Gymnastik- och idrottshögskolan, GIH

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  • 1.
    Adlard, Kirsten N.
    et al.
    Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    Devin, James L.
    Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    Jenkins, David G.
    Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    Bolam, Kate A.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology. Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    Aitken, Joanne F.
    Griffith Univ, Menzies Hlth Inst Queensland, Gold Coast, Qld, Australia.;Canc Council Queensland, Canc Res Ctr, Brisbane, Qld, Australia..
    Chambers, Suzanne K.
    Griffith Univ, Menzies Hlth Inst Queensland, Gold Coast, Qld, Australia.;Canc Council Queensland, Canc Res Ctr, Brisbane, Qld, Australia.;Prostate Canc Fdn Australia, Sydney, NSW, Australia.;Edith Cowan Univ, Hlth & Wellness Inst, Perth, WA, Australia.;Univ Queensland, Clin Res Ctr, Brisbane, Qld, Australia..
    Dunn, Jeffrey C.
    Griffith Univ, Menzies Hlth Inst Queensland, Gold Coast, Qld, Australia.;Canc Council Queensland, Canc Res Ctr, Brisbane, Qld, Australia.;Univ Queensland, Sch Social Sci, Brisbane, Qld, Australia..
    Skinner, Tina L.
    Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    THE INFLUENCE OF EXERCISE INTENSITY ON FATIGUE IN COLORECTAL CANCER SURVIVORS: A RANDOMIZED CONTROLLED TRIAL2016In: Asia-Pacific Journal of Clinical Oncology, ISSN 1743-7563, E-ISSN 1743-7563, Vol. 12, no S5, p. 78-78, article id 44Article in journal (Other academic)
  • 2. Adlard, Kirsten N
    et al.
    Jenkins, David G
    Salisbury, Chloe E
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Gomersall, Sjaan R
    Aitken, Joanne F
    Chambers, Suzanne K
    Dunn, Jeff C
    Courneya, Kerry S
    Skinner, Tina L
    Peer support for the maintenance of physical activity and health in cancer survivors: the PEER trial - a study protocol of a randomised controlled trial.2019In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, no 1, p. 656-, article id 656Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Despite an overwhelming body of evidence showing the benefits of physical activity (PA) and exercise for cancer survivors, few survivors meet the exercise oncology guidelines. Moreover, initiating, let alone maintaining exercise programs with cancer survivors continues to have limited success. The aim of this trial is to evaluate the influence of peer support on moderate-to-vigorous PA (MVPA) and various markers of health 12 months following a brief supervised exercise intervention in cancer survivors.

    METHODS: Men and women previously diagnosed with histologically-confirmed breast, colorectal or prostate cancer (n = 226), who are >1-month post-treatment, will be invited to participate in this trial. Once enrolled, participants will complete 4 weeks (12 sessions) of supervised high intensity interval training (HIIT). On completion of the supervised phase, both groups will be provided with written recommendations and verbally encouraged to achieve three HIIT sessions per week, or equivalent exercise that meets the exercise oncology guidelines. Participants will be randomly assigned to receive 12 months of peer support, or no peer support (control). Primary and secondary outcomes will be assessed at baseline, after the 4-week supervised HIIT phase and at 3-, 6- and 12-months. Primary outcomes will include accelerometry-derived MVPA and prescribed HIIT session adherence; whilst secondary outcomes will include cardiorespiratory fitness ([Formula: see text]), body composition, quality of life and select cytokines, myokines and inflammatory markers. Random effects mixed modelling will be used to compare mean changes in outcomes between groups at each time point. A group x time interaction will be used to formally test for differences between groups (alpha =0.05); utilising intention-to-treat analyses.

    DISCUSSION: If successful, peer support may be proposed, adopted and implemented as a strategy to encourage cancer survivors to maintain exercise beyond the duration of a short-term, supervised intervention. A peer support-exercise model has the long-term potential to reduce comorbidities, improve physical and mental wellbeing, and significantly reduce the burden of disease in cancer survivors.

    ETHICS: Human Research Ethics Committee of Bellberry Ltd. (#2015-12-840).

    TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry 12618001855213 . Retrospectively registered 14 November 2018. Trial registration includes all components of the WHO Trial Registration Data Set, as recommended by the ICMJE.

  • 3. Ansund, Josefin
    et al.
    Mijwel, Sara
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Altena, Renske
    Wengström, Yvonne
    Rullman, Eric
    Rundqvist, Helene
    High intensity exercise during breast cancer chemotherapy - effects on long-term myocardial damage and physical capacity - data from the OptiTrain RCT.2021In: Cardio-oncology (London, England), ISSN 2057-3804, Vol. 7, no 1, p. 7-, article id 7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adjuvant systemic breast cancer treatment improves disease specific outcomes, but also presents with cardiac toxicity. In this post-hoc exploratory analysis of the OptiTrain trial, the effects of exercise on cardiotoxicity were monitored by assessing fitness and biomarkers over the intervention and into survivorship. Methods; Women starting chemotherapy were randomized to 16-weeks of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). Outcome measures included plasma troponin-T (cTnT), Nt-pro-BNP and peak oxygen uptake (VO2peak), assessed at baseline, post-intervention, and at 1- and 2-years.

    RESULTS: For this per-protocol analysis, 88 women met criteria for inclusion. Plasma cTnT increased in all groups post-intervention. At the 1-year follow-up, Nt-pro-BNP was lower in the exercise groups compared to UC. At 2-years there was a drop in VO2peak for patients with high cTnT and Nt-pro-BNP. Fewer patients in the RT-HIIT group fulfilled biomarker risk criteria compared to UC (OR 0.200; 95% CI = 0.055-0.734).

    CONCLUSIONS: In this cohort, high-intensity exercise was associated with lower levels of NT-proBNP 1-year post-baseline, but not with cTnT directly after treatment completion. This may, together with the preserved VO2peak in patients with low levels of biomarkers, indicate a long-term cardioprotective effect of exercise.

    TRIAL REGISTRATION: Clinicaltrials. govNCT02522260 , Registered 13th of august 2015 - Retrospectively Registered.

  • 4. Baguley, Brenton J
    et al.
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Wright, Olivia R L
    Skinner, Tina L
    The Effect of Nutrition Therapy and Exercise on Cancer-Related Fatigue and Quality of Life in Men with Prostate Cancer: A Systematic Review.2017In: Nutrients, E-ISSN 2072-6643, Vol. 9, no 9, article id 1003Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Improvements in diet and/or exercise are often advocated during prostate cancer treatment, yet the efficacy of, and optimal nutrition and exercise prescription for managing cancer-related fatigue and quality of life remains elusive. The aim of this study is to systematically review the effects of nutrition and/or exercise on cancer-related fatigue and/or quality of life.

    METHODS: A literature search was conducted in six electronic databases. The Delphi quality assessment list was used to evaluate the methodological quality of the literature. The study characteristics and results were summarized in accordance with the review's Population, Intervention, Control, Outcome (PICO) criteria.

    RESULTS: A total of 20 articles (one diet only, two combined diet and exercise, and seventeen exercise only studies) were included in the review. Soy supplementation improved quality of life, but resulted in several adverse effects. Prescribing healthy eating guidelines with combined resistance training and aerobic exercise improved cancer-related fatigue, yet its effect on quality of life was inconclusive. Combined resistance training with aerobic exercise showed improvements in cancer-related fatigue and quality of life. In isolation, resistance training appears to be more effective in improving cancer-related fatigue and quality of life than aerobic exercise. Studies that utilised an exercise professional to supervise the exercise sessions were more likely to report improvements in both cancer-related fatigue and quality of life than those prescribing unsupervised or partially supervised sessions. Neither exercise frequency nor duration appeared to influence cancer-related fatigue or quality of life, with further research required to explore the potential dose-response effect of exercise intensity.

    CONCLUSION: Supervised moderate-hard resistance training with or without moderate-vigorous aerobic exercise appears to improve cancer-related fatigue and quality of life. Targeted physiological pathways suggest dietary intervention may alleviate cancer-related fatigue and improve quality of life, however the efficacy of nutrition management with or without exercise prescription requires further exploration.

  • 5.
    Bolam, Kate
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Mijwel, Sara
    Rundqvist, Helene
    Wengström, Yvonne
    Two-year follow-up of the OptiTrain randomised controlled exercise trial.2019In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 175, no 3, p. 637-648Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to determine if there were any differences in health-related outcomes and physical activity (PA) between the two OptiTrain exercise groups and usual care (UC), 2 years post-baseline.

    METHODS: The OptiTrain study was a three-arm randomised controlled trial comparing 16 weeks of concurrent aerobic high-intensity interval training (HIIT) and progressive resistance exercise (RT-HIIT) or concurrent HIIT and continuous moderate-intensity aerobic exercise (AT-HIIT) to UC in 206 patients with breast cancer undergoing chemotherapy. Eligible participants were approached 2 years following baseline to assess cancer-related fatigue, quality of life, symptoms, muscle strength, cardiorespiratory fitness, body mass, PA, sedentary behaviour, and sick leave.

    RESULTS: The RT-HIIT group reported lower total cancer-related fatigue, (- 1.37, 95% CI - 2.70, - 0.04, ES = - 0.06) and cognitive cancer-related fatigue (- 1.47, 95% CI - 2.75, - 0.18, ES = - 0.28), and had higher lower limb muscle strength (12.09, 95% CI 3.77, 20.40, ES = 0.52) than UC at 2 years. The AT-HIIT group reported lower total symptoms (- 0.23, 95% CI - 0.42, - 0.03, ES = - 0.15), symptom burden (- 0.30, 95% CI - 0.60, - 0.01, ES = - 0.19), and body mass - 2.15 (- 3.71, - 0.60, ES = - 0.28) than UC at 2 years.

    CONCLUSION: At 2 years, the exercise groups were generally experiencing positive differences in cancer-related fatigue (RT-HIIT), symptoms (AT-HIIT), and muscle strength (RT-HIIT) to UC. The findings provide novel evidence that being involved in an exercise program during chemotherapy can have long-term benefits for women with breast cancer, but that strategies are needed to create better pathways to support patients to maintain physical activity levels.

    TRIAL REGISTRATION: Clinicaltrials.gov registration number: NCT02522260. Trial registered on 9 June 2015. https://clinicaltrials.gov/ct2/show/NCT02522260 . Retrospectively registered.

