Glioblastoma is the most aggressive primary brain tumor in adults and due to the invasive nature it cannot be completely removed. We have recently shown that the WNT inhibitory factor 1 (WIF1), a secreted inhibitor of WNTs, is downregulated in glioblastoma and acts as strong tumor suppressor. In search of a mediator for this function differential gene expression profiles of WIF1-expressing cells were performed. MALAT1, a long non-coding RNA and key positive regulator of invasion, emerged as the top downregulated gene. Indeed, knock-down of MALAT1 reduced migration in glioblastoma cells, without effect on proliferation.
WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1.
Specimen part, Cell line
View SamplesGlioblastoma (GBM) derived sphere lines and adherent cell lines are an important tool for research in basic and translational neuro-oncology. Documentation of their genetic identity has become a requirement for scientific journals and grant applications to exclude cross-contamination and misidentification that lead to misinterpretation of results. Here, we report expression data for 26 samples including 4 GBM derived sphere lines (4 x 3 replicates), 2 GBM derived sphere lines passaged through intracranial transplantation (2x 1), 2 adherent GBM derived cell lines (2 + 2 x 3 replicates), 4 corresponding glioblastoma tumors and 2 non-tumor brain tissues.
DNA fingerprinting of glioma cell lines and considerations on similarity measurements.
Disease
View SamplesLittle is known about the immune performance and interactions of CNS microglia/macrophages in glioma patients. Microglia/macrophages were found to be the predominant immune cell infiltrating gliomas (approximately 1% of total cells); others identified are myeloid dendritic cells (DCs), plasmacytoid DCs, and T cells. Using a procedure enriching for CD11b/c+CD45+ glioma-infiltrating microglia/macrophages (GIMs) from postoperative tissue specimens of glioma patients (Hussain et al. Neuro Oncol. 2006 J;8(3):261-79) gene expression profiles were obtained form paired samples. The expression profiles are used to identify expression signatures contributed by GIMs in glioblastoma data sets (Murat et al, submitted).
Modulation of angiogenic and inflammatory response in glioblastoma by hypoxia.
Sex, Specimen part
View SamplesNeuronal, endocrine and exocrine cells exhibit regulated exocytosis but there is also a body of evidence for regulated exocytosis from other cell types. Myofibroblasts are a stromal cell type that secretes extracellular matrix proteins, growth factors and cytokines; they are important in wound healing and increasingly are recognised to play a role in modifying the cellular microenvironment in cancer. We have established calcium dependent regulated secretion in a subset of myofibroblasts from gastric cancers, adjacent tissue and from normal tissue. We have used microarrays to look for the expression of genes associated with the regulated secretory phenotype.
The neuroendocrine phenotype of gastric myofibroblasts and its loss with cancer progression.
Specimen part
View SamplesAnalysis of 80 glioblastoma specimen of patients treated within clinical trials and 4 samples of "normal" brain tissue (non-tumoral). The data was used to identify factors of resistance to a chemoradiation therapy protocol of radiotherapy and concomitant and adjuvant temozolomide (alkylating agent).
Stem cell-related "self-renewal" signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma.
