抗人膀胱癌/抗血管内皮生长因子双功能基因抗体对膀胱癌的生长抑制作用

Growth inhibiting effect on bladder carcinoma in vivo and localization of bispecific gene antibody(anti-human bladder carcinoma/anti-VEGF) by immune electron microscope

目的 对抗人膀胱癌 /抗血管内皮生长因子 (VEGF)双功能基因抗体进行免疫定位研究并观察其对人膀胱癌生长的抑制作用。 方法 采用免疫组化和免疫电镜前染色法对 6 0例膀胱癌患者的手术切除标本进行免疫定位研究 ;构建人膀胱癌裸鼠皮下移植瘤模型并注射双功能抗体 ,观察肿瘤生长情况 ,同时检测肿瘤微血管密度 (MVD)值及肿瘤细胞凋亡指数 (AI)。 结果 6 0例膀胱癌标本 ,抗原检测阳性 5 3例 ( 88.3% ) ;对照组 2 0例 ,抗原检测阳性 1例 ( 5 .0 % )。治疗后第 2周 ,实验组小鼠皮下种植肿瘤大小 ( 2 1.4 7± 6 .5 7)mm2 ,对照组 ( 5 9.85± 15 .4 3)mm2 ;实验组MVD 2 14 8± 10 9,对照组为 4 0 5 6± 36 7;实验组肿瘤细胞AI为 17.2 6 ,对照组为 7.0 9。组间比较 ,差异均有显著性意义。 结论 抗人膀胱癌 /抗VEGF双功能基因抗体对人膀胱癌有较好的靶向性 。

Objective To investigate the immune localization of bispecific gene antibody (anti human bladder carcinoma/anti VEGF),and to determine whether bispecific gene antibody can inhibit growth of human experimental bladder carcinoma. Methods Immunohistochemistry and immune electron microscope were used to study the immune localization in 60 samples of bladder cancer (experiment group),and 20 samples from BPH cases served as control group.Bispecific antibody was injected into the sites in nude mice,which was adjacent to the xenograft tumor of human bladder transitional cell carcinoma.The tumor size was measured at different times.The microvascular density(MVD) and apoptotic index(AI) in the tumors were examined. Results Of the 60 bladder cancer samples 53 (88.3%) were positive for antigen,while only 1 (5.0%) of the 20 in control group was positive.Two weeks after treatment,the tumor size of experiment group was ( 21.47 ±6.57)mm 2,while that of control group was (59.85±15.43)mm 2.MVD of experiment group was 2148±109,while that of control group was 4056±367.AI of experiment group was 17.26,while that of control group was 7.09.The differences between the 2 groups were significant (each P < 0.05 ). Conclusions Bispecific gene antibody can suppress xenograft tumor growth of human bladder transitional cell carcinoma by anti angiogenesis and apoptosis.