Tormod Skogstad Nilsen

• Bøhn, Skh; Oldervoll, Line Merethe; Reinertsen, Kristin Valborg; Selland, Mette; Fosså, Alexander & Kiserud, Cecilie E. [Show all 17 contributors for this article] (2024). The feasibility of a multidimensional intervention in lymphoma survivors with chronic fatigue. Supportive Care in Cancer. ISSN 0941-4355. 32(1). doi: 10.1007/s00520-023-08204-5.
• Johansen, Merethe Lia; Eriksrud, Ola; Thorkildsen, Joachim; Norum, Ole-Jacob Anderssen; Wisløff, Torbjørn & Taksdal, Ingeborg [Show all 7 contributors for this article] (2023). Muscle strength characteristics following megaprosthetic knee reconstruction for bone sarcoma. Surgial oncology. ISSN 0960-7404. 48. doi: 10.1016/j.suronc.2023.101944. Full text in Research Archive Show summary

  Objective: To assess muscle strength characteristics in patients with resection and megaprosthetic reconstruction of the knee for bone sarcoma compared to age- and sex-matched controls. Methods: This was a cross-sectional, case-control study. Muscle strength characteristics for knee extension and -flexion were assessed isokinetically at three different joint velocities: 60, 120 and 180°/s, and by the rate of force development (RDFmax) in knee extension. The Toronto Extremity Salvage Score (TESS) was used in patients. Results: Eighteen patients (91.6 months postop.) and 18 controls were included. Relative to controls, patients generated maximal torques of 19%, 23% and 23% in knee extension at 60, 120 and 180°/s, respectively. For knee flexion, patients generated maximal torques of 58%, 53% and 60% at 60, 120, and 180°/s, relative to the controls. RDFmax of the operated leg was 2.75 ± 2.13 N/ms, 7.16 ± 4.78 N/ms for the non-operated leg, and 7.95 ± 4.29 N/ms for the controls. The mean TESS score was 84.0. Conclusion: Patients reached approximately 20% of the maximal knee extension torque. In isometric assessments, they used double the amount of time to generate one-third of the maximal force compared to the controls despite good TESS scores.

• Gorski, Piotr Patryk; Raastad, Truls; Ullrich, Max; Turner, Daniel; Hallén, Jostein & Sarvari, Sebastian [Show all 8 contributors for this article] (2022). Aerobic Exercise Training Resets the Human Skeletal Muscle Methylome Ten Years after Breast Cancer Treatment and Survival. The FASEB Journal. ISSN 0892-6638. 37(1). doi: 10.1096/fj.202201510RR. Show summary

  Background: Cancer survivors suffer impairments in skeletal muscle in terms of reduced mass and function. Interestingly, human skeletal muscle possesses an epigenetic memory of earlier stimuli, such as exercise. Long-term retention of epigenetic changes in skeletal muscle following cancer survival and/or exercise training have not yet been studied. We therefore investigated genome-wide DNA methylation (methylome) in skeletal muscle following a 5-month, 3/week aerobic-training intervention in breast cancer survivors 10-14 years after diagnosis and treatment. These results were compared to breast cancer survivors who remained untrained and to age-matched controls with no history of cancer, who undertook the same training intervention. Methods: Skeletal muscle biopsies were obtained from 23 females before(pre) and after(post) the 5-month training period. InfiniumEPIC 850K DNA methylation arrays and RT-PCR for gene expression performed. Results: The breast cancer survivors displayed a significant retention of increased DNA methylation (i.e.,hypermethylation) at a larger number of differentially methylated positions (DMPs) compared with healthy age-matched controls pre-training. Training in cancer survivors led to an exaggerated number of DMPs with a hypermethylated signature occurring at non-regulatory regions compared with training in healthy age-matched controls. However, the opposite occurred in important gene regulatory regions, where training in cancer survivors elicited a considerable reduction in methylation (i.e.,hypomethylation) in 99% of the DMPs located in CpG islands within promoter regions. Importantly, training was able to reverse the hypermethylation identified in cancer survivors back towards a hypomethylated signature that was observed pre-training in healthy age-matched controls at 300 (out of 881) of these island/promoter associated CpGs. Pathway enrichment analysis identified training in cancer survivors evoked this predominantly hypomethylated signature in pathways associated with: Cell cycle, DNA replication/repair, transcription, translation, mTOR signalling and the proteosome. Differentially methylated region (DMR) analysis also identified genes: BAG1, BTG2, CHP1, KIFC1, MKL2, MTR, PEX11B, POLD2, S100A6, SNORD104 and SPG7 as hypermethylated in breast cancer survivors, with training reversing these CpG island/promoter associated DMRs towards a hypomethylated signature. Training also elicited a largely different epigenetic response in healthy individuals than that observed in cancer survivors, with very few overlapping changes. Only one gene, SIRT2, was identified as having altered methylation in cancer survivors at baseline and after training in both the cancer survivors and healthy controls. Conclusions: Human skeletal muscle muscle may retain a hypermethylated signature as long as 10-14 years after breast cancer treatment/survival. Five months of aerobic training reset the skeletal muscle methylome towards signatures identified in healthy age-matched individuals in gene regulatory regions.

