ABSTRACT

Doxorubicin (DOX) with broad-spectrum antitumor activity has been reported to induce effective immunogenic cell death (ICD) effect. However, the serious cardiotoxicity and chemoresistance severely restrict the widely clinical application of DOX. Herein, for the first time, a bio-inspired nanoplatform via co-assembly of DOX-conjugated polyethyleneimine (PEI-DOX), cancer cell membrane (CCM) and TGF-β1 siRNA (siTGF-β1) was rationally designed, which can not only overcome the drawbacks of DOX but also display high capability to modulate the tumor microenvironment and prevent the tumor progressing and metastasis. Experimental studies confirmed the pH-sensitivity of PEI-DOX and the homotypic-targeting and immuno-escapable ability of CCM, resulting an enhanced accumulation of DOX and siTGF-β1 in tumor sites. In addition to this, the bio-inspired nanoplatform could also improve the stability and facilitate the endosomal escape of siTGF-β1. All these effects ensured the silence efficiency of siTGF-β1 in tumor sites, which could further modulate the chemoresistant and immunosuppressive tumor microenvironment, resulting a synergistic effect with DOX to prevent tumor progressing and metastasis. Additionally, even trapped in cardiac tissues, siTGF-β1 could inhibit the production of TGF-β1 and ROS induced by DOX, resulting a reduced myocardial damage. Therefore, our newly designed bio-inspired nano-delivery system may be a promising nanoplatform with efficient chemoimmunotherapy to ameliorate DOX-induced cardiotoxicity and combat tumor growth and metastasis in chemoresistant cancer.

PMID:37536544 | DOI:10.1016/j.jconrel.2023.07.063

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PubMed articles on: Cardio-Oncology

Patient mortality following new-onset heart failure stratified by cancer type and status

Eur J Heart Fail. 2023 Aug 3. doi: 10.1002/ejhf.2984. Online ahead of print.

ABSTRACT

AIM: Expected 1-year survival is essential to risk stratification of patients with heart failure (HF); however, little is known about the 1-year prognosis of patients with HF and cancer. Thus, the objective was to investigate the 1-year prognosis following new-onset HF stratified by cancer status in patients with breast-, gastrointestinal-, or lung cancer.

METHODS AND RESULTS: All Danish patients with new-onset HF from 2000-2018 were included. Cancer status was categorized as history of cancer (no cancer-related contact within five years of HF diagnosis), non-active cancer (curative intended procedure administered) and active cancer. Standardized 1-year all-cause mortality was reported using G-computation. Age-stratified 1-year all-cause mortality was estimated using the Kaplan-Meier estimator. In total, 193 359 patients with HF were included, 7.3% had either a breast-, gastrointestinal or lung cancer diagnosis. Patients with cancer were older and more comorbid than patients without cancer. Standardized 1-year all-cause mortalities (95% confidence intervals) were 24.6% (23.0%-26.2%), 27.1% (25.5%-28.6%), and 29.9% (25.9%-34.0%) for history of breast-, gastrointestinal-, and lung cancer, which was comparable to patients with non-active cancers. For active breast-, gastrointestinal-, and lung cancer, standardized 1-year all-cause mortalities were 36.2% (33.8%-38.6%), 49.0% (47.2%-50.9%), and 61.6% (59.7%-63.5%), respectively. One-year all-cause mortality increased incrementally with age, except for active lung cancer.

CONCLUSION: Standardized 1-year all-cause mortality were comparable for patients with history of cancer and non-active cancer regardless cancer type, but varied comprehensively for active cancers. Prognostic impact of age was limited for active lung cancer. Thus, granular stratification of cancer is necessary for optimized management of new-onset HF. This article is protected by copyright. All rights reserved.

PMID:37534618 | DOI:10.1002/ejhf.2984

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PubMed articles on: Cardio-Oncology

Cancer Therapy-Related Cardiotoxicity: A Comprehensive Retrospective Analysis at Najran Cancer Center, Saudi Arabia

Cureus. 2023 Jul 2;15(7):e41287. doi: 10.7759/cureus.41287. eCollection 2023 Jul.

