| 1. |
- Rundqvist, Helene, et al.
(författare)
-
Activation of the erythropoietin receptor in human skeletal muscle
- 2009
-
Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 161:3, s. 427-434
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Erythropoietin receptor (EPOR) expression in non-hematological tissues has been shown to be activated by locally produced and/or systemically delivered EPO. Improved oxygen homeostasis, a well-established consequence of EPOR activation, is very important for human skeletal muscle performance. In the present study we investigate whether human skeletal muscle fibers and satellite cells express EPOR and if it is activated by exercise. Design and methods: Ten healthy males performed 65 min of cycle exercise. Biopsies were obtained from the vastus lateralis muscle and femoral arterio-venous differences in EPO concentrations were estimated. Results: The EPOR proteinwas localized in areas corresponding to the sarcolemma and capillaries. Laser dissection identified EPOR mRNA expression in muscle fibers. Also, EPOR mRNA and protein were both detected in human skeletal muscle satellite cells. In the initial part of the exercise bout there was a release of EPO from the exercising leg to the circulation, possibly corresponding to an increased bioavailability of EPO. After exercise, EPOR mRNA and EPOR-associated JAK2 phosphorylation were increased. Conclusions: Interaction with JAK2 is required for EPOR signaling and the increase found in phosphorylation is therefore closely linked to the activation of EPOR. The receptor activation by acute exercise suggests that signaling through EPOR is involved in exercise-induced skeletal muscle adaptation, thus extending the biological role of EPO into the skeletal muscle.
|
|
| 2. |
- Ansund, Josefin, et al.
(författare)
-
High intensity exercise during breast cancer chemotherapy - effects on long-term myocardial damage and physical capacity - data from the OptiTrain RCT.
- 2021
-
Ingår i: Cardio-oncology (London, England). - : Springer Science and Business Media LLC. - 2057-3804. ; 7:1, s. 7-
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 3. |
- Bolam, Kate, et al.
(författare)
-
Association between change in cardiorespiratory fitness and prostate cancer incidence and mortality in 57 652 Swedish men.
- 2024
-
Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 58:7, s. 366-372
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine the associations between changes in cardiorespiratory fitness (CRF) in adulthood and prostate cancer incidence and mortality.METHODS: In this prospective study, men who completed an occupational health profile assessment including at least two valid submaximal CRF tests, performed on a cycle ergometer, were included in the study. Data on prostate cancer incidence and mortality were derived from national registers. HRs and CIs were calculated using Cox proportional hazard regression with inverse probability treatment weights of time-varying covariates.RESULTS: During a mean follow-up time of 6.7 years (SD 4.9), 592 (1%) of the 57 652 men were diagnosed with prostate cancer, and 46 (0.08%) died with prostate cancer as the primary cause of death. An increase in absolute CRF (as % of L/min) was associated with a reduced risk of prostate cancer incidence (HR 0.98, 95% CI 0.96 to 0.99) but not mortality, in the fully adjusted model. When participants were grouped as having increased (+3%), stable (±3%) or decreased (-3%) CRF, those with increased fitness also had a reduced risk of prostate cancer incidence compared with those with decreased fitness (HR 0.65, 95% CI 0.49 to 0.86), in the fully adjusted model.CONCLUSION: In this study of employed Swedish men, change in CRF was inversely associated with risk of prostate cancer incidence, but not mortality. Change in CRF appears to be important for reducing the risk of prostate cancer.
|
|
| 4. |
- Bolam, Kate, et al.
(författare)
-
Two-year follow-up of the OptiTrain randomised controlled exercise trial.
- 2019
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 175:3, s. 637-648
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 5. |
- Ekblom Bak, Elin, 1981-, et al.
(författare)
-
Association Between Cardiorespiratory Fitness and Cancer Incidence and Cancer-Specific Mortality of Colon, Lung, and Prostate Cancer Among Swedish Men.
- 2023
-
Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:6
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 6. |
- Evans, Colin E, et al.
