State of the art review: Chemotherapy-induced cardiotoxicity in children

Loar, Robert W.; Noel, Cory V.; Tunuguntla, Hari; Colquitt, John L.; Pignatelli, Ricardo H.

doi:10.1111/chd.12564

Cited by 36 publications

(37 citation statements)

References 113 publications

(219 reference statements)

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“…Cancer survivors, when compared with their healthy counterparts, are at high risk of cardiovascular-related deaths, including myocardial infarction with coronary artery disease, cardiomyopathy with congestive heart failure, and cerebrovascular events [4,5]. People on cardiotoxic chemotherapy can be considered as a stage A group of heart failure patients [6].…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective Effect of Croton macrostachyus Stem Bark Extract and Solvent Fractions on Cyclophosphamide‐Induced Cardiotoxicity in Rats

Ayza

Balasubramanian²,

Berhe

2020

Evidence-Based Complementary and Alternative Medicine

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Context. Croton macrostachyus Hochst. ex Delile (Euphorbiaceae) has been used in traditional medicine to manage heart failure and other heart diseases in Ethiopia. Objective. To evaluate the antioxidant and cardioprotective activities of stem bark extract and solvent fractions of Croton macrostachyus on cyclophosphamide-induced cardiotoxicity in rats. Materials and Methods. DPPH free radical scavenging assay method was used to determine antioxidant activity whereas Sprague-Dawley rats were used to evaluate the cardioprotective activity. Except for the normal control, all groups were subjected to cyclophosphamide (200 mg/kg, i.p.) toxicity on the first day. Enalapril at 10 mg/kg was used as a reference. The hydromethanolic crude extract (100, 200, and 400 mg/kg) and aqueous and ethyl acetate fractions (100 and 200 mg/kg, each) were administered for 10 days. The cardioprotective activities were evaluated using cardiac biomarkers such as Troponin I, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), and histopathological studies of heart tissue. Results. Crude extract and ethyl acetate and aqueous fractions exhibited free radical scavenging activities at IC50 of 594 μg/mL, 419 μg/mL, and 716 μg/mL, respectively. Crude extract at 400 mg/kg decreased the levels of troponin, AST, ALT, and ALP to 0.29 ± 0.06 ng/mL, 103.00 ± 7.63 U/L, 99.80 ± 6.18 U/L, and 108.80 ± 8.81 U/L, respectively. In addition, ethyl acetate fraction at 200 mg/kg decreased the levels of troponin, AST, ALT, and ALP to 0.22 ± 0.02 ng/mL, 137.00 ± 14.30 U/L, 90.33 ± 6.13 U/L, and 166.67 ± 13.50 U/L, respectively, compared with the cyclophosphamide control group. Conclusions. Croton macrostachyus possesses cardioprotective activities and it could be a possible source of treatment for cardiotoxicity induced by cyclophosphamide.

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Section: Introductionmentioning

confidence: 99%

Cardioprotective Effect of Croton macrostachyus Stem Bark Extract and Solvent Fractions on Cyclophosphamide‐Induced Cardiotoxicity in Rats

Ayza

Balasubramanian²,

Berhe

2020

Evidence-Based Complementary and Alternative Medicine

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“…The mechanism of anthracycline-induced cardiotoxicity has not been fully understood. The existing evidences reveal that it is directly related to the free radicals produced by anthracyclines [7,8]. Unlike their mechanism of anti-tumor activity, the main mechanisms of anthracycline-induced cardiotoxicity involve ironmediated production of reactive oxygen species (ROS) and the promotion of myocardial oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity

Wang¹,

Chen

Zhang³

et al. 2020

BMC Cardiovasc Disord

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Background: The current diagnostic methods and treatments still fail to lower the incidence of anthracyclineinduced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicityrelated abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Methods: Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the Gene Expression Omnibus (GEO) database. The biomarker expression data of women with chemotherapyinduced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the micro RNAs (miRNAs) regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the Gene Ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. Result: The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and Target Scan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain seven cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273 g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. The signaling pathway is mainly concentrated in TGF-β signaling pathway and adhesion signaling pathway. Conclusions: Changes in expression of hsa-miR-4638-3p and hsa-miR-1273 g-3p may contribute to the detection of anthracyclines induced cardiac toxicity, and their potential function may be related to TGF-β signaling pathway and adhesion signaling pathway.

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“…The mechanism of anthracycline-induced cardiotoxicity has not been fully understood. The existing evidences reveal that it is directly related to the free radicals produced by anthracyclines [4,5]. Unlike their mechanism of anti-tumor activity, the main mechanisms of anthracycline-induced cardiotoxicity involve iron-mediated production of reactive oxygen species (ROS) and the promotion of myocardial oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

Wang

Chen

Zhang

et al. 2019

Preprint

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The current diagnostic methods and treatments still fail to lower the incidence of anthracyclineinduced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicityrelated gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions.The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs.Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a.Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of 3 anthracycline cardiotoxicity.

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State of the art review: Chemotherapy-induced cardiotoxicity in children

Cited by 36 publications

References 113 publications

Cardioprotective Effect of Croton macrostachyus Stem Bark Extract and Solvent Fractions on Cyclophosphamide‐Induced Cardiotoxicity in Rats

Cardioprotective Effect of Croton macrostachyus Stem Bark Extract and Solvent Fractions on Cyclophosphamide‐Induced Cardiotoxicity in Rats

Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity

Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

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