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GSE10909
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We have cloned and characterized a fusion gene NUP98/HHEX1 resulting from t(7;10) from a patient with acute myeloid leukemia (AML). As NUP98/HHEX acts as an aberrant transcriptional activator, putative targets were searched upon transient expression of the fusion in primary murine bone marrow cells.
Publication Title
Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 124 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Hepatocellular carcinoma (HCC) is a heterogeneous disease, and despite considerable research efforts, no molecular classification of HCC has been introduced in clinical practice. The existing molecular classification systems were established using resected tumors, which introduces a selection bias towards patients without liver cirrhosis and with early stage HCCs. So far, these classification systems have not been validated in liver biopsy specimens from tumors diagnosed at intermediate and late stages. We generated and analyzed expression profiles from 60 HCC biopsies from an unselected patient population with all tumor stages. Unbiased clustering identified 3 HCC classes. Class membership correlated with survival, tumor size, and with Edmondson and BCLC stage. Most biopsy specimens could be assigned to the classes of published classification systems, demonstrating that gene expression profiles obtained from patients with early stage disease are preserved in all stages of HCC. When a reference set of healthy liver samples was integrated in the analysis, we observed that the differentially regulated genes up- or down-regulated in a given class relative to other classes were actually dysregulated in the same direction in all HCCs, with quantitative rather than qualitative differences between the molecular subclasses. With the exception of a subset of samples with a definitive -catenin gene signature, biological pathway analysis could not identify class specific pathways reflecting the activation of distinct oncogenic programs. Our results suggest that gene expression profiling of HCC biopsies has limited potential to direct therapies that target specific driver pathways, but can identify subgroups of patients with different prognosis.
Publication Title
Gene expression analysis of biopsy samples reveals critical limitations of transcriptome-based molecular classifications of hepatocellular carcinoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pegylated interferon- (pegIFN-) has replaced un-modified recombinant IFN- for the treatment of chronic viral hepatitis because of its superior anti-viral efficacy that is generally attributed to improved pharmacokinetic properties. However, the pharmacodynamic effects of pegIFN- in the liver have not been studied. We analyzed pegIFN- induced signaling and gene regulation in paired liver biopsies obtained before treatment and during the first week after injection of pegIFN- in 18 patients. Despite sustained high serum concentrations of pegIFN- over the entire one-week dosing interval, IFN- signaling through the Jak-STAT pathway occurs only during the first day. PegIFN- induces hundreds of genes that can be classified into 4 clusters based on different temporal expression profiles. In all clusters, gene transcription is mainly driven by IFN stimulated gene factor 3 (ISGF3). IFN induced secondary transcription factors do not cause additional waves of gene expression. We could not confirm a role of un-phosphorylated STAT1 in prolonging IFN- induced gene transcription. Collectively, our results reveal that the major effects of pegIFN- in the liver are caused by an early and transient activation of ISGF3. Prolonging the serum half-life of IFN- does not necessarily improve its pharmacodynamic properties.
Publication Title
Pegylated IFN-α regulates hepatic gene expression through transient Jak/STAT activation.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. In the present study, we aimed to identify resistance mechanisms to the small-molecule tyrosine kinase inhibitor nintedanib in the Py2T murine breast cancer transplantation model. To identify differences in gene expression between short- and long-term nintedanib and untreaded FAC-sorted tumor and endothelial cells, we performed gene expression profiling by using affymetrix microarrays.
Publication Title
Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In the present study we have studied the mechanistic and functional aspects of NCoR1 function in mouse skeletal muscle. NCoR1 muscle-specific knockout mice exhibited an increased oxidative metabolism. Global gene expression analysis revealed a high overlap between the effects of NCoR1 deletion and peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha (PGC-1alpha) overexpression on oxidative metabolism in skeletal muscle. The repressive effect of NCoR1 on oxidative phosphorylation gene expression specifically antagonizes PGC-1alpha-mediated coactivation of ERRalpha. We therefore delineated the molecular mechanism by which a transcriptional network controlled by corepressor and coactivator proteins determines the metabolic properties of skeletal muscle, thus representing a potential therapeutic target for metabolic diseases.
Publication Title
The corepressor NCoR1 antagonizes PGC-1α and estrogen-related receptor α in the regulation of skeletal muscle function and oxidative metabolism.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Interferon-γ-stimulated genes, but not USP18, are expressed in livers of patients with acute hepatitis C.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
There is evidence that brain tumor cells may hijack self-renewal mechanism that regulate stem cell maintenance during normal development. Notch signaling is fundamental for maintaining normal neural stem cells in an undifferentiated state and has been implicated in in the maintenance of brain tumor stem cells as well.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Approximately 50% of patients with chronic hepatitis C (CHC) have a sustained virologic response (SVR) to treatment with pegylated interferon (pegINF)- and ribavirin. Non-response to treatment is associated with constitutively increased expression of IFN-stimulated genes (ISGs) in the liver. Treatment of patients with acute hepatitis C (AHC) is more effective, with SVR rates >90%. We investigated mechanisms of the different responses of patients with CHC and AHC to pegIFN- therapy. We analyzed IFN signaling and ISG expression in liver samples from patients with acute hepatitis C (AHC), patients with chronic hepatitis (CHC), and individuals without hepatitis C (controls) using microarray, immunohistochemical, and protein analyses. Findings were compared with those from primary human hepatocytes stimulated with IFN- or IFN-, as reference sets. Expression levels of 100s of genes, primarily those regulated by IFN-, were altered in liver samples from patients with AHC compared with controls. Expression of IFN-stimulated genes was induced in liver samples from patients with AHC, whereas expression of IFN-stimulated genes was induced in samples from patients with CHC. In an expression analysis of negative regulators of IFN- signaling, we did not observe differences in expression of SOCS1 or SOCS3 between liver samples from patients with AHC and those with CHC. However, USP18 (another negative regulator of IFN- signaling), was upregulated in liver samples of patients with CHC that did not respond to therapy, but not in AHC. In conclusion, differences in expression of ISGs might account for the greater response of patients with AHC, compared to those with CHC, to treatment with pegINF- and ribavirin. Specifically, USP18 is upregulated in liver samples of patients with CHC that do not respond to therapy, but not in patients with AHC.
Publication Title
Interferon-γ-stimulated genes, but not USP18, are expressed in livers of patients with acute hepatitis C.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Klf4 is a transcriptional regulator of genes critical for EMT, including Jnk1 (Mapk8).
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Neurons exploit mRNA localization and local translation to spatio-temporally regulate gene expression during development. Local translation and retrograde transport of transcription factors regulate nuclear gene expression in response to signaling events at distal neuronal ends. Whether epigenetic factors could also be involved in such regulation is not known. We report that the mRNA encoding the high mobility group N5 (HMGN5) chromatin binding protein localizes to growth cones of both neuronal-like cells and of hippocampal neurons. We show that Hmgn5 3UTR drives growth cone localization and translation of a reporter gene, and that HMGN5 can be retrogradely transported into the nucleus along neurites. Loss of HMGN5 function induces transcriptional changes and impairs neurite outgrowth while HMGN5 overexpression induces neurite outgrowth and global chromatin decompaction. Interestingly, control of both neurite outgrowth and chromatin structure is dependent on proper growth cone localization of Hmgn5 mRNA. Our results provide the first evidence that mRNA localization and local translation might serve as a mechanism to couple the dynamic neuronal outgrowth process with chromatin regulation in the nucleus.
Publication Title
Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth.
Sample Metadata Fields
No sample metadata fields
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