Project description:Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Positive cytology in ascites was a significant poor prognostic factor in ovarian cancer. Microarray profiles of cytology-positive cases showed significant correlations with Gene Ontology terms related to immune system process. Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and positive cytology. PD-L1 expression on mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and upon co-culturing with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination. Genome-wide transcriptional changes in human ovarian cancer tissue from ascites-cytology-positive or -negative patients.
Project description:Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Positive cytology in ascites was a significant poor prognostic factor in ovarian cancer. Microarray profiles of cytology-positive cases showed significant correlations with Gene Ontology terms related to immune system process. Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and positive cytology. PD-L1 expression on mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and upon co-culturing with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination.
Project description:Differential transcriptome signature of FACS purified cell population (EpiCAM/CD45 dual positive cells vs EpiCAM only) from the ascites of human serous ovarian cancer. Primary objective: To characterize the phenotypic expression of stem cells markers, elucidation of differential gene expression and oncogenic functions in EpiCAM/CD45 dual positive vs EpiCAM cells. Methods: Cell Sorting (FACS) from ascites of human serous ovarian cancer patients, apoptotic assay, Drug sensitivity assay, tumor spheroid assay, Cell invasion and cell migration assay.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:We 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-α 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. We had access to a unique set of ascites cell samples from patients with advanced ovarian cancer treated with the therapeutic anti-human TNF-α antibody infliximab. Serial samples pre and during treatment were obtained during paracentesis (drainage of ascites fluid for symptomatic relief). In nine of these patients there was sufficient mRNA available for gene expression profile analysis before treatment. The Affymetrix GeneChip Human Genome U133Plus 2.0 arrays were used to define gene expression profiles in each of the ascites cell samples.