Sara Mijwel

Effect of Acute Exercise on Prostate Cancer Cell Growth

Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum) and after completed exercise (exercise serum). The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.

Optitrain: a randomised controlled exercise trial for women with breast cancer undergoing chemotherapy

BackgroundWomen with breast cancer undergoing chemotherapy suffer from a range of detrimental disease and treatment related side-effects. Exercise has shown to be able to counter some of these side-effects and improve physical function as well as quality of life. The primary aim of the study is to investigate and compare the effects of two different exercise regimens on the primary outcome cancer-related fatigue and the secondary outcomes muscle strength, function and structure, cardiovascular fitness, systemic inflammation, skeletal muscle gene activity, health related quality of life, pain, disease and treatment-related symptoms in women with breast cancer receiving chemotherapy. The second aim is to examine if any effects are sustained 1, 2, and 5 years following the completion of the intervention and to monitor return to work, recurrence and survival. The third aim of the study is to examine the effect of attendance and adherence rates on the effects of the exercise programme.MethodsThis study is a randomised controlled trial including 240 women with breast cancer receiving chemotherapy in Stockholm, Sweden. The participants are randomly allocated to either: group 1: Aerobic training, group 2: Combined resistance and aerobic training, or group 3: usual care (control group). During the 5-year follow-up period, participants in the exercise groups will receive a physical activity prescription. Measurements for endpoints will take place at baseline, after 16 weeks (end of intervention) as well as after 1, 2 and 5 years.DiscussionThis randomised controlled trial will generate substantial information regarding the effects of different types of exercise on the health of patients with breast cancer undergoing chemotherapy. We expect that dissemination of the knowledge gained from this study will contribute to developing effective long term strategies to improve the physical and psychosocial health of breast cancer survivors.Trial registrationOptiTrain - Optimal Training Women with Breast Cancer (OptiTrain), NCT02522260; Registration: June 9, 2015, Last updated version Feb 29, 2016. Retrospectively registered.

Adding high-intensity interval training to conventional training modalities: optimizing health-related outcomes during chemotherapy for breast cancer: the OptiTrain randomized controlled trial

PurposeExercise training isxa0an effective and safexa0way to counteract cancer-related fatigue (CRF) and to improve health-related quality of life (HRQoL). High-intensity interval training has proven beneficial for the health of clinical populations. The aim of this randomized controlled trial was to compare the effects of resistance and high-intensity interval training (RT–HIIT), and moderate-intensity aerobic and high-intensity interval training (AT–HIIT) to usual care (UC) in women with breast cancer undergoing chemotherapy. The primary endpoint was CRF and the secondary endpoints were HRQoL and cancer treatment-related symptoms.MethodsTwo hundred and forty women planned to undergo chemotherapy were randomized to supervised RT–HIIT, AT–HIIT, or UC. Measurements were performed at baseline and at 16xa0weeks. Questionnaires included Piper Fatigue Scale, EORTC-QLQ-C30, and Memorial Symptom Assessment Scale.ResultsThe RT–HIIT group was superior to UC for CRF: total CRF (pxa0=xa00.02), behavior/daily life (pxa0=xa00.01), and sensory/physical (pxa0=xa00.03) CRF. Role functioning significantly improved while cognitive functioning was unchanged for RT–HIIT compared to declines shown in the UC group (pxa0=xa00.04). AT–HIIT significantly improved emotional functioning versus UC (pxa0=xa00.01) and was superior to UC for pain symptoms (pxa0=xa00.03). RT–HIIT reported a reduced symptom burden, while AT–HIIT remained stable compared to deteriorations shown by UC (pxa0<xa00.01). Only RT–HIIT was superior to UC for total symptoms (pxa0<xa00.01).Conclusions16xa0weeks of resistance and HIIT was effective in preventing increases in CRF and in reducing symptom burden for patients during chemotherapy for breast cancer. These findings add to a growing body of evidence supporting the inclusion of structured exercise prescriptions, including HIIT, as a vital component of cancer rehabilitation.Trial registrationClinicaltrials.gov Registration Number: NCT02522260.

Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer

Exercise has been suggested to ameliorate the detrimental effects of chemotherapy on skeletal muscle. The aim of this study was to compare the effects of different exercise regimens with usual care on skeletal muscle morphology and mitochondrial markers in patients being treated with chemotherapy for breast cancer. Specifically, we compared moderate‐intensity aerobic training combined with high‐intensity interval training (AT‐HIIT) and resistance training combined with high‐intensity interval training (RT‐HIIT) with usual care (UC). Resting skeletal muscle biopsies were obtained pre‐ and postintervention from 23 randomly selected women from the OptiTrain breast cancer trial who underwent RT‐HIIT, AT‐HIIT, or UC for 16 wk. Over the intervention, citrate synthase activity, muscle fiber cross‐sectional area, capillaries per fiber, and myosin heavy chain isoform type I were reduced in UC, whereas RT‐HIIT and AT‐HIIT were able to counteract these declines. AT‐HIIT promoted up‐regulation of the electron transport chain protein levels vs. UC. RT‐HIIT favored satellite cell count vs. UC and AT‐HIIT. There was a significant association between change in citrate synthase activity and self‐reported fatigue. AT‐HIIT and RT‐ HIIT maintained or improved markers of skeletal muscle function compared with the declines found in the UC group, indicating a sustained trainability in addition to the preservation of skeletal muscle structural and metabolic characteristics during chemotherapy. These findings highlight the importance of supervised exercise programs for patients with breast cancer during chemotherapy.—Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengstrom, Y., Sundberg, C. J., Rundqvist, H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer. FASEB J. 32, 5495–5505 ((2018). www.fasebj.org

Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial

BackgroundAdvanced therapeutic strategies are often accompanied by significant adverse effects, which warrant equally progressive countermeasures. Physical exercise has proven an effective intervention to improve physical function and reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity interval training (HIIT) in this population are not well established although HIIT has proven effective in other clinical populations. The aim of the OptiTrain trial was to examine the effects of concurrent resistance and high-intensity interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high-intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and physiological outcomes in patients with breast cancer during chemotherapy.MethodsTwo hundred and forty women were randomized to 16xa0weeks of RT-HIIT, AT-HIIT, or UC. Outcomes: cardiorespiratory fitness, muscle strength, body mass, hemoglobin levels, and pressure-pain threshold.ResultsPre- to post-intervention, RT-HIIT (ESxa0=xa00.41) and AT-HIIT (ESxa0=xa00.42) prevented the reduced cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT vs. UC: ESxa0=xa00.41, RT-HIIT vs. AT-HIIT: ESxa0=xa00.28; non-surgery side: RT-HIIT vs. UC: ESxa0=xa00.35, RT-HIIT vs. AT-HIIT: ESxa0=xa00.22) and lower-limb muscle strength (RT-HIIT vs. UC: ESxa0=xa00.66, RT-HIIT vs. AT-HIIT: ESxa0=xa00.23) were significantly improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ESxa0=xa0−xa00.16) and AT-HIIT (ESxa0=xa0−xa00.16) versus UC. RT-HIIT reported higher pressure-pain thresholds than UC (trapezius: ESxa0=xa00.46, gluteus: ESxa0=xa00.53) and AT-HIIT (trapezius: ESxa0=xa00.30).ConclusionSixteenxa0weeks of RT-HIIT significantly improved muscle strength and reduced pain sensitivity. Both exercise programs were well tolerated and were equally efficient in preventing increases in body mass and inxa0preventing declines in cardiorespiratory fitness. These results highlight the importance of implementing a combination of resistance and high-intensity interval training during chemotherapy for women with breast cancer.

Cutaneous exposure to hypoxia does not affect skin perfusion in humans

Experiments have indicated that skin perfusion in mice is sensitive to reductions in environmental O2 availability. Specifically, a reduction in skin‐surface PO2 attenuates transcutaneous O2 diffusion, and hence epidermal O2 supply. In response, epidermal HIF‐1α expression increases and facilitates initial cutaneous vasoconstriction and subsequent nitric oxide‐dependent vasodilation. Here, we investigated whether the same mechanism exists in humans.

