With recent medical advances in diagnosis and treatment, the increasing numbers of long-term survivors of breast cancer is considerable and has resulted in the expansion of scientific research to include examination of lifestyle modifications as means of prevention of recurrence, new breast cancer events, and mortality. The objective of this report is to review randomized controlled trials (RCTs) including diet and/or exercise interventions on breast cancer recurrence in women with a history of breast cancer as well as pertinent recent epidemiologic evidence. Implicated biologic mechanisms are discussed to elucidate the impact of diet and exercise on disease recurrence.
Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with adverse effects on numerous physiologic parameters, including alterations in cardio-metabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardio-metabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review 1) discusses the biologic interrelationship between prostate cancer, ADT, and MetS, 2) evaluates the current literature in support of exercise in targeting MetS, and 3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT.
IntroductionProstate cancer survivors (PCS) receiving androgen deprivation therapy (ADT) experience deleterious side effects such as unfavourable changes in cardiometabolic factors that lead to sarcopenic obesity and metabolic syndrome (MetS). While loss of lean body mass (LBM) compromises muscular strength and quality of life, MetS increases the risk of cardiovascular disease and may influence cancer recurrence. Exercise can improve LBM and strength, and may serve as an alternative to the pharmacological management of MetS in PCS on ADT. Prior exercise interventions in PCS on ADT have been effective at enhancing strength, but only marginally effective at enhancing body composition and ameliorating cardiometabolic risk factors. This pilot trial aims to improve on existing interventions by employing periodised resistance training (RT) to counter sarcopenic obesity in PCS on ADT. Secondary aims compare intervention effects on cardiometabolic, physical function, quality of life and molecular skeletal muscle changes. An exploratory aim examines if protein supplementation (PS) in combination with RT elicits greater changes in these outcomes.Methods and analysisA 2×2 experimental design is used in 32 PCS on ADT across a 12-week intervention period. Participants are randomised to resistance training and protein supplementation (RTPS), RT, PS or control. RT and RTPS groups perform supervised RT three times per week for 12 weeks, while PS and RTPS groups receive 50 g whey protein per day. This pilot intervention applies a multilayered approach to ameliorate detrimental cardiometabolic effects of ADT while investigating molecular mechanisms underlying skeletal muscle changes in PCS.Ethics and disseminationThis trial was approved by the University of Southern California Institutional Review Board (HS-13–00315). Results from this trial will be communicated in peer-reviewed publications and scientific presentations.Trial registration numberNCT01909440; Pre-results.
PGC-1α4, a novel isoform of the transcriptional coactivator PGC-1α, was recently postulated to modulate the expression of anabolic and catabolic genes and therefore regulate skeletal muscle hypertrophy. Resting levels of PGC-1α4 mRNA expression were found to increase in healthy adults after resistance training. However, the acute effect of resistance exercise (RE) on PGC-1α4 expression in populations prone to progressive muscle loss, such as postmenopausal women, has not been evaluated. Here we investigated alterations in mRNA expression of PGC-1α4 and PGC-1α1, a regulator of muscle oxidative changes, in postmenopausal women following high-intensity eccentric RE, and analyzed these findings with respect to changes in IGF-1 and catabolic gene expression. Nine postmenopausal women (57.9 ± 3.2 yr) performed 10 sets of 10 maximal eccentric repetitions of single-leg extension with 20 second rest periods between sets. Muscle biopsies were obtained from the vastus lateralis of the exercised leg before and 4 hours after the RE bout with mRNA expression determined by qRT-PCR. No significant changes in the mRNA expression of either PGC-1α isoform were observed following acute eccentric RE (P > 0.05). IGF-1Ea mRNA expression significantly increased (P < 0.05) while IGF-1Eb and MGF did not significantly change (P > 0.05). PGC-1α4 mRNA expression was associated with reduced mRNA expression of the catabolic gene myostatin (R = −.88, P < 0.01), while MGF mRNA expression was associated with reduced mRNA expression of the catabolic gene FOXO3A (R = −.81, P < 0.05). These data demonstrate an attenuated response of PGC-1α isoforms to an acute bout of maximal eccentric exercise with short rest periods in postmenopausal women.
