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- All Subjects: Chemotherapy
- All Subjects: High Load
- Creators: Angadi, Siddhartha
Description
The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.
ContributorsO'Neill, Liam Martin (Author) / Sweazea, Karen (Thesis director) / Angadi, Siddhartha (Committee member) / Dickinson, Jared (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Sedentary behavior and excessive weight gain have been proven to deteriorate many characteristics of muscle. Low muscular power and mass with excess fat mass are risk factors for a multitude of chronic conditions and functional disabilities. Resistance training (RT) has long been accepted as a rehabilitative method of maintaining or enhancing muscular performance and composition. There are various methods of determining lower extremity muscular power; however, isokinetic dynamometry has emerged as one of the most accurate and reliable methods in clinical and research settings. Likewise, various methods exist for determining muscle thickness; however, many of those methods are expensive and can expose individuals to radiation. Ultrasonography has emerged as an accurate and reliable alternative to measuring lower extremity muscle thickness. The objective of this study was to assess the effects of high-load/low-volume (HLLV) and low-load/high-volume (LLHV) RT on isokinetic knee extensor and flexor peak power in sedentary, RT naïve, overweight or obese men and women (Body Mass Index ≥ 25 kg/m2). Twenty-one subjects (n = 21) completed this study and were randomized into one of the following groups: control, a HLLV group that performed three sets of 5 repetitions for all exercises until volitional fatigue, and LLHV which performed three sets of 15 repetitions for all exercises until volitional fatigue. Subjects randomized to the RT groups performed full-body exercises routines on three non-consecutive days per week. Changes in isokinetic knee extensor and flexor peak power, quadriceps ultrasound muscle thickness, and right leg segment of dual-energy X-ray absorptiometry (DEXA) scans were measured before and after the 12-week RT intervention. There were no significant differences found in group, time or, group by time interactions for knee extensor and flexor peak power using isokinetic dynamometry. Other than a group interaction for vastus intermedius muscle thickness (P=0.008), no significant interactions or differences were observed for any of the other variables tested. Based on the results of this study, neither high- nor low-load RT resulted in significant differences between intervention groups in peak power of the knee extensors and flexor, muscle thickness changes of the vastus intermedius, and vastus lateralis and, in the right lower extremity segmented body composition measures using DEXA.
ContributorsSarellis, Sofoklis Demetrios (Author) / Ofori, Edward (Thesis advisor) / Angadi, Siddhartha (Committee member) / Gaesser, Glenn (Committee member) / Arizona State University (Publisher)
Created2020
Description
Estimates indicate that in the United States 1 in 8 women will develop breast cancer in their lifetime. Improved cancer screenings, early detection, and targeted treatments have increased breast cancer survival rates. However, breast cancer patients treated with chemotherapy are at an increased risk for cardiovascular disease, functional impairments, and loss of cardiorespiratory fitness. These negative outcomes have implications for early morbidity and mortality. The purpose of this thesis was to test the hypothesis that high-intensity exercise preconditioning (exercise commenced prior to initiating chemotherapy and continued throughout treatment cycles) preserves health-related outcomes in breast cancer patients treated with anthracycline-containing chemotherapy. Here, we present a subset of preliminary data from an ongoing trial (NCT02842658) that is focused on VO2peak and skeletal muscle outcomes from the first 10 participants that have enrolled in the trial. Breast cancer patients (N=10; 50 ± 11 y; 168 ± 4 cm; 92 ± 37 kg; 32.3 ± 12.3 kg/m2) scheduled to receive anthracycline-containing chemotherapy were randomly assigned to one of two interventions: 1) exercise preconditioning, (3 days per week of supervised exercise throughout treatment) or 2) standard of care (attention-control). Pre-testing occurred 1-2 week prior to chemotherapy. The interventions were initiated 1 week prior to chemotherapy and continued throughout anthracycline treatment. Post-testing occurred 3-7 days following the last anthracycline treatment. VO2peak (L/min) was reduced by 16% in the control group (P < 0.05), whereas VO2peak was preserved in the exercise preconditioning group. Trends for greater preservation and/or improvement in the exercise preconditioning group were also observed for lean body mass and peak heart rate. Hand grip strength was not changed in either group (P > 0.05). Both groups demonstrated an increase in ultrasound-derived echogenicity measures of the vastus lateralis (P < 0.05), indicating changes in the composition of the skeletal muscle during treatment. These preliminary data highlight that exercise preconditioning may serve as a strategy to preserve cardiorespiratory fitness and perhaps lean mass during anthracycline treatment of breast cancer. There remains a need for larger, definitive clinical trials to identify strategies to prevent the array of chemotherapy-induced toxicities that are observed in breast cancer patients treated with anthracyclines.
ContributorsCasey, Kathleen (Author) / Angadi, Siddhartha (Thesis director) / Gaesser, Glenn (Committee member) / Dickinson, Jared (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05