Concentration and time dependent growth inhibition and metabolism in vitro by 2',2'-difluoro-deoxycytidine (gemcitabine).
Concentration and time dependent growth inhibition and metabolism in vitro by 2',2'-difluoro-deoxycytidine (gemcitabine).
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2,2-二氟脱氧胞苷（吉西他滨）在体外的浓度和时间依赖性生长抑制和代谢。
DOI：
10.1007/978-1-4899-2638-8_12
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发表时间：
1991
影响因子：
--
通讯作者：
G. Peters
中科院分区：
文献类型：
--
作者：
V. R. V. Ruiz van Haperen;G. Veerman;P. Noordhuis;J. Vermorken;G. Peters
2 '，2'-二氟脱氧胞苷（dFdC）是一种新的脱氧胞苷类似物。1-β-D-阿拉伯呋喃糖基胞嘧啶（cytosine arabinoside，ara-C）也是一种脱氧胞苷类似物，是治疗急性髓性白血病（AML）最有效的药物之一。然而，在临床前系统和患者中对实体瘤的活性是有限的（1）。与此相反，dFdC在各种临床前实体瘤模型系统中显示出优异的抗肿瘤活性（2，3）。使用不同时间表的几个I期试验已经完成（4，5），该药物目前正在一些临床II期试验中进行评估。在非小细胞肺癌、卵巢癌和胰腺癌患者中观察到一些活性。Ara-C通过其三磷酸ara-CTP的积累表现出其抗肿瘤作用，其随后被掺入DNA中，导致生长抑制（1，6）。阿糖胞苷的抗肿瘤作用具有剂量和时间依赖性（7）。由脱氧胞苷激酶（dCK）催化的ara-C磷酸化为ara-CMP是关键步骤。该药物可通过脱氧胞苷脱氨酶（dCDA）催化脱氨基形成ara-U而灭活（1）。就像阿糖胞苷，dFdC必须被dCK催化转化为dF-dCMP，随后转化为dF-dCTP。dFdC可通过dCDA催化的脱氨基作用失活为dFdU（二氟脱氧尿苷）（8，9）。到目前为止，大多数关于dFdC的研究仅限于白血病细胞系。由于在头颈癌、结肠癌和卵巢癌中有良好的临床前结果，我们使用这些实体瘤细胞系作为实体瘤的模型。我们在体外确定了对药物的敏感性和dF-dCTP的积累是否具有时间和浓度依赖性。
2’,2’-Difluoro-deoxycytidine (dFdC) is a new deoxycytidine analogue. 1-β-D-arabinofuranosylcytosine (cytosine arabinoside, ara-C), also a deoxycytidine analogue, is one of the most effective agents against acute myelogenous leukemia (AML). However, activity against solid tumours both in preclinical systems and patients is limited (1). As opposed to this, dFdC has shown excellent antitumour activity in various preclinical solid tumour model systems (2,3). Several phase I trials using different schedules have been completed (4,5) and the drug is now being evaluated in some clinical phase II trials. Some activity has been observed in patients with non-small-cell lung cancer, ovarian cancer and pancreas cancer. Ara-C exhibits its antitumour effect through accumulation of its triphosphate ara-CTP, which is subsequently incorporated into DNA, leading to growth inhibition (1,6). The antitumour effect of ara-C is dose and time dependent (7). The phosphorylation of ara-C to ara-CMP, catalysed by deoxycytidine kinase (dCK), is the crucial step. The drug can be inactivated by deamination to ara-U, catalysed by deoxycytidine deaminase (dCDA) (1). Like ara-C., dFdC must be converted into dF-dCMP, catalyzed by dCK, and subsequently to dF-dCTP. dFdC can be inactivated by deamination to dFdU (difluorodeoxyuridine), catalysed by dCDA (8,9). Until now, most studies on dFdC have been limited to leukemic cell lines. Because of the promising preclinical results in head & neck, colon and ovarian cancer, we used these solid tumour cell lines as a model for solid tumours. We determined in vitro whether sensitivity to the drug and accumulation of dF-dCTP were time and concentration dependent.
影响因子：
3
作者：
Ali, S;Aranha, O;Philip, PA
通讯作者：
Philip, PA
2,2-二氟脱氧胞苷对阿拉伯糖核苷磷酸化和细胞毒性的调节活性。
影响因子：
11.2
作者：
Gandhi,V;Plunkett,W
通讯作者：
Plunkett,W