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SRP136693
Homo sapiens
96 Downloadable Samples
Illumina HiSeq 1500
Description
We have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue resident innate cell types Overall design: Cells sorted from uninfected and infected lung tissue (24 hrs. post infection)
Publication Title
<i>Mycobacterium tuberculosis</i> Invasion of the Human Lung: First Contact.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 92 Downloadable Samples
- Illumina HiSeq 1500
Description
We have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue resident innate cell types Overall design: Cells sorted from uninfected and infected lung tissue (24 hrs. post infection)
Publication Title
<i>Mycobacterium tuberculosis</i> Invasion of the Human Lung: First Contact.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The NF1 tumor suppressor encodes a RAS GTPase-Activating Protein (RasGAP). Accordingly, deregulated RAS signaling underlies the pathogenesis of NF1-mutant cancers. However, while various RAS effector pathways have been shown to function in these tumors, it is currently unclear which specific proteins within these broad signaling pathways represent optimal therapeutic targets. Here we identify mTORC1 as the key PI3K pathway component in NF1-mutant nervous system malignancies and conversely show that mTORC2 and AKT are dispensable. We also report that combined mTORC1/MEK inhibition is required to promote tumor regression in animal models, but only when the inhibition of both pathways is sustained. Transcriptional profiling studies were also used to establish a predictive signature of effective mTORC1/MEK inhibition in vivo. Within this signature, we unexpectedly found that the glucose transporter gene, GLUT1, was potently suppressed but only when both pathways were effectively inhibited. Moreover, unlike VHL and LKB1 mutant cancers, reduction of 18F-FDG uptake measured by FDG-PET required the effective suppression of both mTORC1 and MEK. Together these studies identify optimal and sub-optimal therapeutic targets in NF1-mutant malignancies and define a non-invasive means of measuring combined mTORC1/MEK inhibition in vivo, which can be readily incorporated into clinical trials.
Publication Title
Defining key signaling nodes and therapeutic biomarkers in NF1-mutant cancers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
mTOR and HDAC inhibitors induce cell death of malignant peripheral nerve sheath tumors (MPNSTs) in vitro, and in vivo
Publication Title
mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Current methods to analyze gene expression measure steady-state levels of mRNA. In order to specifically analyze mRNA transcription, a technique has been developed that can be applied in-vivo. The technique is referred with the acronym NIAC-NTR (Non Invasive Application and Capture of Newly Transcribed RNA). This method makes use of the cellular pyrimidine salvage pathway and is based on affinity-chromatographic isolation of thiolated mRNA. When combined with data on mRNA steady-state levels, this method is able to assess the relative contributions of mRNA synthesis and degradation/stabilization. It overcomes limitations associated with currently available methods such as mechanistic intervention that disrupts cellular physiology, or the inability to apply the techniques in-vivo. The method has been applied to a model of serum response of cultured primary mouse embryonic fibroblasts.
Publication Title
Microarray analysis of newly synthesized RNA in cells and animals.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Current methods to analyze gene expression measure steady-state levels of mRNA. In order to specifically analyze mRNA transcription, a technique has been developed that can be applied in-vivo in intact cells and animals. The technique is referred with the acronym NIAC-NTR (Non Invasive Application and Capture of Newly Transcribed RNA). This method makes use of the cellular pyrimidine salvage pathway and is based on affinity-chromatographic isolation of thiolated mRNA. When combined with data on mRNA steady-state levels, this method is able to assess the relative contributions of mRNA synthesis and degradation/stabilization. It overcomes limitations associated with currently available methods such as mechanistic intervention that disrupts cellular physiology, or the inability to apply the techniques in-vivo. The method was applied to study renal ischemia reperfusion injury, demonstrating its applicability for whole organs in-vivo.
Publication Title
Microarray analysis of newly synthesized RNA in cells and animals.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Interactions between Chronic Lymphocytic Leukemia B-cells (CLL B-cells) and the microenvironment (ME) play a major function in the physiopathology of CLL. Extracellular vesicles (EVs) (composed of exosomes and microparticles) have been shown to play an important role in cell communication. EVs, purified by ultracentrifugation from bone marrow mesenchymal stromal cells (BM-MSC) culture, were added to CLL B-cells. Microarray study highlighted 805 differentially expressed genes between CLL-B-cells cultured with and without EVs. Of these, CCL3/4, EGR1/2/3, MYC (involved in BCR pathway) were increased while pro-apoptotic genes like HRK were decreased. We showed for the first time the potential of EVs alone to induce gene expression modifications in CLL B-cell, notably in BCR and apoptosis pathways. We concluded that a substantial part of communication between CLL B-cells and BM-ME is mediated through EV.
Publication Title
Extracellular vesicles of bone marrow stromal cells rescue chronic lymphocytic leukemia B cells from apoptosis, enhance their migration and induce gene expression modifications.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The clinical efficacy of EGFR kinase inhibitors is limited by the development of drug resistance. The irreversible EGFR kinase inhibitor WZ4002 is effective against the most common mechanism of drug resistance mediated by the EGFR T790M mutation. Here we show that in multiple complementary models harboring EGFR T790M, resistance to WZ4002 develops through aberrant activation of ERK signaling caused by either an amplification of MAPK1 or by downregulation of negative regulators of ERK signaling. Inhibition of MEK or ERK restores sensitivity to WZ4002, and the combination of WZ4002 and a MEK inhibitor prevents the emergence of drug resistance. The WZ4002 resistant MAPK1 amplified cells also demonstrate an increase both in EGFR internalization and a decrease in sensitivity to cytotoxic chemotherapy compared to the parental counterparts. Our findings provide insights into mechanisms of drug resistance to EGFR kinase inhibitors and highlight rational combination therapies that should be evaluated in clinical trials.
Publication Title
Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Endocycle is an alternative cell cycle during which the DNA is replicated in the absence of cytokinesis, resulting in cellular endopolyploidy. The endocycle is frequenctly observed in plant species that grow under extreme conditions. Thus, endopolyploidy has been postulated to be a mechanism facilitating adaptive growth.
Publication Title
A Spatiotemporal DNA Endoploidy Map of the Arabidopsis Root Reveals Roles for the Endocycle in Root Development and Stress Adaptation.
Sample Metadata Fields
Specimen part
View Samples