Aspirin/Folate Prevention of Large Bowel Polyps
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms,Adenomas,Adenoma,Polyps
PROVIDER: 2024912 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Aspirin, is a commonly used non-steroidal anti-inflammatory drug with antipyretic, analgesic, anti-inflammatory, and anti-thrombotic effect. Its antitumoral effect was also demonstrated in several cancer types. In this study our aim was to investigate the genomic effects of ASA in pituitary adenomas using high-throughput profiling approaches and validate our findings by targeted methodologies, using in vitro functional assays. Whole transcriptome profile of RC4-B/C and GH3 pituitary cell lines upon Aspirin treatment was investigated.
2022-06-19 | GSE202934 | GEO
Project description:Periconceptual supplementation of women with folate is considered a great success for public health. Higher folate status, either by supplementation, or via the mandatory fortification of grain products in the United States, has lead to significant reduction in the incidence of neural tube defects. Besides birth defects, folate deficiency has been linked to a variety of morbidities, most notably to increased risk for cancer. However, recent evidence suggests that excess folate may be detrimental - for birth defect incidence or in the progression of cancer. How folate mediates beneficial or detrimental effects is not well understood. It is also unknown what molecular responses are elicited in women taking folate supplements, and thus experience a bolus of folate on top of the status achieved by fortification. To characterize this response, we performed gene expression profiling experiments on uterus tissue of pregnant mice after a preconceptional regimen of supplementation with folinic acid. We suggest that folinic acid supplementation affects expression of genes that contribute to protein synthesis and localization, genes that play a role for mitochondrial biology and oxidative phosphorylation, and genes encoding nucleotide-binding proteins, including protein kinases and GTP-binding intracellular signaling factors. The extent of such a response is strongly modulated by the genetic background. Finally, we suggest that folinic acid supplementation in this paradigm may affect histone methylation status, a potential avenue to mechanisms of gene regulation. Gene expression profiles were generated from uterus tissue. Female mice were either C57BL/6 wildtype, or homozygous for a Folr4 mutation, and received injections of either saline of folininc acid, respectively.
2013-03-31 | E-GEOD-36974 | biostudies-arrayexpress
Project description:Periconceptual supplementation of women with folate is considered a great success for public health. Higher folate status, either by supplementation, or via the mandatory fortification of grain products in the United States, has lead to significant reduction in the incidence of neural tube defects. Besides birth defects, folate deficiency has been linked to a variety of morbidities, most notably to increased risk for cancer. However, recent evidence suggests that excess folate may be detrimental - for birth defect incidence or in the progression of cancer. How folate mediates beneficial or detrimental effects is not well understood. It is also unknown what molecular responses are elicited in women taking folate supplements, and thus experience a bolus of folate on top of the status achieved by fortification. To characterize this response, we performed gene expression profiling experiments on uterus tissue of pregnant mice after a preconceptional regimen of supplementation with folinic acid. We suggest that folinic acid supplementation affects expression of genes that contribute to protein synthesis and localization, genes that play a role for mitochondrial biology and oxidative phosphorylation, and genes encoding nucleotide-binding proteins, including protein kinases and GTP-binding intracellular signaling factors. The extent of such a response is strongly modulated by the genetic background. Finally, we suggest that folinic acid supplementation in this paradigm may affect histone methylation status, a potential avenue to mechanisms of gene regulation.
