Abstract:
:Treatment of mammalian cells with chemotherapeutic drugs can result in perturbations of nucleotide pools. Monitoring these perturbations in cultured tumor cells from human sources is useful for assessment of the effect of drug therapy and a better understanding of the mechanism of action of these drugs. In this study, three classes of chemotherapeutic drugs with different mechanisms of action were used in the development of drug-treated cell models. The LC-based targeted metabolomics analysis of nucleotides in cells of the control group and the drug-treated group was carried out. Several data processing methods were combined for the identification of potential biomarkers associated with the action of drugs, including one-way analysis of variance, principal component analysis, and receiver operating characteristic curves. Intriguingly, tumor cells of both the control group and the drug-treated groups can be distinguished from each other, and several variables were recognized as potential biomarkers, such as ATP, GMP, and UDP for antimetabolite agents, ATP, GMP, and CTP for DNA-damaging agents, as well as GMP, ATP, UDP, and GDP for the mitotic spindle agents. Further validation of the potential biomarkers was performed using the receiver operating characteristic curve. Considering their corresponding area under the curve, which was larger than 0.9, it can be concluded that GMP and ATP are the best potential biomarkers for DNA-damaging drugs, as well as GMP, ATP, and UDP for the other two classes of drugs. This limited nucleotide approach cannot completely distinguish the mechanisms of the nine drugs, but it provides preliminary evidence for the role of pharmacometabolomics in the preclinical development of drugs at least.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Liu X,Zhang CC,Liu Z,Wei L,Liu YJ,Yu J,Sun LXdoi
10.1097/CAD.0000000000000096subject
Has Abstractpub_date
2014-07-01 00:00:00pages
690-703issue
6eissn
0959-4973issn
1473-5741journal_volume
25pub_type
杂志文章abstract::The primary objective was to determine the optimal doses for gemcitabine (prolonged infusion), liposomal doxorubicin (Myocet) and docetaxel as primary (neoadjuvant) chemotherapy for locally advanced breast cancer. Secondary objectives included evaluation of the safety and efficacy of the regimen. Patients (n=19) with ...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00001813-200501000-00003
更新日期:2005-01-01 00:00:00
abstract::ET-743 is a marine anti-cancer drug and is currently in phase I trials in which the effect of combination therapies will be investigated. Its dose-limiting toxicity in patients is hepatotoxicity. In-vitro studies have shown that ET-743 is mainly metabolized by cytochrome P450 (CYP) 3A4, but also by 2C9, 2C19, 2D6 and ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000180121.16407.38
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abstract::Octreotide appears to have a major therapeutic effect in the management of diarrhoea related to cancer therapy. This effect is seen in the acute diarrhoea following radiation therapy and chemotherapy, and also in late radiation enteritis. As well as providing improved symptom control, early treatment can prevent poten...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199601001-00003
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
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更新日期:2006-04-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199010000-00003
更新日期:1990-10-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199302000-00012
更新日期:1993-02-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:
更新日期:2001-06-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000973
更新日期:2020-11-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199306000-00007
更新日期:1993-06-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000172833.70444.ba
更新日期:2005-08-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000205
更新日期:2015-06-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199408000-00010
更新日期:1994-08-01 00:00:00
abstract::Extrachromosomal DNA is the predominant form of gene amplification in human tumors. Hydroxyurea (HU) concentrations of 100-150 microM have been promising in vitro for extrachromosomal DNA elimination. The study objective was to determine the HU dose-concentration relationship in nude mice with HU doses from 0 to 200 m...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199410000-00009
更新日期:1994-10-01 00:00:00
abstract::Chemotherapy for breast cancer is given on the basis of empirical information from clinical trials, an approach which falls to take into account the known heterogeneity of chemosensitivity between patients. Previous attempts to determine chemosensitivity ex vivo have been disappointing, but in this study results from ...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199608000-00002
更新日期:1996-08-01 00:00:00
abstract::In this study the activity of KW-2149 and two of its metabolites, M-16 and M-18, was measured against cell lines with different types of resistance. The influence of these metabolites and of the exposure time on the cytotoxic efficacy of KW-2149 was investigated. Against the human ovarian carcinoma cell lines, AOvC an...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199406000-00013
更新日期:1994-06-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/cad.0b013e3282f3f152
更新日期:2008-03-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-200304000-00003
更新日期:2003-04-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199606000-00007
更新日期:1996-06-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0000000000000053
更新日期:2014-05-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283635a47
更新日期:2013-09-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199809000-00007
更新日期:1998-09-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
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更新日期:2005-10-01 00:00:00
abstract::Advanced stage neuroblastoma is a very aggressive pediatric cancer with limited treatment options and a high mortality rate. Glycogen synthase kinase-3β (GSK-3β) is a potential therapeutic target in neuroblastoma. Using immunohistochemical staining, we observed positive GSK-3β expression in 67% of human neuroblastomas...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000652
更新日期:2018-09-01 00:00:00
abstract::Our previous studies have shown that arsenic trioxide (As2O3), a novel anti-cancer agent, may be active against urothelial carcinomas. A series of bladder urothelial carcinoma cells with progressive As2O3 resistance were established and studied to reveal molecular events in relation to the mechanisms of resistance to ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200409000-00007
更新日期:2004-09-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199404000-00007
更新日期:1994-04-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
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更新日期:2012-06-01 00:00:00
abstract::The goal of this study was to identify clinical characteristics and concurrent medications associated with an increased or decreased incidence of cisplatin-induced nephrotoxicity. The medical records for 62 subjects with head and neck cancer who received cisplatin 100 mg/m2 (day 1) plus fluorouracil 1000 mg/m2 (days 1...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,多中心研究
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更新日期:2006-02-01 00:00:00
abstract::(E)-2'-deoxy-2'-(fluoromethylene) cytidine (MDL101,731) is a new deoxycytidine analog which shows potent antitumor activity against several human tumor models. We previously showed that MDL101,731 inhibited human ribonucleotide reductase (RNR) in HeLa S3 human cervical carcinoma cells. Recently, it has been reported t...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
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更新日期:1998-08-01 00:00:00