Evidence map›Paper›PMID 25480665›Full record

ArticleBMC veterinary research2014

6-Thioguanine and zebularine down-regulate DNMT1 and globally demethylate canine malignant lymphoid cells.

Brian K Flesner, Senthil R Kumar, Jeffrey N Bryan

Open access · goldAbstract read
In one paragraph

Article in BMC veterinary research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 33% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
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  5. Article
  6. Epigenetic Mechanisms in Canine Cancer.Frontiers in oncology · 2020
    Review
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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

3 authors at 1 institution in 1 country.

Brian K FlesnerDepartment of Veterinary Medicine and Surgery, Comparative Oncology and Epigenetics Laboratory, College of Veterinary Medicine, University of Missouri-Columbia, 900 E. Campus Drive, Columbia, MO, 65211, USA. flesnerb@lsu.edu.
Senthil R KumarDepartment of Veterinary Medicine and Surgery, Comparative Oncology and Epigenetics Laboratory, College of Veterinary Medicine, University of Missouri-Columbia, 900 E. Campus Drive, Columbia, MO, 65211, USA. kumars@missouri.edu.
Jeffrey N BryanDepartment of Veterinary Medicine and Surgery, Comparative Oncology and Epigenetics Laboratory, College of Veterinary Medicine, University of Missouri-Columbia, 900 E. Campus Drive, Columbia, MO, 65211, USA. bryanjn@missouri.edu.
University of Missouri · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe antimetabolite 6-thioguanine (6-TG) has been used to treat both human and canine lymphoid malignancies. 6-TG has been shown to be epigenetically active as a demethylating agent in a human lymphoma cell line, causing downregulation of DNA methyltransferase 1 (DNMT1) through ubiquitin-targeted degradation. Zebularine (Zeb), a similar cytidine analog, also has demethylating activity as well as oral bioavailability. The hypothesis of the present study was that 6-TG and Zeb would cause downregulation of DNMT1 and globally demethylate the genomic DNA of canine lymphoma cells. The secondary hypothesis was that these agents would cause a dose-dependent decrease in cell proliferation in canine lymphoma cells. Canine CLGL-90 malignant T cells and CLL 17-7 cells were incubated in modified RPMI media. They were treated with 6-TG, Zeb, or control media at biologically relevant concentrations.

resultsFollowing treatment with each agent, DNMT1 protein and global DNA methylation were significantly decreased. A dose-dependent decrease in cell survival was also observed, with apoptosis being the primary mode of cell death in the CLGL-90 cell line.

conclusionsThese results confirm the demethylating action of 6-TG and Zeb in canine cells which is similar to that shown in human cell lines. Confirmation of this mechanism supports the clinical application of these compounds as demethylating drugs in veterinary patients.

Indexed as

AnimalsAntineoplastic AgentsApoptosisBlotting, WesternCell Line, TumorCell ProliferationCytidineDNA-Cytosine MethylasesDog DiseasesDogsDose-Response Relationship, DrugDown-RegulationLeukemia, B-CellLeukemia, T-CellLymphomaThioguanineAntineoplastic AgentsCytidineDNA-Cytosine Methylasespyrimidin-2-one beta-ribofuranosideThioguanine

Identifiers

PMID25480665
PMCPMC4272768
OpenAlexW2029931651

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Registered trials

None linked

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.