• Nilsen, Tormod Skogstad; Johansen, Sara Hassing; Thorsen, Lene; Fairman, Ciaran M.; Wisløff, Torbjørn & Raastad, Truls (2022). Does Androgen Deprivation for Prostate Cancer Affect Normal Adaptation to Resistance Exercise? International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 19(7). doi: 10.3390/ijerph19073820. Full text in Research Archive Show summary

  Background: Loss of muscle mass and muscle function is a common side effect from androgen deprivation therapy (ADT) for prostate cancer (PCa). Here, we explored effects of heavy-load resistance training (RT) on lean body mass and muscle strength changes reported in randomized controlled trials (RCTs) among PCa patients on ADT and in healthy elderly men (HEM), by comparison of results in separate meta-analysis. Methods: RCTs were identified through databases and reference lists. Results: Seven RCTs in PCa patients (n = 449), and nine in HEM (n = 305) were included. The effects of RT in lean body mass change were similar among PCa patients (Standardized mean difference (SMD): 0.4, 95% CI: 0.2, 0.7) and HEM (SMD: 0.5, 95% CI: 0.2, 0.7). It is noteworthy that the within group changes showed different patterns in PCa patients (intervention: 0.2 kg; control: −0.6 kg) and HEM (intervention: 1.2 kg; control: 0.2 kg). The effects of RT on change in muscle strength (measured as 1 RM) were similar between PCa patients and HEM, both for lower body- (PCa: SMD: 1.9, 95% CI: 1.2, 2.5; HEM: SMD: 2.2, 95% CI: 1.0, 3.4), and for upper body exercises (PCa: SMD: 2.0, 95% CI: 1.3, 2.7; HEM: SMD: 1.9, 95% CI: 1.3, 2.6). Conclusions: The effects of RT on lean body mass and 1 RM were similar in PCa patients on ADT and HEM, but the mechanism for the intervention effect might differ between groups. It seems that RT counteracts loss of lean body mass during ADT in PCa patients, as opposed to increasing lean body mass in HEM.

• Scott, Jessica M.; Thomas, Samantha M.; Herndon, James E.; Douglas, Pamela S.; Yu, Anthony F. & Rusch, Valerie [Show all 15 contributors for this article] (2021). Effects and tolerability of exercise therapy modality on cardiorespiratory fitness in lung cancer: a randomized controlled trial. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 12(6), p. 1456–1465. doi: 10.1002/jcsm.12828. Full text in Research Archive Show summary

  Background: Poor cardiorespiratory fitness (CRF) is a cardinal feature of post-treatment primary lung cancer. The most effective exercise therapy regimen to improve CRF has not been determined. Methods: In this parallel-group factorial randomized controlled trial, lung cancer survivors with poor CRF (below age–sex sedentary values) were randomly allocated to receive 48 consecutive supervised sessions thrice weekly of (i) aerobic training (AT)—cycle ergometry at 55% to >95% of peak oxygen consumption (VO2peak); (ii) resistance training (RT)—lower and upper extremity exercises at 50–85% of maximal strength; (iii) combination training (CT)—AT plus RT; or (iv) stretching attention control (AC) for 16 weeks. The primary endpoint was change in CRF (VO2peak, mL O2·kg−1·min−1). Secondary endpoints were body composition, muscle strength, patient-reported outcomes, tolerability (relative dose intensity of exercise), and safety. Analysis of covariance determined change in primary and secondary endpoints from baseline to post-intervention (Week 17) with adjustment for baseline values of the endpoint and other relevant clinical covariates. Results: Ninety patients (65 ± 9 years; 66% female) were randomized (AT, n = 24; RT, n = 23; CT, n = 20; and AC, n = 23) of the planned n = 160. No serious adverse events were observed. For the overall cohort, the lost-to-follow-up rate was 10%. Mean attendance was ≥75% in all groups. In intention-to-treat analysis, VO2peak increased 1.1 mL O2·kg−1·min−1 [95% confidence interval (CI): 0.0, 2.2, P = 0.04] and 1.4 mL O2·kg−1·min−1 (95% CI: 0.2, 2.5, P = 0.02) in AT and CT, respectively, compared with AC. There was no difference in VO2peak change between RT and AC (−0.1 mL O2·kg−1·min−1, 95% CI: −1.2, 1.0, P = 0.88). Favourable improvements in maximal strength and body composition were observed in RT and CT groups compared with AT and AC groups (Ps < 0.05). No between-group changes were observed for any patient-reported outcomes. Relative dose intensity of exercise was lower in RT and CT compared with AT (Ps < 0.05). Conclusions: In the context of a smaller than planned sample size, AT and CT significantly improved VO2peak in lung cancer survivors; however, the tolerability-to-benefit ratio was superior for AT and hence may be the preferred modality to target impaired CRF in post-treatment lung cancer survivors.

