基于ATP的生物发光肿瘤化疗药敏试验在小儿实体瘤化疗中的应用

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

作者信息

Cheng Hai-yan, Zhu Xiu-dan, Wang Huan-min, Qin Hong

机构信息

Department of Surgery, Beijng Children's Hospital Affiliated to Capital Medical University, Beijing 100045, China.

出版信息

Zhonghua Er Ke Za Zhi. 2009 Aug;47(8):598-603.

PMID:19951493

Abstract

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 malignant neurogenic tumor, 8 malignant germ cell tumors, 10 Wilms' tumors, 10 hepatoblastomas, 6 rhabdomyosarcomas, 1 adrenocortical carcinoma), 8 chemotherapeutic 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 malignant 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 malignant neurogenic tumor respectively, PTX was sensitive to the malignant 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 screening 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.

摘要

目的

探讨基于三磷酸腺苷（ATP）的生物发光法体外肿瘤药敏试验（ATP-TCA）在小儿实体瘤化疗中的临床意义。

方法

采用细胞培养技术及ATP-TCA法，对50例接受实体瘤切除手术的患儿标本（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）进行药敏试验，每个标本应用8种化疗药物及8种联合用药方案。

结果

（1）50例小儿实体瘤患者中46例标本适合评估并进行了评估，总评估率为92%（46/50）。（2）体外实体瘤药敏存在异质性。（3）各类小儿实体瘤高敏感率的联合用药方案如下：恶性神经源性肿瘤：卡铂（CBP）+表柔比星（EPI）+异环磷酰胺（IFO）（12/15，80.0%），长春新碱（VCR）+环磷酰胺（CTX）+顺铂（DDP）+达卡巴嗪（DTIC）（11/15，73.3%）；恶性生殖细胞肿瘤：DDP+VCR+博来霉素（BLM）（8/8，100%），拓扑替康（TPTN）+放线菌素D（ACTD）+IFO（8/8，100%），三氧化二砷（As2O3）（7/8，87.5%）；肾母细胞瘤：VCR+ACTD（6/7，85.7%），CBP+依托泊苷（VP16）（6/8，75.0%）；肝母细胞瘤：VCR+CTX+DDP+VP16（8/9，88.9%），CBP+IFO+替尼泊苷（VM26）（7/9，77.8%），DDP+VP16+TPTN（7/9，77.8%）；横纹肌肉瘤：VCR+CTX+DDP+VP16（5/5，100%）；肾上腺皮质癌：VCR+CTX+多柔比星（ADM）。（4）As2O3在恶性生殖细胞肿瘤和恶性神经源性肿瘤中的体外敏感率分别高达87.5%（7/8）和46.7%（7/15），紫杉醇（PTX）对恶性神经源性肿瘤和横纹肌肉瘤敏感（40.0%（6/15），60.0%（3/5）），吉西他滨（GEM）对小儿恶性生殖细胞肿瘤和横纹肌肉瘤敏感（50.0%（4/8），60.0%（3/5））。