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.

BACKGROUND: 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, cardiorespiratory 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 significantly 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 suppressor 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, or 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 enhance quality of life. Further large-scale studies will help determine whether these promising results translate into improved clinical and oncological outcomes.

Exercise training as a modulator of epigenetic events in prostate tumors.

BACKGROUND: Exercise is increasingly recognized as an effective strategy to improve cancer prevention and prognosis. Several biological mechanisms mediating these benefits have been proposed, but the role of epigenetics remains largely unknown. Since epigenetics is highly susceptible to lifestyle factors, we hypothesized that exercise could affect the epigenome landscape in cancer tissues. METHODS: Rats implanted with AT1 prostate tumors were randomized to either control or exercise training. microRNA expression, DNA methylation and histone acetylation were analyzed in the tumor tissue. RESULTS: MiR-27a-5p appeared to be differently expressed between sedentary and trained rats. Furthermore, exercise increased global DNA methylation and decreased DNA methyltransferases mRNA expression in the tumor tissue. Histone acetylation however remained unaltered. CONCLUSION: Overall, exercise might reverse some of the cancer-related epigenetic alterations in the prostate tumor tissue.

The Effects of 8-Week Combined Exercise Training on Inflammatory Markers in Women with Multiple Sclerosis.

PURPOSE: The present study was designed to investigate the effects of 8-week combined endurance, resistance, and balance exercise training on IL-6, CRP, and IL-10 concentrations in women with multiple sclerosis. METHODS: Thirty participants with multiple sclerosis (Expanded Disability Status Scale ≤6) were randomized into either an exercise and control groups. The exercise group performed 8-weeks of endurance, resistance, and balance exercise training. Serum concentrations of IL-6, CRP, and IL-10 were measured before and after the 8-week intervention. Moreover, anthropometric measures were determined at the onset of and after the intervention. For within- and between groups comparisons of all variables, t test (independent and dependent) was used (p < 0.05). RESULTS: The results revealed that IL-6 and CRP levels significantly decreased after exercise training (from 6.8 ± 1.52 to 3.2 ± 0.96, p < 0.001 and from 2.76 ± 0.98 to 1.55 ± 0.44, p = <0.001; respectively). Also, exercise training significantly increased IL-10 in the exercise group (from 16.4 ± 2.74 to 23.2 ± 2.11, p < 0.001). There was a significant difference between the 2 groups in all markers in the after 8-week exercise (p < 0.05). CONCLUSIONS: One of the characteristics of MS disease is inflammation. Exercise training through physiological mechanisms and without aggravating the inflammatory pathology can be effective in functional and symptom reduction of patients with MS. In confirmation of this, the present study showed that 8 weeks of combined exercise training decreased pro-inflammatory markers (IL-6 and CRP) and increased anti-inflammatory cytokine (IL-10). Our findings suggested that an exercise training program can be an effective strategy for managing the immune system of women with MS at least by its significant effect on inflammatory markers.

High-intensity interval training can modulate the systemic inflammation and HSP70 in the breast cancer: a randomized control trial.

OBJECTIVE: Exercise training is recently considered as a trend in adjuvant therapies for cancer patients, but its mechanisms need to be scrutinized further. This study is aimed to test the hypothesis that the patients who perform the high-intensity interval exercise training (HIIT) during hormone therapy would show improvements in low-grade inflammation and HSP70 compared to the controls receiving standard care. METHODS: Fifty two non-metastatic and hormone-responsive breast cancer patients were randomly assigned to high-intensity interval exercise (HIIT) (n = 26) and usual care (n = 26) groups. The HIIT groups participated in a high-intensity interval training protocol on a treadmill 3 days/week for 12 weeks. The training intensity was determined according to the predicted maximal heart rate. Demographic characteristics and medical history were collected via an interviewer-administered questionnaire at the baseline visit. Body fat was estimated based on skinfold thickness measured with calipers on the participant's nonsurgery side at the triceps, suprailiac crest. [Formula: see text] was estimated by 1-Mile Rockport Walk Test. Blood samples were collected 48 h before starting the exercise protocol and 48 h after the last exercise session. TNF-α, IL-6, IL-1ß, IL-10, and HSP70 levels in serum were measured using the enzyme-linked immunosorbent assay (ELISA) method according to the manufacture's instruction. Supernatant cytokine concentrations were determined by ELISA for IL-4 and IFN-γ. The data were analyzed by ANCOVA test that the pretest values were considered as covariate at P ≤ 0.05. RESULTS: HIIT improved [Formula: see text] in the HIIT group compared to the usual care group (P = 0.002). The serum levels of TNF-α (P = 0.001), IL-6 (P = 0.007), and IL-10 (P = 0.001) were lower in the HIIT group. The level of IL-4 (P = 0.050) in the stimulated peripheral blood mononuclear cells significantly increased in the HIIT group compared to the usual care group. Furthermore, the serum level of the HSP70 was significantly higher in the HIIT group in comparison to the usual care group (P = 0.050). The TNF-α/IL-10 (P = 0.050) and IL-6/IL-10 (P = 0.042) ratios were lower in the HIIT group. CONCLUSION: The results of this study indicated that HIIT has positive impacts on the cardiorespiratory fitness and inflammatory cytokines in the breast cancer patients undergoing hormone therapy.

