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BACKGROUND: Epithelial ovarian cancer (EOC) is a highly lethal malignancy. Improvement in genetic characterization of EOC patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments. One of the most relevant cancer-specific actionable targets are protein tyrosine kinases (PTKs) whose role in EOC need to be better investigated. METHODS: EOC genomic datasets are retrieved and analyzed. The biological and clinical significance of RET genomic aberrations in ovarian cancer context are investigated by a series of in vitro and in vivo experiments. RESULTS: Epithelial ovarian cancer sequencing projects identify recurrent genomic RET missense mutations in 1.98% of patients, ranking as the top-five hit among the 100 receptor tyrosine kinases-encoding genes. RET mutants R693H and A750T show oncogenic transformation properties in NIH3T3 cells. Introduction of the RET mutants into human EOC cells increases RET signaling, cell viability, anchorage-independent cell growth and tumor xenograft growth in nude mice, demonstrating that they are activating mutations. RET mutants significantly enhance the activation of RET and its downstream MAPK and AKT signaling pathway in ovarian cancer cells. Vandetanib, a clinical approved RET inhibitor, inhibits the cell viability and decreases the activation of RET-MAPK signaling pathways in EOC cells expressing oncogenic RET mutants. CONCLUSIONS: The discovery of RET pathogenic variants in the EOC patients, suggests a previously underestimated role for RET in EOC tumorigenesis. The identification of the gain-of-function RET mutations in EOC highlights the potential use of RET in targeted therapy to treat ovarian cancer patients.

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Combinatorial synthesis of (E)-ß-trifluoromethyl vinylsulfones is accomplished through a reaction of alkynes, Togni reagent, and sodium benzenesulfinates in DMSO under metal-free conditions at room temperature. These compounds are evaluated in several assays against different tumor cells. Some hits are identified against ES-2, HO-8910, and K562.

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This retrospective analysis aimed to clarify the clinical and pathologic features of ovarian clear cell carcinoma (OCCC), and to determine the factors predictive of survival.Data waereextracted from OCCC patients who underwent primary surgery followed by adjuvant chemotherapy in Obstetrics & Gynecology Hospital of Fudan University between January2007 and December 2014. Kaplan-Meier survival estimates and Cox proportional hazards model were used for survival analyses.Of 130 patients (mean age = 56.2 years), 66.2% had stage I disease when the 5-year overall survival and 5-year disease-free survival were 89.2% and 88.1%, respectively. Patients frequently presented with large pelvic mass (>10 cm) and mild-to-moderate elevation of serological CA125 (≤200U/ mL). 60.7% of the cases at stage III/IV exhibited resistance to platinum-based chemotherapy; 37.69% of the tumors arose from endometriosis. On multivariate analysis, stage and chemoresistance were independent prognostic factors predictive for poorer survival. Survival at stage IC1 (surgical rupture) was comparable to that at stage IA (capsule intact), whereas survival at stage IC2/IC3 (rupture before surgery) was significantly worse than that at stage IA.OCCC shows distinct features compared to other epithelial ovarian cancers. FIGO stage and response to chemotherapy affect prognosis independently. Arising from endometriosis is not associated with better survival. Preoperative rupture rather than intraoperative rupture confers an adverse prognosis in otherwise stage IA disease.

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OBJECTIVE: To develop predictive models for vaginal operative route selection based on clinical variables that can be easily assessed preoperatively in patients with noninvasive gynecological conditions. DESIGN: Retrospective study. SETTING: University Hospital. POPULATION: Women with routine gynecological surgeries via different approaches. METHODS: The medical records of 315 women without prolapse and undergoing hysterectomy, adnexal cystectomy or myomectomy were reviewed. Multiple logistic regression analysis was used to identify factors associated with the vaginal approach for each procedure. Predictive models were generated and optimal cut-off points were identified using the receiver operating characteristic curve. MAIN OUTCOME MEASURES: Predictive models for different vaginal surgical procedures. RESULTS: For hysterectomy, the patient's body mass index, dysmenorrheal complaints and uterine size were identified as negative predictors for vaginal hysterectomy, whereas previous vaginal delivery was positive. For adnexal cystectomy, adnexal pathology was a negative predictor, whereas previous vaginal delivery and ovarian cyst size were positive. For myomectomy, the body mass index and number of fibroids were negative predictors while previous vaginal delivery was positive. All three models were able to predict the vaginal procedures undergone by women and the areas under the curve were 0.88, 0.95 and 0.92, respectively. Each optimal model cut-off value (logit(p) = 0.53, 0.36, 0.73) resulted in good sensitivity (92.3%, 100% and 87.5%, respectively) and specificity (77.8%, 88.6% and 90.9%, respectively). CONCLUSION: These predictive models, which used clinical variables that can be easily assessed preoperatively, may help surgeons to select candidates for different vaginal procedures.

