Activating mutations in either KIT or PDGFRA are present in approximately 90% of gastrointestinal stromal tumors (GISTs). Although treatment with the KIT and PDGFR inhibitor imatinib can control advanced disease in about 80% of GIST patients, the beneficial effect is not durable. Here, we report that ligands from the FGF family reduced the effectiveness of imatinib in GIST cells, and FGF2 and FGFR1 are highly expressed in all primary GIST samples examined. The combination of KIT and FGFR inhibition showed increased growth inhibition in imatinib-sensitive GIST cell lines in the presence or absence of added FGF2 in vitro, and delayed tumor regrowth in vivo. In addition, inhibition of mitogen-activated protein kinase (MAPK) signaling by imatinib was not sustained in GIST cells. An extracellular signal-regulated kinase (ERK) rebound occurred through activation of FGF signaling, and was repressed by FGFR1 inhibition. Downregultation of Sprouty proteins played a role in the imatinib-induced feedback activation of FGF signaling in GIST cells.
FGFR-Mediated Reactivation of MAPK Signaling Attenuates Antitumor Effects of Imatinib in Gastrointestinal Stromal Tumors.
Cell line
View SamplesThis experiment is designed to detect genes differentially expressed in 2uM erlotinib treatment versus DMSO treatment and to identify differential gene set enrichments.
Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non-Small Cell Lung Cancer.
Specimen part, Cell line
View SamplesKnockdown of mutant and/or wild-type SF3B1 in MEL202 cell line by Degron knock-in, followed by RNA-seq, to identify splicing events governed by mutant SF3B1. Overall design: Control: parental MEL202 cell line. Experiments: mutant-SF3B1 knockdown; wildtype-SF3B1 knockdown; mutant SF3B1 knockout. Treatments: each of these four conditions plus and minus shld.
A chemical genetics approach for the functional assessment of novel cancer genes.
No sample metadata fields
View SamplesNeonates are intrinsically defective at creating memory CD8+ T cells in response to infection with intracellular pathogens. Here we investigated differential of small RNAs, transcription factors, and chemokine receptors regulation in neonates as compared to adults before and during infection. We found that prior to infection, na誰ve cells have a different expression profile for many microRNAs, and gene targets of these microRNAs show widespread expression differences. These targets and other changes in gene expression in na誰ve cells result in neonatal cells that get activated more easily, express chemokine receptors that home to sites of infection, and are less protected from apoptosis during contraction. As a result, changes in neonatal na誰ve cells drive effector cell terminal differentiation at the expense of creating long-lived memory cells. Overall design: total RNAs were sequenced from adult and neonatal CD8+ T cells before and during infection
MicroRNAs and Their Targets Are Differentially Regulated in Adult and Neonatal Mouse CD8+ T Cells.
No sample metadata fields
View SamplesNeonates are intrinsically defective at creating memory CD8+ T cells in response to infection with intracellular pathogens. Here we investigated differential of small RNAs, transcription factors, and chemokine receptors regulation in neonates as compared to adults before and during infection. We found that prior to infection, na誰ve cells have a different expression profile for many microRNAs, and gene targets of these microRNAs show widespread expression differences. These targets and other changes in gene expression in na誰ve cells result in neonatal cells that get activated more easily, express chemokine receptors that home to sites of infection, and are less protected from apoptosis during contraction. As a result, changes in neonatal na誰ve cells drive effector cell terminal differentiation at the expense of creating long-lived memory cells. Overall design: PolyA RNA was selected and sequenced from adult and neonatal CD8+ T cells before and during infection
MicroRNAs and Their Targets Are Differentially Regulated in Adult and Neonatal Mouse CD8+ T Cells.
No sample metadata fields
View SamplesLNCaP-derived MDV3100-resistant clones were treated with MDV3100 for 24h prior to collection
An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide).
Cell line
View SamplesGenetically engineered LNCaPs overexpressing various AR alleles were treated with 0.1% DMSO or 10uM MDV3100 for 24h prior to collection
An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide).
Cell line
View SamplesA375 cells with inducible knockdown HSF1 with and without HSP90 inhibitor treatment
Targeting HSF1 sensitizes cancer cells to HSP90 inhibition.
Cell line, Treatment
View SamplesChronic inflammation leading to pro-inflammatory macrophage infiltration contributes to the pathogenesis of type 2 diabetes and subsequently the development of diabetic nephropathy. Mesenchymal stem cells (MSCs) possess unique immunomodulatory and cytoprotective properties making them an ideal candidate for therapeutic intervention
Human mesenchymal stem cells alter the gene profile of monocytes from patients with Type 2 diabetes and end-stage renal disease.
Sex, Age, Specimen part, Disease
View SamplesThe aim of this study was to quantify the impact of chimeric Foxp3-GFP protein on the Treg cell transcriptional program.
An N-terminal mutation of the Foxp3 transcription factor alleviates arthritis but exacerbates diabetes.
Sex, Age, Specimen part
View Samples