重组人p53 腺病毒注射液联合新辅助化疗治疗局部晚期子宫颈癌的临床观察

 目的　评价重组人p53腺病毒（rhAd-p53）注射液联合新辅助化疗治疗局部晚期子宫颈癌的疗效及安全性。方法　以收治的ⅠB2～ⅢA期局部晚期子宫颈癌患者40例为研究对象，采用简单随机化分组方法分为两组：单纯静脉PVB方案化疗组（PVB组）20例，rhAd基因治疗+静脉PVB方案化疗组（rhAd-p53+PVB组）20例。PVB组PVB方案化疗1个疗程；rhAd-p53+PVB组化疗方案相同，于化疗后第3天第1次注射rhAd-p53制剂1×1012 VP病毒颗粒，然后每3 d 1次，共3次。观察肿瘤体积的变化、患者的不良反应和肿瘤组织中血管内皮生长因子（VEGF）、p53蛋白和微血管密度（MVD）水平，对照组为未用放化疗及基因治疗的子宫颈癌患者。结果　所有患者化疗结束3周后评价疗效，PVB组用药后肿瘤缩小（11.42±2.78）cm2，rhAd-p53+PVB组肿瘤缩小（15.25±4.00）cm2，差异有统计学意义（P＜0.05）。PVB组有效率为75 %（15／20），rhAd-p53+ PVB组有效率为95 %（19／20）。VEGF、p53蛋白、MVD在对照组、PVB组、rhAd-p53+PVB组中的阳性表达率均呈逐渐降低的趋势，差异有统计学意义（P＜0.05）。基因治疗联合化疗未增加化疗患者的不良反应。结论　子宫颈癌患者瘤内注射rAd-p53制剂是有效的，rhAd-p53制剂是子宫颈癌的一种有潜力的基因治疗药物。

Clinical observation on the treatment of locally advanced cervical cancer by recombinant human adenovirus-p53 combined with neoadjuvant chemotherapy

Objective　To evaluate the efficacy and safety of recombinant adenovirus-p53 (rhAd-p53) combined with neoadjuvant chemotherapy in treatment of locally advanced cervical cancer. Methods　Forty patients with stage ⅠＢ2－ⅢA locally advanced cervical cancer were randomly divided into 2 groups, gene therapy + neoadjuvant chemotherapy group (rhAd-p53+PVB group, n = 20. They received one course of chemotherapy consisting of PVB. rhAd-p53 solution 1×1012 VP was injected intratumorally every three days for three circles since the 3rd day of PVB chemotherapy) and chemotherapy group (PVB group, n=20, the above course of chemotherapy was conducted). The volums of tumors was observed. Patients were monitored for adverse event. The expression of VEGF, p53 pertein and MVD in tumor tissue was detected by immunohistochemistry. Results　The evaluation was performed three weeks after the completion of chemotherapy. The PVB group response rate (CR+PR) was 75 %, while the effective rate was 95 % of the PVB combined with gene group. After using of the PVB chemotherapy, the tumor was shrunk by (11.42±2.78) cm2. However, the volums of tumor were significantly shrunk by (15.25±4.00) cm2 using the PVB combined with gene therapy, and P < 0.05. The positive expression rate of VEGF, p53 protein and MVD were reduced respectively in PVB group and rhAd-p53 + PVB group with statistic significance. There were no additional adverse events by recombinant adenovirus-p53 combined with neoadjuvant chemotherapy. Conclusion　A potentially gene therapeutic agent for cervical cancer treatment, intratumoral injection of rhAd-p53 is effective.