Cholesteryl esters have antimicrobial activity and likely contribute to the innate immunity system. Improved separation techniques are needed to characterize these compounds. In this study, optimization of the reversed-phase high-performance liquid chromatography separation of six analyte standards (four cholesteryl esters plus cholesterol and tri-palmitin) was accomplished by modeling with an artificial neural network–genetic algorithm (ANN-GA) approach. A fractional factorial design was employed to examine the significance of four experimental factors: organic component in the mobile phase (ethanol and methanol), column temperature, and flow rate. Three separation parameters were then merged into geometric means using Derringer’s desirability function and used as input sources for model training and testing. The use of genetic operators proved valuable for the determination of an effective neural network structure. Implementation of the optimized method resulted in complete separation of all six analytes, including the resolution of two previously co-eluting peaks. Model validation was performed with experimental responses in good agreement with model-predicted responses. Improved separation was also realized in a complex biological fluid, human milk. Thus, the first known use of ANN-GA modeling for improving the chromatographic separation of cholesteryl esters in biological fluids is presented and will likely prove valuable for future investigators involved in studying complex biological samples.FigureANN-derived response surface plot for two interacting factors and overall responseElectronic supplementary materialThe online version of this article (doi:10.1007/s00216-010-3778-5) contains supplementary material, which is available to authorized users.
Purpose: Prostate cancer survivors (PCS) on androgen deprivation therapy (ADT) experience adverse side effects such as skeletal muscle loss and adiposity gain, together called sarcopenic obesity, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance exercise can increase skeletal muscle mass, but no exercise interventions to date in PCS on ADT have concomitantly improved sarcopenic obesity and cardiometabolic risk factors. Utilizing a 12-week intervention of progressive resistance exercise designed to target skeletal muscle mass, this ongoing pilot trial investigates sarcopenic obesity and as a secondary analyses, MetS components, in PCS on ADT. Methods: Eighteen PCS (65.6±8.8 yr) on current or previous ADT were recruited from the USC Norris Comprehensive Cancer Center and randomized to resistance training (RT; n=9) or a control stretching program (CS; n=9). Body composition, measured through dual-x-ray absorptiometry, and MetS outcomes, including waist circumference, blood pressure, fasting blood glucose, triglycerides and HDL, were assessed at baseline and after the 12-week intervention. Appendicular skeletal muscle index (ASMI), a common index of sarcopenia, was calculated from body composition. RT performed a supervised total-body resistance exercise and stretching program 3 times/week. CS performed home-based stretching 3 times/week. Baseline differences were tested with univariate ANOVA. Differences in all outcomes were tested with 2(group) x 2(time) ANOVA. Results: No significant differences in ADT duration, Gleason score, body fat, skeletal muscle mass, or MetS components were found between groups at baseline (P>0.05). RT program compliance was 98.3%, while CS program compliance was 75.5%. Post-intervention, significant increases were observed in RT compared to CS for appendicular skeletal mass (mean±SE; 0.8±.4 kg; P=0.04) and ASMI (0.3±.1 kg/m2; P=0.041). A nonsignificant decrease in body fat (%) was observed in RT compared to CS (1.3±.7 %; P=.067; d=0.89). No differences were found in MetS components. Conclusions: While 12 weeks of resistance exercise in PCS on ADT improved skeletal muscle mass, no changes in adiposity and MetS variables were observed. Future interventions are needed for PCS to determine the optimal exercise prescription to target both sarcopenic obesity and cardiometabolic risk factors. Citation Format: Jacqueline L. Kiwata, Tanya B. Dorff, E. T. Schroeder, Christina M. Dieli-Conwright. Effect of a supervised exercise intervention on sarcopenic obesity and metabolic syndrome in prostate cancer patients: A randomized pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 988. doi:10.1158/1538-7445.AM2017-988
