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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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Cytokine profile of ascites derived from patients with peritoneal carcinomatosis

Project description:Cytokine profile of ascites derived from patients with peritoneal carcinomatosis

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Expression data of ascites treated peritoneal carcinomatosis human cell lines

Project description:Expression data of ascites treated peritoneal carcinomatosis human cell lines

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MVA.scIL12 treatment in a mouse model of peritoneal carcinomatosis (PCa)

Project description:MVA.scIL12 treatment in a mouse model of peritoneal carcinomatosis (PCa)

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Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Bulk RNA-Seq]

Project description:Peritoneal carcinomatosis (PC) originating from colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Metastasis is the major cause of death in patients with CRC whereas primary locoregionally circumscribed tumors are mostly curable. Due to the lack of appropriate and realistic mouse models for metastasis of CRC until recently, the research about metastasis of these tumors and possible therapeutic options is still in its infancy. With the establishment of murine CRC tumor organoids, mouse models were established which realistically mimic the process of tumor cell metastasis to the liver and the lung. However, to date no appropriate model for PC is described. Here, we establish a realistic model for peritoneal metastasis of colorectal cancer upon surgical transplantation of tumor organoids into the cecum wall. This mouse model for PC recapitulates human PC which makes it an ideal model for research of the biology of metastasis of colorectal cancer to the peritoneal cavity and for its usage for preclinical drug screening as well as for the evaluation of new therapeutic approaches which are highly needed in clinical reality.

2022-06-27 | GSE202454 | GEO

Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [TIL scRNA-Seq]

Project description:Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in UICC stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analysed the transcriptome of single cells derived from murine multivisceral CRC and gave insight into the inter-metastatic cellular heterogeneity regarding tumor epithelium, stroma and immune cells. Interestingly, we found an intercellular site-specific network of cancer associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell dependent antigen presentation and consecutive effector cell exhaustion. Consequently, we demonstrate the high human-mimicking potential of this murine metastatic CRC model and provide a valid tool for future site-specific preclinical drug testing.

2024-01-10 | GSE220175 | GEO

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