Filters
Technology
Platform
GSE57380
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Ovarian clear cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a genetically engineered mouse model of OCCC. We find that ARID1A inactivation is not sufficient for tumor formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, the mice develop highly penetrant tumors with OCCC-like histopathology, culminating in hemorrhagic ascites and a median survival period of 7.5 weeks. Therapeutic treatment with the pan-PI3K inhibitor, BKM120, prolonged mouse survival by inhibiting tumor cell growth. Cross-species gene expression comparisons support a role for IL-6 inflammatory cytokine signaling in OCCC pathogenesis. We further show that ARID1A-PIK3CA mutations cooperate to promote tumor growth through sustained IL-6 overproduction. Our findings establish an epistatic relationship between SWI/SNF chromatin remodeling and PI3K pathway mutations in OCCC and demonstrate that these pathways converge on pro-tumorigenic cytokine signaling. We propose that ARID1A protects against inflammation-driven tumorigenesis.
Publication Title
Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 96 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Assessed steady-state transcription in whole brain and two more specific brain regions.
Publication Title
Transcriptome atlases of mouse brain reveals differential expression across brain regions and genetic backgrounds.
Sample Metadata Fields
Treatment
View Samples- Mus musculus, Homo sapiens
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Topoisomerases facilitate transcription of long genes linked to autism.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Topoisomerases are necessary for the expression of neurodevelopmental genes, and are mutated in some patients with autism spectrum disorder (ASD). We have studied the effects of inhibitors of Topoisomerase 1 (Top1) and Topoisomerase 2 (Top2) enzymes on mouse cortical neurons. We find that topoisomerases selectively inhibit long genes (>100kb), with little effect on all other gene expression. Using ChIPseq against RNA Polymerase II (Pol2) we show that the Top1 inhibitor topotecan blocks transcriptional elongation of long genes specifically. Many of the genes inhibited by topotecan are candidate ASD genes, leading us to propose that topoisomerase inhibition might contribute to ASD pathology.
Publication Title
Topoisomerases facilitate transcription of long genes linked to autism.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 47 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Expression data from 4T1 subclones derived from mammary fat pad tumors (MFP), axillary lymph node tumors (AxLN), and axillary lymph node-derived lung metastases (AxLN-LuM). In parallel, expression data, in the same subclones, of tail vein-derived (TV) lung metastases.
Publication Title
Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarrays were used to evaluate the effects of azithromycin and an inflammatory stimulus (SMM) on human airway epithelium. Effects of azithromycin treatment were evaluated at 6, 24 and 48 hours. Effects of SMM were evaluated at 6 and 24 hours. In addition, pretreatment with azithromycin was used to evaluate the modulatory effects on SMM-induced inflammation. SMM=supernatant from microcorpulent material from human cystic fibrosis airways.
Publication Title
Azithromycin treatment alters gene expression in inflammatory, lipid metabolism, and cell cycle pathways in well-differentiated human airway epithelia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
IFN, an effective therapy against relapsing-remitting (RR) multiple sclerosis (MS) is naturally secreted during the innate immune response against viral pathogens. The objective of this study was to characterize the immunomodulatory mechanisms of IFN targeting innate immune response and their effects on DC-mediated regulation of T-cell differentiation. We found that IFN1a in-vitro treatment of human monocyte-derived dendritic cells (DCs) induced the expression of TLR7 and the members of its downstream signaling pathway, including myeloid differentiation factor 88 (MyD88), IL-1R-associated kinase (IRAK)4, and TNF receptor-associated factor (TRAF)6, while it inhibited the expression of IL-1R. Using siRNA TLR7 gene silencing, we confirmed that IFN-1a-induced changes in MyD88, IRAK4 and IL-1R expression were dependent on TLR7. TLR7 expression was also necessary for the IFN-1a-induced inhibition of IL-1 and IL-23, and the induction of IL-27 secretion by DCs. Supernatant (SN) transfer experiments confirmed that IFN-1a-induced changes in DCs cytokine secretion inhibit Th17 cell differentiation as evidenced by the inhibition of retinoic acid-related orphan nuclear hormone receptor C (RORC) and IL-17A gene expression and IL-17A secretion. Our study has identified a novel therapeutic mechanism of IFN1a, that selectively targets the autoimmune response in MS.
Publication Title
IFN-beta1a inhibits the secretion of Th17-polarizing cytokines in human dendritic cells via TLR7 up-regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Pharmacological inhibition of cyclooxygenase-2 (COX-2) is being explored as a chemotherapeutic option because COX-2 protein expression is often elevated in many cancers. Cancer cells treated with COX-2 inhibitors, such as the selective COX-2 inhibitor celecoxib, show growth inhibition and the induction of apoptosis, through alterations in inflammatory processes, angiogenesis, cell adhesion and transforming growth factor- signaling. This study was conducted to determine if the same processes are relevant to celecoxibs effects on human colorectal adenocarcinomas treated in vivo. A cohort of 23 patients with primary colorectal adenocarcinomas was randomized to receive a 7-day course of celecoxib (400 mg b.i.d.) or no drug prior to surgical resection. Gene expression profiling was performed on resected adenocarcinomas from patients with and without celecoxib pre-treatment. Using fold change (>1.5) and p-value (<0.05) cut-offs, 190 genes were differentially expressed between adenocarcinomas from patients receiving celecoxib and those that did not. Of the differentially expressed genes, multiple genes involved in cellular lipid and glutathione metabolism showed decreased expression levels in celecoxib pre-treated samples; changes associated with diminished cellular proliferation. Other observed gene expression changes consistent with reduced proliferation include: altered expression of genes involved in cell adhesion (including collagen, laminin, von Willebrand factor and tenascin C), increased expression of inflammatory modulators (including inerleukin-6, S100 calcium binding protein A8, and several chemokines) and decreased expression of the pro-angiogenic gene, angiogenin. Celecoxib pre-treatment for 7 days in vivo is associated with alterations in colorectal adenocarcinoma gene expression which are suggestive of diminished cellular proliferation.
Publication Title
Celecoxib pre-treatment in human colorectal adenocarcinoma patients is associated with gene expression alterations suggestive of diminished cellular proliferation.
Sample Metadata Fields
Sex, Disease stage, Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Our results introduce interleukin (IL)-11 as a new cytokine that may play a role in the development of the autoimmune response in patients with relapsing remitting multiple sclerosis (RR MS). IL-11 was found to be the highest up-regulated cytokine in the serum and cerebrospinal fluid (CSF) from patients with clinically isolated syndrome (CIS) suggestive of MS. It was also increased in the serum and CSF of patients with clinically definitive RRMS and during the clinical relapses of the disease. CD4+ cells represent a predominant cell source of IL-11 in the peripheral circulation, and the percentage of IL-11+CD4+ cells is significantly increased in CIS patients in comparison to healthy controls (HCs). Furthermore, we have identified IL-11 as a new Th17-promoting cytokine. IL-11 induces a differentiation of nave CD4+ T cells into Th17 cells, as well as Th17 memory cell expansion, characterized by secretion of IL-17A, IL-17F, IL-21 and IL-22. Since the Th17 cytokines IL-17F, IL-21 and TNF- induced differentiation of nave cells in the IL-11-secreting CD4+ cells, we propose that cross-talk between IL-11+CD4+ and Th17-cells may play a role in the initiation and propagation of the autoimmune response in RRMS.
Publication Title
IL-11 Induces Th17 Cell Responses in Patients with Early Relapsing-Remitting Multiple Sclerosis.
Sample Metadata Fields
Specimen part
View Samples