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GSE31212
Mus musculus
34 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Sample Metadata Fields
Specimen part, Disease stage, Time
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates loss of p53 and Rb function and deregulation of PP2A-controlled mitogenic pathways in human breast cancer. In primiparous mice, WAP-promoter driven expression of SV40 proteins induces well and poorly differentiated mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis.
Publication Title
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transgenic expression in mice of two synergistically acting SV40 early region encoded proteins, large (LT) and small (sT) tumor antigens, in the mammary epithelium recapitulates loss of p53 and Rb function and deregulation of PP2A-controlled mitogenic pathways in human breast cancer. In primiparous mice, WAP-promoter driven expression of SV40 proteins induces well and poorly differentiated mammary adenocarcinomas. We performed a correlative aCGH and gene expression analysis of 25 monofocal tumors, representing four histopathological grades, to explore the molecular traits of SV40-induced mammary tumors and to emphasize the relevance of this tumor model for human breast tumorigenesis.
Publication Title
Low-grade and high-grade mammary carcinomas in WAP-T transgenic mice are independent entities distinguished by Met expression.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 308 Downloadable Samples
Illumina HiSeq 2500
Description
One of sleep's putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience, however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine, and behavioral variables, as well as the brain and blood transcriptome in mice exposed to 9 weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypical variables revealed that rapid-eye-movement sleep (REMS), corticosterone regulation, and coat state were most responsive to UCMS. REMS theta oscillations were enhanced, whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus, and blood were associated with inflammatory and immune responses. A machine-learning approach controlling for unspecific UCMS effects identified transcriptomic predictor sets for REMS parameters that were enriched in 193 pathways, including some involved in stem cells, immune response, apoptosis, and survival. Only three pathways were enriched in predictor sets for non-REMS. Transcriptomic predictor sets for variation in REMS continuity and theta activity shared many pathways with corticosterone regulation, in particular pathways implicated in apoptosis and survival, including mitochondrial apoptotic machinery. Predictor sets for REMS, and anhedonia shared pathways involved in oxidative stress, cell proliferation, and apoptosis. These data identify REMS as a core and early element of the response to chronic stress, and identify apoptosis and survival pathways as a putative mechanism by which REMS may mediate the response to stressful waking experiences. Overall design: Study of transcriptomic changes in three stress- and sleep-related brain regions (prefrontal cortex, hippocampus, hypothalamus) and blood following 9 weeks of Unpredictable Chronic Mild Stress (UCMS) in mice.
Publication Title
REM sleep's unique associations with corticosterone regulation, apoptotic pathways, and behavior in chronic stress in mice.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combined inhibition of receptor tyrosine and p21-activated kinases as a therapeutic strategy in childhood ALL.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Time
View Samples- Homo sapiens
- 75 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The purpose of this study was the principal investigation and frequency of RTK expression in primary T-ALLs. Primary initial T-ALLs were assessed regarding their transcriptome-wide expression profiles and screend for prominent RTK expression.
Publication Title
Combined inhibition of receptor tyrosine and p21-activated kinases as a therapeutic strategy in childhood ALL.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Deregulated RTK activity has been implicated as a causal leukemogenic factor in the context of molecular aberrations that perturb differentiation in the hematopoietic lineage such as in childhood ALL. A deeper understanding of RTK signaling processes on a system-wide scale will be key in defining critical components of signaling networks. To link RTK activity with in vivo output in primary ALL we took a functional approach, which combined SH2 domain binding, mass spectrometry, and transcriptome analyses. Structure and composition of evolving networks were highly diverse with few generic features determined by receptor and cell type. A combinatorial assembly of varying context-dependent and few generic signaling components at multiple levels likely generates output specificity. PAK2 was identified as a phosphoregulated FLT3 target, whose allosteric inhibition resulted in apoptosis of ALL cells. Our studies provide evidence that a functional approach to leukemia signaling may yield valuable information for a network-directed intervention.
Publication Title
Combined inhibition of receptor tyrosine and p21-activated kinases as a therapeutic strategy in childhood ALL.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Platelet reactivity (PR) in cardiovascular (CV) patients is variable between individuals and modulates clinical outcome. However, the determinants of platelet reactivity are largely unknown. Integration of data derived from high-throughput omics technologies may yield novel insights into the molecular mechanisms that govern platelet reactivity. The aim of this study was to identify candidate genes modulating platelet reactivity in aspirin-treated cardiovascular patients PR was assessed in 110 CV patients treated with aspirin 100mg/d by aggregometry using several agonists. 12 CV patients with extreme high or low PR were selected for transcriptomics, proteomics and miRNA analysis.
Publication Title
New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cancer types with lower mutational load and a non-permissive tumor microenvironment are intrinsically resistant to immune checkpoint blockade. While the combination of cytostatic drugs and immunostimulatory antibodies constitutes an attractive concept for overcoming this refractoriness, suppression of immune cell function by cytostatic drugs may limit therapeutic efficacy. Here we show that targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) does not impair dendritic cell-mediated T-cell priming and activation. Accordingly, combining MEK inhibitors (MEKi) with agonist antibodies (Abs) targeting the immunostimulatory CD40 receptor resulted in potent synergistic anti-tumor efficacy. Detailed analysis of the mechanism of action of MEKi GDC-0623 by means of flow cytometric analysis of the tumor immune infiltrate and whole tumor transcriptomics showed that, in addition to its cytostatic impact on tumor cells, this drug exerts multiple pro-immunogenic effects, including the suppression of M2-type macrophages, myeloid derived suppressor cells and CD4+ T-regulatory cells. In addition, MEKi was found to induce tumor-cell intrinsic interferon signaling, which contributed to antigen presentation by tumor cells. Finally, the tumoridical impact of MEKi involves the activation of multiple pro-inflammatory pathways involved in immune cell effector function in the tumor microenvironment. Our data therefore indicate that the combination of MEK inhibition with agonist anti-CD40 Ab is a promising therapeutic concept, especially for the treatment of mutant Kras-driven tumors such as pancreatic ductal adenocarcinoma.
Publication Title
Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy.
Sample Metadata Fields
Specimen part
View Samples