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GSE9782
Homo sapiens
264 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved on the risk stratification provided by the International Staging System. Predictive models and biologic correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents.
Publication Title
Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The arylhydrocarbon receptor is a ligand inducible transcription factor. Known to control xenobiotic metabolizing enzymes, it also affects - depending on the cell type - numerous other genes, either directly or indirectly. With respect to the immune system, persistent activation leads to immunosuppression. We asked how the AhR is involved in Langerhans cells. These antigen presenting cells of the skin are responsible for allergies against chemicals (thus xenobiotic metabolism might be relevant) and a recently detected endogenous ligand, FICZ made by UVB radiation from tryptophane, is particularly abundant in the skin.
Publication Title
Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The transcriptome of murine LC after 24 hours in vivo exposure to a moderate dose of 10 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin was studied.
Publication Title
Langerhans cell maturation and contact hypersensitivity are impaired in aryl hydrocarbon receptor-null mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell-type-specific control of enhancer activity by H3K9 trimethylation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Over activation of the aryl hydrocarbon receptor (AhR) by TCDD results ampng other phenotypes in severe thymic atrophy accompanied by immunosuppression. The link between thymic atrophy, skewed thymocyte differntiation and immunosuppression is still not fully resolved. This study investigates the TCDD elicted exprssion changes in the ET, cortical thymus epithelial cell line.
Publication Title
Promoter analysis of TCDD-inducible genes in a thymic epithelial cell line indicates the potential for cell-specific transcription factor crosstalk in the AhR response.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In dendritic cells, expression of the H3K9me3 demethylase JmjD2d is upregulated by LPS stimulation. To identify genes whose induction by LPS depends on JmjD2d activity, we performed a microarray analysis of wild-type and JmjD2d-knockdown dendritic cells, before and after stimulation with LPS.
Publication Title
Cell-type-specific control of enhancer activity by H3K9 trimethylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to asses gene expression in 3T3 fibroblasts, after knock-down of Brg1 and Brm using stable shRNA interference. Cells were treated with 5ng/ml mouse TNF-alpha to stimulate inducible gene activation.
Publication Title
Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Over-activation of the aryl hydrocarbon receptor by TCDD in mice leads among other phenotypes to a severe thymic atrophy accompanied by immunosuppression. TCDD causes a block in thymocyte maturation and a preferential emigration of immature CD4-CD8- DN thymocytes (recent thymic emigrants) into the periphery. As part of this study gene expression profiles from DN thymocytes and thymic emigrants were generated from TCDD and solvent control mice
Publication Title
Role of the aryl hydrocarbon receptor in thymocyte emigration in vivo.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sphingosine 1-phosphate (S1P) influences T cell migration into and out of secondary lymphoid organs; however, its mechanism of action remains uncertain. Our previous research shows that agonism of the S1P receptor S1P1 inhibits the egress of T lymphocytes from the peripheral tissues into afferent lymphatics. To better define the mechanism of inhibition, we developed an in vitro model to characterize T cell transendothelial migration across lymphatics. Two commercially available endothelial cell lines (MS-1 and SVEC4-10) were characterized by flow cytometry, real time RT-PCR, and Affymetrix Gene Array. These cell lines were grown to confluent monolayers in transwell systems, on either the upper or lower surface of the transwell insert. T cells were isolated from the spleens of (C57BL/6 x C3H/HeJ)F1, S1P1 KO, or S1P1 KO littermate controls, and either treated with the S1P receptor modulator FTY720 or left untreated. Cells were migrated to chemokines (CCL19 or CCL21) for 4 hours, and migration quantified. Flow cytometry, RT-PCR, and array results identified MS-1 as a blood vascular endothelial cell line, expressing high levels of CD31, CD34, and ICAM-1 as well as other endothelial cell markers; while SVEC4-10 closely resemble a lymphatic phenotype, expressing LYVE-1, VEGFR-3, and podoplanin. T cells efficiently migrate across MS-1, whether grown on the upper or lower surface; whereas migration across SVEC4-10 only occurs when cells are grown on the lower surface of the transwell (iSVEC), recapitulating basal (abluminal) to apical (luminal) migration that occurs in vivo. FTY720 inhibits T cell migration across iSVEC, but not across MS-1. Inhibition is due to drug effects only on T cells but not endothelial cells. S1P1 KO T cells treated with FTY720 are not inhibited in their migration across the iSVEC line, showing that S1P1 stimulation is required for migration inhibition. The in vitro model developed here is the first to use endothelial cell lines to analyze the regulation of T cell migration across lymphatic endothelium. The results show there is directional control of T cell migration across lymphatic cells, such that T cells only migrate from a basal to apical direction. Agonism of S1P1 specifically inhibits migration, while absence of the receptor does not. These findings have important implications for the use of S1P1 agonists in transplantation, as inhibition of cell entry into afferent lymphatics and lymph nodes could impede the development of graft rejection.
Publication Title
The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics.
Sample Metadata Fields
Specimen part
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