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Exercise inhibits tumor progression and improves the therapeutic efficacy of PD-1 blockade in colorectal cancer preclinical models

ABSTRACT: Exercise inhibits tumor progression and improves the therapeutic efficacy of PD-1 blockade in colorectal cancer preclinical models

PROVIDER: PRJNA722267 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14244176.fastq.gz	Fastqsanger.gz
	SRR14244177.fastq.gz	Fastqsanger.gz
	SRR14244178.fastq.gz	Fastqsanger.gz
	SRR14244179.fastq.gz	Fastqsanger.gz
	SRR14244180.fastq.gz	Fastqsanger.gz

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Exercise inhibits tumor progression and improves the therapeutic efficacy of PD-1 blockade in colorectal cancer preclinical models

Project description:Exercise training (ExT) has shown antitumor effects in many preclinical cancer models. In the present study, we utilize MC38 and CT26 cells, which represent MSI and MSS colorectal carcinomas respectively, to study the effects and mechanisms of ExT alone or in combination with PD-1 based immunotherapy. Using treadmill running and PD-1/PD-L1 blockade, we demonstrated that post-implant exercise training has broad anticancer activities in murine models of CRC. Specifically, in MSI CRC models, ExT induces beneficial metabolic and immunological adaptations, leading to a more significant inhibition in tumors treated with PD-1/PD-L1 blockade, suggesting a genotype-directed combinatory therapy for the subgroup of CRC patients. Moreover, ExT might be a safe and alternative anticancer strategy for cancers resistant to the PD-1 based immunotherapy, such as patients with MSS CRC tumors.

2021-04-16 | GSE172162 | GEO

Exercise-acclimated microbiota improves skeletal muscle metabolism

Project description:Exercise-acclimated microbiota improves skeletal muscle metabolism

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Kaempferol Improves Exercise Performance and Its Potential Mechanism

Project description:Kaempferol Improves Exercise Performance and Its Potential Mechanism

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A microbiome-dependent gut brain pathway regulates motivation for exercise

Project description:Exercise exerts a wide range of beneficial effects for healthy physiology. However, the mechanisms regulating an individual's motivation to engage in physical activity remain incompletely understood. An important factor stimulating the engagement in both competitive and recreational exercise is the motivating pleasure derived from prolonged physical activity, which is triggered by exercise induced neurochemical changes in the brain. Here, we report on the discovery of a gut brain connection in mice that enhances exercise performance by augmenting dopamine signalling during physical activity. We find that microbiome dependent production of endocannabinoid metabolites in the gut stimulates the activity of TRPV1 expressing sensory neurons and thereby elevates dopamine levels in the ventral striatum during exercise. Stimulation of this pathway improves running performance, whereas microbiome depletion, peripheral endocannabinoid receptor inhibition, ablation of spinal afferent neurons or dopamine blockade abrogate exercise capacity. These findings indicate that the rewarding properties of exercise are influenced by gut derived interoceptive circuits and provide a microbiome dependent explanation for interindividual variability in exercise performance. Our study also suggests that interoceptomimetic molecules that stimulate the transmission of gut derived signals to the brain may enhance the motivation for exercise.

2023-03-15 | MSV000091494 | MassIVE

Histamine footprint on the human exercise transcriptome

Project description:Transcriptome wide analysis of the skeletal muscle response to exercise in humans. Subjects performed one 60-min bout of moderate-intensity single-leg knee-extension exercise, and samples were obtained by biopsy of the vastus lateralis muscle before, immediately after, and at 3 hr post-exercise. Eight subjects were control (no drug), and eight received combined H1/H2-histamine receptor blockade prior to exercise.

2016-03-21 | GSE71972 | GEO

Exercise-acclimated microbiota improves skeletal muscle metabolism

Project description:Habitual exercise modulates the composition of the intestinal microbiota. We examined whether transplanting fecal microbiota from trained mice improved skeletal muscle metabolism in high-fat diet-fed mice. The recipient mice that received fecal samples from trained donor mice for 1 week showed elevated levels of metabolic signalings in skeletal muscle. Glucose tolerance was improved by fecal microbiota transplantation after 8 weeks of HFD administration. Intestinal microbiota may mediate exercise-induced metabolic improvement in mice. We performed a microarray analysis to compare the metabolic gene expression profiles in the skeletal muscle from each mouse.

