胸腺瘤PDC模型的建立及化疗药物筛选

Establishment of thymoma PDC model and screening of chemotherapeutics

目的建立胸腺瘤人源肿瘤细胞(patient-derived tumor cell,PDC)模型,模拟体内化疗药物活性,筛选胸腺瘤有效化疗方案以指导临床用药。方法获取新鲜的胸腺瘤组织标本,于24 h内消化解离,得到存活胸腺瘤细胞并置于培养基中培养,建立PDC模型并稳定传代,选取7种不同的含顺铂化疗方案进行药敏试验,以观察不同药物方案对胸腺瘤细胞的杀伤作用。结果共收集19例胸腺瘤组织标本,成功建立胸腺瘤PDC模型8例,建模成功率为42%(8/19)。其中A型胸腺瘤1例,AB型3例,B2型3例,胸腺癌1例;MasaokaⅡ期3例,Ⅲ期3例,Ⅳa期2例。选取7种含顺铂的药物方案分别对胸腺瘤PDC模型(n=6、7、8)进行药敏测试,白蛋白紫杉醇、长春瑞滨或表柔比星联合顺铂方案对胸腺瘤细胞的杀伤有效率较高,分别为6/8、6/7和5/6,且耐药率较低,分别为2/8、1/7和1/6;而多西他赛、紫杉醇、吉西他滨或培美曲塞联合顺铂方案对胸腺瘤细胞的杀伤有效率较低,分别为4/8、3/8、5/8和3/8,且耐药率较高,分别为4/8、5/8、3/8和5/8。对1例不可切除胸腺肿瘤患者进行胸腔镜活检术,留取部分组织成功建立PDC模型,该患者PDC模型的药敏测试结果为吉西他滨联合顺铂具有强杀伤作用,后进行吉西他滨联合顺铂化疗,化疗后胸腺瘤较前明显缩小。结论胸腺瘤PDC模型建立成功并用于模拟肿瘤体内药物活性的药敏测试。根据测试结果,对1例不可切除的胸腺瘤患者进行化疗并取得明显效果。胸腺瘤化疗推荐使用白蛋白紫杉醇、长春瑞滨或表柔比星联合顺铂方案。

Objective To establish the patient-derived tumor cells(PDC)model of thymoma to simulate the activity of chemotherapeutic drugs in vivo,and to screen effective chemotherapeutic schemes to guide clinical medication.Methods The fresh surgical specimens of thymoma were digested and dissociated within 24 hours,and viable thymic tumor cells were cultured in the culture medium.The PDC model was established and passaged stably.Seven different cisplatin-containing chemotherapy regimens were selected for drug sensitivity test to observe their killing effect on thymoma cells.Results Ninteen specimens of thymoma were collected and 8 cases of thymoma PDC model were successfully established,success rate was 42%(8/19).Models included 1 case of type A,3 cases of type AB,3 cases of type B2,and 1 case of thymic carcinoma.Based on Masaoka staging,there were 3 cases in stageⅡ,3 cases in stageⅢ,and 2 cases in stageⅣa.Among the 7 selected cisplatin-containing drug regimens,drug sensitivity test was carried out in 6,7 and 8 cases of thymoma PDC models,respectively.Albumin paclitaxel,vinorelbine or epirubicin combined with cisplatin regimens had higher killing efficacies on thymoma cells,which were 6/8,6/7 and 5/6 respectively.The drug resistance rates were 2/8,1/7 and 1/6 respectively;while docetaxel,paclitaxel,gemcitabine or pemetrexed combined with cisplatin regimens have lower killing efficacies,which were 4/8,3/8,5/8 and 3/8 respectively.The drug resistance rates were higher,4/8,5/8,3/8 and 5/8 respectively.A thoracoscopic biopsy was performed on a patient with unresectable thymic tumor,and part of the tissue was collected to successfully establish a PDC model.The drug sensitivity test result of the patient’s PDC model showed that gemcitabine combined with cisplatin has a strong killing effect,therefore this treatment plan was performed and the tumor size was significantly reduced after chemotherapy.Conclusion The thymoma PDC models was successfully established to simulate the drug activity in the tumor via drug sensitivity test.According to test results,we performed chemotherapy on a patient with unresectable thymoma and achieved significant effects.Therefore we recommend to use albumin paclitaxel,vinorelbine or epirubicin combined with cisplatin for thymoma chemotherapy.