Cardio-oncology最新文献

Background: SARS-CoV-2 non-structural protein 6 (NSP6) in the host's tissue-specific complexities remains a mystery and needs more in-depth attention because of COVID-19 recurrence and long COVID. Its reported role in immune evasion, viral replication and egress from the cells as well as its gain of function mutations occurring independently in various variants underscores its importance.

Methods: Here we investigated the influence of SARS-CoV-2 transmembrane protein NSP6 (Non-structural protein 6) in three major organs - the brain, heart, and lung in silico. To elucidate the interplay between NSP6 and host proteins, we analyzed the protein-protein interaction network of regulated host proteins interacting with reported SARS-CoV-2 NSP6 interacting proteins - SIGMAR1, ATP13A3, ATP5MG, and ATP6AP1. Tissue-specific protein interactomes and hub genes in these interactomes were found, and drugs targeting them were sought out.

Results: Key hub genes in the brain were CCND1, CDK2, CCNA1, CDC6, CDKN1B, SKP1, CCNB1, etc., whereas in the heart were RAB7A, ATP6V0D1, LAMP2, TGFB1, CANX, LGALS3, etc. Lung hub genes were ATP6V0A1, ATP6V0A2, ATP6V0D1, ATP6V1D, ATP6V1B1, ATP6V1E1, TGFB1, EGF, TGFBR2, and LGALS3. Hub gene associated pathways in the brain were iron uptake and transport, G1/S transition, and small cell Lung cancer. Differentiation of dendritic cells and reduction of intraphagosomal pH to 5 - were prominent pathways in lung. In heart, phagosome associated pathways, and regulation of intracellular were prominent. Key therapeutic targets identified in the brain are CDK2, targeted by acetaminophen and raltitrexed; CCNE1 by palbociclib; and CCND1 by palbociclib, acetaminophen, lapatinib, doxorubicin, and methotrexate. In the heart, TGFB1 and APP are targeted by inositol, while LGALS3, upregulated after COVID-19 can be targeted by non-approved drugs (Belapectin, Olitigaltin, Lactose anhydrous, Davanat). In the lungs, TGFB1 and TGFBR2 are targeted by irinotecan, and EGF by cetuximab.

Conclusions: This study highlights probable hub genes, drugs targeting them, and associated pathways perturbed by SARS-CoV-2 NSP6. Galectin3 (LGALS3) upregulated in both heart and brain after COVID-19 infection is reported to be influencing all the ten hallmarks of cancer. Our bioinformatics and systems study hints probable effect of COVID-19 infection in cancer incidence and warrants in-depth studies for present scenario of long and recurrent COVID-19.

Background: Despite advances in radiotherapeutic techniques, radiation-induced cardiovascular diseases (CVD) remain a leading but often underrecognized cause of morbidity and mortality in cancer survivors. Radiation exposure can trigger a broad spectrum of cardiotoxic effects yet clinical awareness and strategies for managing these long-term complications remain limited. Among emerging indicators of vascular dysfunction, measures of vascular flexibility offer key biomarkers for assessing vascular compliance and cardiovascular risk.

Methods: The present study hence investigated age- and dose-dependent effects of local irradiation on vascular function of the murine Arteria saphena in C57BL/6 wild-type and atherosclerosis-prone apolipoprotein E-knockout (ApoE^-/-) mice, a well established model for human CVD. Pathological effects of irradiation on vascular function of the A. saphena were assessed using in vivo Optical Coherence Tomography. Vascular flexibility in terms of arterial diameters and speed of diameter changes during vasoconstriction and vasodilation were recorded one day and 3, 6, 9, 12, or 18 months following irradiation with single doses of 2, 5, 8, 10, 16 Gy.

Results: Baseline arterial diameters declined with age in both strains, with earlier onset in ApoE^-/- mice. Significant interactions with radiation dose indicate greater radiation sensitivity in ApoE^-/- mice and additive effects of radiation and aging in both strains. Vasoconstriction halved arterial diameters in wild-type and more so in ApoE^-/- mice, reflecting an enhanced vasoconstrictive response that diminished after 16 Gy. Contractility was found to be age-dependent, peaking between 6 and 12 months post-irradiation, while time to half-maximal constriction remained unchanged across conditions. Maximal vasodilation ranged from 1.2 to 2 × baseline, initially higher in ApoE^-/- mice but declining earlier with age than in wildtype mice. ApoE^-/- mice exhibited more sustained vasodilation, which progressively slowed with age and higher radiation doses in both strains.

Conclusion: Both mouse strains exhibited marked age-related vascular changes, with ApoE^-/- mice showing greater radiation sensitivity. The combined effects of aging and radiation were most prominent in reduced arterial diameters at baseline and after vasoconstriction, along with slower vasodilation reflecting elevated vascular resistance linked to hypertension. Early blood pressure management is therefore essential to reduce the risk of radiation-induced CVD.

Background: Children, adolescents, and young adults with cancer (referred to as CAYAs) are at risk of long-term health complications, with cardiovascular disease (CVD) being a major concern. In addition, sociodemographic characteristics and traditional cardiovascular risk factors may also contribute to disparities in outcomes compared with those of the general population. The aim of this study was to investigate the timing, patterns, and combinations of CVDs, as well as associated morbidity, mortality, and sociodemographic factors, in CAYAs with CVD compared with matched controls with CVD.

Methods: A register-based cohort study consisting of all Swedish cancer patients under 25 years old and during a 63-year observation time was used. CAYAs and controls with CVD (n = 58,981) were included and compared in terms of the timing and combinations of CVD, and mortality.

Results: The median age at first CVD was 41.8 years in CAYAs and 49.6 years in controls (p < 0.0001), with male CAYAs being the youngest at 25.0 years. During a median follow-up of 34.6 years, most CAYAs (65.2%) developed one CVD, while two or three coexisting CVDs occurred in 20.2% and 8.2%, respectively. Mostly hypertension in combination with cerebrovascular disease, ischemic heart disease and arrhythmias. More than three CVDs were more common in CAYAs than in controls (6.4% vs. 5.9%). A total of 21.8% of the CAYAs died, and the risk of all-cause mortality after the first CVD was 2.43-fold greater (hazard ratio (HR) 95% confidence interval (CI) 2.31-2.54, p < 0.0001), and for cardiovascular mortality, the risk was 2.17-fold greater (HR 95% CI 2.02-2.33, p < 0.0001) than that of the controls. In CAYAs with CVD, older age, male sex, and living in the central part of Sweden were associated with higher mortality, whereas higher education and marriage were protective (p < 0.0001).

Conclusions: Compared with controls CAYAs develop advanced CVD and combinations of multiple CVDs earlier in life, and they have a greater risk of all-cause and cardiovascular mortality. Factors associated with increased mortality risk include male sex and geographic variation, whereas marriage and higher education appear to be protective.

Background: Anthracyclines can cause dose-dependent cardiotoxicity that may be irreversible. To minimize cardiotoxic effects, substituting doxorubicin for liposomal doxorubicin (LD) has been explored as a cardioprotective strategy.

Objectives: To describe randomized clinical trials (RCTs) comparing the efficacy and safety of LD with other anthracycline-based regimens.

Methods: We conducted a systematic review and meta-analysis of RCTs comparing LD with other anthracycline-based regimens, using data from Medline, Embase, Emcare, the Cochrane Central Register, and LILACS.

Results: Twelve studies including 3027 patients with breast cancer (6), multiple myeloma (2), lymphoma (2), sarcoma (1), and acute lymphocytic leukemia (1) were included. Most participants (86%) were women with breast cancer. Nine studies compared LD with conventional doxorubicin and three with epirubicin. Overall, the risk of bias was classified as "some concerns". Follow-up ranged from 24-72 months - the median follow-up time among the studies was 37 months. There was a reduction in heart failure (HF) incidence in the LD group compared to the control (RR 0.32, 95%CI 0.18-0.55). A significant decrease in left ventricular ejection fraction (LVEF), as defined by each study´s criteria, was less frequent in the LD group compared to other anthracycline-based therapies (RR 0.39, 95%CI 0.30-0.51). All-cause mortality (RR 0.98, 95%CI 0.90-1.07) and tumor response (RR 0.99, 95%CI 0.93-1.05) did not differ between the groups.

Conclusions: LD use was associated with a decrease in the occurrence of HF compared to other anthracycline-based therapies, with no worse cancer outcomes. A significant decrease in LVEF was also less frequent in the LD group; however, no difference was found in cardiovascular mortality.

Background: Treatment of breast cancer by chemotherapy or radiotherapy exposes the patient to the risk of cardiotoxicity, which can be assessed pre-therapeutically using scores such as the Heart Failure Association and International Cardio-Oncology Society (HFA-ICOS) score. We aimed to evaluate the risk of cardiotoxicity using the HFA-ICOS score in a group of Cameroonian women before treatment of breast cancer by chemotherapy and/or radiotherapy.

Methods: We conducted a cross-sectional analytic study using retrospective data collected from the Cardiology and Oncology departments at Yaounde Central Hospital and the Internal Medicine department at Yaounde General Hospital over an eight-year period, from 2017 to 2024, with a focus on the nine months from November 2023 to June 2024. Inclusion criteria consisted of patients with histologically confirmed breast cancer treated with chemotherapy and/or radiotherapy. We performed a multivariate analysis to determine the factors associated with moderate and high risk of cardiotoxicity, with a significance threshold of p ≤ 0.05.