ABSTRACT

Background Cardiotoxicity, produced as an adverse effect of anticancer therapy, is a common issue during cancer treatment. Acute coronary syndrome, myocarditis, arrhythmias, or heart failure can all be symptoms of this issue. Little is known about its occurrence among Saudi Arabian cancer patients. This study aims to investigate factors linked to anticancer therapy-related cardiotoxicity. Methods A retrospective study was conducted from April 2020 to May 2022 at the King Khalid Hospital, Najran, Saudi Arabia. The study included adult cancer patients receiving anticancer therapy, regardless of their cardiovascular disease history. Univariate analysis was used to investigate factors associated with the occurrence of cardiotoxicity related to anticancer therapy. Results Of 78 patients receiving anticancer therapy, cardiotoxicity occurred in 12 (15.4%) patients. The mean age was 56.5 ± 13.4 years, with 33.3% aged over 65 years. Comorbidities included hypertension (44; 56.4%), diabetes (41; 52.6%), dyslipidemia (13; 16.7%), smoking (16; 20.5%), heart disease (6; 7.7%), trastuzumab use (9; 11.5%), and chronic kidney disease (2; 2.6%). The most common cancers were breast cancer and gastrointestinal cancer (27.6% each). Monoclonal anticancer agents 35 (46.1%) and alkylating agents 29 (38.2%) were commonly used chemotherapies. Cardiac protective agents were used in 16 (21.1%) of patients, with angiotensin-converting enzyme (ACE) inhibitors 15 (19.7%) and statins (13; 17.1%) being the most prescribed. Baseline ejection fraction (EF) was normal in 69 (90.8%) of cases. The follow-up duration was 1.93 ± 1.90 years. A drop in EF occurred in five (6.6%) of cases. Dyslipidemia (OR: 0.12; 95% CI: 0.03-0.47, p=0.002), previous heart disease (OR: 0.14; 95% CI: 0.02-0.81, p=0.029), and impaired baseline EF (p=0.029) were associated with increased risk of cardiotoxicity. Statin (OR: 0.22; 95% CI: 0.05 to 0.84, p=0.028) and antiplatelet agents (OR: 0.19; 95% CI: 0.03 to 1.01, p=0.051) were protective agents against cardiac toxicity. Conclusion Effective anti-cancer therapy may be accompanied by an increased risk of cardiotoxicity. In this study, a history of prior heart disease, dyslipidemia, low baseline ejection fraction, and the administration of multiple anticancer therapy agents was associated with cardiotoxicity. Proactive management strategies aimed at mitigating the potential cardiotoxic effects of anti-cancer therapies are crucial.

PMID:37533611 | PMC:PMC10393428 | DOI:10.7759/cureus.41287

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PubMed articles on: Cardio-Oncology

The protective effect of thiolutin on doxorubicin-induced H9c2 cardiomyocyte injury

J Toxicol Sci. 2023;48(8):469-479. doi: 10.2131/jts.48.469.

ABSTRACT

The use of doxorubicin (DOX) may contribute to cardiotoxicity, limiting its clinical application. Thiolutin (THL) has been found to exert protective roles in various biological activities, while its effects on DOX-induced cardiotoxicity are still uncovered. Cell counting kit 8 assay was utilized to detect cell viability and half maximal inhibitory concentration of THL in H9c2 cardiomyocytes. The level of lactate dehydrogenase (LDH), adenosine triphosphate (ATP), interleukin (IL)-18 and IL-1 beta (IL-1β) were measured using the corresponding detection kits, and flow cytometry determined cell apoptosis rate. The reactive oxygen species (ROS) accumulation was evaluated by utilizing immunofluorescence or flow cytometry assay. The protein levels of NLR family Pyrin domain 3 (NLRP3), pro-Caspase1, cleaved-Caspase1, gasdermin D (GSDMD) and cleaved-GSDMD (GSDMD-N) in H9c2 cells were detected by immunoblotting assay. The treatment of THL reduced H9c2 cell viability in a gradient-dependent manner. THL treatment reversed the DOX-induced inhibition of proliferation, decrease of ATP, up-regulation of LDH, IL-18, IL-1β and production of ROS, activation of NLRP3 and inflammasome-mediated pyroptosis in H9c2 cells. Additionally, NLRP3 knockdown abolished the effects of THL in DOX-treated H9c2 cells remarkably. This investigation proved that THL notably ameliorated DOX-induced apoptosis, oxidative stress, and pyroptosis in H9c2 cardiomyocytes. Besides, THL effectively inactivated DOX-induced NLRP3 inflammasome in H9c2 cells. These findings revealed a promising drug to assist DOX in its anti-cancer effects and protect the heart of patients.

PMID:37532580 | DOI:10.2131/jts.48.469

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PubMed articles on: Cardio-Oncology

Cardiorenal Syndrome: A Literature Review

Cureus. 2023 Jul 1;15(7):e41252. doi: 10.7759/cureus.41252. eCollection 2023 Jul.

ABSTRACT

Cardiorenal syndrome (CRS) is a condition characterized by the intricate two-way relationship between the heart and kidneys, which can lead to acute or chronic dysfunction in these organs. The interplay between cardiorenal connectors and both hemodynamic and non-hemodynamic factors is crucial to understanding this syndrome. The clinical importance of these interactions is evident in the changes observed in hemodynamic factors, neurohormonal markers, and inflammatory processes. Identifying and understanding biomarkers associated with CRS is valuable for early detection and enabling intervention before significant organ dysfunction occurs. This comprehensive review focuses on the clinical significance of biomarkers in the diagnosis, prognosis, and management of CRS. Finally, it highlights the necessity for further advancements in managing this condition.

