Abstract
PURPOSE: It has been supposed that cardiac toxicity of doxorubicin is due to its production of free radicals and inflammatory cytokines. Dapsone, an antibiotic drug which is the principal in a multidrug regimen for the treatment of leprosy, is a sulfone with anti-inflammatory and antioxidant immunosuppressive properties. Therefore, we designed this study to investigate the possible effects of dapsone on doxorubicin-induced cardiotoxicity.
METHODS: Male rats were administrated doxorubicin (2.5 mg/kg) and dapsone (1, 3, 10 mg/kg) intraperitoneally six times in 2 weeks. Then electrocardiographic (ECG) parameters (QRS complexes, RR and QT intervals) alternation, papillary muscle contraction and excitation, and histopathological changes were assessed. Also, the heart tissue levels of malondialdehyde (MDA) as oxidant factor and superoxide dismutase (SOD) as antioxidant enzyme, tumor necrosis factor-alpha (TNF-α) and serum level of CK-MB were analyzed.
RESULTS: Administration of dapsone with doxorubicin significantly reversed alterations induced by doxorubicin in serum levels of CK-MB, ECG parameters, papillary muscle contractility and excitation. Furthermore, the measurement of MDA, SOD and TNF-α tissue level indicated that dapsone significantly reduced oxidative stress and inflammation. These findings were consistent with histopathological analysis.
CONCLUSION: Dapsone exerts cardioprotective effects on doxorubicin-induced cardiotoxicity through its anti-inflammatory and antioxidant mechanism.
PMID: 31915967 [PubMed - as supplied by publisher]
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Realgar transforming solution as a novel arsenic agent with a lower risk of cardiotoxicity.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles
Realgar transforming solution as a novel arsenic agent with a lower risk of cardiotoxicity.
J Pharmacol Sci. 2019 Jun;140(2):162-170
Authors: Hai Y, Song P, Wang X, Zhao L, Xie Q, Li J, Li Y, Li H
Abstract
QTc prolongation has been observed during arsenic trioxide and realgar's clinical use, and become a huge obstacle for the application. Our lab has obtained the soluble arsenic from realgar named realgar transforming solution or RTS. In this study, we first evaluated the cytotoxicity on NB4 cell and found that RTS could remarkably inhibit proliferation of NB4 than arsenic trioxide. Then we figured out the QTc prolongation of RTS treatment contrasted with arsenic trioxide; results revealed that arsenic trioxide prolonged corrected QTc of mice by 20.1% and showed 1.9-fold higher cytotoxicity on H9c2 cell than RTS. On the contrary, there could not find any QTc prolongation of mice in RTS treatment. Also, arsenic trioxide elevated the intercellular calcium accumulation of H9c2 cell by 2.02-fold v.s control and RTS. HE staining and Masson's trichrome staining had shown that there was no injured section after RTS treatments. IK1 currents of rat ventricular cardiomyocytes were diminished by 45.0% after treating with arsenic trioxide while RTS showed no significance than the control group. The results above indicated that RTS could serve as an alternative arsenic agent on leukemia and had a lower risk of cardiotoxicity.
PMID: 31285125 [PubMed - indexed for MEDLINE]
11 January 2020
13:25
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Trastuzumab emtansine (T-DM1)-associated cardiotoxicity: Pooled analysis in advanced HER2-positive breast cancer.
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Trastuzumab emtansine (T-DM1)-associated cardiotoxicity: Pooled analysis in advanced HER2-positive breast cancer.
Eur J Cancer. 2020 Jan 07;126:65-73
Authors: Pondé N, Amaye L, Lambertini M, Paesmans M, Piccart M, de Azambuja E
Abstract
INTRODUCTION: T-DM1 has been approved for the treatment of HER2+ breast cancer. Cardiac dysfunction is a side effect of trastuzumab, a component of T-DM1. However, little is known about T-DM1-associated cardiotoxicity.
