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GSE11121
Homo sapiens
200 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motives we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified co-regulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B cell and T cell infiltration. We calculated metagenes as surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation associated genes. In multivariate Cox regression analysis the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort (Hazard Ratio (HR) 2.20, 95% confidence interval (CI) 1.40-3.46). The B cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR 0.66, 95% CI 0.46 - 0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high grade tumors (n=286, HR 0.78, 95% CI 0.62-0.98), and a second validation cohort enriched for younger patients (n=302, HR 0.83, 95% CI 0.7-0.97). Thus, we could demonstrate in three cohorts of untreated node-negative breast cancer patients, that the humoral immune system plays a pivotal role for metastasis-free survival of carcinomas of the breast.
Publication Title
The humoral immune system has a key prognostic impact in node-negative breast cancer.
Sample Metadata Fields
Disease stage
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Expression profiling of cell cycle genes in human pancreatic islets with and without type 2 diabetes
Publication Title
Autoimmunity against INS-IGF2 protein expressed in human pancreatic islets.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Targets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours.
Publication Title
The effect of two endogenous retinoids on the mRNA expression profile in human primary keratinocytes, focusing on genes causing autosomal recessive congenital ichthyosis.
Sample Metadata Fields
Treatment
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
YEAST STRAIN:
Publication Title
Excess mannose limits the growth of phosphomannose isomerase PMI40 deletion strain of Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 10 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used microarrays to identify differentially expressed genes. We focused on those genes that were dramatically induced (>2-fold) in WT but not in the rpp4 mutant at 2 dpi when WT and rpp4 first showed distinct phenotypes
Publication Title
Timing of plant immune responses by a central circadian regulator.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to gain insights into how PPARg regulates different facets of dendritic cell (DC) differentiation, we sought to identify PPARg regulated genes and gene networks in monocyte-derived dendritic cells using global gene expression profiling. We employed an exogenous ligand activation approach using a selective PPARg ligand (rosiglitazone abbreviated as RSG). In addition, we have defined culture conditions in which human serum (HS) induces PPARg activation via a yet uncharacterized endogenous mechanism. We also compared the gene expression profile of developing dendritic cells obtained from patients harboring dominant negative mutations of the PPARg receptor (C114R and C131Y).
Publication Title
PPARgamma regulates the function of human dendritic cells primarily by altering lipid metabolism.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have carried out global gene expression analysis to clarify the interrelationship between 1,25-dihydroxyvitamin D3 and differentiation-driven gene expression patterns in developing human monocyte-derived dendritic cells. Monocytes were treated with 10 nM 1,25-dihydroxyvitamin D3 or vehicle 14 hours after plating for 12 hours or 5 days. Monocytes, differentiating dendritic cells (+/-1,25-dihydroxyvitamin D3 for 12 hours) and immature dendritic cells (+/-1,25-dihydroxyvitamin D3 for 5 days) were harvested. This design allows one to identify genes regulated by differentiation and/or 1,25-dihydroxyvitamin D3 in human monocyte-derived dendritic cells.
Publication Title
1,25-dihydroxyvitamin D3 is an autonomous regulator of the transcriptional changes leading to a tolerogenic dendritic cell phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Ewing sarcoma family of tumors (ESFT) are aggressive bone and soft tissue tumors of unknown cellular origin. Most ESFT express EWS-FLI1, a chimeric protein which functions as a growth-promoting oncogene in ESFT but is toxic to most normal cells. A major difficulty in understanding EWS-FLI1 function has been the lack of an adequate model in which to study EWS-FLI1-induced transformation. Although the cell of origin of ESFT remains elusive, both mesenchymal (MSC) and neural crest (NCSC) have been implicated. We recently developed the tools to generate NCSC from human embryonic stem cells (hNCSC). In the current study we used this model to test the hypothesis that neural crest-derived stem cells are the cells of origin of ESFT and to evaluate the consequences of EWS-FLI1 expression on human neural crest biology.
Publication Title
Modeling initiation of Ewing sarcoma in human neural crest cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The full complement of molecular pathways contributing to Parkinsons disease (PD) pathogenesis remains unknown. Here, to address this issue, we began by using a high-resolution variant of functional magnetic resonance imaging (fMRI) to pinpoint brainstem regions differentially affected by, and resistant to, the disease. Then, relying on the imaging information as a guide, we profiled gene expression levels of postmortem brain samples and used a factorial statistical model to identify a disease related decrease in the expression of the polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a series of studies were performed to confirm the pathogenic relevance of this finding. First, to test for a causal link between polyamines and -synuclein toxicity, we investigated a yeast model expressing -synuclein. Polyamines were found to enhance the toxicity of -synuclein, and an unbiased genome-wide screen for modifiers of -synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology we investigated a mouse model expressing -synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, while Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, we genotyped PD patients and controls and isolated a rare but novel variant in the SAT1 gene, although the functional significance of this genetic variant was not identified. Taken together, the results suggest that the polyamine pathway contributes to PD pathogenesis.
Publication Title
Polyamine pathway contributes to the pathogenesis of Parkinson disease.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Drosophila melanogaster
- 58 Downloadable Samples
Illumina HiSeq 2000
Description
Transcriptome analysis may provide means to investigate the underlying genetic causes of shared and divergent phenotypes in different populations and help to identify potential targets of adaptive evolution. Applying RNA sequencing to whole male Drosophila melanogaster from the ancestral tropical African environment and a very recently colonized cold-temperate European environment at both standard laboratory conditions and following a cold shock, we seek to uncover the transcriptional basis of cold adaptation. In both the ancestral and the derived populations, the predominant characteristic of the cold shock response is the swift and massive upregulation of heat shock proteins and other chaperones. Although we find ~30% of the genome to be differentially expressed following a cold shock, only relatively few genes (n=26) are up- or down-regulated in a population-specific way. Intriguingly, 24 of these 26 genes show a greater degree of differential expression in the African population. Likewise, there is an excess of genes with particularly strong cold-induced changes in expression in Africa on a genome-wide scale. The analysis of the transcriptional cold shock response most prominently reveals an upregulation of components of a general stress response, which is conserved over many taxa and triggered by a plethora of stressors. Despite the overall response being fairly similar in both populations, there is a definite excess of genes with a strong cold-induced fold-change in Africa. This is consistent with a detrimental deregulation or an overshooting stress response. Thus, the canalization of European gene expression might be responsible for the increased cold tolerance of European flies. Overall design: mRNA profiles of whole Drosophila melanogaster adult males from a Africa (4 lines) and Europe (4 lines) during a 7h cold shock experiment. Samples include room temperature controls, 3.5h into the cold shock, 15 minutes after recovery and 90 minutes after recovery. 2 biological replicates each.
Publication Title
Canalization of gene expression is a major signature of regulatory cold adaptation in temperate Drosophila melanogaster.
Sample Metadata Fields
Sex, Subject
View Samples