BackgroundAn increasing body of evidence shows that miR-34 family has tumor suppressive properties mediating apoptosis, cell cycle arrest and senescence. In ovarian cancer, miR34 family members were found to be under expressed. Particularly miR-34a has been revealed to be a direct transcriptional target of p53 which is frequently mutated in epithelial ovarian carcinomas especially in high grade serous cancer. Moreover, methylation of miR-34a CpG Islands was found to down-regulate miR-34a expression. The aim of this study was to investigate the clinical relevance of mir34a as well as its promoter methylation in a subset of 133 ovarian cancers with a special focus on the p53 mutation status, the dualistic type I and type II ovarian cancer model and the different histotypes.MethodsOne hundred thirty-three epithelial ovarian cancers and 8 samples of healthy ovarian surface epithelium were retrospectively analysed for miR-34a expression with quantitative real-time reverse transcription PCR (qRT-PCR). Gene-specific DNA methylation was evaluated with MethyLight technique.ResultsSignificantly lower miR-34a expression was found in ovarian cancers than in healthy ovarian epithelium (p = 0.002). The expression of miR-34a was found lower in type II than in type I cancers (p = 0.037), in p53 mutated as compared to p53 wild type cancers (p = 0.003) and in high grade compared to in low grade cancers (p = 0.028). In multivariate COX regression model low expressing miR-34a cancers exhibited a reduced PFS (p = 0.039) and OS (p = 0.018). In serous cancers low miR-34a levels showed a worse OS confirmed also in multivariate analysis (p = 0.022). miR-34a promoter methylation was found higher in type II cancers than in type I (p = 0.006). mir34a expression and promoter methylation showed an inverse correlation in cancer samples (p = 0.05).ConclusionWe demonstrated a clinical independent role of miR-34a in epithelial ovarian cancers. Moreover, we corroborated the correlation between miR-34a expression and its promoter methylation in a large set of ovarian cancers. The inverse association between miR-34a expression and grading, p53 mutation status and dualistic tumor type classification, together with its prognostic relevance may underline the tumor-suppressive character of miR-34a in ovarian cancer.

We experimentally study the formation and stability of miscible fluid threads made of high-viscosity liquids using hydrodynamic focusing sections. Miscible core annular flows are useful for transporting viscous materials and can be destabilized for enhancing mass transfer. We delineate phase-diagrams of the generation of lubricated threads from low to large viscosity contrasts with various di↵usion coe cients. Depending on fluid properties and flow rates of injection, stable microflows are classified into engulfment, thread, and tubing regimes. For low Péclet numbers, we examine thread dynamics when di↵usive e↵ects strongly alter basic flow structures and induce new flow configurations, including ultra-di↵usive and di↵usive instability regimes. Another unstable flow arrangement is investigated for moderate Reynolds numbers where small threads are rapidly destabilized in the inertial flow field of the sheath fluid near the fluid junction. This study provides an overview of stable and unstable flow regimes and their transitions during the formation of miscible viscous fluid filaments in square microchannels.

The clinical outcome of completely cytoreduced patients was significantly better for PDS group than for IDS group, and therefore, the achievement of no gross RD after surgery seemed to have a different prognostic relevance for the 2 groups.