Suppression of colorectal cancer by ketogenic diet and beta-hydroxybutyrate
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ABSTRACT:
PROVIDER: PRJNA808081 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-02-22 | GSE196965 | GEO
Project description:Rationale: Sepsis patients suffer from severe metabolic and immunologic dysfunction that may be amplified by standard carbohydrate-based nutritional regimes. We therefore hypothesize that a ketogenic diet improves sepsis treatment. Objectives: We investigated the safety and feasibility of a ketogenic diet in sepsis patients. Methods: We conducted a monocentric open-labeled randomized controlled trial (DRKS00017710) enrolling adult sepsis patients randomly assigned to either ketogenic or standard high-carbohydrate diet for 14 days with follow-up until day 30. The primary outcome measure was β-hydroxybutyrate serum concentration on day 14. Secondary outcomes included safety, clinical and immunological changes. Measurements and Main Results: 40 critically ill septic patients were assigned to the study groups. Increase in β-hydroxybutyrate concentrations from baseline to day 14 was markedly greater under ketogenic diet (1.2 ±0.9) compared to controls (-0.3 ±0.4); estimated mean difference 1.4 (95%-CI 1.0-1.8; p<0.0001). During ketogenic diet, no patient required insulin treatment beyond day 4, whereas 35% to 60% of control patients did (p=0.0095). Metabolic side effects were not observed under ketogenic diet. Ventilation-free (IRR 1.7; 95%-CI: 1.5 to 2.1; p<0.0001), vasopressor-free (IRR 1.7; 95%-CI: 1.5 to 2.0; p<0.0001), dialysis-free (IRR 1.5; 95%-CI: 1.3 to 1.8; p<0.0001), and ICU-free days (IRR 1.7; 95%-CI: 1.4 to 2.1; p<0.0001) significantly increased in patients under ketogenic diet. There was no difference in 30-day mortality. Analyses indicated favorable changes towards immune homeostasis. Conclusions: Ketogenic diet is a feasible and safe nutritional regimen in septic patients promoting recovery from sepsis-related organ dysfunction and could become a new tool in modern treatment concepts.
2024-06-13 | PXD046061 | Pride
Project description:Prostate cancer is the second leading cause of cancer deaths in men in the US. In the past decade, immune checkpoint blockade (ICB) drugs targeting programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) have revolutionized the field of cancer therapeutics, but the objective response rate in prostate cancers is in the low single digits. A major complicating issue is that immunotherapies can have significant adverse effects, so there is a clinical need for novel combinatorial strategies that do not involve additional or compounding adverse effects. We developed a model system of advanced prostate cancer that has acquired resistance to ICB therapy. The PD-1 resistant sublines showed strong downregulation of the mouse major histocompatibility complex (MHC-I), which was reversed by treating cells with either the pan-histone deacetylase (HDAC) inhibitor Vorinostat or β-hydroxybutyrate. When mice bearing these ICB resistant tumor are treated with either Vorinostat, with a cyclical ketogenic diet (CKD), or with a 1,3-butanediol diet (BD), tumors are resensitized to ICB therapy. We analyzed changes in the tumor immune microenvironment and showed that this effect is driven by a shift in monocyte differentiation, changing from M2 polarized immunosuppressive macrophages into iNOS+ dendritic cells instead. This differentiation is dependent on an ICB-induced increase in CD40L+ CD8+ T-cells in the tumor immune microenvironment. Our results indicate a novel mechanism in which a ketogenic diet can be used to increase therapeutic efficacy of ICB therapy.
2024-02-13 | GSE206561 | GEO
Project description:Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility. We previously showed that an agent that promotes chromatin opening, the histone deacetylase inhibitor (HDACi) AR-42, ameliorates the deficiency of adult neurogenesis in the granule cell layer of the dentate gyrus, and rescues hippocampal memory defects in a mouse model of Kabuki syndrome (Kmt2d+/βGeo). Unlike a drug, a dietary intervention could be quickly transitioned to the clinic. Therefore, we have explored whether treatment with a ketogenic diet could lead to a similar rescue through increased amounts of beta-hydroxybutyrate, an endogenous HDACi. Here, we report that a ketogenic diet in Kmt2d+/βGeo mice modulates H3ac and H3K4me3 in the granular cell layer, with concomitant rescue of both the neurogenesis defect and hippocampal memory abnormalities seen in Kmt2d+/βGeo mice; similar effects on neurogenesis were observed upon exogenous administration of beta-hydroxybutyrate. These data suggests that dietary modulation of epigenetic modifications through elevation of beta-hydroxybutyrate may provide a feasible strategy to treat the intellectual disability seen in Kabuki syndrome and related disorders. We used microarrays to query global gene expression changes in the hippocampus of wild type and Kmt2d+/βGeo (Kabuki syndrome model) mice on a regular diet to identify specific gene expression abnormalities in the hippocampus of the Kabuki syndrome mouse model.
2016-12-03 | GSE90836 | GEO
Project description:The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model were analyzed. Two-condition experiment, Normal diet-fed rat brain vs. Ketogenic diet-fed rat brain. Duplicate per array
2010-05-19 | E-GEOD-19277 | biostudies-arrayexpress
Project description:Specific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks Keywords: RNA Expression Array Hearts from 12 week-old mice that were maintained on a standard polysacchardide-rich chow until the age of 8 weeks, at which time they were switched to a ketogenic diet (ad libitum) and maintained for 4 additional weeks prior to collection of tissues
2010-06-16 | E-GEOD-21368 | biostudies-arrayexpress
Project description:The aim of this study is to assess the feasibility of beta-hydroxybutyrate (BHB) supplementation in individuals who are undergoing a standard-of-care colonoscopy or flexible sigmoidoscopy.
| 2719536 | ecrin-mdr-crc
Project description:The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model were analyzed.
2009-12-02 | GSE19277 | GEO