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Mus musculus
31 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We exploited microarrays to detail the global program of gene expression underlying normal stem cells and cancer stem cells in the cerebellum and in medulloblastomas (MBs).
Publication Title
Gene signatures associated with mouse postnatal hindbrain neural stem cells and medulloblastoma cancer stem cells identify novel molecular mediators and predict human medulloblastoma molecular classification.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The first clinical trial testing the combination of targeted therapy with a BRAF inhibitor vemurafenib and immunotherapy with a CTLA-4 antibody ipilimumab was terminated early due to significant liver toxicities, possibly due to paradoxical activation of the MAPK pathway by BRAF inhibitors in tumors with wild type BRAF. MEK inhibitors can potentiate the MAPK inhibition in tumor, while potentially alleviating the unwanted paradoxical MAPK activation. With a mouse model of syngeneic BRAFV600E driven melanoma (SM1), we tested whether the addition of the MEK inhibitor trametinib would enhance the immunosensitization effects of the BRAF inhibitor dabrafenib. Combination of dabrafenib and trametinib with pmel-1 adoptive cell transfer (ACT) showed complete tumor regression. Bioluminescent imaging and tumor infiltrating lymphocyte (TIL) phenotyping showed increased effector infiltration to tumors with dabrafenib, trametinib or dabrafenib plus trametinib with pmel-1 ACT combination. Intracellular IFN gamma staining of the TILs and in vivo cytotoxicity studies showed trametinib was not detrimental to the effector functions in vivo. Dabrafenib increased tumor associated macrophages and T regulatory cells (Tregs) in the tumors, which can be overcome by addition of trametinib. Microarray analysis revealed increased melanoma antigen, MHC expression, and global immune-related gene upregulation with the triple combination therapy. Given the up-regulation of PD-L1 seen with dabrafenib and/or trametinib combined with antigen specific ACT, we tested the triple combination of dabrafenib, trametinib with anti-PD1 therapy, and observed superior anti-tumor effect to SM1 tumors. Our findings support the testing of these combinations in patients with BRAFV600E mutant metastatic melanoma.
Publication Title
Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma.
Sample Metadata Fields
Specimen part, Treatment, Compound
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
BRAF inhibitors are highly effective therapies for patients with BRAF V600 mutated metastatic melanoma. Patients who receive BRAF inhibitors develop a variety of hyper-proliferative skin conditions, whose pathogenic basis is the paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyper-proliferative skin changes improve when a MEK inhibitor is co-administered, as a MEK inhibitor blocks paradoxical MAPK activation. We tested whether we could take advantage of the mechanistic understanding of the skin hyper-proliferative side effects of BRAF inhibitors to accelerate skin wound healing by inducing paradoxical MAPK activation. Here we show that the BRAF inhibitor vemurafenib accelerates human keratinocyte proliferation and migration by increasing ERK phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing models in mice accelerated cutaneous wound healing and improved the tensile strength of healing wounds through paradoxical MAPK activation; addition of a MEK inhibitor reversed the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor did not increase the incidence of cutaneous squamous cell carcinomas in mice even after the application of a carcinogen. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds. Overall design: Full depth incisional wound mice tissues with/without Vemurafenib treatment were sent for RNAseq analysis on day 2, 6 and 14
Publication Title
Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
Description
Pheochromocytomas/paragangliomas are the most heritable of all tumors. However, there are still cases that are not explained by mutations in the known genes. We aimed to identify the genetic cause of disease in a patient strongly suspected of having hereditary tumors. We identified a novel de novo mutation in DNMT3A, affecting a highly conserved residue. Among other results from other techniques, a different global expression profile was observed in the patient carrying the mutated DNMT3A compared to controls (parents) by RNA-seq
Publication Title
Gain-of-function mutations in DNMT3A in patients with paraganglioma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Single O-GlcNAc modification orchestrate by O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA alias MGEA5) enzymes, affects signal transduction and gene expression by chromatin modulation. We developed Oga deleted MEF (mouse embryonic fibroblast) cells to investigate effects of O-GlcNAc modification in mice. RNA isolated from Mouse Embryonic Fibroblast cells generated from Oga Knock out (KO) Heterozygous (Het) and wild type (WT) cells and subjected to microarray analysis.
Publication Title
Conditional knock-out reveals a requirement for O-linked N-Acetylglucosaminase (O-GlcNAcase) in metabolic homeostasis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Loss of Amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase (AGL) drives bladder cancer growth. Low AGL expression predicts poor patient outcome. Currently no specific therapeutically tractable targets/pathways exist that could be used to treat patients with low AGL expressing bladder tumors.
Publication Title
Loss of Glycogen Debranching Enzyme AGL Drives Bladder Tumor Growth via Induction of Hyaluronic Acid Synthesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Vitamin C supplementation modulates gene expression in peripheral blood mononuclear cells specifically upon an inflammatory stimulus: a pilot study in healthy subjects.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A role of vitamin C (ascorbic acid) as an antioxidant molecule has been recognized, largely based on in vitro studies. However, more recently, the concept of antioxidant molecule has been reconsidered and its biological function is no longer considered to be simply due to its ability to act as electron donors, rather, it appears to act by modulating signaling and gene expression.
Publication Title
Vitamin C supplementation modulates gene expression in peripheral blood mononuclear cells specifically upon an inflammatory stimulus: a pilot study in healthy subjects.
Sample Metadata Fields
Specimen part
View Samples
GSE1462- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Extremely variable clinic and genetic features characterize Mitochondrial Encephalomyopathy Disorders (MED). Pathogenic mitochondrial DNA (mtDNA) defects can be divided into large-scale rearrangements and single point mutations. Clinical manifestations become evident when a threshold percentage of the total mtDNA is mutated. In some MED, the "mutant load" in an affected tissue is directly related to the severity of the phenotype. However, the clinical phenotype is not simply a direct consequence of the relative abundance of mutated mtDNA. Other factors, such as nuclear background, can contribute to the disease process, resulting in a wide range of phenotypes caused by the same mutation. Using Affymetrix oligonucleotide cDNA microarrays (HG-U133A), we studied the gene expression profile of muscle tissue biopsies obtained from 12 MED patients (4 common 4977-bp deleted mtDNA and 8 A3243G: 4 PEO and 4 MELAS phenotypes) compared with age-matched healthy individuals.
Publication Title
Skeletal muscle gene expression profiling in mitochondrial disorders.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Prostate cancer is dependent on androgen receptor (AR) signaling at all stages of the disease and cyclin D1 has been shown to negatively modulate the expression of the AR-dependent gene prostate specific antigen (KLK3/PSA).
Publication Title
Cyclin D1 is a selective modifier of androgen-dependent signaling and androgen receptor function.
Sample Metadata Fields
Cell line, Treatment
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