  • 6. Campbell, Kristin L
    et al.
    Cormie, Prue
    Weller, Sarah
    Alibhai, Shabbir M H
    Bolam, Kate
    Karolinska institutet, Stockholm, Sweden.
    Campbell, Anna
    Cheville, Andrea L
    Dalzell, Mary-Ann
    Hart, Nicolas H
    Higano, Celestia S
    Lane, Kirstin
    Mansfield, Sami
    McNeely, Margaret L
    Newton, Robert U
    Quist, Morten
    Rauw, Jennifer
    Rosenberger, Friederike
    Santa Mina, Daniel
    Schmitz, Kathryn H
    Winters-Stone, Kerri M
    Wiskemann, Joachim
    Goulart, Jennifer
    Exercise Recommendation for People With Bone Metastases: Expert Consensus for Health Care Providers and Exercise Professionals.2022In: JCO oncology practice, ISSN 2688-1535, Vol. 18, no 5, p. e697-e709Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion.

    METHODS: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement.

    RESULTS: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment-related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential.

    CONCLUSION: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases.

  • 7. Cornish, Rahchell S
    et al.
    Bolam, Kate A
    School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD, Australia.
    Skinner, Tina L
    Effect of caffeine on exercise capacity and function in prostate cancer survivors.2015In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 47, no 3, p. 468-75Article in journal (Refereed)
    Abstract [en]

    PURPOSE: This study aimed to examine the acute effect of caffeine on exercise capacity, exercise-related fatigue, and functional performance in prostate cancer survivors.

    METHODS: In this randomized, placebo-controlled, double-blind crossover study, 30 prostate cancer survivors (age, 70.3 ± 7.7 yr; body mass, 80.5 ± 13.0 kg; mean ± SD) consumed 6.04 ± 0.16 mg·kg(-1) of anhydrous caffeine or a placebo 1 h before completing a battery of exercise capacity and functional performance tests. Testing sessions were separated by 3-4 wk. Immediate fatigue and perceived exertion were measured directly pre- and postexercise at both testing sessions.

    RESULTS: Caffeine increased exercise capacity by 7.93 s (+3.0%; P = 0.010); however, postexercise fatigue and perception of exertion were comparable with the placebo session (P = 0.632 and P = 0.902, respectively). Increases in isometric grip strength trended toward significance in both dominant (+2.9%; P = 0.053) and nondominant (+2.1%; P = 0.061) hands in the caffeine trial compared with placebo. Caffeine ingestion did not result in improvements in performance for any of the remaining functional measures, including the timed up-and-go test, repeated chair stands, 6-m fast walk, and 6-m backward tandem walk. Systolic blood pressure and HR were significantly increased (P = 0.006 and P = 0.040, respectively) upon completion of the testing battery when compared with placebo.

    CONCLUSIONS: Consumption of caffeine 1 h before exercise induced improvements in exercise capacity and muscular strength in prostate cancer survivors. However, there was no change in exercise-related fatigue when compared with placebo despite reduction in timed performance of the 400-m walk. Caffeine seems to enhance exercise tolerance through improved performance with no subsequent increase in fatigue or perception of exertion and may be an appropriate strategy to promote exercise participation in prostate cancer survivors.

  • 8.
    de Boniface, Jana
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Altena, Renske
    Karolinska Institutet, Stockholm, Sweden.
    Haddad Ringborg, Cecilia
    Karolinska Institutet, Stockholm, Sweden.
    Bolam, Kate
    Karolinska Institutet, Stockholm, Sweden.
    Wengström, Yvonne
    Karolinska Institutet, Stockholm, Sweden.
    Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: Trial protocol of the randomized Neo-ACT trial.2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 10, p. e0274804-, article id e0274804Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: In early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT.

    METHOD: The Neo-ACT trial is a prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR; secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes at least 150 min of moderate to vigorous physical activity per week, inclusive of two weekly 60-min exercise sessions. In order to show an improvement in pCR of 10%, a total of 712 participants need to be included in the analysis. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582).

    EXPECTED RESULTS: If Neo-ACT can prove the oncological efficacy of physical exercise, implementation of training programmes into NACT schedules will be pursued. The use of a digitally led exercise intervention aims to test the potential of such a strategy for use in rural areas and areas of limited resources.

  • 9.
    Devin, James L.
    et al.
    Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    Jenkins, David G.
    Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    Sax, Andrew T.
    Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    Hughes, Gareth I.
    Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    Aitken, Joanne F.
    Canc Council Queensland, Canc Res Ctr, Brisbane, Qld, Australia.;Griffith Univ, Menzies Hlth Inst Queensland, Gold Coast, Qld, Australia..
    Chambers, Suzanne K.
    Canc Council Queensland, Canc Res Ctr, Brisbane, Qld, Australia.;Griffith Univ, Menzies Hlth Inst Queensland, Gold Coast, Qld, Australia.;Prostate Canc Fdn Australia, Sydney, NSW, Australia.;Edith Cowan Univ, Hlth & Wellness Inst, Perth, WA, Australia.;Univ Queensland, Clin Res Ctr, Brisbane, Qld, Australia..
    Dunn, Jeffrey C.
    Canc Council Queensland, Canc Res Ctr, Brisbane, Qld, Australia.;Griffith Univ, Menzies Hlth Inst Queensland, Gold Coast, Qld, Australia.;Univ Queensland, Sch Social Sci, Brisbane, Qld, Australia..
    Bolam, Kate A.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology. Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    Skinner, Tina L.
    Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia..
    THE INFLUENCE OF EXERCISE INTENSITY AND FREQUENCY ON CARDIORESPIRATORY FITNESS AND BODY COMPOSITION IN COLORECTAL CANCER SURVIVORS: A RANDOMIZED CONTROLLED TRIAL2016In: Asia-Pacific Journal of Clinical Oncology, ISSN 1743-7563, E-ISSN 1743-7563, Vol. 12, no S5, p. 109-109, article id 191Article in journal (Other academic)
  • 10. Devin, James L
    et al.
    Jenkins, David G
    Sax, Andrew T
    Hughes, Gareth I
    Aitken, Joanne F
    Chambers, Suzanne K
    Dunn, Jeffrey C
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Skinner, Tina L
    Cardiorespiratory Fitness and Body Composition Responses to Different Intensities and Frequencies of Exercise Training in Colorectal Cancer Survivors.2018In: Clinical colorectal cancer, ISSN 1938-0674, Vol. 17, no 2, p. e269-e279, article id S1533-0028(17)30268-2Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Deteriorations in cardiorespiratory fitness (V˙o2peak) and body composition are associated with poor prognosis after colorectal cancer treatment. However, the optimal intensity and frequency of aerobic exercise training to improve these outcomes in colorectal cancer survivors is unknown.

    PATIENTS AND METHODS: This trial compared 8 weeks of moderate-intensity continuous exercise (MICE; 50 minutes; 70% peak heart rate [HRpeak]; 24 sessions), with high-intensity interval exercise (HIIE; 4 × 4 minutes; 85%-95% HRpeak) at an equivalent (HIIE; 24 sessions) and tapered frequency (HIIE-T; 16 sessions) on V˙o2peak and on lean and fat mass, measured at baseline, 4, 8, and 12 weeks.

    RESULTS: Increases in V˙o2peak were significantly greater after both 4 (+3.0 mL·kg-1·min-1, P = .008) and 8 (+2.3 mL·kg-1·min-1, P = .049) weeks of HIIE compared to MICE. After 8 weeks, there was a significantly greater reduction in fat mass after HIIE compared to MICE (-0.7 kg, P = .038). Four weeks after training, the HIIE group maintained elevated V˙o2peak (+3.3 mL·kg-1·min-1, P = .006) and reduced fat mass (-0.7 kg, P = .045) compared to the MICE group, with V˙o2peak in the HIIE-T also being superior to the MICE group (+2.8 mL·kg-1·min-1, P = .013).

    CONCLUSION: Compared to MICE, HIIE promotes superior improvements and short-term maintenance of V˙o2peak and fat mass improvements. HIIE training at a reduced frequency also promotes maintainable cardiorespiratory fitness improvements. In addition to promoting accelerated and superior benefits to the current aerobic exercise guidelines, HIIE promotes clinically relevant improvements even with a substantial reduction in exercise training and for a period after withdrawal.

  • 11. Devin, James L
    et al.
    Sax, Andrew T
    Hughes, Gareth I
    Jenkins, David G
    Aitken, Joanne F
    Chambers, Suzanne K
    Dunn, Jeffrey C
    Bolam, Kate A
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Skinner, Tina L
    The influence of high-intensity compared with moderate-intensity exercise training on cardiorespiratory fitness and body composition in colorectal cancer survivors: a randomised controlled trial.2016In: Journal of cancer survivorship, ISSN 1932-2259, E-ISSN 1932-2267, Vol. 10, no 3, p. 467-479Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Following colorectal cancer diagnosis and anti-cancer therapy, declines in cardiorespiratory fitness and body composition lead to significant increases in morbidity and mortality. There is increasing interest within the field of exercise oncology surrounding potential strategies to remediate these adverse outcomes. This study compared 4 weeks of moderate-intensity exercise (MIE) and high-intensity exercise (HIE) training on peak oxygen consumption (V̇O2peak) and body composition in colorectal cancer survivors.

    METHODS: Forty seven post-treatment colorectal cancer survivors (HIE = 27 months post-treatment; MIE = 38 months post-treatment) were randomised to either HIE [85-95 % peak heart rate (HRpeak)] or MIE (70 % HRpeak) in equivalence with current physical activity guidelines and completed 12 training sessions over 4 weeks.

    RESULTS: HIE was superior to MIE in improving absolute (p = 0.016) and relative (p = 0.021) V̇O2peak. Absolute (+0.28 L.min(-1), p < 0.001) and relative (+3.5 ml.kg(-1).min(-1), p < 0.001) V̇O2 peak were increased in the HIE group but not the MIE group following training. HIE led to significant increases in lean mass (+0.72 kg, p = 0.002) and decreases in fat mass (-0.74 kg, p < 0.001) and fat percentage (-1.0 %, p < 0.001), whereas no changes were observed for the MIE group. There were no severe adverse events.

    CONCLUSIONS: In response to short-term training, HIE is a safe, feasible and efficacious intervention that offers clinically meaningful improvements in cardiorespiratory fitness and body composition for colorectal cancer survivors.

    IMPLICATIONS FOR CANCER SURVIVORS: HIE appears to offer superior improvements in cardiorespiratory fitness and body composition in comparison to current physical activity recommendations for colorectal cancer survivors and therefore may be an effective clinical utility following treatment.

  • 12.
    Ekblom Bak, Elin
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health.
    Bojsen-Møller, Emil
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health.
    Wallin, Peter
    Research Department, HPI Health Profile Institute, Stockholm, Sweden.
    Paulsson, Sofia
    Research Department, HPI Health Profile Institute, Stockholm, Sweden.
    Lindwall, Magnus
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health. Department of Psychology, University of Gothenburg, Stockholm, Sweden.
    Rundqvist, Helene
    Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bolam, Kate
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden..
    Association Between Cardiorespiratory Fitness and Cancer Incidence and Cancer-Specific Mortality of Colon, Lung, and Prostate Cancer Among Swedish Men.2023In: JAMA Network Open, E-ISSN 2574-3805, Vol. 6, no 6, article id e2321102Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Cardiorespiratory fitness (CRF) levels appear to be an important risk factor for cancer incidence and death.

    OBJECTIVES: To examine CRF and prostate, colon, and lung cancer incidence and mortality in Swedish men, and to assess whether age moderated any associations between CRF and cancer.

    DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted in a population of men who completed an occupational health profile assessment between October 1982 and December 2019 in Sweden. Data analysis was performed from June 22, 2022, to May 11, 2023.

    EXPOSURE: Cardiorespiratory fitness was assessed as maximal oxygen consumption, estimated using a submaximal cycle ergometer test.

    MAIN OUTCOMES AND MEASURES: Data on prostate, colon, and lung cancer incidence and mortality were derived from national registers. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression.

    RESULTS: Data on 177 709 men (age range, 18-75 years; mean [SD] age, 42 [11] years; mean [SD] body mass index, 26 [3.8]) were analyzed. During a mean (SD) follow-up time of 9.6 (5.5) years, a total of 499 incident cases of colon, 283 of lung, and 1918 of prostate cancer occurred, as well as 152 deaths due to colon cancer, 207 due to lung cancer, and 141 deaths due to prostate cancer. Higher levels of CRF (maximal oxygen consumption as milliliters per minute per kilogram) were associated with a significantly lower risk of colon (HR, 0.98, 95% CI, 0.96-0.98) and lung cancer (HR, 0.98; 95% CI, 0.96-0.99) incidence, and a higher risk of prostate cancer incidence (HR, 1.01; 95% CI, 1.00-1.01). Higher CRF was associated with a lower risk of death due to colon (HR, 0.98; 95% CI, 0.96-1.00), lung (HR, 0.97; 95% CI, 0.95-0.99), and prostate (HR, 0.95; 95% CI, 0.93-0.97) cancer. After stratification into 4 groups and in fully adjusted models, the associations remained for moderate (>35-45 mL/min/kg), 0.72 (0.53-0.96) and high (>45 mL/min/kg), 0.63 (0.41-0.98) levels of CRF, compared with very low (<25 mL/min/kg) CRF for colon cancer incidence. For prostate cancer mortality, associations remained for low (HR, 0.67; 95% CI, 0.45-1.00), moderate (HR, 0.57; 95% CI, 0.34-0.97), and high (HR, 0.29; 95% CI, 0.10-0.86) CRF. For lung cancer mortality, only high CRF (HR, 0.41; 95% CI, 0.17-0.99) was significant. Age modified the associations for lung (HR, 0.99; 95% CI, 0.99-0.99) and prostate (HR, 1.00; 95% CI, 1.00-1.00; P < .001) cancer incidence, and for death due to lung cancer (HR, 0.99; 95% CI, 0.99-0.99; P = .04).

    CONCLUSIONS AND RELEVANCE: In this cohort of Swedish men, moderate and high CRF were associated with a lower risk of colon cancer. Low, moderate, and high CRF were associated with lower risk of death due to prostate cancer, while only high CRF was associated with lower risk of death due to lung cancer. If evidence for causality is established, interventions to improve CRF in individuals with low CRF should be prioritized.

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  • 13. Hiensch, Anouk E
    et al.
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Mijwel, Sara
    Jeneson, Jeroen A L
    Huitema, Alwin D R
    Kranenburg, Onno
    van der Wall, Elsken
    Rundqvist, Helene
    Wengstrom, Yvönne
    May, Anne M
    Doxorubicin-induced skeletal muscle atrophy: Elucidating the underlying molecular pathways.2020In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 229, no 2, article id e13400Article in journal (Refereed)
    Abstract [en]

    AIM: Loss of skeletal muscle mass is a common clinical finding in cancer patients. The purpose of this meta-analysis and systematic review was to quantify the effect of doxorubicin on skeletal muscle and report on the proposed molecular pathways possibly leading to doxorubicin-induced muscle atrophy in both human and animal models.

    METHODS: A systematic search of the literature was conducted in PubMed, EMBASE, Web of Science and CENTRAL databases. The internal validity of included studies was assessed using SYRCLE's risk of bias tool.

    RESULTS: Twenty eligible articles were identified. No human studies were identified as being eligible for inclusion. Doxorubicin significantly reduced skeletal muscle weight (ie EDL, TA, gastrocnemius and soleus) by 14% (95% CI: 9.9; 19.3) and muscle fibre cross-sectional area by 17% (95% CI: 9.0; 26.0) when compared to vehicle controls. Parallel to negative changes in muscle mass, muscle strength was even more decreased in response to doxorubicin administration. This review suggests that mitochondrial dysfunction plays a central role in doxorubicin-induced skeletal muscle atrophy. The increased production of ROS plays a key role within this process. Furthermore, doxorubicin activated all major proteolytic systems (ie calpains, the ubiquitin-proteasome pathway and autophagy) in the skeletal muscle. Although each of these proteolytic pathways contributes to doxorubicin-induced muscle atrophy, the activation of the ubiquitin-proteasome pathway is hypothesized to play a key role. Finally, a limited number of studies found that doxorubicin decreases protein synthesis by a disruption in the insulin signalling pathway.

    CONCLUSION: The results of the meta-analysis show that doxorubicin induces skeletal muscle atrophy in preclinical models. This effect may be explained by various interacting molecular pathways. Results from preclinical studies provide a robust setting to investigate a possible dose-response, separate the effects of doxorubicin from tumour-induced atrophy and to examine underlying molecular pathways. More research is needed to confirm the proposed signalling pathways in humans, paving the way for potential therapeutic approaches.

  • 14. Hiensch, Anouk E
    et al.
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Mijwel, Sara
    May, Anne M
    Wengström, Yvonne
    Sense of coherence and its relationship to participation, cancer-related fatigue, symptom burden, and quality of life in women with breast cancer participating in the OptiTrain exercise trial.2020In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 28, no 11, p. 5371-5379Article in journal (Refereed)
    Abstract [en]

    PURPOSE: This study examined the Sense of Coherence (SOC) of patients participating in the randomized controlled 'Optimal Training for Women with Breast Cancer' (OptiTrain) study and assessed how patient characteristics were associated with SOC. Secondary aims were to assess the association between SOC and patients' participation in this study and to determine whether SOC moderates the effect of the 16-week exercise intervention on fatigue, quality of life (QoL), and symptom burden in women with breast cancer undergoing chemotherapy.

    METHODS: Modified Poisson regression analyses were conducted to determine the relative risk of weak-normal SOC versus strong SOC in terms of exercise session attendance, study and intervention dropout, and long absence rates. Analyses of covariance were performed to assess whether SOC moderated the effect of the exercise intervention (pinteraction ≤ 0.10).

    RESULTS: Two hundred and forty women with early breast cancer (mean age 53 ± 10) participated in the OptiTrain study. Women with strong SOC reported less fatigue, lower symptom burden, and higher QoL. Women with weak-normal SOC were significantly more likely to drop out from the OptiTrain study and tended to have slightly poorer exercise session attendance. Women with breast cancer and weaker SOC benefitted as much from the exercise intervention, in terms of fatigue and QoL, as those with stronger SOC (pinteraction > 0.10).

    CONCLUSIONS: Strong SOC appears to be associated with a more positive subjective state of health. Women with weak-normal SOC may need additional support to encourage participation and adherence in exercise trials. Assessing SOC may assist clinicians to identify and provide extra support for participants with weak SOC, who may be less inclined to participate in exercise programs.

  • 15. Hiensch, Anouk E
    et al.
    Monninkhof, Evelyn M
    Schmidt, Martina E
    Zopf, Eva M
    Bolam, Kate
    Karolinska institutet, Stockholm, Sweden.
    Aaronson, Neil K
    Belloso, Jon
    Bloch, Wilhelm
    Clauss, Dorothea
    Depenbusch, Johanna
    Lachowicz, Milena
    Pelaez, Mireia
    Rundqvist, Helene
    Senkus, Elzbieta
    Stuiver, Martijn M
    Trevaskis, Mark
    Urruticoechea, Ander
    Rosenberger, Friederike
    van der Wall, Elsken
    de Wit, G Ardine
    Zimmer, Philipp
    Wengström, Yvonne
    Steindorf, Karen
    May, Anne M
    Design of a multinational randomized controlled trial to assess the effects of structured and individualized exercise in patients with metastatic breast cancer on fatigue and quality of life: the EFFECT study.2022In: Trials, E-ISSN 1745-6215, Vol. 23, no 1, p. 610-, article id 610Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Many patients with metastatic breast cancer experience cancer- and treatment-related side effects that impair activities of daily living and negatively affect the quality of life. There is a need for interventions that improve quality of life by alleviating fatigue and other side effects during palliative cancer treatment. Beneficial effects of exercise have been observed in the curative setting, but, to date, comparable evidence in patients with metastatic breast cancer is lacking. The aim of this study is to assess the effects of a structured and individualized 9-month exercise intervention in patients with metastatic breast cancer on quality of life, fatigue, and other cancer- and treatment-related side effects.

    METHODS: The EFFECT study is a multinational, randomized controlled trial including 350 patients with metastatic breast cancer. Participants are randomly allocated (1:1) to an exercise or control group. The exercise group participates in a 9-month multimodal exercise program, starting with a 6-month period where participants exercise twice a week under the supervision of an exercise professional. After completing this 6-month period, one supervised session is replaced by one unsupervised session for 3 months. In addition, participants are instructed to be physically active for ≥30 min/day on all remaining days of the week, while being supported by an activity tracker and exercise app. Participants allocated to the control group receive standard medical care, general written physical activity advice, and an activity tracker, but no structured exercise program. The primary outcomes are quality of life (EORTC QLQ-C30, summary score) and fatigue (EORTC QLQ-FA12), assessed at baseline, 3, 6 (primary endpoint), and 9 months post-baseline. Secondary outcomes include physical fitness, physical performance, physical activity, anxiety, depression, pain, sleep problems, anthropometric data, body composition, and blood markers. Exploratory outcomes include quality of working life, muscle thickness, urinary incontinence, disease progression, and survival. Additionally, the cost-effectiveness of the exercise program is assessed. Adherence and safety are monitored throughout the intervention period.

    DISCUSSION: This large randomized controlled trial will provide evidence regarding the (cost-) effectiveness of exercise during treatment of metastatic breast cancer. If proven (cost-)effective, exercise should be offered to patients with metastatic breast cancer as part of standard care.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT04120298 . Registered on October 9, 2019.

  • 16.
    Khan, Yusuf
    et al.
    Inland Norway University of Applied Sciences, Hamar, Norway.
    Hammarström, Daniel
    Swedish School of Sport and Health Sciences, GIH. Inland Norway University of Applied Sciences, Lillehammer, Norway.
    Rønnestad, Bent R
    Inland Norway University of Applied Sciences, Lillehammer, Norway.
    Ellefsen, Stian
    Inland Norway University of Applied Sciences, Lillehammer, Norway.
    Ahmad, Rafi
    Inland Norway University of Applied Sciences, Hamar, Norway.
    Increased biological relevance of transcriptome analyses in human skeletal muscle using a model-specific pipeline.2020In: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 21, no 1, article id 548Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Human skeletal muscle responds to weight-bearing exercise with significant inter-individual differences. Investigation of transcriptome responses could improve our understanding of this variation. However, this requires bioinformatic pipelines to be established and evaluated in study-specific contexts. Skeletal muscle subjected to mechanical stress, such as through resistance training (RT), accumulates RNA due to increased ribosomal biogenesis. When a fixed amount of total-RNA is used for RNA-seq library preparations, mRNA counts are thus assessed in different amounts of tissue, potentially invalidating subsequent conclusions. The purpose of this study was to establish a bioinformatic pipeline specific for analysis of RNA-seq data from skeletal muscles, to explore the effects of different normalization strategies and to identify genes responding to RT in a volume-dependent manner (moderate vs. low volume). To this end, we analyzed RNA-seq data derived from a twelve-week RT intervention, wherein 25 participants performed both low- and moderate-volume leg RT, allocated to the two legs in a randomized manner. Bilateral muscle biopsies were sampled from m. vastus lateralis before and after the intervention, as well as before and after the fifth training session (Week 2).

    RESULT: Bioinformatic tools were selected based on read quality, observed gene counts, methodological variation between paired observations, and correlations between mRNA abundance and protein expression of myosin heavy chain family proteins. Different normalization strategies were compared to account for global changes in RNA to tissue ratio. After accounting for the amounts of muscle tissue used in library preparation, global mRNA expression increased by 43-53%. At Week 2, this was accompanied by dose-dependent increases for 21 genes in rested-state muscle, most of which were related to the extracellular matrix. In contrast, at Week 12, no readily explainable dose-dependencies were observed. Instead, traditional normalization and non-normalized models resulted in counterintuitive reverse dose-dependency for many genes. Overall, training led to robust transcriptome changes, with the number of differentially expressed genes ranging from 603 to 5110, varying with time point and normalization strategy.

    CONCLUSION: Optimized selection of bioinformatic tools increases the biological relevance of transcriptome analyses from resistance-trained skeletal muscle. Moreover, normalization procedures need to account for global changes in rRNA and mRNA abundance.

  • 17. Kiss, Nicole
    et al.
    Baguley, Brenton J
    Dalla Via, Jack
    Fraser, Steve F
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Daly, Robin M
    Exercise and Nutritional Approaches to Combat Cancer-Related Bone and Muscle Loss.2020In: Current osteoporosis reports, ISSN 1544-2241, Vol. 18, no 3, p. 291-300Article in journal (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW: The aim of this narrative review is to summarise recent literature on the effects of exercise and nutrition interventions alone or in combination on muscle and bone loss in people with cancer.

    RECENT FINDINGS: There is emerging evidence to support the inclusion of targeted exercise and nutrition strategies to counter loss of muscle and bone associated with cancer treatments. Although research in this field is advancing, the optimal exercise and nutrition prescription to combat cancer-related bone and muscle loss remain unknown. This review identifies specific components of nutrition and exercise interventions that are promising although require further exploration through studies designed to determine the effect on muscle and bone. A focused research effort is required to elucidate the full potential of exercise and nutrition intervention for people with cancer at risk of bone and muscle loss.

  • 18.
    Kotte, Melissa
    et al.
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Bolam, Kate
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Mijwel, Sara
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway.
    Altena, Renske
    Medical Unit Breast, Endocrine Tumors and Sarcoma, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden..
    Cormie, Prue
    Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.; EX-MED Cancer, Melbourne, VIC, Australia..
    Wengström, Yvonne
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.; Medical Unit Breast, Endocrine Tumors and Sarcoma, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden..
    Distance-based delivery of exercise for people treated for breast, prostate or colorectal cancer: a study protocol for a randomised controlled trial of EX-MED Cancer Sweden.2023In: Trials, E-ISSN 1745-6215, Vol. 24, no 1, p. 116-, article id 116Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Regular exercise has been shown to have beneficial health effects in cancer survivors, including improving quality of life and other important health outcomes. However, providing people with cancer with easily accessible, high-quality exercise support and programs is a challenge. Therefore, there is a need to develop easily accessible exercise programs that draw upon the current evidence. Supervised, distance-based exercise programs have the benefit of reaching out to many people whilst providing the support of an exercise professional. The aim of the EX-MED Cancer Sweden trial is to examine the effectiveness of a supervised, distance-based exercise program, in people previously treated for breast, prostate, or colorectal cancer, on health-related quality of life (HRQoL), as well as other physiological and patient-reported health outcomes.

    METHODS: The EX-MED Cancer Sweden trial is a prospective randomised controlled trial including 200 people that have completed curative treatment for breast, prostate, or colorectal cancer. Participants are randomly allocated to an exercise group or a routine care control group. The exercise group will participate in a supervised, distanced-based exercise program delivered by a personal trainer who has undertaken specialised exercise oncology education modules. The intervention consists of a combination of resistance and aerobic exercises with participants completing two 60-min sessions per week for 12 weeks. The primary outcome is HRQoL (EORTC QLQ-C30) assessed at baseline, 3- (end of intervention and primary endpoint) and 6-months post-baseline. Secondary outcomes are physiological (cardiorespiratory fitness, muscle strength, physical function, body composition) and patient-reported outcomes (cancer-related symptoms, fatigue, self-reported physical activity), and self-efficacy of exercise. Furthermore, the trial will explore and describe the experiences of participation in the exercise intervention.

    DISCUSSION: The EX-MED Cancer Sweden trial will provide evidence regarding the effectiveness of a supervised, distance-based exercise program for survivors of breast, prostate, and colorectal cancer. If successful, it will contribute to the implementation of flexible and effective exercise programs as part of the standard of care for people following cancer treatment, which is likely to contribute to a reduction in the burden of cancer on the individual, health care system and society.

    CLINICALTRIALS: gov NCT05064670. Registered on October 1, 2021.

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  • 19.
    Maturi, Naga Prathyusha
    et al.
    Uppsala universitet, Neuroonkologi.
    Tan, E-Jean
    Uppsala universitet, Människans evolution.
    Xie, Yuan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sundström, Anders
    Uppsala universitet, Neuroonkologi.
    Bergström, Tobias
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jiang, Yiwen
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Uhrbom, Lene
    Uppsala universitet, Neuroonkologi.
    A molecularly distinct subset of glioblastoma requires serum-containing media to establish sustainable bona fide glioblastoma stem cell cultures2020In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 68, no 6, p. 1228-1240Article in journal (Refereed)
    Abstract [en]

    Glioblastoma (GBM) is the most frequent and deadly primary malignant brain tumor. Hallmarks are extensive intra-tumor and inter-tumor heterogeneity and highly invasive growth, which provide great challenges for treatment. Efficient therapy is lacking and the majority of patients survive less than 1 year from diagnosis. GBM progression and recurrence is caused by treatment-resistant glioblastoma stem cells (GSCs). GSC cultures are considered important models in target identification and drug screening studies. The current state-of-the-art method, to isolate and maintain GSC cultures that faithfully mimic the primary tumor, is to use serum-free (SF) media conditions developed for neural stem cells (NSCs). Here we have investigated the outcome of explanting 218 consecutively collected GBM patient samples under both SF and standard, serum-containing media conditions. The frequency of maintainable SF cultures (SFCs) was most successful, but for a subgroup of GBM specimens, a viable culture could only be established in serum-containing media, called exclusive serum culture (ESC). ESCs expressed nestin and SOX2, and displayed all functional characteristics of a GSC, that is, extended proliferation, sustained self-renewal and orthotopic tumor initiation. Once adapted to the in vitro milieu they were also sustainable in SF media. Molecular analyses showed that ESCs formed a discrete group that was most related to the mesenchymal GBM subtype. This distinct subgroup of GBM that would have evaded modeling in SF conditions only provide unique cell models of GBM inter-tumor heterogeneity.

  • 20.
    Mijwel, S.
    et al.
    Karolinska Institutet.
    Cardinale, Daniele A.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Ekblom Bak, Elin
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Sundberg, C. J.
    Karolinska Institutet.
    Wengstrom, Y.
    Karolinska Institutet.
    Rundqvist, H.
    Karolinska Institutet.
    Validation of two submaximal exercise tests in breast cancer patients undergoing chemotherapy treatment2015In: European Journal of Cancer (ISSN 0959-8049), 2015, Vol. 51, p. S300-S301Conference paper (Other academic)
  • 21. Mijwel, Sara
    et al.
    Backman, Malin
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Jervaeus, Anna
    Sundberg, Carl Johan
    Margolin, Sara
    Browall, Maria
    Rundqvist, Helene
    Wengström, Yvonne
    Adding high-intensity interval training to conventional training modalities: optimizing health-related outcomes during chemotherapy for breast cancer2018In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 168, no 1, p. 79-93Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Exercise training is an effective and safe way 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.

    METHODS: Two 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 16 weeks. Questionnaires included Piper Fatigue Scale, EORTC-QLQ-C30, and Memorial Symptom Assessment Scale.

    RESULTS: The RT-HIIT group was superior to UC for CRF: total CRF (p = 0.02), behavior/daily life (p = 0.01), and sensory/physical (p = 0.03) CRF. Role functioning significantly improved while cognitive functioning was unchanged for RT-HIIT compared to declines shown in the UC group (p = 0.04). AT-HIIT significantly improved emotional functioning versus UC (p = 0.01) and was superior to UC for pain symptoms (p = 0.03). RT-HIIT reported a reduced symptom burden, while AT-HIIT remained stable compared to deteriorations shown by UC (p < 0.01). Only RT-HIIT was superior to UC for total symptoms (p < 0.01).

    CONCLUSIONS: 16 weeks 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 REGISTRATION: Clinicaltrials.gov Registration Number: NCT02522260.

  • 22. Mijwel, Sara
    et al.
    Backman, Malin
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Olofsson, Emil
    Norrbom, Jessica
    Bergh, Jonas
    Sundberg, Carl Johan
    Wengström, Yvonne
    Rundqvist, Helene
    Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial.2018In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 169, no 1, p. 93-103Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Advanced 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.

    METHODS: Two hundred and forty women were randomized to 16 weeks of RT-HIIT, AT-HIIT, or UC.

    OUTCOMES: cardiorespiratory fitness, muscle strength, body mass, hemoglobin levels, and pressure-pain threshold.

    RESULTS: Pre- to post-intervention, RT-HIIT (ES = 0.41) and AT-HIIT (ES = 0.42) prevented the reduced cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT vs. UC: ES = 0.41, RT-HIIT vs. AT-HIIT: ES = 0.28; non-surgery side: RT-HIIT vs. UC: ES = 0.35, RT-HIIT vs. AT-HIIT: ES = 0.22) and lower-limb muscle strength (RT-HIIT vs. UC: ES = 0.66, RT-HIIT vs. AT-HIIT: ES = 0.23) were significantly improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ES = - 0.16) and AT-HIIT (ES = - 0.16) versus UC. RT-HIIT reported higher pressure-pain thresholds than UC (trapezius: ES = 0.46, gluteus: ES = 0.53) and AT-HIIT (trapezius: ES = 0.30).

    CONCLUSION: Sixteen weeks 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 in preventing 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.

  • 23. Mijwel, Sara
    et al.
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Gerrevall, Jacob
    Foukakis, Theodoros
    Wengström, Yvonne
    Rundqvist, Helene
    Effects of Exercise on Chemotherapy Completion and Hospitalization Rates: The OptiTrain Breast Cancer Trial.2020In: The Oncologist, ISSN 1083-7159, E-ISSN 1549-490X, Vol. 25, no 1, p. 23-32Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Exercise during chemotherapy is suggested to provide clinical benefits, including improved chemotherapy completion. Despite this, few randomized controlled exercise trials have reported on such clinical endpoints. From the OptiTrain trial we previously showed positive effects on physiological and health-related outcomes after 16 weeks of supervised exercise in patients with breast cancer undergoing chemotherapy. Here, we examined the effects of exercise on rates of chemotherapy completion and hospitalization, as well as on blood cell concentrations during chemotherapy.

    PATIENTS AND METHODS: Two hundred forty women scheduled for chemotherapy were randomized to 16 weeks of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). Outcomes included chemotherapy completion, hospitalization, hemoglobin, lymphocyte, thrombocyte, and neutrophil concentrations during chemotherapy.

    RESULTS: No significant between-groups differences were found in the proportion of participants who required dose reductions (RT-HIIT vs. UC: odds ratio [OR], 1.08; AT-HIIT vs. UC: OR, 1.39), or average relative dose intensity of chemotherapy between groups (RT-HIIT vs. UC: effect size [ES], 0.08; AT-HIIT vs. UC: ES, -0.07). A significantly lower proportion of participants in the RT-HIIT group (3%) were hospitalized during chemotherapy compared with UC (15%; OR, 0.20). A significantly lower incidence of thrombocytopenia was found for both RT-HIIT (11%) and AT-HIIT (10%) versus UC (30%; OR, 0.27; OR, 0.27).

    CONCLUSION: No beneficial effects of either RT-HIIT or AT-HIIT on chemotherapy completion rates were found. However, combined resistance training and high-intensity interval training were effective to reduce hospitalization rates, and both exercise groups had a positive effect on thrombocytopenia. These are important findings with potential positive implications for the health of women with breast cancer and costs associated with treatment-related complications.

    IMPLICATIONS FOR PRACTICE: Completing the prescribed chemotherapy regimen is strongly associated with a good prognosis for patients with primary breast cancer. Despite this, treatment-induced side effects make it necessary to reduce or alter the treatment regimen and can also lead to hospitalization. Exercise during chemotherapy is suggested to provide clinical benefits, including improved chemotherapy completion. This study showed that combined resistance and high-intensity interval training during chemotherapy resulted in lower hospitalization rates and a lower incidence of thrombocytopenia in women with breast cancer undergoing chemotherapy. However, no beneficial effects of either exercise program on chemotherapy completion rates were found, which is in contrast to previous findings in this population. The findings reported in the current article have positive implications for the health of women with breast cancer and costs associated with treatment-related complications.

  • 24. Mijwel, Sara
    et al.
    Cardinale, Daniele
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll.
    Ekblom-Bak, Elin
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Sundberg, Carl Johan
    Wengström, Yvonne
    Rundqvist, Helene
    Validation of 2 Submaximal Cardiorespiratory Fitness Tests in Patients With Breast Cancer Undergoing Chemotherapy.2016In: Rehabilitation oncology (American Physical Therapy Association. Oncology Section), ISSN 2168-3808, Vol. 34, no 4, p. 137-143Article in journal (Refereed)
    Abstract [en]

    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. Pearson's 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.

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  • 25. Mijwel, Sara
    et al.
    Jervaeus, Anna
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Norrbom, Jessica
    Bergh, Jonas
    Rundqvist, Helene
    Wengström, Yvonne
    High-intensity exercise during chemotherapy induces beneficial effects 12 months into breast cancer survivorship.2019In: Journal of cancer survivorship, ISSN 1932-2259, E-ISSN 1932-2267, Vol. 13, no 2, p. 244-256Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Whether the benefits of exercise during chemotherapy continue into survivorship is not well-known. Here, the aim was to examine the effects of two exercise interventions on self-reported health-related and objectively measured physiological outcomes 12 months following commencement of chemotherapy.

    METHODS: Two hundred and forty women with breast cancer stage I-IIIa were randomized to 16 weeks of high-intensity aerobic interval training combined with either resistance training (RT-HIIT), or moderate-intensity aerobic training (AT-HIIT), or to usual care (UC).

    PRIMARY OUTCOME: cancer-related fatigue (CRF); secondary outcomes: quality of life (QoL), symptom burden, muscle strength, cardiorespiratory-fitness, body mass, and return to work.

    RESULTS: Compared to UC, both RT-HIIT and AT-HIIT significantly counteracted increases in total CRF (ES = - 0.34; ES = - 0.10), daily life CRF (ES=-0.76; ES=-0.50, and affective CRF (ES=-0.60; ES=-0.39). Both RT-HIIT and AT-HIIT reported significantly lower total symptoms (ES = - 0.46, ES = - 0.46), and displayed gains in lower limb (ES = 0.73; ES = 1.03) and handgrip muscle strength (surgery side ES = 0.70, ES = 0.71; non-surgery side ES = 0.57, ES = 0.59). AT-HIIT displayed significant reductions in body mass (ES = - 0.24), improved QoL: role (ES = 0.33) and emotional functioning (ES = 0.40), and a larger proportion had returned to work (p = 0.02) vs UC.

    CONCLUSION: These findings emphasize the beneficial effects of supervised high-intensity exercise during chemotherapy to improve the health and to reduce societal costs associated with prolonged sick leave for patients with breast cancer several months following chemotherapy.

    IMPLICATIONS FOR CANCER SURVIVORS: These findings provide important information with substantial positive consequences for breast cancer survivorship. High-intensity exercise programs during chemotherapy and support to maintain physical activity can be a powerful strategy to manage or prevent many of the short- and long-term adverse effects of treatment for the increasing cohort of cancer survivors.

  • 26. Newton, Robert U
    et al.
    Galvão, Daniel A
    Spry, Nigel
    Joseph, David
    Chambers, Suzanne K
    Gardiner, Robert A
    Wall, Brad A
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Taaffe, Dennis R
    Exercise Mode Specificity for Preserving Spine and Hip Bone Mineral Density in Prostate Cancer Patients.2019In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 51, no 4, p. 607-614Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with an array of adverse effects, including reduced bone mineral density (BMD) predisposing patients to increased fracture risk. Our purpose was to examine the effects of targeted exercise modes on BMD in men with PCa undergoing ADT.

    METHODS: Between 2009 and 2012, 154 PCa patients 43-90 yr old on ADT were randomized to exercise targeting the musculoskeletal system (impact loading + resistance training [ImpRes], n = 57) supervised for 12 months, cardiovascular and muscular systems (aerobic + resistance training, n = 50) supervised for 6 months followed by a 6-month home-based program, or delayed aerobic exercise (DelAer, n = 47) received exercise information for 6 months followed by 6 months of supervised aerobic exercise (stationary cycling). End points were lumbar spine, hip and whole-body BMD measured by dual-energy x-ray absorptiometry with secondary end points of lean and fat mass, appendicular skeletal muscle mass, and neuromuscular strength. ANOVA was used to compare the exercise groups with DelAer at 6 and 12 months.

    RESULTS: There was a between-group difference in BMD for ImpRes and DelAer at the spine (6 months, P = 0.039; 12 months, P = 0.035) and femoral neck (6 months, P = 0.050), with decline attenuated in ImpRes (~-1.0% vs ~-2.0%). Compared with DelAer, ImpRes increased appendicular skeletal muscle at 6 months (0.3 kg, P = 0.045) and improved muscle strength at 6 and 12 months (P ≤ 0.012) by 9%-34%. A limitation was inclusion of well-functioning patients.

    CONCLUSION: Combined impact loading and resistance exercise attenuates bone loss at the spine and enhances overall musculoskeletal function in PCa patients undergoing ADT.

  • 27. Nilsson, Hanna
    et al.
    Angerås, Ulf
    Bock, David
    Börjesson, Mats
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's and Mats Börjesson's research group.
    Onerup, Aron
    Fagevik Olsen, Monika
    Gellerstedt, Martin
    Haglind, Eva
    Angenete, Eva
    Is preoperative physical activity related to post-surgery recovery? A cohort study of patients with breast cancer.2016In: BMJ Open, E-ISSN 2044-6055, Vol. 6, no 1, article id e007997Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of our study is to assess the association between preoperative level of activity and recovery after breast cancer surgery measured as hospital stay, length of sick leave and self-assessed physical and mental recovery.

    DESIGN: A prospective cohort study.

    SETTING: Patients included were those scheduled to undergo breast cancer surgery, between February and November 2013, at two participating hospitals in the Western Region of Sweden.

    PARTICIPANTS: Patients planned for breast cancer surgery filled out a questionnaire before, as well as at 3 and 6 weeks after the operation. The preoperative level of activity was self-assessed and categorised into four categories by the participants using the 4-level Saltin-Grimby Physical Activity Level Scale (SGPALS).

    MAIN OUTCOME MEASURE: Our main outcome was postoperative recovery measured as length of sick leave, in-hospital stay and self-assessed physical and mental recovery.

    RESULTS: 220 patients were included. Preoperatively, 14% (31/220) of participants assessed themselves to be physically inactive, 61% (135/220) to exert some light physical activity (PA) and 20% (43/220) to be more active (level 3+4). Patients operated with mastectomy versus partial mastectomy and axillary lymph node dissection versus sentinel node biopsy were less likely to have a short hospital stay, relative risk (RR) 0.88 (0.78 to 1.00) and 0.82 (0.70 to 0.96). More active participants (level 3 or 4) had an 85% increased chance of feeling physically recovered at 3 weeks after the operation, RR 1.85 (1.20 to 2.85). No difference was seen after 6 weeks.

    CONCLUSIONS: The above study shows that a higher preoperative level of PA is associated with a faster physical recovery as reported by the patients 3 weeks post breast cancer surgery. After 6 weeks, most patients felt physically recovered, diminishing the association above. No difference was seen in length of sick leave or self-assessed mental recovery between inactive or more active patients.

  • 28.
    Onerup, Aron
    et al.
    Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden..
    Mehlig, Kirsten
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Af Geijerstam, Agnes
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Ekblom Bak, Elin
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health.
    Kuhn, Hans-Georg
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Institute of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany..
    Lissner, Lauren
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Rosengren, Annika
    Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Sahlgrenska University Hospital/Östra, Region Västra Götaland, Gothenburg, Sweden..
    Börjesson, Mats
    Department of Molecular and Clinical Medicine, Center for Lifestyle Intervention, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden..
    Åberg, Maria
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Gothenburg, Sweden..
    Associations between BMI in youth and site-specific cancer in men: A cohort study with register linkage.2024In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 32, no 2, p. 376-389Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study examined BMI in young men and incident site-specific cancer to estimate population attributable fractions due to BMI based on projected obesity prevalence.

    METHODS: A population-based cohort study with measured height and weight at age 18. Cox regression models assessed linear associations for BMI and included age, year, and site of conscription as well as parental level of education as covariates.

    RESULTS: Primary analyses were performed in 1,489,115 men, of whom 78,217 subsequently developed cancer during a mean follow-up of 31 years. BMI was linearly associated with risk of developing all 18 site-specific cancers assessed (malignant melanoma; leukemia; myeloma; Hodgkin lymphoma; non-Hodgkin lymphoma; and cancer in the lungs, head and neck, central nervous system, thyroid, esophagus, stomach, pancreas, liver and gallbladder, colon, rectum, kidney, and bladder), in some instances evident at BMI levels usually defined as normal (20-25 kg/m2 ). Higher BMI was associated with lower risk of prostate cancer. The highest hazard ratios and population attributable fractions were seen for some gastrointestinal cancers.

    CONCLUSIONS: This study reports linear associations between BMI at age 18 and subsequent site-specific cancers, calling for rapid action to stem the obesity epidemic and to prepare the health care system for steep increases in cancer cases.

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  • 29.
    Onerup, Aron
    et al.
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Pediatric Oncology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Mehlig, Kirsten
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Ekblom Bak, Elin
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health.
    Lissner, Lauren
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Börjesson, Mats
    Department of Molecular and Clinical Medicine, Center for Lifestyle Intervention, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.; Department of MGAÖ, Region of Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden..
    Åberg, Maria
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Regionhälsan, Gothenburg, Sweden..
    Cardiorespiratory fitness and BMI measured in youth and 5-year mortality after site-specific cancer diagnoses in men: A population-based cohort study with register linkage.2023In: Cancer Medicine, E-ISSN 2045-7634, Vol. 12, no 19, p. 20000-20014Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Our aim was to assess associations between cardiorespiratory fitness (CRF) and body mass index (BMI) in youth and 5-year mortality after site-specific cancer diagnoses in men.

    METHODS: Men with cancer from a population who underwent military conscription at ages 16-25 during 1968-2005 in Sweden were included. CRF was assessed as maximal aerobic workload on a cycle ergometer test and was classified as low, moderate, or high. BMI (kg/m2 ) was classified as underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), or obesity (>30). Conscription data were linked with register data on cancer diagnosis and mortality. Analyses included CRF, BMI, date of diagnosis, and age, year, and center for conscription.

    RESULTS: A total of 84,621 cancer cases were included. Mean age at diagnosis was 52 years. Follow-up data were available during a mean of 6.5 years. There were linear protective associations between CRF and mortality after any cancer diagnosis (hazard ratio [HR] for high vs. low CRF 0.70), malignant skin cancer (HR 0.80), non-Hodgkin lymphoma (HR 0.78), and cancer in the lungs (HR 0.80), head and neck (HR 0.68), pancreas (HR 0.83), stomach (HR 0.78), liver (HR 0.84), rectum (HR 0.79), and bladder (HR 0.71). Overweight and/or obesity were associated with increased mortality after any cancer (HR for obesity vs. normal weight 1.89), malignant skin cancer (HR 2.03), Hodgkin lymphoma (HR 2.86) and cancer in the head and neck (HR 1.38), thyroid (HR 3.04), rectum (HR 1.53), kidney (HR 1.90), bladder (HR 2.10), and prostate (HR 2.44).

    CONCLUSION: We report dose-dependent associations between CRF and BMI in youth and mortality after site-specific cancer diagnoses in men. The associations with mortality could be due to both cancer inhibition and an improved tolerance to withstand cancer treatment. These results strengthen the incentive for public health efforts aimed at establishing a high CRF and normal weight in youth.

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  • 30.
    Onerup, Aron
    et al.
    Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
    Mehlig, Kirsten
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Geijerstam, Agnes Af
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Ekblom Bak, Elin
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health.
    Kuhn, Hans Georg
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
    Lissner, Lauren
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Åberg, Maria
    School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Börjesson, Mats
    Department of Molecular and Clinical Medicine, Center for Health and Performance, University of Gothenburg, Gothenburg, Sweden..
    Associations between cardiorespiratory fitness in youth and the incidence of site-specific cancer in men: a cohort study with register linkage.2023In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 57, p. 1248-1256Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To assess the associations between cardiorespiratory fitness (CRF) in young men and the incidence of site-specific cancer.

    METHODS: A Swedish population-based cohort study with register linkage of men who underwent military conscription in 1968-2005 was undertaken. CRF was assessed by maximal aerobic workload cycle test at conscription. Cox regression models assessed linear associations and included CRF, age, year and site of conscription, body mass index and parental level of education. CRF was also categorised into low, moderate and high for facilitated interpretation and results comparing high and low CRF are reported.

    RESULTS: Primary analyses were performed in 1 078 000 men, of whom 84 117 subsequently developed cancer in at least one site during a mean follow-up of 33 years. Higher CRF was linearly associated with a lower hazard ratio (HR) of developing cancer in the head and neck (n=2738, HR 0.81, 95% CI 0.74 to 0.90), oesophagus (n=689, HR 0.61, 95% CI 0.50 to 0.74), stomach (n=902, HR 0.79, 95% CI 0.67 to 0.94), pancreas (n=1280, HR 0.88, 95% CI 0.76 to 1.01), liver (n=1111, HR 0.60, 95% CI 0.51 to 0.71), colon (n=3222, HR 0.82, 95% CI 0.75 to 0.90), rectum (n=2337, HR 0.95, 95% CI 0.85 to 1.05), kidney (n=1753, HR 0.80, 95% CI 0.70 to 0.90) and lung (n=1635, HR 0.58, 95% CI 0.51 to 0.66). However, higher CRF predicted a higher hazard of being diagnosed with prostate cancer (n=14 232, HR 1.07, 95% CI 1.03 to 1.12) and malignant skin cancer (n=23 064, HR 1.31, 95% CI 1.27 to 1.36).

    CONCLUSION: We report a number of protective associations between higher CRF in healthy young men and the subsequent hazard of site-specific cancers. These results have implications for public health policymaking, strengthening the incentive to promote health through improving CRF in youth.

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  • 31. Rose, Grace L
    et al.
    Skinner, Tina L
    Keating, Shelley E
    Friedrich, Nina K
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    The effects of exercise on the bone health of people with cancer: a systematic review and meta-analysis.2022In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 33, no 2, p. 327-338Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To determine the pooled effect of exercise on the bone health of people diagnosed with cancer.

    METHODS: Four electronic databases were systematically searched. Controlled trials that assessed the effect of exercise on the bone mineral density (BMD) or content (BMC) measured by dual-energy x-ray absorptiometry or peripheral quantitative computed tomography in people who had been diagnosed with cancer were included in the study. Random-effect meta-analyses of effect size (ES) were conducted. Sub-group analyses were performed to explore the influence of intervention duration, prescription and participant characteristics.

    RESULTS: Of 66 full-text articles screened, 22 studies, from 21 interventions, were included (primarily breast/prostate cancer, sample range n = 36-498). When all interventions were grouped, a significant pooled ES was observed for exercise on hip (ES = 0.112, 95% CI: 0.026 to 0.198; p = 0.011) and lumbar spine BMD (ES = 0.269, 95% CI: 0.036 to 0.501; p = 0.024) compared to control. There was also an influence of sex, where females had greater improvements in hip (ES = 0.120, 95% CI: 0.017 to 0.223; p = 0.022) and spine BMD (ES = 0.415, 95% CI: 0.056 to 0.774; p = 0.23) compared to males.

    CONCLUSION: Overall, exercise regimens of studies included in this review appear to improve bone health at the hip and spine in people diagnosed with cancer. Sub-analyses suggest some influence of sex, where females had greater improvements in BMD compared to males. It is essential that future studies evaluate the dose-response of exercise training on bone health and create exercise protocols that better align with the laws of bone modelling to enhance osteogenic potential.

  • 32. Taaffe, Dennis R
    et al.
    Newton, Robert U
    Spry, Nigel
    Joseph, David
    Chambers, Suzanne K
    Gardiner, Robert A
    Wall, Brad A
    Cormie, Prue
    Bolam, Kate A
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Galvão, Daniel A
    Effects of Different Exercise Modalities on Fatigue in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Year-long Randomised Controlled Trial.2017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, no 2, p. 293-299, article id S0302-2838(17)30108-2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Physical exercise mitigates fatigue during androgen deprivation therapy (ADT); however, the effects of different exercise prescriptions are unknown.

    OBJECTIVES: To determine the long-term effects of different exercise modes on fatigue in prostate cancer patients undergoing ADT.

    DESIGN, SETTING, AND PARTICIPANTS: Between 2009 and 2012, 163 prostate cancer patients aged 43-90 y on ADT were randomised to exercise targeting the musculoskeletal system (impact loading+resistance training; ILRT; n=58), the cardiovascular and muscular systems (aerobic+resistance training; ART; n=54), or to usual care/delayed exercise (DEL; n=51) for 12 mo across university-affiliated exercise clinics in Australia.

    INTERVENTION: Supervised ILRT for 12 mo, supervised ART for 6 mo followed by a 6-mo home program, and DEL received a printed booklet on exercise information for 6 mo followed by 6-mo stationary cycling exercise.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Fatigue was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 36 and vitality using the Short Form-36. Analysis of variance was used to compare outcomes for groups at 6 mo and 12 mo.

    RESULTS AND LIMITATIONS: Fatigue was reduced (p=0.005) in ILRT at 6 mo and 12 mo (∼5 points), and in ART (p=0.005) and DEL (p=0.022) at 12 mo. Similarly, vitality increased for all groups (p≤0.001) at 12 mo (∼4 points). Those with the highest levels of fatigue and lowest vitality improved the most with exercise (ptrend<0.001). A limitation was inclusion of mostly well-functioning individuals.

    CONCLUSIONS: Different exercise modes have comparable effects on reducing fatigue and enhancing vitality during ADT. Patients with the highest levels of fatigue and lowest vitality had the greatest benefits.

    PATIENT SUMMARY: We compared the effects of different exercise modes on fatigue in men on androgen deprivation therapy. All exercise programs reduced fatigue and enhanced vitality. We conclude that undertaking some form of exercise will help reduce fatigue, especially in those who are the most fatigued.

  • 33.
    Thomsen, Simon N.
    et al.
    Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
    Lahart, Ian M.
    University of Wolverhampton, UK.
    Thomsen, Laura M.
    Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
    Fridh, Martin K.
    Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
    Larsen, Anders
    Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
    Mau-Sørensen, Morten
    Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
    Bolam, Kate
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Fairman, Ciaran M.
    University of South Carolina, Columbia, SC, USA.
    Christensen, Jesper F.
    Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; University of Southern Denmark, Odense, Denmark: Bispebjerg Hospital, Copenhagen, Denmark.
    Simonsen, Casper
    Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
    Harms of exercise training in patients with cancer undergoing systemic treatment: a systematic review and meta-analysis of published and unpublished controlled trials2023In: eClinicalMedicine, E-ISSN 2589-5370, Vol. 59, article id 101937Article in journal (Refereed)
    Abstract [en]

    Background

    Exercise is recommended for people with cancer. The aim of this study was to evaluate the harms of exercise in patients with cancer undergoing systemic treatment.

    Methods

    This systematic review and meta-analysis included published and unpublished controlled trials comparing exercise interventions versus controls in adults with cancer scheduled to undergo systemic treatment. The primary outcomes were adverse events, health-care utilization, and treatment tolerability and response. Eleven electronic databases and trial registries were systematically searched with no date or language restrictions. The latest searches were performed on April 26, 2022. The risk of bias was judged using RoB2 and ROBINS-I, and the certainty of evidence for primary outcomes was assessed using GRADE. Data were statistically synthesised using pre-specified random-effect meta-analyses. The protocol for this study was registered in the PROESPERO database (ID: CRD42021266882).

    Findings

    129 controlled trials including 12,044 participants were eligible. Primary meta-analyses revealed evidence of a higher risk of some harms, including serious adverse events (risk ratio [95% CI]: 1.87 [1.47–2.39], I2 = 0%, n = 1722, k = 10), thromboses (risk ratio [95% CI]: 1.67 [1.11–2.51], I2 = 0%, n = 934, k = 6), and fractures (risk ratio [95% CI]: 3.07 [3.03–3.11], I2 = 0%, n = 203, k = 2) in intervention versus control. In contrast, we found evidence of a lower risk of fever (risk ratio [95% CI]: 0.69 [0.55–0.87], I2 = 0% n = 1109, k = 7) and a higher relative dose intensity of systemic treatment (difference in means [95% CI]: 1.50% [0.14–2.85], I2 = 0% n = 1110, k = 13) in intervention versus control. For all outcomes, we downgraded the certainty of evidence due to imprecision, risk of bias, and indirectness, resulting in very low certainty of evidence.

    Interpretation

    The harms of exercise in patients with cancer undergoing systemic treatment are uncertain, and there is currently insufficient data on harms to make evidence-based risk-benefits assessments of the application of structured exercise in this population.

    Funding

    There was no funding for this study.

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  • 34.
    Wallmann, Tatjana
    et al.
    Karolinska Inst, Dept Oncol Pathol, CCK, R8 01, S-17176 Stockholm, Sweden.
    Zhang, Xing-Mei
    Karolinska Inst, Karolinska Hosp Solna, Dept Clin Neurosci, CMM, S-17176 Stockholm, Sweden.
    Wallerius, Majken
    Karolinska Inst, Dept Oncol Pathol, CCK, R8 01, S-17176 Stockholm, Sweden.
    Bolin, Sara
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Joly, Anne-Laure
    Karolinska Inst, Dept Med, CMM, S-17176 Stockholm, Sweden.
    Sobocki, Caroline
    Karolinska Inst, Dept Oncol Pathol, CCK, R8 01, S-17176 Stockholm, Sweden.
    Leiss, Lina
    Haukeland Hosp, Neuro Clin, Bergen, Norway;Univ Bergen, Oncomatrix Res Lab, Bergen, Norway.
    Jiang, Yiwen
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergh, Jonas
    Karolinska Inst, Dept Oncol Pathol, CCK, R8 01, S-17176 Stockholm, Sweden;Karolinska Univ Hosp, Radiumhemmet, S-17176 Stockholm, Sweden.
    Holland, Eric C.
    Fred Hutchinson Canc Res Ctr, Div Human Biol Solid Tumor & Translat Res, Seattle, WA 98109 USA.
    Enger, Per O.
    Univ Bergen, Oncomatrix Res Lab, Bergen, Norway;Haukeland Hosp, Dept Neurosurg, Bergen, Norway.
    Andersson, John
    Karolinska Inst, Dept Med, CMM, S-17176 Stockholm, Sweden.
    Swartling, Fredrik J.
    Uppsala universitet, Neuroonkologi.
    Miletic, Hrvoje
    Haukeland Hosp, Dept Pathol, Bergen, Norway;Univ Bergen, Dept Biomed, Bergen, Norway.
    Uhrbom, Lene
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Harris, Robert A.
    Karolinska Inst, Karolinska Hosp Solna, Dept Clin Neurosci, CMM, S-17176 Stockholm, Sweden.
    Rolny, Charlotte
    Karolinska Inst, Dept Oncol Pathol, CCK, R8 01, S-17176 Stockholm, Sweden.
    Microglia Induce PDGFRB Expression in Glioma Cells to Enhance Their Migratory Capacity2018In: iScience, E-ISSN 2589-0042, Vol. 9, p. 71-83Article in journal (Refereed)
    Abstract [en]

    High-grade gliomas (HGGs) are the most aggressive and invasive primary brain tumors. The platelet-derived growth factor (PDGF) signaling pathway drives HGG progression, and enhanced expression of PDGF receptors (PDGFRs) is a well-established aberration in a subset of glioblastomas (GBMs). PDGFRA is expressed in glioma cells, whereas PDGFRB is mostly restricted to the glioma-associated stroma. Here we show that the spatial location of TAMMs correlates with the expansion of a subset of tumor cells that have acquired expression of PDGFRB in both mouse and human low-grade glioma and HCGs. Furthermore, M2-polarized microglia but not bone marrow (BM)-derived macrophages (BMDMs) induced PDGFRB expression in glioma cells and stimulated their migratory capacity. These findings illustrate a heterotypic cross-talk between microglia and glioma cells that may enhance the migratory and invasive capacity of the latter by inducing PDGFRB.

  • 35.
    Weishaupt, Holger
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Čančer, Matko
    Uppsala universitet, Institutionen för immunologi, genetik och patologi.
    Rosén, Gabriela
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Holmberg, Karl O.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Häggqvist, Susana
    Uppsala universitet, Institutionen för immunologi, genetik och patologi.
    Bunikis, Ignas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jiang, Yiwen
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sreedharan, Smitha
    Uppsala universitet, Institutionen för immunologi, genetik och patologi.
    Gyllensten, Ulf
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Becher, Oren J.
    Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA.;Northwestern Univ, Dept Biochem & Mol Genet, Chicago, IL 60611 USA.;Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA..
    Uhrbom, Lene
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ameur, Adam
    Uppsala universitet, Institutionen för immunologi, genetik och patologi.
    Swartling, Fredrik J.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas2023In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 25, no 1, p. 97-107Article in journal (Refereed)
    Abstract [en]

    Background Malignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site. Methods Here we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next-generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies. Results A large fraction of common integration sites contained genes that have been dysregulated or misexpressed in glioma. Others overlapped with loci identified in previous glioma-related forward genetic screens, but several novel putative cancer-causing genes were also found. Integrating retroviral tagging and clinical data, Ppfibp1 was highlighted as a frequently tagged novel glioma-causing gene. Retroviral integrations into the locus resulted in Ppfibp1 upregulation, and Ppfibp1-tagged cells generated tumors with shorter latency on orthotopic transplantation. In human gliomas, increased PPFIBP1 expression was significantly linked to poor prognosis and PDGF treatment resistance. Conclusions Altogether, the current study has demonstrated a novel approach to tagging glioma genes via forward genetics, validating previous results, and identifying PPFIBP1 as a putative oncogene in gliomagenesis.

