High-grade gliomas (HGGs) include the most common and the most aggressive primary brain tumor of adults and children. Despite multimodality treatment, most high grade gliomas eventually recur and are ultimately incurable. Several studies suggest that the initiation, progression, and recurrence of gliomas are driven, at least partly, by cancer stem-like cells. A defining characteristic of these cancer stem-like cells is their capacity to self-renew. We have identified a hypoxia-induced pathway that utilizes the Hypoxia Inducible Factor 1 (HIF-1) transcription factor and the JAK1/2-STAT3 (Janus Kinase 1/2 - Signal Transducer and Activator of Transcription 3) axis to enhance the self-renewal of glioma stem-like cells. Hypoxia is a commonly found pathologic feature of HGGs. Under hypoxic conditions, HIF-1 levels are greatly increased in glioma stem-like cells. Increased HIF-1 activates the JAK1/2-STAT3 axis and enhances tumor stem-like cell self-renewal. Our data further demonstrate the importance of Vascular Endothelial Growth Factor (VEGF) secretion for this pathway of hypoxia-mediated self-renewal. Brefeldin A and EHT-1864, agents that significantly inhibit VEGF secretion, decreased stem cell self-renewal, inhibited tumor growth, and increased the survival of mice allografted with S100-v-erbB/p53-/- glioma stem-like cells. These agents also inhibit the expression of a hypoxia gene expression signature that is associated with decreased survival of HGG patients. These findings suggest that targeting the secretion of extracellular, autocrine/paracrine mediators of glioma stem-like cell self-renewal could potentially contribute to the treatment of HGG.
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View SamplesExposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone.
Laboratory diet profoundly alters gene expression and confounds genomic analysis in mouse liver and lung.
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View SamplesExposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone.
Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung.
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View SamplesThere are no effective treatments or clinical response markers for systemic sclerosis (SSc). We sought to assess the potential of novel imaging biomarkers and gene expression profiling approaches in a clinical trial of the tyrosine kinase inhibitor dasatinib in SSc patients with interstitial lung disease (SSc-ILD).
Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease.
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View SamplesFVB mice were engineered to express wild-type human cyclin E under control of the human surfactant C promoter (CEO mice; Ma et al, PNAS 2007). These mice develop spontaneous lung tumors, which were shown to be adenocarcinoma by histological analysis. Here we compare whole-genome RNA expression levels between the tumors and normal lung of 4 CEO mice as well as 4 nontransgenic animals.
Evidence for tankyrases as antineoplastic targets in lung cancer.
Sex, Specimen part
View SamplesThe transcription factor Anr regulates the response to low oxygen in P. aeruginosa and is inhibited by oxygen. We used microarrys to compare gene expression in P. aeruginosa PAO1 wild-type with an isogenic anr mutant in order to determine which transcripts are affected by Anr. We grew P. aeruginosa cells as biofilms on CFBE cells in order to model cystic fibrosis airways infections.
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View SamplesGenomic DNA from Pseudomonas aeruginosa strains PAO1 and PA14
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View SamplesAnalysis of gene expression in pathologically confirmed glioblastoma (GBM) samples. These data were used to test a classifier that was generated to distinguish GBM tumor samples with loss of neurofibromin 1 (NF1) function
A machine learning classifier trained on cancer transcriptomes detects NF1 inactivation signal in glioblastoma.
Sex, Age, Specimen part
View SamplesIron-deficiency repsonses in Arabidopsis are controlled by several bHLH transcription factors. FIT, for example has been shown to direct iron-uptake responses. However, the role of shoot and root expressed genes bHLH100 and bHLH101 has not be clarified. We used microarray to study what genes might be miss-regulated in the double mutant bhlh100/bhlh101 background
Arabidopsis bHLH100 and bHLH101 control iron homeostasis via a FIT-independent pathway.
Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PDGF Engages an E2F-USP1 Signaling Pathway to Support ID2-Mediated Survival of Proneural Glioma Cells.
Specimen part, Treatment
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