The contribution of dementia to the disablement process and modifying factors

The objective of this study was to examine the impact of dementia on disability progression and mortality, and to analyze the modifying effect of risk factors and extra-individual factors. A sample of 3,403 participants in the PAQUID study was followed for 10 years. Disability was assessed on a 4-grade scale: no disability, disabled only on the Rosow-Breslau scale, disabled on the Rosow-Breslau scale and on instrumental activities of daily living (IADL) scales, and disabled on the Rosow-Breslau, IADL and activities of daily living (ADL) scales. A Markov model was used to estimate the effect of explanatory variables on disability and mortality. Controlling for age, gender, education, place of residence, medical care and informal support, dementia had a strong significant effect on progression to IADL and then to ADL disability. Dementia did not increase the risk of death, once disability was taken into account, except from the lowest disability grade.     

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.