In this study, we investigated the therapeutic effects of c-MET inhibition in ovarian clear cell carcinoma (OCCC). Expression levels of c-MET in the epithelial ovarian cancers (EOCs) and normal ovarian tissues were evaluated using real-time PCR. To test the effects of c-MET inhibitors in OCCC cell lines, we performed MTT and apoptosis assays. We used Western blots to evaluate the expression of c-MET and its down-stream pathway. In vivo experiments were performed to test the effects of c-MET inhibitor on tumor growth in orthotopic mouse xenografts of OCCC cell line RMG1 and a patient-derived tumor xenograft (PDX) model of OCCC. c-MET expression was significantly greater in OCCCs compared with serous carcinomas and normal ovarian tissues (p < 0.001). In in vitro study, inhibition of c-MET using c-MET inhibitors (SU11274 or crizotinib) significantly decreased the proliferation, and increased the apoptosis of OCCC cells. SU11274 decreased expression of the p-c-MET proteins and blocked the phosphorylation of down-stream proteins Akt and Erk. Furthermore, SU11274 treatment significantly decreased the in vivo tumor weight in xenograft models of RMG1 cell and a PDX model for OCCC compared to control (p = 0.004 and p = 0.009, respectively).

ObjectiveThis study was designed to compare survival outcomes of patients with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CC) to those of patients with grade 3 endometrioid carcinoma (G3EC) according to 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) staging systems.MethodsWe retrospectively reviewed all patients with endometrial cancer treated at a single institution between 1995 and 2009. Among the 647 patients with endometrial cancer, 51 with G3EC and 46 with UPSC and CC histology were confirmed.Results1988 FIGO stage, 2009 FIGO stage, and extrauterine metastasis were significantly different between the UPSC and CC group and G3EC group (p=0.002, p=0.041, and p=0.020, respectively). Restaging from the 1988 FIGO to the 2009 FIGO criteria increased the number of stage I cases by 10 (11.0%). Overall, 8 in the UPSC and CC and 2 in the G3EC group were down-staged to stage I. In the UPSC and CC group, the 3-year overall survival for 1988 FIGO stage I was 92.9%. When UPSC and CC patients were restaged using the 2009 staging system, the 3-year overall survival of 2009 FIGO stage I dropped to 81.6%. UPSC and CC was associated with poor OS outcome compared with G3EC, after adjustment for 2009 FIGO stage and other clinicopathologic factors.ConclusionWe observed that UPSC and CC patients had different prognosis according to the old and new FIGO staging system. Our results suggest that UPSC and CC compared with the G3EC may retain the 1988 FIGO to be a slightly better discriminator than 2009 FIGO.

The combination of omental extension to the stomach or spleen and involvement of inguinal or pelvic lymph nodes in preoperative CT scans is considered predictive of suboptimal cytoreduction. These patients may be more appropriately treated with neoadjuvant chemotherapy followed by surgical cytoreduction.

The combination of aprepitant, ramosetron, and high-dose dexamethasone demonstrated efficacy for CINV prevention in ovarian cancer patients receiving paclitaxel and carboplatin.