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BackgroundWomen with platinum-resistant ovarian cancer are a heterogeneous group whose median overall survival is 12 months. We hypothesized that their quality of life (QoL) scores would be prognostic.Patients and methodsData from AURELIA (n = 326), a randomized trial of chemotherapy with or without bevacizumab, were used to identify baseline QoL domains [EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 and OV28] that were significantly associated with overall survival in multivariable Cox regression analyses. Patients were classified as having good, medium, or poor risk. Cutpoints were validated in an independent dataset, CARTAXHY (n = 136). Multivariable analyses of significant QoL domains on survival were adjusted for clinicopathological prognostic factors. The additional QoL information was assessed using C statistic.ResultsIn AURELIA, all domains, except cognitive function, predicted overall survival in univariable analyses. Physical function (P 93) risk categories for physical function, median overall survival was 11.0, 14.7, and 19.3 months, respectively (P 44), medium- (13-44), and low- (

Bluetongue virus (BTV) is the cause of an economically important arboviral disease of domestic and wild ruminants. The occurrence of BTV infection of livestock is distinctly seasonal in temperate regions of the world, thus we determined the dynamics of BTV infection (using BTV-specific real time reverse transcriptase polymerase chain reaction) among sentinel cattle and vector Culicoides sonorensis (C. sonorensis) midges on a dairy farm in northern California throughout both the seasonal and interseasonal (overwintering) periods of BTV activity from August 2012 until March 2014. The data confirmed widespread infection of both sentinel cattle and vector midges during the August-November period of seasonal BTV transmission, however BTV infection of parous female midges captured in traps set during daylight hours also was detected in February of both 2013 and 2014, during the interseasonal period. The finding of BTV-infected vector midges during mid-winter suggests that BTV may overwinter in northern California by infection of long-lived female C. sonorensis midges that were infected during the prior seasonal period of virus transmission, and reemerged sporadically during the overwintering period; however the data do not definitively preclude other potential mechanisms of BTV overwintering that are also discussed.

Phosphorylase is regulated by a number of small-molecular-weight effectors that bind to three sites on the enzyme. Recently, a fourth site referred to as the indole-inhibitor site has been identified. Synthetic compounds bind to the site and inhibit activity. However, the effects of these compounds in the presence of other endogenous effectors are unknown. We have determined the effects of four indole derivative glycogen phosphorylase inhibitors (GPI) on recombinant human liver glycogen phosphorylase a activity. The GPIs tested were all potent inhibitors. However, the endogenous inhibitors (glucose, ADP, ATP, fructose 1-phosphate, glucose 6-phosphate, UDP-glucose) and the activator (AMP) markedly reduced the inhibitory effect of GPIs. Consistent with these in vitro findings, the I[C.sub.50] for the inhibition of glycogenolysis in cells and the liver drug concentration associated with glucose-lowering activity in diabetic ob/ob mice in vivo were also significantly higher than those determined in in vitro enzyme assays. The inhibitory effect of indole-site effectors is modulated by endogenous small-molecularweight effectors of phosphorylase a activity. However, at higher concentrations (10-30 [micro]M), the GPI effect was dominant and resulted in inhibition of phosphorylase a activity irrespective of the presence or absence of the other modulators of the enzyme. glucose

Facilitative glucose transporters exhibit variable hexose affinity and tissue-specific expression. These characteristics contribute to specialized metabolic properties of cells. Here we describe the characterization of a novel glucose transporter-like molecule, GLUT-12. GLUT-12 was identified in MCF-7 breast cancer cells by homology to the insulin-regulatable glucose transporter GLUT-4. The GLUT-12 cDNA encodes 617 amino acids, which possess features essential for sugar transport. Di-leucine motifs are present in [NH.sup.2] and COOH termini at positions similar to the GLUT-4 FQQI and LL targeting motifs. GLUT-12 exhibits 29% amino acid identity with GLUT-4 and 40% to the recently described GLUT-10. Like GLUT-10, a large extracellular domain is predicted between transmembrane domains 9 and 10. Genomic organization of GLUT-12 is highly conserved with GLUT-10 but distinct from GLUTs 1-5. Immunofluorescence showed that, in the absence of insulin, GLUT-12 is localized to the perinuclear region in MCF-7 cells. Immunoblotting demonstrated GLUT-12 expression in skeletal muscle, adipose tissue, and small intestine. Thus GLUT-12 is potentially part of a second insulin-responsive glucose transport system. facilitative glucose transporter; insulin-responsive tissues; breast cancer

Genetically diabetic (db/db) mice were analyzed to determine the effects of diabetes on cerebral glucose utilization (CGU), cerebral glucose homeostasis and GLUT-1 or GLUT-3 expression. The genetically diabetic db/db mice exhibited reduced cerebral metabolism, CGU and altered brain growth. Diabetes also increased the expression of GLUT-1 and reduced GLUT-3 expression. Furthermore, altered brain metabolism in diabetic mice indicated the insulin sensitivity of normal brain growth.

The intense activity of phosphatidylinositol 3'-kinase (PtdIns 3'-kinase) results from the association of two phosphorylated tyrosines carrying YMXM sequences on insulin receptor substrate 1 with two carboxy SH2 domains of PtdIns 3'-kinase. Phosphotyrosine peptides carrying phosphorylated tyrosine YZPZ motifs in 3T3-L1 adipocytes exhibit enormous affinity for binding SH2 domains of PtdIns-3'kinase compared to those containing singular YZPZ sequence.