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SRP162274
Homo sapiens
4 Downloadable Samples
Illumina HiSeq 2000
Description
Triple-Negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is associated with poor prognosis due to its propensity to form metastases. Unfortunately, the current treatment options are limited to chemotherapy such that identification of actionable targets are needed. The receptor tyrosine kinase AXL plays a role in the tumor cell dissemination and its expression in TNBC correlates with poor patients? survival. Here, we explored whether exploiting an AXL knockdown gene signature in TNBC cells may offer an opportunity for drug repurposing. To this end, we queried the PharmacoGx pharmacogenomics platform with an AXL gene signature which revealed Phenothiazines, a class of Dopamine Receptors antagonists (Thioridazine, Fluphenazine and Trifluoperazine) typically used as anti-psychotics. We next tested if drugs may be active to limit growth and metastatic progression of TNBC cells, similarly to AXL depletion. We found that the Phenothiazines were able to reduce cel l invasion, proliferation and viability, and also increased apoptosis of TNBC cells in vitro. Mechanistically, these drugs did not affect AXL activity but instead reduced PI3K/AKT/mTOR and ERK signaling. When administered to mice bearing TNBC xenografts, these drugs showed were able to reduce tumor growth and metastatic burden. Collectively, these results suggest that these antipsychotics are novel anti-tumor and anti-metastatic agents that could potentially be repurposed, in combination with standard chemotherapy, for use in TNBC. Overall design: RNA-seq of the Triple Negative Breast Cancer cell line MDA-MB-231 treated with siCt or siAXL Differential gene expression profile between MDA-MB-231 siCt and siAXL by RNA sequencing (Illumina HiSEq 2000)
Publication Title
AXL knockdown gene signature reveals a drug repurposing opportunity for a class of antipsychotics to reduce growth and metastasis of triple-negative breast cancer.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 16 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Neuronal cultures were treated with candesartan at neuroprotective concentrations followed by excitotoxic glutamate amounts. Candesartan significantly reduced glutamate-induced inflammation. To provide mechanistic insight into the potential targets and pathways that may underlie these benefits, we performed genome wide expression profile analysis and evaluated the data by Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA). We found that the inflammation signal transduction pathways were major components of the neuronal response to glutamate excitotoxicity, and that candesartan significantly ameliorated glutamate-induced alterations in gene expression. Further analysis showed significant associations of these genes with two independent published networks identified by microarray analysis of hippocampal samples obtained post-mortem from brains of patients diagnosed with AD .
Publication Title
An integrative genome-wide transcriptome reveals that candesartan is neuroprotective and a candidate therapeutic for Alzheimer's disease.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2500
Description
We applied RNA-seq analysis to human islet cells, received from 3 independent donors, treated with either redifferentiation cocktail + ARX shRNA, or redifferentiation cocktail + control shRNA or left untreated. Overall design: Examination of the effect of ARX inhibition on redifferentiation of ß-cell-derived (BCD) cells
Publication Title
Redifferentiation of expanded human islet β cells by inhibition of ARX.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Behavioral analysis confirmed that the 14-day social defeat sessions resulted in induction of depressive-like states measured in social interaction and light/dark tests. The combined data show that stress-induced depressive states are associated with molecular and structural changes that demyelinate the prefrontal cortex.
Publication Title
Chronic social defeat reduces myelination in the mouse medial prefrontal cortex.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 19 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Maternal immune activation is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother's immune system and alter the fetal environment with sub-sequence effects of CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on embryonic day 15. LPS significantly elevated pro-inflammatory cytokines in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-dams exhibited reduced social and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate possible molecular mechanisms by which MIA effects the fetal brain. We observed dysregulation of 3,285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain-specific genes, specifically those that regulate neuronal migration of GABAergic interneurons.
Publication Title
Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Telmisartan Protects a Microglia Cell Line from LPS Injury Beyond AT1 Receptor Blockade or PPARγ Activation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Intercellular communication is critical for integrating complex signals in multicellular eukaryotes. Vascular endothelial cells and T lymphocytes closely interact during the recirculation and trans-endothelial migration of T cells. In addition to direct cell-cell contact, we show that T cell derived extracellular vesicles can interact with endothelial cells and modulate their cellular functions. Thrombospondin-1 and its receptor CD47 are expressed on exosomes/ectosomes derived from T cells, and these extracellular vesicles are internalized and modulate signaling in both T cells and endothelial cells. Extracellular vesicles released from cells expressing or lacking CD47 differentially regulate activation of T cells induced by engaging the T cell receptor. Similarly, T cell-derived extracellular vesicles modulate endothelial cell responses to vascular endothelial growth factor and tube formation in a CD47-dependent manner. Uptake of T cell derived extracellular vesicles by recipient endothelial cells globally alters gene expression in a CD47-dependent manner. CD47 also regulates the mRNA content of extracellular vesicles in a manner consistent with some of the resulting alterations in target endothelial cell gene expression. Therefore, the thrombospondin-1 receptor CD47 directly or indirectly regulates intercellular communication mediated by the transfer of extracellular vesicles between vascular cells.
Publication Title
CD47-dependent immunomodulatory and angiogenic activities of extracellular vesicles produced by T cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
LPS and Telmisartan co-treatment of microglial BV2 cells.
Publication Title
Telmisartan Protects a Microglia Cell Line from LPS Injury Beyond AT1 Receptor Blockade or PPARγ Activation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
The goal of this study was to determine what genes are up- and down-regulated in response to lupus immune complexes in purified CD14+ monocyte stimulations. Our results have shown that novel genes are induced by immune complexes but the response is less robust when using purified monocytes versus total PBMCs
Publication Title
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples