Ewing Sarcoma is caused by a pathognomonic genomic translocation that places an N-terminal EWSR1 gene in approximation with one of several ETS genes (typically FLI1). This aberration, in turn, alters the transcriptional regulation of more than five hundred genes and perturbs a number of critical pathways that promote oncogenesis, cell growth, invasion, and metastasis. Among them, translocation-mediated up-regulation of the insulin-like growth factor receptor 1 (IGF-1R) and mammalian target of rapamycin (mTOR) are of particular importance since they work in concert to facilitate IGF-1R expression and ligand-induced activation, respectively, of proven importance in ES transformation. When used as a single agent in Ewing sarcoma therapy, IGF-1R or mTOR inhibition leads to rapid counter-regulatory effects that blunt the intended therapeutic purpose. Therefore, identify new mechanisms of resistance that are used by Ewing sarcoma to evade cell death to single-agent IGF-1R or mTOR inhibition might suggest a number of therapeutic combinations that could improve their clinical activity.
IGF-1R and mTOR Blockade: Novel Resistance Mechanisms and Synergistic Drug Combinations for Ewing Sarcoma.
Specimen part
View SamplesResponse to allergen was studied in bronchial epithelial cell line H292. Cells were cultured and subsequently exposed to House dust mite or vessel (saline)
Allergen induced gene expression of airway epithelial cells shows a possible role for TNF-alpha.
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View SamplesResponse to allergen was studied in epithelial cells derived from allergic pantients and from healthy controls. Cells were cultured after isolation from a nasal biopsy. Cells were exposed to Housed dust mite or vessel (saline)
Primary nasal epithelium exposed to house dust mite extract shows activated expression in allergic individuals.
No sample metadata fields
View SamplesThe link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium.
The impact of allergic rhinitis and asthma on human nasal and bronchial epithelial gene expression.
Sex, Specimen part
View SamplesPurpose: Assess whether knocking out the UMLILO lncRNA altered the expression of genes transcribed within the CXCL chemokine TAD Outcome: To confirm whether the effect of UMLILO was limited to the CXCL TAD. Adeno-associated viral vectors (AAVs) were constructed that contain CRISPR/Cas9 and guides targeting UMLILO to delete the full length UMLILO transcript. RNAseq was performed on a transduced THP-1 population to verify genome-wide effects of UMLILO depletion. This revealed that IL8, CXCL1, 2, 3 transcription was abrogated, but a similar effect was not seen for genes located outside of the CXCL TAD boundary Overall design: AAVs were constructed that contain CRISPRs that harness non homologous end joining (NHEJ) to target UMLILO by deleting the genomic region encoding UMLILO, but not its promoter. The THP-1 monocytic cell line was transduced with the AAVs containing the CRISPRs for 1.5 weeks. Controls were transduced with AAV vector plasmids expressing SpCas9.
Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
Sex, Age, Specimen part, Treatment
View SamplesAnalysis of the effect of gene expression in the livers of old mice (25 months of age) fed rapamycin chronically (21 months) from 4 months of age.
Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
Sex, Age, Specimen part, Treatment
View SamplesAnalysis of the effect of gene expression in the livers of old mice (25 months of age) fed rapamycin short term (6 months) Rapamycin from 19 months of age.
Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.
Sex, Age, Specimen part, Treatment
View SamplesWe applied LY294002 in mesoderm downstream differentiation. LY294002-induced cells enriched in cardiomyocytes as well as WNT inhibitor IWP2.
Endogenous IGF Signaling Directs Heterogeneous Mesoderm Differentiation in Human Embryonic Stem Cells.
Specimen part, Cell line, Treatment
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