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GSE51373
Homo sapiens
25 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer. Methods: The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with the same standard platinum-based chemotherapy. Twelve patient tumors demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumors from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using a Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumors from the resistant group and the sensitive group. Results: Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels, which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NFB/ERK gene signalling networks. Conclusions: This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. Future studies to validate these markers are necessary to apply this knowledge to biomarker-based clinical trials.
Publication Title
Identification of the IGF1/PI3K/NF κB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Tissue injury, such as incisional wound, results in an inflammatory response as well as acute to chronic mechanical and thermal pain. It is now understood that there is a strong contribution of these immune cells to the pain phenotype.
Publication Title
CD11b+Ly6G- myeloid cells mediate mechanical inflammatory pain hypersensitivity.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
TGFbeta is the major cytokine driver of fibrosis in the kidney and other tissue. Epithelial-mesenchymal transition has been postulated to contibrute to renal fibrosis in diseases such as diabetic nephropathy.
Publication Title
Next-generation sequencing identifies TGF-β1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy.
Sample Metadata Fields
Cell line, Time
View Samples- Populus tremula x populus alba
- 6 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
Trichomes are specialised epidermal cells that generally play a role in reducing transpiration and act as a deterrent to herbivory. In a screen of activation tagged Populus tremula x P. alba 717-1B4 trees, we identified a mutant line, fuzzy, with increased foliar trichome density. This mutant also had a 35% increase in growth rate and a 200% increase in the rate of photosynthesis as compared to wild-type poplar. The fuzzy mutant had significant resistance to feeding by larvae of the white spotted tussock moth (Orgyia leucostigma), a generalist insect pest of poplar trees. The fuzzy phenotype is attributable to activation tagging and increased expression of the gene encoding PtaMYB186, which is related to Arabidopsis thaliana MYB106, a known regulator of trichome initiation. The fuzzy phenotype can be recapitulated by overexpressing PtaMYB186 in poplar. PtaMYB186 overexpression results in reconfiguration of the poplar transcriptome, with changes in the transcript abundance of suites of genes that are related to trichome differentiation. It is notable that this gene responsible for trichome development also altered traits related to growth rate and pest resistance, suggesting that non-intuitive facets of plant development might be useful targets for plant improvement.
Publication Title
Endogenous overexpression of Populus MYB186 increases trichome density, improves insect pest resistance, and impacts plant growth.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina Genome Analyzer II, Affymetrix Human Exon 1.0 ST Array [AltAnalyze 2.0.6 beta probeset-to-Ensembl mapping (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress.
Sample Metadata Fields
Treatment
View Samples- Pseudomonas aeruginosa
- 16 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Pseudomonas aeruginosa airway infection is the primary cause of death in Cystic Fibrosis (CF). During early infection P. aeruginosa produces multiple virulence factors, which cause acute pulmonary disease and are largely regulated by quorum sensing (QS) intercellular signalling networks. Longitudinal clinical studies have observed the loss, through adaptive mutation, of QS and QS-related virulence in late chronic infection. Although the mechanisms are not understood, infection with QS mutants has been linked to a worse outcome for CF patients. By comparing QS-active and QS-inactive P. aeruginosa CF isolates, we have identified novel virulence factors and pathways associated with QS disruption. In particular, we noted factors implicating increased intra-phagocyte survival. Our data present novel targets as candidates for future CF therapies. Some of these targets are already the subject of drug development programmes for the treatment of other bacterial pathogens and may provide cross-over benefit to the CF population.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa
- 12 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Pseudomonas aeruginosa is a common pathogen in the lungs of the cystic fibrosis patients. As infection develops the organism progressively adapts to its environment and its mode of pathogenesis alters, frequently including the loss of quorum sensing regulated virulence factors.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [AltAnalyze 2.0.6 beta probeset-to-Ensembl mapping (huex10st)
Description
In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying epithelia to maintain proliferative capacity or drive proliferation of squamous cell carcinomas, where TP63 is frequently overexpressed/amplified. Here we use ChIP-sequencing, integrated with microarray analysis, to define the genome wide interplay between TP53 and TP63 in response to genotoxic stress in normal cells. We reveal that TP53 and TP63 bind to overlapping, but distinct cistromes of sites through utilization of distinctive consensus motifs and that TP53 is constitutively bound to a number of sites. We demonstrate that cisplatin and adriamycin elicit distinct effects on TP53 and TP63 binding events, through which TP53 can induce or repress transcription of an extensive network of genes by direct binding and/or modulation of TP63 activity. Collectively, this results in a global TP53 dependent repression of cell cycle progression, mitosis and DNA damage repair concomitant with activation of anti-proliferative and pro-apoptotic canonical target genes. Further analyses reveals that in the absence of genotoxic stress TP63 plays an important role in maintaining expression of DNA repair genes, loss of which results in defective repair
Publication Title
Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress.
Sample Metadata Fields
Treatment
View Samples- Pseudomonas aeruginosa
- 9 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
To verify the imapct of DSF and C23 on P. aeruginosa during infection
Publication Title
No associated publication
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute myeloid leukaemia (AML) is a highly heterogeneous entity of disorders in haematopoietic progenitors, characterised by an arrest in differentiation and an outgrowth of myeloid blasts in the bone marrow. AML is a disease of the aging, many patients are unable to withstand standard chemotherapy therefore novel approaches for anti-cancer agents has arisen in the understanding of epigenetic regulation in cancer cells, such as chromatin remodelling. Acetylation of histones is a reversible process, whereby acetyl groups are transferred on the -amino groups of specific lysine residues by a specific group of enzymes, histone acetyltransferases (HATs) and removed by histone deacetylase complexes (HDACs). HDACs are involved in regulating a number of processes in the cell, such as cell proliferation, differentiation as well as apoptosis. Deregulation of the activity of these enzymes is associated with cancer; therefore it is important that the HAT and HDAC equilibrium is regained. This equilibrium can be improved through the inhibition of HDAC enzymes using HDAC inhibitors. Vorinostat is a HDAC inhibitor, clinically approved for the treatment of CTCL, and is in phase II clinical trials for AML and a number of haematological malignancies. Studies have shown that some patients are non-responsive/resistant to Vorinostat; therefore a fuller characterisation of Vorinostat needs to be made so an adequate combination drug can be identified, as understanding of resistance is crucial to overcoming it. The purpose of this study was to provide a comprehensive analysis of Vorinostat in AML cell lines and to identify potential synergistic therapies that could be used in combination with Vorinostat to provide a better outlook in AML. The global identification of genes associated with Vorinostat induced histone H3 lysine 9 (H3K9) acetylation, investigated using chromatin immunoprecipitation coupled with next generation sequencing (ChIP-SEQ), was integrated with data from gene expression studies to provide a comprehensive approach to understanding Vorinostat. This study has identified the sonic hedgehog homolog (SHH) as a rational and potential therapeutic target for combination therapy with Vorinostat
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples