恶性实体瘤化疗患儿ATP生物荧光肿瘤体外药敏检测研究

目的 探讨ATP生物荧光肿瘤体外药敏检测技术(ATP-TCA)指导恶性实体瘤患儿临床化疗的意义,为恶性肿瘤患儿的个性化治疗提供参考.方法 应用ATP-TCA检测50例恶性实体瘤患儿(15例恶性神经源性肿瘤、8例恶性生殖细胞肿瘤、10例肾母细胞瘤、10例肝母细胞瘤、6例横纹肌肉瘤、1例肾上腺皮质癌)标本的8种单独用药和8种联合用药方案的敏感性.结果 (1)50例儿童恶性实体瘤标本中,46例结果具有可评价性,ATP-TCA总可评价率为92%(46/50).(2)不同个体的肿瘤在药物敏感方面具有明显的异质性.(3)各种恶性实体瘤患儿体外敏感率较高的药物组合如下:恶性神经源性肿瘤:卡铂+表阿霉素+异环磷酰胺(12/15、80.0%)、长春新碱+环磷酰胺+顺铂+氮烯脒胺(11/15、73.3%);恶性生殖细胞肿瘤:顺铂+长春新碱+博来霉素(8/8、100%)、金喜素+更生霉素+异环磷酰胺(8/8、100%)、三氧化二砷(As2O3)(7/8、87.5%);肾母细胞瘤:长春新碱+更生霉素(6/7、85.7%)、卡铂+依托泊苷(6/8、75.0%);肝母细胞瘤:长春新碱+环磷酰胺+顺铂+依托泊苷(8/9、88.9%)、卡铂+异环磷酰胺+替尼泊甙(7/9、77.8%)、顺铂+依托泊苷+金喜素(7/9、77.8%);横纹肌肉瘤:长春新碱+环磷酰胺+顺铂+依托泊苷(5/5、100%);肾上腺皮质癌:药物体外抑制率最高者为长春新碱+环磷酰胺+阿霉素.(4)As2O3对儿童恶性生殖细胞肿瘤、恶性神经源性肿瘤单药敏感率较高,分别是87.5%(7/8)、46.7%(7/15).紫杉醇对恶性神经源性肿瘤和横纹肌肉瘤化疗敏感性较高,分别为40.0%(6/15)、60.0%(3/5),吉西他滨对儿童生殖细胞肿瘤和横纹肌肉瘤敏感性较高,分别为50.0%(4/8)、60.0%(3/5).结论 ATP-TCA是一种适用于儿童实体瘤药敏检测并与临床相关性较好的实验技术,对抗儿童恶性肿瘤药物筛选、已有药物新适应证研究、联合化疗方案筛选和评估具有实际应用价值.

Application of ATP based bioluminescence tumor chemosensitivity assay in the chemotherapy of pediatric solid tumor

Objective To explore the clinical significance of ATP based bioluminescence in vitro tumor chemosensitivity assay (ATP-TCA) in the chemotherapy of pediatric solid tumor. Methods The cell culture technique and ATP-TCA were used to study chemosensitivity assay in specimens from 50 cases who underwent resection surgery for solid tumor (15 maglignant neurogenic tumor, 8 malignant germ cell tumors, 10 Wilms' tumors, 10 hepatoblastomas, 6 rhabdomyosarcomas, 1 adrenecortical carcinoma), 8 chemo-therapeutic drugs and 8 drug combination schedules were applied in every specimen. Results (1) Specimens of 46 of 50 pediatric patients with solid tumors were suitable for evaluation and were evaluated, the overall evaluation rate was 92% (46/50). (2) There was the heterogeneity in the chemosensitivity of the solid tumors in vitro. (3) The drug combination schedules of high sensitivity rate of every kind of pediatric solid tumor are as follows: the maglignant neurogenic tumor: CBP + EPI + IFO (12/15, 80.0%), VCR + CTX + DDP + DTIC ( 11/15, 73.3% ) ; malignant germ cell tumor: DDP + VCR + BLM ( 8/8, 100% ), TPTN + ACTD + IFO ( 8/8, 100% ), As2O3 ( 7/8, 87.5 % ) ; Wilms' tumor: VCR + ACTD ( 6/7, 85.7% ), CBP + VP16 (6/8, 75.0% ) ;hepatoblastoma: VCR + CTX + DDP + VP16 (8/9, 88.9% ), CBP +IFO+VM26 (7/9, 77.8%), DDP+VP16 +TPTN(7/9, 77.8%) ;rhabdomyosarcoma: VCR +CTX +DDP+VP16 (5/5, 100% ) ;adrenocortical carcinoma: VCR +CTX+ ADM. (4) As2O3 reached a high in vitro sensitive rate of 87.5% (7/8) and 46.7% (7/15) in malignant germ cell tumor and the maglignant neurogenic tumor respectively, PTX was sensitive to the magliguant neurogenic tumor and rhabdomyosarcoma (40.0% ( 6/15 ), 60.0% ( 3/5 ) ), GEM was sensitive to pediatric malignant germ cell tumor and rhabdomyosarcoma (50.0% (4/8), 60.0% (3/5)). Conclusions ATP-TCA is a sensitive method for the chemotherapeutic agents sere, erring of pediatric malignant solid tumor, and ATP-TCA assay results correlated well with clinical response. It appears to be useful in screening new drugs for pediatric solid tumor, exploring the possible combination plots and principles, evaluating the efficacy of existing chemotherapy, and optimize chemotherapy on an individual basis.