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GSE95042
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Cancer progression is associated with alterations of epigenetic regulators such as histone-lysine demethylases 4 (KDM4)2-5. During breast cancer therapy, classical treatments fail to address resistant cancer stem cell populations6-10. Here, we identified a novel KDM4 inhibitor (KDM4(i)) with unique preclinical characteristics. KDM4(i) is a highly potent pan KDM4 inhibitor that specifically blocks the demethylase activity of KDM4A, B, C, and D but not that of the other members of the KDM family. We validated the KDM4(i) anti-tumoral properties under conditions recapitulating patient tumors. Therefore, we established a method to isolate and grow triple-negative breast cancer stem cells (BCSCs) from individual patient tumors after neoadjuvant chemotherapy. Limiting dilution orthotopic xenografts of these BCSCs faithfully regenerate original patient tumor histology and gene expression. KDM4(i) blocks proliferation, sphere formation and xenograft tumor growth of BCSCs. Importantly, KDM4(i) abrogates expression of EGFR, a driver of therapy-resistant triple-negative breast tumor cells11, via inhibition of the KDM4A demethylase activity. Taken together, we present a unique BCSC culture system as a basis for therapeutic compound identification and demonstrate that KDM4 inhibition is a new therapeutic strategy for the treatment of triple-negative breast cancer.
Publication Title
KDM4 Inhibition Targets Breast Cancer Stem-like Cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In recent years, several approaches have been taken in the peptide-based immunotherapy of metastatic renal cell carcinoma (RCC), although little is known about HLA presentation on metastases compared to primary tumor and normal tissue of RCC. In this study we compared primary tumor, normal tissue and metastases with the aim of identifying similarities and differences between these tissues. We performed this comparison for two RCC patients on the level of the HLA ligandome using mass spectrometry and for three patients on the level of the transcriptome using oligonucleotide microarrays. The quantitative results show that primary tumor is more similar to metastasis than to normal tissue, both on the level of HLA ligand presentation and mRNA. We were able to characterize a total of 142 peptides in the qualitative analysis of HLA-presented peptides. Six of them were significantly overpresented on metastasis, among them a peptide derived from CD151; fourteen were overpresented on both primary tumor and metastasis compared to normal tissue, among them an HLA ligand derived from tumor protein p53. Thus, we could demonstrate that peptide-based immunotherapy might affect tumor as well as metastasis of RCC, but not healthy kidney tissue. Furthermore we were able to identify several peptides derived from tumor-associated antigens that are suitable for vaccination of metastatic RCC.
Publication Title
HLA ligand profiles of primary renal cell carcinoma maintained in metastases.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 72 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (N=45) with all stages of NAFLD and controls (N=18) were analysed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, PLCG1) and insulin/insulin-like signalling (including IGF1, IGFBP2, PRKCE) and replicated by bisulfite pyrosequening (independent N=39). Transcription factor binding sites at NAFLD-specific CpG sites were >1000-fold enriched for ZNF274, PGC1A and SREBP2. Intra-individual comparison of liver biopsies before and after bariatric surgery showed NAFLD-associated methylation changes to be partially reversible. Post-bariatric and NAFLD-specific methylation signatures were clearly distinct both in gene-ontology and transcription factor binding site analyses, with >400-fold enrichment of NRF1, HSF1 and ESRRA sites. Our findings provide one of the first examples of treatment-induced epigenetic organ remodelling in humans.
Publication Title
DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
TTCA: an R package for the identification of differentially expressed genes in time course microarray data.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for the detection of significant expression dynamics often fail when the expression dynamics show a large heterogeneity, and often cannot cope with irregular and sparse measurements.
Publication Title
TTCA: an R package for the identification of differentially expressed genes in time course microarray data.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for the detection of significant expression dynamics often fail when the expression dynamics show a large heterogeneity, and often cannot cope with irregular and sparse measurements.
Publication Title
TTCA: an R package for the identification of differentially expressed genes in time course microarray data.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from asthmatic children fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n=36), healthy atopic (n=23) and healthy non-atopic controls (n=53) were investigated by microarray, gene expression and silencing, transcript regulation analysis and ability to close mechanical wounds. Results: Wound repair of AEC from healthy and atopic children were not significantly different and were both faster than AEC from asthmatics. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by qPCR and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in non-asthmatic AEC inhibited wound repair, while addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5, 2deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells.
Publication Title
Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
To understand the developing striatum, key genes during development were identified using microarray analsyis tha could be considered as marker of medium spiny neurons. The ages studied is at peak striatal neurogenesis.
Publication Title
FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The recruitment of mesenchymal stem cells in order to reconstruct damaged cartilage of osteoarthritis joints is a challenging tissue engineering task. Vision towards this goal is blurred by a lack of knowledge about the underlying differences between chondrocytes and MSC during the chondrogenic cultivation process. The aim of this study was to shed light on the differences between chondrocytes and MSC occurring during chondral differentiation through tissue engineering.
Publication Title
Expression pattern differences between osteoarthritic chondrocytes and mesenchymal stem cells during chondrogenic differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 54 Downloadable Samples
IlluminaHiSeq2500
Description
Transcriptome profiling of de novo-derived ccRCC cell cultures and their matching parental tumours. VHL-mutant and VHL wild-type cultures were established by isolating CA9+ and CA9- cells from tumor samples using FACS. Overall design: RNASeq expression profiling of 18 renal cell carcinoma samples, including 6 patient tumours, 6 VHL mutant and 6 VHL WT derivative cell cultures
Publication Title
Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine.
Sample Metadata Fields
No sample metadata fields
View Samples