E-TABM-674
Ontology highlight
ABSTRACT:
PROVIDER: E-TABM-674 | ExpressionAtlas | 2015-11-02
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-TABM-674-analysis-methods.tsv | Tabular | |||
| E-TABM-674-atlasExperimentSummary.Rdata | Rdata | |||
| E-TABM-674-configuration.xml | Xml | |||
| E-TABM-674-configuration.xml.beforeQC | Xml | |||
| E-TABM-674-percentile-ranks.tsv | Tabular |
Items per page: 5 1 - 5 of 60 |
Similar Datasets
Project description:This experiment is part of the FunGenES project (FunGenES - Functional Genomics in Embryonic Stem Cells partially funded by the 6th Framework Programme of the European Union, http://www.fungenes.org).The experiment was conducted at the Unyversity of Bath, Bath, UK. Aim of the experiment is the identification of genes regulated by PI3K-dependent signaling in undifferentiated ES cells. Materials and methods: To identify target genes of PI3-K signalling, the PI3-K signalling inhibitor LY294002 was used at a concentration which was shown to perturb self-renewal in the presence of LIF and which knocks down PI3K signals. CGR8 cells cultivated in serum-free conditions in the presence of LIF were starved for 24h in media lacking LIF and then pre-inubated for 30 minutes with 5 mM LY294002 in DMSO or with DMSO alone. Cells were then stimulated with LIF for 2h, prior to preparation of RNA samples. Relationships between samples: Samples were either maintained in LIF or LIF plus LY294002 (PI3K inhibitor) for the required treatment times. Treatments: Treatment times with PI3K inhibitor LY294002 at 5 uM 2h (n=5), 3h (n=5).
2009-05-07 | E-TABM-673 | biostudies-arrayexpress
Project description:Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. However, the use of mTOR inhibitors as single agents have shown limited clinical efficacy in relation with drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we evaluated the antitumor activity of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in primary MCL cells. We found that dual PI3K/mTOR inhibitor modulated angiogenesis, tumor invasiveness and cytokine signaling compared to a mTOR inhibitor and a pan-PI3K inhibitor in MCL. We used microarrays to compare the effect of these three compounds in MCL and identified distinct classes of down-regulated genes modulated by each compound. Global RNA expression in primary cells from two MCL patients treated with a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor for 8 hours
2013-12-14 | E-GEOD-53309 | biostudies-arrayexpress
Project description:Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by cutaneous manifestations. We first identified the profiles of noncoding RNAs (lncRNAs and miRNAs) in peripheral neutrophil exosomes (EXOs) of DM patients and explored their potential functional roles. Bioinformatics analyses were performed with R packages. Real-time quantitative PCR was used to validate the altered RNAs in DM neutrophil EXO-stimulated human dermal microvascular endothelial cells (HDMECs) and human skeletal muscle myoblasts (HSkMCs). In DM neutrophil EXOs, 124 upregulated lncRNAs (with 1,392 target genes), 255 downregulated lncRNAs (with 1867 target genes), 17 upregulated miRNAs (with 2,908 target genes), and 15 downregulated miRNAs (with 2,176 target genes) were identified. GO analysis showed that the differentially expressed (DE) lncRNAs and DE miRNAs participated in interleukin-6 and interferon-beta production, skeletal muscle cell proliferation and development, and endothelial cell development and differentiation. KEGG analysis suggested that DE lncRNAs and DE miRNAs were enriched in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways. Many novel and valuable DE lncRNAs and DE miRNAs interacted and cotargeted in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways. Our study suggests that neutrophil EXOs participate in DM pathogenesis through lncRNAs and miRNAs in the PI3K–Akt, MAPK, AMPK and FoxO signalling pathways.
2021-09-17 | GSE155281 | GEO
Project description:We previously noted that combination glucocorticoids and PI3K inhibition induces synergistic cell death. To identify genes involved in myeloma cell death we examined mRNA expression in each individual treatment and in the combination. The glucocoriticoid resistant cells (MM.1RL) are used as a negative control. Gene expression is assessed using Illumina Human HT-12v4 bead chips For this experiment, the lab is using human multiple myeloma cell lines that were isolated from a patient. MM.1S cells display sensitivity to glucocorticoids. MM.1RL cells display resistance to glucocorticoid treatment due to spontaneous mutations that render the glucocorticoid receptor inoperable. In this experiment, there will be 4 conditions for the MM.1S cells, and 2 conditions for the MM.1RL cells. We will be treating the MM.1S cells with a glucocorticoid alone (Dexamethasone - 1 uM), a PI3K inhibitor alone (LY249002 - 25 uM), a combination of the two drugs, and a vehicle control. The MM.1RL cells will be treated with a PI3K inhibitor alone, and with a vehicle control. Since the PI3K inhibitor is diluted in DMSO, as a control an equal volume of DMSO will be added to all conditions not containing the PI3K inhibitor. Conditions within the MM.1S cell line will be compared with each other. Specifically, we hope to identify genes that are similarly affected by all three experimental conditions. The MM.1RL conditions will not be analyzed at this time. There will be 4 biological replicates of each condition.
