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GSE77651
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Downregulation of the hematopoietic transcription factor PU.1 in PU.1 low acute myeloid leukemia cells (AML) by novel heterocyclic diamidines or PU.1 inhibitors leads to decrease cell proliferation and apoptosis, representing a new therapeutic strategy for AML treatment. These inhibitors induces decreased PU.1 binding on its target sites, as well as deregulation in PU.1 canonical target genes
Publication Title
Pharmacological inhibition of the transcription factor PU.1 in leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
New IDH1 mutant inhibitors for treatment of acute myeloid leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st), Illumina HiSeq 2000
Description
Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are driver mutations in acute myeloid leukemia (AML) and other cancers. We report the development of new allosteric inhibitors of mutant IDH1. Crystallographic and biochemical results demonstrated that compounds of this chemical series bind to an allosteric site and lock the enzyme in a catalytically inactive conformation, thereby enabling inhibition of different clinically relevant IDH1 mutants. Treatment of IDH1 mutant primary AML cells uniformly led to a decrease in intracellular 2-HG, abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells, in vitro and in vivo. Molecularly, treatment with the inhibitors led to a reversal of the DNA cytosine hypermethylation patterns caused by mutant IDH1 in AML patients cells. Our study provides proof-of-concept for the molecular and biological activity of novel allosteric inhibitors for targeting different mutant forms of IDH1 in leukemia. To obtain insight into the molecular mechanism for the induction of granulocytic differentiation and cell death following inhibition of IDH1 mutant protein in primary AML cells, we performed gene expression microarrays following treatment with either GSK321 IDH1 inhibitor or Controls (DMSO or GSK990 inactive inhibitor).
Publication Title
New IDH1 mutant inhibitors for treatment of acute myeloid leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Primary pediatric Ewing sarcoma (ES), one uncharacterized sarcoma as well as primary and well established ES cell lines were compared to probes of different normal tissues
Publication Title
Distinct transcriptional signature and immunoprofile of CIC-DUX4 fusion-positive round cell tumors compared to EWSR1-rearranged Ewing sarcomas: further evidence toward distinct pathologic entities.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 48 Downloadable Samples
- Illumina mouseRef-8 v1.1 expression beadchip
Description
A/J mice are genetically predisposed to spontaneous and/or chemically-induced lung tumors while C57BL/6J (B6) mice are resistant. This genetic disparity provides a unique scenario to identify molecular mechanisms associated with the lung response to welding fume at the transcriptome level.
Publication Title
Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 55 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 52 Downloadable Samples
- IlluminaHiSeq2000
Description
We utilized RNA-Seq on rat Schwann (S16) cells to determine global gene expression. This information was generated as part of a larger effort to characterize cis-regulatory elements and global gene expression within Schwann cells. To achieve this, we generated RPKM values across two independent biological replicates. This dataset was also used to predict cis-regulatory element function on genes following CRISPR knockout studies. Overall design: Performed two technical replicates of RNA-Seq on two independent biological replicates of S16 cells
Publication Title
A genome-wide assessment of conserved SNP alleles reveals a panel of regulatory SNPs relevant to the peripheral nerve.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
There is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology.
Publication Title
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 28 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
There is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology.
Publication Title
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 119 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Liposarcoma is the most common soft tissue sarcoma, accounting for about 20% of cases. Liposarcoma is classified into 5 histologic subtypes that fall into 3 biological groups characterized by specific genetic alterations. To identify genes that contribute to liposarcomagenesis and to better predict outcome for patients with the disease, we undertook expression profiling of liposarcoma. U133A expression profiling was performed on 140 primary liposarcoma samples, which were randomly split into training set (n=95) and test set (n=45). A multi-gene predictor for distant recurrence-free survival (DRFS) was developed using the supervised principal component method. Expression levels of the 588 genes in the predictor were used to calculate a risk score for each patient. In validation of the predictor in the test set, patients with low risk score had a 3-year DRFS of 83% vs. 45% for high risk score patients (P=0.001). The hazard ratio for high vs. low score, adjusted for histologic subtype, was 4.42 (95% confidence interval 1.26-15.55; P=0.021). The concordance probability for risk score was 0.732. Genes related to adipogenesis, DNA replication, mitosis, and spindle assembly checkpoint control were all highly represented in the multi-gene predictor. Three genes from the predictor, TOP2A, PTK7, and CHEK1, were found to be overexpressed in liposarcoma samples of all five subtypes and in liposarcoma cell lines. Knockdown of these genes in liposarcoma cell lines reduced proliferation and invasiveness and increased apoptosis. Thus, genes identified from this predictor appear to have roles in liposarcomagenesis and have promise as therapeutic targets. In addition, the multi-gene predictor will improve risk stratification for individual patients with liposarcoma.
Publication Title
Expression profiling of liposarcoma yields a multigene predictor of patient outcome and identifies genes that contribute to liposarcomagenesis.
Sample Metadata Fields
Specimen part
View Samples