ArticleCirculation2009
Acute doxorubicin cardiotoxicity is associated with p53-induced inhibition of the mammalian target of rapamycin pathway.
Article in Circulation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
131 citing papers in PubMed, 1 synthesis or guideline pooled it, 224 citations in OpenAlex.
- The Role of mTOR in the Doxorubicin-Induced Cardiotoxicity: A Systematic Review.Cell biochemistry and biophysics · 2025Pooled it
- Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease.JACC. Cardiovascular imaging · 2018Trial
- Effects of mitochondrial ABCB7 transporter upregulation on acute doxorubicin cardiorespiratory muscle injury.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Article
- Minimally invasive delivery of engineered heart tissues restores cardiac function in rats with chronic myocardial infarction.Acta biomaterialia · 2026Article
- Integrated Omics Approach to Delineate the Mechanisms of Doxorubicin-Induced Cardiotoxicity.Pharmaceuticals (Basel, Switzerland) · 2026Article
- MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis.Nature communications · 2025Article
- Vitamin C as a Cardioprotective Agent Against Doxorubicin-Induced Cardiotoxicity.Journal of the American Heart Association · 2025Review
- Tumour initiated purinergic signalling promotes cardiomyocyte RBFOX1 degradation and cardiotoxicity from DNA damaging anticancer agents.Nature communications · 2025Article
- Non-Coding RNAs in the Regulation of Doxorubicin-Induced Cardiotoxicity.Biomolecules · 2025Review
- Comprehensive review of non-invasive-treatment-related cardiovascular toxicity in breast cancer.iScience · 2025Review
- Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025Review
- Review
- Evolution of Theories on Doxorubicin-Induced Late Cardiotoxicity-Role of Topoisomerase.International journal of molecular sciences · 2024Review
- Microparticle Mediated Delivery of Apelin Improves Heart Function in Post Myocardial Infarction Mice.Circulation research · 2024Article
- HMGB1 as an extracellular pro-inflammatory cytokine: Implications for drug-induced organic damage.Cell biology and toxicology · 2024Review
- Exploring Anthracycline-Induced Cardiotoxicity from the Perspective of Protein Quality Control.Reviews in cardiovascular medicine · 2024Review
- Prevention and treatment of anthracycline-induced cardiotoxicity: A bibliometric analysis of the years 2000-2023.Heliyon · 2024Article
- NADPH oxidase 2 mediates cardiac sympathetic denervation and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced cardiomyopathy.Scientific reports · 2024Article
- Potential role of endoplasmic reticulum stress in doxorubicin-induced cardiotoxicity-an update.Frontiers in pharmacology · 2024Review
- An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity.Frontiers in pharmacology · 2024Review
71 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDoxorubicin is used to treat childhood and adult cancer. Doxorubicin treatment is associated with both acute and chronic cardiotoxicity. The cardiotoxic effects of doxorubicin are cumulative, which limits its chemotherapeutic dose. Free radical generation and p53-dependent apoptosis are thought to contribute to doxorubicin-induced cardiotoxicity. METHODS AND
resultsAdult transgenic (MHC-CB7) mice expressing cardiomyocyte-restricted dominant-interfering p53 and their nontransgenic littermates were treated with doxorubicin (20 mg/kg cumulative dose). Nontransgenic mice exhibited reduced left ventricular systolic function (predoxorubicin fractional shortening [FS] 61+/-2%, postdoxorubicin FS 45+/-2%, mean+/-SEM, P<0.008), reduced cardiac mass, and high levels of cardiomyocyte apoptosis 7 days after the initiation of doxorubicin treatment. In contrast, doxorubicin-treated MHC-CB7 mice exhibited normal left ventricular systolic function (predoxorubicin FS 63+/-2%, postdoxorubicin FS 60+/-2%, P>0.008), normal cardiac mass, and low levels of cardiomyocyte apoptosis. Western blot analyses indicated that mTOR (mammalian target of rapamycin) signaling was inhibited in doxorubicin-treated nontransgenic mice but not in doxorubicin-treated MHC-CB7 mice. Accordingly, transgenic mice with cardiomyocyte-restricted, constitutively active mTOR expression (MHC-mTORca) were studied. Left ventricular systolic function (predoxorubicin FS 64+/-2%, postdoxorubicin FS 60+/-3%, P>0.008) and cardiac mass were normal in doxorubicin-treated MHC-mTORca mice, despite levels of cardiomyocyte apoptosis similar to those seen in doxorubicin-treated nontransgenic mice.
conclusionsThese data suggest that doxorubicin treatment induces acute cardiac dysfunction and reduces cardiac mass via p53-dependent inhibition of mTOR signaling and that loss of myocardial mass, and not cardiomyocyte apoptosis, is the major contributor to acute doxorubicin cardiotoxicity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.