The stomach is often considered a single compartment, but morphological differences among different areas are well known. Oxyntic mucosa (OXY) is primarily equipped for acid secretion, while it is not enough clear if gastric functional control are shared with other areas.
Differential gene expression in the oxyntic and pyloric mucosa of the young pig.
Sex, Specimen partView Samples
Regulatory T (Treg) maintain the tumor microenvironment in an immunosuppressive state preventing effective anti-tumor immune response. A possible strategy to overcome Treg cell suppression focuses on OX40, a costimulatory molecule expressed constitutively by Treg cells while induced in activated effector T (Teff) cells. OX40 stimulation by the agonist mAb OX86 inhibits Treg cell suppression and boosts Teff cell activation. Here we uncover the mechanisms underlying the therapeutic activity of OX86 treatment dissecting its distinct effects on Treg and on effector memory T (Tem) cells, which are the most abundant CD4+ populations strongly expressing OX40 at the tumor site. In response to OX86, tumor-infiltrating Treg cells produced significantly less interleukin 10 (IL-10), possibly in relation to a decrease in the transcription factor IRF1. Tem cells responded to OX86 by upregulating surface CD40L expression, providing a licensing signal to dendritic cells (DCs). The CD40L/CD40 axis was required for Tem cell-mediated in vitro DC maturation and in vivo DC migration. Accordingly, OX86 treatment was no longer therapeutic in CD40 KO mice. In conclusion, following OX40 stimulation, blockade of Treg cell suppression and enhancement of the Tem cell adjuvant effect both concurred to free DCs from immunosuppression and to activate the immune response against the tumor.
Intratumor OX40 stimulation inhibits IRF1 expression and IL-10 production by Treg cells while enhancing CD40L expression by effector memory T cells.
No sample metadata fieldsView Samples
Several studies demonstrated IgVH mutation status and ZAP-70 expression as the most relevant prognostic markers in CLL, suggesting the separation of two patient subgroups: with good (MTZAP-70-) and poor prognosis (UMZAP-70+). We determined gene expression of B cells in 112 CLL patients divided into three classes: the first with IgVHMT and ZAP-70-, the second with IgVHUM and ZAP-70+, and the third included both IgVHUM ZAP-70- and IgVHMT ZAP-70+. We found LPL, AGPAT2, MBOAT1, CHPT1, AGPAT4, PLD1 genes encoding enzymes involved in lipid (glycerolipid/glycerophospholipid) metabolism overexpressed in UMZAP-70+. In addition, this study demonstrates the role of ARSD, a gene belonging to the sphingolipid metabolism, as a new gene significantly overexpressed in UMZAP-70+ in respect to MTZAP-70-. ARSD protein was found at significantly higher concentrations in UMZAP-70+ compared to MTZAP-70- CLL B cells and B cells from healthy individuals by Western blotting. Statistical analysis identified a strong correlation between ARSD and IgVH mutation status; ARSD protein level was associated with the requirement of therapy for CLL patients and for this purpose it is as good as IgVH mutational status. Our study highlights ARSD as a promising new prognostic factor in CLL and sphingolipid metabolism as a putative new biological mechanism in CLL.
Gene expression profiling identifies ARSD as a new marker of disease progression and the sphingolipid metabolism as a potential novel metabolism in chronic lymphocytic leukemia.
Sex, Age, Disease, Disease stageView Samples
We have generated a mouse model for tumor initiation carrying a mutation in APC and lacking IKKa in intestinal epithelial cells. IKKa-deficient intestinal cells primarily failed to generate adenomas, and the few adenomas arising in this background displayed a significant reduction in cell proliferation. Using an in vitro model for intestinal tumoroids (derived from adenoma initiating cells), we have performed RNA sequencing of wild type and IKKa-deficient intestinal tumoroids. This has demonstrated that epithelial IKKa controls transcription of stem cell-related genes and genes associated with proliferation and apoptosis. Overall design: RNA sequencing of IKKa WT and KO tumoroids, done in triplicates
IKKα is required in the intestinal epithelial cells for tumour stemness.