• Fairman, Ciaran M.; Nilsen, Tormod Skogstad; Newton, Robert U.; Taaffe, Dennis R.; Spry, Nigel & Joseph, David [Show all 13 contributors for this article] (2020). Reporting of Resistance Training Dose, Adherence, and Tolerance in Exercise Oncology. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 52(2), p. 315–322. doi: 10.1249/MSS.0000000000002127. Full text in Research Archive Show summary

  Purpose: While general guidelines (such as CONSORT or Consensus on Exercise Reporting Template) exist to enhance the reporting of exercise interventions in the field of exercise science, there is inadequate detail facilitating the standardized reporting of resistance training adherence in the oncology setting. The purpose of this study was to apply a novel method to report resistance training dose, adherence, and tolerance in patients with cancer. Methods: A total of 47 prostate cancer patients (70.1 ± 8.9 yr, body mass index, 28.6 ± 4.0) with bone metastatic disease completed an exercise program for 12 wk. We assessed traditional metrics of adherence (attendance and loss to follow-up), in addition to novel proposed metrics (exercise-relative dose intensity, dose modification, and exercise interruption). Total training volume in kilograms (repetitions × sets × training load (weight)) was calculated for each patient. Results: Attendance assessed from traditional metrics was 79.5% ± 17.0% and four patients (9%) were lost to follow-up. The prescribed and actual cumulative total dose of resistance training was 139,886 ± 69,150 kg and 112,835 ± 83,499 kg, respectively, with a mean exercise-relative dose intensity of 77.4% ± 16.6% (range: 19.4% –99.4%). Resistance training was missed (1–2 consecutive sessions) or interrupted (missed ≥3 consecutive sessions) in 41 (87%) and 24 (51%) participants, respectively. Training dose was modified (reduction in sets, repetitions, or weight) in 40 (85%) of patients. Importantly, using attendance as a traditional metric of adherence, these sessions would have all counted as adherence to the protocol. Conclusions: Traditional reporting metrics of resistance training in exercise oncology may overestimate exercise adherence. Our proposed metrics to capture resistance training dose, adherence, and tolerance may have important applications for future studies and clinical practice.

• Scott, Jessica M; Li, Nan; Liu, Qi; Yasui, Yutaka; Leisenring, Wendy & Nathan, Paul C [Show all 15 contributors for this article] (2018). Association of Exercise with Mortality in Adult Survivors of Childhood Cancer. JAMA Oncology. ISSN 2374-2437. 4(10), p. 1352–1358. doi: 10.1001/jamaoncol.2018.2254. Show summary

