Obesity is a serious health problem and critically related to poor prognosis in cancer, presumably through induction of chronic inflammation. The major culprit for cancer progression in obesity is presumed to be macrophages. Accumulation of macrophages in adipose tissue due to obesity induced chronic inflammation has been observed. However, obesity-induced macrophage accumulation related to ovarian cancer progression remains unclear. So, the role of macrophage in cancer progression is needed to be further defined for therapeutic intervention. Here we determined the effect of macrophage type 1 (M1 macrophage) on ovarian cancer cells in relation to the metastasis. Ovarian cancer cell lines (PA-1, SKOV3) and monocyte-derived macrophages were used in this study. Treatment with M1 macrophage conditioned media on ovarian cancer cells increased the metastatic potential, such as migration and invasion capabilities. Interestingly, upon treatment with M1 macrophage conditioned media, nuclear translocation of NF-κB, p60, and p50, from the cytosol was enhanced together with increased transcriptional activity of the NF-κB. Pre-treatment with TPCK (NF-κB inhibitor) and NF-κB siRNA on ovarian cancer cells suppressed M1 macrophage-induced metastatic potential. Furthermore, Treatment of TNF-α on ovarian cancer cells showed NF-κB activation. Co-treatment with TNF-α inhibitor, etanercept, and M1 macrophage conditioned media on ovarian cancer cell lines reversed M1 macrophage conditioned media induced NF-κB activation. Taken together, TNF-α released from M1 macrophage increased metastatic potential in ovarian cancer cells through the activation of NF-κB signaling pathway. These results provide a new insight into the critical role of M1 macrophage in the tumor microenvironment in ovarian cancer.
Purpose Discovery of models predicting the exact prognosis of epithelial ovarian cancer (EOC) is necessary as the first step of implementation of individualized treatment. This study aimed to develop nomograms predicting treatment response and prognosis in EOC. Materials and Methods We comprehensively reviewed medical records of 866 patients diagnosed with and treated for EOC at two tertiary institutional hospitals between 2007 and 2016. Patients’ clinico-pathologic characteristics, details of primary treatment, intra-operative surgical findings, and survival outcomes were collected. To construct predictive nomograms for platinum sensitivity, 3-year progression-free survival (PFS), and 5-year overall survival (OS), we performed stepwise variable selection by measuring the area under the receiver operating characteristic curve (AUC) with leave-one-out cross-validation. For model validation, 10-fold cross-validation was applied. Results The median length of observation was 42.4 months (interquartile range, 25.7 to 69.9 months), during which 441 patients (50.9%) experienced disease recurrence. The median value of PFS was 32.6 months and 3-year PFS rate was 47.8% while 5-year OS rate was 68.4%. The AUCs of the newly developed nomograms predicting platinum sensitivity, 3-year PFS, and 5-year OS were 0.758, 0.841, and 0.805, respectively. We also developed predictive nomograms confined to the patients who underwent primary debulking surgery. The AUCs for platinum sensitivity, 3-year PFS, and 5-year OS were 0.713, 0.839, and 0.803, respectively. Conclusion We successfully developed nomograms predicting treatment response and prognosis of patients with EOC. These nomograms are expected to be useful in clinical practice and designing clinical trials.
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