Project description:Characterizations of ascites proteome from ovarian PC and gastric PC have demonstrated that ascites contains elevated pro-tumorigenic factors. Reasoning that the composition of ascitic fluid might offer insight into the memory of key biological events occurring intra-abdominally, we hypothesized that paracrine factors essential for survival and growth of peritoneal deposits are secreted into and circulate within ascitic fluid. Our data suggest that ascites contains biologically active ligands capable of supporting cellular functions of cancer cells.
Project description:Characterizations of ascites proteome from ovarian peritoneal carcinomatosis (PC) and gastric PC have demonstrated that ascites contains elevated pro-tumorigenic factors. Reasoning that the composition of ascitic fluid might offer insight into the memory of key biological events occurring intra-abdominally, we hypothesized that paracrine factors essential for survival and growth of peritoneal deposits are secreted into and circulate within ascitic fluid. Our data from cytokine array profile suggest that ascites contains biologically active ligands capable of supporting cellular functions of cancer cells. To decipher downstream signalling pathways activated in cancer cells when exposed to ascites, we performed gene expression analysis of Colo-205 cells upon exposure to PC ascites and ligand inhibitor.
Project description:Characterizations of ascites proteome from ovarian PC and gastric PC have demonstrated that ascites contains elevated pro-tumorigenic factors. Reasoning that the composition of ascitic fluid might offer insight into the memory of key biological events occurring intra-abdominally, we hypothesized that paracrine factors essential for survival and growth of peritoneal deposits are secreted into and circulate within ascitic fluid. Our data from cytokine array profile suggest that ascites contains biologically active ligands capable of supporting cellular functions of cancer cells. To decipher downstream signalling pathways activated in cancer cells when exposed to ascites, we performed gene expression analysis of Colo-205 and SNU-C1 cells upon exposure to PC ascites.
Project description:Peritoneal carcinomatosis is a frequent finding in patients with primary gastric cancer, and it is associated with a poor prognosis. A major mechanism in peritoneal carcinomatosis is the dissemination of cancer cells into the abdominal cavity, mainly in diffuse gastric adenocarcinoma. The features that enable diffuse primary gastric tumours to develop peritoneal dissemination have been little investigated and are only incompletely understood. We therefore compared the gene expression profile in patients with diffuse primary gastric cancer with and without peritoneal carcinomatosis. Specimens from consecutive gastric cancer patients with and without peritoneal carcinomatosis were investigated using oligonucleotide microarrays. Keywords: Disease state analysis
Project description:Peritoneal carcinomatosis with malignant ascites is associated with dismal prognosis in gastric cancer. Malignant ascites is the most relevant body fluid in which to seek diagnostic biomarkers for peritoneal carcinomatosis. We aimed to identify and validate ascites-derived circulating microRNAs (miRNAs) that are differentially expressed between liver cirrhosis-associated benign ascites (LC-ascites) and gastric cancer-associated malignant ascites (GC-ascites). MiRNA expression levels were investigated in three independent cohorts. Overall, 165 ascites samples (73 LC-ascites and 92 GC-ascites) were obtained from the National Biobank of Korea. Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n = 22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were used to validate the expression levels of selected miRNAs in the training (n = 70) and validation (n= 73) cohorts. In addition, the levels of carcinoembryonic antigen (CEA), a commonly used tumor marker, were determined in the ascites samples. Expression levels of miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly lower in the GC-ascites samples than in the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC] = 0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved if CEA and miR-181b-5p were analyzed together (AUC = 0.981 and 0.946 for the training and validation cohorts, respectively). Overall, we identified ascites-derived circulating miRNAs capable of differentiating non-malignant ascites and GC-ascites, and demonstrated that the combined use of miR-181b-5p and CEA produces the optimal diagnostic yield.
Project description:The presence of ascites in peritoneal metastases (PM) portends a poor prognosis for all intra-abdominal malignancies. However, the molecular ligands within ascites and their biological relevance remain unclear. We report a comprehensive proteomics analysis of cell-free ascites in PM, including 160 malignant PM ascites covering a spectrum of 17 histological origins and 15 ascites of benign origin. This is the first large-scale proteomic analysis of cell-free ascites across diverse histological subsets of PM that can be harnessed for discovery of novel therapeutics and understanding of PM biology.
Project description:Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesising that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage sub-populations. The proportion of CRIgHi macrophages differed between patients, and in the same patient over time, and a high proportion of CRIgHi macrophages was associated with reduced disease severity (Model for End Stage Liver Disease (MELD)) score. As compared to CRIgLow macrophages, CRIgHi macrophages were highly phagocytic and displayed enhanced antimicrobial effector activity. Transcriptional profiling by RNA Sequencing and comparison with human macrophage and murine peritoneal macrophage expression signatures highlighted similarities between CRIgHi cells, human macrophages and mouse F4/80Hi resident peritoneal macrophages, and between CRIgLow macrophages, human monocytes and mouse F4/80Low monocyte-derived peritoneal macrophages. These data suggest CRIgHi and CRIgLow macrophages may represent a tissue-resident population and a monocyte-derived population, respectively. In conclusion, ascites fluid macrophage subset distribution and phagocytic capacity is highly variable between patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients.