ABSTRACT

Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore, overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment. Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicin-induced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice. These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.

PMID:37425037 | PMC:PMC10326298 | DOI:10.1016/j.apsb.2023.03.019

08:30

PubMed articles on: Cardio-Oncology

Comparison of the effects of high-intensity interval and moderate-intensity continuous training on inflammatory markers, cardiorespiratory fitness, and quality of life in breast cancer patients

J Sport Health Sci. 2023 Jul 7:S2095-2546(23)00070-4. doi: 10.1016/j.jshs.2023.07.001. Online ahead of print. ABSTRACTBACKGROUND: As the effectiveness of breast cancer treatment has improved, a growing number of long-term breast cancer survivors are seeking help for unique health problems. These patients may be at increased risk of cardiovascular disease due to the side effects of treatment. The positive impact of most types of exercise has been repeatedly reported in people with cancer, but the most effective exercise approaches for maximum beneficial adaptations remain controversial. Thus, this study aimed to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on inflammatory indices, adipokines, metabolic markers, body composition, cardiorespiratory fitness, and quality of life in breast cancer patients during adjuvant endocrine therapy.

METHODS: Thirty non-metastatic breast cancer patients during adjuvant endocrine therapy who had been treated with chemotherapy and/or radiotherapy were recruited from Iran and randomized to HIIT, MICT, or control groups for a supervised exercise intervention that took place 3 times a week for 12 weeks. The training intensity was determined based on the peak oxygen uptake (VO2peak), and the volume of training was matched in HIIT and MICT based on the VO2peak. Body composition, functional capacity, cardio-respiratory fitness, metabolic indices, sex hormones, adipokines, and inflammatory markers were assessed before and after the intervention.

RESULTS: The VO2peak increased by 16.8% in the HIIT group in comparison to baseline values (mean difference = 3.61 mL/kg/min). HIIT significantly improved the VO2peak compared to control (mean difference = 3.609 mL/kg/min) and MICT (mean differences = 2.974 mL/kg/min) groups. Both HIIT (mean difference = 9.172 mg/dL) and MICT (mean difference = 7.879 mg/dL) interventions significantly increased high-density lipoprotein cholesterol levels compared to the control group. The analysis of covariance showed that physical well-being sginificantly improved in MICT compared to control group (mean difference = 3.268). HIIT significantly improved the social well-being compared to the control group (mean difference = 4.412). Emotional well-being subscale was significantly improved in both MICT (mean difference = 4.248) and HIIT (mean difference = 4.412) compared to the control group. Functional well-being scores significantly increased in HIIT group compared with control group (mean difference = 3.35) . Significant increase were also observed in total functional assessment of cancer therapy-General scores in both HIIT (mean difference = 14.204) and MICT groups (mean difference = 10.036) compared with control group. The serum level of supressor of cytokine signaling 3 increased significantly (mean difference = 0.09 pg/mL) in the HIIT group compared to the baseline. There were no significant differences between groups for body weight, body mass index, fasting blood glucose, insulin resistance, sex hormone binding globulin, total cholesterol, low-density lipoprotein cholesterol, adipokines, interleukin-6, tumor necrosis factor-α, and interleukin-10.

CONCLUSION: HIIT can be used as a safe, feasible, and time-efficient intervention to improve cardiovascular fitness in breast cancer patients. Both HIIT and MICT modalities enhanced quality of life. Further large-scale studies will help determine whether these promising results translate into improved clinical and oncological outcomes.

PMID:37423313 | DOI:10.1016/j.jshs.2023.07.001

08:31

PubMed articles on: Cardio-Oncology

Emergency management of patients with Glanzmann thrombasthenia: consensus recommendations from the French reference center for inherited platelet disorders

Orphanet J Rare Dis. 2023 Jun 29;18(1):171. doi: 10.1186/s13023-023-02787-2.