Background: Central nervous system (CNS) metastases represent a major problem in the treatment of HER2-positive breast cancer due to the disappointing efficacy of HER2-targeted therapies in the brain microenvironment. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. Here, we tested the hypothesis that T-DM1 could overcome trastuzumab resistance in preclinical models of brain metastases.
Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment.
Specimen part, Disease, Time
View SamplesAnalysis of umbilical vein endothelial cells (HUVEC) treated with Egr-3 siRNA under the VEGF treatment for 0,1, and 4 h. Egr-3, a member of early growth response family, is immediately and dramatically induced by VEGF in HUVEC, which regulates expression of many genes related to endothelial activation.
Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3.
No sample metadata fields
View SamplesAlthough HSF1 is known to play an important role in regulating the cellular response to proteotoxic stressors, little is known about the structure and function of the HSF1 signaling network under both stressed and unstressed conditions. In this study, we used a combination of chromatin immunoprecipitation (ChIP) microarray analysis and time course gene expression microarray analysis with and without siRNA-mediated inhibition of HSF1 comprehensively identify genes directly and indirectly regulated by HSF1 and examine the structure of the extended HSF1 signaling network. Correlation between promoter binding and gene expression was not significant for all genes bound by HSF1 suggesting that HSF1 binding per se is not sufficient for expression. However, the correlation with promoter binding was significant for genes identified as HSF1-regulated following siRNA knockdown allowing the identification of direct transcriptional targets of HSF1. Among promoters bound by HSF1 following heat shock, a gene ontology (GO) analysis showed significant enrichment only in categories related to protein folding. In contrast, analysis of the extended HSF1 signaling network showed enrichment in a variety of categories related to protein folding, anti-apoptosis, RNA splicing, ubiquitination and others, highlighting a complex transcriptional program directly and indirectly regulated by HSF1.
Genome-wide analysis of human HSF1 signaling reveals a transcriptional program linked to cellular adaptation and survival.
No sample metadata fields
View SamplesFezf2 is highly and specifically expressed in mTECs in mouse thymus and Fezf2 deficiency (Fezf2 KO) in the thymus leads to autoimmunity. However, it is unclear how Fezf2 contributes to thymic gene expression.
Fezf2 Orchestrates a Thymic Program of Self-Antigen Expression for Immune Tolerance.
Age, Specimen part
View SamplesGenes regulated by miR-206 were identified by microarray analysis in RD cells transfected with a Negative Control (NC) or miR-206 Mimic
PAX7 is a required target for microRNA-206-induced differentiation of fusion-negative rhabdomyosarcoma.
Specimen part, Cell line, Time
View SamplesTo investigate how the phenotype of macrophages that have engulfed engineered nanoparticles (ENPs) differs from normal macrophages, we conducted Affymetrix microarray studies to identify the gene regulatory pathways affected by the ENPs. To mimic potential occupational exposure scenarios, the experimental design involved pretreatment of mouse primary bone marrow macrophages with the ENPs (25 mg/ml) for 24 hr, followed by removal of residual ENPs and challenging the macrophages with the TLR4 ligand and surrogate bacterial stimulus, lipopolysachharide (LPS) for 4 hr. The 4 hr challenge time was chosen based on preliminary studies which showed many of the proinflammatory gene expression responses peak between 2-6 hr after LPS treatment.
Dysregulation of macrophage activation profiles by engineered nanoparticles.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide approaches reveal functional vascular endothelial growth factor (VEGF)-inducible nuclear factor of activated T cells (NFAT) c1 binding to angiogenesis-related genes in the endothelium.
Specimen part, Treatment
View SamplesExperiment design
Glucose-dependent cell size is regulated by a G protein-coupled receptor system in yeast Saccharomyces cerevisiae.
No sample metadata fields
View SamplesWe performed the newly mapping of genome-wide NFATc1 binding events in VEGF-stimulated primary cultured endothelial cells, by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Combined NFATc1 ChIP-seq profile and the epigenetic histone marks revealed that predominant NFATc1-occupied peaks were overlapped with promoter marking but not silencer marking. DNA microarrays with NFATc1 expression or knockdown indicated the predominant NFATc1 binding targets were correlated with induced patterns.
Genome-wide approaches reveal functional vascular endothelial growth factor (VEGF)-inducible nuclear factor of activated T cells (NFAT) c1 binding to angiogenesis-related genes in the endothelium.
Specimen part, Treatment
View SamplesFoxp3 is indispensable for Treg suppressive function, but the stability of Foxp3 has been controversial. In autoimmune arthritis, Th17 cells play a critically important pathological role, but the origin of Th17 cells remains unknown
Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis.
Specimen part
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