  Importance: Adult survivors of childhood cancer are at excess risk for mortality compared with the general population. Whether exercise attenuates this risk is not known. Objective: To examine the association between vigorous exercise and change in exercise with mortality in adult survivors of childhood cancer. Design, Setting, and Participants: Multicenter cohort analysis among 15 450 adult cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970 and 1999 enrolled in the Childhood Cancer Survivor Study, with follow-up through December 31, 2013. Exposures: Self-reported vigorous exercise in metabolic equivalent task (MET) hours per week. The association between vigorous exercise and change in vigorous exercise and cause-specific mortality was assessed using multivariable piecewise exponential regression analysis to estimate rate ratios. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary end points were cause-specific mortality (recurrence/progression of primary malignant neoplasm and health-related mortality). Outcomes were assessed via the National Death Index. Results: The 15 450 survivors had a median age at interview of 25.9 years (interquartile range [IQR], 9.5 years) and were 52.8% male. During a median follow-up of 9.6 years (IQR, 15.5 years), 1063 deaths (811 health-related, 120 recurrence/progression of primary cancer, 132 external/unknown causes) were documented. At 15 years, the cumulative incidence of all-cause mortality was 11.7% (95% CI, 10.6%-12.8%) for those who exercised 0 MET-h/wk, 8.6% (95% CI, 7.4%-9.7%) for 3 to 6 MET-h/wk, 7.4% (95% CI, 6.2%-8.6%) for 9 to 12 MET-h/wk, and 8.0% (95% CI, 6.5%-9.5%) for 15 to 21 MET-h/wk (P < .001). There was a significant inverse association across quartiles of exercise and all-cause mortality after adjusting for chronic health conditions and treatment exposures (P = .02 for trend). Among a subset of 5689 survivors, increased exercise (mean [SD], 7.9 [4.4] MET-h/wk) over an 8-year period was associated with a 40% reduction in all-cause mortality rate compared with maintenance of low exercise (rate ratio, 0.60; 95% CI, 0.44-0.82; P = .001). Conclusions and Relevance: Vigorous exercise in early adulthood and increased exercise over 8 years was associated with lower risk of mortality in adult survivors of childhood cancer.

• Nilsen, Tormod Skogstad; Scott, Jessica M; Michalski, Meghan; Capaci, Catherine; Thomas, Samantha M & Herndon, James E [Show all 9 contributors for this article] (2018). Novel Methods for Reporting of Exercise Dose and Adherence: An Exploratory Analysis. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 50(6), p. 1134–1141. doi: 10.1249/MSS.0000000000001545. Full text in Research Archive Show summary

  Purpose: The purpose of this study was to explore whether methods adapted from oncology pharmacological trials have utility in reporting adherence (tolerability) of exercise treatment in cancer. Methods: Using a retrospective analysis of a randomized trial, 25 prostate cancer patients received an aerobic training regimen of 72 supervised treadmill walking sessions delivered thrice weekly between 55% and 100% of exercise capacity for 24 consecutive weeks. Treatment adherence (tolerability) was assessed using conventional (lost to follow-up and attendance) and exploratory (e.g., permanent discontinuation, dose modification, and relative dose intensity) outcomes. Results: The mean total cumulative ‘‘planned’’ and ‘‘completed’’ dose was 200.7 T 47.6 and 153.8 T 68.8 METIh, respectively, equating to a mean relative dose intensity of 77% T 24%. Two patients (8%) were lost to follow-up, and mean attendance was 79%. A total of 6 (24%) of 25 patients permanently discontinued aerobic training before week 24. Aerobic training was interrupted (missing Q3 consecutive sessions) or dose reduced in a total of 11 (44%) and 24 (96%) patients, respectively; a total 185 (10%) of 1800 training sessions required dose reduction owing to both health-related (all nonserious) and non–health-related adverse events. Eighteen (72%) patients required at least one session to be terminated early; a total of 59 (3%) sessions required early termination. Conclusions: Novel methods for the conduct and reporting of exercise treatment adherence and tolerability may provide important information beyond conventional metrics in patients with cancer.

• Sedliak, Milan; Zeman, Michal; Buzgó, Gabriel; Cvečka, Ján; Hamar, Dušan & Laczo, Eugen [Show all 15 contributors for this article] (2018). Morphological, molecular and hormonal adaptations to early morning versus afternoon resistance training. Chronobiology International. ISSN 0742-0528. 35(4), p. 450–464. doi: 10.1080/07420528.2017.1411360. Show summary

