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GSE11870
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ligand-mediated activation of the nuclear hormone receptor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. Two naturally occurring mutations (P467L, V290M) in the ligand binding domain of PPAR gamma have been described in humans that lead to severe insulin resistance and hypertension. Experimental evidence suggests that these mutant versions of PPAR gamma act in a dominant negative fashion. To better understand the molecular mechanisms underlying PPAR gamma action in the vasculature, we determined the global gene expression profile in primary aortic endothelial cells in response to endothelial cell specific expression of a dominant negative isoform of PPAR gamma (V290M).
Publication Title
Endothelium-specific interference with peroxisome proliferator activated receptor gamma causes cerebral vascular dysfunction in response to a high-fat diet.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ligand-mediated activation of the nuclear hormone receptor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. Two naturally occurring mutations (P467L, V290M) in the ligand binding domain of PPAR gamma have been described in humans that lead to severe insulin resistance and hypertension. Experimental evidence suggests that these mutant versions of PPAR gamma act in a dominant negative fashion. To better understand the molecular mechanisms underlying PPAR gamma action in the vasculature, we determined the gene expression patterns in mouse aorta in response to activation or interference with the PPAR gamma signaling pathway.
Publication Title
Bioinformatic analysis of gene sets regulated by ligand-activated and dominant-negative peroxisome proliferator-activated receptor gamma in mouse aorta.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 769 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We used microarrays to measure the expression levels of genes in irradiated immortalized B cells, lymphoblastoid cells, from members of Centre d'Etude du Polymorphisme Humain (CEPH) Utah pedigrees. Data were collected for cells at baseline and 2 hours and 6 hours after exposure to 10 Gy of ionizing radiation (IR).
Publication Title
Genetic variation in radiation-induced cell death.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Transcriptome analysis of human peripheral blood T cells
Publication Title
Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Transcriptome analysis of human peripheral blood monocytes
Publication Title
Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells.
Publication Title
Differential effects of interleukin-2 and interleukin-15 versus interleukin-21 on CD4+ cutaneous T-cell lymphoma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells.
Publication Title
Differential effects of interleukin-2 and interleukin-15 versus interleukin-21 on CD4+ cutaneous T-cell lymphoma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we compared the effects of ALK inhibitor on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from a patient with Anaplastic Large Cell Lymphoma. we used microarrays to map the genome-wide gene expression patterns in ALK+TCL cells in response to ALK inhibition.
Publication Title
Malignant transformation of CD4+ T lymphocytes mediated by oncogenic kinase NPM/ALK recapitulates IL-2-induced cell signaling and gene expression reprogramming.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
Illumina HiSeq 2500
Description
We report changes in B cells in patients treated with combination immune checkpoint blockade (CCB; anti-CTLA4 and anti-PD1) Overall design: We examine CD19+ sorted B cells before and after CCB therapy
Publication Title
Early B cell changes predict autoimmunity following combination immune checkpoint blockade.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 70 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The primary goal of toxicology and safety testing is to identify agents that have the potential to cause adverse effects in humans. Unfortunately, many of these tests have not changed significantly in the past 30 years and most are inefficient, costly, and rely heavily on the use of animals. The rodent cancer bioassay is one of these safety tests and was originally established as a screen to identify potential carcinogens that would be further analyzed in human epidemiological studies. Today, the rodent cancer bioassay has evolved into the primary means to determine the carcinogenic potential of a chemical and generate quantitative information on dose-response behavior in chemical risk assessments. Due to the resource-intensive nature of these studies, each bioassay costs $2 to $4 million and takes over three years to complete. Over the past 30 years, only 1,468 chemicals have been tested in a rodent cancer bioassay. By comparison, approximately 9,000 chemicals are used by industry in quantities greater than 10,000 lbs and nearly 90,000 chemicals have been inventoried by the U.S. Environmental Protection Agency as part of the Toxic Substances Control Act. Given the disparity between the number of chemicals tested in a rodent cancer bioassay and the number of chemicals used by industry, a more efficient and economical system of identifying chemical carcinogens needs to be developed.
Publication Title
Application of genomic biomarkers to predict increased lung tumor incidence in 2-year rodent cancer bioassays.
Sample Metadata Fields
Sex, Age, Subject
View Samples