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GSE72253
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
- 16 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
TEM differentiated in vitro were exposed to treatments increasing or decreasing their proangiogenic activity. We used microarrays to identify the genes differentially expressed among the treatments and associated to changes in TEM proangiogenic and protumoral functions.
Publication Title
TIE-2 and VEGFR kinase activities drive immunosuppressive function of TIE-2-expressing monocytes in human breast tumors.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The goal of this experiment was to identify possible genes affected directly or indirectly by anti-miR-191.
Publication Title
hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. Hitherto, indoleamine-2,3-dioxygenase 1 (IDO1) or tryptophan- 2, 3-dioxygenase (TDO2) are recognized as the main Trp-catabolizing enzymes (TCEs) responsible for the generation of AHR agonists. Here, the ability of the aromatic L-amino acid oxidase, interleukin 4 induced 1 (IL4I1), to activate the AHR was investigated using IL4I1 knockout CAS-1 glioblastoma cells.
Publication Title
IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Analysis of the effect of IL4I1 on gene expression of CD8 T-cells in CLL
Publication Title
IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Indole-3-pyruvate (I3P), an endogenous metabolite derived from tryptophan by gut microbiota and IL4I1 enzyme in humans can potentially activate the transcriptional activity of the Aryl Hydrocarbon receptor. Here we test this by stimulating AHR proficient U-87MG cells with I3P alone or in combination with the AHR antagonist SR1.
Publication Title
IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Illumina Genome Analyzer IIx
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-Wide Definition of Promoter and Enhancer Usage during Neural Induction of Human Embryonic Stem Cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genome-wide mapping of transcriptional regulatory elements are essential tools for the understanding of the molecular events orchestrating self-renewal, commitment and differentiation of stem cells. We combined high-throughput identification of nascent, Pol-II-transcribed RNAs by Cap Analysis of Gene Expression (CAGE-Seq) with genome-wide profiling of histones modifications by chromatin immunoprecipitation (ChIP-seq) to map active promoters and enhancers in a model of human neural commitment, represented by embryonic stem cells (ESCs) induced to differentiate into self-renewing neuroepithelial-like stem cells (NESC). We integrated CAGE-seq, ChIP-seq and gene expression profiles to discover shared or cell-specific regulatory elements, transcription start sites and transcripts associated to the transition from pluripotent to neural-restricted stem cell. Our analysis showed that >90% of the promoters are in common between the two cell types, while approximately half of the enhancers are cell-specific and account for most of the epigenetic changes occurring during neural induction, and most likely for the modulation of the promoters to generate cell-specific gene expression programs. Interestingly, the majority of the promoters activated or up-regulated during neural induction have a bivalent histone modification signature in ESCs, suggesting that developmentally-regulated promoters are already poised for transcription in ESCs, which are apparently pre-committed to neuroectodermal differentiation. Overall, our study provide a collection of differentially used enhancers, promoters, transcription starts sites, protein-coding and non-coding RNAs in human ESCs and ESC-derived NESCs, and a broad, genome-wide description of promoter and enhancer usage and gene expression programs occurring in the transition from a pluripotent to a neural-restricted cell fate.
Publication Title
Genome-Wide Definition of Promoter and Enhancer Usage during Neural Induction of Human Embryonic Stem Cells.
Sample Metadata Fields
Specimen part
View Samples