Effect of a high-intensity interval training on serum microRNA levels in women with breast cancer undergoing hormone therapy. A single-blind randomized trial.

BACKGROUND: The role of microRNAs (miRs) in hormone therapy (HT) is of keen interest in developing biomarkers and treatments for individuals with breast cancer. Although miRs are often moderate regulators under homeostatic conditions, their function is changed more in response to physical activity. OBJECTIVE: This single-blind randomized trial aimed to explore the effect of high-intensity interval training (HIIT) on serum levels of miRs in individuals with early-stage breast cancer undergoing HT. METHODS: Hormone receptor-positive women with breast cancer and healthy women were randomly assigned to a healthy control group (n=15), healthy group with HIIT (n=15), breast cancer group with HT (HT, n=26), and breast cancer group with HT and HIIT (HT+HIIT, n=26). The exercise groups underwent interval uphill walking training on a treadmill 3 times a week for 12weeks. At the end of the study, we analyzed changes in levels of cancer-related miRs (oncomiRs) and tumour suppressor miRs (TSmiRs) in response to the HT and HIIT. RESULTS: In women with breast cancer versus healthy controls, the expression of some oncomiRs was significantly increased - miR-21 (P<0.001), miR-155 (P=0.001), miR-221 (P=0.008), miR-27a (P<0.001), and miR-10b (P=0.007) - and that of some TSmiRs was significantly decreased - miR-206 (P=0.048), miR-145 (P=0.011), miR-143 (P=0.008), miR-9 (P=0.020), and let-7a (P=0.005). Moreover, HT considerably downregulated oncomiRs and upregulated TSmiRs. HIIT for 12weeks with HT significantly decreased the expression of the oncomiRs and significantly increased that of the TSmiRs as compared with HT alone. CONCLUSIONS: HITT could amplify the decrease and/or increase in expression of miRs associated with HT in women with breast cancer. A prospective trial could determine whether the use of circulating miRs for monitoring treatment can be useful in therapy decisions. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (No.: IRCT201202289171N1).

Oxytocin mediates the beneficial effects of the exercise training on breast cancer.

NEW FINDINGS: What is the central question of this study? We hypothesized that potential anti-tumour effects of exercise training might be mediated by oxytocin and explored the underlying mechanisms in a mouse model of breast cancer. What is the main finding and its importance? Interval exercise training, by inducing oxytocin secretion, may reduce the activity of the PI3K/Akt and ERK pathways, and consequently, results in a smaller tumour volume in a mouse model of breast cancer. Exercise training can affect the growth of breast tumours. We hypothesized that exercise training might reduce breast tumour growth by inducing oxytocin (OT) secretion and its related signalling pathways, such as PI3K/Akt and ERK. Therefore, 56 BALB/c mice were equally divided into seven groups to study the effects of OT and atosiban (an oxytocin receptor antagonist) together with interval exercise training on mammary tumour growth, as well as tumour-related signalling pathways, including PI3K/Akt and ERK. Animal weight, OT plasma concentration, tumour weight and volume were measured at the end of the study. PI3K/Akt and ERK were evaluated by Western blot and qPCR assays. The results showed that OT plasma concentration was significantly increased in trained animals. The volume and weight of tumours were decreased significantly after both exercise training and OT administration. The expression of genes involved in tumour cell proliferation, such as PI3KR2, Akt and mTOR, was notably lower in the exercise-trained and OT-treated groups. Furthermore, the expression of genes involved in cell apoptosis, such as caspase-3 and Bax, was significantly increased in the tumour tissues. In addition, Western blot results showed that phosphorylated Akt and ERK were significantly decreased in the exercise training and OT groups compared with the tumour group. Interestingly, atosiban reversed these effects. These results indicated that interval exercise training, acting via OT secretion, may reduce PI3K/Akt and ERK axis activities, and consequently, decrease tumour volume and weight in a mouse model of breast cancer.