  It has been clearly established that maximal force and power is lower in the morning compared to noon or afternoon hours. This morning neuromuscular deficit can be diminished by regularly training in the morning hours. However, there is limited and contradictory information upon hypertrophic adaptations to time-of-day-specific resistance training. Moreover, no cellular or molecular mechanisms related to muscle hypertrophy adaptation have been studied with this respect. Therefore, the present study examined effects of the time-of-day-specific resistance training on muscle hypertrophy, phosphorylation of selected proteins, hormonal concentrations and neuromuscular performance. Twenty five previously untrained males were randomly divided into a morning group (n = 11, age 23 ± 2 yrs), afternoon group (n = 7, 24 ± 4 yrs) and control group (n = 7, 24 ± 3 yrs). Both the morning and afternoon group underwent hypertrophy-type of resistance training with 22 training sessions over an 11-week period performed between 07:30–08:30 h and 16:00–17:00 h, respectively. Isometric MVC was tested before and immediately after an acute loading exclusively during their training times before and after the training period. Before acute loadings, resting blood samples were drawn and analysed for plasma testosterone and cortisol. At each testing occasion, muscle biopsies from m. vastus lateralis were obtained before and 60 min after the acute loading. Muscle specimens were analysed for muscle fibre cross-sectional areas (CSA) and for phosphorylated p70S6K, rpS6, p38MAPK, Erk1/2, and eEF2. In addition, the right quadriceps femoris was scanned with MRI before and after the training period. The control group underwent the same testing, except for MRI, between 11:00 h and 13:00 h but did not train. Voluntary muscle strength increased significantly in both the morning and afternoon training group by 16.9% and 15.2 %, respectively. Also muscle hypertrophy occurred by 8.8% and 11.9% (MRI, p < 0.001) and at muscle fibre CSA level by 21% and 18% (p < 0.01) in the morning and afternoon group, respectively. No significant changes were found in controls within these parameters. Both pre- and post-training acute loadings induced a significant (p < 0.001) reduction in muscle strength in all groups, not affected by time of day or training. The post-loading phosphorylation of p70S6Thr421/Ser424 increased independent of the time of day in the pre-training condition, whereas it was significantly increased in the morning group only after the training period (p < 0.05). Phosphorylation of rpS6 and p38MAPK increased acutely both before and after training in a time-of-day independent manner (p < 0.05 at all occasions). Phosphorylation of p70S6Thr389, eEF2 and Erk1/2 did not change at any time point. No statistically significant correlations were found between changes in muscle fibre CSA, MRI and cell signalling data. Resting testosterone was not statistically different among groups at any time point. Resting cortisol declined significantly from pre- to post-training in all three groups (p < 0.05). In conclusion, similar levels of muscle strength and hypertrophy could be achieved regardless of time of the day in previously untrained men. However, at the level of skeletal muscle signalling, the extent of adaptation in some parameters may be time of day dependent.

• Scott, Jessica M; Iyengar, Neil M; Nilsen, Tormod Skogstad; Michalski, Meghan; Thomas, Samantha M & Herndon, James G. [Show all 14 contributors for this article] (2018). Feasibility, safety, and efficacy of aerobic training in pretreated patients with metastatic breast cancer: A randomized controlled trial. Cancer. ISSN 0008-543X. 124(12), p. 2552–2560. doi: 10.1002/cncr.31368.
• Scott, Jessica M; Nilsen, Tormod Skogstad; Gupta, Dipti & Jones, Lee W. (2018). Exercise therapy and cardiovascular toxicity in cancer. Circulation. ISSN 0009-7322. 137(11), p. 1176–1191. doi: 10.1161/CIRCULATIONAHA.117.024671. Show summary

  Cardio-oncology is an emerging discipline focused predominantly on the detection and management of cancer treatment– induced cardiac dysfunction (cardiotoxicity), which predisposes to development of overt heart failure or coronary artery disease. The direct adverse consequences, as well as those secondary to anticancer therapeutics, extend beyond the heart, however, to affect the entire cardiovascular-skeletal muscle axis (ie, whole-organism cardiovascular toxicity). The global nature of impairment creates a strong rationale for treatment strategies that augment or preserve global cardiovascular reserve capacity. In noncancer clinical populations, exercise training is an established therapy to improve cardiovascular reserve capacity, leading to concomitant reductions in cardiovascular morbidity and its attendant symptoms. Here, we overview the tolerability and efficacy of exercise on cardiovascular toxicity in adult patients with cancer. We also propose a conceptual research framework to facilitate personalized risk assessment and the development of targeted exercise prescriptions to optimally prevent or manage cardiovascular toxicity after a cancer diagnosis.

• Scott, Jessica M; Zabor, Emily C; Schwitzer, Emily; Koelwyn, Graeme J; Adams, Scott C & Nilsen, Tormod Skogstad [Show all 11 contributors for this article] (2018). Efficacy of exercise therapy on cardiorespiratory fitness in patients with cancer: A systematic review and meta-analysis. Journal of Clinical Oncology. ISSN 0732-183X. 36(22), p. 2297–2304. doi: 10.1200/JCO.2017.77.5809. Show summary

