The aim of this study was to identify the transcriptomic response 6 hours after the MRT irradiation, in normal brain tissue (11 samples) and in glioma tissue (11 samples), in rat.
Early gene expression analysis in 9L orthotopic tumor-bearing rats identifies immune modulation in molecular response to synchrotron microbeam radiation therapy.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions.
No sample metadata fields
View SamplesThe goal of the study was to identify on a genome-wide scale RNAs that are enriched at the leading edge of migrating cells. For this, we employed a fractionation method in which cells are plated on a microporous filter whose bottom side only is coated with fibronectin. The cells thus polarize and extend pseudopodial protrusions towards the bottom surface. These protruding pseudopodia can then be physically isolated from the bottom surface of the filter and their contents compared with the remaining cell bodies, which are isolated from the upper surface of the filter.
Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions.
No sample metadata fields
View SamplesThe goal of the study was to identify on a genome-wide scale RNAs that are enriched at the leading edge of migrating cells. For this, we employed a fractionation method in which serum-starved cells are first plated and allowed to spread on a microporous filter. Addition of LPA at the bottom side of the filter induces the cells to polarize and extend pseudopodial protrusions. These protruding pseudopodia can then be physically isolated from the bottom surface of the filter and their contents compared with the remaining cell bodies, which are isolated from the upper surface of the filter.
Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions.
No sample metadata fields
View SamplesThe rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of novel therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus Kinase (JAK) activity with no precedent in adipose tissue biology that permanently confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a novel role for the JAK/STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity. Overall design: Human pluripotent stem-cell derived mesenchymal progenitor cells (PSC-MPCs), white adipose cells (PSC-WA), and brown adipose cells (PSC-BA) were treated with DMSO (as control), a JAK3-inhibitor compound, and a SYK-inhibitor compound respectively. Transcriptomic expression profiling was performed at 24 hours and 7 days respectively. Three biological replicates are available for each condition defined by cell type, compound, and time.
White-to-brown metabolic conversion of human adipocytes by JAK inhibition.
No sample metadata fields
View SamplesPURPOSE To identify retinal pigment epithelial (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. METHODS Differential gene expression of over 34,000 well-characterized mouse genes, in the RPE/choroid of 6 week old C57BL/6J mice were analyzed after intravitreal steroid injections at 1 week and 1 month post injection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpringGX12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. RESULTS Both triamcinolone and dexamethasone caused differential activation of genes involved in Circadian Rhythm Signaling pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in Calcium Signaling (1 week) and Glutamate Signaling pathways (1month). In contrast, Dexamethasone (Dex) affected the GABA Receptor Signaling (1 week) and Serotonin Receptor Signaling (1month) pathways. CONCLUSIONS Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid cells during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina.
Comparison of In Vivo Gene Expression Profiling of RPE/Choroid following Intravitreal Injection of Dexamethasone and Triamcinolone Acetonide.
Sex, Specimen part, Treatment
View SamplesInterleukin-6 (IL-6) is a pleiotropic cytokine that plays a major role in responding to injury or infection as well as immune response, inflammation, and hematopoiesis. High levels of circulating IL-6 are observed in many tumor types and are associated with poor outcomes. We show that knockdown of IL-6 or IL-6 receptor (IL-6R) inhibits IL-6 signaling and cell viability. In contrast, over-expression of IL-6 enhances tumor growth in vitro and in vivo, thereby supporting the role of IL-6 in tumorigenesis. We developed a human monoclonal antibody against human IL-6 (MEDI5117) that bears Fc mutations (YTE) to extend its half-life. We tested this antibody in several cancer cell lines that secrete high levels of IL-6, soluble IL-6R, and express gp130. High constitutive pSTAT3 (phosphorylated signal transducer and activator of transcription 3) activation is seen in several of these cell lines, suggesting autocrine growth stimulation by IL-6. Treating these cell lines with MEDI5117 effectively blocked phosphorylation of STAT3 and inhibited IL-6-induced cell proliferation. In vivo, MEDI5117 suppressed the growth of multiple cancer xenograft models and specifically modulated IL-6 signaling and downstream gene expression. Combining MEDI5117 with chemotherapy or gefitinib demonstrated significantly enhanced anti-tumor activities in vivo. Taken together, our data suggest that IL-6 signaling contributes to tumor growth, thereby supporting the development of MEDI5117 as a therapy to treat solid tumors.
A Novel IL6 Antibody Sensitizes Multiple Tumor Types to Chemotherapy Including Trastuzumab-Resistant Tumors.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global gene expression analysis of amniotic fluid cell-free RNA from recipient twins with twin-twin transfusion syndrome.
Sex
View SamplesTo understand the biological pathways involved in twin-twin transfusion syndrome (TTTS) by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA
Global gene expression analysis of amniotic fluid cell-free RNA from recipient twins with twin-twin transfusion syndrome.
Sex
View SamplesExpression data from xenograft in BALB/c 6-wk-old nude mice with PC3 prostate cancer cells stably expressing PML or a vector control after treatment of the mice with palbociclib (100mg/kg/day diluted in sodium lactate 50mM pH4 given by gavage) during 5 consecutive days
A CDK4/6-Dependent Epigenetic Mechanism Protects Cancer Cells from PML-induced Senescence.
Specimen part, Cell line
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