Antitumor effect of VEGF neutralizing antibody on gastrointestinal carcinoma.

将4只人癌、2只人结肠癌和2只胃癌裸鼠原位移植到裸鼠体内，Northern印迹分析证实4只裸鼠移植瘤中均有血管内皮生长因子基因的表达，ELISA法检测均可表达血管内皮生长因子蛋白。对于四种异种移植瘤中的每一种，抗体的注射不仅显著地抑制了原发肿瘤的生长，而且显著地抑制了宏观上的肝转移，尽管4种异种移植瘤的生长速度不同。各治疗组体质量增加与对照组相当。未观察到该抗体的毒性。这些结果表明，抗血管内皮生长因子抗体可以有效地对抗多种癌症，并且血管内皮生长因子可能是癌症治疗的有效靶点。中和抗体对十二指肠来源的内分泌肿瘤也有良好的治疗作用，并对其作用机制进行了探讨。免疫组织化学定量显示中和抗体抑制血管生成，继而抑制肿瘤细胞的凋亡，主要是通过抑制肿瘤生长和转移来实现的。

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.