Evidence map›Paper›PMID 27142468›Full record

ArticleScientific reports2016

Modeling Doxorubicin-Induced Cardiotoxicity in Human Pluripotent Stem Cell Derived-Cardiomyocytes.

Agnes Maillet, Kim Tan, Xiaoran Chai, Singh N Sadananda, Ashish Mehta, Jolene Ooi, Michael R Hayden, Mahmoud A Pouladi, Sujoy Ghosh, Winston Shim and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
14.6field-weighted citation impact, top 1% 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

113 citing papers in PubMed, 184 citations in OpenAlex.

  1. Article
  2. Article
  3. Doxorubicin-Induced Cytotoxicity in Adipose-Derived Stem Cells Is Associated With Altered SAPK/JNK Signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  4. Review
  5. Impact of CaInternational journal of molecular sciences · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Caught in the crossfire: cardiac complications of cancer therapy.The Journal of clinical investigation · 2026
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

53 more citing papers are in PubMed but not listed here.

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

11 authors at 5 institutions in 2 countries.

Agnes MailletTranslational Laboratory in Genetic Medicine, National University of Singapore and the Agency for Science Technology and Research (A*STAR), Singapore.
Kim TanTranslational Laboratory in Genetic Medicine, National University of Singapore and the Agency for Science Technology and Research (A*STAR), Singapore.
Xiaoran ChaiCenter for Computational Biology, Duke-NUS Graduate Medical School, Singapore.
Singh N SadanandaTranslational Laboratory in Genetic Medicine, National University of Singapore and the Agency for Science Technology and Research (A*STAR), Singapore.
Ashish MehtaNational Heart Research Institute, National Heart Centre Singapore, Singapore.
Jolene OoiTranslational Laboratory in Genetic Medicine, National University of Singapore and the Agency for Science Technology and Research (A*STAR), Singapore.
Michael R HaydenTranslational Laboratory in Genetic Medicine, National University of Singapore and the Agency for Science Technology and Research (A*STAR), Singapore.
Mahmoud A PouladiTranslational Laboratory in Genetic Medicine, National University of Singapore and the Agency for Science Technology and Research (A*STAR), Singapore.
Sujoy GhoshCenter for Computational Biology, Duke-NUS Graduate Medical School, Singapore.
Winston ShimNational Heart Research Institute, National Heart Centre Singapore, Singapore.
Liam R BrunhamTranslational Laboratory in Genetic Medicine, National University of Singapore and the Agency for Science Technology and Research (A*STAR), Singapore.
Agency for Science, Technology and Research · SGNational University of Singapore · SGDuke-NUS Medical School · SGNational Heart Centre Singapore · SGUniversity of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Doxorubicin is a highly efficacious anti-cancer drug but causes cardiotoxicity in many patients. The mechanisms of doxorubicin-induced cardiotoxicity (DIC) remain incompletely understood. We investigated the characteristics and molecular mechanisms of DIC in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). We found that doxorubicin causes dose-dependent increases in apoptotic and necrotic cell death, reactive oxygen species production, mitochondrial dysfunction and increased intracellular calcium concentration. We characterized genome-wide changes in gene expression caused by doxorubicin using RNA-seq, as well as electrophysiological abnormalities caused by doxorubicin with multi-electrode array technology. Finally, we show that CRISPR-Cas9-mediated disruption of TOP2B, a gene implicated in DIC in mouse studies, significantly reduces the sensitivity of hPSC-CMs to doxorubicin-induced double stranded DNA breaks and cell death. These data establish a human cellular model of DIC that recapitulates many of the cardinal features of this adverse drug reaction and could enable screening for protective agents against DIC as well as assessment of genetic variants involved in doxorubicin response.

Indexed as

CardiotoxicityModels, BiologicalAntibiotics, AntineoplasticCells, CulturedCell SurvivalDoxorubicinElectrophysiological PhenomenaGene Expression ProfilingHumansMyocytes, CardiacPluripotent Stem CellsAntibiotics, AntineoplasticDoxorubicin

Identifiers

PMID27142468
PMCPMC4855185
OpenAlexW2346631874

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.