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吉西他滨对膀胱癌细胞中卡铂-DNA 单加合物的形成和修复的调节作用很小。

Gemcitabine causes minimal modulation of carboplatin-DNA monoadduct formation and repair in bladder cancer cells.

机构信息

Division of Hematology & Oncology, Department of Internal Medicine, UC Davis Cancer Center, Sacramento, California 95817, USA.

出版信息

Chem Res Toxicol. 2010 Nov 15;23(11):1653-5. doi: 10.1021/tx1003547. Epub 2010 Oct 28.

DOI:10.1021/tx1003547
PMID:21028869
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2987236/
Abstract

We are developing a method to identify cellular resistance to carboplatin by using accelerator mass spectrometry to measure carboplatin-DNA adducts formed from drug microdoses (∼1/100th the therapeutic dose). Such an approach would be particularly useful if it is still valid in combination chemotherapy. We examined whether the addition of gemcitabine, another chemotherapeutic drug, could influence carboplatin-DNA adduct levels. There were no substantial differences in the levels of carboplatin-DNA adducts in cells upon exposure to the carboplatin/gemcitabine combination at various doses and schedules. These data demonstrate that microdosing is feasible for the characterization of carboplatin resistance when given in combination with gemcitabine.

摘要

我们正在开发一种方法,通过使用加速器质谱法来测量由药物微剂量(约为治疗剂量的 1/100)形成的卡铂-DNA 加合物,从而鉴定细胞对卡铂的耐药性。如果这种方法在联合化疗中仍然有效,那么它将特别有用。我们研究了另一种化疗药物吉西他滨的加入是否会影响卡铂-DNA 加合物的水平。在不同剂量和方案下,细胞暴露于卡铂/吉西他滨联合用药时,卡铂-DNA 加合物的水平没有明显差异。这些数据表明,微剂量在与吉西他滨联合使用时,可用于鉴定卡铂耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be3d/2987236/d71a495c92b7/nihms249068f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be3d/2987236/d6e4bf4c8ca8/nihms249068f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be3d/2987236/0d6c46d1e1c7/nihms249068f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be3d/2987236/d71a495c92b7/nihms249068f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be3d/2987236/d6e4bf4c8ca8/nihms249068f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be3d/2987236/0d6c46d1e1c7/nihms249068f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be3d/2987236/d71a495c92b7/nihms249068f3.jpg

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DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine.来自抗癌药物的DNA加合物作为精准医学的候选预测标志物。
Chem Res Toxicol. 2017 Jan 17;30(1):388-409. doi: 10.1021/acs.chemrestox.6b00380. Epub 2017 Jan 3.
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Microdose-Induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice.微剂量诱导的药物-DNA加合物作为人类和小鼠化疗耐药性的生物标志物
Mol Cancer Ther. 2017 Feb;16(2):376-387. doi: 10.1158/1535-7163.MCT-16-0381. Epub 2016 Nov 30.
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Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology.加速器质谱在人类健康与分子毒理学中的应用。
Chem Res Toxicol. 2016 Dec 19;29(12):1976-1986. doi: 10.1021/acs.chemrestox.6b00234. Epub 2016 Oct 11.
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Diagnostic Microdosing Approach to Study Gemcitabine Resistance.研究吉西他滨耐药性的诊断性微剂量给药方法。
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Expression of ERCC1 antisense RNA abrogates gemicitabine-mediated cytotoxic synergism with cisplatin in human colon tumor cells defective in mismatch repair but proficient in nucleotide excision repair.ERCC1反义RNA的表达消除了吉西他滨与顺铂在错配修复缺陷但核苷酸切除修复功能正常的人结肠肿瘤细胞中介导的细胞毒性协同作用。
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