INTRODUCTION: Consistent, moderate-to-vigorous intensity exercise has been associated with a lower risk of upper respiratory tract infection (URI). However, the molecular basis for this apparent protection has not yet been fully resolved. Host-derived lipids such as cholesteryl esters (CEs) have emerged as important effector molecules of innate defense against infections. Here, we compared antimicrobial CEs in nasal fluid before and after moderate-to-vigorous exercise between active and inactive subjects. METHODS: Nasal fluid was collected from fourteen healthy, recreationally-active subjects (32 ± 11 yr, 7 males, 7 females) and 14 healthy, inactive subjects (25 ± 3 yr, 7 males, 7 females) before and after treadmill exercise at 70% heart rate reserve. Nasal fluid was analyzed for lysozyme, cholesteryl linoleate (CL), cholesteryl arachidonate (CA), and albumin (Alb) concentrations. RESULTS: Baseline concentrations (means ± SEM, inactive vs. active) of lysozyme (117.7±31.1 μg/mL vs. 122.9±15.5 μg/mL), CL+CA (15.3±1.8 μg/mL vs.26.2±10.05 μg/mL), and albumin (156.6± 54.5μg/mL vs.126.9±32.8 μg/mL) were similar to previously reported levels and did not differ significantly between study groups. However, post-exercise, CL+CA concentration was significantly lower in inactive compared to active subjects (7.8 ± 1.5 μg/mL vs. 20.1 ± 4.8 μg/mL, p = 0.036) dropping below the antimicrobial effective range. Once adjusted to albumin concentrations the changes were no longer significant, suggesting that plasma transudation accounted for the increased CA+CL concentration post-exercise in the active group relative to the inactive group. CONCLUSION: Moderate-to-vigorous aerobic exercise acutely decreases the antimicrobial CE response in inactive subjects, but does not modify baseline levels of CEs between active and inactive subjects. This suggests that compared to active individuals, inactive individuals may be at greater risk for URI immediately post-exercise.
223 Background: Cardiovascular disease is the leading cause of death in men with prostate cancer. ADT is effective treatment, but can induce loss of skeletal muscle, plus increase central fat, lipids, and insulin resistance. These changes in MetS components may contribute to excess cardiac risk. We tested whether a resistance exercise program, designed to increase skeletal muscle mass, could offset adverse changes in MetS parameters during ADT. Methods: Men on ADT for at least 12 weeks were randomized to exercise (EX) or no exercise (NOEX). EX was supervised, periodized resistance training followed by stretching 3x/week for 12 weeks, 45 min/session. NOEX did home-based stretching 3x/week. Baseline and post-intervention measurements included weight, waist circumference, lean body mass, lipids, insulin, glucose, hsCRP. Quality of life (QOL) was evaluated with FACT-P and BFI, and muscle biopsies were obtained pre- and post-intervention. Mean of changes from baseline were compared between groups using ANCOVA. Results: 24 men (mean age 65; range 49-81) completed protocol with 100% compliance (n = 12 EX, n = 12 NOEX). Baseline PSA ranged from 0 – 8.1 ng/mL and did not change; subjects had been on ADT for a mean of 17 months (range 3-84). In multivariable analysis controlling for baseline muscle mass, age, and ADT duration, the mean change in waist circumference after 12 weeks was significantly different between EX (-2.05 cm +/- 2.82) and NOEX (+0.69 cm +/- 2.01) groups (p = 0.011, t-test). There were no significant differences for other parameters. However, consistent patterns were noted in: mean fasting glucose -4.59 mg/dL in EX compared with +1.12 mg/dL in NOEX (p = 0.21, t-test) and diastolic blood pressure -2.17 mmHg in EX vs +2.0 mmHg in NOEX (p = 0.27, t-test). In the EX group 5/12 had MetS at baseline which remained stable while the NOEX group increased from 2/12 with MetS at baseline to 3/12 post intervention. Analysis of QOL and muscle biopsies are ongoing. Conclusions: Supervised resistance exercise for 12 weeks is feasible and decreases waist circumference in men receiving ADT for prostate cancer. Longer follow-up may reveal additional impacts of resistance training on MetS. Clinical trial information: NCT01909440.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.