摘要目的 探讨靶向胶质瘤干细胞的新化疗策略及初步应用的安全性和有效性.方法 回顾性纳入2013年1月至2017年4月苏州大学附属第二医院神经外科收治的12例胶质母细胞瘤患者.以替莫唑胺化疗为基础,联合丙戊酸钠及尼卡地平的新化疗方案,治疗三磷酸腺苷结合盒转运体G2(ABCG2)阳性且O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)甲基化阴性的术后胶质母细胞瘤患者,以及规范化治疗后复发、经评估无再手术可能的胶质母细胞瘤患者.采用Karnofsky功能状态评分(KPS)、世界卫生组织(WHO)实体肿瘤客观疗效评定及患者生存期等指标评估疗效及临床应用的安全性.结果 12例患者的肿瘤组织免疫组织化学检测显示,肿瘤组织均不同程度地表达ABCG2、MGMT.甲基化特异性PCR结果显示,入组患者的MGMT甲基化阴性.MRI增强扫描评估客观疗效,完全缓解2例,部分缓解3例,疾病稳定2例,疾病进展5例(其中4例死亡);平均生存期为(18.4±10.9)个月,无治疗相关的严重不良事件.治疗后KPS评分的均值为(51.7±31.6)分.结论 替莫唑胺联合丙戊酸钠及尼卡地平靶向胶质瘤干细胞的化疗方案对耐药的胶质母细胞瘤有效,患者可耐受联合化疗方案的不良反应.

abstractsObjective To explore the safety and efficacy of new targeting chemotherapy strategy of glioma stem cells (GSCs) and its preliminary applications.Methods A total of 12 patients with glioblastoma (GBM) admitted to Department of Neurosurgery,the Second Affiliated Hospital of Soochow University from January 2013 to April 2017 were enrolled into this retrospective study.The patients underwent new chemotherapy if tumor analysis showed ABCG2 (+),MGMT methylation (-),or recurrence of GBM after standardized treatment.The temozolomide (TMZ),sodium valproate (VPA) and nicardipine combined drug regimen was implemented for 6 cycles.Evaluation of the efficacy with KPS (Karnofsky performance status scale),Response Evaluation Criteria in Solid Tumors of WHO and lifetime was carried out.Results Immunohistochemical examination of tumor tissues in the 12 patients showed that ABCG2 and MGMT were expressed at different levels.Methylation-specific PCR (polymerase chain reaction) results showed that the MGMT methylation was negative in the enrolled patients.Enhanced MR scan was used to evaluate treatment efficacy.Complete remission was achieved in 2 cases,partial remission in 3 cases,stable disease in 2 cases,and progressive disease in 5 cases (including 4 deaths).The average survival time was 18.4 ± 10.9 months.There were no treatment-related serious adverse events.The average KPS post treatment was 51.7 ± 31.6.Conclusion The new chemotherapy strategy of TMZ combined with VPA and nicardipine targeting GSCs has certain curative effect on chemo-resistant GBM and those drug regimens could be relatively well tolerated.