In the past three years the role of inflammatory cytokines and chemokines in tumour promotion and progression has been intensively studied. The chemokine receptor CXCR4 and its ligand CXCL12 are commonly expressed in malignant cells from primary tumours, metastases and also in malignant cell lines. To investigate the biological significance of this receptor/ligand pair, we knocked-down CXCR4 expression in ovarian cancer cell line IGROV-1 using shRNA, and established stable cell lines.
A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment.
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View SamplesWe present evidence for an autocrine cytokine network in human ovarian cancer that has paracrine actions on the tumour microenvironment. In experiments using bioinformatics analysis of large gene expression array datasets and ovarian cancer biopsies, we found that the inflammatory cytokines TNF- and IL-6, the chemokine receptor CXCR4 and its ligand CXCL12, are co-regulated in malignant cells. We named this co-regulation the TNF network.
A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
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View SamplesWe used microarrays to profile the expression levels of 285 ovarian samples in order to identify molecular subtypes of the tumour
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
No sample metadata fields
View SamplesWe used microarrays to profile the expression levels of 5 tumour samples
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
No sample metadata fields
View SamplesWe used unsupervised hierarchical clustering to analyse expression in primary ovarian tumors and associated abdominal deposits. GeneGo pathway analysis of differentially expressed genes between primary tumors and deposits revealed 4 of the top 10 pathways related to cytoskeleton remodeling and cell adhesion.
LRP1B deletion in high-grade serous ovarian cancers is associated with acquired chemotherapy resistance to liposomal doxorubicin.
Sex, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver.
Disease, Disease stage, Subject
View SamplesLow-grade serous ovarian carcinomas are typically Ras-pathway mutated, TP53 wild-type, have limited chromosomal aberration, and are frequently associated with borderline tumors. By contrast, high-grade serous ovarian carcinoma lack Ras-pathway mutations, are invariably TP53 mutated, show widespread genomic change, and are commonly BRCA-pathway disrupted. We sought to identify differentially expressed genes between co-existing borderline and invasive components of serous carcinoma.
Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver.
Disease, Disease stage, Subject
View SamplesThe Japanese Serous Ovarian Cancer Study Group
High-risk ovarian cancer based on 126-gene expression signature is uniquely characterized by downregulation of antigen presentation pathway.
Specimen part
View SamplesBackground: Blocking the action of the pro-inflammatory cytokine interleukin-1 (IL-1) reduces beta-cell secretory dysfunction and apoptosis in vitro, diabetes incidence in animal models of Type 1 diabetes mellitus (T1D), and glycaemia via improved beta-cell function in patients with T2D. We hypothesised that anakinra, a recombinant human IL-1 receptor antagonist, improves beta-cell function in patients with new-onset T1D. Methods: In an individually randomised, two-group parallel trial involving 14 European tertiary referral centers, 69 patients aged 18-35 with T1D, < 12 weeks of symptoms, and standard mixed meal test (MMT) stimulated C-peptide 200 pM were enrolled between January, 2009 and July, 2011 and assigned by centralised computer-generated blocked randomisation with locked computer-file concealment to treatment with 100 mg anakinra (n=35) subcutaneously once daily or placebo (n=34) for 9 months as add-on to conventional therapy. Participants and care-givers, but not data monitoring unit, were masked to group assignment. The primary end-point was change in the two-hour area-under-the-curve C-peptide response to MMT, and secondary end-points changes in insulin requirements, glycaemia, and inflammatory markers at one, three, six, and nine months. Findings: The study was prematurely terminated due to slow accrual and is closed to follow-up. No interim analysis was performed. Ten patients withdrew in the anakinra and eight in the placebo arm, leaving 25 and 26 patients to be analysed, respectively. There was no statistical difference in adverse event category reporting between arms. Interpretation: Anakinra-treatment in T1D was safe, but the trial failed to meet primary and secondary outcome measures.
Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.
Subject, Time
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