(författare)
-
Modelling pulmonary microthrombosis coupled to metastasis : Distinct effects of thrombogenesis on tumorigenesis
- 2017
-
Ingår i: Biology Open. - : The Company of Biologists. - 2046-6390. ; 6:5, s. 688-697
-
Tidskriftsartikel (refereegranskat)abstract
- Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular microocclusion can occur as a result of arrest of circulating tumour cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we modelled the effect of microvascular occlusion in metastatic efficiency by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumour cell injection.We found that controlled induction of a specific number of these microthrombotic insults in the lungs caused an increase in expression of the hypoxia-inducible transcription factors (HIFs), a pro-Angiogenic and pro-Tumorigenic environment, as well as an increase in myeloid cell infiltration. Induction of pulmonary microthrombosis prior to introduction of tumour cells to the lungs had no effect on tumorigenic success, but thrombosis at the time of tumour cell seeding increased number and size of tumours in the lung, and this effect was strikingly more pronounced when the microocclusion occurred on the day following introduction of tumour cells. The tumorigenic effect of microbead treatment was seen even when thrombosis was induced five days after tumour cell injection. We also found positive correlations between thrombotic factors and expression of HIF2α in human tumours. The model system described here demonstrates the importance of thrombotic insult in metastatic success and can be used to improve understanding of thrombosis-Associated tumorigenesis and its treatment.
|
|
| 7. |
- Hiensch, Anouk E, et al.
(författare)
-
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.
- 2022
-
Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 23:1, s. 610-
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 8. |
- Hiensch, Anouk E, et al.
(författare)
-
Doxorubicin-induced skeletal muscle atrophy : Elucidating the underlying molecular pathways.
- 2020
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 229:2
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 9. |
- Koivula, Tiia, et al.
(författare)
-
The effect of acute exercise on circulating immune cells in newly diagnosed breast cancer patients
- 2023
-
Ingår i: Scientific Reports. - London : Nature Publishing Group. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- The role of exercise in cancer prevention and control is increasingly recognized, and based on preclinical studies, it is hypothesized that mobilization of leukocytes plays an important role in the anti-tumor effect. Thus, we examined how 10-min acute exercise modulates immune cells in newly diagnosed breast cancer patients. Blood samples were taken at rest, immediately after exercise and 30 min after exercise and phenotypic characterization of major leukocyte subsets was done using 9-color flow cytometry. Total leukocyte count increased by 29%, CD8+ T cell count by 34%, CD19+ B cell count by 18%, CD56+CD16+ NK cell count by 130%, and CD14+CD16+ monocyte count by 51% immediately after acute exercise. Mobilization of CD45+, CD8+, CD19+, and CD56+CD16+ cells correlated positively with exercising systolic blood pressure, heart rate percentage of age predicted maximal heart rate, rate pressure product, and mean arterial pressure. Our findings indicate that a single bout of acute exercise of only 10 min can cause leukocytosis in breast cancer patients. Mobilization of leukocytes appear to be directly related to the intensity of exercise. It is possible that the positive effect of exercise on oncologic outcome might be partly due to immune cell mobilization as documented in the present study. © 2023, The Author(s).
|
|
| 10. |
- Lanner, Johanna, et al.
(författare)
-
Running reverses tumor-induced muscle weakness in mice with breast cancer
- 2019
-
Konferensbidrag (refereegranskat)abstract
- Introduction: Patients with breast cancer experience muscle dysfunction, which is a clinical challenge that is not restricted to advanced stage patients, but also observed in newly diagnosed weight-stable patients with low tumor burden. Recent data indicate that physical activity can reduce breast cancerassociated mortality, suggesting that improved muscle performance per secan have positive impact on survival. Here, the transgenic PyMT mouse model of breast cancer was used to elucidate molecular mechanisms underlying breast cancer-induced muscle impairments.Materials and Methods: PyMT mice and wildtype (WT) littermates w/wo access to an in-cage running wheel for four weeks (week 8-12). Functional readouts included Ca2+imaging; isometric force measurement on single fibers and intact fast-and slow-twitchmuscles. Intramuscular signaling was assessed using immunofluorescence, immunoblotting and enzymatic assays.Results: The specific force (i.e. force/cross-sectional area) was significantly decreased by ~ 35% in slow-twitch soleus muscles from breast cancermice as compared to WT muscles, which was the result of reduced Ca2+release and impaired myofibrillar function. There were no difference in muscle size or fiber type between the two groups. However, higher intramuscular stress (e.g. p38 activation and carbonylation (DNP)) was observed in PyMT than in WT. Intriguingly, voluntary running for four weeks reversed the weakness and PyMT soleus muscles generated similar forces as muscles of exercised WT mice. The running induced higher SOD2 expression and normalized levels of p38 and DNP.Conclusion: Intrinsic contractile dysfunction and higher intramuscular stress was present in mice with breast cancer, which was counteracted with voluntary running.
|
|
