Targeting proinflammatory cytokines, oxidative stress, TGF-β1 and STAT-3 by rosuvastatin and ubiquinone to ameliorate trastuzumab cardiotoxicity

Kabel, Ahmed M.; Elkhoely, Abeer

doi:10.1016/j.biopha.2017.06.033

Cited by 39 publications

(25 citation statements)

References 49 publications

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“…We observed that a single dose of 20 mg/kg trastuzumab for 3 weeks induced severe LV systolic dysfunction, as LVIDs and ESV were significantly increased and EF and FS were remarkably decreased compared to baseline. Although our results were compatible with several in vivo experiments [14,17,25,26] and clinical data [27,28], controversial observations regarding the correlation of trastuzumab treatment and cardiac dysfunction have been reported. Jassal et al demonstrated that 5 days treatment with 10mg/kg trastuzumab did not change the EF or FS in C57Bl/6 mice [29].…”

Section: Discussionsupporting

confidence: 92%

In Vivo Evaluation of Carvedilol Cardiac Protection Against Trastuzumab Cardiotoxicity

et al. 2020

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Cardiac dysfunction is a major side effect of trastuzumab therapy for patients with HER2-positive breast cancer. Beta blockers, such as carvedilol, have been used for protection of trastuzumab cardiotoxicity but there is no definitive conclusive clinical report on their efficacy. In the present study, the preservability effects of carvedilol on trastuzumab-induced left ventricular (LV) dysfunction and the reversibility of trastuzumab-induced cardiotoxicity were evaluated in Wistar rats by echocardiography method. We showed that trastuzumab treatment of rats could induce the LV dysfunction through increasing the LV internal systolic diameter (LVIDs), increasing the end-systolic volume (ESV), decreasing the ejection fraction (EF), and decreasing the fractional shortening (FS). These parameters were not reversed after 14 days of stopping trastuzumab administration. Interestingly, carvedilol improved LVIDs, ESV, EF, and FS. Collectively, the results of this study have verified clinical observations which simultaneously administration of carvedilol may be considered as a possible therapeutic strategy to prevent trastuzumab-mediated LV dysfunction.

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Section: Discussionsupporting

confidence: 92%

In Vivo Evaluation of Carvedilol Cardiac Protection Against Trastuzumab Cardiotoxicity

et al. 2020

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“…Because TZB cannot penetrate the brain-blood barrier, it cannot act on the brain directly. It has been previously reported that IL-6 is increased after administration of TZB [29]. Therefore, cognitive impairment during TZB therapy may be explained by increased IL-6 levels [30].…”

Section: Discussionmentioning

confidence: 99%

Trastuzumab Induced Chemobrain, Atorvastatin Rescued Chemobrain with Enhanced Anticancer Effect and without Hair Loss-Side Effect

Lee

Kang

et al. 2019

JCM

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The authors identified that chemo-brain was induced after trastuzumab (TZB) therapy. In addition, atorvastatin (ATV) could rescue chemo-brain during trastuzumab (TZB) therapy. Enhanced therapeutic effect of TZB was confirmed after ATV therapy. We also investigated that there was no hair loss side effect due to ATV therapy. In an animal model, 150 μg TZB and five serial doses of 20 mg/kg ATV were administered. 18F-fluorodeoxyglucose Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) data were acquired. Statistical parametric mapping analysis and voxel-based morphometry analysis were performed to identify differences in glucose metabolism and gray matter concentration. The enhanced therapeutic efficacy of TZB after ATV treatment was assessed using a human epidermal growth factor receptor 2-positive gastric cancer model. We found a decrease in cerebral glucose metabolism and gray matter concentration in the frontal lobe following TZB therapy (p < 0.005). After subsequent ATV administration, glucose metabolism and regional gray matter concentration were rescued (p < 0.005). Cognitive impairment due to TZB and the rescue effect of ATV were confirmed using a passive avoidance test and quantitative real-time reverse transcription PCR. Furthermore, the penetration and accumulation of TZB in tumors increased by 100% after ATV co-administration, which resulted in an enhanced anti-cancer effect. Our study collectively demonstrates that ATV co-administration with TZB rescued the TZB-induced chemo-brain and enhances the therapeutic efficacy of TZB in tumors. We also showed that there was no hair loss during ATV therapy.

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“…STAT-3 is a transcription factor that is activated by tyrosine phosphorylation in response to certain ligand, such as interferon and epidermal growth factor ( Tkach et al, 2013 ). It plays a key role in cell growth and differentiation, leading to ultrastructural changes in cardiomyocytes ( Kabel and Elkhoely, 2017 ). ErbB2 inhibition can lead to increased Bcl-xS/Bcl-xL ratio, activation of mitochondrial caspase-9 and caspase-3, and causing apoptosis ( Rohrbach et al, 2005 ).…”

Section: Mechanism Of Cardiotoxicitymentioning

confidence: 99%

Cardiotoxicity of Epidermal Growth Factor Receptor 2-Targeted Drugs for Breast Cancer

Yang¹,

Wang²,

Wang³

et al. 2021

Front. Pharmacol.

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Breast cancer is the most common form of cancer in women and its incidence has been increasing over the years. Human epidermal growth factor receptor 2 (HER2 or ErbB2) overexpression is responsible for 20 to 25% of invasive breast cancers, and is associated with poor prognosis. HER2-targeted therapy has significantly improved overall survival rates in patients with HER2-positive breast cancer. However, despite the benefits of this therapy, its cardiotoxicity is a major concern, especially when HER2-targeted therapy is used in conjunction with anthracyclines. At present, the mechanism of this cardiotoxicity is not fully understood. It is thought that HER2-targeting drugs inhibit HER2/NRG 1 dimer formation, causing an increase in ROS in the mitochondria of cardiomyocytes and inhibiting the PI3K/Akt and Ras/MAPK pathways, resulting in cell apoptosis. Antioxidants, ACE inhibitors, angiotensin II receptor blockers, β-blockers, statins and other drugs may have a cardioprotective effect when used with ErbB2-targeting drugs. NT-proBNP can be used to monitor trastuzumab-induced cardiotoxicity during HER2-targeted treatment and may serve as a biological marker for clinical prediction of cardiotoxicity. Measuring NT-proBNP is non-invasive, inexpensive and reproducible, therefore is worthy of the attention of clinicians. The aim of this review is to discuss the potential mechanisms, clinical features, diagnostic strategies, and intervention strategies related to cardiotoxicity of ErbB2-targeting drugs.

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Targeting proinflammatory cytokines, oxidative stress, TGF-β1 and STAT-3 by rosuvastatin and ubiquinone to ameliorate trastuzumab cardiotoxicity

Cited by 39 publications

References 49 publications

In Vivo Evaluation of Carvedilol Cardiac Protection Against Trastuzumab Cardiotoxicity

In Vivo Evaluation of Carvedilol Cardiac Protection Against Trastuzumab Cardiotoxicity

Trastuzumab Induced Chemobrain, Atorvastatin Rescued Chemobrain with Enhanced Anticancer Effect and without Hair Loss-Side Effect

Cardiotoxicity of Epidermal Growth Factor Receptor 2-Targeted Drugs for Breast Cancer

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