| 1. |
- Henriksson, Anna, et al.
(författare)
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Does inflammation markers or treatment type moderate exercise intensity effects on changes in muscle strength in cancer survivors participating in a 6-month combined resistance- and endurance exercise program? : Results from the Phys-Can trial
- 2023
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Ingår i: BMC Sports Science, Medicine and Rehabilitation. - : BioMed Central (BMC). - 2052-1847. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Resistance exercise has a beneficial impact on physical function for patients receiving oncological treatment. However, there is an inter-individual variation in the response to exercise and the tolerability to high-intensity exercise. Identifying potential moderating factors, such as inflammation and treatment type, for changes in muscle strength is important to improve the effectiveness of exercise programs. Therefore, we aimed to investigate if inflammation and type of oncological treatment moderate the effects of exercise intensity (high vs. low-moderate) on muscular strength changes in patients with breast (BRCA) or prostate cancer (PRCA).METHODS: Participants with BRCA (n = 286) and PRCA (n = 65) from the Physical training and Cancer study (Phys-Can) were included in the present study. Participants performed a combined resistance- and endurance exercise program during six months, at either high or low-moderate intensity. Separate regression models were estimated for each cancer type, with and without interaction terms. Moderators included in the models were treatment type (i.e., neo/adjuvant chemotherapy-yes/no for BRCA, adjuvant androgen deprivation therapy (ADT)-yes/no for PRCA)), and inflammation (interleukin 6 (IL6) and tumor necrosis factor-alpha (TNFα)) at follow-up.RESULTS: For BRCA, neither IL6 (b = 2.469, 95% CI [- 7.614, 12.552]) nor TNFα (b = 0.036, 95% CI [- 6.345, 6.418]) levels moderated the effect of exercise intensity on muscle strength change. The same was observed for chemotherapy treatment (b = 4.893, 95% CI [- 2.938, 12.724]). Similarly, for PRCA, the effect of exercise intensity on muscle strength change was not moderated by IL6 (b = - 1.423, 95% CI [- 17.894, 15.048]) and TNFα (b = - 1.905, 95% CI [- 8.542, 4.732]) levels, nor by ADT (b = - 0.180, 95% CI [- 11.201, 10.841]).CONCLUSIONS: The effect of exercise intensity on muscle strength is not moderated by TNFα, IL6, neo/adjuvant chemotherapy, or ADT, and therefore cannot explain any intra-variation of training response regarding exercise intensity (e.g., strength gain) for BRCA or PRCA in this setting.TRIAL REGISTRATION: ClinicalTrials.gov NCT02473003.
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| 2. |
- Mattsson-Carlgren, Niklas, et al.
(författare)
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A beta deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer's disease
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:16
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Tidskriftsartikel (refereegranskat)abstract
- The links between beta-amyloid ( A beta ) and tau in Alzheimer's disease are unclear. Cognitively unimpaired persons with signs of A beta pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without A beta pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when A beta aggregation started. These results show that A beta pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.
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| 3. |
- Mazzoni, Anne-Sophie, et al.
(författare)
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Reallocating sedentary time to physical activity : effects on fatigue and quality of life in patients with breast cancer in the Phys-Can project
- 2023
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Ingår i: Supportive Care in Cancer. - : Springer Nature. - 0941-4355 .- 1433-7339. ; 31:2
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We aimed to investigate the effects of reallocating sedentary time to an equal amount of light (LPA) or moderate-to-vigorous intensity physical activity (MVPA) on cancer-related fatigue and health-related quality of life (HRQoL) in patients with breast cancer. We also aimed to determine the daily amount of sedentary time needed to be reallocated to LPA or MVPA to produce minimal clinically important changes in these outcomes.METHODS: Pooled baseline data from three studies were used, including women with breast cancer who participated in the Phys-Can project. Fatigue was assessed with the Multidimensional Fatigue Inventory questionnaire (MFI; five dimensions, 4-20 scale) and HRQoL with the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30; 0-100 scale). Sedentary time and physical activity were measured with accelerometry. Isotemporal substitution modelling was used for the analyses.RESULTS: Overall, 436 participants (mean age 56 years, fatigue 11 [MFI], HRQoL 66 [EORTC QLQ-C30], LPA 254 min/day, MVPA 71 min/day) were included. Fatigue significantly decreased in two MFI dimensions when reallocating 30 min/day of sedentary time to LPA: reduced motivation and reduced activity (β = - 0.21). Fatigue significantly decreased in three MFI dimensions when reallocating 30 min/day of sedentary time to MVPA: general fatigue (β = - 0.34), physical fatigue (β = - 0.47) and reduced activity (β = - 0.48). To produce minimal clinically important changes in fatigue (- 2 points on MFI), the amount of sedentary time needed to be reallocated to LPA was ≈290 min/day and to MVPA was ≥ 125 min/day. No significant effects were observed on HRQoL when reallocating sedentary time to LPA or MVPA.CONCLUSIONS: Our results suggest that reallocating sedentary time to LPA or MVPA has beneficial effects on cancer-related fatigue in patients with breast cancer, with MVPA having the greatest impact. In relatively healthy and physically active breast cancer populations, a large amount of time reallocation is needed to produce clinically important changes. Future studies are warranted to evaluate such effects in broader cancer populations.TRIAL REGISTRATION: NCT02473003 (10/10/2014) and NCT04586517 (14/10/2020).
