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GSE87433
Mus musculus
17 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Hyperglycemic memory is part of the pathogenesis of diabetic retinopathy. We established a novel mouse model of intermediate-term hyperglycemic memory and demonstrated that changes in gene expression and microvascular damage in the neurovascular unit of the diabetic retina persist after euglycemic reentry, indicating memory.
Publication Title
Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
In this study we obtained gene expression profiles of MCFS and parental MCF7 cell lines using Illumina microarrays
Publication Title
In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bromodomain-containing proteins bind acetylated lysine residues on histone tails and are involved in the recruitment of additional factors that mediate histone modifications and enable transcription. A compound, I-BET-762, that inhibits binding of an acetylated histone peptide to BRD4 and other proteins of the BET (bromodomain and extra-terminal domain) family, was previously shown to suppress the production of pro-inflammatory proteins by macrophages and block acute inflammation in mice. Here we investigate the effect of I-BET-762 on T cell function. We show that treatment of nave CD4+ T cells with I-BET-762 during early differentiation modulates subsequent cytokine production, and inhibits the ability of Th1-skewed cells to induce autoimmune pathogenesis in a model of experimental autoimmune encephalomyelitis (EAE) in vivo. The suppressive effects of I-BET-762 on T-cell mediated inflammation were not due to inhibition of expression of the pro-inflammatory cytokines, IFN-. or IL-17, but correlated with the ability to suppress GM-CSF production from CNS-infiltrating T cells, resulting in decreased recruitment of macrophages and granulocytes. The effects of I-BET-762 were distinct from those of the fumarate ester, dimethyl fumarate (DMF), a candidate drug for treatment of multiple sclerosis (MS). Our data suggest that I-BET and DMF could have complementary roles in the treatment of MS, and provide a strong rationale for inhibitors of BET-family proteins in the treatment of autoimmune diseases, based on their dual ability to suppress granulocyte and macrophage recruitment by T cells as well as production of pro-inflammatory proteins by macrophages.
Publication Title
Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations in the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis, a pediatric neurodegenerative disorder characterized by visual loss, epilepsy and psychomotor deterioration. Although most CLN3 patients carry the same 1 kb deletion in the CLN3 gene, their disease phenotype can be variable. The aims of this study were (1) to identify genes that are dysregulated in CLN3 disease regardless of the clinical course that could be useful as biomarkers, and (2) to find modifier genes that affect the progression rate of the disease.
Publication Title
Analysis of potential biomarkers and modifier genes affecting the clinical course of CLN3 disease.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGF pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.
Publication Title
Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Two genes have a synthetic lethal relationship when silencing or inhibition of one gene is only lethal in the context of a mutation or activation of the second gene. This situation offers an attractive therapeutic strategy, as inhibition of such a gene will only trigger cell death in tumor cells with an activated second oncogene but spare normal cells without activation of the second oncogene. Here we present evidence that CDK2 is synthetic lethal to neuroblastoma cells with MYCN amplification and overexpression. Neuroblastomas are childhood tumors with an often lethal outcome. Twenty percent of the tumors have MYCN amplification and these tumors are ultimately refractory to any therapy. Targeted silencing of CDK2 by three RNA interference techniques induced apoptosis in MYCN-amplified neuroblastoma cell lines, but not in MYCN single copy cells. Silencing of MYCN abrogated this apoptotic response in MYCN-amplified cells. Inversely, silencing of CDK2 in MYCN single copy cells did not trigger apoptosis, unless a MYCN transgene was activated. The MYCN induced apoptosis after CDK2 silencing was accompanied by nuclear stabilization of P53 and mRNA profiling showed up-regulation of P53 target genes. Silencing of P53 rescued the cells from MYCN-driven apoptosis. The synthetic lethality of CDK2 silencing in MYCN activated neuroblastoma cells can also be triggered by inhibition of CDK2 with a small molecule drug. Treatment of neuroblastoma cells with Roscovitine, a CDK inhibitor, at clinically achievable concentrations induced MYCN-dependent apoptosis. The synthetic lethal relation between CDK2 and MYCN indicates CDK2 inhibitors as potential MYCN-selective cancer therapeutics.
