Abstract
Introduction: Cardiotoxicity is an adverse reaction associated with the use of anthracyclines.
Objective: To estimate the factors associated with the development of anthracycline cardiotoxicity in pediatric patients surviving cancer.
Method: Retro-prolective cohort of children diagnosed with cancer and treated with anthracyclines. Baseline echocardiographic determination of ejection fraction (LVEF0) was carried out before the start of treatment and again at 12 months (LVEF1). Demographic characteristics and treatment were obtained from the medical record. A multiple logistic regression (MLR) model was constructed; LVEF1 < 50 % was the dependent variable, which was adjusted for the main confounding variables.
Results: Sixty-five patients were included, out of which 36.9 % were females and 56.8 % had a solid tumor. LVEF0 was 74.79 ± 7.3 % and LVEF1, 67.96 ± 6.7 % (p = 0.001); 60 % developed cardiotoxicity. In the MLR, only a cumulative dose > 430 mg was associated with cardiotoxicity (p = 0.001).
Conclusions: In Mexican children, an anthracycline cumulative dose > 430 mg should be avoided in order to prevent cardiotoxicity.
PMID: 32539021 [PubMed - in process]
13:30
pubmed: tutte cardiotoxicity...
Metformin and/or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1/SOD and BAX/Bcl-2 pathways in rats.
Related Articles
Metformin and/or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1/SOD and BAX/Bcl-2 pathways in rats.
Mol Biol Rep. 2020 Jun 14;:
Authors: El Kiki SM, Omran MM, Mansour HH, Hasan HF
Abstract
Cyclophosphamide (CP) is a nitrogen mustard alkylating agent with effective antineoplastic, immunomodulatory and immunosuppressive properties. Despite its vast therapeutic uses, it is known to trigger strict cardiac toxicity. The objective of the current study was to examine the protective role of metformin (MET) and/or low dose radiation (LDR) on cardiotoxicity and apoptosis induced by CP in rats. CP (200 mg/kg i.p) induces cardiotoxicity and apoptosis as indicated by elevation of troponin, cardiac caspase-3 and Endothelin-I (ET-1). While, treatment with MET (150 mg/kg, orally for 14 days) and/or LDR (0.5 Gy) before CP hindered CP-induced toxicity. By estimating the apoptotic index (BAX/Bcl-2 ratio) CP showed significantly the highest BAX/Bcl-2 ratio. Administration of MET and/or LDR showed a significant improvement in oxidative stress indices and reverse the inhibitory effect of CP on SIRT-1. Also, Histological examination of cardiac tissues showed a sign of necrosis of myocardium after CP treatment. Conclusions: The results revealed that MET and/or LDR attenuate CP-induced cardiotoxicity by inhibiting oxidative stress and preserving the activity of antioxidant enzymes through SIRT-1/SOD and BAX/Bcl-2 pathways.
PMID: 32537703 [PubMed - as supplied by publisher]
13:30
Video file
Not included, change data exporting settings to download.
00:00, 4.2 KB
13:30
In reply to this message
pubmed: tutte cardiotoxicity...
Protective Role of Enalapril in Anthracycline-Induced Cardiotoxicity: A Systematic Review.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles
Protective Role of Enalapril in Anthracycline-Induced Cardiotoxicity: A Systematic Review.
Front Pharmacol. 2020;11:788
Authors: Zhang Y, Liu J, Li Y, Tan N, Du K, Zhao H, Wang J, Zhang J, Wang W, Wang Y
Abstract
Background: Evidence of the preventive and therapeutic effects of enalapril on cardiotoxicity caused by chemotherapy needs to be further confirmed and updated.
Methods: We performed a systematic review of studies from electronic databases that were searched from inception to January 29, 2019, and included relevant studies analyzing enalapril as a cardioprotective agent before or during the use of anthracyclines by oncology patients. Homogeneous results from different studies were pooled using RevMan 5.3 software. The Cochrane risk-of-bias tool was used to determine the quality of the studies.
Results: We examined and screened 626 studies according to specific criteria and ultimately included seven studies that were relevant to the indicated topic. Among them, three studies reported the incidence of death during 6- and 12-month follow-up periods. Six of the seven included studies showed possible positive results, suggesting that enalapril plays a cardioprotective role, while five of these studies showed that there was a significant difference in the left ventricular ejection fraction (LVEF) between an enalapril group and a control group (weighted mean difference (WMD) = 7.18, 95% CI: 2.49-11.87, I2 = 96%, P < .001). Moreover, enalapril was beneficial in reducing troponin I (TnI), creatine kinase myocardial band (CK-MB) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels in cancer patients treated with anthracycline.
Conclusions: Although a protective effect of enalapril on myocardial toxicity was observed in terms of the LVEF values and TnI, CK-MB and NT-proBNP levels, its use in the prevention and treatment of cardiotoxicity caused by anthracycline needs to be investigated by more scientific research.
PMID: 32536868 [PubMed]
13:30
pubmed: tutte cardiotoxicity...
Underuse of ECG monitoring in oncology patients receiving QT-interval prolonging drugs.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-bmjjournals_final.gif Related Articles
Underuse of ECG monitoring in oncology patients receiving QT-interval prolonging drugs.
Heart. 2019 11;105(21):1649-1655
Authors: Pezo RC, Yan AT, Earle C, Chan KK
Abstract
OBJECTIVE: We examined use of ECG monitoring in oncology patients prescribed QT-prolonging drugs.
METHODS: Patients ≥66 years diagnosed with cancer between 2005 and 2011 were identified through the Ontario Cancer Registry and linked to multiple population-based administrative databases to ascertain demographics, comorbidities, prescription drug use, systemic therapy and ECG. QT-prolonging drugs were identified as per drug lists developed by the Arizona Center for Education and Research on Therapeutics. Univariable and multivariable analyses were used to examine factors associated with ECG use in patients on first-line systemic therapy.
RESULTS: A total of 48 236 patients (median age 74; 49% women) received one or more drugs associated with a risk of QT-interval prolongation but only 27% of patients had an ECG performed. Factors associated with more ECG use on multivariable analysis included recent cancer diagnosis (p for trend <0.001
CONCLUSIONS: Our study highlights common use of QT-prolonging drugs and underuse of ECG in oncology patients. Since ECG is an inexpensive, non-invasive and widely available test, it may be readily incorporated in the monitoring of patients for toxicities in routine clinical practice.
PMID: 31129611 [PubMed - indexed for MEDLINE]
18 June 2020
14:48
Cardiotoxicity News
pubmed: tutte cardiotoxicity...
The Diagnostic and Prognostic Value of Echocardiographic Strain.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--jamanetwork.com-images-JAMA_cardio_linkout.gif Related Articles
The Diagnostic and Prognostic Value of Echocardiographic Strain.
JAMA Cardiol. 2019 06 01;4(6):580-588
Authors: Singh A, Voss WB, Lentz RW, Thomas JD, Akhter N
Abstract
Importance: Myocardial deformation or strain by speckle-tracking echocardiography (STE) has become an established echocardiographic modality for the diagnostic and prognostic evaluation of cardiac dysfunction. Current literature supports the incremental value of strain in diagnosis, risk stratification, and prognostication of a multitude of cardiac disease states.
Observations: Strain has been studied across the clinical spectrum from common to obscure pathologic conditions. This review presents the current literature evaluating characteristic strain patterns across this clinical spectrum, discusses prognostic implications, and provides a case series of classic strain polar maps, which are also known as bull's-eye plots.
Conclusions and Relevance: Characteristic bull's-eye patterns can be used to guide patient evaluation and management.
PMID: 31042262 [PubMed - indexed for MEDLINE]
20 June 2020
12:25
Cardiotoxicity News
pubmed: tutte cardiotoxicity...
Uncoupling DNA damage from chromatin damage to detoxify doxorubicin.
Related Articles
Uncoupling DNA damage from chromatin damage to detoxify doxorubicin.
