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Inhibition of inflammatory angiogenesis by distant subcutaneous tumor in mice

机译:小鼠远处皮下肿瘤对炎性血管生成的抑制作用

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We investigated angiogenesis, inflammatory cells accumulation and endogenous production of cytokines in sponge implants of tumor-bearing mice. Seven days after inoculation of Ehrlich tumor cells (2.5 x 10(6)), sponge discs were implanted subcutaneously in the dorsa of mice to induce the formation of fibrovascular tissue. The implants of tumor-bearing and non tumor-bearing animals were assessed for neovascularization and leukocyte accumulation, together with levels of relevant cytokines, vascular endothelial growth factor VEGF), tumor necrosis factor alpha (TNF-alpha), CXCL1-3/KC and CCL2/JE. In the implants of tumor-bearing animals angiogenesis (assessed by hemoglobin content and VEGF levels in the implants) and leukocyte accumulation (assessed by myeloperoxidase -MPO- and N- acetylglucosaminidase-NAG-enzyme activities) were all significantly less than those in the implants of non tumor-bearing animals. Although the chemokine CXCL1-3/ KC was lower in the implants of tumor-bearing animals, the chemokine CCL2/JE was increased in this group. The production of TNF-alpha in the implants was not modified by the presence of the subcutaneous tumor. The combination of the methodologies used in this study has provided a novel approach to investigate the interaction between two distinct proliferating tissues that share common features (angiogenesis, cell recruitment, inflammation) and has shown that the predominant inhibitory effect of a tumor mass over repair process is associated with altered cytokine production. (C) 2004 Elsevier Inc. All rights reserved.
机译:我们调查了荷瘤小鼠海绵植入物中的血管生成,炎性细胞积累和细胞因子的内源性产生。接种Ehrlich肿瘤细胞(2.5 x 10(6))7天后,将海绵圆盘皮下植入小鼠的背部,以诱导纤维血管组织的形成。评估了荷瘤和非荷瘤动物的植入物的新血管形成和白细胞积累,以及相关细胞因子,血管内皮生长因子(VEGF),肿瘤坏死因子α(TNF-alpha),CXCL1-3 / KC和CCL2 / JE。在荷瘤动物的植入物中,血管生成(通过植入物中的血红蛋白含量和VEGF水平评估)和白细胞积累(通过髓过氧化物酶-MPO-和N-乙酰氨基葡糖苷酶-NAG-酶活性评估)均显着低于植入物中的血管生成。非荷瘤动物尽管在荷瘤动物的植入物中趋化因子CXCL1-3 / KC较低,但该组趋化因子CCL2 / JE升高。皮下肿瘤的存在并未改变植入物中TNF-α的产生。在这项研究中使用的方法的组合提供了一种新颖的方法来研究具有共同特征(血管生成,细胞募集,炎症)的两个不同的增生组织之间的相互作用,并显示出肿瘤块对修复过程的主要抑制作用与细胞因子产生改变有关。 (C)2004 Elsevier Inc.保留所有权利。

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