Publication Title
Inactivation of CDK2 is synthetically lethal to MYCN over-expressing cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genomic aberrations of Cyclin D1 (CCND1) and CDK4 in neuroblastoma indicate that dysregulation of the G1 entry checkpoint is an important cell cycle aberration in this pediatric tumor. Here we report that analysis of Affymetrix expression data of primary neuroblastic tumors shows an extensive over-expression of Cyclin D1 and CDK4 which correlates with histological subgroups and prognosis respectively. Immunohistochemical analysis demonstrated an over-expression of Cyclin D1 in neuroblasts and a low Cyclin D1 expression in all cell types in ganglioneuroma. This suggests an involvement of G1 regulating genes in neuronal differentiation processes which we further evaluated using RNA interference against Cyclin D1 and its kinase partner CDK4 in several neuroblastoma cell lines. This resulted in pRb pathway inhibition as shown by an almost complete disappearance of CDK4 specific pRb phosphorylation; reduction of E2F transcriptional activity and a decrease of Cyclin A protein levels. The Cyclin D1 and CDK4 knock-down resulted in a significant reduction in cell proliferation, a G1 specific cell cycle arrest and moreover an extensive neuronal differentiation. Affymetrix microarray profiling of siRNA treated cells revealed a shift in expression profile towards a neuronal phenotype. Several new potential downstream players are identified. We conclude that neuroblastoma functionally depend on over-expression of G1 regulating genes to maintain their undifferentiated phenotype.
Publication Title
Cyclin D1 and CDK4 activity contribute to the undifferentiated phenotype in neuroblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
There is differential expression of genes between cases and controls using microarray analysis, and genes that are crucial for host defence responses are significantly up-regulated in cases during pneumococcal infection.
Publication Title
Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case-control study.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The majority of sporadic colorectal cancer cases are initiated by mutations in the APC tumor suppressor gene leading to constitutive activation of the Wnt/b-catenin signaling pathway and adenoma formation. Several pre-clinical models carrying germline mutations in the endogenous mouse Apc tumor supressor gene have been generated and their phenotype characterized. The predisposition of these mouse models to multiple intestinal adenomas closely resembles the FAP phenotype at the molecular, cellular and phenotypic level and may prove valuable to elucidate the molecular and cellular mechanisms underlying colorectal tumorigenesis. The goal of this study is to establish an expression signature characteristic of intestinal tumors characterized by the inactivation of Apc.
Publication Title
Cross-species comparison of human and mouse intestinal polyps reveals conserved mechanisms in adenomatous polyposis coli (APC)-driven tumorigenesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neuroblastoma is a pediatric tumor of the sympathetic nervous system. MYCN (V-myc myelocytomatosis viral-related oncogene, neuroblastoma derived [avian]) is amplified in 20% of neuroblastomas, and these tumors carry a poor prognosis. However, tumors without MYCN amplification also may have a poor outcome. Here, we identified downstream targets of MYCN by shRNA-mediated silencing MYCN in neuroblastoma cells. From these targets, 157 genes showed an expression profile correlating with MYCN mRNA levels in NB88, a series of 88 neuroblastoma tumors, and therefore represent in vivo relevant MYCN pathway genes. This 157-gene signature identified very poor prognosis tumors in NB88 and independent neuroblastoma cohorts and was more powerful than MYCN amplification or MYCN expression alone. Remarkably, this signature also identified poor outcome of a group of tumors without MYCN amplification. Most of these tumors have low MYCN mRNA levels but high nuclear MYCN protein levels, suggesting stabilization of MYCN at the protein level. One tumor has an MYC amplification and high MYC expression. Chip-on-chip analyses showed that most genes in this signature are directly regulated by MYCN. MYCN induces genes functioning in cell cycle and DNA repair while repressing neuronal differentiation genes. The functional MYCN-157 signature recognizes classical neuroblastoma with MYCN amplification, as well as a newly identified group marked by MYCN protein stabilization.
Publication Title
Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples