Interferon-α/β and anti-fibroblast growth factor receptor 1 monoclonal antibody suppress hepatic cancer cells in vitro and in vivo.
Interferon-α/β and anti-fibroblast growth factor receptor 1 monoclonal antibody suppress hepatic cancer cells in vitro and in vivo.
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DOI：
10.1371/journal.pone.0019618
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发表时间：
2011-05-09
期刊：
影响因子：
3.7
通讯作者：
Imai K
中科院分区：
文献类型：
--
作者：
Sasaki S;Ishida T;Toyota M;Ota A;Suzuki H;Takaoka A;Yasui H;Yamamoto H;Takagi H;Maeda M;Seito T;Tsujisaki M;Shinomura Y;Imai K
肝细胞癌 (HCC) 是最常见的原发性肝癌，总体上是第五大最常见的癌症，也是全球癌症死亡的第三大原因。目前，针对 HCC 的有效治疗选择有限；因此，这些患者的预后很差。我们本研究的目的是确定针对 HCC 的抗体治疗的新靶点。我们使用蛋白质印迹、流式细胞术和免疫细胞化学分析来研究干扰素-α/β 在几种人肝癌细胞系中对 FGFR1 表达的调节。此外，我们还在人类 HCC 的小鼠异种移植模型中测试了抗 FGFR1 单克隆抗体和干扰素-α/β 联合治疗的疗效。我们发现干扰素-α/β诱导人肝癌细胞系中FGFR1的表达，并且针对诱导的FGFR1的抗FGFR1单克隆抗体（mAb）可以在体外和体内有效抑制肝癌细胞的生长和存活。此外，干扰素-α、抗FGFR1 mAb和外周血单核细胞（PBMC）的组合在体外发挥了显着的抗肿瘤作用。我们的结果表明，抗 FGFR1 抗体和干扰素-α/β 的联合使用是治疗 HCC 的一种有前途的方法。
Hepatocellular carcinoma (HCC) is the most commonly occurring primary liver cancer and ranks as the fifth most frequently occurring cancer, overall, and the third leading cause of cancer deaths, worldwide. At present, effective therapeutic options available for HCC are limited; consequently, the prognosis for these patients is poor. Our aim in the present study was to identify a novel target for antibody therapy against HCC. We used Western blot and flow cytometric and immunocytochemical analyses to investigate the regulation of FGFR1 expression by interferon-α/β in several human hepatic cancer cell lines. In addition, we tested the efficacy of combined treatment with anti-FGFR1 monoclonal antibody and interferon-α/β in a murine xenograft model of human HCC. We found that interferon-α/β induces expression of FGFR1 in human HCC cell lines, and that an anti-FGFR1 monoclonal antibody (mAb) targeting of the induced FGFR1 can effectively inhibit growth and survival of HCC cells in vitro and in vivo. Moreover, the combination of interferon-α, anti-FGFR1 mAb and peripheral blood mononuclear cells (PBMCs) exerted a significant antitumor effect in vitro. Our results suggest that the combined use of an anti-FGFR1 antibody and interferon-α/β is a promising approach to the treatment of HCC.
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DOI：
10.1038/nri2744
发表时间：
2010-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
8
作者：
Hildebrandt, M. A. T.;Gu, J.;Wu, X.
通讯作者：
Wu, X.
影响因子：
56.9
作者：
GREINER, JW;GUADAGNI, F;SCHLOM, J
通讯作者：
SCHLOM, J
影响因子：
4.7
作者：
Hu, ZY;Evarts, RP;Thorgeirsson, SS
通讯作者：
Thorgeirsson, SS
影响因子：
158.5
作者：
Cunningham, D;Humblet, Y;Van Cutsem, E
通讯作者：
Van Cutsem, E