PMID:37529809 | PMC:PMC10389294 | DOI:10.7759/cureus.41252

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PubMed articles on: Cardio-Oncology

M2b macrophages protect against doxorubicin induced cardiotoxicity via alternating autophagy in cardiomyocytes

PLoS One. 2023 Jul 27;18(7):e0288422. doi: 10.1371/journal.pone.0288422. eCollection 2023.

ABSTRACT

OBJECTIVE: Doxorubicin (DOX) is an anthracycline antibiotic which is widely used for the treatment of various cancers, while the dose-related cardiotoxicity limits its potential therapeutic application. The underlying mechanism of DOX induced cardiotoxicity is complex and remains elusive. Our previous studies have shown that M2b macrophage plays an important role in reducing inflammation due to ischemic reperfusion injury in the myocardium. The purpose of this study was to investigate the potential protective role of M2b macrophages in DOX induced cardiotoxicity.

METHODS: In vivo, we conducted DOX induced cardiac injury in C57BL/6 mice and treated them with M2b macrophages. Then, the mice were examined by echocardiography. The heart specimens were harvested for histological examination, transmission electron microscope analysis, and autophagy molecules evaluation. In vitro, HL-1 cardiac cell lines treated with DOX were cocultured with or without M2b macrophages. Then, Autophagy related genes and protein expression were assessed by real-time quantitative PCR and western blot; cell proliferation was assessed by cell counting kit-8.

RESULTS: We found that M2b macrophages can improve cardiac function and alleviate cardiac injury in DOX induced cardiac injury mice. M2b macrophages can enhance cardiac autophagy levels both in vivo and in vitro in DOX induced cardiac injury model. In addition, this protective effect can be blocked by an autophagy inhibitor.

CONCLUSION: Our study shows that M2b macrophages can help attenuate the DOX induced cardiotoxicity by regulating the autophagy level of cardiomyocytes.

PMID:37498828 | PMC:PMC10374082 | DOI:10.1371/journal.pone.0288422

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PubMed articles on: Cardio-Oncology

Cardiovascular outcomes in breast cancer survivors: a systematic review and meta-analysis

Eur J Prev Cardiol. 2023 Jul 27:zwad243. doi: 10.1093/eurjpc/zwad243. Online ahead of print.

ABSTRACT

BACKGROUND: It is unclear whether the future risk of cardiovascular events in breast cancer (BC) survivors is greater than in the general population.

OBJECTIVES: This meta-analysis quantifies the risk of cardiovascular disease development in breast cancer patients, compared to the risk in a general matched cancer-free population and reports the incidence of cardiovascular events in patients with BC.

METHODS: We searched PubMed, Scopus, and Web of Science databases (up to March 23, 2022) for observational studies and post-hoc analyses of RCTs. Cardiovascular death, heart failure (HF), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), stroke were the individual endpoints for our meta-analysis. We pooled incidence rates (IRs) and risk in hazard ratios (HRs), using random-effects meta-analyses. Heterogeneity was reported through the I^2 statistic, and publication bias was examined using funnel plots and Egger's test in the meta-analysis of risk.

RESULTS: 142 studies were identified in total, 26 (836,301 patients) relevant to the relative risk, and 116 (2,111,882 patients) relevant to IRs. Compared to matched cancer-free controls, BC patients had higher risk for cardiovascular death within five years of cancer diagnosis (HR = 1.09; 95% CI: 1.07, 1.11), HF within ten years (HR = 1.21; 95% CI: 1.1, 1.33), and AF within three years (HR = 1.13; 95% CI: 1.05, 1.21). The pooled IR for cardiovascular death was 1.73 (95% CI 1.18, 2.53), 4.44 (95% CI 3.33, 5.92) for HF, 4.29 (95% CI 3.09, 5.94) for CAD, 1.98 (95% CI 1.24, 3.16) for MI, 4.33 (95% CI 2.97, 6.30) for stroke of any type, and 2.64 (95% CI 2.97, 6.30) for ischemic stroke.

CONCLUSION: breast cancer exposure was associated with the increased risk for cardiovascular death, HF and AF. The pooled incidence for cardiovascular endpoints varied depending on population characteristics and endpoint studied.

PMID:37499186 | DOI:10.1093/eurjpc/zwad243

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PubMed articles on: Cardio-Oncology

An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications

Cell Death Discov. 2023 Jul 27;9(1):266. doi: 10.1038/s41420-023-01558-z.