Exercise protocols: The gap between preclinical and clinical exercise oncology studies.

INTRODUCTION: Preclinical studies provide foundational knowledge to develop new effective treatments for use in clinical practice. Similar to clinical exercise oncology studies, it is also important to monitor, identify and/or avoid cancer-induced complications in preclinical (e.g., murine) exercise oncology studies. This may help close the gap between preclinical and clinical exercise oncology studies. The aim of the present mini review is to provide insight into exercise protocol design in preclinical exercise oncology studies in order to close the preclinical-clinical gap. A secondary aim was to examine exercise-responsive outcomes in the preclinical versus clinical setting. METHOD: We reviewed animal studies in exercise oncology. A literature search was performed in PubMed/Medline and studies in English were screened. RESULTS: We found that the majority of preclinical exercise protocols have not been at least tested clinically. We found some evidence that certain outcomes of preclinical studies (e.g., markers of cellular and molecular adaptation) that translate to clinical studies. However, this translation was dependent on the use, by investigators in their study design, of suitable and applicable preclinical exercise protocols. CONCLUSIONS: Cancer and its treatment-induced complications (e.g., fatigue, cardiac atrophy, cachexia, etc.) have largely been ignored in the exercise protocols of preclinical oncology studies. Preclinical exercise oncology studies should consider the limitations of human exercise oncology studies when conducting gap analysis for their study design to increase the probability that findings related to mechanistic adaptations in exercise oncology will be translatable to the clinical setting. By virtue of paying heed to patient compliance and adverse effects, clinical exercise oncology research teams must design relevant, feasible exercise protocols; researchers in preclinical exercise oncology should also take such factors into consideration in order to help bridge the gap between preclinical and clinical studies in exercise oncology.

High intensity interval training improves diabetic cardiomyopathy via miR-1 dependent suppression of cardiomyocyte apoptosis in diabetic rats.

PURPOSE: Diabetes and its complications such as diabetic cardiomyopathy still account for significant morbidity and mortality. High-quality evidence was shown the importance of exercise in controlling diabetes complications, but the molecular mechanism on diabetic cardiomyopathy is not yet fully understood. This study aimed to compare and investigate the effect of high intensity interval training (HIIT) and continuous endurance training (CET) on the signaling pathway of diabetic cardiomyopathy. METHODS: Hence, 21 Wistar rats with an average weight of 260 ± 10 g, after induction of diabetes (STZ 50 mg/kg BW) were randomly divided into three groups (control, CET and HIIT; n = 7). Training programs were conducted 5 days a week for 5 weeks. CET program was defined as running at 60% vVO2max for 30 min in each session and the HIIT program was defined as running at 85-90% vVO2max for 3 min followed by 1 min recovery (30-35% vVO2max), that was repeated four times in each session. The cardiac performance was analyzed via determination of end systolic and diastolic dimensions and the ejection fraction by echocardiography. To elucidate the responsible molecular mechanism of miR-1, IGF-1 and IGF-1R mRNA and apoptosis marker protein expression were investigated. RESULTS: Both training programs specifically HIIT, significantly reduced the blood glucose, enhanced heart performance, reduced miR-1 expression, induced IGF-1 and IGF-1R expression and reduced apoptotic protein expression. CONCLUSION: We showed that HIIT is more effective than CET for reduction of diabetic cardiomyopathy as a complication of diabetes in animal models through suppressing miR-1 and its downstream apoptosis pathway.

Associations of branched-chain amino acids with parameters of energy balance and survival in colorectal cancer patients: Results from the ColoCare Study.