Sex, Age, Specimen part, Disease, Treatment, Subject
View SamplesSustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early response gene activated in the heart under beta-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by NR4A2 expression in cardiomyocytes, and their impact on the physiological response of those cells to sustained beta-adrenergic stimulation. Treatment of adult rat ventricular myocytes (ARVMs) with isoproterenol induced a rapid (< 4 hours) but transient (< 24 hours) increase in NR4A2 expression levels that was accompanied by increased nuclear localization of the transcription factor. Adenovirus-mediated overexpression of NR4A2 modulated the expression of genes linked to adrenoceptor signaling, calcium signaling, cell growth and proliferation, and counteracted the increase in protein synthesis rate and cell surface area mediated by chronic isoproterenol stimulation. In consistence with those findings, NR4A2 overexpression also blocked the phosphorylative activation of ERK1/2, Akt, and of their downstream effector in protein synthesis p70S6K. Prominent among the transcriptional changes induced by NR4A2 was the > 7-fold up-regulation of the dual-specificity phosphatases DUSP2 and DUSP14, two known inhibitors of ERK1/2. Pre-treatment of NR4A2-overexpressing cardiomyocytes with the DUSPs inhibitor BCI prevented the inhibition of ERK1/2 and p70S6K following isoproterenol stimulation. In conclusion, our results suggest that NR4A2 acts as a novel negative feedback regulator of the beta-adrenergic receptor-mediated growth response in cardiomyocytes, and this at least partly through DUSP-mediated inhibition of ERK1/2 signaling. Overall design: Isolated adult rat ventricular myocytes (ARVMs) were transduced at 50 m.o.i. with a recombinant adenovirus containing the full-length cDNA of human NR4A2 under the transcriptional control of the CMV promoter (Vector Biolabs Ad-h-NR4A2; Cat. No: ADV-217057). ARVMs transduced with a recombinant eGFP adenovirus (Vector Biolabs Ad-GFP; Cat. No. 1060) were used as the cell transduction control. At 48 hours post transduction, total RNA was etracted. A total of six independent experiments were performed using ARVMs isolated from different Sprague Dawley rats.
Nuclear receptor subfamily 4 group A member 2 inhibits activation of ERK signaling and cell growth in response to β-adrenergic stimulation in adult rat cardiomyocytes.
Specimen part, Cell line, Subject
View SamplesPolyamines (putrescine, spermidine, and spermine) are major organic polycations essential for a wide spectrum of cellular processes. The cells require mechanisms to maintain homeostasis of intracellular polyamines to prevent otherwise severe adverse effects. We performed a detailed transcriptome profile analysis of P. aeruginosa in response to agmatine and putrescine with an emphasis in polyamine catabolism. Agmatine serves as precursor compound for putrescine (and hence spermidine and spermine), which was proposed to convert into GABA and succinate before entering the TCA cycle in support of cell growth as the sole source of carbon and nitrogen. Two acetylpolyamine amidohydrolases, AphA and AphB, were identified to be involved in the conversion of agmatine into putrescine. Enzymatic products of AphA were confirmed by mass spectrometry analysis. Interestingly, the alanine-pyruvate cycle was shown indispensable for polyamine utilization. The newly identified dadRAX locus, encoding the regulator, alanine transaminase and racemase respectively, coupled with SpuC, the major putrescine-pyruvate transaminase, were key components to maintain alanine homeostasis. Corresponding mutant strains were severely hampered in polyamine utilization. On the other hand, the alternative gamma-glutamylation pathway for the conversion of putrescine into GABA was also discussed. Subsequently, GabD, GabT and PA5313 were identified for GABA utilization. Growth defect of PA5313 gabT double mutant in GABA suggested the importance of these two transaminases. The succinic-semialdehyde dehydrogenase activity of GabD and its induction by GABA was also demonstrated in vitro. Polyamine utilization in general was proven independent of the PhoPQ two-component system even the expression of which was induced by polyamines. Multiple potent catabolic pathways as depicted in this study could serve pivotal roles in control of intracellular polyamine levels.
Transcriptome analysis of agmatine and putrescine catabolism in Pseudomonas aeruginosa PAO1.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas.
Specimen part
View SamplesWe report findings that illuminate a dynamic metastasis pathway in the common pediatric brain tumor medulloblastoma.
ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas.
No sample metadata fields
View SamplesTo understand the global view of dysregulated genes and pathwyas in CRYAAN101D lenses, RNA sequencing of 2 & 4 months old CRYAAWT and CRYAAN101D lenses was carried out. Overall design: Determination of differential gene expression between CRYAAWT and CRYAAN101D in 2 & 4 months old lenses
Molecular mechanism of formation of cortical opacity in CRYAAN101D transgenic mice.
No sample metadata fields
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