Evidence map›Paper›PMID 27082761›Full record

ArticleJournal of chromatography. B, Analytical technologies in the biomedical and life sciences2016

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.

Nicole M Anders, Jianyong Liu, Teresia Wanjiku, Hugh Giovinazzo, Jianya Zhou, Ajay Vaghasia, William G Nelson, Srinivasan Yegnasubramanian, Michelle A Rudek

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04482621 (Decitabine for COVID-19 Pneumonia-ARDS Treatment), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04482621 phase2suspendednot on this mapstarted 2020, after this paper: background citation

Decitabine for COVID-19 Pneumonia-ARDS Treatment: DART Trial

TypeinterventionalSponsorJohns Hopkins UniversityRan2020 to 2026Enrolled33ConditionsCOVID-19ArmsDecitabine, Placebo Saline
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Nicole M AndersThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA.
Jianyong LiuThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA.
Teresia WanjikuThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA.
Hugh GiovinazzoDepartment of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA.
Jianya ZhouThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA; Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou, PR China.
Ajay VaghasiaThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA.
William G NelsonThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA; Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA; Department of Pathology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA; Brady Urological Institute, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA.
Srinivasan YegnasubramanianThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA; Brady Urological Institute, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA. Electronic address: syegnasu@jhmi.edu.
Michelle A RudekThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA; Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231 USA. Electronic address: mrudek2@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 1992 to 2020
$43.9M
UPLC with Tandem MS for Sensitive Quantitative Analysis of Small MoleculesS10RR026824 · NCRR · JOHNS HOPKINS UNIVERSITY · PI RUDEK, MICHELLE A · 2010 to 2010
$429k
Small Molecule Inhibitors of Methyl CpG Binding Domain 2 ProteinF31CA196227 · NCI · JOHNS HOPKINS UNIVERSITY · PI GIOVINAZZO, HUGH · 2015 to 2017
$131k
NCATS NIH HHS UL1 TR001079NCI NIH HHS F31 CA196227NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA058236NCRR NIH HHS S10 RR026824
6 · The paper itself

Abstract

The epigenetic and anti-cancer activities of the nucleoside analog DNA methyltransferase (DNMT) inhibitors decitabine (5-aza-2'-deoxycytidine, DAC), azacitidine, and guadecitabine are thought to require cellular uptake, metabolism to 5-aza-2'-deoxycytidine triphosphate, and incorporation into DNA. This genomic incorporation can then lead to trapping and degradation of DNMT enzymes, and ultimately, passive loss of DNA methylation. To facilitate measurement of critical exposure-response relationships of nucleoside analog DNMT inhibitors, a sensitive and reliable method was developed to simultaneously quantitate 5-aza-2'-deoxycytidine genomic incorporation and genomic 5-methylcytosine content using LC-MS/MS. Genomic DNA was extracted and digested into single nucleosides. Chromatographic separation was achieved with a Thermo Hyperpcarb porous graphite column (100mm×2.1mm, 5μm) and isocratic elution with a 10mM ammonium acetate:acetonitrile with 0.1% formic acid (70:30, v/v) mobile phase over a 5min total analytical run time. An AB Sciex 5500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of 5-aza-2'-deoxycytidine, 2'-deoxycytidine, and 5-methyl-2'-deoxycytidine. The assay range was 2-400ng/mL for 5-aza-2'-deoxycytidine, 50-10,000ng/mL for 2'-deoxycytidine, and was 5-1000ng/mL for 5-methyl-2'-deoxycytidine. The assay proved to be accurate (93.0-102.2%) and precise (CV≤6.3%) across all analytes. All analytes exhibited long-term frozen digest matrix stability at -70°C for at least 117 days. The method was applied for the measurement of genomic 5-aza-2'-deoxycytidine and 5-methyl-2'-deoxycytidine content following exposure of in vitro cell culture and in vivo animal models to decitabine.

Indexed as

5-MethylcytosineAnimalsAzacitidineCell Line, TumorChromatography, LiquidDecitabineDNADNA MethylationHumansLimit of DetectionLinear ModelsMethyltransferasesMiceMice, NudeReproducibility of ResultsTandem Mass Spectrometry5-MethylcytosineAzacitidineDecitabineDNAMethyltransferases5-Aza-2′-deoxycytidine5-Methyl-2′-deoxycytidine5-MethylcytosineDecitabineDNA methyltransferase inhibitorGenomic DNAGlobal DNA demethylationLC/MS/MS

Identifiers

PMID27082761
PMCPMC4866886
OpenAlexW2310976863

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

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.