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Translating Preclinical Research for Exercise Oncology: Take It to the VO2max.

ABSTRACT: Several observational studies have found that the risk for breast cancer is significantly reduced in persons who engage in greater amounts of physical activity. Additional observational studies of breast cancer survivors indicate that greater physical activity before or after diagnosis associates with reduced disease-specific mortality. However, no large randomized controlled trials have examined the effect of structured exercise training on disease outcomes in breast cancer. Among the many hurdles in designing such trials lies the challenge of determining how a given regimen of exercise from efficacious preclinical studies can be extrapolated to an equivalent "dose" in humans to guide decisions around treatment regimen in early-phase studies. We argue that preclinical researchers in exercise oncology could better facilitate this endeavor by routinely measuring changes in exercise capacity in the subjects of their breast cancer models. VO2max, the maximal rate of whole-organism oxygen consumption during a progressive exercise test, is emphasized here because it has become a standard measure of cardiorespiratory fitness, is well-integrated in clinical settings, and scales allometrically among nonhuman animals in preclinical research and breast cancer patients/survivors in the clinic. We also conduct secondary analyses of existing whole-transcriptome datasets to highlight how greater uptake and delivery of oxygen during exercise may reverse the typically hypoxic microenvironment of breast tumors, which often associates with more aggressive disease and worse prognosis.

SUBMITTER: Lamkin DM

PROVIDER: S-EPMC7573565 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Translating Preclinical Research for Exercise Oncology: Take It to the VO<sub>2max</sub>.

Lamkin Donald M DM Garland Theodore T

Frontiers in oncology 20201002

Several observational studies have found that the risk for breast cancer is significantly reduced in persons who engage in greater amounts of physical activity. Additional observational studies of breast cancer survivors indicate that greater physical activity before or after diagnosis associates with reduced disease-specific mortality. However, no large randomized controlled trials have examined the effect of structured exercise training on disease outcomes in breast cancer. Among the many hurd ...[more]

PMID: 33123481

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Project description:BackgroundThe negative impact of anemia on work capacity has been studied extensively in male and female workers; however, the simultaneous contributions of confounding variables such as physical activity, as well as other behavioral and sociodemographic characteristics have not been considered. The purpose of this study was to examine cross-sectionally the multivariable correlates of work capacity in non-pregnant women (n = 330) living in rural India.MethodsThe Reduction in Anemia through Normative Innovations (RANI) Project is a norms-based, clustered randomized controlled trial to reduce anemia among women (15-49 years) living in Odisha, India between 2018 and 2021. For the larger trial, 89 clusters of villages were randomized into treatment and control groups on a 1:1 basis. Women (2055/group) living in 15 selected clusters (40-41 villages) were then randomly selected for data collection. The sampling design also randomly-generated a subset (n = 375) of non-pregnant participants who performed a modified Queen's College Step Test (QCST) and who wore an activity monitor for 3 days. Predicted work capacity (VO2max) was determined using the QCST. Levels (h/day) of daily reclining, sitting, standing, walking (steps/day), and energy expenditure (MET∙h/day) were determined using an ActivPAL accelerometer. Hemoglobin concentrations (g/dL) were determined using a HemoCue photometer. Predetermined hierarchical (non-multilevel) regression models tested the independent associations between the primary study variables of interest (physical activity, hemoglobin concentrations) and predicted VO2max, while adjusting for age, body mass index (BMI: kg/m2), education, parity, and dietary diversity score.ResultsApproximately 61% of the participants had anemia (Hb < 12 g/dL). Age2 (β = - 0.01; 95% CI: - 0.01, 0.00), BMI (β = - 0.19; 95% CI:-0.28, - 0.09), educational attainment (β = - 1.35; 95% CI: - 2.34, - 0.36), and MET∙h/day (β = 0.19; 95% CI: 0.00, 0.38) were significant and independent determinants of work capacity. Hemoglobin concentration was marginally associated with work capacity in the presence of the other covariables (β = 0.22; 95% CI:-0.02, 0.47).ConclusionsOur data indicate that factors other than anemia are important correlates of work capacity and should be considered when promoting the health and economic capacity of rural Indian women.Trial registrationClinical Trial Registry- India (CTRI) http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=26285&EncHid=&userName=CTRI/2018/10/016186 on 29 October 2018.

Project description:The aim of this study is to compare the effects of concurrent strength and endurance training sequences on VO2max and lower limb strength performance to provide scientific guidance for training practice. We searched PubMed, EBSCO, Web of Science (WOS), Wanfang, and China National Knowledge Infrastructure (CNKI) databases up to December 2022. The included articles were randomized controlled trials that allowed us to compare the strength-endurance (S-E) sequence and endurance-strength (E-S) sequence on VO2max, maximum knee extension strength, maximum knee flexion strength, and lower limb power. The Cochrane bias risk tool was used to evaluate the methodological quality of the included literature, and Stata 12.0 was used for the heterogeneity test, subgroup analysis, draw forest map, sensitivity analysis, and publication bias evaluation. The results have been presented as standardized mean differences (SMDs) between treatments with 95% confidence intervals and calculations performed using random effects models. Significance was accepted when p < 0.05. The studies included 19 randomized controlled trials (285 males and 197 females), 242 subjects in S-E sequence, and 240 subjects in E-S sequence in the analyses. No difference changes between S-E and E-S sequences has been observed on VO2max in the overall analysis (SMD = 0.02, 95% CI: -0.21-0.25, p = 0.859). The S-E sequence shows a greater increase in lower limb strength performance than does the E-S sequence (SMD = 0.19, 95% CI: 0.02-0.37, p = 0.032), which was manifested in the elderly (p = 0.039) and women (p = 0.017); in training periods >8 weeks (p = 0.002) and training frequencies twice a week (p = 0.003); and with maximum knee flexion (p = 0.040) and knee extension strength (p = 0.026), while no difference was found in lower limb power (p = 0.523). In conclusion, the effect of VO2max will not change with different concurrent training sequences. The S-E sequence improves lower limb strength more significantly, mainly in the improvement of knee flexion and knee extension. This advantage is more related to factors such as age, gender, training period, and training frequency.

Dataset Information

Translating Preclinical Research for Exercise Oncology: Take It to the VO2max.

Publications

Translating Preclinical Research for Exercise Oncology: Take It to the VO<sub>2max</sub>.

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