Microarray based mRNA profiling was used to identify the mechanism of action for the small molecule b-AP15.
Inhibition of proteasome deubiquitinating activity as a new cancer therapy.
Cell line, Treatment
View SamplesVitamin A is the only known compound that produces spontaneous fractures in rats. In an effort to resolve the molecular mechanism behind this effect, we fed young rats high doses of vitamin A and performed a global transcriptional analysis of diaphyseal bone after one week, i.e. just before the first fractures appeared. Microarray gene expression analysis revealed that 68 transcripts were differentially expressed in hypervitaminotic cortical bone and 118 transcripts were found when the bone marrow was also included. 98% of the differentially expressed genes in the bone marrow sample were up-regulated. In contrast, hypervitaminotic cortical bone without marrow showed reduced expression of 37% of differentially expressed genes. Gene Ontology (GO) analysis revealed that only samples containing bone marrow were associated to a GO term, which principally represented extracellular matrix (ECM). This is consistent with the histological findings of increased endosteal bone formation. Four of the genes in this ECM cluster and four other genes, including Cyp26b1 which is known to be up-regulated by vitamin A, were selected and verified by real-time PCR. In addition, immunohistochemical staining of bone sections confirmed that the bone-specific molecule, osteoadherin (Omd) was up-regulated. Further analysis of the major gene expression changes revealed distinct differences between cortical bone and bone marrow, e.g. there appeared to be augmented Wnt signaling in the bone marrow but reduced Wnt signaling in cortical bone. Moreover, induced expression of hypoxia-associated genes was only found in samples containing bone marrow. Together, these results corroborate our previous observations of compartment-specific effects of vitamin A, with reduced periosteal but increased endosteal bone formation, and suggest important roles for Wnt signaling and hypoxia in the processes leading to spontaneous fractures.
Microarray profiling of diaphyseal bone of rats suffering from hypervitaminosis A.
Sex, Age, Specimen part, Disease
View SamplesWe performed microarray analysis to investigate the gene expression profile changes induced by Hmg20b knock down in I/11 cells.
The DNA binding factor Hmg20b is a repressor of erythroid differentiation.
Specimen part
View SamplesHuman adipose stem cells (ASCs) have been shown, in pre-clinical studies, to have therapeutic applicability in diverse fields, but a standard expansion method for clinical applications remains yet to be established. Isolated ASCs are typically expanded in medium containing fetal bovine serum (FBS). However, sera and other animal-derived culture reagents stage numerous safety issues in clinical therapy, including possible infections and severe immune reactions. By expanding the ASCs in medium containing human serum (HS), the problem can be eliminated.
Differential gene expression in adipose stem cells cultured in allogeneic human serum versus fetal bovine serum.
Specimen part
View SamplesHeme Oxygenase-1 (HO-1) is expressed in many cancers and influences the growth, survivall and metastasis of tumors, however, the molecular mechanisms remains largely unknown. To identify a common mechanism of action of HO-1 in cancer, we studied the global effect of HO-1 on the transcriptome of multiple tumors. Genome-wide expression profiling of HO-1 expressing versus HO-1 silenced cancer cells and a further data mining analysis of the preexisting expression database of 190 human tumors of 14 cancer types led us to identify 14 genes, the expression of which correlated firmly and universally with that of HO-1 (P < 0.001). These genes included regulators of cell plasticity and extracellular matrix remodeling (MMP2, ADAM8, TGF1, BGN, COL21A1, PXDN), signaling (CRIP2, MICB), amino acid transport and glycosylation (SLC7A1 and ST3GAL2), estrogen and phospholipid biosynthesis (AGPAT2 and HSD17B1), protein stabilization (IFI30) and phosphorylation (ALPPL2). PXDN, one of the genes being co-expressed with HO-1, was selected for further analysis. Immunofluorescence and western blotting confirmed positive correlation of PXDN with HO-1 levels in BeWo cancer cells as well as co-localization in invasive extravillous trophoblast cells of first trimester placenta. Loss of HO-1 in BeWo cells correlated with reduced cell adhesion to Collagen type I, Fibronectin and Laminin. The adhesion-promoting effects of HO-1 were dependent on PXDN expression, as loss of PXDN in HO-1 expressing BeWo cells led to reduced cell attachment to Laminin and Fibronectin coated wells.
Transcriptome analysis of human cancer reveals a functional role of heme oxygenase-1 in tumor cell adhesion.
Specimen part
View SamplesThe specific contribution of the two TNF-receptors Tnfr1 and Tnfr2 to TNF-induced inflammation in the glomerulus is unknown. In mice, TNF exposure induces glomerular expression of inflammatory mediators like adhesion molecules and chemokines in vivo, and glomerular accumulation of leukocytes.
Distinct contributions of TNF receptor 1 and 2 to TNF-induced glomerular inflammation in mice.
Specimen part, Treatment
View Samples593 FFPE colorectal cancer samples were used to generate three prediction models: Recurrence prediction, 5FU efficacy prediction, and FOLFOX efficacy prediction
Building personalized treatment plans for early-stage colorectal cancer patients.
Specimen part
View SamplesExpression profiling of cultured HL-1 cardiomyocytes subjected to hypoxia for 8 hours.
The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction.
Cell line
View SamplesSepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to determine if the pathogen is bacterial, fungal or neither of the two. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97%) for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83%) for an additional dataset comprising Cryptococcus neoformans infections. Furthermore, the noise-robustness of the classifier suggests high rates of correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.
Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study.
Sex, Specimen part, Subject, Time
View SamplesMaternal obesity during the pre-implantation period leads to a pro-inflammatory milieu in the ovaries. We conducted a global transcriptomic profiling in ovaries from TEN fed rats during the pre-implantation period. Microarray analysis revealed that obesity lead to increased expression of genes related to inflammation, decreased glucose transporters, and dysregulation of ovarian function-related genes in the ovaries. Our results suggest maternal obesity led to an up-regulation of inflammatory genes and Egr-1 protien expression in peri-implantation ovarian tissue, and a concurrent down-regulation of glucose transporters mRNA and AKT and PI3K protein levels.
Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1.
Sex, Specimen part
View Samples