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Ovarian neoplasms are group of aggressive and lethal diseases. Surgical and radiochemical therapies on ovarian neoplasm are conventional approaches but with limited progress in years. Targeted therapy with drugs targeting specific genetic alterations and/or protein molecules have brought new hope fighting against ovarian neoplasms. Targeted therapy on genetic alterations of BRAF, ROS-1 and HER2 have been carried out in melanoma, lung cancer and breast cancer with promising results. However, knowledge of these genetic alterations in ovarian neoplasms is limited and deserves further exploration. In this study, we screened genetic alterations of BRAF, ROS-1 and HER2 by immunohistochemistry (IHC) on a variety of ovarian neoplasm, including 13 mucinous carcinomas, 12 clear cell carcinomas, 9 endometrioid carcinomas, 9 serous borderline tumors and 10 high grade serous tumor of fallopian tube. Although ROS-1 and HER2 abnormalities were not identified, BRAF V600E mutations were identified in 2 of 9 (22%) in borderline serous tumors. This finding has provided a knowledge base to further study the possibility of targeted therapy using BRAF inhibitor, such as vemurafeni, on borderline serous tumor of the ovary.

The molecular structure of the ground electronic state(X2Σ+) of 35 ClF-and 37 ClF-molecular ions have been calculated using single and double substitution quadratic configuration interaction calculations with the triple contribution [QCISD(T)] method and the simple and double excitation coupled-cluster theory with noniterative treatment with the triple excitations [CCSD(T)] method in combination with the correlation consistent basis sets aug-cc-pVXZ(X=D,T,Q,5).Basis set extrapolation procedures were employed to estimate the complete basis set limit using results obtained with the CCSD(T) method.The analytical potential energy curves for the ground state of the systems were determined by fitting the data of single point energy scans that were calculated at the CCSD(T)/aug-cc-pVXZ(X=D,T,Q,5) level of theory.The obtained potential energy curves correctly described the configuration and dissociation energy of the molecular ion and was well reproduced by the Murrell-Sorbie function.The corresponding spectroscopic parameters for the ground states of 35 ClF-and 37 ClF-molecular ions were also deduced.Parallel computations were carried out for the neutral ClF-radical on the same level of theory.The results were in good agreement with available experimental data.The consistency between our results and previously reported experimentally determined values demonstrated the feasibility of the theoretical approach performed in this work.The optimized equilibrium geometric parameters were further used to derive the electron affinities of the neutral ClF-radical.The vertical detachment energy of ClF-was also determined.Based on computation results for ClF-,the vibrational levels and corresponding molecular constants for the X2Σ+ states of 35 ClF-and 37 ClF-molecular ions were obtained by solving the radical Schro dinger equation of the nuclear motion.

Activated N-doped carbon aerogel (N-ACA) is synthesized by the sol-gel polycondensation of resorcinol with formaldehyde using the melamine as nitrogen source, and then the carbon derivative being activated in CO2 flow. The surface morphology and porous structure are analyzed using scanning electron microscopy (SEM) and N2 adsorption at 77 K. The contained nitrogen of surface and monolith is tested by X-ray photoelectron spectroscopy (XPS) and elemental analysis. The electrochemical performances of N-dope carbon aerogels as electrodes are confirmed using constant-current charge-discharge test (GV), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). It reveals that the rich porous structure and the chemical state of nitrogen functionalities have crucial effect on the electrochemical performance of the electric double-layer capacitors. The appropriate CO2 activation can increase the number of micropores and mesopores as well as the specific surface area (4082 m2g-1).Furthermore, the presence of amount of pyrrolic nitrogen is reinforced in the electron donor capacity. The specific capacitance of N-ACA electrode is up to 211.9 Fg-1 and retains about 98% after 500 charge-discharge cycles.

