymphoma. Inhibition of the NF-kappa B signal pathway should provide a potential target for the treatment of HLH and EBV-associated T-cell lymphoma.
    关键词: Oncology
    日期: 2007-09
    關聯: Cancer Science. 2007 Sep;98(9):1281-1287.
    Link to: http://dx.doi.org/10.1111/j.1349-7006.2007.00549.x
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1347-9032&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000248968500001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34547842304
    显示于类别:[蘇益仁(2002-2015)] 期刊論文
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