dehydroxymethylepoxyquinomicin and Ovarian-Neoplasms

dehydroxymethylepoxyquinomicin has been researched along with Ovarian-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for dehydroxymethylepoxyquinomicin and Ovarian-Neoplasms

ArticleYear
Immunosuppression through constitutively activated NF-κB signalling in human ovarian cancer and its reversal by an NF-κB inhibitor.
    British journal of cancer, 2014, Jun-10, Volume: 110, Issue:12

    Although T-cell immunity is thought to be involved in the prognosis of epithelial ovarian cancer (EOC) patients, immunosuppressive conditions hamper antitumour immune responses. Thus, their mechanisms and overcoming strategies need to be investigated.. The role of NF-κB in human EOC cells and macrophages was evaluated by in vitro production of immunosuppressive IL-6 and IL-8 by EOC cells and in vivo analysis of immune responses in nude mice implanted with human EOC cells using an NF-κB inhibitor DHMEQ.. In EOC patients, increased plasma IL-6, IL-8, and arginase were observed. The NF-κB inhibitor DHMEQ inhibited the production of IL-6 and IL-8 by EOC cell lines. Immunosuppression of human DCs and macrophages by culture supernatant of EOC cells was reversed with the pretreatment of DHMEQ. Administration of DHMEQ to nude mice implanted with human EOC resulted in the restoration of T-cell stimulatory activity of murine DCs along with the reduction of tumour accumulation and arginase expression of MDSCs. Nuclear factor-κB inhibition in tumour-bearing mice also enhanced antitumour effects of transferred murine naive T cells.. NF-κB is involved in the immunosuppression induced by human EOC, and its inhibitor may restore antitumour immune responses, indicating that NF-κB is an attractive target for EOC treatment.

    Topics: Adoptive Transfer; Animals; Arginase; Benzamides; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Culture Media, Conditioned; Cyclohexanones; Dendritic Cells; Female; Humans; Immune Tolerance; Interleukin-6; Interleukin-8; Macrophages; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Signal Transduction; Transcription Factor RelA; Transplantation, Heterologous

2014
Ligand-dependent EGFR activation induces the co-expression of IL-6 and PAI-1 via the NFkB pathway in advanced-stage epithelial ovarian cancer.
    Oncogene, 2012, Sep-13, Volume: 31, Issue:37

    The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, is expressed in up to 70% of epithelial ovarian cancers (EOCs), where it correlates with poor prognosis. The majority of EOCs are diagnosed at an advanced stage, and at least 50% present malignant ascites. High levels of IL-6 have been found in the ascites of EOC patients and correlate with shorter survival. Herein, we investigated the signaling cascade led by EGFR activation in EOC and assessed whether EGFR activation could induce an EOC microenvironment characterized by pro-inflammatory molecules. In vitro analysis of EOC cell lines revealed that ligand-stimulated EGFR activated NFkB-dependent transcription and induced secretion of IL-6 and plasminogen activator inhibitor (PAI-1). IL-6/PAI-1 expression and secretion were strongly inhibited by the tyrosine kinase inhibitor AG1478 and EGFR silencing. A significant reduction of EGF-stimulated IL-6/PAI-1 secretion was also obtained with the NFkB inhibitor dehydroxymethylepoxyquinomicin. Of 23 primary EOC tumors from advanced-stage patients with malignant ascites at surgery, 12 co-expressed membrane EGFR, IL-6 and PAI-1 by immunohistochemistry; both IL-6 and PAI-1 were present in 83% of the corresponding ascites. Analysis of a publicly available gene-expression data set from 204 EOCs confirmed a significant correlation between IL-6 and PAI-1 expression, and patients with the highest IL-6 and PAI-1 co-expression showed a significantly shorter progression-free survival time (P=0.028). This suggests that EGFR/NFkB/IL-6-PAI-1 may have a significant impact on the therapy of a particular subset of EOC, and that IL-6/PAI-1 co-expression may be a novel prognostic marker.

    Topics: Benzamides; Biomarkers, Tumor; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cell Proliferation; Cyclohexanones; Disease-Free Survival; ErbB Receptors; Female; Humans; Interleukin-6; Neoplasms, Glandular and Epithelial; NF-kappa B; Ovarian Neoplasms; Plasminogen Activator Inhibitor 1; Quinazolines; RNA Interference; RNA, Small Interfering; Signal Transduction; Tumor Microenvironment; Tyrphostins

2012
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