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

Overview of attention for article published in BMC Veterinary Research, December 2014
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (94th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

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2 news outlets
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1 blog
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1 X user
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1 Facebook page

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17 Dimensions

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52 Mendeley
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Title
6-Thioguanine and zebularine down-regulate DNMT1 and globally demethylate canine malignant lymphoid cells
Published in
BMC Veterinary Research, December 2014
DOI 10.1186/s12917-014-0290-8
Pubmed ID
Authors

Brian K Flesner, Senthil R Kumar, Jeffrey N Bryan

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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 51 98%

Demographic breakdown

Readers by professional status Count As %
Student > Postgraduate 9 17%
Other 8 15%
Researcher 7 13%
Student > Doctoral Student 4 8%
Student > Ph. D. Student 4 8%
Other 13 25%
Unknown 7 13%
Readers by discipline Count As %
Veterinary Science and Veterinary Medicine 13 25%
Medicine and Dentistry 13 25%
Biochemistry, Genetics and Molecular Biology 7 13%
Agricultural and Biological Sciences 4 8%
Unspecified 2 4%
Other 4 8%
Unknown 9 17%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 23. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 April 2015.
All research outputs
#1,399,722
of 22,774,233 outputs
Outputs from BMC Veterinary Research
#76
of 3,045 outputs
Outputs of similar age
#20,595
of 359,669 outputs
Outputs of similar age from BMC Veterinary Research
#2
of 96 outputs
Altmetric has tracked 22,774,233 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,045 research outputs from this source. They receive a mean Attention Score of 3.8. This one has done particularly well, scoring higher than 97% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 359,669 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 94% of its contemporaries.
We're also able to compare this research output to 96 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.