  Purpose: To evaluate the effects of exercise therapy on cardiorespiratory fitness (CRF) in randomized controlled trials (RCTs) among patients with adult-onset cancer. Secondary objectives were to evaluate treatment effect modifiers, safety, and fidelity. Methods: A systematic search of PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library was conducted to identify RCTs that compared exercise therapy to a nonexercise control group. The primary end point was change in CRF as evaluated by peak oxygen consumption (VO2peak; in mL O2 × kg−1 × min−1) from baseline to postintervention. Subgroup analyses evaluated whether treatment effects differed as a function of exercise prescription (ie, modality, schedule, length, supervision), study characteristics (ie, intervention timing, primary cancer site), and publication year. Safety was defined as report of any adverse event (AE); fidelity was evaluated by rates of attendance, adherence, and loss to follow-up. Results: Forty-eight unique RCTs that represented 3,632 patients (mean standard deviation age, 55 ± 7.5 years; 68% women); 1,990 (55%) and 1,642 (45%) allocated to exercise therapy and control/usual care groups, respectively, were evaluated. Exercise therapy was associated with a significant increase in CRF (+2.80 mL O2 × kg−1 × min−1) compared with no change (+0.02 mL O2 × kg−1 × min−1) in the control group (weighted mean differences, +2.13 mL O2 × kg−1 × min−1; 95% CI, 1.58 to 2.67; I2, 20.6; P < .001). No statistical significant differences were observed on the basis of any treatment effect modifiers. Thirty trials (63%) monitored AEs; a total of 44 AEs were reported. The mean standard deviation loss to follow-up, attendance, and adherence rates were 11% ± 13%, 84% ± 12%, and 88% ± 32%, respectively. Conclusion: Exercise therapy is an effective adjunctive therapy to improve CRF in patients with cancer. Our findings support the recommendation of exercise therapy for patients with adult-onset cancer.

• Nilsen, Tormod Skogstad; Thorsen, Lene; Kirkegaard, Camilla; Ugelstad, Ingrid; Fosså, Sophie Dorothea & Raastad, Truls (2016). The effect of strength training on muscle cellular stress in prostate cancer patients on ADT. Endocrine Connections. ISSN 2049-3614. 5(2), p. 74–82. doi: 10.1530/EC-15-0120. Show summary

  Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with several side effects, including loss of muscle mass. Muscle atrophy is associated with reduced mitochondrial function and increased muscle cellular stress that may be counteracted by strength training. Thus, the aim of this study was to investigate the effect of strength training on mitochondrial proteins and indicators of muscle cellular stress in PCa patients on ADT. Methods: Men diagnosed with locally advanced PCa receiving ADT were randomised to a strength training group (STG) (n=16) or a control group (CG) (n=15) for 16 weeks. Muscle biopsies were collected pre- and post-intervention from the vastus lateralis muscle, and analysed for mitochondrial proteins (citrate synthase, cytochrome c oxidase subunit IV (COXIV), HSP60) and indicators of muscle cellular stress (heat shock protein (HSP) 70, alpha B-crystallin, HSP27, free ubiquitin, and total ubiquitinated proteins) using Western blot and ELISA. Results: No significant intervention effects were observed in any of the mitochondrial proteins or indicators of muscle cellular stress. However, within-group analysis revealed that the level of HSP70 was reduced in the STG and a tendency towards a reduction in citrate synthase levels was observed in the CG. Levels of total ubiquitinated proteins were unchanged in both groups. Conclusion: Although reduced HSP70 levels indicated reduced muscle cellular stress in the STG, the lack of an intervention effect precluded any clear conclusions.

• Nilsen, Tormod Skogstad; Thorsen, Lene; Fosså, Sophie Dorothea; Wiig, Martin; Kirkegaard, Camilla & Skovlund, Eva [Show all 8 contributors for this article] (2016). Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy. Scandinavian Journal of Medicine & Science in Sports. ISSN 0905-7188. 26(9), p. 1026–1035. doi: 10.1111/sms.12543. Show summary

  Androgen deprivation therapy (ADT) improves lifeexpectancy in prostate cancer (PCa) patients, but is asso-ciated with adverse effects on muscle mass. Here, weinvestigated the effects of strength training during ADTon muscle fiber cross-sectional area (CSA) and regulatorsof muscle mass. PCa patients on ADT were randomizedto 16 weeks of strength training (STG) (n = 12) or acontrol group (CG; n = 11). Muscle biopsies wereobtained from m. vastus lateralis and analyzed by immu-nohistochemistry and western blot. Muscle fiber CSAincreased with strength training (898 μm2, P = 0.04), withthe only significant increase observed in type II fibers(1076 μm2, P = 0.03). There was a trend toward a differ-ence in mean change between groups myonuclei number(0.33 nuclei/fiber, P = 0.06), with the only significantincrease observed in type I fibers, which decreased themyonuclear domain size of type I fibers (P = 0.05). Satel-lite cell numbers and the content of androgen receptorand myostatin remained unchanged. Sixteen weeks ofstrength training during ADT increased type II fiber CSAand reduced myonuclear domain in type I fibers in PCapatients. The increased number of satellite cells normallyseen following strength training was not observed.

