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pubmed: tutte cardiotoxicity...

MiR-526b-3p mediates doxorubicin-induced cardiotoxicity by targeting STAT3 to inactivate VEGFA.

Biomed Pharmacother. 2020 Jan 17;123:109751

Authors: Zhang L, Liu L, Li X

Abstract

Doxorubicin (DOX), a wide-spectrum chemotherapeutic agent, is recognized to have cardiotoxic side effects when it is applied in hematological diseases and solid tumor management. However, the mechanisms behind the DOX-induced anomaly of vascular homeostasis remain mostly elusive. qRT-PCR and immumohistochemical staining indicated cardiac increase of miR-526b-3p, and decrease of CD31 and CD34 in DOX-treated mice. The regulatory function of miR-526b-3p on cardiac function and cardiac microvessel density was detected via the transfection of miR-526b-3p mimics or inhibitor into Human Umbilical Vein Endothelial Cells (HUVECs) and the administration of rAAV in mice. HUVECs proliferation, apoptosis, tube formation, and migration were inspected by EdU, flow cytometry, tube formation and transwell assays. MiR-526b-3p was anti-proliferative but apoptosis-initiating in HUVECs, and aggravated cardiac abnormalities caused by DOX. Mechanically, the relationship between miR-526b-3p and VEGFA was disclosed by qRT-PCR. VEGFA and STAT3 interaction was confirmed by ChIP and luciferase reporter assay. MiR-526b-3p targeted STAT3 to reduce VEGFA transcription. We designed rescue assays and presented that the negative effects of miR-526b-3p on cardiac dysfunction and HUVECs were rescued by VEGFA reintroduction in DOX-affected mice. Overall, miR-526b-3p accelerated doxorubicin-induced cardiotoxicity through modulating STAT3/VEGFA, highlighting that targeting miR-526b-3p as a potential method to protect against DOX-induced cardiac dysfunction.

PMID: 31958751 [PubMed - as supplied by publisher]

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pubmed: tutte cardiotoxicity...

Effect of niraparib on cardiac repolarization in patients with platinum-sensitive, recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer.

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Effect of niraparib on cardiac repolarization in patients with platinum-sensitive, recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer.

Cancer Chemother Pharmacol. 2019 04;83(4):717-726

Authors: Moore K, Chan JK, Secord AA, Patel MR, Callahan T, Guo W, Zhang ZY

Abstract

PURPOSE: Anticancer drugs may cause cardiovascular toxicities, including QT interval prolongation. Niraparib, a potent and selective once-daily oral poly (ADP-ribose) polymerase inhibitor, is approved as a maintenance therapy in platinum-sensitive recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC). Here, we present the effects of niraparib on cardiac repolarization, and the correlation between changes in baseline QT interval corrected by Fridericia's formula (ΔQTcF) and niraparib plasma concentrations.

METHODS: Patients with EOC from the NOVA study (subset of n = 15), the food effect NOVA substudy (n = 17), and a QTc substudy (n = 26) underwent intensive electrocardiographic (ECG) monitoring that included triplicate ECG testing on Day 1 at baseline (predose) and at 1, 1.5, 2, 3, 4, 6, and 8 h postdose concurrent with time-matched blood sampling for determination of niraparib plasma concentrations. All patients received once-daily 300-mg niraparib until disease progression or toxicity.

RESULTS: Across the 3 substudies, the upper limit of the two-sided 90% confidence interval (CI) of ΔQTcF was ≤ 10 ms at every postdose timepoint, with a maximum upper limit of 4.3 ms, which indicates no clinically meaningful effect on QTc prolongation. No statistically significant relationship between ΔQTcF and niraparib plasma concentration was observed (estimated slope: 0.0049; 95% CI: - 0.0020, 0.0117; P = 0.164). There were no clinically relevant changes in other ECG parameters that could be attributable to niraparib.

CONCLUSION: Niraparib administration at the recommended daily dose of 300 mg for EOC is not associated with clinically relevant alteration of ECGs, including QTc prolongation.

PMID: 30680521 [PubMed - indexed for MEDLINE]

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pubmed: tutte cardiotoxicity...

