CRIPTO overexpression promotes mesenchymal differentiation in prostate carcinoma cells through parallel regulation of AKT and FGFR activities

Members of the EGF-CFC (Cripto, FRL-1, Cryptic) protein family are increasingly recognized as key mediators of cell movement and cell differentiation during vertebrate embryogenesis. The founding member of this protein family, CRIPTO, is overexpressed in various human carcinomas. Yet, the biological role of CRIPTO in this setting remains unclear. Here, we find CRIPTO expression as especially high in a subgroup of primary prostate carcinomas with poorer outcome, wherein resides cancer cell clones with mesenchymal traits. Experimental studies in PCa models showed that one notable function of CRIPTO expression in prostate carcinoma cells may be to augment PI3K/AKT and FGFR1 signaling, which promotes epithelial-mesenchymal transition and sustains a mesenchymal state. In the observed signaling events, FGFR1 appears to function parallel to AKT, and the two pathways act cooperatively to enhance migratory, invasive and transformation properties specifically in the CRIPTO overexpressing cells. Collectively, these findings suggest a novel molecular network, involving CRIPTO, AKT, and FGFR signaling, in favor of the emergence of mesenchymal-like cancer cells during the development of aggressive prostate tumors.     

A(H1N1) pandemic influenza and its prevention by vaccination: Paediatricians' opinions before and after the beginning of the vaccination campaign

Background  

In June 2009, the World Health Organization declared an A(H1N1) influenza pandemic. In October 2009, the largest vaccination campaign in Canadian history began. The aim of this study was to document paediatricians' knowledge, attitudes and practices (KAP) regarding A(H1N1) pandemic influenza and its prevention by vaccination just after the beginning of the A(H1N1) vaccination campaign and to compare the results with those obtained before campaign initiation.     

Postsynaptic injection of calcium-independent phospholipase A2 inhibitors selectively increases AMPA receptor-mediated synaptic transmission

The calcium-independent form of phospholipase A2 (iPLA2), an enzyme known to generate arachidonic acid (AA), was recently identified as the predominant constitutive phospholipase in the hippocampus. The present study shows that the iPLA2 inhibitor bromoenol lactone, when introduced into hippocampal CA1 pyramidal cells through a patch pipette, generated a dose-dependent increase in the amplitude of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs). The iPLA2 inhibitor by itself interfered with neither paired pulse facilitation nor N-methyl-D-aspartate (NMDA) receptor-mediated EPSCs, suggesting that its influence on synaptic transmission is postsynaptic in origin and specific to the AMPA subtype of glutamate receptors. Comparable results were obtained with palmitoyl trifluoromethyl ketone, a second structurally distinct iPLA2 inhibitor. The ability of iPLA2 inhibitors to increase AMPA receptor-mediated currents was also reproduced by MK-866, an inhibitor recognized to interfere with the generation of 5-lipoxygenase by-products of AA. At the biochemical level, we found that AMPA, but not NMDA glutamate receptor subunits, were upregulated in rat brain sections pre-incubated with the iPLA2 inhibitors. Collectively, these results provide the first experimental evidence that constitutive iPLA2 and/or its metabolites play an important role in the postsynaptic modulation of neurotransmission in CA1 pyramidal cells of the hippocampus.     

Posterior reversible encephalopathy induced by intravenous immunoglobulin.

Sir, Intravenous immunoglobulin (IvIg) is commonly used in nephrologyunits for the treatment of auto-immune diseases, antibody-mediatedrenal allograft rejection and immune deficiencies. Minor adverseeffects, such as myalgia, headache, shiver, nausea, vomitingor fever occur in <20% of patients. Major reactions includingrenal failure, thromboembolism, aseptic meningitis and anaphylaxisare less common. Whereas osmotic nephropathy resulting frommaltose and saccharose toxicity is well-known to nephrologists,posterior reversible encephalopathy syndrome (PRES) is a rareand potentially severe adverse event of IvIg therapy. A 42-year-old man was admitted     

Coping with recurrent breast cancer: predictors of distressing symptoms and health-related quality of life

Little is known about how postmenopausal women with recurrent breast cancer cope with distressing symptoms and which factors predict health-related quality of life (HRQOL). In the present study, 56 consecutively enrolled patients completed questionnaires measuring symptom occurrence, coping capacity, coping efforts, and HRQOL at the time of recurrence. Results from this study illustrate that women with recurrent breast cancer suffer from multiple, concurrent, and interrelated symptoms of illness, anxiety, depression, and fatigue. Highly prevalent symptoms are lack of energy, difficulty sleeping, pain, worrying, problems with sexual interest, feeling sad, and dry mouth. The most frequently occurring symptom is problem with sexual interest, and the most severe symptom is worrying. The most distressing symptom experienced is pain. The majority of the women report 10-23 symptoms. Women who experience multiple symptoms also report higher levels of symptom distress. The experience of distressing symptoms is predicted by coping capacity, and the coping efforts experienced predict HRQOL. Patients with lower coping capacity report higher prevalence of symptoms, experience higher levels of distress, and experience worse perceived health, which in turn may decrease their HRQOL. To help women manage recurrent breast cancer, it is important to use multidimensional measurement to identify, evaluate, and treat distressing symptoms, and not assess single symptoms only. Care must be based upon the awareness of critical factors that exacerbate vulnerability to distress, as well as the ability to adapt to a recurrent breast cancer disease.