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Short term Water-only Fasting prior to chemotherapy Trial (SWiFT)

ABSTRACT: Background and study aims We would like to find out whether it is possible for people to follow a short-term fast before their chemotherapy. Fasting involves avoiding all food for a set amount of time. Some research suggests that fasting might help to protect our cells during chemotherapy, by switching them from a state of growth and development to a state of maintenance and repair. However, we don’t know if fasting is of benefit. Ultimately, we would like to find out whether fasting before chemotherapy can help to reduce its side effects. In order to answer this question, we first need to find out whether it is possible for people to fast before their chemotherapy. This has been tested in some previous studies but not in people receiving chemotherapy for colorectal cancer. So, we are inviting 30 people to take part in a trial that will compare a 36-hour fast to usual diet before chemotherapy. Who can participate? Adults with stage 2 or 3 colorectal cancer who are due to receive capecitabine oxaliplatin (CAPOX) chemotherapy. What does the study involve? Participants will be randomly allocated to either the intervention group or the control group. The intervention group will spend 36 hours prior to their chemotherapy fasting and drinking water-only. Each chemotherapy cycle will be 21 days long and participants in this group will fast before each of their first 3 cycles of chemotherapy. The control group will receive the usual advice prior to their first cycle of chemotherapy, including written or verbal information on their diet and the effects of chemotherapy on appetite.

DISEASE(S): Colorectal Cancer

PROVIDER: 2412952 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Expression profile of PBMCs from human healthy volunteers in 36-hours-fasting conditions versus basal conditions (12-hours-fasting).

Project description:Short-term fasting elicits beneficial effects in mice and humans, including protection from chemotherapy toxicity, but the involved mechanisms are not well understood. We collected blood samples from healthy human volunteers and mice before and after 36 or 24 hours of fasting, respectively, to measure fatty acid composition of erythrocyte membranes, circulating miRNAs, and RNA expression at PBMCs. In both mice and humans, fasting affected the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane. Also, fasting significantly reduced the expression at PBMCs of insulin signaling-related genes, including the SREBP lipid-metabolizing pathway, in correlation with changes in membrane fatty acids. We tested the relevance of these fatty acid homeostasis parameters using a complete platform to monitor chemotherapy toxicity in mice. When fasted for 24 hours before and 24 hours after administration of the chemotherapeutic drug oxaliplatin, mice showed a strong protection from kidney, liver, heart and bone marrow toxicity. Importantly, the newly discovered fasting parameters defined two clearly separated groups of individuals that accurately predicted a differential protection from chemotherapy toxicity. Our results reveal a novel mechanism of fasting associated with fatty acids homeostasis, and provide novel biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity.

2022-06-12 | GSE173241 | GEO

Fasting does not promote a metabolic memory effect in mouse liver

Project description:Background: Tissues may respond differently to a particular stimulus if they have been previously exposed to that same stimulus. Here we tested the hypothesis that a strong metabolic stimulus may elicit a memory effect in the liver. To that end, we examined whether prior fasting, which profoundly impacts hepatic nutrient metabolism, may influence the metabolic response to a subsequent fast. Methods: 24 mice were exposed to two 16h fasts over a 8 week period, each time being allowed to return to their normal growth trajectory, while another group of 24 mice was fed ad libitum throughout. Of each group, half of the mice were euthanized after a 16h fast, whereas the other half was euthanized in the ab libitum fed state. Results: An acute fast significantly increased plasma NEFA, glycerol, β-hydroxybutyrate and liver triglycerides, and decreased plasma glucose, triglycerides, and liver glycogen levels. An acute fast also markedly changed the liver transcriptome, upregulating genes involved in fatty acid catabolism and downregulating genes involved in cholesterol synthesis, and majorly impacted the liver metabolome, reducing the levels of numerous amino acids, glycolysis and TCA cycle intermediates, and nucleotides. However, none of the these changes were significantly influenced by prior fasting. The limited number of genes that were significantly altered by prior fasting are likely false positives. Finally, no significant effect was observed of prior fasting on glucose tolerance. Conclusion: We conclude that previous exposure to fasting in mice does not influence the metabolic response to a subsequent fast, thus arguing against the concept of metabolic memory in the hepatic response to fasting.

2020-10-20 | GSE156254 | GEO

Transcriptomic signature of fasting in murine adipose tissue

Project description:Little is known about the impact of fasting on gene regulation in human adipose tissue. Accordingly, the objective of this study was to investigate the effects of fasting on adipose tissue gene expression in humans. To that end, subcutaneous adipose tissue biopsies were collected from volunteers 2h and 26h after consumption of a standardized meal. For comparison, epididymal adipose tissue was collected from C57Bl/6J mice after a 16h fast and in the ab-libitum fed state. Transcriptome analysis was carried out using Affymetrix microarrays. We found that, 1) fasting downregulated numerous metabolic pathways in human adipose tissue, including triglyceride and fatty acid synthesis, glycolysis and glycogen synthesis, TCA cycle, oxidative phosphorylation, mitochondrial translation, and insulin signaling; 2) fasting downregulated genes involved in proteasomal degradation in human adipose tissue; 3) fasting had much less pronounced effects on the adipose tissue transcriptome in humans than mi ce; 4) although major overlap in fasting-induced gene regulation was observed between human and mouse adipose tissue, many genes were differentially regulated in the two species, including genes involved in insulin signaling (PRKAG2, PFKFB3), PPAR signaling (PPARG, ACSL1, HMGCS2, SLC22A5, ACOT1), glycogen metabolism (PCK1, PYGB), and lipid droplets (PLIN1, PNPLA2, CIDEA, CIDEC). In conclusion, although numerous genes and pathways are regulated similarly by fasting in human and mouse adipose tissue, many genes show very distinct responses to fasting in humans and mice. Our data provide a useful resource to study adipose tissue function during fasting.

