Abstract
Open-access gene expression data sets provide a useful resource for identifying novel drug targets and biomarkers. The IGF1-PI3K pathway is a critical mediator of physiological cardiac enlargement/hypertrophy and protection. This study arose after mining a gene microarray data set from a previous study that compared heart tissue from cardiac-specific PI3K transgenic mouse models. The top-ranked candidate identified from the microarray data was clusterin. Clusterin has been proposed as a biomarker for multiple diseases including heart failure, and as a cancer drug target. Here, we show that clusterin gene expression is increased in hearts of transgenic mice with increased PI3K and decreased in mice with depressed cardiac PI3K. In vitro, clusterin secretion was elevated in media from neonatal rat ventricular myocytes treated with IGF1. Furthermore, by mining gene expression data from hearts during normal mouse postnatal growth, we also report an increase in clusterin expression with postnatal heart growth. Given we show that clusterin is regulated by the IGF1-PI3K pathway in the heart, and this pathway mediates physiological cardiac hypertrophy and cardioprotection, caution is required when considering clusterin as a biomarker for heart failure and as a cancer target. Mining pre-existing cardiac profiling data sets may be a useful approach to assess whether regulating new drug targets is likely to lead to cardiac damage/toxicity.
PMID: 32172307 [PubMed - as supplied by publisher]
14:35
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pubmed: tutte cardiotoxicity...
Detection of chemotherapy-induced cardiotoxicity with antimyosin pretargeted imaging.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles
Detection of chemotherapy-induced cardiotoxicity with antimyosin pretargeted imaging.
J Nucl Cardiol. 2019 08;26(4):1345-1347
Authors: Strauss HW, Mariani G
PMID: 29392625 [PubMed - indexed for MEDLINE]
18 March 2020
12:27
Cardiotoxicity News
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Digoxin Enhances the Anticancer Effect on Non-Small Cell Lung Cancer While Reducing the Cardiotoxicity of Adriamycin.
Digoxin Enhances the Anticancer Effect on Non-Small Cell Lung Cancer While Reducing the Cardiotoxicity of Adriamycin.
Front Pharmacol. 2020;11:186
Authors: Wang Y, Ma Q, Zhang S, Liu H, Zhao B, Du B, Wang W, Lin P, Zhang Z, Zhong Y, Kong D
Abstract
Digoxin is widely used to treat heart failure. Epidemiological studies suggested it might be used as an anticancer drug or sensitizing agent for cancer therapy. Adriamycin is a well-known anticancer drug, but often causes cardiotoxicity which limits its use. We recently investigated the anticancer effects of digoxin alone or in combination with adriamycin on human non-small cell lung cancer in vitro and in vivo. Digoxin reduced the viability of A549 and H1299 cells in vitro, increased DNA damage by promoting ROS generation and inhibiting both DNA double strand break (DSB) and single strand break (SSB) repair. Combination with adriamycin showed synergistic antiproliferative effects at the ratios of 1/2IC50DIG:IC50ADR and IC50DIG:IC50ADR on A549 and H1299 cells, respectively. In vivo, digoxin potently inhibited A549 growth in both zebrafish and nude mouse xenograft model. Co-treatment with adriamycin not only enhanced the antitumor efficacy, but also reduced the cardiotoxicity. Our findings suggest that digoxin has the potential to be applied as an antitumor drug via inhibiting both DNA DSB and SSB repair, and combination with adriamycin for therapy of human non-small cell lung cancer is reasonable.
PMID: 32180730 [PubMed]
12:28
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pubmed: tutte cardiotoxicity...
Cancer therapy cardiotoxicity detection: understanding the limitations of cardiac imaging.
Cancer therapy cardiotoxicity detection: understanding the limitations of cardiac imaging.
Heart. 2020 Mar 16;:
Authors: Palaskas N, Lopez-Mattei J
PMID: 32179588 [PubMed - as supplied by publisher]
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pubmed: tutte cardiotoxicity...
Hypertension and incident cardiovascular events following ibrutinib initiation.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--ashpublications.org-images-pubmed-logo.png Related Articles
Hypertension and incident cardiovascular events following ibrutinib initiation.
Blood. 2019 11 28;134(22):1919-1928
Authors: Dickerson T, Wiczer T, Waller A, Philippon J, Porter K, Haddad D, Guha A, Rogers KA, Bhat S, Byrd JC, Woyach JA, Awan F, Addison D
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