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GSE45544
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- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The expression profile of primary pediatric Ewing sarcoma (ES) and osteosarcoma (OS) were analyzed.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
CD25 monoclonal antibody binding to the alpha-chain of the Interleukin-2 (IL-2) receptor, blocks high affinity IL-2 binding thereby preventing complete T cell activation and being of ample importance in transplantation medicine and potentially the treatment of autoimmune disease. However, CD25 antibodies do not only block T cell activation but also prevent activation induced cell death (AICD) attributing a dual function to IL-2. In this study, the modulation of the genomic expression profile of human peripheral blood mononuclear cells (PBMC) with therapeutic concentrations of humanized anti-CD25 mAb was investigated. PBMC were stimulated with CD3 antibody OKT-3 together with recombinant IL-2 in the absence or presence of anti-CD25 mAb. RNA was extracted and subjected to microarray analysis on U133A microarrays (Affymetrix). The expression profile revealed the up-regulation of 62 genes and down-regulation of 38 genes by anti-CD25 mAb, respectively.
Publication Title
CD25 blockade protects T cells from activation-induced cell death (AICD) via maintenance of TOSO expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Ewing Tumors (ET) are highly malignant tumors, localized in bone or soft tissue and are molecularly defined by ews/ets translocations. We identified histone methyl-transferase Enhancer of Zeste, Drosophila, Homolog 2 (EZH2) to be increased in ET. EZH2s suppressive activity maintains stemness in normal and malignant cells. Here we found EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in ET and mesenchymal stem cells. Downregulation of EZH2 by RNA interference in ET suppressed oncogenic transformation by inhibiting clonogenicity in vitro. Similarly, tumor development and metastasis in immunodeficient Rag2-/-C-/- mice was suppressed. EZH2-mediated gene silencing was shown to be dependent on histone deacetylase (HDAC) activity. Subsequent microarray analysis of EZH2 knock down, HDAC-inhibitor treatment and confirmation in independent assays revealed an undifferentiated phenotype maintained by EZH2 in ET. Downregulation of EZH2 decreased histone H3 lysine 27 trimethylation (H3K27me3) at target loci. EZH2 regulated stemness genes such as nerve growth factor receptor (NGFR) as well as genes involved in neuroectodermal differentiation (EMP1, EPHB2, GFAP, GAP43). These data suggest that EZH2 might play a central role in Ewing Tumor pathology shaping the oncogenicity and stem cell phenotype of this tumor presumably by epigenetic regulation.
Publication Title
EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Osteoblasts are adherent cells. Under physiological conditions they attach to mineralized and non-mineralized osseous surfaces. However, how exactly osteoblasts respond to these different osseous surfaces is largely unknown. Our hypothesis was that the state of matrix mineralization provides a functional signal to osteoblasts. To assess the osteoblast response to mineralized compared to demineralized osseous surfaces, we assessed the transcriptom.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Inducible co-stimulator (ICOS) interaction with its ligand (ICOSL) is involved in several T cell effector functions. While blockade of ICOS:ICOSL interaction in chronic graft versus host disease (GVHD) seems benefi cial, results for acute GVHD remain controversial. To further elucidate its role in acute GVHD, C57BL / 6 mice were lethally irradiated and reconstituted with allogeneic spleen cells in the absence or presence of ICOSL-blocking mAb. Mice reconstituted with allogeneic spleen cells experienced severe GVHD and died untreated within 6 9 days after transplantation. Mice treated with an anti-ICOSL mAb starting from day 3 after transplantation gained weight again and survived for at least additional 12 days, although the treatment was already stopped at day 11 after transplantation. In contrast, the anti-ICOSL treatment starting from day 0 did not prevent GVHD. The diff erence between therapeutic (day 3) and prophylactic (day 0) anti-ICOSL treatment was independent of CD25 + CD4 + regulatory T cells since their depletion did not abrogate the therapeutic eff ect of ICOSL blockade. Microarray analysis revealed IFN- and chemokine up-regulation in spleen cells of prophylactically treated mice, emphasizing kinetic dependence of acute GVHD modulation via blockade of ICOS:ICOSL interaction.
Publication Title
Only therapeutic ICOS:ICOSL blockade alleviates acute graft versus host disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Oncogene addiction provides ideal targets for immunotherapy. We previously showed that the high expression of the conserved transcription factor MondoA mediates glucose consumption and stemness of a cALL cell line. We now report the expression of MondoA (MLXIP) in cALL compared to other malignancies, its role in malignancy of cALL in vivo, downstream pathways and correlation with relapse risk. Given the non-accessibility of transcription factors by drugs or chimeric antigen receptor transgenic T cells, we assessed the targetability of MondoA by allo-restricted, peptide-specific T cells. We found MondoA to be most highly expressed in pediatric cALL. MondoA knock down (KD) in cALL cell lines and their subsequent analysis in xenograft mice reduced the number of leukemic blasts in blood, marrow and spleen. Spleen size and weight normalized in mice after MondoA KD. Consistent with these data, MondoA overexpression correlated with relapse risk in cALL patients, as its expression was 63% higher in the very high-risk group relative to the non-high-risk group. Transcriptomic profiling of cALL cell lines after MondoA KD revealed an induction of aerobic glycolysis switch genes and hypoxia-response by MondoA. Indeed, MondoA appeared to be required for HIF1A protein stabilization. Therapeutically, MondoA-derived peptide antigens and HLA-A*02:01+ cALL lines were successfully recognized and killed by specific, allo-restricted CD8+ T cells. In conclusion, our findings demonstrate that MondoA maintains leukemic burden and aggressiveness of cALL in vivo possibly by modulating metabolic and hypoxia stress response. Moreover, we identified MondoA as a promising target for immunotherapy of cALL.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by early metastasis into lung and bone. Genetically, ES are defined by balanced chromosomal EWS/ETS translocations, which give rise to chimeric proteins (EWS-ETS) that generate an oncogenic transcriptional program associated with altered epigenetic marks throughout the genome. By use of an inhibitor (JQ1) blocking BET bromodomain binding proteins (BRDs) we strikingly observed a strong down-regulation of the predominant EWS-ETS protein EWS/FLI1 in a dose dependent manner. Microarray analysis further revealed JQ1 treatment to block a typical ES associated expression program. The effect on this expression program could be mimicked by RNA interference with BRD3 or BRD4 expression, indicating that the EWS/FLI1 mediated expression profile is at least in part mediated via such epigenetic readers. Consequently, contact dependent and independent proliferation of different ES lines was strongly inhibited. Mechanistically, treatment of ES resulted in a partial arrest of the cell cycle as well as induction of apoptosis. Tumor development was suppressed dose dependently in a xeno-transplant model in immune deficient mice, overall indicating that ES may be susceptible to treatment with epigenetic inhibitors blocking BET bromodomain activity and the associated pathognomonic EWS-ETS transcriptional program in ES.
Publication Title
Targeting the EWS-ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression profiling of in vitro differentiated murine Th cell subsets. Flow cytometrically sorted naive Th cells (CD4+ CD44- Foxp3-) were polyclonally stimulated in vitro for 3 days using 4 g/ml plate-bound antibody to CD3 (145-2C11) and 2 g/ml soluble antibody to CD28 (PV-1).
Publication Title
IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
Examination of gene expression patterns in lineage negative FLT3-ITD and pMIG-transduced BM cells via microarray study.
Publication Title
RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells.
Sample Metadata Fields
Specimen part
View Samples