• Nilsen, Tormod Skogstad; Raastad, Truls; Skovlund, Eva; Courneya, Kerry S.; Langberg, Carl W. & Lilleby, Wolfgang [Show all 8 contributors for this article] (2015). Effects of strength training on body composition, physical functioning, and quality of life in prostate cancer patients during androgen deprivation therapy. Acta Oncologica. ISSN 0284-186X. 54(10), p. 1805–1813. doi: 10.3109/0284186X.2015.1037008.
• Hanssen, Knut Egil; Kvamme, Nils Helge; Nilsen, Tormod Skogstad; Rønnestad, Bent; Ambjørnsen, Inger Karine & Norheim, Frode [Show all 10 contributors for this article] (2013). The effect of strength training volume on satellite cells, myogenic regulatory factors, and growth factors. Scandinavian Journal of Medicine & Science in Sports. ISSN 0905-7188. 23(6), p. 728–739. doi: 10.1111/j.1600-0838.2012.01452.x.
• Sedliak, Milan; Zeman, Michal; Buzgó, Gabriel; Cvečka, Ján; Hamar, Dušan & Laczo, Eugen [Show all 14 contributors for this article] (2013). Effects of time of day on resistance exercise-induced anabolic signaling in skeletal muscle. Biological rhythm research. ISSN 0929-1016. 44(5), p. 756–770. doi: 10.1080/09291016.2012.740314.
• Wernbom, Mathias; Apro, William; Paulsen, Gøran; Nilsen, Tormod Skogstad; Blomstrand, Eva & Raastad, Truls (2013). Acute low‑load resistance exercise with and without blood flow restriction increased protein signalling and number of satellite cells in human skeletal muscle. European Journal of Applied Physiology. ISSN 1439-6319. 113(12), p. 2953–2965. doi: 10.1007/s00421-013-2733-5. Show summary

  Purpose: To investigate hypertrophic signalling after a single bout of low-load resistance exercise with and without blood flow restriction (BFR). Methods: Seven subjects performed unilateral knee extensions at 30 % of their one repetition maximum. The subjects performed five sets to failure with BFR on one leg, and then repeated the same amount of work with the other leg without BFR. Biopsies were obtained from m. vastus lateralis before and 1, 24 and 48 h after exercise. Results: At 1-h post-exercise, phosphorylation of p70S6KThr389 and p38MAPKThr180/Tyr182 was elevated in the BFR leg, but not in the free-flow leg. Phospho-p70S6KThr389 was elevated three- to fourfold in both legs at 24-h post-exercise, but back to baseline at 48 h. The number of visible satellite cells (SCs) per muscle fibre was increased for all post-exercise time points and in both legs (33–53 %). The proportion of SCs with cytoplasmic extensions was elevated at 1-h post in the BFR leg and the number of SCs positive for myogenin and/or MyoD was increased at 1- and 24-h post-exercise for both legs combined. Conclusion: Acute low-load resistance exercise with BFR resulted in early (1 h) and late (24 h) enhancement of phospho-p70S6KThr389, an early response of p38MAPK, and an increased number of SCs per muscle fibre. Enhanced phospho-p70S6KThr389 at 24-h post-exercise and increases in SC numbers were seen also in the free-flow leg. Implications of these findings for the hypertrophic effects of fatiguing low-load resistance exercise with and without BFR are discussed.

• Wernbom, Mathias; Paulsen, Gøran; Nilsen, Tormod Skogstad; Hisdal, Jonny & Raastad, Truls (2012). Contractile function and sarcolemmal permeability after acute low-load resistance exercise with blood flow restriction. European Journal of Applied Physiology. ISSN 1439-6319. 112(6), p. 2051–2063. doi: 10.1007/s00421-011-2172-0. Show summary

