Relationship between plasma Ara-C and intracellular Ara-CTP pools under conditions of continuous infusion and high-dose Ara-C treatment.
Relationship between plasma Ara-C and intracellular Ara-CTP pools under conditions of continuous infusion and high-dose Ara-C treatment.
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连续输注和大剂量Ara-C治疗条件下血浆Ara-C与细胞内Ara-CTP池的关系。
DOI：
10.1002/mpo.2950100706
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Preisler,H
中科院分区：
文献类型：
--
作者：
Rustum,YM;Slocum,HK;Wang,G;Bakshi,D;Kelly,E;Buscaglia,D;Wrzosek,C;Early,AP;Preisler,H
用高效液相色谱法和放射免疫法测定血浆Ara-C、Ara-uin活体和细胞内Ara-CTP活性。在大剂量治疗过程中，血浆Ara-C有两个阶段：一个在tç时达到峰值，大约5-8分钟，另一个接近持续输液，tü大约6到8小时。在大剂量治疗期间，血浆Ara-C峰值水平与细胞内Ara-CTP的形成之间似乎没有关系。在高剂量治疗期间，患者外周血中的Ara-CTP池比骨髓中的Ara-CTP池更高，并且接受高剂量而不是常规剂量Ara-C治疗的患者的骨髓中也更高。在治疗前对患者细胞进行的不同浓度的Ara-C的体外实验表明，当细胞内Ara-CTP增加且细胞外Ara-C浓度更高时，患者可能从高剂量治疗中受益。相反，在由于激活酶耗尽而没有增加体外Ara-CTP池的患者中，可能没有必要进行大剂量治疗。因此，有可能通过检测治疗前体外细胞内Ara-CTP来确定最有可能从大剂量化疗中获益的患者。
Plasma level Ara‐C and Ara‐Uin vivoand intracellular Ara‐CTP poolsin vivoandin vitrowere measured using high‐performance liquid chromatography and radioimmunoassay. Plasma Ara‐C during High Dose therapy was found in two phases; one, a peak at t½ of approximately 5‐8 minutes, the other approaching that of Continuous Infusion with a t½ of about 6 to 8 hours. There appears to be no relationship between peak levels of plasma Ara‐C and intracellular Ara‐CTP formed during High Dose therapy. Intracellular Ara‐CTP pools were found to be higher in peripheral blood than in bone marrow during High Dose treatment and were also higher in bone marrow of patients treated with High Dose rather than conventional dose Ara‐C.In vitroexperiments with various concentrations of Ara‐C on patient cells prior to treatment suggest that patients may benefit from High Dose therapy when an increase in intracellular Ara‐CTP occurred with higher extracellular concentrations of Ara‐C. In patients with metabolically sensitive cells containing the necessary enzymes to activate Ara‐C to Ara‐CTP, where resistance is due to limited drug transport, High Dose therapy may prove beneficial. Conversely, in patients with no increase in Ara‐CTP poolsin vitrodue to a depletion of activating enzymes, High Dose treatment may not be warranted. Therefore, it may be possible to determine patients most likely to benefit from High Dose chemotherapy by measuring pre‐treatmentin vitrointracellular Ara‐CTP.
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DOI：
10.1016/s0021-9258(19)68705-3
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. W. Thomas;J. Tallman
通讯作者：
J. Tallman
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影响因子：
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作者：
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DOI：
10.1002/j.1460-2075.1987.tb04791.x
发表时间：
1987
期刊：
The EMBO Journal
影响因子：
--
作者：
C. Mamalaki;F. Stephenson;E. Barnard
通讯作者：
E. Barnard
DOI：
10.1002/j.1460-2075.1986.tb04247.x
发表时间：
1986-03
期刊：
The EMBO Journal
影响因子：
--
作者：
M. Seiki;J. Inoue;T. Takeda;M. Yoshida
通讯作者：
M. Seiki;J. Inoue;T. Takeda;M. Yoshida
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影响因子：
2.9
作者：
M. D. Majewska;R. D. Schwartz
通讯作者：
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