2013-03-31 | GSE36974 | GEO
Project description:Defects in homocysteine and folate metabolism are associated with increased risks for neural tube and congenital heart defects, cardiovascular disease and stroke, cancers, and neurodegeneration. In many but not all cases, dietary supplementation with folate significantly reduces the severity and incidence of these conditions. Common polymorphisms modulate these metabolic pathways and disease risks, but do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test whether other pathways contribute to disease pathogenesis, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared to the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and translated to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting an interplay between homocysteine and folate metabolism and cholesterol metabolism. Absence of measurable changes in global methylation patterns or amelioration of effects with supplementation with an alternative methyl donor suggest that dietary folate perturbations do not act through large-scale or general changes in methylation. These results suggest that homeostatic responses in cholesterol metabolism contribute to the beneficial effects of dietary folate supplementation. Keywords: time course, stress response, diet, genetic, homeostasis
2008-08-27 | GSE9242 | GEO
Project description:Background & Aims: Previous studies have suggested that dietary folic acid (FA) can protect against certain types of cancers. However, the findings have varied and the mechanisms by which this vitamin exerts chemopreventive effects remain to be clarified. We examined the effects of FA supplementation on DNA methylation, gene expression and gastric dysplasia in a transgenic mouse model that is etiologically and histologically well matched with human gastric cancers. Methods: Hypergastrinemic mice (INS-GAS) infected with Helicobacter felis were studied at multiple stages of gastric dysplasia and early cancer, with FA supplementation initiated both at weaning and later in life. Global DNA methylation was assessed by a methylation-sensitive cytosine incorporation assay, bisulfite pyrosequencing of B1 repetitive elements and immunohistochemistry (IHC) with anti-5-methylcytosine. We also profiled gene expression in the same tissues. Results: We found a decrease in global DNA methylation and tissue folate and an increase in serum homocysteine with progression of gastric dysplasia. FA supplementation prevented this loss of global DNA methylation and markedly reduced gastric dysplasia and mucosal inflammation. FA protected against the loss of global DNA methylation both in the dysplastic gastric epithelial cells and in gastric stromal myofibroblasts. In addition, FA supplementation had an anti-inflammatory effect, as indicated by expression profiling and IHC for lymphocyte markers. Conclusions: We conclude that FA supplementation is chemopreventive in this model of Helicobacter-associated gastric cancer. The beneficial effect of FA is likely due to its ability to reverse global loss of methylation and suppress inflammation. Study the difference in gene expression between transgenic hypergastrinemic (INS-GAS) mice fed a folate-supplemented diet and a diet with normal folate content. Because folate had a substantial protective effect, we matched the animals not only by folate status but also by dysplasia score (DYS). The degree of dysplasia was scored on a 1-4 scale. True replicates are not included. The first five samples are from folate supplemented animals, and the latter five are from controls on regular chow.
2011-07-20 | E-GEOD-30830 | biostudies-arrayexpress
Project description:Aspirin and Inflammation: Mutations, Genes, Pathways and Prevention
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Project description:Aspirin and Inflammation: Mutations, Genes, Pathways and Prevention
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Project description:Oral aspirin challenge may induce different global CpG methylation patterns between aspirin-exacerbated respiratory disease (AERD) and aspirin-tolerant asthma (ATA), which may affect gene expression several hours later. Therefore, in the present study, we compared global CpG methylation profiles before and after an oral aspirin challenge in patients with asthma. In addition, we compared differences in methylation profiles between AERD and ATA using an Illumina 860K Infinium Methylation EPIC BeadChip array platform, which had greater coverage than in the previous study (26,485 CpGs) to discover new methylated CpGs in PBLs associated with aspirin-induced bronchospasm.
2023-06-27 | GSE235569 | GEO
Project description:Folate is crucial for diverse biological processes including neurogenesis. While folate supplementation during pregnancy is standard for preventing neural tube defects (NTDs), concerns are growing over the potential risks of excessive maternal intake. In this study, we employed spatial transcriptomics and single-nucleus multi-omics techniques to investigate the impact of increased maternal folate intake on offspring brain development. Elevated folate intake broadly affected gene pathways linked to neurogenesis and neuronal axon myelination across multiple brain regions. Furthermore, specific gene expression alterations related to learning and memory processes emerged in thalamic and ventricular regions. Single-nucleus multi-omics analysis revealed that maturing excitatory neurons in dentate gyrus are particularly vulnerable to suboptimal maternal folate intake. Aberrant gene expression and chromatin accessibility changes were primarily centered on pathways governing ribosomal biogenesis, which is critical for synaptic formation. Altogether, our findings provide novel insights into how excessive maternal folate supplementation affects offspring brain development, notably by influencing gene expression and chromatin accessibility.
2024-07-10 | GSE269543 | GEO
Project description:Defects in homocysteine and folate metabolism are associated with increased risks for neural tube and congenital heart defects, cardiovascular disease and stroke, cancers, and neurodegeneration. In many but not all cases, dietary supplementation with folate significantly reduces the severity and incidence of these conditions. Common polymorphisms modulate these metabolic pathways and disease risks, but do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test whether other pathways contribute to disease pathogenesis, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared to the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and translated to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting an interplay between homocysteine and folate metabolism and cholesterol metabolism. Absence of measurable changes in global methylation patterns or amelioration of effects with supplementation with an alternative methyl donor suggest that dietary folate perturbations do not act through large-scale or general changes in methylation. These results suggest that homeostatic responses in cholesterol metabolism contribute to the beneficial effects of dietary folate supplementation. Keywords: time course, stress response, diet, genetic, homeostasis
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