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Effects of cytarabine on activation of human T cells – cytarabine has concentration-dependent effects that are modulated both by valproic acid and all-trans retinoic acid

Overview of attention for article published in BMC Pharmacology and Toxicology, May 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (78th percentile)

Mentioned by

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2 tweeters
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2 patents

Citations

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21 Dimensions

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32 Mendeley
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Title
Effects of cytarabine on activation of human T cells – cytarabine has concentration-dependent effects that are modulated both by valproic acid and all-trans retinoic acid
Published in
BMC Pharmacology and Toxicology, May 2015
DOI 10.1186/s40360-015-0012-2
Pubmed ID
Authors

Elisabeth Ersvaer, Annette K Brenner, Kristin Vetås, Håkon Reikvam, Øystein Bruserud

Abstract

Cytarabine is used in the treatment of acute myeloid leukemia (AML). Low-dose cytarabine can be combined with valproic acid and all-trans retinoic acid (ATRA) as AML-stabilizing treatment. We have investigated the possible risk of immunotoxicity by this combination. We examined the effects of cytarabine combined with valproic acid and ATRA on in vitro activated human T cells, and we tested cytarabine at concentrations reached during in vivo treatment with high doses, conventional doses and low doses. T cells derived from blood donors were activated in vitro in cell culture medium alone or supplemented with ATRA (1 μM), valproic acid (500 or 1000 μM) or cytarabine (0.01-44 μM). Cell characteristics were assessed by flow cytometry. Supernatants were analyzed for cytokines by ELISA or Luminex. Effects on primary human AML cell viability and proliferation of low-dose cytarabine (0.01-0.5 μM) were also assessed. Statistical tests include ANOVA and Cluster analyses. Only cytarabine 44 μM had both antiproliferative and proapoptotic effects. Additionally, this concentration increased the CD4:CD8 T cell ratio, prolonged the expression of the CD69 activation marker, inhibited CD95L and heat shock protein (HSP) 90 release, and decreased the release of several cytokines. In contrast, the lowest concentrations (0.35 and 0.01 μM) did not have or showed minor antiproliferative or cytotoxic effects, did not alter activation marker expression (CD38, CD69) or the release of CD95L and HSP90, but inhibited the release of certain T cell cytokines. Even when these lower cytarabine concentrations were combined with ATRA and/or valproic acid there was still no or minor effects on T cell viability. However, these combinations had strong antiproliferative effects, the expression of both CD38 and CD69 was altered and there was a stronger inhibition of the release of FasL, HSP90 as well as several cytokines. Cytarabine (0.01-0.05 μM) showed a dose-dependent antiproliferative effect on AML cells, and in contrast to the T cells this effect reached statistical significance even at 0.01 μM. Even low levels of cytarabine, and especially when combined with ATRA and valproic acid, can decrease T cell viability, alter activation-induced membrane-molecule expression and decrease the cytokine release.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 22%
Student > Master 4 13%
Student > Doctoral Student 3 9%
Researcher 3 9%
Student > Bachelor 3 9%
Other 4 13%
Unknown 8 25%
Readers by discipline Count As %
Medicine and Dentistry 6 19%
Biochemistry, Genetics and Molecular Biology 4 13%
Agricultural and Biological Sciences 4 13%
Immunology and Microbiology 4 13%
Unspecified 1 3%
Other 4 13%
Unknown 9 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 19 August 2020.
All research outputs
#3,616,273
of 18,687,462 outputs
Outputs from BMC Pharmacology and Toxicology
#64
of 364 outputs
Outputs of similar age
#51,132
of 238,868 outputs
Outputs of similar age from BMC Pharmacology and Toxicology
#1
of 1 outputs
Altmetric has tracked 18,687,462 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 364 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one has done well, scoring higher than 81% 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 238,868 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 78% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them