Synuclein-γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG-8023).High-density tissue microarrays (TMAs) of tumor tissues from 313 patients with USC were stained by immunohistochemistry for SNCG, p53, p16, FOLR1, pERK, pAKT, ER, PR, and HER2/neu. Associations of SNCG and other tumor markers with overall and progression-free survival were assessed using log-rank tests and Cox proportional-hazards models, which also were adjusted for age, race, and stage.The overall survival at 5 years was 46% for women with high SNCG expression and 62% for those with low SNCG expression (log-rank P = .021; hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.91-1.9 in adjusted Cox model). The progression-free survival rate at 5 years was worse for women who had high SNCG expression, at 40%, compared with 56% for those who had low SNCG expression (log-rank P = .0081; HR, 1.36; 95% CI, 0.96-1.92 in adjusted Cox model). High levels of both p53 and p16 were significantly associated with worse overall survival (p53: HR, 4.20 [95% CI, 1.54-11.45]; p16: HR, 1.95 [95% CI, 1.01-3.75]) and progression-free survival (p53: HR, 2.16 [95% CI, 1.09-4.27]; p16: HR, 1.53 [95% CI, 0.87-2.69]) compared with low levels.This largest collection of USCs to date demonstrates that SNCG was associated with poor survival in univariate analyses. SNCG does not predict survival outcome independent of p53 and p16 in models that jointly consider multiple markers. Cancer 2017;123:1144-1155. © 2016 American Cancer Society.

Introduction: Many ovarian cancers likely originate in the fallopian tube and then colonize the ovary. An FTE origin for some HGSC is well established and there is increasing evidence that some endometrioid cancers may also originate in the FT. The loss of PTEN was found in 33% of STIC lesions. According to the TCGA, the PI3K/AKT pathway is altered in 45% of HGSC, and this could amplify downstream signaling similarly to the loss of PTEN, such as pAKT activation. PTEN mutations have also been found in about 20% of endometrioid ovarian carcinoma. Purpose of the Study: The signaling events involved in the onset of ovarian cancer from the fallopian tube epithelium (FTE) are crucial for early detection and treatment of the disease, but they remain poorly defined. Therefore, we aim to identify drivers of transformation and tumorigenesis from FTE. Experimental Procedures: We employed cells engineered with PTEN knocked down using shRNA and performed RNA-seq to identify the pathways involved in tumorigenesis. To uncover the mechanism underlying the invasion of cancerous fallopian tube cells to the ovary, PTEN-deficient cells were tagged with green fluorescent protein to study colonization of the ovary ex vivo. Finally, we generated a novel transgenic model of PAX8-driven loss of PTEN in the FTE to study early lesions in FT and ovarian cancer progression. Results: Conditional homozygous knockout of PTEN mediated by PAX8-cre recombinase was sufficient to drive endometrioid and serous borderline ovarian carcinoma, providing the first model of FTE-derived borderline tumors. In addition, heterozygous PTEN deletion in the FTE resulted in hyperplasia, providing a model to study early events of ovarian cancer pathogenesis. Loss of PTEN increased cell migration, invasion, and upregulated WNT4, a key regulator of Müllerian duct development during embryogenesis. An inhibitor of the WNT canonical and noncanonical pathways, LKG-974, as well as knockdown of WNT4 by siRNA, inhibited loss of PTEN-induced migration, whereas inhibitors of the canonical pathway alone (PRI724) did not. Further investigation revealed that WNT4 was required for increased migration and colonization of the ovary by PTEN-deficient oviductal cells in a β-catenin-independent manner. WNT4 was expressed in human ovarian cancer lines, especially in OVCAR8 and OVCAR4, and in several cancer histotypes, as revealed by the TMA analysis using IHC. LKG-974 also inhibited migration in the human ovarian cancer lines OVCAR4 and OVCAR8. Conclusions: Together, these findings provide a novel model to study the mechanism of fallopian tube tumor initiation and invasion to the ovary mediated by loss of PTEN, which may help to define early events of human ovarian carcinogenesis. Citation Format: Angela Russo, Austin Czarnecki, Matthew Dean, Wei Jian-Jun. PTEN loss in the fallopian tube induces hyperplasia and ovarian tumor formation. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B56.

Expression of SNCG mRNA in benign fallopian tube epithelium and ovarian cancer tissues. RNA from human benign fallopian tube epithelium and ovarian cancer tissues was subjected to RT-real time PCR for SNCG. SNCG as a ratio of the housekeeping gene TBP is presented using delta delta CT calculations. * = p

Hazard ratios (HR) from multivariate Cox regression models for PFS and OS involving SNCG expression and adjusting for relevant demographic and clinical factors. (DOCX 123Â kb)