  Conflicting findings have been reported regarding muscle damage with low-intensity resistance exercise with blood flow restriction (BFR) by pressure cuffs. This study investigated muscle function and muscle fibre morphology after a single bout of low-intensity resistance exercise with and without BFR. Twelve physically active subjects performed unilateral knee extensions at 30% of their one repetition maximum (1RM), with partial BFR on one leg and the other leg without occlusion. With the BFR leg, five sets were performed to concentric torque failure, and the free-flow leg repeated the exact same number of repetitions and sets. Biopsies were obtained from vastus lateralis before and 1, 24 and 48 h after exercise. Maximum isometric torque (MVC) and resting tension were measured before and after exercise and at 4, 24, 48, 72, 96 and 168 h post-exercise. The results demonstrated significant decrements in MVC (lasting ≥48 h) and delayed onset muscle soreness in both legs, and increased resting tension for the occluded leg both acutely and at 24 h post-exercise. The percentage of muscle fibres showing elevated intracellular staining of the plasma protein tetranectin, a marker for sarcolemmal permeability, was significantly increased from 9% before exercise to 27–38% at 1, 24 and 48 h post-exercise for the BFR leg. The changes in the free-flow leg were significant only at 24 h (19%). We conclude that an acute bout of low-load resistance exercise with BFR resulted in changes suggesting muscle damage, which may have implications both for safety aspects and for the training stimulus with BFR exercise.

• Thorsen, Lene; Nilsen, Tormod Skogstad; Raastad, Truls; Courneya, Kerry S.; Skovlund, Eva & Fosså, Sophie Dorothea (2012). A randomized controlled trial on the effectiveness of strength training on clinical and muscle cellular outcomes in patients with prostate cancer during androgen deprivation therapy: rationale and design. BMC Cancer. ISSN 1471-2407. 12. doi: 10.1186/1471-2407-12-123. Show summary

  Background: Studies indicate that strength training has beneficial effects on clinical health outcomes in prostate cancer patients during androgen deprivation therapy. However, randomized controlled trials are needed to scientifically determine the effectiveness of strength training on the muscle cell level. Furthermore, close examination of the feasibility of a high-load strength training program is warranted. The Physical Exercise and Prostate Cancer (PEPC) trial is designed to determine the effectiveness of strength training on clinical and muscle cellular outcomes in non-metastatic prostate cancer patients after high-dose radiotherapy and during ongoing androgen deprivation therapy. Methods/design: Patients receiving androgen deprivation therapy for 9-36 months combined with external high-dose radiotherapy for locally advanced prostate cancer are randomized to an exercise intervention group that receives a 16 week high-load strength training program or a control group that is encouraged to maintain their habitual activity level. In both arms, androgen deprivation therapy is continued until the end of the intervention period. Clinical outcomes are body composition (lean body mass, bone mineral density and fat mass) measured by Dual-energy X-ray Absorptiometry, serological outcomes, physical functioning (muscle strength and cardio-respiratory fitness) assessed with physical tests and psycho-social functioning (mental health, fatigue and health-related quality of life) assessed by questionnaires. Muscle cellular outcomes are a) muscle fiber size b) regulators of muscle fiber size (number of myonuclei per muscle fiber, number of satellite cells per muscle fiber, number of satellite cells and myonuclei positive for androgen receptors and proteins involved in muscle protein degradation and muscle hypertrophy) and c) regulators of muscle fiber function such as proteins involved in cellular stress and mitochondrial function. Muscle cellular outcomes are measured on muscle cross sections and muscle homogenate from muscle biopsies obtained from muscle vastus lateralis. Discussion: The findings from the PEPC trial will provide new knowledge on the effects of high-load strength training on clinical and muscle cellular outcomes in prostate cancer patients during androgen deprivation therapy.

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• Nilsen, Tormod Skogstad; Sæter, Mali; Sarvari, Sebastian; Reinertsen, Kristin Valborg; Johansen, Sara Hassing & Edvardsen, Elisabeth Rustad [Show all 17 contributors for this article] (2023). Effects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial. JMIR Research Protocols. ISSN 1929-0748. 12. doi: 10.2196/45244. Full text in Research Archive
• Wernbom, Mathias; Paulsen, Gøran; Nilsen, Tormod Skogstad; Hisdal, Jonny & Raastad, Truls (2012). Sarcolemmal permeability and muscle damage as hypertrophic stimuli in blood flow restricted resistance exercise (Reply to Loenneke and Abe). European Journal of Applied Physiology. ISSN 1439-6319. 112(9), p. 3447–3449. doi: 10.1007/s00421-012-2309-9.
• Raastad, Truls; Wernbom, M.; Paulsen, Gøran; Nilsen, Tormod S & Koskinen, Satu (2008). Neuromuscular fatigue, cellular stress and recovery after low load resistance exercise with or without vascular occlusion.

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