Adoptive T-cell Therapy (ACT) involves using tumor-infiltrating lymphocytes (TIL) isolated from metastatic melanoma and expanding them ex vivo prior to infusion into lympho-depleted patients. This is one of the most promising approaches to treat metastatic melanoma, with the rates of clinical response between 48-50% based on studies done at NCI, M.D. Anderson Cancer Center (Houston, TX), and Sheba Medical Center (Tel Aviv, Israel). In the Phase II ACT Trial at M.D. Anderson Cancer Center , our group has uncovered an association between positive clinical response and the amount of CD8+ tumor-infiltrating lymphocytes expressing B and T Lymphocyte Attenuator (BTLA), a reported inhibitory receptor on T-cells.
BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties.
Sex, Age, Specimen part, Subject
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Expression quantitative trait loci mapping identifies new genetic models of glutathione S-transferase variation.
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View SamplesRationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses.
A pathway-based analysis on the effects of obstructive sleep apnea in modulating visceral fat transcriptome.
Subject
View SamplesAeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus. Microarray profiling of murine small intestinal extracts, 24 hours after oral infection with an A. caviae strain, provides evidence of a Th1 type immune response. A large number of gamma-interferon (-IFN) induced genes are up-regulated as well as several tumor necrosis factor-alpha (TNF-) transcripts. A. caviae has always been considered an opportunistic pathogen because it lacks obvious virulence factors. This current effort suggests A. caviae colonizes murine intestinal tract and causes what has been described by others as a dysregulatory cytokine response leading to an irritable bowel-like syndrome. This response would explain why a number of diarrheal waterborne outbreaks have been attributed to A. caviae even though it lacks obvious enteropathogenic properties.
Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract.
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View SamplesRationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures.
Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes.
Treatment, Subject
View SamplesA study of diabetic neuropathy in dorsal root ganglia from streptozotocin-diabetic male wistar rats over the first 8 weeks of diabetes
Identification of changes in gene expression in dorsal root ganglia in diabetic neuropathy: correlation with functional deficits.
Sex, Age, Specimen part, Disease, Disease stage, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Drosophila larvae fed palm fruit juice (PFJ) delay pupation via expression regulation of hormetic stress response genes linked to ageing and longevity.
Age, Specimen part, Treatment
View SamplesPFJ (4 ml for a final concentration of 19,000 mg gallic acid equivalent (GAE) per kg diet or 0.86 mg GAE per kcal diet) was supplemented to larvae of fruit flies (Drosophila melanogaster) given a semi-purified diet to observe for possible effects on energy metabolism and lifespan. Larvae were used five days since the egg stage for gene expression studies. Results from the microarray data analysis carried out show that fruit fly larvae given PFJ had up-regulated transport and metabolic processes, while development and morphogenesis processes were down-regulated.
Drosophila larvae fed palm fruit juice (PFJ) delay pupation via expression regulation of hormetic stress response genes linked to ageing and longevity.
Age, Specimen part, Treatment
View SamplesPFJ (4 ml for a final concentration of 19,000 mg gallic acid equivalent (GAE) per kg diet or 0.86 mg GAE per kcal diet) was supplemented to larvae of fruit flies (Drosophila melanogaster) given a semi-purified diet to observe for possible effects on energy metabolism and lifespan. Fat bodies extracted from these larvae were used five days since the egg stage for gene expression studies. Results from the microarray data analysis carried out show that fruit fly larva fat bodies given PFJ had up-regulated heat shock protein genes, while cell cycle and growth genes were down-regulated.
Drosophila larvae fed palm fruit juice (PFJ) delay pupation via expression regulation of hormetic stress response genes linked to ageing and longevity.
Age, Specimen part, Treatment
View SamplesCD8+ T-cells inhibit virus replication in SIV-infected rhesus macaques (RM). However, it is unclear to what extent the viral suppression mediated by CD8+ T-cells reflects direct killing of infected cells as opposed to indirect, non-cytolytic mechanisms. In this study, we used functional genomics to investigate potential mechanisms of in vivo viral suppression mediated by CD8+ lymphocytes. Eight chronically SIVmac239-infected RMs underwent CD8+ lymphocyte depletion, and RNA from whole blood was obtained prior to depletion, at the nadir of CD8+ lymphocytes (5 days post-depletion), and during the repopulation phase (11 days post-depletion). Principal components analysis demonstrated that overall gene expression during the nadir of CD8+ T-cells was highly divergent from other intervals. Conversely, the genomic signature of samples from the CD8+ cell rebound phase was similar to that of pre-depletion samples. During CD8+ lymphocyte depletion we detected a strongly significant decrease in the expression of the genes encoding CD8 and CD8 chains, consistent with the near complete CD8+ T-cell depletion measured by flow cytometry. Of note, we observed significant down-regulation of the expression of genes encoding for factors that can suppress SIV replication, including the CCR5-binding chemokine CCL5/Rantes, several retroviral restriction factors (TRIM10, TRIM15, APOBEC3G/H) and defensins. Reduced expression of various genes related to T cell activation and proliferation was also observed. Collectively, these data indicate that depletion of CD8+ lymphocytes in SIV-infected RMs is associated with the establishment of a pattern of gene expression that may result in increased intrinsic permissivity to virus replication.
Transcriptional profiling of experimental CD8(+) lymphocyte depletion in rhesus macaques infected with simian immunodeficiency virus SIVmac239.
No sample metadata fields
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