ABSTRACT

Trastuzumab (Tra), the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2), is commonly used alongside doxorubicin (Dox) as a combination therapy in HER2-positive breast cancer. Unfortunately, this leads to a more severe cardiotoxicity than Dox alone. NLRP3 inflammasome is known to be involved in Dox-induced cardiotoxicity and multiple cardiovascular diseases. However, whether the NLRP3 inflammasome contributes to the synergistic cardiotoxicity of Tra has not been elucidated. In this study, primary neonatal rat cardiomyocyte (PNRC), H9c2 cells and mice were treated with Dox (15 mg/kg in mice or 1μM in cardiomyocyte) or Tra (15.75 mg/kg in mice or 1μM in cardiomyocyte), or Dox combined Tra as cardiotoxicity models to investigate this question. Our results demonstrated that Tra significantly potentiated Dox-induced cardiomyocyte apoptosis and cardiac dysfunction. These were accompanied by the increased expressions of NLRP3 inflammasome components (NLRP3, ASC and cleaved caspase-1), the secretion of IL-β and the pronounced production of ROS. Inhibiting the activation of NLRP3 inflammasome by NLRP3 silencing significantly reduced cell apoptosis and ROS production in Dox combined Tra-treated PNRC. Compared with the wild type mice, the systolic dysfunction, myocardial hypertrophy, cardiomyocyte apoptosis and oxidative stress induced by Dox combined Tra were alleviated in NLRP3 gene knockout mice. Our data revealed that the co-activation of NLRP3 inflammasome by Tra promoted the inflammation, oxidative stress and cardiomyocytes apoptosis in Dox combined Tra-induced cardiotoxicity model both in vivo and in vitro. Our results suggest that NLRP3 inhibition is a promising cardioprotective strategy in Dox/Tra combination therapy.

PMID:37331637 | DOI:10.1016/j.bcp.2023.115662

18:22

PubMed articles on: Cardio-Oncology

Atrial fibrillation in cancer survivors - a systematic review and meta-analysis

Cardiooncology. 2023 Jun 17;9(1):29. doi: 10.1186/s40959-023-00180-3.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is a common cardiac complication during cancer treatment. It is unclear if cancer survivors have increased AF risk when compared to the population. AF screening is now recommended in patients ≥65 years, however there are no specific recommendations in the oncology population. We sought to compare the AF detection rate of cancer survivors compared to the general population.

METHODS: We searched the Pubmed, Embase and Web of Science databases using search terms related to AF and cancer mapped to subject headings. We included English language studies, limited to adults > 18 years who were > 12 months post completion of cancer treatment. Using a random-effects model we calculated the overall AF detection rate. Meta-regression analysis was performed to assess for potential causes for study heterogeneity.

RESULTS: Sixteen studies were included in the study. The combined AF detection rate amongst all the studies was 4.7% (95% C.I 4.0-5.4%), which equated to a combined annualised AF rate of 0.7% (95% C.I 0.1-0.98%). There was significant heterogeneity between studies (I2 = 99.8%, p < 0.001). In the breast cancer cohort (n = 6 studies), the combined annualised AF rate was 0.9% (95% C.I 0.1-2.3%), with significant heterogeneity (I2 = 99.9%, p < 0.001).

CONCLUSION: Whilst the results should be interpreted with caution due to study heterogeneity, AF rates in patients with cancer survival >12 months were not significantly increased compared to the general population.

STUDY REGISTRATION: Open Science Framework - DOI: https://doi.org/10.17605/OSF.IO/APSYG .

PMID:37330583 | PMC:PMC10276447 | DOI:10.1186/s40959-023-00180-3

18:22

PubMed articles on: Cardio-Oncology

A comparative review and computational assessment of acetochlor toxicity in fish: A novel endocrine disruptor?

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Jun 14:109685. doi: 10.1016/j.cbpc.2023.109685. Online ahead of print.

ABSTRACT

Acetochlor is a chloroacetamide herbicide applied to various crops worldwide and is one of the top selling herbicides on the global market. Due to rain events and run-off, the potential for acetochlor-induced toxicity is a concern for aquatic species. Here we review the current state of knowledge regarding the concentrations of acetochlor in aquatic ecosystems globally and synthesize the biological impacts of acetochlor exposure to fish. We compile toxicity effects of acetochlor, outlining evidence for morphological defects, developmental toxicity, endocrine and immune system disruption, cardiotoxicity, oxidative stress, and altered behavior. To identify mechanisms of toxicity, we utilized computational toxicology and molecular docking approaches to uncover putative toxicity pathways. Using the comparative toxicogenomics database (CTD), transcripts responsive to acetochlor were captured and graphically depicted using String-DB. Gene-ontology analysis revealed that acetochlor may disrupt protein synthesis, blood coagulation, signaling pathways, and receptor activity in zebrafish. Further pathway analysis revealed potential novel targets for acetochlor disruption at the molecular level (e.g., TNF alpha, heat shock proteins), highlighting cancer, reproduction, and the immune system as biological processes associated with exposure. Highly interacting proteins in these gene networks (e.g., nuclear receptors) were selected to model binding potential of acetochlor using SWISS-MODEL. The models were used in molecular docking to strengthen evidence for the hypothesis that acetochlor acts as an endocrine disruptor, and results suggest estrogen receptor alpha and thyroid hormone receptor beta may be preferential targets for disruption. Lastly, this comprehensive review reveals that, unlike other herbicides, immunotoxicity nor behavioral toxicity have been fully investigated as sub-lethal endpoints for acetochlor, and such mechanisms of toxicity should be emphasized in future research investigating biological responses of fish to the herbicide.

PMID:37328132 | DOI:10.1016/j.cbpc.2023.109685

18:22

PubMed articles on: Cardio-Oncology

Perspective on AHFTC Specialty by Women in Heart Transplant and MCS (WiTMCS)

J Card Fail. 2023 Jun 14:S1071-9164(23)00203-8. doi: 10.1016/j.cardfail.2023.05.022. Online ahead of print.

ABSTRACT

BACKGROUND: The Advanced Heart Failure & Transplant cardiology specialty has seen a decline in applicants seeking training in the field. Data is needed to identify principal reform areas to generate and maintain interest in the field for sustainability.

METHODS: Women in Transplant and Mechanical Circulatory support (WiTMCS) conducted a survey across their membership group investigating the barriers to attracting new talent and areas that need reform to improve the status of the specialty . A Likert scale was utilized to assess various perceived barriers to attracting new trainees and reform needed to improve the specialty.

RESULTS: A total of 131 women physicians in transplant and MCS responded to the survey. Five principal areas in need of reform were identified. : need for practice model variety 86.9%, inadequate compensation for non-RVU activities and total compensation at 86.4% and 79.1 % respectively, challenging work life balance at 78.5%, need for curriculum reform & specialized pathways at 73.1% and 65.4% respectively, and exposure during general cardiology fellowship at 65.1%.

CONCLUSION: Given the rising number of heart failure patients and the increased demand for more heart failure specialists,reformation is needed to restructure the five elements identified in our survey to increase interest in the field of AHFTC and maintain the current talent.

PMID:37328051 | DOI:10.1016/j.cardfail.2023.05.022

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PubMed articles on: Cardio-Oncology

[Retracted] CtBP1 interacts with SOX2 to promote the growth, migration and invasion of lung adenocarcinoma

Oncol Rep. 2023 Aug;50(2):151. doi: 10.3892/or.2023.8588. Epub 2023 Jun 16.

ABSTRACT

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that, for the western blots showing the CtBP1 and SOX2 bands in Fig. 5C on p. 74, the data were in fact the same, but flipped horizontally; moreover, two pairs of overlapping data panels were identified comparing between the cell invasion and assay data images shown in Figs. 3E and 6C, such that these were likely to have been derived from the same original sources even though they were intended to show the results from differently performed experiments; similarly, the 'shSOX2 / 24 h' and 'shCtBP1 / 24 h' data panels in Fig. 6B showing the results of differently performed scratch‑wound assay experiments appeared to be overlapping, albeit with one of the panels being slightly rotated relative to the other. Finally, there were erroneous calculations included for the CtBP1 expression data shown in Table III. Given the large number of apparent errors that were made during the assembly of various of the figures and Table III in this paper, the Editor of Oncology Reportshas decided that this paper should be retracted from the Journal due to an overall lack of confidence in the presented data. After contacting the authors, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 42: 67‑78, 2019; DOI: 10.3892/or.2019.7142].

PMID:37326128 | DOI:10.3892/or.2023.8588

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PubMed articles on: Cardio-Oncology

2023 National Heart Center/Saudi Heart Association Focused Update of the 2019 Saudi Heart Association Guidelines for the Management of Heart Failure

J Saudi Heart Assoc. 2023 May 25;35(1):71-134. doi: 10.37616/2212-5043.1334. eCollection 2023.