2020-09-01 | GSE154611 | GEO

Transcriptomic signature of fasting in human adipose tissue

2020-09-01 | GSE154610 | GEO

Prospective randomized control trial of fast track surgery on postoperative gastrointestinal tumor

Project description:Interventions: Regular group:Same as regular group.;Water before operation group:No lavation and nasogastric intubation. Oral intake of water 250ml 1.5-2 hours before operation; others are the same as regular group. ;Fast track group:No lavation and nasogastric intubation and oral intake of water 250ml within 1.5-2 hours before operation; place nasojejunic feeding tube during operation; other approaches same as regular group. ;Regular group:Preoperative fasting 6-8 hours, nasogastric intubation before operation; early ambulation in 24-48 hours, removing catheter at 48 hour after operation and control blood sugar under 12 mmol/l.;Glucose before operation:No lavation and nasogastric intubation. Oral 5% glucose solution 250ml within 1.5-2 hours before operation; other treatment same as regular group. ;Fast track group:Place nasojejunic feeding tube in patients with gastric cancer during operation and others are the same as regular group. Primary outcome(s): Length of hospital stay after operation Study Design: Randomized parallel controlled trial

| 2672681 | ecrin-mdr-crc

Gene expression profile (RNAseq) in atrophic gastrocnemius muscle of wild type, ZEB1 and ZEB2 knock out mice

Project description:Purpose: Characterize the gene expression profile of gastrocnemius muscle in wild type, ZEB1 and ZEB2 knock out mice subjected to 36 hours of fasting Methods: RNA sequencing of RNA from total gastrocnemius muscle after 36h of fasting from the three genotypes used in this study: ZEB1-control, ZEB1-KO, ZEB2-control, ZEB2-KO. Males and females were used from the four genotype (ZEB1flx/flx, ZEB1flx/flx;HSACre, ZEB2flx/flx, ZEB2flx/flx;HSACre). Results: Knockout of ZEB1 or ZEB2 results in differential gene expression in atrophic gastrocnemius muscle Conclusions: Comparison of wild type, ZEB1 and ZEB2 KO muscles displayed differential gene expression profiles after fasting

2023-09-28 | GSE179619 | GEO

The effects of moderate weight gain in adipose tissue gene expression in metabolically-normal (MNO) and metabolically-abnormal (MAO) subjects

Project description:Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. We tested the hypothesis that MNO, but not MAO, people are protected from the adverse metabolic effects of weight gain. To this end, global transcriptional profile in adipose tissue before and after weight gain was evaluated by microarray analyses. We collected subcutaneous adipose tissue samples from MNO (n=11) and MAO (n=7) subjects before and after moderate (~6%) weight gain (total 36 samples). We evaluated the effects of weight gain on adipose tissue gene expression in both MNO and MNO subjects.We used the GeneChip Human Gene 1.0 ST array (Affymetrix, Santa Clara, CA, USA).

2015-01-09 | E-GEOD-62832 | biostudies-arrayexpress

Post-fast refeeding enhances intestinal stem cell mediated regeneration and tumorigenesis through mTORC1 signaling and polyamine

Project description:For more than a century, fasting regimens have been shown to improve health, lifespan, and tissue regeneration in diverse model organisms and humans. However, important questions remain regarding how fasting and refeeding cycles stimulate stem cell output and how this influences their role in early tumor formation. Here, we demonstrate that in the mammalian intestine, a short 24-hour fast followed by a 24-hour refeeding period (that is, post-fast refeeding) and not fasting itself elevates the stemness program and regenerative capacity of Lgr5+ intestinal stem cells (ISCs). Furthermore, loss of the tumor suppressor APC in post-fast refed ISCs significantly boosts tumor incidence in the small intestine and colon compared to those in the fasted or ad libitum fed states. Mechanistically, robust induction of insulin-PI3K-mTORC1 signaling as well as elevated intestinal polyamines level increase protein synthesis in post-fast refed ISCs to mediate these changes as inhibition of mTORC1, polyamine, or protein synthesis abrogate the regenerative or tumorigenic effects of post-fast refeeding. Thus, our data indicate that post-fast refeeding leads to a burst not only in stem cell-driven regeneration but also in tumorigenicity and that careful consideration be given to fast-refeeding cycles when planning diet-based strategies.

2023-08-08 | GSE192482 | GEO

Transcriptome profile of ENDOC-BH1 cells overexpressing TFEB-V5 or controls

Project description:To analyse gene expression differences between the TFEB overexpressing cells vs. Controls, under growing conditions (GC) vs. Fasting conditions (Fast).

2023-07-31 | GSE154059 | GEO

Transcriptome profile of INS-1E Ctrl and hTFEB OE cells

Project description:To analyse gene expression differences between the human TFEB overexpressing cells vs. Controls, under growing conditions (GC) vs. Fasting conditions (Fast)

2023-07-31 | GSE155221 | GEO

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