Physical Activity During and After Adjuvant Treatment for Breast Cancer : An Integrative Review of Women's Experiences

Background: In oncology, physical activity (PA) is recognized to improve psychological and physiological functions. Motivating women with breast cancer to sustain a physically active lifestyle is important for promoting positive health after diagnosis. To review and synthesize what is known about how women with breast cancer experience supervised and unsupervised PA during and after adjuvant treatment. PubMed, PsycINFO, and CINAHL were searched, yielding 994 citations. The final review included 17 articles published between 2004 and 2014 in English. The CASP (Critical Appraisal Skills Programme) instrument was used to appraise quality. Results: Exercise is experienced as a positive element with multiple benefits. However, maintaining a physically active lifestyle during and after chemotherapy is sometimes challenging. Reported benefits of PA include feeling empowered, and improving and reclaiming health. Facilitators to PA comprised exercising with peers and skilled instructors. Barriers included social factors and lack of information. Conclusions: Findings highlight the importance of incorporating PA programs from a patient experience perspective as routine treatment. Health care professionals play a crucial “gateway” role in providing information on implementation and benefits of PA. Providing support and educated advice about how to safely start or continue regular PA to minimize symptoms, reduce morbidity, and increase well-being during or after treatment is vital for women with breast cancer. Implications for Practice: Health care professionals need increased knowledge of the breast cancer patients’ perspectives on facilitators and barriers to PA during and after treatment, in order to provide sufficient support for women to stay physically active during a breast cancer illness.

Validation of 2 Submaximal Cardiorespiratory Fitness Tests in Patients With Breast Cancer Undergoing Chemotherapy.

Background: Patients with breast cancer have an impaired cardiorespiratory fitness, in part, due to the toxic effects of anticancer therapy. Physical exercise as a means of rehabilitation for patients with cancer is an emerging area of research and treatment, emphasizing the need for accurate and feasible physical capacity measurements. The purpose of this study was to evaluate the validity of peak oxygen consumption ( O2peak) predicted by the Ekblom-Bak test (E-B) and the Åstrand-Rhyming prediction model (A-R). Methods: Eight patients with breast cancer undergoing chemotherapy participated in the study. Submaximal exercise tests were performed at 2 different submaximal workloads. Estimated O2peak values were obtained by inserting the heart rate (HR) from the 2 workloads into the E-B prediction model and the HR of only the higher workload into the Åstrand nomogram. A 20-W incremental cycle test-to-peak effort was performed to obtain O2peak values. Results: Results from A-R overestimated O2peak by 6% (coefficient of variation = 7%), whereas results from E-B overestimated O2peak with 42% (coefficient of variation = 21%) compared with measured O2peak. Pearsons correlation coefficient revealed a significant strong relationship between the estimated O2peak from A-R and the measured O2peak (r = 0.86; P < .05), whereas the relationship between the estimated O2peak from E-B and the measured O2peak resulted in a nonsignificant weak correlation (r = 0.21). Conclusion: In a situation where maximal exercise testing is not practical or undesirable from a patient safety perspective, submaximal exercise testing provides an alternative way of estimating O2peak. The A-R prediction model appears to be a valid submaximal exercise test for determining cardiorespiratory fitness in this population.

Abstract 836: Effect of voluntary running on metastasis in a mouse model of breast cancer

Introduction: Emerging evidence states that regular physical exercise provides a risk reduction for breast cancer by approximately 25%. In addition, recent studies suggest that physical activity may also have an effect on recurrence and mortality. Mouse models are suitable tools to study anti-neoplastic mechanisms. Aim: to evaluate the effect of voluntary running on tumor initiation, growth and metastasis in the Polyoma Middle T (PyMT) model of breast cancer. Methods: PyMT mice were housed with access either to wirelessly recording running wheels or locked control wheels. Running distances and tumor volumes were recorded. At 12 weeks, mice were sacrificed. Mammary glands were histologically staged and pulmonary metastases were quantified. In a follow up study, pre-trained mice were injected intravenously with tumor cells derived from the PyMT model and after an additional 10 weeks of voluntary running, pulmonary metastases were quantified. Results: PyMT mice ran significantly more than wildtype mice (6.4 vs 3.4 km/day). No significant effects of voluntary running on tumor- initiation, volume or stage were found. However, a trend for reduced metastasis was observed. After intravenous injections of tumor cells, runners had a significantly lower pulmonary metastasis frequency than non-runners. Conclusion: In this aggressive breast cancer model, an average of 6 km/day of voluntary running did not induce any effect on tumor formation or growth. However, the findings suggest that physical activity has impact on the metastatic process. Citation Format: Sara Mijwel, Helene Rundqvist, Carolin Lindholm, Carina Strell, Pernilla Roswall, Kristian Pietras, Randall S. Johnson, Arne Ostman. Effect of voluntary running on metastasis in a mouse model of breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 836.

1905 Validation of two submaximal exercise tests in breast cancer patients undergoing chemotherapy treatment

Validation of two submaximal exercise tests in breast cancer patients undergoing chemotherapy treatment