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Monodispersed mesoporous phenolic polymer nanospheres with uniform diameters were prepared and used as the core for the further growth of core-shell mesoporous nanorattles. The hierarchical mesoporous nanospheres have a uniform diameter of 200 nm and dual-ordered mesopores of 3.1 and 5.8 nm. The hierarchical mesostructure and amphiphilicity of the hydrophobic carbon cores and hydrophilic silica shells lead to distinct benefits in multidrug combination therapy with cisplatin and paclitaxel for the treatment of human ovarian cancer, even drug-resistant strains.

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OBJECTIVE: To introduce a model incorporating expected risks for a vaginal procedure based on objective measurements of a patient's characteristics and propose it as a potential tool to assist in the selection of candidates for vaginal surgery. STUDY DESIGN: A quantitative model consisting of 13 clinical variables identified as risk factors in a prospective vaginal procedure was developed. Medical records of 315 women undergoing a set of routine gynecological surgeries via the vaginal, laparoscopic, and abdominal routes were obtained during January 2010 and November 2011. These surgeries included hysterectomy, myomectomy, bilateral or unilateral salpingo-oophorectomy and adnexal cystectomy. After that, each patient was scored according to the model. Sensitivity and specificity of the model were analyzed in one data set (cohort I) by receiver operating characteristic (ROC) curve and independently validated in a second data set (cohort II). RESULTS: 175 patients were included in cohort I while the other 140 patients formed cohort II. The intra- and post-operative complication rates were 0.6% and 0%, respectively. A vaginal procedure was predicted with good accuracy (AUC=0.852). The sensitivity was 86.0% and specificity was 72.0% at an optimal cut-off point of score=3. The predication accuracy of this model was further validated in cohort II and reached as high as 85.7%. Furthermore, the score was significantly associated with the volume of estimated blood loss and the duration of operation time (P<0.05). CONCLUSION: Our quantitative risk assessment model predicts safe vaginal surgery with good accuracy. Predictive tools based on such a model could help surgeons to optimize patient selection and thus contribute to reducing costs while enhancing patients' satisfaction. We invite other researchers to modify and validate the model in other populations.

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microRNAs (miRNAs) are important regulators of gene expression during tumorigenesis. The downregulation of microRNA-9 (miR-9) has been reported in ovarian serous carcinoma (OSC), indicating a role for miR-9 in this type of cancer. In this study, we investigated the biological significance of miR-9 in OSC in vitro. Using 3 OSC cell lines, SKOV3, CAOV3 and OVCAR3, which underexpresss miR-9, we demonstrate that the exogenous miR-9 transfection inhibits OSC cell proliferation, migration and invasion. In addition, we demonstrate that the focal adhesion protein, talin 1 (TLN1), whose expression has been associated with OSC development and progression to metastasis, is a direct target of miR-9. TLN1 knockdown mimicked the effects of miR-9 overexpression. Moreover, the activation of the TLN1-modulated FAK/AKT pathway was inhibited by the increased miR-9 levels. These results suggest that miR-9 plays a role as a tumor suppressor in OSC by suppressing TLN1 expression.

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Neovascularization is essential for tumor growth and metastasis. An adequate vasculature feeds tumor growth and enhances the potential of metastasis. For many years, tumor vessels were thought to be lined exclusively by endothelial cells (ECs). However, therapeutic benefits from the promising antiangiogenic strategy targeting genetically stable ECs are frequently limited by the development of resistance, implying an oversimplified view of tumor vasculature. In fact, latest studies have revealed that in addition to ECs, other cells including bone marrow-derived and plastic tumor cells do contribute to tumor vascularization, which is also indicated in ovarian cancer, the most lethal gynecologic malignancy characterized by widespread metastases within the peritoneal cavity upon diagnosis. Given the principle that tumor progression and metastasis are dependent on a persistent blood supply, it is logical that the capability of generating neovessels through diverse mechanisms of ovarian cancer is associated with its malignant potential. This review will discuss the diverse origins of ovarian cancer vascular cells and emphasize their clinical relevance (in the hope of providing insight into the prognostic assessment of women at risk for aggressive disease behavior) and alternative targets for therapeutic intervention.

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