國家衛生研究院 NHRI:Item 3990099045/10125
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    题名: Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells
    作者: Chan, TS;Hsu, CC;Pai, VC;Liao, WY;Huang, SS;Tan, KT;Yen, CJ;Hsu, SC;Chen, WY;Shan, YS;Li, CR;Lee, MT;Jiang, KY;Chu, JM;Lien, GS;Weaver, VM;Tsai, KK
    贡献者: National Institute of Cancer Research;Division of Vaccine Research and Development
    摘要: Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-kappaB activity in carcinoma-associated fibroblasts. This induction results in the expression and secretion of ELR motif-positive (ELR+) chemokines, which signal through CXCR-2 on carcinoma cells to trigger their phenotypic conversion into TICs and promote their invasive behaviors, leading to paradoxical tumor aggression after therapy. In contrast, the same overall dose administered as a low-dose metronomic chemotherapy regimen largely prevented therapy-induced stromal ELR+ chemokine paracrine signaling, thus enhancing treatment response and extending survival of mice carrying desmoplastic cancers. These experiments illustrate the importance of stroma in cancer therapy and how its impact on treatment resistance could be tempered by altering the dosing schedule of systemic chemotherapy.
    日期: 2016-12
    關聯: Journal of Experimental Medicine. 2016 Dec;213 (13):2967-2988.
    Link to: http://dx.doi.org/10.1084/jem.20151665
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1007&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000391122900012
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85008433322
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