Severe left atrial enlargement due to carfilzomib use in multiple myeloma.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journals.sagepub.com-pb-assets-sage-pubmed-sage.png Related Articles

Severe left atrial enlargement due to carfilzomib use in multiple myeloma.

J Oncol Pharm Pract. 2019 Dec;25(8):2045-2048

Authors: Dasanu CA, Plaxe SC, Popescu IM, Gupta V, Sontz E, Codreanu I

Abstract

Several cardiovascular effects have been attributed to carfilzomib in the recent literature. These side effects must be recognized promptly by treating physicians and pharmacists. Special attention is required in patients with pre-existing cardiac conditions, liver function abnormalities and/or advanced age. This is the first report of a severe left atrial enlargement due to carfilzomib use in the setting of multiple myeloma. This condition improved dramatically seven months after cessation of carfilzomib. The authors discuss further various cardiac and vascular abnormalities linked with carfilzomib in the medical literature. Prompt withdrawal of this agent is essential in these cases as it may prevent dismal outcomes.

PMID: 30636528 [PubMed - indexed for MEDLINE]

22 January 2020

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pubmed: tutte cardiotoxicity...

Immune Checkpoint Inhibitor Myocarditis: Pathophysiological Characteristics, Diagnosis, and Treatment.

J Am Heart Assoc. 2020 Jan 21;9(2):e013757

Authors: Palaskas N, Lopez-Mattei J, Durand JB, Iliescu C, Deswal A

PMID: 31960755 [PubMed - in process]

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pubmed: tutte cardiotoxicity...

The Role of Angiotensin-Converting Enzyme Inhibitors and β-Blockers in Primary Prevention of Cardiac Dysfunction in Breast Cancer Patients.

J Am Heart Assoc. 2020 Jan 21;9(2):e015327

Authors: Brown SA, Okwuosa TM, Barac A, Volgman AS

PMID: 31960742 [PubMed - in process]

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pubmed: tutte cardiotoxicity...

Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction.

J Am Heart Assoc. 2020 Jan 21;9(2):e014708

Authors: Demissei BG, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan V, Domchek SM, DeMichele A, Shah P, Clark AS, Fox K, Matro J, Bradbury AR, Knollman H, Getz KD, Armenian SH, Januzzi JL, Tang WHW, Liu P, Ky B

Abstract

Background We examined the longitudinal associations between changes in cardiovascular biomarkers and cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer treated with cardotoxic cancer therapy. Methods and Results Repeated measures of high-sensitivity cardiac troponin T (hs-cTnT), NT-proBNP (N-terminal pro-B-type natriuretic peptide), myeloperoxidase, placental growth factor, and growth differentiation factor 15 were assessed longitudinally in a prospective cohort of 323 patients treated with anthracyclines and/or trastuzumab followed over a maximum of 3.7 years with serial echocardiograms. CTRCD was defined as a ≥10% decline in left ventricular ejection fraction to a value <50%.14 ng/L at anthracycline completion were associated with a 2-fold increased CTRCD risk (hazard ratio, 2.01; 95% CI, 1.00-4.06). There was a modest association between changes in NT-proBNP and left ventricular ejection fraction in the overall cohort; this was most pronounced with sequential anthracycline and trastuzumab (1.1% left ventricular ejection fraction decline [95% CI, -1.8 to -0.4] with each NT-proBNP doubling). Increases in NT-proBNP were also associated with CTRCD (hazard ratio per doubling, 1.56; 95% CI, 1.32-1.84). Increases in myeloperoxidase were associated with CTRCD in patients who received sequential anthracycline and trastuzumab (hazard ratio per doubling, 1.28; 95% CI, 1.04-1.58). Conclusions Cardiovascular biomarkers may play an important role in CTRCD risk prediction in patients with breast cancer who receive cardiotoxic cancer therapy, particularly in those treated with sequential anthracycline and trastuzumab therapy. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01173341.

PMID: 31959034 [PubMed - in process]

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pubmed: tutte cardiotoxicity...

Simultaneous Left Ventricular Volume and Strain Changes During Chemotherapy Associate With 2-Year Postchemotherapy Measures of Left Ventricular Ejection Fraction.