Evaluation of lecithinized human recombinant super oxide dismutase as cardioprotectant in anthracycline‐treated breast cancer patients

Broeyer, Freerk; Osanto, Susanne; Suzuki, Jun; Jongh, Felix de; Slooten, H. van; Tanis, Bea C.; Bruning, T. A.; Bax, Jeroen J.; Eck, Henk J. Ritsema van; Kam, Marieke L. de; Cohen, Adam F.; Mituzhima, Yutaka; Burggraaf, Jacobus

doi:10.1111/bcp.12429

Cited by 25 publications

(19 citation statements)

References 43 publications

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“…However, recent evidence suggests that the primary event in the pathogenesis of anthracycline cardiotoxicity is the inhibition of topoisomerase II activity ( 11 ). Consistent with this hypothesis, a randomized study performed in breast cancer patients to investigate whether free radical scavenger super oxide dismutase (SOD) would protect against anthracycline-mediated cardiotoxicity gave negative results ( 12 ). Regardless of the molecular event at the origin of anthracycline cardiotoxicity, this latter then develops through the impairment of many cardiac cell functions, such as decreased expression of key proteins, disruption of Ca2+ homeostasis, induction of mitochondrial DNA lesions and perturbation of mitochondrial bioenergetics, degradation of myofilamental and cytoskeletal proteins, and interference with various pro-survival kinases [for an extensive review of these alternative mechanisms the reader is referred to Simunek et al ( 13 )].…”

Section: Cardiotoxicity Associated With Common Agents Used For Cancermentioning

confidence: 97%

The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors

Rizzo

Mele²,

Caliceti

et al. 2015

Front. Oncol.

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Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells, which are considered responsible for tumor recurrence and metastasis. Additionally, since Delta-like ligand 4 (Dll4)-activated Notch signaling is a major modulator of angiogenesis, anti-Dll4 agents are being investigated to reduce vascularization of the tumor. Notch plays a major role in the heart during the development and, after birth, in response to cardiac damage. Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents) could potentially affect myocardial repair. The past experience with trastuzumab and other tyrosine kinase inhibitors used for cancer therapy demonstrates that the possible cardiotoxicity of agents targeting shared pathways between cancer and heart and the vasculature should be considered. To date, Notch inhibition in cancer patients has resulted only in mild gastrointestinal toxicity. Little is known about the potential long-term cardiotoxicity associated to Notch inhibition in cancer patients. In this review, we will focus on mechanisms through which inhibition of Notch signaling could lead to cardiomyocytes and endothelial dysfunctions. These adverse effects could contrast with the benefits of therapeutic responses in cancer cells during times of increased cardiac stress and/or in the presence of cardiovascular risk factor.

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Section: Cardiotoxicity Associated With Common Agents Used For Cancermentioning

confidence: 97%

The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors

Rizzo

Mele²,

Caliceti

et al. 2015

Front. Oncol.

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“…It is known that AIC is partly caused by production of free radicals [ 73 ]. Therefore, DEX has been approved as a cardioprotective agent, being considered the treatment of first choice for AIC [ 74 ].…”

Section: Antioxidant Agents – Dexrazoxanementioning

confidence: 99%

Cardiotoxicity of anthracycline therapy: current perspectives

Valcovici¹,

Andrica²,

Şerban³

et al. 2016

aoms

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Anthracyclines, especially doxorubicin and daunorubicin, are the drugs of first choice in the treatment of patients with hematologic malignancies, soft-tissue sarcomas, and solid tumors. Unfortunately, the use of anthracyclines is limited by their dose-dependent and cumulative cardiotoxicity. The molecular mechanism responsible for anthracycline-induced cardiotoxicity remains poorly understood, although experimental and clinical studies have shown that oxidative stress plays the main role. Hence, antioxidant agents, especially dexrazoxane, and also other drug classes (statins, β-blockers) proved to have a beneficial effect in protecting against anthracycline-induced cardiotoxicity. According to previous clinical trials, the major high-risk factors for anthracycline-induced cardiotoxicity are age, body weight, female gender, radiotherapy, and other diseases such as Down syndrome, familial dilated cardiomyopathy, diabetes and hypertension. Consequently, further studies are needed to elucidate the molecular pathogenesis of anthracycline-induced cardiotoxicity and also to discover new cardioprotective agents against anthracycline-induced cardiotoxicity.

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“…Based on the concept that free radicals involve in DOX cardiotoxicity, a number of antioxidant compounds were tested in animal models and cancer patients [ 7 – 9 ]. Studies with animal models of cardiac overexpression of certain antioxidants such as catalase and metallothionein have shown the well protection from DOX-induced cardiotoxicity [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Low dose radiation prevents doxorubicin-induced cardiotoxicity

et al. 2017

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This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

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Evaluation of lecithinized human recombinant super oxide dismutase as cardioprotectant in anthracycline‐treated breast cancer patients

Cited by 25 publications

References 43 publications

The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors

The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors

Cardiotoxicity of anthracycline therapy: current perspectives

Low dose radiation prevents doxorubicin-induced cardiotoxicity

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