2022-06-30 | GSE201202 | GEO

Kaempferol Improves Exercise Performance and Its Potential Mechanism

Project description:Kaempferol is a natural flavonoid with reported bioactivities, however its effects on exercise performance and muscle metabolism are unclear. This study investigated kaempferol for improving exercise performance and potential underlying mechanism in vivo and in vitro. In vitro, kaempferol promoted glucose uptake, protein synthesis and mitochondrial function along with decreasing oxidative stress in C2C12 myotubes. Moreover, the PI3K-AKT and MAPK signaling pathways were proved be activated with kaempferol by transcriptomic analysis.

2024-02-02 | GSE252790 | GEO

Blockade of High-Fat Diet Phenotypes using Exercise as Prevention versus Treatment

Project description:The increasing consumption of high-fat western foods combined with a lack of exercise is a major contributor to the burden of obesity in humans. Aerobic exercise such as running is known to provide metabolic benefits, but how the over-consumption of a high fat diet (HFD) and exercise interact is not well characterized at the molecular level. Here, we examined the plasma proteome in mice for the effects of aerobic exercise as both a treatment and as a preventative regime for animals on either HFD or a healthy control diet. This analysis detected large changes in the plasma proteome induced by the HFD intervention, such as increased abundance of SERPINA7, ALDOB, APOE, and down-regulation of SERPINA1E, CFD (adipsin), LIFR. Some of these changes were only significantly reverted using aerobic exercise as a preventative measure, but not as a treatment regime. To determine if either the intensity, or duration, of exercise influenced the outcome, we compared high-intensity interval training (HIIT) and endurance running. Endurance running slightly outperformed HIIT exercise, but overall both provided similar reversion in abundance of plasma proteins modulated by the high-fat diet including SERPINA7, APOE, SERPINA1E, and CFD. Finally, we compared the changes induced by over-consumption of HFD to previous data from mice fed an isocaloric high saturated fat (SFA) or polyunsaturated fat (PUFA) diet. This identified several common changes including increased APOC2 and APOE, but also highlighted changes specific for either over-consumption of HFD (ALDOB, SERPINA7, CFD), SFA-based diets (SERPINA1E), or PUFA-based diets (Haptoglobin - Hp). Together, these data highlight the importance of early intervention with exercise to revert HFD-induced phenotypes and suggest some of the molecular mechanisms leading to the changes in the plasma proteome generated by high fat diet consumption in both mice and humans.

2020-11-02 | PXD018561 | Pride

The effects of exercise on gene expression in abdominal subcutaneous adipose tissue

Project description:Exercise improves health and well-being across diverse organ systems, and elucidating mechanisms underlying the beneficial effects of exercise on health can lead to new therapies for disease. We find that exercise training in humans causes profound changes in subcutaneous adipose tissue (scWAT) gene expression, including genes encoding secreted proteins. In addition, we used our previously published microarray dataset derived from scWAT from mice housed in static cages (sedentary controls) or mice housed in cages with running wheels for 11 days. Genes that were significantly changed by exercise training in humans and mice were further selected by annotation for Extracellular Space in Gene Ontology. Of these genes, the most significantly correlated with the total wheel running distance in the trained mice was Tgfb2. We validated that exercise training increased TGFB2 mRNA in scWAT of human subjects using RT-qPCR. This led us to hypothesize that TGF-β2 is an exercise-induced adipokine. To determine the therapeutic potential and mechanism for increased TGF-β2, we investigated mouse models of exercise training and obesity. Our findings indicate that exercise training improves metabolism through inter-organ communication with fat via a TGF-β2 signaling, providing a novel mechanism for counteracting metabolic disease.

2018-11-21 | GSE116801 | GEO

Low-Dose Irradiation of the Gut Improves the Efficacy of PD-L1 Blockade in Metastatic Cancer Patients

Project description:Low-Dose Irradiation of the Gut Improves the Efficacy of PD-L1 Blockade in Metastatic Cancer Patients

| PRJEB85676 | ENA