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Downregulation of histone H2A and H2B pathways is associated with anthracycline sensitivity in breast cancer

Overview of attention for article published in Breast Cancer Research, February 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (87th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (62nd percentile)

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1 news outlet
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Citations

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24 Dimensions

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90 Mendeley
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Title
Downregulation of histone H2A and H2B pathways is associated with anthracycline sensitivity in breast cancer
Published in
Breast Cancer Research, February 2016
DOI 10.1186/s13058-016-0676-6
Pubmed ID
Authors

Marsela Braunstein, Linda Liao, Nicola Lyttle, Nazleen Lobo, Karen J. Taylor, Paul M. Krzyzanowski, Irina Kalatskaya, Cindy Q. Yao, Lincoln D. Stein, Paul C. Boutros, Christopher J. Twelves, Richard Marcellus, John M. S. Bartlett, Melanie Spears

Abstract

Drug resistance in breast cancer is the major obstacle to effective treatment with chemotherapy. While upregulation of multidrug resistance genes is an important component of drug resistance mechanisms in vitro, their clinical relevance remains to be determined. Therefore, identifying pathways that could be targeted in the clinic to eliminate anthracycline-resistant breast cancer remains a major challenge. We generated paired native and epirubicin-resistant MDA-MB-231, MCF7, SKBR3 and ZR-75-1 epirubicin-resistant breast cancer cell lines to identify pathways contributing to anthracycline resistance. Native cell lines were exposed to increasing concentrations of epirubicin until resistant cells were generated. To identify mechanisms driving epirubicin resistance, we used a complementary approach including gene expression analyses to identify molecular pathways involved in resistance, and small-molecule inhibitors to reverse resistance. In addition, we tested its clinical relevance in a BR9601 adjuvant clinical trial. Characterisation of epirubicin-resistant cells revealed that they were cross-resistant to doxorubicin and SN-38 and had alterations in apoptosis and cell-cycle profiles. Gene expression analysis identified deregulation of histone H2A and H2B genes in all four cell lines. Histone deacetylase small-molecule inhibitors reversed resistance and were cytotoxic for epirubicin-resistant cell lines, confirming that histone pathways are associated with epirubicin resistance. Gene expression of a novel 18-gene histone pathway module analysis of the BR9601 adjuvant clinical trial revealed that patients with low expression of the 18-gene histone module benefited from anthracycline treatment more than those with high expression (hazard ratio 0.35, 95 % confidence interval 0.13-0.96, p = 0.042). This study revealed a key pathway that contributes to anthracycline resistance and established model systems for investigating drug resistance in all four major breast cancer subtypes. As the histone modification can be targeted with small-molecule inhibitors, it represents a possible means of reversing clinical anthracycline resistance. ClinicalTrials.gov identifier NCT00003012 . Registered on 1 November 1999.

X Demographics

X Demographics

The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 90 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 1%
Unknown 89 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 19%
Researcher 11 12%
Student > Master 11 12%
Student > Bachelor 10 11%
Other 5 6%
Other 13 14%
Unknown 23 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 18%
Medicine and Dentistry 15 17%
Agricultural and Biological Sciences 9 10%
Nursing and Health Professions 5 6%
Pharmacology, Toxicology and Pharmaceutical Science 4 4%
Other 13 14%
Unknown 28 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 15 February 2016.
All research outputs
#2,983,335
of 25,374,647 outputs
Outputs from Breast Cancer Research
#308
of 2,053 outputs
Outputs of similar age
#49,939
of 406,225 outputs
Outputs of similar age from Breast Cancer Research
#13
of 35 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,053 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one has done well, scoring higher than 84% 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 406,225 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 87% of its contemporaries.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.