METHODS: We have conducted a pooled analysis of T-DM1 trials in advanced HER2+ breast cancer cases to understand the incidence, clinical presentation as well as to establish possible risk factors for T-DM1-associated cardiotoxicity. The primary endpoint was the incidence of cardiac events (CEs). CEs were categorized as follows: (1) congestive heart failure (CHF) or grade 3/4 LVEF drop; (2) cardiac ischemia, (3) cardiac arrhythmia, (4) grade 1/2 LVEF drop. Secondary endpoints included CE recovery rate and impact of CEs on treatment discontinuation. Logistic regression was used to assess possible risk factors for CEs.
RESULTS: Individual patient-level data from 1961 patients exposed to T-DM1 in seven trials were pooled. Of these, 1544 received T-DM1 and 417 T-DM1 + pertuzumab. CHF/LVEF drop grade 3/4 was reported in 0.71%, cardiac ischemia in 0.1%, cardiac arrhythmia in 0.71% and grade 1/2 LVEF drop in 2.04%. The total CE rate was 3.37% (95% confidence interval (CI), 2.6%-4.3%). Multivariate analysis showed patient's age ≥65 (OR 3.0; 95% CI, 1.77-5.14; P-value <0.001)<55%
CONCLUSION: The incidence of CEs in patients receiving T-DM1 was low. Older patients receiving T-DM1 should be carefully followed for cardiac safety during treatment.
PMID: 31923729 [PubMed - as supplied by publisher]
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The circadian clock protects against ionizing radiation-induced cardiotoxicity.
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The circadian clock protects against ionizing radiation-induced cardiotoxicity.
FASEB J. 2020 Jan 10;:
Authors: Dakup PP, Porter KI, Gajula RP, Goel PN, Cheng Z, Gaddameedhi S
Abstract
Radiation therapy (RT) is commonly used to treat solid tumors of the breast, lung, and esophagus; however, the heart is an unintentional target of ionizing radiation (IR). IR exposure to the heart results in chronic toxicities including heart failure. We hypothesize that the circadian system plays regulatory roles in minimizing the IR-induced cardiotoxicity. We treated mice in control (Day Shift), environmentally disrupted (Rotating Shift), and genetically disrupted (Per 1/2 mutant) circadian conditions with 18 Gy of IR to the heart. Compared to control mice, circadian clock disruption significantly exacerbated post-IR systolic dysfunction (by ultrasound echocardiography) and increased fibrosis in mice. At the cellular level, Bmal1 protein bound to Atm, Brca1, and Brca2 promoter regions and its expression level was inversely correlated with the DNA damage levels based on the state of the clock. Further studies with circadian synchronized cardiomyocytes revealed that Bmal1 depletion increased the IR-induced DNA damage and apoptosis. Collectively, these findings suggest that the circadian clock protects from IR-induced toxicity and potentially impacts RT treatment outcome in cancer patients through IR-induced DNA damage responses.
PMID: 31919902 [PubMed - as supplied by publisher]
12 January 2020
13:55
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Various Manifestations of 5-Fluorouracil Cardiotoxicity: A Multicenter Case Series and Review of Literature.
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Various Manifestations of 5-Fluorouracil Cardiotoxicity: A Multicenter Case Series and Review of Literature.
Cardiovasc Toxicol. 2020 Jan 10;:
Authors: Allison JD, Tanavin T, Yang Y, Birnbaum G, Khalid U
Abstract
5-Fluorouracil is a key element to the treatment of colon cancer. But it is also one of the most cardiotoxic chemotherapies, and the management of those that experience cardiotoxicity can be challenging. We present three cases of 5-FU cardiac toxicity that manifested as myocardial infarction, cardiogenic shock, and ventricular fibrillation. Additionally, we discuss the current literature regarding 5-fluorouracil cardiotoxicity mechanisms as well as management.
PMID: 31925673 [PubMed - as supplied by publisher]
14 January 2020
12:43
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Prostaglandin E2 as a Therapeutic Target in Bladder Cancer: From Basic Science to Clinical Trials.
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Prostaglandin E2 as a Therapeutic Target in Bladder Cancer: From Basic Science to Clinical Trials.
