Prognostic Significance of Wnt-1, β-catenin and E-cadherin Expression in Advanced Colorectal Carcinoma

Wnt/β-catenin pathway plays an important role in initiation and progression of colorectal oncogenesis. The aim of this study was to determine expression and localization of E-cadherin, β-catenin and Wnt-1 proteins in colorectal tumors. Expression of β-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on advanced colorectal cancers. Abnormal expression of E-cadherin, β-catenin, Wnt-1 was observed. Additionally, we revealed correlations between levels of studied proteins and histoclinical data. In multivariate analysis nuclear β-catenin, higher carcinoembryonic antigen serum level before treatment, female sex and tumor localized in colon or rectum were independent unfavorable prognostic factors. These findings support the hypothesis that Wnt/β-catenin pathway plays an important role in advanced colorectal carcinoma

Solvent effects on Raman Optical Activity spectra calculated using the Polarizable Continuum Model

The integral equation formulation of the polarizable continuum model (IEFPCM) has been extended to the calculation of solvent effects on vibrational Raman optical activity spectra. Gauge-origin independence of the differential scattering intensities of right and left circularly polarized light is ensured through the use of London atomic orbitals. Density functional theory (DFT) calculations have been carried out for bromochlorofluoromethane, methyloxirane, and epichlorhydrin. The results indicate that solvent effects on the ROA differential scattering intensities can be substantial, and vary in sign and magnitude for different vibrational modes. It is demonstrated that both direct and indirect effects are important in determining the total solvent effects on the ROA differential scattering intensities. Local field effects are shown to be in general small, whereas electronic nonequilibrium solvation has a profound effect on the calculated solvent effects compared to an equilibrium solvation model. For molecules with several conformations, the changes in the relative stability of the different conformers also lead to noticeable changes in the ROA spectra

Lysosomal membrane permeabilization in cell death

18 páginas, 3 figuras, 2 tablas -- PAGS nros. 6434-6451Mitochondrial outer membrane permeabilization (MOMP) constitutes one of the major checkpoint(s) of apoptotic and necrotic cell death. Recently, the permeabilization of yet another organelle, the lysosome, has been shown to initiate a cell death pathway, in specific circumstances. Lysosomal membrane permeabilization (LMP) causes the release of cathepsins and other hydrolases from the lysosomal lumen to the cytosol. LMP is induced by a plethora of distinct stimuli including reactive oxygen species, lysosomotropic compounds with detergent activity, as well as some endogenous cell death effectors such as Bax. LMP is a potentially lethal event because the ectopic presence of lysosomal proteases in the cytosol causes digestion of vital proteins and the activation of additional hydrolases including caspases. This latter process is usually mediated indirectly, through a cascade in which LMP causes the proteolytic activation of Bid (which is cleaved by the two lysosomal cathepsins B and D), which then induces MOMP, resulting in cytochrome c release and apoptosome-dependent caspase activation. However, massive LMP often results in cell death without caspase activation; this cell death may adopt a subapoptotic or necrotic appearance. The regulation of LMP is perturbed in cancer cells, suggesting that specific strategies for LMP induction might lead to novel therapeutic avenuesResearch in our labs is supported by grants from Ministry of Science (BFU-2006-00508) and from Fundación La Caixa (BM06-125-1) to PB and Ligue Nationale contre le Cancer (Equipe labellisée), European Commission (Active p53, Apo-Sys, RIGHT, TransDeath, ChemoRes, DeathTrain), Agence Nationale pour la Recherche, Institut National contre le Cancer, Cancéropôle Ile-de-France and Fondation pour la Recherche Médicale to GKPeer reviewe