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GSE7848
Homo sapiens
15 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Previous studies indicate that the triterpene glycoside actein from the herb black cohosh inhibits growth of human breast cancer cells. This study seeks to identify genes altered in human breast cancer cells by treatment with actein, using gene expression analysis. We treated MDA-MB-453 human breast cancer cells with actein at 2 doses, 20 or 40 g/mL, for 6 or 24 h. We identified 5 genes that were activated after each of the treatments that are known to play a role in cellular responses to diverse stresses, including the DNA damage and unfolded protein responses. In addition, four genes that mediate the integrated stress response (ISR), including activating transcription factor 4, were induced under at least one of the 4 treatment conditions. We used hierarchical clustering to define clusters comprising patterns of gene expression. Two ISR genes, activating transcription factor 3 (ATF3) and DNA damage- inducible transcript 3, and lipid biosynthetic genes were activated after exposure to actein at 40 g/mL for 6 h, whereas the cell cycle genes cyclin E2 and cell division cycle 25A were repressed. Our results suggest that actein induces 2 phases of the ISR, the survival phase and the apoptotic phase, depending on the dose and duration of treatment. We confirmed the results of gene expression analysis with real-time RT-PCR for 18 selected genes and Western blot analysis for ATF3. Since actein activated transcription factors that enhance apoptosis, and repressed cell cycle genes, it may be useful in the prevention and therapy of breast cancer.
Publication Title
The growth inhibitory effect of actein on human breast cancer cells is associated with activation of stress response pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Microarray analysis and quantitative real-time PCR revealed that TB40E infection of DCs led to changes of the gene expression pattern. A variety of pro-inflammatory cytokines and chemokines (CXCL10, CXCL11, CCL5), TLR3 and genes whose products function downstream of the TLR3 signalling pathway (e.g. IFN-, IFN-) were significantly upregulated.
Publication Title
Toll-like receptor 3 has no critical role during early immune response of human monocyte-derived dendritic cells after infection with the human cytomegalovirus strain TB40E.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
DCs are localized under the mucosa of the lungs and the gastrointestinal tract, and therefore come into close contact with A. fumigatus germ tubes during early steps of infection as soon as fungi become invasive. For a more detailed insight into differentially regulated genes, whole genome microarray analysis was performed.
Publication Title
Impact of mycophenolic acid on the functionality of human polymorphonuclear neutrophils and dendritic cells during interaction with Aspergillus fumigatus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
In a whole-transcriptome study, cellular responses of DCs confronted with the fungi A. fumigatus, C. albicans or the bacterial cell wall component LPS were investigated. Therefore DCs of four independent donors were analyzed after 6 hours co-culture with A. fumigatus, C. albicans and LPS by Affymetrix whole genome expression arrays. In general, transcriptomic analysis revealed a clustering of the A. fumigatus and C. albicans stimulated DCs. However, LPS and fungi-dependent gene expression showed more common similarities compared to the untreated control. Stimulation with LPS induced a differential regulation of 2793 genes after 6h, while confrontation with A. fumigatus and C. albicans resulted in 743 and 974 differentially regulated genes, respectively. Kruppel-like factor 4 (KLF4) was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS.
Publication Title
Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
Illumina HiSeq 2500
Description
Background: Preeclampsia, traditionally characterized by high blood pressure and proteinuria, is a common pregnancy complication, which affects 2-8% of all pregnancies. Although children born to women with preeclampsia have a higher risk of hypertension in later life, the mechanism of this increased risk is unknown. DNA methylation is an epigenetic modification that has been studied as a mediator of cellular memory of adverse exposures in utero. Since each cell type in the body has a unique DNA profile, cell subtype composition is a major confounding factor in studies of tissues with heterogeneous cell types. The best way to avoid this confounding effect is by using purified cell types. However, the use purified cell types in large cohort translational studies is difficult. The amnion, the inner layer of the fetal membranes of placenta, is derived from the epiblast and consists of two cell types, which are easy to isolate from the delivered placenta. In this study, we demonstrate the value of using amnion samples for DNA methylation studies, revealing distinctive patterns between fetuses exposed to preeclampsia or hypertension and fetuses from normal pregnancies. Results: We performed a genome-wide DNA methylation analysis, HELP-tagging, on 62 amnion samples from placentas of uncomplicated, normal pregnancies, and those with complications of preeclampsia or hypertension. Using a regression model approach, we found 123, 85 and 99 loci with high confidence hypertension-associated, proteinuria-associated and hypertension and proteinuria-associated DNA methylation changes, respectively. We also found that these differentially methylated regions overlap loci previously reported as differentially methylated regions in preeclampsia. Conclusions: Our findings support prior observations that preeclampsia is associated with changes of DNA methylation near genes that have previously been found to be dysregulated in preeclampsia. We propose that amnionic membranes represent a valuable surrogate fetal tissue on which to perform epigenome-wide association studies of adverse intrauterine conditions. Overall design: Directional RNA profiles of amnion membranes were generated by deep sequencing using Illumina HiSeq2500. Twenty-nine human amnion specimens were used: 12 control and 17 preeclampsia exposed.
Publication Title
Amnion as a surrogate tissue reporter of the effects of maternal preeclampsia on the fetus.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 282 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Kidney transplants that develop dysfunction or proteinuria after one year post transplant are at considerable risk for progression to renal failure. Identifying the molecules associated with graft failure could potentially lead to interventions that would slow the progression of organ failure.
Publication Title
A molecular classifier for predicting future graft loss in late kidney transplant biopsies.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers.
Publication Title
Molecular phenotypes of acute kidney injury in kidney transplants.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy towards this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of haematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B) as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3% sensitivity and 74.6% specificity. Moreover, we validated the expression of S100B in a real-time RT-PCR assay and we also found a down-regulation of S100B in A.fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis.
Publication Title
Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
In a whole-transcriptome study, cellular responses of DCs confronted with the fungi A. fumigatus, C. albicans or the bacterial cell wall component lipopolysaccharide (LPS) were investigated. Therefore, DCs of four independent donors were harvested after 12 hours co-culture with A. fumigatus, C. albicans and LPS and analyzed with Affymetrix whole genome expression arrays. In general, transcriptomic analysis revealed a clustering of the A. fumigatus- and C. albicans-stimulated DCs. However, LPS and fungi-dependent gene expression showed more common similarities compared to the untreated control.
Publication Title
Specific and Novel microRNAs Are Regulated as Response to Fungal Infection in Human Dendritic Cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 304 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The authors report that in INTERCOM, a prospective international study of 300 kidney transplant biopsies, a microarray-based molecular score for T cell-mediated rejection changed the assessment of 26% of all biopsies, illustrating the potential of precision diagnostics to impact practice.
Publication Title
Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: The INTERCOM study.
Sample Metadata Fields
Specimen part
View Samples