Association of NADPH Oxidase Polymorphisms with Anthracycline-Induced Cardiotoxicity in the RICOVER-60 Trial of Patients with Aggressive CD20
            <sup>+</sup>
            B-Cell Lymphoma

Reichwagen, Annegret; Ziepert, Marita; Kreuz, Markus; Gödtel-Armbrust, Ute; Rixecker, Torben; Poeschel, Viola; Toliat, Mohammad Reza; Nürnberg, Peter; Tzvetkov, Mladen V.; Deng, Shiwei; Trümper, Lorenz; Hasenfuß, Gerd; Pfreundschuh, Michael; Wojnowski, Leszek

doi:10.2217/pgs.14.179

Cited by 52 publications

(55 citation statements)

References 29 publications

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“…The characteristics of the included studies are presented in Table 1. Eighteen of the studies were case control studies 20–23, 30–43 , of which eight were nested case-control studies 22, 23, 32, 34–37, 42 . Another seven were prospective cohort studies 44–50 while two were retrospective cohort study 51, 52 .…”

Section: Resultsmentioning

confidence: 99%

“…The remaining one was a case report 53 . These studies were conducted in the North America (n = 16) 20, 21, 23, 30, 31, 33–37, 42–44, 46, 47, 52 , Europe (n = 9) 22, 32, 38–41, 45, 48, 51 , and Asia (n = 1) 50 while two did not report the study location 49, 53 . Almost equal number of studies were conducted in children (n = 10) and adults (n = 13) population.…”

Section: Resultsmentioning

confidence: 99%

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Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis

Leong

Chaiyakunapruk

Lee

2017

Sci Rep

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Anthracyclines play an important role in the management of patients with cancer but the development of anthracycline-induced cardiotoxicity (ACT) remains a significant concern for most clinicians. Recently, genetic approach has been used to identify patients at increased risk of ACT. This systematic review assessed the association between genomic markers and ACT. A systematic literature search was performed in Medline, PubMed, Cochrane Central Register of Controlled Studies, CINAHL Plus, AMED, EMBASE and HuGE Navigator from inception until May 2016. Twenty-eight studies examining the association of genetic variants and ACT were identified. These studies examined 84 different genes and 147 single nucleotide polymorphisms. Meta-analyses showed 3 risk variants significantly increased the risk for ACT; namely ABCC2 rs8187710 (pooled odds ratio: 2.20; 95% CI: 1.36–3.54), CYBA rs4673 (1.55; 1.05–2.30) and RAC2 rs13058338 (1.79; 1.27–2.52). The current evidence remains unclear on the potential role of pharmacogenomic screening prior to anthracycline therapy. Further research is needed to improve the diagnostic and prognostic role in predicting ACT.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis

Leong

Chaiyakunapruk

Lee

2017

Sci Rep

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“…Genetic disruption of NOX2 is known to protect against doxorubicin cardiotoxicity, while doxorubicin-treated wild-type mice display NOX2 and NOX4 up-regulation and increased oxidase activity (Deng et al, 2007;Zhao et al, 2010). Notably, the association between cardiotoxicity and gene variants in the subunits of human NADPH oxidases reinforce the relevance of these enzymes in anthracycline cardiomyopathy (Wojnowski et al, 2005;Reichwagen et al, 2015). By counteracting doxorubicin-induced increases of NOX2 and NOX4 expression, ranolazine positively affected late consequences of doxorubicin, supporting the early initiation of ranolazine treatment to prevent the development of late anthracycline cardiomyopathy.…”

Section: Bjpmentioning

confidence: 98%

Effects of ranolazine in a model of doxorubicin‐induced left ventricle diastolic dysfunction

