Antitumor effect of VEGF neutralizing antibody on gastrointestinal carcinoma.

将4例人结肠癌和2例胃癌异种移植物原位移植到裸鼠体内，Northern blot分析结果显示，4例异种移植物均表达VEGF mRNA， ELISA检测结果显示，4例异种移植物均产生VEGF蛋白。移植后第10天起隔天腹腔注射VEGF神经化抗体或等量生理盐水。虽然4种肿瘤的生长速度不同，但在每一种异种移植物中，给药抗体不仅能显著抑制原发肿瘤的生长，还能显著抑制肉眼可见的肝转移。每个治疗组的体重增加与对照组相当。抗体无毒性反应。这些结果表明，抗VEGF抗体可以有效对抗多种癌症，VEGF可能是癌症治疗的有效靶点。中和抗体对十二指肠源性内分泌肿瘤也有良好的治疗效果。并对中和抗体的作用机制进行了探讨。免疫组化定量显示，中和抗体对血管生成的抑制作用紧随其后的是肿瘤细胞的凋亡，这是其抑制肿瘤生长和转移的主要原因。

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.