Cutaneous exposure to hypoxia does not affect skin perfusion in humans.

$\textbf{Aim:}$ Experiments have indicated that skin perfusion in mice is sensitive to reductions in environmental O$_2$ availability. Specifically, a reduction in skin-surface PO$_2$ attenuates transcutaneous O$_2$ diffusion, and hence epidermal O$_2$ supply. In response, epidermal HIF-1$\alpha$ expression increases and facilitates initial cutaneous vasoconstriction and subsequent nitric oxide-dependent vasodilation. Here, we investigated whether the same mechanism exists in humans. $\textbf{Methods:}$ In a first experiment, eight males rested twice for 8 h in a hypobaric chamber. Once, barometric pressure was reduced by 50%, while systemic oxygenation was preserved by O$_2$-enriched (42%) breathing gas (Hypoxia$_\text{Skin}$), and once barometric pressure and inspired O$_2$ fraction were normal (Control$_1$). In a second experiment, nine males rested for 8 h with both forearms wrapped in plastic bags. O$_2$ was expelled from one bag by nitrogen flushing (Anoxia$_\text{Skin}$), whereas the other bag was flushed with air (Control$_2$). In both experiments, skin blood flux was assessed by laser Doppler on the dorsal forearm, and HIF-1$\alpha$ expression was determined by immunohistochemical staining in forearm skin biopsies. $\textbf{Results:}$ Skin blood flux during Hypoxia$_\text{Skin}$ and Anoxia$_\text{Skin}$ remained similar to the corresponding Control trial ($P$ = 0.67 and $P$ = 0.81). Immunohistochemically stained epidermal HIF-1$\alpha$ was detected on 8.2 ± 6.1 and 5.3 ± 5.7% of the analysed area during Hypoxia$_\text{Skin}$ and Control$_1$ ($P$ = 0.30) and on 2.3 ± 1.8 and 2.4 ± 1.8% during Anoxia$_\text{Skin}$ and Control$_2$ ($P$ = 0.90) respectively. $\textbf{Conclusion:}$ Reductions in skin-surface PO$_2$ do not affect skin perfusion in humans. The unchanged epidermal HIF-1$\alpha$ expression suggests that epidermal O$_2$ homoeostasis was not disturbed by Hypoxia$_\text{Skin}$/Anoxia$_\text{Skin}$, potentially due to compensatory increases in arterial O$_2$ extraction.Gösta Fraenckel Foundatio

Cytotoxic T-cells mediate exercise-induced reductions in tumor growth

Funder: Vetenskapsrådet; FundRef: http://dx.doi.org/10.13039/501100004359Funder: Cancerfonden; FundRef: http://dx.doi.org/10.13039/501100002794Funder: Barncancerfonden; FundRef: http://dx.doi.org/10.13039/501100006313Funder: Svenska Läkaresällskapet; FundRef: http://dx.doi.org/10.13039/501100007687Funder: Cancer Research UK; FundRef: http://dx.doi.org/10.13039/501100000289Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Exercise has a wide range of systemic effects. In animal models, repeated exertion reduces malignant tumor progression, and clinically, exercise can improve outcome for cancer patients. The etiology of the effects of exercise on tumor progression are unclear, as are the cellular actors involved. We show here that in mice, exercise-induced reduction in tumor growth is dependent on CD8+ T cells, and that metabolites produced in skeletal muscle and excreted into plasma at high levels during exertion in both mice and humans enhance the effector profile of CD8+ T-cells. We found that activated murine CD8+ T cells alter their central carbon metabolism in response to exertion in vivo, and that immune cells from trained mice are more potent antitumor effector cells when transferred into tumor-bearing untrained animals. These data demonstrate that CD8+ T cells are metabolically altered by exercise in a manner that acts to improve their antitumoral efficacy

Cytotoxic t-cells mediate exercise-induced reductions in tumor growth

Exercise has a wide range of systemic effects. In animal models, repeated exertion reduces malignant tumor progression, and clinically, exercise can improve outcome for cancer patients. The etiology of the effects of exercise on tumor progression are unclear, as are the cellular actors involved. We show here that in mice, exercise-induced reduction in tumor growth is dependent on CD8+ T cells, and that metabolites produced in skeletal muscle and excreted into plasma at high levels during exertion in both mice and humans enhance the effector profile of CD8 + T-cells. We found that activated murine CD8+ T cells alter their central carbon metabolism in response to exertion in vivo, and that immune cells from trained mice are more potent antitumor effector cells when transferred into tumor-bearing untrained animals. These data demonstrate that CD8+ T cells are metabolically altered by exercise in a manner that acts to improve their antitumoral efficacy

Optitrain : a randomised controlled exercise trial for women with breast cancer undergoing chemotherapy.

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