The aim was to investigate mechanisms contributing to quercetins previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anti-carcinogenic potency. In a 10-day experiment, 40 M quercetin stabilized by 1mM ascorbate reduced Caco-2 differentiation up to 50% (P<0.001). Caco-2 RNA from days 5 and 10, hybridized on HG-U133A2.0 Affymetrix GeneChips, showed 1,743 affected genes on both days (P<0.01). All 14 Caco-2 differentiation-associated genes showed decreased expression (P<0.01), including intestinal alkaline phosphatase that was confirmed technically (qRT-PCR) and functionally (enzyme-activity).
Pathway and single gene analyses of inhibited Caco-2 differentiation by ascorbate-stabilized quercetin suggest enhancement of cellular processes associated with development of colon cancer.
No sample metadata fields
View SamplesCell cycle sensing of oxidative stress in Saccharomyces cerevisiae by oxidation of a specific cysteine residue in the transcription factor Swi6p.
Cell cycle sensing of oxidative stress in Saccharomyces cerevisiae by oxidation of a specific cysteine residue in the transcription factor Swi6p.
Treatment
View SamplesQuercetin has been shown to act as an anti-carcinogen in experimental colorectal cancer (CRC). The aim of the present study was to characterise transcriptome and proteome changes occurring in the distal colon mucosa of rats supplemented with 10 g quercetin/kg diet for 11 weeks. Transcriptome data analysed with Gene Set Enrichment Analysis showed that quercetin significantly downregulated the potentially oncogenic mitogen-activated protein kinase (Mapk) pathway. In addition, quercetin enhanced expression of tumor suppressor genes, including Pten, Tp53 and Msh2, and of cell cycle inhibitors, including Mutyh. Furthermore, dietary quercetin enhanced genes involved in phase I and II metabolism, including Fmo5, Ephx1, Ephx2 and Gpx2. Quercetin increased PPAR target genes, and concomitantly enhanced expression genes in volved in of mitochondrial fatty acid degradation. Proteomics performed in the same samples revealed 33 affected proteins, of which 4 glycolysis enzymes and 3 heatshock proteins were decreased. A proteome-transcriptome comparison showed a low correlation, but both pointed out towards altered energy metabolism.
Transcriptome and proteome profiling of colon mucosa from quercetin fed F344 rats point to tumor preventive mechanisms, increased mitochondrial fatty acid degradation and decreased glycolysis.
No sample metadata fields
View SamplesMutations in CCAAT/enhancer binding protein alpha (CEBPA) are seen in 5-14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPA mutations simultaneously carry two mutations (CEBPAdouble-mut), usually biallelic, while single heterozygous mutations (CEBPAsingle-mut) are less frequently seen. Using denaturing high performance liquid chromatography and nucleotide sequencing we identified among a cohort of 598 newly diagnosed AMLs a subset of 41 CEBPA mutant cases, i.e. 28 CEBPAdouble-mut and 13 CEBPAsingle-mut cases. CEBPAdouble-mut associated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multivariable analysis that included cytogenetic risk, FLT3-ITD and NPM1 mutation, white blood cell count and age. In contrast, CEBPAsingle-mut AMLs did not express a discriminating signature and could not be distinguished from wild type cases as regards clinical outcome. These results demonstrate significant underlying heterogeneity within CEBPA mutation positive AML with prognostic relevance.
Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of Circulating Fibrocytes and Dendritic Derivatives in Corneal Endothelium of Patients With Fuchs' Dystrophy.
Sex, Age, Specimen part
View SamplesPURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a degenerative eye disorder affecting 4% of Americans older than 40. It is the leading indication for corneal endothelial (CE) transplantation for which there is a global donor shortage. This study aimed to gain further insight into the pathophysiology of FECD and identify targets for nonsurgical therapy.
Identification of Circulating Fibrocytes and Dendritic Derivatives in Corneal Endothelium of Patients With Fuchs' Dystrophy.
Sex, Age, Specimen part
View SamplesGene expression microarrays were used to compare gene alterations induced by exposure to equitoxic doses of crocidolite asbestos and cristobalite silica in an isolate of normal human bronchial epithelial cells.
Indications for distinct pathogenic mechanisms of asbestos and silica through gene expression profiling of the response of lung epithelial cells.
Specimen part
View SamplesThe pretreatment karyotype of leukemic blasts is currently the key determinant in therapy decision-making in acute myeloid leukemia (AML). However, approximately fifty percent of AML patients, often carrying a normal karyotype, are currently unclassifiable based these established methods. Gene expression profiling has proven to be valuable for risk stratification of AML.
Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesFicolled AML-M0 sample gene expression profiles on Affymetrix HGU133Plus2.0 GeneChips. Acute myeloid leukemia (AML) classified as FAB-M0 is defined as a subtype with minimally differentiated morphology. Here we investigated by gene expression (GEP) profiling whether AML-M0 cases should be considered as one or more unique molecular subgroups that discriminates them from other AML patients. By applying GEP and subsequent unsupervised analysis of 35 AML-M0 samples and 253 previously reported AML cases, we demonstrate that AML-M0 cases express a unique signature. Hematological transcription regulators such as CEBPA, CEBPD, PU.1 and ETV6 and the differentiation associated gene MPO appeared strongly down-regulated, in line with the very primitive state of this type of leukemia. Moreover, AML M0 cases appeared to have a strong positive correlation with a previously defined immature AML subgroup with adverse prognosis. AML-M0 leukemias frequently carry loss-of-function RUNX-1 mutation and unsupervised analyses revealed a striking distinction between cases with and without mutations. RUNX1 mutant AML-M0 samples showed a distinct up-regulation of B-cell-related genes, e.g. members of the B-cell receptor complex, transcriptions regulators RUNX3, ETS2, IRF8 or PRDM1 and major histocompatibility complex class II genes. Importantly, expression of one single gene, i.e. BLNK, enabled prediction of RUNX1 mutations in AML-M0 with high accuracy. We propose that RUNX1 mutations in this subgroup of AML cause lineage infidelity, leading to aberrant co-expression of myeloid and B-lymphoid genes in the same cells.
Gene expression profiling of minimally differentiated acute myeloid leukemia: M0 is a distinct entity subdivided by RUNX1 mutation status.
Specimen part
View SamplesTumour hypoxia exhibits a highly dynamic spatial and temporal distribution and is associated with increased malignancy and poor prognosis.
Two phases of disulfide bond formation have differing requirements for oxygen.
Treatment
View Samples