Gastric cancer can be divided in two major histological subtypes: diffuse and intestinal-type adenocarcinomas. Since both types diverge in many clinical and molecular characteristics, is widely accepted that both represent distinct disease entities that may benefit from different therapeutic approaches. The diffuse type is explicitly more invasive and affected patients possess extremely poor prognosis. Gene expression profiling studies identified numerous genes with differences in mRNA expression between the two types. However, little overlap of published gene lists exists forcing the need for further and more comprehensive analyses.
THBS4, a novel stromal molecule of diffuse-type gastric adenocarcinomas, identified by transcriptome-wide expression profiling.
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View SamplesAn branched-chain amino acids auxotroph eca39 mutant fission yeast exhibits an unusual adaptive growth phenotype on solid minimal media containing Ile, Leu and Val when other strains are growing nearby.
The SAGA histone acetyltransferase complex regulates leucine uptake through the Agp3 permease in fission yeast.
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View SamplesTcf1 is necessary for optimal T lineage development. Tcf1 deficient progenitors fail to initiate the T lineage program in vitro and development is severely defective in vivo. We used microarrays to assess the overal global gene expression differences from Tcf1 wildtype and deficient lymphoid biased progenitors cultures on Notch-ligand expressing stroma to determine if Tcf1 deficient progenitors are able to intiate the T lineage specification program.
A critical role for TCF-1 in T-lineage specification and differentiation.
Specimen part
View SamplesWe used microarrays to perform a global gene expression analysis in Tcf1-expressing Thy1+CD25+ T lineage cells that develop on OP9 stroma in the absence of Notch1 signals. We compare this to the starting population, LMPP progenitors, and to control expressing T lineage cells that developed on OP9 stroma expressing Notch ligand DL4. The overall goal of this study was to determine if Tcf1 initiates T lineage specification in lymphoid progenitors. We found that Tcf1 was sufficient to upregulate many T lineage genes as compared to control expressing progenitors on OP9-DL4.
A critical role for TCF-1 in T-lineage specification and differentiation.
Specimen part
View SamplesThe differences of clinical characteristics in complex seizures induced by influenza A(H1N1)pdm09 and rotavirus gastroenteritis are well known, but the pathogenic mechanisms remain unclear. We analyzed the gene expression profiles in the peripheral whole blood cells isolated from pediatric patients using an Affymetrix oligonucleotide microarray.
Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesTranscriptome analysis of LPS-stimulated bone marrow-derived dendritic cells with NR4A3 gene silencing
The Orphan Nuclear Receptor NR4A3 Is Involved in the Function of Dendritic Cells.
Specimen part
View SamplesTankyrase enhances beta-catenin signaling via PARsylation and subsequent degradation of Axin, a negative regulator of beta-catenin. Tankyrase inhibitors stabilize Axin and suppress beta-catenin signaling. We developed a novel tankyrase inhibitor, RK-287107.
RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model.
Specimen part, Treatment
View SamplesPersistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. We examined the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and found that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene was increased in Hp-positive human gastric biopsies as compared to Hp-negative controls. Moreover silencing of miR-210 in gastric epithelial cells promoted proliferation. We identified STMN1 and DIMT1 as miR-210 target genes and demonstrated that inhibition of miR-210 expression augmented cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.
Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection.
Cell line
View SamplesDiffuse-type gastric carcinoma is a poor-prognostic cancer with high expression of transforming growth factor (TGF)- and thick stromal fibrosis. However, detailed investigations on the roles of TGF- signaling in diffuse-type gastric carcinoma have not been performed. We generated two diffuse-type gastric carcinoma cell lines, dominant-negative TGF- type II receptor expressing cells (2MLN-dnTRII) and GFP-expressing cells (2MLN-GFP). Cells were subcutaneously or orthotopically injected into nude mice. Although dnTRII did not affect the growth of OCUM-2MLN in vitro, it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo. By microarray analysis, we found gene expression of TSP-1, an angiogenic inhibitor, was down-regulated in dnTRII tumors. This results suggested disruption of TGF- signaling in diffuse-type gastric carcinoma cells leads to alteration of tumor microenvironment and acceleration of tumor growth.
Diffuse-type gastric carcinoma: progression, angiogenesis, and transforming growth factor beta signaling.
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View SamplesThe character of the earliest cardiac precursor cells remains largely unknown. To elucidate this further, we constructed single cell cDNAs from the mouse embryonic cardiac precurcsor cells of the early allantoic bud stage and the early headfold stage, and subjected them to deep sequencing. Overall design: The most anterior part of the embryos where cardiac precursor cells exist was digested by trypsin to separate into single cells. After a cell was transferred into a reaction tube, single cell cDNAs were constructed as PCR amplicons. cDNAs of cardiac precursor cells were identified by PCR of marker genes.
Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
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