E-GEOD-40776
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA174869
PROVIDER: E-GEOD-40776 | ExpressionAtlas | 2025-01-24
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-40776-analysis-methods.tsv | Tabular | |||
| E-GEOD-40776-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-40776-configuration.xml | Xml | |||
| E-GEOD-40776-percentile-ranks.tsv | Tabular | |||
| E-GEOD-40776.condensed-sdrf.tsv | Tabular |
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Similar Datasets
Project description:MGMT modulates glioblastoma angiogenesis and response to the tyrosine kinase inhibitor sunitinib
| PRJNA174869 | ENA
Project description:Angiogenesis inhibitors, such as sunitinib, represent a promising strategy to improve glioblastoma (GBM) tumor response. In this study, we used the O6-methylguanine methyltransferase (MGMT)-negative GBM cell line U87MG stably transfected with MGMT (U87/MGMT) to assess whether MGMT expression affects the response to sunitinib. We showed that the addition of sunitinib to standard therapy (temozolomide [TMZ] and radiation therapy [RT]) significantly improved the response of MGMT positive but not of MGMT-negative cells. Gene expression profiling revealed alterations in the angiogenic profile, as well as differential expression of several receptor tyrosine kinases targeted by sunitinib. MGMT-positive cells displayed higher levels of vascular endothelial growth factor receptor 1 (VEGFR-1) compared with U87/EV cells, whereas they displayed decreased levels of VEGFR-2. Depleting MGMT using O6-benzylguanine suggested that the expression of these receptors was directly related to the MGMT status. Also, we showed that MGMT expression was associated with a dramatic increase in the soluble VEGFR-1/VEGFA ratio, thereby suggesting a decrease in bioactive VEGFA and a shift towards an antiangiogenic profile. The reduced angiogenic potential of MGMT-positive cells is supported by: (i) the decreased ability of their secreted factors to induce endothelial tube formation in vitro and (ii) their low tumorigenicity in vivo compared with the MGMT-negative cells. Our study is the first to show a direct link between MGMT expression and decreased angiogenicity and tumorigenicity of GBM cells and suggests the combination of sunitinib and standard therapy as an alternative strategy for GBM patients with MGMT-positive tumors.
2012-09-11 | GSE40776 | GEO
Project description:Angiogenesis inhibitors, such as sunitinib, represent a promising strategy to improve glioblastoma (GBM) tumor response. In this study, we used the O6-methylguanine methyltransferase (MGMT)-negative GBM cell line U87MG stably transfected with MGMT (U87/MGMT) to assess whether MGMT expression affects the response to sunitinib. We showed that the addition of sunitinib to standard therapy (temozolomide [TMZ] and radiation therapy [RT]) significantly improved the response of MGMT positive but not of MGMT-negative cells. Gene expression profiling revealed alterations in the angiogenic profile, as well as differential expression of several receptor tyrosine kinases targeted by sunitinib. MGMT-positive cells displayed higher levels of vascular endothelial growth factor receptor 1 (VEGFR-1) compared with U87/EV cells, whereas they displayed decreased levels of VEGFR-2. Depleting MGMT using O6-benzylguanine suggested that the expression of these receptors was directly related to the MGMT status. Also, we showed that MGMT expression was associated with a dramatic increase in the soluble VEGFR-1/VEGFA ratio, thereby suggesting a decrease in bioactive VEGFA and a shift towards an antiangiogenic profile. The reduced angiogenic potential of MGMT-positive cells is supported by: (i) the decreased ability of their secreted factors to induce endothelial tube formation in vitro and (ii) their low tumorigenicity in vivo compared with the MGMT-negative cells. Our study is the first to show a direct link between MGMT expression and decreased angiogenicity and tumorigenicity of GBM cells and suggests the combination of sunitinib and standard therapy as an alternative strategy for GBM patients with MGMT-positive tumors. RNA was isolated from parental U87 (U87_EV) and MGMT-transfected U87 (U87_MGMT) triplicate. Pairwise gene expression differences were compared between the two cell lines. Features selected had more than 2-fold up-or down-regulated (P values of >05, unpaired Studentâs t-test with Bonferroni multiple testing correction) were identified. Database for annotation, visualization, and integrated discovery23 was used to identify enriched gene ontology (GO) biological themes.24 The GO data mining was conducted at a term specificity level 3.25 The EASE score was set at 0.05 and the minimum number of genes in a category was 5.
2012-09-11 | E-GEOD-40776 | biostudies-arrayexpress
Project description:Sensitivity to temozolomide (TMZ) is restricted to a subset of glioblastoma patients, with the major determinant of resistance a lack of promoter methylation of the gene encoding the DNA methyltransferase MGMT, although other mechanisms are thought to be active. In a genome-wide screen of paediatric and adult glioma cells, we identified a co-ordinated upregulation of HOX gene expression in the MGMT-independent cell line KNS42. As a recent study has proposed a mechanism for this observation whereby transcriptional activation of the HOXA cluster is reversible by a PI3-kinase inhibitor through an epigenetic mechanism involving histone H3K27 trimethylation, we sought to investigate whether this was active in our system. We thus treated KNS42 cells for 24 hours with the dual PI3-kinase / mTOR inhibitor PI-103 at 5x IC50 and carried out gene expression profiling using Illumina HT-12 microarrays.
