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GSE76848
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
APC inactivation is the early process in the tumorigenesis of colorectal cancer. We established organoid cultures from intestines of genetically modifeid mice harboring Apcfl/fl, Tacc3wt/wt or Apcfl/fl, Tacc3fl/fll and R26CreERT2 allele
Publication Title
Suppression of intestinal tumors by targeting the mitotic spindle of intestinal stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a key causal role in tumorigenesis. According to an alternative view, chromosomal instabilities are mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that deregulation of some key pathways, such as MAPK, p53, cell cycle regulation and Polycomb group factors, in addition to activation of several genes like Myc, AML, B-Catenin and the ETS family transcription factors, are key steps in cancer development driven by 20q amplification. Finally we identified 13 cancer initiating genes, located on 20q13, which were significantly overexpressed in many tumors, with expression levels correlated with tumor grade and outcome; these probably play key roles in inducing malignancy via20q amplification.
Publication Title
Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 19 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Epithelial appendages are the product of epithelial mesenchymal interactions. Tissue recombination experiments showed that in general, the dermis determines the phenotype of the epithelial appendage. Chicken dorsal skin epithelium interacts with its underlying mesenchyme to form feathers beginning at E7 (H&H stage 31), while metatarsal scale epithelium interacts with its mesenchyme to form scales beginning at E9 (H&H stage 35) which stabilize around E12 (H&H stage 38).
Publication Title
Emergence of differentially regulated pathways associated with the development of regional specificity in chicken skin.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We enriched for prostate cancer cells by the selection system used in human iPS purification. Gene expression signature-based chemical prediction enabled us to identify candidate drugs for reverting the EOS (early transposon promoter, OCT4 and SOX2 enhancer) signature with chemoresistance into a chemosensitive phenotype.
Publication Title
Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Polycomb repressive complex (PRC) 2, containing minimally EZH2, EED and Suz12, is the H3 lysine 27 methyltransferase playing pivotal roles in transcriptional regulation. EZH2 is the catalytic subunit, and H3K27me3 activates PRC2 through binding EED to propagate the repressive mark. Cofactor SAM-competitive (SAM-C) PRC2 inhibitors (PRC2is) have been discovered to treat lymphoma and rhabdoid tumors. Here we report the discovery of EED226, a potent and selective PRC2i directly binding to the H3K27me3 pocket of EED. Upon binding, EED226 induces conformational change in EED protein. Interestingly, it inhibits both the basal and the H3K27me3-stimulated PRC2 activities. Furthermore, EED226 selectively pulled down the endogenous PRC2 complex from human cell lysates, specifically modulates H3K27 methylation and target genes similarly as SAM-C PRC2 inhibitors, and effectively regresses human lymphoma xenograft tumor in mouse. More importantly, EED226 potently inhibits the SAM-C inhibitor-resistant PRC2 and synergizes with SAM-C PRC2i in cell proliferation blocking. Together, EED226 is an inhibitor of PRC2 with a novel mechanism and represent a potential complementary strategy for PRC2-targeted cancer therapy.
Publication Title
An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The aim of this study was to analyze gene response to a 10-week dietary intervention for weight loss in peripheral blood mononuclear cells of overweight/obese male children.
Publication Title
Peripheral blood mononuclear cell gene expression profile in obese boys who followed a moderate energy-restricted diet: differences between high and low responders at baseline and after the intervention.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Considering the numerous complex and different pathological mechanisms involved in Alzheimers disease (AD) progression, treatments targeting a single cause may lead to limited benefits. The goal of this study was the identification of a novel mode of action for this unmet need. Pharmacological tool compounds: suberoylanilide hydroxamic acid (SAHA) and tadalafil, targeting histone deacetylases (HDAC) and phosphodiesterase 5 (PDE5) respectively, were utilized simultaneously for in-vitro and in-vivo Proof-of-Concept (PoC). A synergistic effect was observed in the amelioration of AD signs using the combination therapy in Tg2576 mice. Finally, a therapeutic agent, CM-414, inhibiting simultaneously HDAC2/6 and PDE5 was generated and tested in Tg2576 mice. CM-414 reversed cognitive impairment, reduced amyloid and tau pathology, and rescued dendritic spine density loss in the hippocampus in AD mice. Importantly, the effect obtained was present after a 4-weeks wash-out period.
Publication Title
Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 142 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Quantitative phosphoproteome and transcriptome analysis of ligand-stimulated MCF-7 human breast cancer cells was performed to understand the mechanisms of tamoxifen resistance at a systems level. Phosphoproteome data revealed that wild type (WT) cells were more enriched with phospho-proteins than tamoxifen-resistant (TamR) cells after stimulation with ligands. Surprisingly, decreased phosphorylation after ligand perturbation was more common than increased phosphorylation. In particular, 17beta-estradiol (E2) induced down-regulation in WT cells at a very high rate. E2 and the ErbB ligand, heregulin (HRG) induced almost equal numbers of up-regulated phospho-proteins in WT cells. Pathway and motif activity analyses using transcriptome data additionally suggested that deregulated activation of GSK3B(glycogen synthase kinase 3 beta) and MAPK1/3 signaling might be associated with altered activation of CREB and AP-1 transcription factors in TamR cells and this hypothesis was validated by reporter assays. An examination of clinical samples revealed that, inhibitory phosphorylation of GSK3B at serine 9 was significantly lower in tamoxifen-treated breast cancer patients that eventually had relapses, implying that activation of GSK3B may be associated with the tamoxifen resistant phenotype. Thus, the combined phosphoproteome and transcriptome dataset analyses revealed distinct signal-transcription programs in tumor cells and provided a novel molecular target to understand tamoxifen resistance.
Publication Title
Integrated quantitative analysis of the phosphoproteome and transcriptome in tamoxifen-resistant breast cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Cell line, Treatment, Race, Time
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts.
Publication Title
Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis without increased bleeding risk.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of human iPSCs and could be used for therapeutic and regenerative medicine applications. In this study, we showed that a new first-in-class dual G9a/DNMT inhibitor CM272 compound improves the standard four-factor reprogramming efficiency of human fibroblast. The use of CM272 facilitates the generation of iPSC with only two factors, OCT4 and SOX2, allowing the removal of potentially oncogenic factors such as cMYC or KLF4. Taking a closer look at the early events occurring during cell reprogramming we demonstrated that treatment with our G9a/DNMT dual inhibitor induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to the genome and promotes mesenchymal to epithelial transition during cell reprogramming. Thus, the use of this new G9a/DNMT dual inhibitor compound may represent an interesting alternative for improving cell reprogramming.
Publication Title
Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line
View Samples