摘要
目的：通过检测急性白血病（AL）及非霍奇金淋巴瘤（NHL）患儿骨髓单个核细胞内阿糖胞苷（Ara—C）代谢关键酶-脱氧胞苷激酶（DCK）、胞苷脱氨酶（CDA）活性及静滴大剂量阿糖胞苷（HD—AraC）后2h外周血中Ara—C、阿糖尿苷（Ara—U）的浓度，分析DCK、CDA活性与外周血中Ara—C、Ara—U血浆峰浓度的关系。探索Ara—C的体内代谢特征，以及Ara—C代谢关键酶活性表达对儿童恶性血液肿瘤接受HD—AraC治疗时药物血浓度的影响。方法：采用同位素。H—Cytidine做为放射底物检测24例患儿骨髓单个核细胞内DCK、CDA酶活性．同时采用高效液相色谱法（HPLC）和Ara—C、Ara—U标准品测定静滴HD—AraC2h后血浆Ara—C、Ara—U的峰浓度，统计分析DCK、CDA酶活性表达强弱与外周血Ara—C、Ara—U峰浓度的相关性。结果：CDA酶活性表达强弱明显影响Ara—C、Ara—U的血浆峰浓度（P〈0．05）：CDA酶活性高的患儿，Ara—U血浆峰浓度高，Ara—C血浆峰浓度低；CDA酶活性低的患几，Ara—U血浆峰浓度低，Ara—C血浆峰浓度相对高。但是，DCK酶活性与Ara—C、Ara—U的血浆峰浓度未见显著性相关（P〉O．05）。结论：HD—AraC是治疗儿童难治型恶性血液肿瘤的有效疗法，但是CDA酶活性表达强弱将显影响患儿个体所能达到Ara—C、Ara—U的血浆峰浓度，进而对Ara—C疗效和骨髓抑制等治疗反应产生影响。因此，检测CDA酶活性表达，有可能为临床适当调整药物剂量，开展个体化治疗，提供较为可靠的参考依据。
Objective： To detect the concentrations of cytosine arabinoside （Ara-C） and 1-β-D-arabinofuranosyluracil （Ara-U） in plasma, at two hours, when high dose cytosine arabinoside （HD-AraC） intravenous drip was completed, in cases of acute leukemia （AL） and non-Hodgkin＇s lymphoma （NHL）, and to analyze the correlation between activity of Ara-C-metabolizine enzymes and the concentrations of Ara-C and Ara-U in plasma. This study aimed to investigate the metabolic characteristics of Ara-C in vivo and the influence of key enzyme expression on the drug concentration in plasma during HD-AraC treatment for childhood hematological malignancies. Methods： High performance liquid chromatography （HPLC） was used to detect the concentrations of Ara-C and Ara-U in plasma, at two hours, when intravenous drip was completed, in 24 cases, including 21 cases of AL and 3 cases of NHL. Deoxy-[5-^3H]-cytidine was employed to detect the deoxycytidine kinase （DCK） and cytidine deaminase （CDA） activity in these same cases. The relationship of the expression of key enzymes of Ara-C metabolism with the peak concentrations of Ara-C and Ara-U in plasma was also analyzed. Results- The expression of CDA remarkably affected the peak concentrations of Ara-C and Ara-U in plasma （P〈0.05）： patients with higher CDA activity had higher concentrations of Ara-U in plasma and lower concentrations of Ara-C in plasma; patients with lower CDA activity had lower concentrations of Ara-U in plasma and higher concentrations of Ara-C in plasma. No correlation was found between DCK expression and peak concentrations of Ara-C and Ara-U in plasma （P〉0.05）. Conclusion： HD-AraC is a very effective protocol for childhood refractory hematological malignancies. But the effect of CDA expression on the peak concentrations of Ara-C and Ara-U may affect the therapeutic reaction of HD-AraC. Therefore, detecting the expression of CDA may provide reliable reference for clinical dose adjustment and individualized treatment.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第13期742-744,748,共4页
Chinese Journal of Clinical Oncology
基金
上海市科研计划项目资助(编号:09411964000)~~
