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Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis

ABSTRACT: Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis

PROVIDER: PRJNA781833 | ENA |

REPOSITORIES: ENA

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Peritoneal Carcinomatosis of gastric cancer

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

2008-01-31 | GSE8657 | GEO

Expression data of peritoneal carcinomatosis human cell lines co-treated with patient derived ascites and ligand inhibitor

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.

2022-02-22 | GSE189137 | GEO

Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis.

Project description:Peritoneal carcinomatosis (PC) present a ubiquitous clinical conundrum in all intra-abdominal malignancies. Via functional and transcriptomic experiments of ascites-treated PC cells, we identify STAT3 as a key signaling pathway. Integrative analysis of publicly available databases and correlation with clinical cohorts (n = 7,359) reveal putative clinically significant activating ligands of STAT3 signaling. We further validate a 3-biomarker prognostic panel in ascites independent of clinical covariates in a prospective study (n = 149). Via single-cell sequencing experiments, we uncover that PAI-1, a key component of the prognostic biomarker panel, is largely secreted by fibroblasts and mesothelial cells. Molecular stratification of ascites using PAI-1 levels and STAT3 activation in ascites-treated cells highlight a therapeutic opportunity based on a phenomenon of paracrine addiction. These results are recapitulated in patient-derived ascites-dependent xenografts. Here, we demonstrate therapeutic proof of concept of direct ligand inhibition of a prognostic target within an enclosed biological space.

| S-EPMC8861959 | biostudies-literature

Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-02-22 | GSE189169 | GEO

Expression data of peritoneal carcinomatosis human cell lines co-treated with patient derived ascites and ligand inhibitor

Project description:Expression data of peritoneal carcinomatosis human cell lines co-treated with patient derived ascites and ligand inhibitor

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Project description:To identify the proteome of human peritoneal tissue, 43 FFPE and 5 fresh frozen peritoneal tissue samples at healthy or non-cancerous state were collected and subjected to mass spectrometry analysis. The resulting findings represnt a baseline catalog of the proteomic composition of the peritoneum, as a comparison dataset for future studies focused on alterations in pathologic states such as peritoneal carcinomatosis.

2025-12-31 | PXD071403 | Pride

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