2015-12-07 | E-GEOD-64704 | biostudies-arrayexpress
Project description:Esophageal squamous cell carcinoma (OSCC) is a lethal digestive tract malignancy with limited effective interventions. This study aims to explore a new potential inhibitor on OSCC and investigate the underlying mechanisms. Based on a drug screen of an FDA-proven library consisting of 1404 compounds, we demonstrated that Omipalisib, a dual PI3K/mTOR inhibitor, markedly inhibited cell proliferation and colony formation in a panel of OSCC cell lines. Mechanistically, Omipalisib induced G0/G1 phase cell cycle arrest and apoptosis. Moreover, RNA-seq, KEGG and GSEA confirmed that the PI3K/mTOR signalling pathway is the primary target of Omipalisib in OSCC cells. Omipalisib treatment suppressed the PI3K/mTOR signalling pathway. Furthermore, Omipalisib exerted a significant antineoplastic effect on OSCC tumour xenografts in BALB/c nude mice without obvious side effects. The present study supports the rationale for using Omipalisib as a therapeutic approach for OSCC cases and suggests the potential clinical evaluation of this strategy.
2020-01-11 | GSE143462 | GEO
Project description:The PI3K/mTOR pathway is a constitutively active in multiple myeloma. Single inhibition of mTOR usually confers reactivation of the pathway. VS-5584 (SB2343) is a bispecific PI3K/mTOR inhibitor which effectively and specifically inhibits the target pathways and shows potent anti-myeloma activity. We utilised a gene microarray analysis to analyse and identify the genes that were sensitively regulated by VS-5584 treatment in OPM2.
2016-07-27 | GSE84862 | GEO
Project description:Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. However, the use of mTOR inhibitors as single agents have shown limited clinical efficacy in relation with drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we evaluated the antitumor activity of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in primary MCL cells. We found that dual PI3K/mTOR inhibitor modulated angiogenesis, tumor invasiveness and cytokine signaling compared to a mTOR inhibitor and a pan-PI3K inhibitor in MCL. We used microarrays to compare the effect of these three compounds in MCL and identified distinct classes of down-regulated genes modulated by each compound.
2013-12-14 | GSE53309 | GEO
Project description:Gp130 receptor engagement on neoplastic cells provides a link by which an inflammatory microenvironment facilitates tumour promotion. Although hyperactivation of the gp130-dependent Stat3 signalling node is commonly observed in solid tumours, Stat3 remains a challenging therapeutic target. To mimic excessive Stat3 signalling, we molecularly validate the gp130FF mouse as a preclinical model for inflammation-associated intestinal-type gastric cancer (IGC), with aberrant mammalian target of rapamycin (mTOR) pathway activity as shared feature. Accordingly, administration of the mTorc1 inhibitor RAD001 reversibly reduced IGC burden in gp130FF mice and suppressed colitis-associated cancer in wild-type mice. Since the therapeutic effect of RAD001 occurs independently of Stat3 hyperactivation, which is also dispensable for gp130-dependent engagement of the PI3K/Akt/mTorc1 pathway, we conclude that mTorc1 signalling limits tumour promoting Stat3 activity The mouse whole-genome gene expression profiling was performed on Illumina's MouseWG-6 v2.0 Expression BeadChips for 24 mice, with 8 mice in each group (gp130WT antral tissue, gp130FF unaffected antral tissue and gp130FF tumour tissue).
2013-01-29 | E-GEOD-35808 | biostudies-arrayexpress
Project description:This research trial is testing a combination of two experimental drugs, MSC1936369B (Mitogen-activated protein extracellular signal-regulated kinase (MEK) Inhibitor) and SAR245409 (Phosphatidylinositol 3-kinase (Pi3K)/Mammalian Target of Rapamycin (mTOR) inhibitor), in the treatment of locally advanced or metastatic solid tumors. The primary purpose of the study is to determine the maximum tolerated dose of the drug combination.
| 2109499 | ecrin-mdr-crc
Project description:Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Further, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. Affymetrix U133 Plus 2.0 profiling of SY5Y-TetR-FOXO3A cells treated with doxycycline and/or the PI3K/mTOR inhibitor PI-103. Each condition profiled in triplicate.
2013-05-01 | E-GEOD-42762 | biostudies-arrayexpress