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以重组ag43/FGFR1嵌合蛋白作为模型抗原的抗肿瘤血管生成

Anti-tumor angiogenesis with a recombinant ag43/FGFR1 chimeric protein as a model antigen.

作者信息

Zheng Shaoping, Weng Zhihong, Zheng Shaojiang, Guo Junli, Huang Fengying, Xie Mingxing

机构信息

Department of Ultrasonography, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2010 Feb;30(1):25-8. doi: 10.1007/s11596-010-0105-5. Epub 2010 Feb 14.

Abstract

In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein (AF) vaccine in a mouse H22 hepatoma model, tumor volume and survival rate of the mice were studied at a 3-day interval. Microvessel density (MVD) was detected by immunohistochemistry. The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining, and anti-FGFR1 antibody-producing B cells (APBCs) were tested by enzyme-linked immunospot (ELISPOT) assay. Compared with the three control groups, the tumor volume was significantly decreased and the survival time was significantly prolonged in AF-immunized group (P<0.05). The number of APBCs in AF-immunized mice (129.6+/-10.9) was more than in controls [6.2+/-1.1 (FGFR1), 6.0+/-1.2 (Ag43) and 5.2+/-1.4 (NS), P<0.01]. Moreover, the endothelial deposition of autoantibodies was found in tumor tissues from AF-immunized mice, but not in control groups. MVD in AF-immunized group was significantly lower than in FGFR1-immunized group, Ag43-immunized group and NS group (10.3+/-3.1 vs 39.4+/-8.6 vs 42.3+/-9.8 and 43.6+/-10.6, P<0.01). These findings demonstrated that the AF protein vaccine effectively inhibited tumor angiogenesis and growth via production of autoantibodies against self-FGFR1.

摘要

为了在小鼠H22肝癌模型中研究重组Ag43/FGFR1嵌合蛋白(AF)疫苗的抗肿瘤血管生成活性,每隔3天研究小鼠的肿瘤体积和存活率。通过免疫组织化学检测微血管密度(MVD)。通过免疫荧光染色检查肿瘤组织内自身抗体的内皮沉积,并通过酶联免疫斑点(ELISPOT)试验检测产生抗FGFR1抗体的B细胞(APBCs)。与三个对照组相比,AF免疫组的肿瘤体积显著减小,生存时间显著延长(P<0.05)。AF免疫小鼠的APBCs数量(129.6±10.9)多于对照组[6.2±1.1(FGFR1)、6.0±1.2(Ag43)和5.2±1.4(NS),P<0.01]。此外,在AF免疫小鼠的肿瘤组织中发现了自身抗体的内皮沉积,而对照组中未发现。AF免疫组的MVD显著低于FGFR1免疫组、Ag43免疫组和NS组(10.3±3.1对39.4±8.6对42.3±9.8和43.6±10.6,P<0.01)。这些发现表明,AF蛋白疫苗通过产生针对自身FGFR1的自身抗体有效抑制肿瘤血管生成和生长。

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