Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Improvements in the diagnosis and treatment of cancer have revealed long-term side effects of chemotherapeutics, particularly cardiotoxicity. Here, we present paired transcriptomics and metabolomics data characterizing in vitro cardiotoxicity to three compounds: 5-fluorouracil, acetaminophen, and doxorubicin. Standard gene enrichment and metabolomics approaches identify some commonly affected pathways and metabolites but are not able to readily identify metabolic adaptations in response to cardiotoxicity. The paired data was integrated with a genome-scale metabolic network reconstruction of the heart to identify shifted metabolic functions, unique metabolic reactions, and changes in flux in metabolic reactions in response to these compounds. Using this approach, we confirm previously seen changes in the p53 pathway by doxorubicin and RNA synthesis by 5-fluorouracil, we find evidence for an increase in phospholipid metabolism in response to acetaminophen, and we see a shift in central carbon metabolism suggesting an increase in metabolic demand after treatment with doxorubicin and 5-fluorouracil.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10931521 | PMC |
| http://dx.doi.org/10.1371/journal.pcbi.1011919 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of features and differences in PD-1 inhibitor-associated myocarditis and acute myocardial infarction using proteomic analysis: A clinical and preclinical study.
Biochem Cell Biol
August 2025
Nanchang University Second Affiliated Hospital, Department of Oncology, Nanchang, Jiangxi, China.
Immune checkpoint inhibitors (ICIs)-related myocarditis, a severe complication characterized by elevated cardiac troponin I, poses significant clinical challenges in distinguishing it from acute myocardial infarction (AMI). Our study aimed to identify plasma protein biomarkers that differentiate ICIs-myocarditis from AMI. Plasma samples from 5 ICIs-myocarditis patients (with paired baseline and diagnosis samples) and 5 angiography-confirmed AMI patients, matched for age, gender, smoking history, and pre-existing heart disease, were analyzed using label-free liquid chromatography-mass spectrometry (LC-MS) proteomics.
View Article and Find Full Text PDFDoxorubicin (DOX) is an effective chemotherapy whose clinical utility is limited by cardiotoxicity. To investigate underlying mechanisms, we employed a multi-omics approach integrating transcriptomic and proteomic profiling leveraging established mouse models of chronic DOX- induced cardiotoxicity. Five-week-old male mice received weekly DOX (4 mg/kg) or saline injections for six weeks, with heart tissues harvested 4 days post-treatment.
View Article and Find Full Text PDFFenofibrate attenuates doxorubicin-induced cardiotoxicity in patients with breast cancer: a randomized controlled trial.
Naunyn Schmiedebergs Arch Pharmacol
June 2025
Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Doxorubicin-induced cardiotoxicity (DIC) is a serious condition that limits its use. Thus, this study aimed at evaluating the efficacy and safety of fenofibrate in attenuating DIC in patients with breast cancer. In this randomized controlled parallel study, 44 patients with stage II and/or stage III breast cancer were randomly allocated into two groups: group 1 (control group; n = 22) which received doxorubicin/cyclophosphamide (AC regimen) for four cycles (cycle is every 3 weeks) and group 2 (fenofibrate group; n = 22) which received AC regimen for four cycles (cycle is every 3 weeks) plus 160 mg of oral fenofibrate 24 h prior to the first cycle of chemotherapy and then once daily until the end of the four chemotherapy cycles.
View Article and Find Full Text PDFEffect of cyclophospamide, doxorubicin, vincristine and prednisone/prednisolone (CHOP) chemotherapy regimens on left ventricular systolic function and cardiac structural abnormalities in non-Hodgkin lymphoma patients.
J Egypt Natl Canc Inst
May 2025
Faculty of Medicine, Airlangga University, Surabaya, Indonesia.
Background: The cyclophospamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) regimen, a standard treatment for aggressive non-Hodgkin lymphoma (NHL), is effective but linked to chemotherapy-induced cardiotoxicity (CDIC), such as heart failure and left ventricular dysfunction. Anthracyclines like doxorubicin are key contributors to CDIC. This study examines left ventricular dysfunction and structural abnormalities in NHL patients receiving CHOP therapy with cumulative doxorubicin doses ≥ 250 mg/m, aiming to improve early CDIC detection and guide timely cardioprotective interventions.
View Article and Find Full Text PDFLoperamide-induced severe cardiotoxicity: a toxicokinetic and toxicodynamic analysis derived from a case series and the published literature.
Clin Toxicol (Phila)
April 2025
New South Wales Poisons Information Centre, Sydney Children's Hospitals Network, Sydney, Australia.
Introduction: Chronic loperamide overdose is associated with cardiotoxicity. We describe the toxicokinetics of loperamide and N-desmethyl loperamide, and their concentration-response relationship on cardiotoxicity in newly described and published cases.
Materials And Methods: We obtained serial loperamide and N-desmethyl loperamide concentrations, and corresponding electrocardiographic intervals in three episodes (two patients) of loperamide-related cardiotoxicity.