  • 36. Weller, Sarah
    et al.
    Hart, Nicolas H
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Mansfield, Sami
    Santa Mina, Daniel
    Winters-Stone, Kerri M
    Campbell, Anna
    Rosenberger, Friederike
    Wiskemann, Joachim
    Quist, Morten
    Cormie, Prue
    Goulart, Jennifer
    Campbell, Kristin L
    Exercise for individuals with bone metastases: A systematic review.2021In: Critical reviews in oncology/hematology, ISSN 1040-8428, E-ISSN 1879-0461, Vol. 166, p. 103433-, article id 103433Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Exercise has the potential to improve physical function and quality of life in individuals with bone metastases but is often avoided due to safety concerns. This systematic review summarizes the safety, feasibility and efficacy of exercise in controlled trials that include individuals with bone metastases.

    METHODS: MEDLINE, Embase, Pubmed, CINAHL, PEDro and CENTRAL databases were searched to July 16, 2020.

    RESULTS: A total of 17 trials were included incorporating aerobic exercise, resistance exercise or soccer interventions. Few (n = 4, 0.5%) serious adverse events were attributed to exercise participation, with none related to bone metastases. Mixed efficacy results were found, with exercise eliciting positive changes or no change. The majority of trials included an element of supervised exercise instruction (n = 16, 94%) and were delivered by qualified exercise professionals (n = 13, 76%).

    CONCLUSIONS: Exercise appears safe and feasible for individuals with bone metastases when it includes an element of supervised exercise instruction.

  • 37. Wengström, Y
    et al.
    Bolam, Kate A.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Mijwel, S
    Sundberg, C J
    Backman, M
    Browall, M
    Norrbom, J
    Rundqvist, H
    Optitrain: a randomised controlled exercise trial for women with breast cancer undergoing chemotherapy.2017In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, article id 100Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Women 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.

    METHODS: This 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.

    DISCUSSION: This 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 REGISTRATION: OptiTrain - Optimal Training Women with Breast Cancer (OptiTrain), NCT02522260 ; Registration: June 9, 2015, Last updated version Feb 29, 2016. Retrospectively registered.

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  • 38.
    Wengström, Yvonne
    et al.
    Karolinska Institutet.
    Mijwel, Sara
    Karolinska Institutet.
    Cardinale, Daniele A.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Högintensiv träning hjälper patienter med bröstcancer2018In: Idrottsforskning.se, ISSN 2002-3944, article id 12 novemberArticle in journal (Other (popular science, discussion, etc.))
  • 39. Wiggenraad, Fleur
    et al.
    Bolam, Kate
    Karolinska Institute, Stockholm, Sweden.
    Mijwel, Sara
    van der Wall, Elsken
    Wengström, Yvonne
    Altena, Renske
    Long-Term Favorable Effects of Physical Exercise on Burdensome Symptoms in the OptiTrain Breast Cancer Randomized Controlled Trial.2020In: Integrative Cancer Therapies, ISSN 1534-7354, E-ISSN 1552-695X, Vol. 19, article id 1534735420905003Article in journal (Refereed)
    Abstract [en]

    Purpose: We evaluate longitudinal changes in symptom clusters and core burdensome symptoms in breast cancer patients who participated in the OptiTrain trial. Methods: 240 women were randomized to 16 weeks of supervised exercise (RT-HIIT or AT-HIIT) or usual care (UC) during adjuvant chemotherapy. Symptom clusters were composed using the Memorial Symptom Assessment Scale (MSAS), assessed at baseline, 16 weeks and 12 months later. Three symptom clusters were formed. Results: Three symptom clusters were identified: "emotional," "treatment-related toxicity," and "physical," with core burdensome symptoms present over time. At 16 weeks, the reported burdens of "feeling sad" (RT-HIIT vs UC: effect size [ES] = -0.69; AT-HIIT vs UC: ES = -0.56) and "feeling irritable" (ES = -0.41 RT-HIIT; ES = -0.31 AT-HIIT) were significantly lower in both intervention groups compared with UC. At 12 months, the AT-HIIT group continued to have significantly lower scores for the core burdensome symptoms "feeling sad" (ES = -0.44), "feeling irritable" (ES = -0.44), and "changes in the way food tastes" (ES = -0.53) compared with UC. No between-group differences were found for physical symptoms. Conclusion: We identified 3 symptom clusters in breast cancer patients during and after adjuvant chemotherapy, composed of "emotional," "treatment-related toxicity," and "physical" symptoms. After treatment completion up to 12 months post-baseline, patients in the physical exercise groups reported lower symptom burden scores for emotional symptoms, compared with UC. Our findings indicate a preserved and long-term beneficial effect of physical exercise on self-reported emotional well-being in chemotherapy-treated breast cancer patients.

  • 40.
    Xie, Yuan
    et al.
    Uppsala universitet, Neuroonkologi.
    Bergström, Tobias
    Uppsala universitet, Neuroonkologi.
    Jiang, Yiwen
    Uppsala universitet, Neuroonkologi.
    Johansson, Patrik
    Uppsala universitet, Neuroonkologi.
    Marinescu, Voichita Dana
    Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi.
    Lindberg, Nanna
    Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA..
    Segerman, Anna
    Uppsala universitet, Neuroonkologi.
    Wicher, Grzegorz
    Uppsala universitet, Neuroonkologi.
    Niklasson, Mia
    Uppsala universitet, Neuroonkologi.
    Baskaran, Sathishkumar
    Uppsala universitet, Neuroonkologi.
    Sreedharan, Smitha
    Uppsala universitet, Neuroonkologi.
    Everlien, Isabelle
    Uppsala universitet, Neuroonkologi.
    Kastemar, Marianne
    Uppsala universitet, Neuroonkologi.
    Hermansson, Annika
    Uppsala universitet, Neuroonkologi.
    Elfineh, Lioudmila
    Uppsala universitet, Neuroonkologi.
    Libard, Sylwia
    Uppsala universitet, Institutionen för immunologi, genetik och patologi.
    Holland, Eric Charles
    Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA..
    Hesselager, Göran
    Uppsala universitet, Neurokirurgi.
    Alafuzoff, Irina
    Uppsala universitet, Institutionen för immunologi, genetik och patologi.
    Westermark, Bengt
    Uppsala universitet, Neuroonkologi.
    Nelander, Sven
    Uppsala universitet, Neuroonkologi.
    Forsberg-Nilsson, Karin
    Uppsala universitet, Neuroonkologi.
    Uhrbom, Lene
    Uppsala universitet, Neuroonkologi.
    The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes2015In: EBioMedicine, E-ISSN 2352-3964, Vol. 2, no 10, p. 1351-1363Article in journal (Refereed)
    Abstract [en]

    Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called gliomastem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional sub-types. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.

  • 41.
    Xie, Yuan
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sundström, Anders
    Uppsala universitet, Neuroonkologi.
    Maturi, Naga P
    Uppsala universitet, Neuroonkologi.
    Tan, E-Jean
    Uppsala universitet, Neuroonkologi.
    Marinescu, Voichita D
    Uppsala universitet, Institutionen för immunologi, genetik och patologi.
    Jarvius, Malin
    Uppsala universitet, Cancerfarmakologi och beräkningsmedicin.
    Tirfing, Malin
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jin, Chuan
    Uppsala universitet, Klinisk immunologi.
    Chen, Lei
    Uppsala universitet, Molekylära verktyg.
    Essand, Magnus
    Uppsala universitet, Klinisk immunologi.
    Johansson, Fredrik J.
    Uppsala universitet, Neuroonkologi.
    Nelander, Sven
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jiang, Yiwen
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Uhrbom, Lene
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    LGR5 promotes tumorigenicity and invasion of glioblastoma stem-like cells and is a potential therapeutic target for a subset of glioblastoma patients2019In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 247, no 2, p. 228-240Article in journal (Refereed)
    Abstract [en]

    Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor which lacks efficient treatment and predictive biomarkers. Expression of the epithelial stem cell marker Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been described in GBM, but its functional role has not been conclusively elucidated. Here, we have investigated the role of LGR5 in a large repository of patient-derived GBM stem cell (GSC) cultures. The consequences of LGR5 overexpression or depletion have been analyzed using in vitro and in vivo methods, which showed that, among those with highest LGR5 expression (LGR5(high)), there were two phenotypically distinct groups: one that was dependent on LGR5 for its malignant properties and another that was unaffected by changes in LGR5 expression. The LGR5-responding cultures could be identified by their significantly higher self-renewal capacity as measured by extreme limiting dilution assay (ELDA), and these LGR5(high)-ELDA(high) cultures were also significantly more malignant and invasive compared to the LGR5(high)-ELDA(low) cultures. This showed that LGR5 expression alone would not be a strict marker of LGR5 responsiveness. In a search for additional biomarkers, we identified LPAR4, CCND2, and OLIG2 that were significantly upregulated in LGR5-responsive GSC cultures, and we found that OLIG2 together with LGR5 were predictive of GSC radiation and drug response. Overall, we show that LGR5 regulates the malignant phenotype in a subset of patient-derived GSC cultures, which supports its potential as a predictive GBM biomarker. Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  • 42.
    Zhang, Lei
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Laaniste, Liisi
    Uppsala universitet, Institutionen för immunologi, genetik och patologi.
    Jiang, Yiwen
    Uppsala universitet, Neuroonkologi.
    Alafuzoff, Irina
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Uhrbom, Lene
    Uppsala universitet, Neuroonkologi.
    Dimberg, Anna
    Uppsala universitet, Vaskulärbiologi.
    Pleiotrophin enhances PDGFB-induced gliomagenesis through increased proliferation of neural progenitor cells2016In: Oncotarget, E-ISSN 1949-2553, Vol. 7, no 49, p. 80382-80390Article in journal (Refereed)
    Abstract [en]

    Pleiotrophin (PTN) augments tumor growth by increasing proliferation of tumor cells and promoting vascular abnormalization, but its role in early gliomagenesis has not been evaluated. Through analysis of publically available datasets, we demonstrate that increased PTN mRNA expression is associated with amplification of chromosome 7, identified as one of the earliest steps in glioblastoma development. To elucidate the role of PTN in tumor initiation we employed the RCAS/tv-a model that allows glioma induction by RCAS-virus mediated expression of oncogenes in neural progenitor cells. Intracranial injection of RCAS-PTN did not induce glioma formation when administrated alone, but significantly enhanced RCAS-platelet derived growth factor (PDGF) B-induced gliomagenesis. PTN co-treatment augmented PDGFBinduced Akt activation in neural progenitor cells in vitro, and enhanced neural sphere size associated with increased proliferation. Our data indicates that PTN expression is associated with chromosome 7 gain, and that PTN enhances PDGFB-induced gliomagenesis by stimulating proliferation of neural progenitor cells.

1 - 42 of 42
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