BACKGROUND: Branched-chain amino acids (BCAA) have been previously linked to survival in colorectal cancer (CRC) patients. It is unclear whether BCAAs are prognostic biomarkers or surrogate markers for energy balance. OBJECTIVES: We aimed to determine correlations of BCAAs with markers of energy balance over time and to investigate prognostic significance of BCAAs in CRC. METHODS: We used urinary samples from newly diagnosed CRC patients [n=163; (stage I - IV)] from the ColoCare study in Heidelberg, Germany, collected at surgery (n=163), 6 (n=83) and 12 months follow-up (n=54). Isoleucine, leucine, valine, (2Z)-3-methylglutaconic acid (3HM), 2-ethylhydracrylic acid (2EA), 2-methyl-3-hydroxybutyrate (2M3H) were detected using gas-chromatography mass-spectrometry and proton-nuclear-magnetic-resonance spectroscopy. Partial correlation coefficients between BCAAs with body mass index (BMI), physical activity (metabolic equivalent [MET]) and muscle area were computed and adjusted for sex and age at diagnosis. We used Cox proportional hazard models to investigate overall survival (OS) after 24 months of follow-up. RESULTS: We did not observe significant correlations between BCAAs and parameters of energy balance at all time points (correlation ranges: BMI: r= -0.13 to -0.01; METs: r=-0.14 to 0.02; dorsal muscle: r=-0.03 to 0.10). BCAAs were not associated with risk of death in stage I-III (e.g., valine: HRlog2=1.62, p=0.25) or in stage IV tumors. Elevated concentrations of 2EA and 2M3H were significantly associated with OS, independent of stage (2EA: stage I-III: HRlog2=0.42, p=0.04; stage IV: HRlog2=0.51, p=0.01). CONCLUSION: Our study suggests that BCAAs in colorectal cancer patients do not reflect parameters of energy balance and may be independently associated with overall survival.

Signals from the Adipose Microenvironment and the Obesity-Cancer Link-A Systematic Review.

Obesity and its associated metabolic dysregulation are established risk factors for many cancers. However, the biologic mechanisms underlying this relationship remain incompletely understood. Given the rising rates of both obesity and cancer worldwide, and the challenges for many people to lose excess adipose tissue, a systematic approach to identify potential molecular and metabolic targets is needed to develop effective mechanism-based strategies for the prevention and control of obesity-driven cancer. Epidemiologic, clinical, and preclinical data suggest that within the growth-promoting, proinflammatory microenvironment accompanying obesity, crosstalk between adipose tissue (comprised of adipocytes, macrophages and other cells) and cancer-prone cells may occur via obesity-associated hormones, cytokines, and other mediators that have been linked to increased cancer risk and/or progression. We report here a systematic review on the direct "crosstalk" between adipose tissue and carcinomas in humans. We identified 4,641 articles with n = 20 human clinical studies, which are summarized as: (i) breast (n = 7); (ii) colorectal (n = 4); (iii) esophageal (n = 2); (iv) esophageal/colorectal (n = 1); (v) endometrial (n = 1); (vi) prostate (n = 4); and (vii) ear-nose-throat (ENT) cancer (n = 1). Findings from these clinical studies reinforce preclinical data and suggest organ-dependent crosstalk between adipose tissue and carcinomas via VEGF, IL6, TNFα, and other mechanisms. Moreover, visceral white adipose tissue plays a more central role, as it is more bioenergetically active and is associated with a more procancer secretome than subcutaneous adipose tissue. Efforts to eavesdrop and ultimately interfere with this cancer-enhancing crosstalk may lead to new targets and strategies for decreasing the burden of obesity-related cancers. Cancer Prev Res; 10(9); 494-506. ©2017 AACR.

A systematic review of the interrelation between diet- and surgery-induced weight loss and vitamin D status.

Obesity is a major global health problem and has been associated with vitamin D deficiency. Intentional weight loss may alter vitamin D status and, conversely, vitamin D supplementation has been hypothesized to aid in weight loss. A systematic literature search in PubMed/Medline identified 3173 articles of which 37 studies (randomized controlled trials (RCT) [n=17], non-RCTs [n=20]) are summarized as effect of: (I) diet-induced weight loss on vitamin D status (n=7), (II) vitamin D supplementation on diet-induced weight loss (n=11), (III) surgery-induced weight loss on vitamin D status (n=15), and (IV) vitamin D supplementation after surgery-induced weight loss on vitamin D status (n=5). While all studies on the effect of diet-induced weight loss on vitamin D status have consistently reported increased vitamin D levels, the targeted percentage of weight loss that is necessary for an increase has varied between 5% and >10%. N=11 RCTs testing the effect of vitamin D supplementation observe that vitamin D supplementation does not result in increased weight loss, but may affect body fat loss. Vitamin D deficiency and subsequent hyperparathyroidism have been detected in post-surgery patients, and there is evidence that vitamin D supplementation improves these post-surgery complications. We review the current evidence addressing the role of vitamin D status and supplementation in diet- and surgery-induced weight loss. Subsequently, we highlight gaps in current research and suggest directions for future research including differences in vitamin D supplementation dosages, indoor vs. outdoor exercise, and the assessment of vitamin D status in different body pools.