Changes in Gene Expression and Cellular Architecture in an Ovarian Cancer Progression Model

BACKGROUND: Ovarian cancer is the fifth leading cause of cancer deaths among women. Early stage disease often remains undetected due the lack of symptoms and reliable biomarkers. The identification of early genetic changes could provide insights into novel signaling pathways that may be exploited for early detection and treatment. METHODOLOGY/PRINCIPAL FINDINGS: Mouse ovarian surface epithelial (MOSE) cells were used to identify stage-dependent changes in gene expression levels and signal transduction pathways by mouse whole genome microarray analyses and gene ontology. These cells have undergone spontaneous transformation in cell culture and transitioned from non-tumorigenic to intermediate and aggressive, malignant phenotypes. Significantly changed genes were overrepresented in a number of pathways, most notably the cytoskeleton functional category. Concurrent with gene expression changes, the cytoskeletal architecture became progressively disorganized, resulting in aberrant expression or subcellular distribution of key cytoskeletal regulatory proteins (focal adhesion kinase, α-actinin, and vinculin). The cytoskeletal disorganization was accompanied by altered patterns of serine and tyrosine phosphorylation as well as changed expression and subcellular localization of integral signaling intermediates APC and PKCβII. CONCLUSIONS/SIGNIFICANCE: Our studies have identified genes that are aberrantly expressed during MOSE cell neoplastic progression. We show that early stage dysregulation of actin microfilaments is followed by progressive disorganization of microtubules and intermediate filaments at later stages. These stage-specific, step-wise changes provide further insights into the time and spatial sequence of events that lead to the fully transformed state since these changes are also observed in aggressive human ovarian cancer cell lines independent of their histological type. Moreover, our studies support a link between aberrant cytoskeleton organization and regulation of important downstream signaling events that may be involved in cancer progression. Thus, our MOSE-derived cell model represents a unique model for in depth mechanistic studies of ovarian cancer progression

Can we improve outcome of congenital diaphragmatic hernia?

This review gives an overview of the disease spectrum of congenital diaphragmatic hernia (CDH). Etiological factors, prenatal predictors of survival, new treatment strategies and long-term morbidity are described. Early recognition of problems and improvement of treatment strategies in CDH patients may increase survival and prevent secondary morbidity. Multidisciplinary healthcare is necessary to improve healthcare for CDH patients. Absence of international therapy guidelines, lack of evidence of many therapeutic modalities and the relative low number of CDH patients calls for cooperation between centers with an expertise in the treatment of CDH patients. The international CDH Euro-Consortium is an example of such a collaborative network, which enhances exchange of knowledge, future research and development of treatment protocols

Perturbation and numerical study of double-diffusive dissipative reactive convective flow in an open vertical duct containing a non-darcy porous medium with robin boundary conditions

A mathematical model for thermosolutal convection flow in an open two-dimensional vertical channel containing a porous medium saturated with reactive Newtonian fluid is developed and studied. Robin boundary conditions are prescribed, and a first-order homogenous chemical reaction is considered. The Darcy–Forchheimer model is used to simulate both the first- and second-order porous mediums’ drag effects. For the general non-Darcy-case, a numerical solution is presented using the Runge–Kutta quadrature and a shooting method. The influences of thermal (0≤λ1≤15) and solute Grashof numbers (0≤λ2≤20) , Biot numbers (1≤Bi1≤10,Bi2=10) , Brinkman number (0≤Br≤0.5) , first-order chemical reaction parameter (2≤α≤8) , porous medium parameter (2≤σ≤8) and Forchheimer (inertial drag) parameter (0≤I≤12) on the evolutions of velocity, temperature and concentration (species) distributions are visualized graphically. Nusselt number and skin friction at the walls are also computed for specific values of selected parameters. The study is relevant to the analysis of geothermal energy systems with chemical reaction