Chen Jing, Wang Zheng-rong, Li Hao, Wei Yu-quan, Wang Wei, Zhu Bin
Biomedical Engineering, West China of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Sep;37(5):708-11, 716.
To evaluate whether the sustained expression by adenovirus-mediated gene (sFLK-1) transfer can enhance the treatment efficacy of gamma knife radiosurgery.
The mouse sFLK-1 gene was cloned to construct the recombinant adenovirus. The gliomata growing in BALB/c female nude mice with an initial mean volume of (109.3 +/- 20.5) mm3 were treated with gamma knife alone (13 Gy on day 12), sFLK-1 adenovirus alone (1 x 10(9) plaque-forming units, PFU was given to two mouse tail vein by injections, 7 and 14 days), gamma knife associated with sFLK-1 adenovirus or control adenovirus (1 x 10(9) PFU was given to two mouse tail vein by injections, 13 and 17 days). After the completion of therapy, the tumor size was recorded. The microvessel density (MVD) and tumor apoptosis were evaluated by immunohistochemical means.
As comparing with three other control groups, the combination treatment group with sFLK-1 gene therapy and gamma knife not only significantly reduced tumor volume and prolonged the life span of tumor burden mice as well. In addition, the average tumor weights were lower in sFLK-1 combined with gamma knife group than in any other control group. Immunohistochemical analysis of glioma demonstrated a decreased MVD and a high apoptosis cell rate in sFLK-1 combined with gamma knif group.
The antitumor effect of gamma knife can be potentiated by sFLK-1 gene therapy. Thus the combination of sFLK-1 gene therapy and gamma knife results an additive effect of antitumor. The observation may provide an important strategy for treatment cancer metastasis.
评估腺病毒介导的基因（sFLK-1）持续表达是否能提高伽玛刀放射外科治疗的疗效。
克隆小鼠sFLK-1基因以构建重组腺病毒。对初始平均体积为（109.3±20.5）mm³的BALB/c雌性裸鼠体内生长的胶质瘤，分别进行单独伽玛刀治疗（第12天给予13 Gy）、单独sFLK-1腺病毒治疗（1×10⁹空斑形成单位，通过尾静脉注射分两次给予小鼠，分别在第7天和第14天）、伽玛刀联合sFLK-1腺病毒治疗或联合对照腺病毒治疗（1×10⁹空斑形成单位，通过尾静脉注射分两次给予小鼠，分别在第13天和第17天）。治疗结束后，记录肿瘤大小。通过免疫组化方法评估微血管密度（MVD）和肿瘤凋亡情况。
与其他三个对照组相比，sFLK-1基因治疗联合伽玛刀的联合治疗组不仅显著减小了肿瘤体积，还延长了荷瘤小鼠的生存期。此外，sFLK-1联合伽玛刀组的平均肿瘤重量低于其他任何对照组。胶质瘤的免疫组化分析显示，sFLK-1联合伽玛刀组的MVD降低，凋亡细胞率较高。
sFLK-1基因治疗可增强伽玛刀的抗肿瘤作用。因此，sFLK-1基因治疗与伽玛刀联合可产生抗肿瘤的叠加效应。该观察结果可能为癌症转移的治疗提供重要策略。