Cappetta

Esposito

Coppini

et al. 2017

British J Pharmacology

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Doxorubicin is a highly effective anticancer drug, but its clinical application is hampered by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of doxorubicin cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent later development of cardiotoxicity is warranted. Increased doxorubicin-dependent ROS may explain, in part, Ca 2+ and Na + overload that contributes to diastolic dysfunction and development of heart failure. Therefore, we tested whether the administration of ranolazine, a selective blocker of late Na + current, immediately after completing doxorubicin therapy, could affect diastolic dysfunction and interfere with the progression of functional decline. EXPERIMENTAL APPROACHFischer 344 rats received a cumulative dose of doxorubicin of 15 mg·kg À1 over a period of 2 weeks. After the assessment of diastolic dysfunction, the animals were treated with ranolazine (80 mg·kg À1 , daily) for the following 4 weeks. KEY RESULTSWhile diastolic and systolic function progressively deteriorated in doxorubicin-treated animals, treatment with ranolazine relieved diastolic dysfunction and prevented worsening of systolic function, decreasing mortality. Ranolazine lowered myocardial NADPH oxidase 2 expression and oxidative/nitrative stress. Expression of the Na + /Ca 2+ exchanger 1 and Na v 1.5 channels was reduced and of the sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase 2 protein was increased. In addition, ranolazine lowered doxorubicin-induced hyper-phosphorylation and oxidation of Ca 2+ /calmodulin-dependent protein kinase II, and decreased myocardial fibrosis. CONCLUSIONS AND IMPLICATIONSRanolazine, by the increased Na + influx, induced by doxorubicin, altered cardiac Ca 2+ and Na + handling and attenuated diastolic dysfunction induced by doxorubicin, thus preventing the progression of cardiomyopathy. LINKED ARTICLES

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“…Individual predisposition to anthracycline cardiotoxicity can also build on high expression levels of topoisomerase IIβ [60] or genetic variants of topoisomerase IIβ coregulating factors (retinoic acid receptor-γ) [61], polymorphisms of drug transporters that contribute to anthracycline distribution and elimination (ATP-binding cassette proteins of the multidrug resistance proteins family) [62], prooxidant enzymes (NADPH oxidase) [63], and matrix-remodeling enzymes (type 3 hyaluronan synthase) [64]. In brief, a constellation of factors may cause an unpredictable aggravation of cardiotoxicity.…”

Section: Primary Prevention Of Anthracycline Cardiotoxicitymentioning

confidence: 99%

Primary Prevention Strategies for Anthracycline Cardiotoxicity: A Brief Overview

Menna¹,

Salvatorelli

2017

Chemotherapy

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The clinical use of doxorubicin and other antitumor anthracyclines is limited by a dose-related risk of cardiomyopathy and heart failure which may occur “on treatment” or any time, from months to years, after completing chemotherapy. Dose reductions diminish the incidence of cardiac events attributable to anthracyclines, but heart failure still occurs in some patients exposed to low or moderate anthracycline doses. Because anthracyclines improve the life expectancy of patients with, for example, breast cancer or lymphomas, preventing or diminishing the risk of early or delayed cardiotoxicity is of obvious clinical importance. Here, we briefly review some potential strategies of primary prevention that are based on what we know about the molecular mechanisms of cardiotoxicity, and what can be done, or might be done, to interfere with the pharmacokinetic, pharmacodynamic, and genetic determinants of cardiotoxicity.

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Association of NADPH Oxidase Polymorphisms with Anthracycline-Induced Cardiotoxicity in the RICOVER-60 Trial of Patients with Aggressive CD20 ⁺ B-Cell Lymphoma

Abstract: Our results support the theory that NADPH oxidase is involved in anthracycline-induced cardiotoxicity. Original submitted 9 July 2014; Revision submitted 19 December 2014.

Cited by 52 publications

References 29 publications

Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis

Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis

Effects of ranolazine in a model of doxorubicin‐induced left ventricle diastolic dysfunction

Primary Prevention Strategies for Anthracycline Cardiotoxicity: A Brief Overview

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Association of NADPH Oxidase Polymorphisms with Anthracycline-Induced Cardiotoxicity in the RICOVER-60 Trial of Patients with Aggressive CD20 + B-Cell Lymphoma

Abstract: Our results support the theory that NADPH oxidase is involved in anthracycline-induced cardiotoxicity. Original submitted 9 July 2014; Revision submitted 19 December 2014.

Cited by 52 publications

References 29 publications

Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis

Candidate Gene Association Studies of Anthracycline-induced Cardiotoxicity: A Systematic Review and Meta-analysis

Effects of ranolazine in a model of doxorubicin‐induced left ventricle diastolic dysfunction

Primary Prevention Strategies for Anthracycline Cardiotoxicity: A Brief Overview

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Product

Resources

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Association of NADPH Oxidase Polymorphisms with Anthracycline-Induced Cardiotoxicity in the RICOVER-60 Trial of Patients with Aggressive CD20 ⁺ B-Cell Lymphoma