Prediction of dystocia-related cesarean section risk in uncomplicated Taiwanese nulliparas at term.

PURPOSE: We aimed to assess risk factors for dystocia-related cesarean section (CS) in uncomplicated Taiwanese nulliparas at term METHODS: We reviewed 1,272 deliveries by 1 obstetrician in a Taiwanese hospital between February 2004 and December 2011. These parturients were nulliparas with singleton pregnancies ≥ 37 weeks gestation who had liveborn cephalic deliveries. The CS group consisted of parturients with dystocia-related CS for the following indications: prolonged latent phase, failure to progress, or arrest of descent. Eight confounding variables [maternal age, height, weight, body mass index (BMI) in labor, gestational age, infant birth weight, gender, and cervical dilatation] were obtained from the medical records. Multivariate logistic regression analysis was used to determine the association between each variable and route of delivery. A predictive formula for CS probability was generated using a logistic regression model. RESULTS: Overall 15.0 % of nulliparas in our population underwent CS. Logistic regression analysis revealed a significant association between maternal BMI and CS (adjusted OR 1.112; 95 % CI 1.065-1.161; P < 0.001). The association between maternal age and CS was also statistically significant (adjusted OR 1.074, 95 % CI 1.033-1.116, P = 0.001). Maternal height, weight in labor, gestational age, infant birth weight, gender, and cervical dilatation were not significantly associated with the route of delivery. A predictive formula for CS probability was developed based on a combination of maternal BMI and age. CONCLUSIONS: Our results show that maternal age and BMI in labor are significantly associated with dystocia-related CS in uncomplicated Taiwanese nulliparas at term. We develop a practical formula to predict the probability for CS. Using this formula, obstetricians can estimate the risk of CS according to maternal age and BMI in labor.

Tumor-induced endothelial cell apoptosis: roles of NAD(P)H oxidase-derived reactive oxygen species.

Many tumor cells are capable of migrating through endothelial cell (EC) junctions and disintegrating sub-endothelial extracellular matrix to achieve extravasation. We demonstrate in this study that certain solid tumor cells can induce EC apoptosis to facilitate their escape from the circulation. The EC apoptosis is triggered by elevated intracellular reactive oxygen species (ROS) levels and direct contacts with tumor cells are required. Treating ECs with antioxidants, such as ascorbate and N-acetyl-L-cysteine (NAC), and a glutathione precursor can rescue the ECs from tumor-induced apoptosis and reduce the number of tumor cells migrating across endothelial barriers. NAD(P)H oxidase was identified as the major ROS producer in the event since inhibitors and small interference RNA specific to the enzyme could abrogate the tumor-induced ROS production and hence EC death. This study also provides evidence showing that the interaction between tumor and EC increases intracellular Ca(2+) concentration and activates protein kinase C (PKC) activity, which leads to NAD(P)H oxidase activation through the serine-phosphorylation of p47(phox) subunit. These findings suggest that blocking the tumor-induced EC apoptosis is a potential way to prevent tumor metastasis.

Dynamic analysis of hepatoma spheroid formation: roles of E-cadherin and beta1-integrin.

A spheroid is an in vitro multicellular aggregate that provides a microenvironment resembling that of normal tissue in vivo. Although cell adhesion molecules such as integrins and cadherins have been implicated in participating in the process of spheroid formation, little is known about the timing of their action. In this study, we have employed an image-based quantitative method to investigate the compactness of cell aggregates during hepatoma spheroid formation in a dynamic fashion. By modulating beta1-integrin and E-cadherin activity with specific blocking antibodies, ion chelators, and RGD-sequence-containing peptides, we show that these cell adhesion molecules mediate the formation of spheroids through the establishment of complex cell-cell and cell-extracellular matrix (ECM) interactions. The dynamics of spheroid formation can be separated into three stages. In the first stage, ECM fibers act as a long-chain linker for the attachment of dispersed single-cells to form loose aggregations through the binding of integrins. This is followed by a delay period in which cell aggregates pause in compaction, presumably because of the accumulation of sufficient amounts of E-cadherins. In the third stage, strong homophilic interaction of E-cadherins is a major factor for the morphological transition from loose cell aggregates to compact spheroids. These findings thus provide comprehensive information on the molecular mechanisms and dynamics of hepatoma spheroid formation.