Similar Datasets
Project description:This experiment is part of a larger study examining the anti-tumour properties of interferon epsilon in ovarian cancer. The goal of this experiment was to test the direct effects of interferon epsilon and interferon beta on human ovarian tumours in vivo, using patient derived xenografts (PDX) in immunocompromised (NSG) mice.
2023-03-28 | GSE201337 | GEO
Project description:Investigation of the anti-tumour properties of interferon epsilon in high grade serous ovarian cancer
| PRJNA832125 | ENA
Project description:Investigation of the anti-tumour properties of interferon epsilon in high grade serous ovarian cancer in vivo.
| PRJNA830890 | ENA
Project description:High-grade serous ovarian cancer (HGSC) disseminates early and extensively throughout the peritoneal space, causing multiple lesions that are a major clinical problem. The aim of this study was to investigate the cellular composition of peritoneal tumour deposits in patient biopsies and their evolution in mouse models using immunohistochemistry, intravital microscopy, confocal microscopy, and 3D modelling. Tumour deposits from the omentum of HGSC patients contained a prominent leukocyte infiltrate of CD3(+) T cells and CD68(+) macrophages, with occasional neutrophils. Alpha-smooth muscle actin(+) (?-SMA(+) ) pericytes and/or fibroblasts surrounded these well-vascularized tumour deposits. Using the murine bowel mesentery as an accessible mouse peritoneal tissue that could be easily imaged, and two different transplantable models, we found multiple microscopic tumour deposits after i.p. injection of malignant cells. Attachment to the peritoneal surface was rapid (6-48 h) with an extensive CD45(+) leukocyte infiltrate visible by 48 h. This infiltrate persisted until end point and in the syngeneic murine ID8 model, it primarily consisted of CD3(+) T lymphocytes and CD68(+) macrophages with ?-SMA(+) cells also involved from the earliest stages. A majority of tumour deposits developed above existing mesenteric blood vessels, but in avascular spaces new blood vessels tracked towards the tumour deposits by 2-3 weeks in the IGROV-1 xenografts and 6 weeks in the ID8 syngeneic model; a vigorous convoluted blood supply was established by end point. Inhibition of tumour cell cytokine production by stable expression of shRNA to CXCR4 in IGROV-1 cells did not influence the attachment of cells to the mesentery but delayed neovascularization and reduced tumour deposit size. We conclude that the multiple peritoneal tumour deposits found in HGSC patients can be modelled in the mouse. The techniques described here may be useful for assessing treatments that target the disseminated stage of this disease.
| S-EPMC3609073 | biostudies-literature
Project description:Ovarian cancer is the most lethal gynaecologic malignancy. Although there are various subtypes of ovarian cancer, high-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer deaths. Chemoresistance is the primary reason for the unfavourable prognosis of HGSOC. Kallistatin (KAL), also known as SERPINA4, is part of the serpin family. Kallistatin has been discovered to exert multiple effects on angiogenesis, inflammation and tumour progression. However, the roles and clinical significance of kallistatin in HGSOC remain unclear. Here, we showed that kallistatin was significantly downregulated in HGSOC compared to normal fallopian tube (FT) tissues. Low expression of kallistatin was associated with unfavourable prognosis and platinum resistance in HGSOC. Overexpression of kallistatin significantly inhibited proliferation and metastasis, and enhanced platinum sensitivity and apoptosis in ovarian cancer cells. Collectively, these findings demonstrate that kallistatin serves as a prognostic predictor and provide a potential therapeutic target for HGSOC.
| S-EPMC6935502 | biostudies-literature
Project description:ObjectiveDue to limited immunological profiles of high-grade serous ovarian cancer (HGSOC), we aimed to characterize its molecular features to determine whether a specific subset that can respond to immunotherapy exists.Materials and methodsA training cohort of 418 HGSOC samples from TCGA was analysed by consensus non-negative matrix factorization. We correlated the expression patterns with the presence of immune cell infiltrates, immune regulatory molecules and other genomic or epigenetic features. Two independent cohorts containing 482 HGSOCs and in vitro experiments were used for validation.ResultsWe identified immune and non-immune groups where the former was enriched in signatures that reflect immune cells, infiltration and PD-1 signalling (all, P < 0.001), and presented with a lower chromosomal aberrations but increased neoantigens, tumour mutation burden, and microsatellite instability (all, P < 0.05); this group was further refined into two microenvironment-based subtypes characterized by either immunoactivation or carcinoma-associated fibroblasts (CAFs) and distinct prognosis. CAFs-immune subtype was enriched for factors that mediate immunosuppression and promote tumour progression, including highly expressed stromal signature, TGF-β signalling, epithelial-mesenchymal transition and tumour-associated M2-polarized macrophages (all, P < 0.001). Robustness of these immune-specific subtypes was verified in validation cohorts, and in vitro experiments indicated that activated-immune subtype may benefit from anti-PD1 antibody therapy (P < 0.05).ConclusionOur findings revealed two immune subtypes with different responses to immunotherapy and indicated that some HGSOCs may be susceptible to immunotherapies or combination therapies.
| S-EPMC7941229 | biostudies-literature
Project description:Precision medicine approaches in ovarian cancer require the accurate diagnosis of histotypes. In particular, there is a critical need to distinguish endometroid (EC) from high grade serous (HGSC) carcinomas, which differ greatly in outcomes, genetic predisposition and optimal treatment approaches. Herein, we performed label-free quantitative proteomics on freshly frozen tumour tissues to discover biomarkers that may distinguish EC from HGSC, and then used IHC to validate these using a contemporarily classified cohort of EC and HGSC samples.
