摘要

UNLABELLED:Primary liver cancer, hepatocellular carcinoma (HCC), is the fifth most common cancer and the third leading cancer killer in the world. There is no effective therapeutic option for most HCC patients. A new therapeutic strategy is essential. Granulin-epithelin precursor (GEP, also called progranulin, acrogranin, or PC-derived growth factor) was identified as a potential therapeutic target for HCC from our earlier genome-wide expression profiles. We aimed to conduct a detailed investigation with in vitro and animal experiments. We developed the anti-GEP monoclonal antibody (mAb), and examined its effect on hepatoma cells and normal liver cells in vitro. A nude mice model transplanted with human HCC was used to investigate if anti-GEP mAb can inhibit tumor growth in vivo. We demonstrated that anti-GEP mAb inhibited the growth of hepatoma cells but revealed no significant effect on normal liver cells. In the nude mice model transplanted with human HCC, anti-GEP mAb decreased the serum GEP level and inhibited the growth of established tumors in a dose-dependent manner. The anti-GEP mAb reduced tumor cell proliferation via the p44/42 MAPK and Akt pathways, and reduced tumor angiogenesis to deprive the nutrient supply with reduced microvessel density and tumor vascular endothelial growth factor level.
CONCLUSION:We have shown that anti-GEP antibody can inhibit HCC growth, providing evidence that GEP is a therapeutic target for HCC treatment.

译文

未标记: 原发性肝癌,即肝细胞癌 (HCC),是世界上第五大最常见的癌症和第三大癌症杀手。对于大多数肝癌患者没有有效的治疗选择。新的治疗策略至关重要。Granulin-epithelin 前体 (GEP,也称为 progranulin,acrogranin,或 PC 衍生的生长因子) 从我们早期的全基因组表达谱中被确定为肝癌的潜在治疗靶点。我们的目的是通过体外和动物实验进行详细的研究。我们开发了抗 GEP 单克隆抗体 (mAb),并在体外检测了其对肝癌细胞和正常肝细胞的影响。使用人肝癌移植的裸小鼠模型来研究抗 GEP mAb 是否能抑制体内肿瘤生长。我们证明抗 GEP mAb 抑制肝癌细胞的生长,但对正常肝细胞没有显著影响。在移植人肝癌的裸小鼠模型中,抗 GEP mAb 以剂量依赖的方式降低血清 GEP 水平并抑制已建立的肿瘤的生长。抗 GEP mAb 通过 p44/42 MAPK 和 Akt 通路减少肿瘤细胞增殖,减少肿瘤血管生成,剥夺营养供应,降低微血管密度和肿瘤血管内皮生长因子水平。
结论: 我们已经证明抗 GEP 抗体可以抑制肝癌的生长,为 GEP 是肝癌治疗的治疗靶点提供了证据。

Granulin

内分泌 蛋白 临床研究术语
概述  :  

颗粒蛋白是人类中由GRN基因编码的一种蛋白质。每个颗粒蛋白都从前体颗粒蛋白前体中切出,前体颗粒蛋白长593个氨基酸,蛋白含量为68.5kDa。尽管尚未确定前颗粒蛋白和颗粒蛋白的功能,但两种蛋白形式均与发育,炎症,细胞增殖和蛋白稳态有关。 分子结构 每个单独的颗粒蛋白结构域肽的长度为60个氨基酸。颗粒蛋白肽富含半胱氨酸,每个残基能够形成6个二硫键。二硫键形成一个中心杆状核心,将每个颗粒蛋白肽穿梭成堆叠的β-折叠结构。颗粒蛋白的结

granulin

释    义   n. [生化] 颗粒体蛋白

例    句   Granulin is a protein that in humans is encoded by the GRN gene.颗粒蛋白是人类中由GRN基因编码的蛋白质。

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