MicroRNA-206, let-7a and microRNA-21 pathways involved in the anti-angiogenesis effects of the interval exercise training and hormone therapy in breast cancer.

AIMS: MicroRNAs (miRNAs) are the targeting signal-transduction pathways that can mediate tumorigenesis via their down and/or up-regulation. For example, miR-21 and miR-206 can effect on the tumor angiogenesis as an oncomir and a tumor suppressor, respectively. MATERIALS AND METHODS: The present study is aimed to investigate the effects of the interval exercise training in combination with tamoxifen and/or letrozole on miR-21, miR-206 and let-7 as well as their underlying pathways in regard to tumor angiogenesis in sixty four mice with breast tumor. ELISA, immunohistochemistry, qRT-PCR assays were performed accomplish the study. KEY FINDINGS: The results showed that the tumor size was significantly declined in the exercise training, tamoxifen and letrozole groups compared to tumor group. Mir-206 and let-7 were up-regulated, and mir-21 expression was down-regulated in the exercise training compared to tumor group. Exercise training decreased the expression of ER-α, HIF-α, VEGF, CD31 and Ki67 in tumor tissue. The combination tamoxifen and/or letrozole with the exercise training could down-regulate the expression of ERα, miR-21, HIF-1α, TNF-α, CD31, Ki67 and VEGF, and up-regulate the expression of miR-206, PDCD-4, let-7 and IL-10 that led to reducing the angiogenesis and tumor growth. SIGNIFICANCE: Our results showed that miR-21, miR-206 and let-7a pathways may involve in the anti-angiogenesis effects of the interval exercise training with hormone therapy in mice model of breast tumor.

Effects of exercise training together with tamoxifen in reducing mammary tumor burden in mice: Possible underlying pathway of miR-21.

Exercise training has an anti-tumor effect and can reduce tumor growth; however, the exact underlying mechanisms of its protective effects are still obscure. MicroRNA (miR)-21 is a predictor in cancer survival, and has a potential use as an indicator of therapeutic outcome in breast malignancies. Forty-eight female BALB/c mice were equally divided into six groups to investigate the effects of interval exercise training with tamoxifen on miR-21 expression and its possible assumed mechanisms in an estrogen receptor-positive breast cancer model. ELISA, immunohistochemistry, western blot, qRT-PCR assays were performed at the end of the study. Tumor size was significantly declined in exercise training and tamoxifen groups compared to tumor group (P<0.05). Expression of miR-21 was significantly down-regulated in trained and tamoxifen treated mice in comparison with tumor group (P<0.05). Exercise training was as effective as tamoxifen treatment in decreasing serum estradiol and ER-α expression (P<0.05). Exercise training and tamoxifen reduced tumor IL-6 levels, NF-kB and STAT3 expressions, and up-regulated TPM1 and PDCD4 expressions (P<0.05). Both exercise and tamoxifen had synergistic effects in reducing miR-21 and Bcl-2, and up-regulating PDCD4 expression. Results showed that interval exercise training may reduce mammary tumor burden in mice through possible underlying pathway of miR-21.

The effect of endurance training and downhill running on the expression of IL-1ß, IL-6, and TNF-α and HSP72 in rat skeletal muscle.

This study investigated changes in the myokines IL-1ß, IL-6, and TNF-α, as well as HSP72, after endurance training and after a session of downhill running. Twenty-eight rats were allocated to four different groups: 1. Eight weeks of endurance training at 65-70% VO2max (Trained); 2. Endurance training and a single session of downhill running on a 16° slope (Trained plus downhill); 3. A single session of downhill running (Sedentary plus downhill); and 4. Sedentary (Control, no exercise). Soleus and extensor digitorum longus (EDL) muscles were harvested 48h after training and/or a single session of downhill running and protein levels of IL-1ß, IL-6, TNF-α, and HSP72 were measured and compared to the levels in the control animals. Creatine kinase (CK) was measured in plasma. Endurance training augmented intramuscular levels of HSP72 and IL-6 in both soleus and EDL muscles (p<0.05). Endurance training elevated IL-1ß and decreased TNF-α significantly only in EDL (P<0.05). IL-6 increased in both sedentary and trained rats after downhill running (P<0.05), while HSP72 increased only in the previously sedentary rats. CK was lower in trained than sedentary rats after downhill running. In conclusion, endurance training for 8weeks elevated muscular HSP72 protein levels, which might have preconditioned the muscles for a single session of downhill running, as indicated by the CK and HSP72 responses. Interestingly, IL-6 was augmented by endurance training and further increased by downhill running. IL-1ß, along with IL-6, was increased by endurance training, and these myokines thus appear to be differently regulated than TNF-α.