Severe Cardiotoxicity in a Patient with Colorectal Cancer Treated with Bevacizumab

Pericardiocentesis should be the first intervention but has high recurrence rates (30-60%). For patients with recurrence, repeat pericardiocentesis is indicated in those with limited expected lifespans. Extended pericardial drainage decreases recurrence to 10-20%. The addition of sclerosing agents decreases recurrence slightly but creates significant pain and can lead to pericardial constriction and therefore has fallen out of favor. Most patients with symptomatic pericardial disease have a short median survival time due to their underlying disease. In patients with a longer life expectancy, surgical drainage offers the lowest recurrence rate. Surgical approach is based on effusion location and clinical condition. Subxiphoid and thoracoscopic approaches lead to similar outcomes. Thoracotomy should be avoided as it increases morbidity without improving outcomes.

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miR-140-5p mediates bevacizumab-induced cytotoxicity to cardiomyocytes by targeting the VEGFA/14-3-3γ signal pathway

Chen

Huang

Peng

et al. 2019

Toxicology Research

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Bevacizumab (BVZ) is the first recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGFA) approved by the FDA for the treatment of different kinds of cancers, especially colorectal cancer. Although the anti-tumor effects have been verified, the side effects of BVZ are also noteworthy, among which, cardiotoxicity may be the most serious side effect of BVZ. However, the exact mechanisms of cardiotoxicity induced by BVZ have been little explored. This study was conducted in vitro in a human cardiac myocyte (HCM) model. MTT assay was conducted to determine BVZ-stimulated cell viability. For testing the function and mechanism, the cells were transfected with miR-140-5p mimics, miR-140-5p inhibitor and/or VEGFA small interfering RNA (si-VEGFA). Then, apoptosis of the cells was detected via annexin V/propidium iodide (AV-PI) staining followed by flow cytometry. qRT-PCR and western blot assays were applied to measure gene expression (i.e. mRNA) and protein levels, respectively. The CK, LDH, SOD, CAT and GSH-Px activities and MDA level were determined using commercial kits. ROS levels were determined by DCFH-DA assay. Mitochondrial membrane potential was measured by JC-1 assay. Dual-luciferase reporter assay was used to detect the interaction between miR-140-5p and VEGFA. BVZ could inhibit HCM proliferation and induce apoptosis. miR-140-5p was upregulated in response to BVZ treatment and miR-140-5p restraint could alleviate HCM damage caused by BVZ treatment. In contrast, VEGFA and 14-3-3γ expressions were down-regulated by BVZ, and miR-140-5p could inhibit the expression of 14-3-3γ by directly targeting VEGFA. Moreover, VEGFA suppression enhanced HCM injury stimulated by BVZ and partially reversed the functional role of the miR-140-5p inhibitor in BVZ-treated cells. Taken together, miR-140-5p promoted BVZ-treated cardiomyocyte toxicity by targeting the VEGFA/14-3-3γ signal pathway. Collectively, miR-140-5p mediated the BVZ-induced cytotoxicity to cardiomyocytes by targeting the VEGFA/14-3-3γ signal pathway, indicating that miR-140-5p may be a novel target for treating BVZ-induced cardiotoxicity.

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Severe Cardiotoxicity in a Patient with Colorectal Cancer Treated with Bevacizumab

Abstract: Although clinically-effective, the severe cardiotoxicity of bevacizumab developed after over 20 courses of treatment prompted us to look for optimal chemotherapy prescription in order to achieve a better clinical outcome.

Cited by 7 publications

References 17 publications

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miR-140-5p mediates bevacizumab-induced cytotoxicity to cardiomyocytes by targeting the VEGFA/14-3-3γ signal pathway

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