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A combination of p53-activating APR-246 and phosphatidylserine-targeting antibody potently inhibits tumor development in hormone-dependent mutant p53-expressing breast cancer xenografts

Overview of attention for article published in Breast cancer targets and therapy, March 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#3 of 184)
  • High Attention Score compared to outputs of the same age (96th percentile)

Mentioned by

news
10 news outlets
blogs
1 blog
twitter
6 tweeters
facebook
1 Facebook page
googleplus
1 Google+ user

Citations

dimensions_citation
5 Dimensions

Readers on

mendeley
6 Mendeley
Title
A combination of p53-activating APR-246 and phosphatidylserine-targeting antibody potently inhibits tumor development in hormone-dependent mutant p53-expressing breast cancer xenografts
Published in
Breast cancer targets and therapy, March 2018
DOI 10.2147/bctt.s156285
Pubmed ID
Authors

Yayun Liang, Benford Mafuvadze, Cynthia Besch-Williford, Salman M Hyder

Abstract

Between 30 and 40% of human breast cancers express a defective tumor suppressor p53 gene. Wild-type p53 tumor suppressor protein promotes cell-cycle arrest and apoptosis and inhibits vascular endothelial growth factor-dependent angiogenesis, whereas mutant p53 protein (mtp53) lacks these functions, resulting in tumor cell survival and metastasis. Restoration of p53 function is therefore a promising drug-targeted strategy for combating mtp53-expressing breast cancer. In this study, we sought to determine whether administration of APR-246, a small-molecule drug that restores p53 function, in combination with 2aG4, an antibody that targets phosphatidylserine residues on tumor blood vessels and disrupts tumor vasculature, effectively inhibits advanced hormone-dependent breast cancer tumor growth. APR-246 reduced cell viability in mtp53-expressing BT-474 and T47-D human breast cancer cells in vitro, and significantly induced apoptosis in a dose-dependent manner. However, APR-246 did not reduce cell viability in MCF-7 breast cancer cells, which express wild-type p53. We next examined APR-246's anti-tumor effects in vivo using BT-474 and T47-D tumor xenografts established in female nude mice. Tumor-bearing mice were treated with APR-246 and/or 2aG4 and tumor volume followed over time. Tumor growth was more effectively suppressed by combination treatment than by either agent alone, and combination therapy completely eradicated some tumors. Immunohistochemistry analysis of tumor tissue sections demonstrated that combination therapy more effectively induced apoptosis and reduced cell proliferation in tumor xenografts than either agent alone. Importantly, combination therapy dramatically reduced the density of blood vessels, which serve as the major route for tumor metastasis, in tumor xenografts compared with either agent alone. Based on our findings, we contend that breast tumor growth might effectively be controlled by simultaneous targeting of mtp53 protein and tumor blood vessels in mtp53-expressing cancers.

Twitter Demographics

The data shown below were collected from the profiles of 6 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 6 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 6 100%

Demographic breakdown

Readers by professional status Count As %
Librarian 1 17%
Student > Doctoral Student 1 17%
Student > Ph. D. Student 1 17%
Researcher 1 17%
Professor > Associate Professor 1 17%
Other 0 0%
Unknown 1 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 33%
Materials Science 1 17%
Medicine and Dentistry 1 17%
Engineering 1 17%
Unknown 1 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 85. 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 26 February 2020.
All research outputs
#252,160
of 15,712,594 outputs
Outputs from Breast cancer targets and therapy
#3
of 184 outputs
Outputs of similar age
#9,322
of 281,517 outputs
Outputs of similar age from Breast cancer targets and therapy
#1
of 2 outputs
Altmetric has tracked 15,712,594 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 184 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one has done particularly well, scoring higher than 98% 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 281,517 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 96% of its contemporaries.
We're also able to compare this research output to 2 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