Specimen part, Cell line, SubjectView Samples
Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of diseases of large vessels, including abdominal aortic aneurysm (AAA). We tested the hypothesis that locally restricted transcriptional profiles characterize PVAT surrounding AAA. Using a genome-wide approach, we investigated the PVAT transcriptome of AAA in 30 patients with either large (55 mm) or small (<55 mm) aneurysm diameter. We performed a data adjustment step using the DaMiRseq R/Bioconductor package, to remove the effect of confounders as produced by high-throughput gene expression techniques. We compared PVAT of AAA with PVAT of not-dilated abdominal aorta of each patient to limit the effect of inter-individual variability, using the limma R/Bioconductor package. We found highly consistent differences in PVAT gene expression clearly distinguishing PVAT of AAA from PVAT of not-dilated aorta, which increased in number and magnitude with increasing AAA diameter. These changes did not systemically affect other abdominal adipose depots (omental or subcutaneous fat). We dissected putative mechanisms associated with PVAT involvement in AAA through a functional enrichment network analysis: both innate and adaptive immune-response genes along with genes related to cell-death pathways, metabolic processes of collagen, sphingolipids, aminoglycans and extracellular matrix degradation were strongly overrepresented in PVAT of AAA compared with PVAT of not-dilated aorta. Our results provide support to a possible role of PVAT in AAA pathogenesis and suggest that AAA is an immunologic disease with an underlying autoimmune component. These disease-specific expression signatures could help identifying pharmacological targets for preventing AAA progression.
Genome-Wide Expression Profiling Unveils Autoimmune Response Signatures in the Perivascular Adipose Tissue of Abdominal Aortic Aneurysm.
Sex, Age, Specimen part, SubjectView Samples
Aminaphtone, a drug used in the treatment of chronic venous insufficiency (CVI), showed a remarkable role in the modulation of several vasoactive factors, like endothelin-1 and adhesion molecules. We analysed in vitro the effects of Aminaphtone on whole-genome gene expression. ECV304 endothelial cells were stimulated with IL-1 100 U/ml in the presence or absence of Aminaphtone 6 g/ml. Gene expression profiles were compared at 1, 3, and 6 h after stimulation by microarray.
Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells.
Cell lineView Samples
We set up a pilot study using Affymetrix Gene Chip Porcine Genome Arrays to evaluate the impact of time lags from death on gene expression profiling of porcine skeletal muscle at four post mortem time points (up to 24 hrs) during the routine processing of fresh tights
Microarray gene expression analysis of porcine skeletal muscle sampled at several post mortem time points.
Sex, Specimen part, TimeView Samples
Classical regeneration experiments in insects have demonstrated an important role for imaginal tissues (also called discs, the larval tissues that give rise to the adult appendages) in coupling tissue growth, maturation and patterning during development We used the rotund-Gal4 driver (Rn>) for disc-targeted silencing of the avalanche gene (avl; Rn>avl-RNAi), encoding a syntaxin that functions in the early endocytic machinery (H. Lu, D. Bilder, Nat Cell Biol 7, 1232; Dec, 2005). Rn>avl-RNAi discs reach near to normal size after 5 days of development, and then undergo unrestricted neoplastic growth. We were interested in identifying genes showing differential expression profiles in control and in neoplastic growth. We identified dilp8 as one of the most differentially expressed gene in control and Rn>avl-RNAi discs.
Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing.
Specimen partView Samples
AIRmax and AIRmin mouse lines show a differential lung inflammatory response and differential lung tumor susceptibility after urethane treatment, thus constituting a good genetic model to investigate differences in gene expression profiles related to inflammatory response and lung tumor susceptibility. The transcript profile of ~24,000 known genes was analyzed in normal lung tissue of untreated and urethane-treated AIRmax and AIRmin mice. In lungs of untreated mice, inflammation associated genes involved in pathways such as leukocyte transendothelial migration, cell adhesion and tight junctions were differentially expressed in AIRmax versus AIRmin mice. Moreover, gene expression levels differed significantly in urethane-treated mice even at 21 days after treatment. In AIRmin mice, modulation of expression of genes involved in pathways associated with inflammatory response paralleled the previously observed persistent infiltration of inflammatory cells in the lung of these mice. In conclusion, a specific gene expression profile in normal lung tissue is associated with mouse line susceptibility or resistance to lung tumorigenesis and with different inflammatory response, and urethane treatment causes a long-lasting alteration of the lung gene expression profile that correlates with persistent inflammatory response of AIRmin mice.
Transcriptome of normal lung distinguishes mouse lines with different susceptibility to inflammation and to lung tumorigenesis.
Sex, Specimen partView Samples
This SuperSeries is composed of the SubSeries listed below.
Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers.
Age, Specimen part, Cell lineView Samples