体外药敏试验及化疗耐药和敏感分子特征指导的恶性脑胶质瘤临床个体化化疗研究  

Individualized chemotherapy based on in vitro chemotherapy sensitivity and resistance assays and molecular characteristics in patients with malignant gliomas.

作　　者：张俊平[1,2] 魏大年[1] 史泓浏[1] 岳伟英[1] 于春江[3] 陈忠平[1] 

机构地区：[1]中山大学肿瘤防治中心神经外科/神经肿瘤科,广州510060 [2]北京三博脑科医院神经肿瘤科 [3]北京三博脑科医院神外二病区

出　　处：《中国神经精神疾病杂志》2009年第8期476-480,共5页Chinese Journal of Nervous and Mental Diseases

摘　　要：目的探讨恶性脑胶质瘤临床个体化化疗的策略。方法恶性脑胶质瘤新鲜肿瘤组织用MTT法进行化疗药物体外药敏试验;用免疫组织化学方法检测肿瘤组织O6-甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNA methyltransferase,MGMT)蛋白表达,据MGMT测定结果选择化疗方案;经手术后病理确诊的MGMT表达阳性的恶性脑胶质瘤患者,接受3组化疗方案化疗:含亚硝脲类药物化疗组,含替莫唑胺化疗组,不含亚硝脲和替莫唑胺化疗组。评价3组化疗方案的近期疗效和不良反应;用FISH方法检测间变性少突胶质细胞瘤组织1p/19q LOH,据检测结果选择化、放疗模式。结果体外药敏试验阴性符合率较高,为14/15。据MGMT表达情况选择化疗方案的客观有效率为34%,疾病控制率为72%。MGMT阳性表达的恶性脑胶质瘤,含亚硝脲类化疗组、含替莫唑胺化疗组、不含亚硝脲和替莫唑胺化疗组的客观有效率及疾病控制率分别为:0和2/11、3/18和11/18、7/22和17/22。不含亚硝脲和TMZ化疗组的客观有效率和疾病控制率均较含亚硝脲化疗组高,有统计学差异(P<0.05)。结论据体外药敏试验及MGMT测定选择化疗方案,可提高近期疗效;MGMT阳性表达的恶性胶质瘤病人,不含亚硝脲和替莫唑胺化疗方案有较好疗效;但含替莫唑胺化疗方案也可应用。Objective To explore the methods and strategies of individualized chemotherapy based on in vitro chemotherapy sensitivity and resistance assays, MGMT protein expression and l p/19q loss of heterozygosity （LOH） in patients with malignant glioma. Methods The response of malignant brain tumor cells to seven chemotherapeutic agents in vitro was determined using MTT assay, and the results were used as a guide for chemotherapy protocol for individual patient. MGMT protein expression in gliomas was examined by immunohistochemistry. The chemotherapeutic regimen for patients with MGMT positive tumors did not include nitrosourea or temozolomide whereas chemotherapeutic regimen for patients with MGMT negative tumors included nitrosourea or temozolomide. The patients with MGMT positive gliomas were further divided into three groups based on their chemotherapeutic regimen： nitrosourea group （ 11 cases） ,temozolomide group, （ 18 cases） and no alkylating agent group （22 cases）. The 1 p and 19q status in anaplastic oligodendrogliomas （AO） was determined by FISH analysis on paraffin embedded archival material using locus specific probes. The selection of radiotherapy and/or chemotherapy for treatment was determined according to lp and 19q status. Results The positive predictive value of chemotherapy sensitivity and resistance assays was 10/14, and negative predictive value was 14/15. The response to chemotherapy （ based on MGMT expression） was satisfactory. Objective response rate （ CR ＋ PR） was 34%, and response plus stable disease rate （ CR ＋ PR ＋ SD） was 72% ; In MGMT position glioma patients, the objective response rate and dis-ease control rate in nitrosourea group, temozolomide group, and no alkylating agent group were 0, 2/11, 3/18 and 11/18, 7/22, 17/22, respectively （P 〈 0.05）. Conclusions Chemotherapy sensitivity and resistance assays as well as MGMT expression evaluation can be used for individualized chemotherapy of glioma patients. Regimen containing no alkylating agent g

关 键 词：恶性脑胶质瘤 体外药敏试验 MGMT 1p/19q LOH 化学治疗 

分 类 号：R739.4[医药卫生—肿瘤] R730.53[医药卫生—临床医学]