2011-01-08 | E-TABM-890 | biostudies-arrayexpress
Project description:Amplification of the epidermal growth factor receptor (EGFR, A0 for non-amplified and A1 for amplified) gene is one of the most common oncogenic alterations in glioblastoma (45%) making it a prime target for therapy. However, small molecule inhibitors of the EGFR tyrosine kinase showed disappointing efficacy in clinical trials for glioblastoma. Here we report expression data for 33 samples including 6 GBM derived xenografts (3 controls and 3 treated by tyrosine kinase inhibitor gefitinib) and 27 glioblastoma tumors (11 controls and 16 treated by tyrosine kinase inhibitor gefitinib). Note that T0, T1 and T2 treatment types mean that control, Gefitinib treatment and Gefitinib treatment (but not according to protocol schedule), respectively.
2024-10-21 | GSE279426 | GEO
Project description:Tyrosine Kinase Inhibitor Cardiotoxicity
| PRJNA352077 | ENA
Project description:Quantitative methylation-specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status, raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. Samples of glioblastoma and respective glioblastoma-derived spheres (GS), cultured under stem cell conditions, were analyzed for the degree and pattern of MGMT promoter methylation by methylation-specific clone sequencing, MGMT gene dosage, chromatin status, and respective effects on MGMT expression and MGMT activity.
2017-12-15 | GSE108098 | GEO
Project description:Patients diagnosed with glioblastoma (GBM) with sustained synthesis of the DNA repair enzyme, O6-methyl guanine DNA methytransferase (MGMT), are rendered resistant to Temozolomide (TMZ) chemotherapy. Here, we hypothesized that pretreatment with the proteasome inhibitor Bortezomib (BTZ, Velcade) might sensitize these GBM to TMZ by depleting MGMT.
2019-08-20 | PXD007193 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below. BACKGROUND: Gliomas evade current therapies through primary and acquired resistance and the effect of temozolomide is mainly restricted to the subgroup of methylguanin-O6-methyltransferase promoter (MGMT) hypermethylated tumors. Further resistance markers and pathways against chemotherapy and radiotherapy are largely unknown and would help for better stratification. METHODS: The diagnostic cohorts involved clinical data and methylation profiles of the NOA-08 (n = 104, elderly glioblastoma) and the EORTC 26101 (n = 297, glioblastoma) studies and 398 patients with glioblastoma from the Heidelberg center. Twenty-eight glioblastoma CpGs from 17 DNA damage response (DDR) genes that negatively correlate with expression derived from a 450 DDR gene list as well as telomerase reverse transcriptase (TERT) promoter mutations were investigated for outcome and interaction with therapy and classifier assignments. RESULTS: CpG methylation in IDH wildtype tumors had the highest association with the mesenchymal (MES) and receptor tyrosine kinase (RTK) I glioblastoma subgroup. MES tumors have lower tumor purity and differ in copy number variations on chromosomes 7 and 10 from the RTK I and II subtypes. CpG hypomethylation of DDR genes (TP73, CCND3, CSNK1E, EXO1, CUL4A and PRPF19) correlated with worse patient survival in particular in MGMT unmethylated tumors. TERT promoter mutation is most frequent in RTK I and II subtypes and associated with worse survival in primary glioblastoma. Primary glioma cells show methylation pattern that resemble RTK I and II glioma and differ from long term established cell lines. Knock-down of selected resistance genes PRPF19 and TERT increase sensitivity to temozolomide treatment in vitro. CONCLUSION: Methylation of DDR genes and TERT promoter mutations are associated with tumor prognosis, dependent on the methylation cluster and MGMT promoter methylation status in high-grade glioma.
2020-11-18 | GSE143843 | GEO
Project description:Glioblastoma is the most common malignant primary brain tumor. Clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutation and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNA (lncRNA) alterations may contribute to glioblastoma pathogenesis and potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was analyzed in multiple glioblastoma gene expression data sets for associations with prognosis and IDH mutation and MGMT promoter methylation status. The role of HOTAIRM1 in glioblastoma biology and radiotherapy resistance was characterized in vitro and in vivo. We identified HOTAIRM1 as a candidate lncRNA whose up-regulation is significantly associated with shorter survival of glioblastoma patients independent from IDH mutation and MGMT promoter methylation. Glioblastoma cell line models uniformly showed reduced cell viability, less invasive growth and diminished colony formation capacity upon HOTAIRM1 down-regulation. Integrated proteogenomic analyses and determination of reactive oxygen species (ROS) levels revealed impaired mitochondrial function and increased ROS levels upon HOTAIRM1 knock-down. HOTAIRM1 knock-down decreased expression of transglutaminase 2 (TGM2) as a candidate protein implicated in mitochondrial function, and knock-down of TGM2 mimicked the phenotype of HOTAIRM1 down-regulation in glioblastoma cells. Moreover, HOTAIRM1 modulates radiosensitivity of glioblastoma cells in vitro and in vivo. Our data support a role for HOTAIRM1 as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. Targeting HOTAIRM1 may be a promising new therapeutic approach.
2022-01-19 | PXD020141 | Pride