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Antitumor effect of VEGF neutralizing antibody on gastrointestinal carcinoma.

VEGF中和抗体对胃肠道癌的抗肿瘤作用。

基本信息

批准号：
09671295
负责人：
KONNO Hiroyuki
金额：
$ 1.98万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671295/
关键词：
VEGF Human Gastrointestinal Carcinoma Metastasis Neuralizing antibody

项目摘要

Four human carcinoma xenografts, two human colon carcinomas and two gastric carcinomas, were transplanted orthotopically into nude mice : Northern blot analysis demonstrated the expression of VEGF mRNA in all 4 xenografts and VEGF protein was also demonstrated to be produced from all of them by ELISA.The VEGF neurtralizing antibody or same volume of saline was administered intraperitoneally on alternative days from day 10 after transplantation. With each of the four xenografts, administration of antibody significantly inhibited not only primary tumor growth but also macroscopic liver metastasis, although the growth rate varied among the 4 cancer xenografts. Body weight gain in each treated group was comparable with that in the control group. No toxicity of the antibody was observed. These results suggest that an anti-VEGF antibody can be effective against a wide variety of cancers and that VEGF may be a potent target for cancer therapy. The excellent therapeutic effect of netralizing antibody was also demonstrated against endocrine neoplasm derived from duodenum.The mechanism of the effect of neutralizing antibody was also investigated. The inhibition of angiogenesis by neutralizing antibody which was shown quntitatively by immunohistochemistry followed by the apoptosis of tumor cells was mainly contributed to its inhibitory effect on tumor growth and metastasis.

将四个人类癌异种移植物（两个人类结肠癌和两个胃癌）原位移植到裸鼠中：Northern印迹分析显示所有4个异种移植物中都有VEGF mRNA的表达，并且ELISA也证明它们都产生VEGF蛋白。施用VEGF中和抗体或等体积的盐水从移植后第10天起每隔几天腹腔注射。对于四个异种移植物中的每一个，抗体的施用不仅显着抑制原发性肿瘤生长，而且还显着抑制肉眼可见的肝转移，尽管4个癌症异种移植物的生长速度各不相同。每个治疗组的体重增加与对照组相当。没有观察到抗体的毒性。这些结果表明抗 VEGF 抗体可以有效对抗多种癌症，并且 VEGF 可能是癌症治疗的有效靶标。中和抗体对十二指肠内分泌肿瘤也具有良好的治疗效果，并对其作用机制进行了研究。免疫组化定量显示中和抗体抑制血管生成进而导致肿瘤细胞凋亡，这主要是其抑制肿瘤生长和转移的作用。