2019-03-13 | PXD012998 | Pride
Project description:High-grade serous ovarian cancer (HGSOC) harbours aberrant epigenetic features, including DNA methylation. In this study we delineate pathways and networks altered by DNA methylation and associated with HGSOC initiation and progression to a platinum-resistant state. By including tumours from patients who had been treated with the hypomethylating agent (HMA) guadecitabine, we also addressed the role of HMAs in treatment of HGSOC. Tumours from patients with primary (platinum-naïve) HGSOC (n = 20) were compared to patients with recurrent platinum-resistant HGSOC and enrolled in a recently completed clinical trial (NCT01696032). Human ovarian surface epithelial cells (HOSE; n = 5 samples) served as normal controls. Genome-wide methylation profiles were determined. DNA methyltransferase (DNMT) expression levels were examined by immunohistochemistry and correlated with clinical outcomes. Cancer-related and tumorigenesis networks were enriched among differentially methylated genes (DMGs) in primary OC vs. HOSE. When comparing platinum-resistant and primary tumours, 452 CpG island (CGI)-containing gene promoters acquired DNA methylation; of those loci, decreased (P < 0.01) methylation after HMA treatment was observed in 42% (n = 189 CGI). Stem cell pluripotency and cytokine networks were enriched in recurrent platinum-resistant OC tumours, while drug metabolism and transport-related networks were downregulated in tumours from HMA-treated patients compared to HOSE. Lower DNMT1 and 3B protein levels in pre-treatment tumours were associated with improved progression-free survival. The findings provide important insight into the DNA methylation landscape of HGSOC tumorigenesis, platinum resistance and epigenetic resensitization. Epigenetic reprogramming plays an important role in HGSOC aetiology and contributes to clinical outcomes.
| S-EPMC8813084 | biostudies-literature
Project description:The aim of this study was to assess the feasibility of rapid sodium MRI (23Na-MRI) for the imaging of peritoneal cancer deposits in high grade serous ovarian cancer (HGSOC) and to evaluate the relationship of 23Na-MRI with tumour cellularity. 23Na-MRI was performed at 3?T on twelve HGSOC patients using a 3D-cones acquisition technique. Tumour biopsies specimens were collected after imaging and cellularity was measured from histology. Total 23Na-MRI scan time for each patient was approximately 11?min. At an isotropic resolution of 5.6?mm, signal-to-noise ratios (SNRs) of 82.2 ± 15.3 and 15.1 ± 7.1 (mean?±?standard deviation) were achieved for imaging of tumour tissue sodium concentration (TSC) and intracellular weighted sodium concentration (IWS) respectively. Tumour TSC and IWS concentrations were: 56.8?±?19.1?mM and 30.8?±?9.2?mM respectively and skeletal muscle TSC and IWS concentrations were 33.2?±?16.3?mM and 20.5?±?9.9?mM respectively. There were significant sodium concentration differences between cancer and skeletal muscle, Wilcoxon signed-rank test, P?<? 0.001 for TSC and P?=? 0.01 for IWS imaging. Tumour cellularity displayed a strong negative correlation with TSC, Spearman's rho = -0.92, P?<? 0.001, but did not correlate with IWS. This study demonstrates that 23Na-MRI using 3D-cones can rapidly assess sodium concentration in peritoneal deposits of HGSOC and that TSC may serve as a biomarker of tumour cellularity.
| S-EPMC6477161 | biostudies-literature
Project description:Loss-of-function mutations of the breast cancer type 1 susceptibility protein (BRCA1) are associated with breast (BC) and ovarian cancer (OC). To identify gene signatures regulated by epigenetic mechanisms in OC cells carrying BRCA1 mutations, we assessed cellular responses to epigenome modifiers and performed genome-wide RNA- and chromatin immunoprecipitation-sequencing in isogenic OC cells UWB1.289 (carrying a BRCA1 mutation, BRCA1-null) and UWB1.289 transduced with wild-type BRCA1 (BRCA1+). Increased sensitivity to histone deacetylase inhibitors (HDACi) was observed in BRCA1-null vs. BRCA1+ cells. Gene expression profiles of BRCA1-null vs. BRCA1+ cells and treated with HDACi were integrated with chromatin mapping of histone H3 lysine 9 or 27 acetylation. Gene networks activated in BRCA1-null vs. BRCA1 + OC cells related to cellular movement, cellular development, cellular growth and proliferation, and activated upstream regulators included TGFβ1, TNF, and IFN-γ. The IFN-γ pathway was altered by HDACi in BRCA1+ vs. BRCA1-null cells, and in BRCA1-mutated/or low vs. BRCA1-normal OC tumors profiled in the TCGA. Key IFN-γ-induced genes upregulated at baseline in BRCA1-null vs. BRCA1+OC and BC cells included CXCL10, CXCL11, and IFI16. Increased localization of STAT1 in the promoters of these genes occurred in BRCA1-null OC cells, resulting in diminished responses to IFN-γ or to STAT1 knockdown. The IFN-γ signature was associated with improved survival among OC patients profiled in the TCGA. In all, our results support that changes affecting IFN-γ responses are associated with inactivating BRCA1 mutations in OC. This signature may contribute to altered responses to anti-tumor immunity in BRCA1-mutated cells or tumors.
| S-EPMC6897992 | biostudies-literature