Immunohistochemistry Evaluation of the Effect in Vivo of Tumor Necrosis Factor (TNF)-alpha on Blood Vessel Density in Murine Fibrosarcoma.
Immunohistochemistry Evaluation of the Effect in Vivo of Tumor Necrosis Factor (TNF)-alpha on Blood Vessel Density in Murine Fibrosarcoma.
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DOI：
10.1080/13577140310001607275
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Lifschitz-Mercer, Beatriz
中科院分区：
文献类型：
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作者：
Eisenthal, Avi;Schwartz, Ignat;Issakov, Josephine;Klausner, Yossef;Misonzhnik, Faina;Lifschitz-Mercer, Beatriz
目的：血管生成对于肿瘤生长和转移是必不可少的，因此对能够抑制其的方法给予明显的重要性。 材料：C57 BL/6雌性小鼠，皮下（s.c.）使用MCA 205纤维肉瘤。 方法：10只小鼠随机分为两组，每组10只。一组腹腔注射（i. p.）用10 μg肿瘤坏死因子-α（TNF-α）和另一种（对照）用Hanks平衡盐溶液（HBSS）。每周至少两次监测肿瘤生长。通过使用血管内皮生长因子（VEGF）和因子8抗体对石蜡包埋的肿瘤组织切片进行染色来评估微血管中的内皮细胞的数量。p53基因的表达同样通过荧光染色进行评估。 结果如下：向荷瘤小鼠注射10 μg TNF-α，在注射后第3天，血管微血管中的内皮细胞数量减少了46%，同时这些细胞中的p53表达增加（37%）。与HBSS注射组相比，它还在细胞因子注射后17天开始抑制肿瘤生长。 讨论：TNF-α对小鼠皮下肉瘤的体内抗肿瘤作用。肿瘤的发生可能是由于细胞因子对肿瘤微血管的早期作用，可能是通过涉及p53基因的凋亡机制。
Purpose: Angiogenesis is essential for tumor growth and metastases, thus bestowing obvious importance upon methodologies which could enable its inhibition. Materials: C57BL/6 female mice bearing a subcutaneous (s.c.) MCA205 fibrosarcoma were used. Methods: Ten mice were divided equally into two groups. One group was injected intraperitoneally (i.p.) with 10 μg tumor necrosis factor-α (TNF-α and the other (controls) with Hanks balanced salt solution (HBSS). Tumor growth was monitored at least twice weekly. The number of endothelial cells in the blood microvessels was assessed by immunohistostaining on paraffin-embedded tumor tissue sections using vascular endothelial growth factor (VEGF) and Factor 8 antibodies. Expression of the p53 gene was similarly assessed by immunohistostaining. Results: Injection of 10 μg TNF-α into the tumor-bearing mice reduced the number of endothelial cells in the blood microvessels by 46% on day 3 post-injection which was accompanied by an increase (by 37%) in the expression of p53 in these cells. It also inhibited tumor growth compared to the HBSS-injected group starting at 17 days post-cytokine injection. Discussion: The antitumor in vivo effect exerted by TNF-α on established murine sarcoma s.c. tumors may be due to an earlier effect of the cytokine on the tumor's blood microvessels, probably through an apoptotic mechanism involving the p53 gene.