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糖基化软体动物血蓝蛋白通过 Guerin 腹水瘤的抗肿瘤活性。

Antitumor activity of glycosylated molluscan hemocyanins via Guerin ascites tumor.

机构信息

Institute of Organic Chemistry, Bulgarian Academy of Sciences, G. Bonchev 9, Sofia 1113, Bulgaria. pda54@ abv.bg

出版信息

Immunol Invest. 2011;40(2):130-49. doi: 10.3109/08820139.2010.513408. Epub 2010 Oct 5.

Abstract

As observed in most molluscan hemocyanins, high-mannose type glycans were identified in hemocyanins from Rapana venosa (RvH), Helix lucorum (HlH) and keyhole limpet (Megatura crenulata). In addition, a glycan with a branching structure containing xylose, fucose and terminal methyl hexose was identified in β-HlH. We have examined the immuno-adjuvant properties of hemocyanins, their derivatives and conjugates associated with the cell mediated immunity in experimental tumor-bearing animals with ascites tumor of Guerin. After immunization of the animals with the experimental vaccine preparations, the highest values of splenic lymphocytes were observed in groups immunized with the conjugates RvH-TAg, β-HlH-TAg and KLH-TAg (42.3%; 40.8% and 40.58%, respectively) than with the native hemocyanins (36.5%; 35.1% and 32.4%, respectively). The immunization of rats with the hemocyanins β-HlH, RvH and KLH and their conjugates, prolonged the median survival time of tumor-bearing animals compared with non-immunized animals (39, 33, 31 and 7 days, respectively). Both hemocyanins β-HlH and RvH activate the immune system of the experimental animals and therefore could be a good alternative for KLH. For this reason they could be included into the composition of non-specific anti-tumor vaccines to enhance their effectiveness.

摘要

与大多数软体动物血蓝蛋白一样,在泥螺血蓝蛋白(RvH)、中华园田螺血蓝蛋白(HlH)和石鳖血蓝蛋白(Megatura crenulata)中鉴定出高甘露糖型聚糖。此外,在β-HlH 中还鉴定出一种具有分支结构的聚糖,其含有木糖、岩藻糖和末端甲基己糖。我们已经研究了血蓝蛋白、其衍生物及其与实验性荷瘤动物中细胞介导免疫相关的缀合物的免疫佐剂特性,这些动物患有 Guerin 腹水瘤。用实验疫苗制剂免疫动物后,用缀合物 RvH-TAg、β-HlH-TAg 和 KLH-TAg 免疫的动物脾淋巴细胞最高(分别为 42.3%、40.8%和 40.58%)高于天然血蓝蛋白(分别为 36.5%、35.1%和 32.4%)。用β-HlH、RvH 和 KLH 及其缀合物免疫大鼠,与未免疫动物相比,延长了荷瘤动物的中位生存时间(分别为 39、33、31 和 7 天)。两种血蓝蛋白β-HlH 和 RvH 均能激活实验动物的免疫系统,因此可以替代 KLH。因此,它们可以被包含在非特异性抗肿瘤疫苗的成分中,以增强其有效性。

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