Prostaglandins Other Lipid Mediat. 2020 Jan 10;:106409
Authors: Woolbright BL, Pilbeam CC, Taylor JA
Abstract
Bladder cancer (BCa) is a common solid tumor marked by high rates of recurrence, especially in non-muscle invasive disease. Prostaglandin E2 (PGE2) is a ubiquitously present lipid mediator responsible for numerous physiological actions. Inhibition of cyclooxygenase (COX) enzymes by the non-steroidal anti-inflammatory (NSAID) class of drugs results in reduced PGE2 levels. NSAID usage has been associated with reductions in cancers such as BCa. Clinical trials using NSAIDs to prevent recurrence have had mixed results, but largely converge on issues with cardiotoxicity. The purpose of this review is to understand the basic science behind how and why inhibitors of PGE2 may be effective against BCa, and to explore alternate therapeutic modalities for addressing the role of PGE2 without the associated cardiotoxicity. We will address the role of PGE2 in a diverse array of cancer-related functions including stemness, immunosuppression, proliferation, cellular signaling and more.
PMID: 31931078 [PubMed - as supplied by publisher]
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Cardiac Safety of the Trastuzumab Biosimilar ABP 980 in Women with HER2-Positive Early Breast Cancer in the Randomized, Double-Blind, Active-Controlled LILAC Study.
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Cardiac Safety of the Trastuzumab Biosimilar ABP 980 in Women with HER2-Positive Early Breast Cancer in the Randomized, Double-Blind, Active-Controlled LILAC Study.
Drug Saf. 2020 Jan 11;:
Authors: Kolberg HC, Colleoni M, Demetriou GS, Santi P, Tesch H, Fujiwara Y, Tomasevic Z, Hanes V
Abstract
INTRODUCTION: Although the human epidermal growth factor receptor 2 (HER2) blocker trastuzumab is generally well tolerated, cardiotoxicity can be an important therapeutic limitation.
OBJECTIVE: In this prespecified analysis, we compared the cardiac safety of the trastuzumab biosimilar ABP 980 (KANJINTI™) and the trastuzumab reference product (RP; Herceptin®) in the phase III LILAC study (ClinicalTrials.gov identifier NCT01901146).
METHODS: In the neoadjuvant phase of LILAC, after run-in chemotherapy, 725 patients were randomized 1:1 to ABP 980 (n = 364) or trastuzumab RP (n = 361) plus paclitaxel (every 3 weeks [Q3W] or every week [QW]) for four cycles. After surgery, patients continued treatment Q3W for up to 1 year; ABP 980-treated patients continued ABP 980 (ABP 980/ABP 980; n = 364), and trastuzumab RP-treated patients either continued on the RP (trastuzumab RP/trastuzumab RP; n = 190) or switched to ABP 980 (trastuzumab RP/ABP 980; n = 171). Cardiac safety was monitored by computerized 12-lead electrocardiogram, and left ventricular ejection fraction (LVEF) was assessed by two-dimensional (2D) echocardiogram. LVEF decline was defined as LVEF value decrease from study baseline by ≥ 10 percentage points and to
RESULTS: Over the entire study, 22 (3.1%) patients had protocol-defined LVEF decline; no meaningful between-group differences were observed (ABP 980/ABP 980: 2.8%; trastuzumab RP/trastuzumab RP: 3.3%; trastuzumab RP/ABP 980: 3.5%). The incidence of cardiac adverse events was low and comparable in the treatment groups. One grade 3 cardiac failure event reported in the trastuzumab RP/ABP 980 arm, and another in the trastuzumab RP/trastuzumab RP arm, were coincident with LVEF decline. One patient discontinued the investigational product during the adjuvant phase because of cardiac failure.
CONCLUSION: These prespecified analyses confirm the tolerability of ABP 980 and demonstrate clinical similarity of ABP 980 and trastuzumab RP with respect to cardiac safety. No new cardiac safety signals were observed whether patients were receiving ABP 980 or switched from the RP to ABP 980.
PMID: 31927716 [PubMed - as supplied by publisher]
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Cardiac Magnetic Resonance and Cardio-Oncology: Does T2 Signal the End of Anthracycline Cardiotoxicity?
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles
Cardiac Magnetic Resonance and Cardio-Oncology: Does T2 Signal the End of Anthracycline Cardiotoxicity?
J Am Coll Cardiol. 2019 02 26;73(7):792-794
Authors: Yu AF, Chan AT, Steingart RM
PMID: 30784672 [PubMed - indexed for MEDLINE]
15 January 2020
01:27
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