ArticleThe AAPS journal2013
In vivo quantification of active decitabine-triphosphate metabolite: a novel pharmacoanalytical endpoint for optimization of hypomethylating therapy in acute myeloid leukemia.
Article in The AAPS journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Pharmacokinetic assessment of low dose decitabine in combination therapies: Development and validation of a sensitive UHPLC-MS/MS method for murine plasma analysis.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2024Article
- DNA methyltransferase inhibitor exposure-response: Challenges and opportunities.Clinical and translational science · 2023Review
- Is Monitoring of the Intracellular Active Metabolite Levels of Nucleobase and Nucleoside Analogs Ready for Precision Medicine Applications?European journal of drug metabolism and pharmacokinetics · 2022Review
- Decitabine- and 5-azacytidine resistance emerges from adaptive responses of the pyrimidine metabolism network.Leukemia · 2021Article
- Intracellular Pharmacokinetics of Pyrimidine Analogues used in Oncology and the Correlation with Drug Action.Clinical pharmacokinetics · 2020Review
- Mass balance and metabolite profiling ofInvestigational new drugs · 2020Article
- AZA-MS: a novel multiparameter mass spectrometry method to determine the intracellular dynamics of azacitidine therapy in vivo.Leukemia · 2018Article
- Enhanced inhibition of clonogenic survival of human medulloblastoma cells by multimodal treatment with ionizing irradiation, epigenetic modifiers, and differentiation-inducing drugs.Journal of experimental & clinical cancer research : CR · 2016Article
- Simultaneous quantitative determination of 5-aza-2'-deoxycytidine genomic incorporation and DNA demethylation by liquid chromatography tandem mass spectrometry as exposure-response measures of nucleoside analog DNA methyltransferase inhibitors.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2016Article
- Quantitative determination of decitabine incorporation into DNA and its effect on mutation rates in human cancer cells.Nucleic acids research · 2014Article
- Epigenetics in clinical practice: the examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia.Leukemia · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Decitabine (DAC) is used for treatment of patients with myelodysplastic syndromes and acute myeloid leukemia (AML). Following cellular uptake, DAC is activated to DAC-triphosphate (TP) and incorporated into DNA. Once incorporated into the DNA, DAC-TP binds and inactivates DNA methyltransferases (DNMTs), thereby leading to hypomethylation and re-expression of epigenetically silenced tumor suppressor genes and ultimately antileukemia activity. However, direct evidence of in vivo DAC-TP occurrence in DAC-treated patients has been difficult to demonstrate due to a lack of suitable validated analytical methodology. Thus, we developed and validated a nonradioactive sensitive and specific LC-MS/MS assay for quantification of DAC-TP. The assay is linear from 50 to 1,000 nM and from 1 to 10 μM and has a lower limit of quantitation of 50 nM and a coefficient of variation for both within- and between-day precision <20%. Following DAC treatment, we detected DAC-TP in parental and DAC-resistant AML cells (in vitro) and bone marrow (BM) and spleen of normal and leukemic mice (in vivo). Downregulation of DNMTs and correlation of DAC-TP concentration with proteins involved in mechanisms of DAC resistance were also demonstrated. The clinical applicability of this method was proven by measuring DAC-TP level in BM and blood mononuclear cells from DAC-treated AML patients. Higher levels are seemingly associated with clinical response. Monitoring the DAC-TP intracellular level may serve as a novel pharmacological endpoint for designing more effective DAC-based regimens.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.