Results: Of the 130 patients recruited, the median age was 46.5 years (interquartile range, IQR, 36.75-58.00), with extremes of 21 and 76 years. Comorbidities mainly were overweight/obesity in 92 (70.7%) cases and arterial hypertension in 32 (24.6%) cases. Invasive ductal carcinoma was the main histological type, accounting for 126 (96.9%) cases, and triple-negative carcinoma was the most frequent molecular subtype, comprising 55 (42.3%) cases. Treatment consisted of exclusive chemotherapy in 96 (73.8%) cases and radiotherapy associated with chemotherapy in 27 (20.8%) cases. Based on the HFA-ICOS score, the cardiotoxicity risk was low in 93 (71.5%) patients. The independent factors associated with the risk of moderate to severe cardiotoxicity were age ≥ 60 years (adjusted OR: 5.97; 95% CI 1.73-20.60; adjusted p = 0.005), obesity (adjusted OR: 5.81; 95% CI 1.78-18.91; p = 0.003) and hypertension (adjusted OR: 27.10; 95% CI 7.51-97.76; p < 0.001). Exclusive chemotherapy was a protective factor (adjusted OR: 0.24; 95% CI 0.07-0.81; adjusted p = 0.021).

Conclusion: Women with breast cancer in Cameroon tend to be relatively young and present a low risk of cardiotoxicity before starting anti-cancer treatment.

Background: Anthracycline-induced cardiomyopathy is a leading cause of morbidity and mortality in survivors of childhood cancer. The mitochondrion is a key mediator of the cytotoxic effects of anthracycline treatment and mitochondrial dysfunction is a hallmark of cardiomyopathy and heart failure. We sought to evaluate whether mitochondrial processes differ between anthracycline-exposed childhood cancer survivors who developed cardiomyopathy versus those who did not.

Methods: Peripheral blood was collected from 40 childhood cancer survivors who developed cardiomyopathy (cases) and 64 matched survivors who did not (controls). From these samples, gene expression was determined by RNA-Sequencing. Following bioinformatic processing, differential gene expression at the mRNA-level between cases and controls was determined. Human MitoCarta3.0, was utilized to determine if genes involved in mitochondrial processes were enriched for differential expression, and to identify differentially regulated mitochondrial pathways at the mRNA-level.

Results: 900 genes were identified as differentially expressed at the mRNA-level. The odds of a gene being differentially expressed were 2.43 times greater if it encodes for a protein that localizes to the mitochondria. Mitochondrial processes that were enriched for differentially expressed genes at the mRNA-level included electron transport chain complexes; reactive oxygen species metabolism; apoptosis, mitophagy, and autophagy; mitochondrial ribosome; mitochondrial transport and chaperones; and heme synthesis and processing. Additionally, we observed that a measure of pro-apoptotic balance (BAX to BCL-2 gene expression at the mRNA-level) was highest in severe cardiomyopathy, intermediate in mild cardiomyopathy, and lowest in survivors without cardiomyopathy.

Conclusions: We observed substantial evidence that the expression of genes involved in mitochondrial processes differs in childhood cancer survivors who develop cardiomyopathy versus those who do not.

Background: Early identification of cardiac involvement in oncology patients is critical but challenging. To date, no validated protocol integrates dedicated cardiac magnetic resonance imaging (CMR) within routine whole-body (WB) ¹⁸F-FDG PET/MRI examinations.

Objectives: This proof-of-concept study evaluated the feasibility and effectiveness of a novel hybrid imaging protocol combining CMR and WB ¹⁸F-FDG PET/MRI for oncology patients.

Methods: Fifteen patients with suspected or confirmed multiple myeloma (MM) were enrolled. All participants scheduled for oncologic ¹⁸F-FDG PET/MRI underwent an integrated protocol incorporating dedicated CMR sequences prior to WB PET/MRI. The CMR sequences included cine imaging, native T1 and T2 mapping, and feature-tracking to assess cardiac structure, function, and tissue characteristics. Feasibility, safety, and the prevalence of clinically relevant cardiac abnormalities were evaluated.

Results: The protocol was successfully completed in all participants without adverse events, enabling comprehensive cardiac and oncologic assessment within an average procedure time of 115 min (cumulative scanning time 65.5 ± 9.8 min). Clinically relevant cardiac abnormalities were identified in 4 patients (27%), including reduced left ventricular ejection fraction, concentric hypertrophy, and increased myocardial ¹⁸F-FDG uptake.

Conclusions: This study demonstrates the feasibility of a novel, time-efficient, integrated ¹⁸F-FDG PET/MRI protocol combining oncologic staging with comprehensive cardiac assessment in a single examination. This approach serves as an ideal strategy for cardio-oncology, bridging the gap between cancer treatment and cardiac care.