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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. [ABSTRACT FROM AUTHOR]

Introduction A truncated PGC-1 α splice variant ( PGC-1 α4) has been implicated in the regulation of resistance exercise ( RE)-induced muscle hypertrophy, and basal expression levels said to be augmented in response to concurrent aerobic ( AE) and RE training. Aim The current study investigated human muscle truncated and non-truncated PGC-1 α transcripts in response to both acute and chronic RE, and with or without preceding AE ( AE+ RE). Methods Ten men performed 5 weeks of unilateral AE+ RE and RE training. Before (untrained) and after (trained) this intervention, PGC-1 α transcripts were assessed in vastus lateralis muscle biopsies obtained before and 3 h after acute RE, with or without preceding AE. Additionally, samples were collected 72 h after the last exercise bout of the training programme. Results The truncated splice variant increased ( P < 0.05) its expression after acute exercise regardless of mode. However, the expression was greater ( P < 0.05) after AE+ RE than RE. Other PGC-1 α transcripts showed similar response. Truncated transcripts originated from both the alternative and proximal promoter, and AE+ RE increased PGC-1 α expression from both promoter sites. RE induced transcripts from the alternative promoter only. PGC-1 α expressions after acute exercise were comparable across isoforms in both untrained and trained muscle. Steady-state levels of isoforms were unchanged after 5-week training ( P > 0.05). Exercise-induced expression of PGC-1 α variants did not correlate with changes in muscle size or strength ( P > 0.05). Conclusion Our results do not support the view that truncated PGC-1 α coordinates exercise-induced hypertrophy in human skeletal muscle. Rather, all PGC-1 α isoforms appear to be regulated transiently in response to acute exercise and regardless of mode. [ABSTRACT FROM AUTHOR]

The present study investigated whether exercise induces the expression of PGC-1α splice variants in human skeletal muscle and the possible influence of metabolic perturbation on this response. The subjects exercised one leg for 45 min with restricted blood flow (R-leg), followed by 45 min of exercise using the other leg at the same absolute workload but with normal blood flow (NR-leg). This ischemic model (R-leg) has been shown previously to induce a greater metabolic perturbation and enhance the expression of PGC-1α beyond that observed in the NR-leg. Cultured human myotubes were used to test suggested exercise-induced regulatory stimuli of PGC-1α. We showed, for the first time, that transcripts from both the canonical promoter (PGC-1α-a) and the proposed upstream-located promoter (PGC-1α-b) are present in human skeletal muscle. Both transcripts were upregulated after exercise in the R-leg, but the fold change increase of PGC-1α-b was much greater than that of PGC-1a-a. No differences were observed between the two conditions regarding the marker for calcineurin activation, MCIP1, or p38 phosphorylation. AMPK phosphorylation increased to a greater extent in the R-leg, and AICAR stimulation of cultured human myotubes induced the expression of PGC-1α-a and PGC-1α-b. AICAR combined with norepinephrine yielded an additive effect on the PGC-1α-b expression only. Our results indicate clearly that exercise can activate an upstream promoter in humans and support AMPK as a major regulator of transcripts from the canonical PGC-1α promoter and the involvement of β-adrenergic stimulation in combination with AMPK in the regulation of PGC-1α-b. [ABSTRACT FROM AUTHOR]

Eleven subjects performed one-legged exercise four times per week for 5 wk. The subjects exercised one leg for 45 mm with restricted blood flow (R leg), followed by exercise with the other leg at the same absolute workload with unrestricted blood flow (UR leg). mRNA and protein expression were measured in biopsies from the vastus lateralis muscle obtained at rest before the training period, after 10 days, and after 5 wk of training, as well as 120 mm after the first and last exercise bouts. Basal Ang-2 and Tie- 1 mRNA levels increased in both legs with training. The Ang-2-to-Ang- 1 ratio increased to a greater extent in the R leg. The changes in Ang-2 mRNA were followed by similar changes at the protein level. In the R leg, VEGF-A mRNA expression responded transiently after acute exercise both before and after the 5-wk training program. Over the course of the exercise program, there was a concurrent increase in basal VEGF-A protein and VEGFR-2 mRNA in the R leg. Ki-67 mRNA showed a greater increase in the R leg and the protein was localized to the endothelial cells. In summary, the increased translation of VEGF-A is suggested to be caused by the short mRNA burst induced by each exercise bout. The concurrent increase in the Ang-2-to-Ang- 1 ratio and the VEGF-expression combined with the higher level of Ki-67 mRNA in the R leg indicate that changes in these systems are of importance also in nonpathological angiogenic condition such as voluntary exercise in humans. It further establish that hypoxialischemia-related metabolic perturbation is likely to be involved as stimuli in this process in human skeletal muscle. [ABSTRACT FROM AUTHOR]

Aims: Studies from genetically modified animals have been instrumental in highlighting genes and their products involved in the regulation of muscle fibre type and oxidative phenotypes; however, evidence in humans is limited. Our aim was therefore to investigate expression of those genes implicated in the regulation of oxidative fibre phenotypes in humans. Methods: Using quantitative polymerase chain reaction we determined mRNA expression of selected genes in skeletal muscle from three different groups, displaying physiological and pathological variations in muscle fibre type, activity and skeletal muscle metabolism respectively: (i) elite athletes (cyclists), with an increased proportion of type I slow twitch, oxidative fibres, (ii) normally active subjects with an average fibre type distribution, and (iii) spinal cord-injured subjects with a low proportion of type I fibres. Results: Skeletal muscle mRNA expression of calcineurin A α and A β, peroxisome proliferator-activated receptor (PPAR)- α and - δ, and PPAR gamma coactivator (PGC)-1 α and -1 β was determined. Calcineurin A α and calcineurin A β mRNA expression was similar between groups. In contrast, mRNA expression of PPAR α, PPAR δ, PGC-1 α and -1 β was increased in athletes, when compared with normally active subjects. Furthermore, mRNA expression of PPAR α, PPAR δ, PGC-1 α and -1 β was reduced in spinal cord-injured subjects. Additionally, PPAR α, PPAR δ and PGC-1 α correlated with oxidative fibre content. Conclusion: Skeletal muscle mRNA expression of PPAR α, PPAR δ, PGC-1 α and -1 β reflects differences in type I muscle fibres associated with pathologically and physiologically induced skeletal muscle fibre type differences. [ABSTRACT FROM AUTHOR]