HEK293 cells were heatshocked and differentially expressed transcripts were identified Overall design: Transcriptomes of heatshocked HEK293 cells were compared to control cells. Heatshock and control samples were treated and sequenced in triplicate.
RNA Directed Modulation of Phenotypic Plasticity in Human Cells.
Cell line, Subject
View SamplesCD25 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.
CD25 blockade protects T cells from activation-induced cell death (AICD) via maintenance of TOSO expression.
Specimen part
View SamplesInducible 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.
Only therapeutic ICOS:ICOSL blockade alleviates acute graft versus host disease.
Sex, Specimen part
View SamplesComparison of gene expression profiles between neuroblastoma samples and Ewing family tumor samples. RNA from native tumor samples was processed for DNA-microarray analysis using Affymetrix HG-U133A microarrays. Primary image analysis was performed using MAS 5.0 and data were scaled to an target intesity of 500.
DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets.
No sample metadata fields
View SamplesWe found the PRC2 component EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in Ewing tumors and mesenchymal stem cells (Richter GH et al., Proc Natl Acad Sci U S A. 2009;106:5324-9). Downregulation of EZH2 by RNA interference in Ewing tumor cell lines suppressed oncogenic transformation in vitro and in vivo. These data suggest that EZH2 might play a central role in Ewing Tumor pathology.
Epigenetic maintenance of stemness and malignancy in peripheral neuroectodermal tumors by EZH2.
No sample metadata fields
View SamplesGene expression analysis of cell lines initially established as neuroblastoma cell lines. Cells were harvested and processed for DNA-microarray analysis using Affymetrix HG-U133A microarrays. Primary image analysis was performed using MAS 5.0 and data were scaled to an target intesity of 500.
DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets.
No sample metadata fields
View SamplesBy using high-density DNA microarrays, we analyzed the gene-expression profile of Hodgkin's lymphoma cell lines.
Gene expression profiles of Hodgkin's lymphoma cell lines with different sensitivity to cytotoxic drugs.
Cell line
View SamplesKrppel-like factor 3 (KLF3) is a transcriptional repressor that has roles in adipogenesis, B-cell maturation and erythropoiesis (for review see Pearson et al., 2012).
Regions outside the DNA-binding domain are critical for proper in vivo specificity of an archetypal zinc finger transcription factor.
Specimen part
View SamplesEwing 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.
Targeting the EWS-ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma.
Specimen part, Cell line
View SamplesEwing sarcoma, an osteolytic malignancy that mainly affects children and young adults, is characterized
DKK2 mediates osteolysis, invasiveness, and metastatic spread in Ewing sarcoma.
Cell line
View Samples