Antitumor effect of VEGF neutralizing antibody on gastrointestinal carcinoma.

将人结肠癌和胃癌各2例移植于裸鼠体内，北方印迹法检测VEGF mRNA的表达，ELISA法检测VEGF蛋白的表达。对于四种异种移植物中的每一种，抗体的施用不仅显著抑制原发性肿瘤生长，而且显著抑制肉眼可见的肝转移，尽管生长速率在4种癌症异种移植物中不同。各给药组的体重增量与对照组相当。未观察到抗体的毒性。这些结果表明，抗VEGF抗体可以有效地对抗多种癌症，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有良好的治疗效果，并探讨了中和抗体的作用机制。免疫组化结果显示，中和抗体抑制肿瘤血管生成，继而诱导肿瘤细胞凋亡，是其抑制肿瘤生长和转移的主要机制。

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.