Long-term treatment of Kasumi-1 cells at clinically attained doses of dasatinib led to decreased drug-sensitivity by means of IC50 values (relative to treatment-naive cells). Changes were paralled by profound alterations in c-KIT expression and cell signaling signatures. Upon brief discontinuation of dasatinib treatment, these alterations reversed and drug sensitivity was restored.
Transitory dasatinib-resistant states in KIT(mut) t(8;21) acute myeloid leukemia cells correlate with altered KIT expression.
Cell line
View SamplesGenome-wide comparative gene expression analysis of callus tissue of osteoporotic mice (Col1a1-Krm2 and Lrp5-/-) and wild-type were performed to identify candidate genes that might be responsible for the impaired fracture healing observed in Col1a1-Krm2 and Lrp5-/- mice.
Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice.
Sex, Age, Specimen part
View SamplesIn this experiment, mucous neck cells from the gastric epithelium of normal, adult C57/B6 mice were laser-capture microdissected to determine gene expression in neck cells relative to pit cells, parietal cells, and zymogenic cells, whose expression profiles were previously deposited in GEO.
Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3.
No sample metadata fields
View SamplesThe aim of this study is to survey global gene expression of total thymocytes from wild-type mice and Atg16l1 mutant (hypomorph) mice.
A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells.
No sample metadata fields
View SamplesSusceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells.
A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells.
No sample metadata fields
View SamplesIt is widely accepted that a womans lifetime risk of developing breast cancer at menopause is reduced by early full term pregnancy and multiparity. This phenomenon is associated with the development and differentiation of the breast, which ultimately imprints a specific genomic profile in the mammary epithelium. In the present work we demonstrate that this profile represents a permanent signature that could be associated with the breast cancer risk reduction conferred by pregnancy.
Defining the genomic signature of the parous breast.
No sample metadata fields
View SamplesInflammation is a key component of pathological angiogenesis. Here we monitor gene expression profiles of the pre-sprouting phase of corneal angiogenesis in the rat model, as influenced by topically applied treatments.
Genome-wide expression differences in anti-Vegf and dexamethasone treatment of inflammatory angiogenesis in the rat cornea.
Sex, Specimen part
View SamplesInflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase.
Factors regulating capillary remodeling in a reversible model of inflammatory corneal angiogenesis.
Sex, Specimen part
View SamplesSevere cerebral ischemia caused by events such as ischemic stroke or cardiac arrest is a relatively common and life-threating condition. Those who survive frequently suffer from significant cerebral dysfunction, often with poor outcome. To date the treatment options are limited. Concomitant hyperglycemia is frequently perceived both in focal and global transient ischemia, augmenting the ischemic brain injury as revealed by experimental and clinical studies.
Hyperglycemia Alters Expression of Cerebral Metabolic Genes after Cardiac Arrest.
Specimen part, Treatment
View SamplesThe goal of this study was to assess whether the presence of HLA-B*35 contributes to activation of ER stress/UPR and inflammation in lcSScPAH PBMC.
The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients.
Specimen part
View Samples