Studying primordial events in cancer is pivotal for identifying predictive molecular indicators and for targeted intervention. While the involvement of G-protein-coupled receptors (GPCRs) in cancer is growing, GPCR-based therapies are yet rare. Here, we demonstrate the overexpression of protease-activated receptor 2 (PAR2), a GPCR member in the fallopian tubes (FTs) of high-risk BRCA carriers as compared to null in healthy tissues of FT. FTs, the origin of ovarian cancer, are known to express genes of serous tubal intraepithelial carcinoma (STICs), a precursor lesion of high-grade serous carcinoma (HGSC). PAR2 expression in FTs may serve as an early prediction sensor for ovarian cancer. We show now that knocking down Par2 inhibits ovarian cancer peritoneal dissemination in vivo, pointing to the central role of PAR2. Previously we identified pleckstrin homology (PH) binding domains within PAR1,2&4 as critical sites for cancer-growth. These motifs associate with PH-signal proteins via launching a discrete signaling network in cancer. Subsequently, we selected a compound from a library of backbone cyclic peptides generated toward the PAR PH binding motif, namely the lead compound, Pc(4-4). Pc(4-4) binds to the PAR PH binding domain and blocks the association of PH-signal proteins, such as Akt or Etk/Bmx with PAR2. It attenuates PAR2 oncogenic activity. The potent inhibitory function of Pc(4-4) is demonstrated via inhibition of ovarian cancer peritoneal spread in mice. While the detection of PAR2 may serve as a predictor for ovarian cancer, the novel Pc(4-4) compound may serve as a powerful medicament in STICs and ovarian cancer. This is the first demonstration of the involvement of PAR PH binding motif signaling in ovarian cancer and Pc(4-4) as a potential therapy treatment.

Objective: Postpartum maternal readmission is a significant burden for patients as well as the health system. Postpartum readmission rate is a known factor in evaluating quality of care and in guiding potential beneficial interventions. Use of the Robson Group (RG) classification, initially used for analysis of cesarean section (CS) rates, has been recently expanded to evaluate other obstetrical outcomes. We aimed to describe the rates of postpartum maternal readmission across RG classification and to identify risk factors among the different maternity groups. Study Design: We carried out a retrospective register-based cohort study of all women who delivered >24 weeks gestation at a tertiary medical center over an 18-year period, with classification into the 10 RGs. Rates of postpartum readmission within 42 days of delivery were calculated for each group, as well as indications for readmission. The risk for maternal readmission was analyzed by univariate binary logistic regressions with comparison of results among RC groups, as well as by multivariate analysis models. Results: During the study period, 296,768 deliveries were classified according to Robson Group (RG) classification. The overall readmission rate for the study population was 0.5%. The following groups had a significant risk of readmission: RG 9 (transverse lie), 1.9%; RG 8 (multifetal pregnancies), 1.90=3%; RG 7 (multiparous breech pregnancies) 1.2% and RG2 (nulliparous pregnancies > 37 w, labor induction or prelabor cesarean), 1.2%. The most common indication for readmission among all RGs was fever (61.4%). Conclusions: Postpartum readmission rates varied among the RGs. The highest-risk groups were those with a higher risk of operative delivery, prolonged labor, or malpresentations. Interventions aimed to reduce the number of women in these groups; these included use of external cephalic version, vaginal delivery of breech, and multifetal pregnancies, all of which may be beneficial.