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| 4. |
- Schauer, Tim, et al.
(författare)
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Pre-treatment levels of inflammatory markers and chemotherapy completion rates in patients with early-stage breast cancer
- 2023
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Ingår i: International Journal of Clinical Oncology. - : Springer Nature. - 1341-9625 .- 1437-7772. ; 28:1, s. 89-98
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chemotherapy efficacy is largely dependent on treatment adherence, defined by the relative dose intensity (RDI). Identification of new modifiable risk factors associated with low RDI might improve chemotherapy delivery. Here, we evaluated the association between low RDI and pre-chemotherapy factors, including patient- and treatment-related characteristics and markers of inflammation.METHODS: This exploratory analysis assessed data from 267 patients with early-stage breast cancer scheduled to undergo (neo-)adjuvant chemotherapy included in the Physical training and Cancer (Phys-Can) trial. The association between low RDI, defined as < 85%, patient-related (age, body mass index, co-morbid condition, body surface area) and treatment-related factors (cancer stage, receptor status, chemotherapy duration, chemotherapy dose, granulocyte colony-stimulating factor) was investigated. Analyses further included the association between RDI and pre-chemotherapy levels of interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and Tumor Necrosis Factor-alpha (TNF-α) in 172 patients with available blood samples.RESULTS: An RDI of < 85% occurred in 31 patients (12%). Univariable analysis revealed a significant association with a chemotherapy duration above 20 weeks (p < 0.001), chemotherapy dose (p = 0.006), pre-chemotherapy IL-8 (OR 1.61; 95% CI (1.01; 2.58); p = 0.040) and TNF-α (OR 2.2 (1.17; 4.53); p = 0.019). In multivariable analyses, inflammatory cytokines were significant association with low RDI for IL-8 (OR: 1.65 [0.99; 2.69]; p = 0.044) and TNF-α (OR 2.95 [1.41; 7.19]; p = 0.007).CONCLUSIONS: This exploratory analysis highlights the association of pre-chemotherapy IL-8 and TNF-α with low RDI of chemotherapy for breast cancer. IL-8 and TNF-α may therefore potentially help to identify patients at risk for experiencing dose reductions. Clinical trial number NCT02473003 (registration: June 16, 2015).
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| 5. |
- Strandberg, Emelie, et al.
(författare)
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Effects of heavy-load resistance training during (neo-)adjuvant chemotherapy on muscle cellular outcomes in women with breast cancer
- 2021
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Ingår i: Medicine. - 0025-7974 .- 1536-5964. ; 100:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: (Neo-)adjuvant chemotherapy for breast cancer has a deleterious impact on muscle tissue resulting in reduced cardiorespiratory fitness, skeletal muscle mass and function. Physical exercise during treatment may counteract some of these negative effects. However, the effects of resistance training (RT) alone have never been explored. The present study aims to investigate if heavy-load RT during (neo-)adjuvant chemotherapy counteracts deleterious effects on skeletal muscle in women diagnosed with breast cancer. We hypothesize that (neo-)adjuvant treatment with chemotherapy will reduce muscle fiber size, impair mitochondrial function, and increase indicators of cellular stress and that RT during treatment will counteract these negative effects. We also hypothesize that RT during (neo-)adjuvant chemotherapy will increase muscle and blood levels of potential antitumor myokines and reduce treatment-related side effects on muscle strength and cardiorespiratory fitness.Methods: Fifty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to either randomized to either intervention group or to control group.The intervention group will perform supervised heavy-load RT twice a week over the course of chemotherapy (approximately 16-weeks) whereas the control group will be encouraged to continue with their usual activities. Muscle biopsies from m. vastus lateralis will be collected before the first cycle of chemotherapy (T0), after chemotherapy (T1), and 6 months later (T2) for assessment of muscle cellular outcomes. The primary outcome for this study is muscle fiber size. Secondary outcomes are: regulators of muscle fiber size and function, indicators of cellular stress and mitochondrial function, myokines with potential antitumor effects, muscle strength, and cardiorespiratory fitness.Ethics and dissemination: Ethical approval has been obtained from the Regional Ethical Review Board in Uppsala, Sweden (Dnr:2016/230/2). Results will be disseminated through presentations at scientific meetings, publications in peer-reviewed journals, social media, and patient organizations.Trial registration number: NCT04586517.
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| 6. |
- Strandberg, Emelie, et al.
(författare)
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Who makes it all the way? : Participants vs. decliners, and completers vs. drop-outs, in a 6-month exercise trial during cancer treatment. Results from the Phys-Can RCT
- 2022
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Ingår i: Supportive Care in Cancer. - : Springer Nature. - 0941-4355 .- 1433-7339. ; 30:2, s. 1739-1748
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To compare sociodemographic, health- and exercise-related characteristics of participants vs. decliners, and completers vs. drop-outs, in an exercise intervention trial during cancer treatment.Methods Patients with newly diagnosed breast, prostate, or colorectal cancer were invited to participate in a 6-month exercise intervention. Background data for all respondents (n = 2051) were collected at baseline by questionnaire and medical records. Additional data were collected using an extended questionnaire, physical activity monitors, and fitness testing for trial participants (n = 577). Moreover, a sub-group of decliners (n = 436) consented to additional data collection by an extended questionnaire . Data were analyzed for between-group differences using independent t-tests and chi2-tests.Results Trial participants were younger (59 ± 12yrs vs. 64 ± 11yrs, p < .001), more likely to be women (80% vs. 75%, p = .012), and scheduled for chemotherapy treatment (54% vs. 34%, p < .001), compared to decliners (n = 1391). A greater proportion had university education (60% vs 40%, p < .001), reported higher anxiety and fatigue, higher exercise self-efficacy and outcome expectations, and less kinesiophobia at baseline compared to decliners. A greater proportion of trial participants were classified as ‘not physically active’ at baseline; however, within the group who participated, being “physically active” at baseline was associated with trial completion. Completers (n = 410) also reported less kinesiophobia than drop-outs (n = 167).Conclusion The recruitment procedures used in comprehensive oncology exercise trials should specifically address barriers for participation among men, patients without university education and older patients. Individualized efforts should be made to enroll patients with low exercise self-efficacy and low outcome expectations of exercise. To retain participants in an ongoing exercise intervention, extra support may be needed for patients with kinesiophobia and those lacking health-enhancing exercise habits at baseline.
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| 7. |
- Vikmoen, Olav, et al.
(författare)
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Effects of High and Low-To-Moderate Intensity Exercise During (Neo-) Adjuvant Chemotherapy on Muscle Cells, Cardiorespiratory Fitness, and Muscle Function in Women With Breast Cancer : Protocol for a Randomized Controlled Trial
- 2022
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Ingår i: JMIR Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: (Neo-)adjuvant chemotherapy for breast cancer is effective but has deleterious side effects on muscle tissue, resulting in reduced skeletal muscle mass, muscle function, and cardiorespiratory fitness. Various exercise regimens during cancer treatment have been shown to counteract some of these side effects. However, no study has compared the effect of high-intensity training versus low-to-moderate intensity training on muscle tissue cellular outcomes and physical function in patients with breast cancer during chemotherapy.Objective: The aim of this substudy within the Physical Training in Cancer (Phys-Can) consortium is to evaluate and compare the effects of high and low-to-moderate intensity exercise on muscle cellular outcomes, muscle function, and cardiorespiratory fitness in women with breast cancer undergoing (neo-)adjuvant chemotherapy. We further aim to investigate if the effects of chemotherapy including taxanes on muscles will be different from those of taxane-free chemotherapy.Methods: Eighty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to a combination of strength and endurance training, either at high intensity or at low-to-moderate intensity. Testing of muscle function and cardiorespiratory fitness and collection of muscle biopsies from the vastus lateralis muscle will be performed before the first cycle of chemotherapy (or after 1 week, when not possible) (T0), halfway through chemotherapy (T1), and after completion of chemotherapy (T2). It is estimated that approximately 50% of the participants will be willing to undergo muscle biopsies. To separate the effect of the treatment itself, a usual care group with no supervised training will also be included, and in this group, testing and collection of muscle biopsies will be performed at T0 and T2 only.Results: This study is funded by Active Against Cancer (Aktiv mot kreft) (May 2013) and the Norwegian Cancer Society (December 2018). Inclusion started in December 2016 and the last participant is expected to be recruited in December 2022. As of June 2022, we enrolled 38 (19 with biopsies) participants to the high-intensity training group, 36 (19 with biopsies) participants to the low-to-moderate intensity training group, and 17 (16 with biopsies) participants to the usual care group. Data analyses will start in fall 2022. The first results are expected to be published in spring 2024.Conclusions: This study will generate new knowledge about the effects of different training intensities for women with breast cancer during chemotherapy treatment. It will give further insight into how chemotherapy affects the muscle tissue and how physical training at different intensities may counteract the treatment side effects in muscles. The results of this study will inform
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