Filters
Technology
Platform
GSE17777
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human microvascular endothelial cells (HMVEC) treated with vascular endothelial growth factor (VEGF), Antrhax Edema Toxin (ET), or the Epac activator, 8-pCPT-2'-O-Me-cAMP (8CPT)
Publication Title
Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: Information on the carcinogenic potential of chemicals is only availably for High Production Volume products. There is however, a pressing need for alternative methods allowing for the chronic toxicity of substances, including carcinogenicity, to be detected earlier and more reliably. Here we applied advanced genomics to a cellular transformation assay to identify gene signatures useful for the prediction of risk for carcinogenicity. Methods: Genome wide gene expression analysis and qRT-PCR were applied to untransformed and transformed Balb/c 3T3 cells that exposed to 2, 4-diaminotoluene (DAT), benzo(a)pyrene (BaP), 2-Acetylaminoflourene (AAF) and 3-methycholanthrene (MCA) for 24h and 120h, at different concentrations, respectively. Furthermore, various bioinformatics tools were used to identify gene signatures predicting for the carcinogenic risk. Results: Bioinformatics analysis revealed distinct datasets for the individual chemicals tested while the number of significantly regulated genes increased with ascending treatment concentration of the cell cultures. Filtering of the data revealed a common gene signature that comprised of 13 genes whose regulation in cancer tissue has already been established. Strikingly, this gene signature was already identified prior to cell transformation therefore confirming the predictive power of this gene signature in identifying carcinogenic risks of chemicals. Comparison of fold changes determined by microarray analysis and qRT-PCR were in good agreement. Conclusion: Our data describes selective and commonly regulated carcinogenic pathways observed in an easy to use in vitro carcinogenicity assay. Here we defined a set of genes which can serve as a simply assay to predict the risk for carcinogenicity by use of an alternative in vitro testing strategy.
Publication Title
Toxicogenomics applied to in vitro carcinogenicity testing with Balb/c 3T3 cells revealed a gene signature predictive of chemical carcinogens.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Patient selection and specimen collection. Thirty-six freshly frozen tumor samples were prospectively collected from patients undergoing surgery or biopsy for HNSCC at the University of North Carolina (UNC) at Chapel Hill (21 patients) and Vanderbilt University (15 patients). All tissues were snap-frozen in liquid nitrogen within 30 minutes of surgical resection or biopsy, and kept at -80oC until further processing. All patients consented to participation in this study under protocols approved by IRB at the two institutions.
Publication Title
A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Protein Kinase C alpha (PKC) is a critical mediator of cell signaling and cancer growth. We show that PKC inhibitors decrease proliferation in squamous cell carcinoma of the head and neck (SCCHN) cells and abrogate growth of SCCHN tumors in mouse xenografts. Analysis of gene expression arrays reveals that PKC regulates cell cycle genes required for DNA synthesis. In particular, PKC increases cyclin E protein expression, cyclinE/cdk2 complex formation, and transcription of cyclin E and E2F target genes. Consistent with this mechanism, expression of cyclin E rescues the block in DNA synthesis caused by PKC inhibition. In SCCHN tissue, PKC and cyclin E expression increase progressively from normal and dysplastic to malignant human head and neck tissue. Furthermore, PKC expression correlates with poor prognosis in SCCHN. These results demonstrate that PKC regulates growth by stimulating DNA synthesis through cyclin E and E2F and identify PKC as a therapeutic target that is highly expressed in aggressive SCCHN.
Publication Title
A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
IlluminaHiSeq2000
Description
Background: Kawasaki Disease (KD) is a childhood illness of suspected infectious etiology that causes medium-sized muscular arteritis, most critically affecting the coronary arteries. No single diagnostic test exists, hampering early diagnosis and treatment. Approximately 25% of untreated patients develop coronary artery disease, and children who are treated with intravenous gammaglobulin but do not respond are also at high risk. Subacute/chronic arteritis and luminal myofibroblastic proliferation are the pathologic processes occurring in KD CA after the second week of illness, when neutrophilic necrotizing arteritis has subsided. The specific dysregulated immune pathways contributing to subacute/chronic arteritis have been unknown, hampering the development of effective immunomodulatory therapies for patients not responding to intravenous gammaglobulin therapy. Methods and Results: Deep RNA sequencing was performed on KD (n=8) and childhood control (n=7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Molecular pathways involving T helper cell, cytotoxic T lymphocyte, dendritic cells, and antigen presentation were the most significantly dysregulated. There was significant upregulation of immunoglobulin and type I interferon-stimulated genes. 80 upregulated extracellular genes encoding secreted proteins are candidate biomarkers of KD arteritis. Conclusions: The immune transcriptional profile in KD coronary artery tissues is primarily T helper and cytotoxic lymphocyte-mediated, and has features of an antiviral immune response such as type I interferon-stimulated gene expression. This first report of the KD coronary artery transcriptome identifies specific dysregulated immune response pathways that can inform the development of new therapies for and biomarkers of KD arteritis, and provide direction for future etiologic studies. Overall design: Primary analysis: 8 KD coronary arteries versus 7 childhood control coronary arteries. Subanalysis 1: 4 untreated KD coronary arteries versus 7 childhood control coronary arteries and subanalysis 2: 4 treated KD coronary arteries versus 7 childhood control coronary arteries
Publication Title
The transcriptional profile of coronary arteritis in Kawasaki disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 79 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Transcription profiling of sense and antisense transcripts of 10 tissues each from human, mouse, and rat.
Publication Title
Conserved expression of natural antisense transcripts in mammals.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 39 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Transcription profiling of sense transcripts of 10 tissues each from human, mouse, and rat.
Publication Title
Conserved expression of natural antisense transcripts in mammals.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 40 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Transcription profiling of antisense transcripts of 10 tissues each from human, mouse, and rat.
Publication Title
Conserved expression of natural antisense transcripts in mammals.
Sample Metadata Fields
Specimen part
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
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The CLS1/CAF co-culture maintained the cancer stemness. This cancer stemness was lost when the CAF feeder cells were removed during passaging.
Publication Title
Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling.
Sample Metadata Fields
Cell line
View Samples