Proc Natl Acad Sci U S A. 2020 Jun 17;:
Authors: Qiao X, van der Zanden SY, Wander DPA, Borràs DM, Song JY, Li X, van Duikeren S, van Gils N, Rutten A, van Herwaarden T, van Tellingen O, Giacomelli E, Bellin M, Orlova V, Tertoolen LGJ, Gerhardt S, Akkermans JJ, Bakker JM, Zuur CL, Pang B, Smits AM, Mummery CL, Smit L, Arens R, Li J, Overkleeft HS, Neefjes J
Abstract
The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. It is unclear whether these side effects are coupled to the chemotherapeutic efficacy. Doxo, Daun, Epi, and Ida execute two cellular activities: DNA damage, causing double-strand breaks (DSBs) following poisoning of topoisomerase II (Topo II), and chromatin damage, mediated through histone eviction at selected sites in the genome. Here we report that anthracycline-induced cardiotoxicity requires the combination of both cellular activities. Topo II poisons with either one of the activities fail to induce cardiotoxicity in mice and human cardiac microtissues, as observed for aclarubicin (Acla) and etoposide (Etop). Further, we show that Doxo can be detoxified by chemically separating these two activities. Anthracycline variants that induce chromatin damage without causing DSBs maintain similar anticancer potency in cell lines, mice, and human acute myeloid leukemia patients, implying that chromatin damage constitutes a major cytotoxic mechanism of anthracyclines. With these anthracyclines abstained from cardiotoxicity and therapy-related tumors, we thus uncoupled the side effects from anticancer efficacy. These results suggest that anthracycline variants acting primarily via chromatin damage may allow prolonged treatment of cancer patients and will improve the quality of life of cancer survivors.
PMID: 32554494 [PubMed - as supplied by publisher]
12:25
pubmed: tutte cardiotoxicity...
Successful Heart Transplant in a Childhood Cancer Survivor With Chemoradiotherapy-Induced Cardiomyopathy.
Related Articles
Successful Heart Transplant in a Childhood Cancer Survivor With Chemoradiotherapy-Induced Cardiomyopathy.
Exp Clin Transplant. 2020 Jun 16;:
Authors: Sipahi NF, Akhyari P, Aubin H, Mehdiani A, Erbel S, Westenfeld R, Scheiber D, Dalyanoglu H, Lichtenberg A, Boeken U
Abstract
Cancer therapy-related cardiotoxicity has been presenting a major problem in cancer survivors, who constitute a growing population caused by a significant improvement in cancer therapy during the past decades. Although some listing criteria have been defined for these patients, it is still a compelling decision to list patients with a complex cancer anamnesis. We describe herein a childhood cancer survivor after a cancer anamnesis with 2 different malignancies and an end-stage heart failure following chemoradiotherapy who was successfully treated with orthotopic heart transplant.
PMID: 32552629 [PubMed - as supplied by publisher]
12:26
pubmed: tutte cardiotoxicity...
A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles
A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity.
Cancer Lett. 2020 01 01;468:1-13
Authors: Vicente C, Arriazu E, Martínez-Balsalobre E, Peris I, Marcotegui N, García-Ramírez P, Pippa R, Rabal O, Oyarzábal J, Guruceaga E, Prósper F, Mateos MC, Cayuela ML, Odero MD
Abstract
Acute myeloid leukemia (AML) is an aggressive disease associated with very poor prognosis. Most patients are older than 60 years, and in this group only 5-15% of cases survive over 5 years. Therefore, it is urgent to develop more effective targeted therapies. Inactivation of protein phosphatase 2 A (PP2A) is a recurrent event in AML, and overexpression of its endogenous inhibitor SET is detected in ~30% of patients. The PP2A activating drug FTY720 has potent anti-leukemic effects; nevertheless, FTY720 induces cardiotoxicity at the anti-neoplastic dose. Here, we have developed a series of non-phosphorylable FTY720 analogues as a new therapeutic strategy for AML. Our results show that the lead compound CM-1231 re-activates PP2A by targeting SET-PP2A interaction, inhibiting cell proliferation and promoting apoptosis in AML cell lines and primary patient samples. Notably, CM-1231 did not induce cardiac toxicity, unlike FTY720, in zebrafish models, and reduced the invasion and aggressiveness of AML cells more than FTY720 in zebrafish xenograft models. In conclusion, CM-1231 is safer and more effective than FTY720; therefore, this compound could represent a novel and promising approach for treating AML patients with SET overexpression.
PMID: 31593801 [PubMed - indexed for MEDLINE]
21 June 2020
12:55
Cardiotoxicity News
pubmed: tutte cardiotoxicity...
Pluripotent Stem Cell Modeling of Anticancer Therapy-Induced Cardiotoxicity.
Related Articles
Pluripotent Stem Cell Modeling of Anticancer Therapy-Induced Cardiotoxicity.
Curr Cardiol Rep. 2020 Jun 19;22(8):56
Authors: Lyra-Leite DM, Burridge PW
Comments
Post a Comment
اكتب تعليق حول الموضوع