Bcl-2 family proteins and cytoskeleton changes involved in DM-1 cytotoxic effect on melanoma cells

Melanoma is one of the most aggressive types of skin cancer and its incidence rate is still increasing. All existing treatments are minimally effective. Consequently, new therapeutic agents for melanoma treatment should be developed. The DM-1 compound is a curcumin analog that possesses several curcumin characteristics, such as antiproliferative, antitumor, and anti-metastatic properties. The aim of this study was to evaluate the different signaling pathways involved in the cytotoxic effect of DM-1 on melanoma cells. The apoptotic process and cytoskeletal changes were evaluated by immunoblotting and immunofluorescence, respectively, in melanoma cells. After DM-1 treatment, SK-MEL-5 melanoma cells showed actin filament disorganization with spicule formation throughout the cytoskeleton and significant reduction of focal adhesion as well as they were present only at cell extremities, conferring a poor connection between the cell and the substrate. Besides this, there was significant filopodium retraction and loss of typical cytoskeleton scaffold. These modifications contributed to cell detachment followed by cell death. Furthermore, DM-1-induced apoptosis was triggered by multiple Bcl-2 proteins involved in both the extrinsic and the intrinsic apoptotic pathways. SK-MEL-5 cells showed a death mechanism mainly by Bcl-2/Bax ratio decrease, whereas A375 cells presented apoptosis induction by Mcl-1 and Bcl-xL downregulation. In SK-MEL-5 and A375 melanoma cells, there was a significant increase in the active form of caspase 9, and the inactive form of the effector caspase 3 was decreased in both cell lines. Expression of cleaved poly ADP ribose polymerase was increased after DM-1 treatment in these melanoma cell lines, demonstrating that the apoptotic process occurred. Altogether, these data elucidate the cellular and molecular mechanisms involved in the cytotoxicity induced by the antitumor agent DM-1 in melanoma cells.

Status convulsivo

1. CONCEPTO Sindrome comicial prolongado (duración superior a los 30 minutos) o recidivante sin lograr recuperar la conciencia en los intervalos. Cualquier tipo de comicialidad tanto generalizada como focal puede cursar en forma de status, aunque lo más frecuente son las crisis tónico-clónicas generalizadas...

On the physical realizability of highly focused electromagnetic field distributions

A method to evaluate the physical realizability of an arbitrary three-dimensional vectorial field distribution in the focal area is proposed. A parameter that measures the similarity between the designed (target) field and the physically achievable beam is provided. This analysis is carried out within the framework of the closest electromagnetic field to a given vectorial function, and the procedure is applied to two illustrative cases.

Experimental implementation of tightly focused beams with unpolarized transversal component at any plane

The aim of this paper is to provide a formal framework for designing highly focused fields with specific transversal features when the incoming beam is partially polarized. More specifically, we develop a field with a transversal component that remains unpolarized in the focal area. Moreover, its longitudinal component exhibits non-zero values on axis. Special attention is paid to the design of the input beam and the development of the experiment. The implementation of such fields is possible by using an interferometric setup combined with the use of digital holography techniques. Experimental results are compared with those obtained numerically.

Marcas territoriales y desarrollo local en la Cataluña interior. Estudio de caso: Territoris serens (el Lluçanès)

La denominada «reestructuración rural» pasa ineludiblemente por la transformación de la economía de sector primario que tradicionalmente ha sustentado al campo. En los últimos tiempos, se experimenta una clara tercerización de la economía rural, en muy buena medida capitalizada por la industria turística. En este sentido, surge la necesidad de repensar la ruralidad, de construirla socialmente a partir de la proyección de imaginarios comunicados interna y externamente mediante la ayuda de marcas territoriales. El presente trabajo tiene como objetivo prioritario explorar de qué forma la marca espacial Territoris serens permite la creación de una imagen competitiva para la agrupación territorial del Lluçanès, por medio de la difusión de relatos asociados a diversos valores intangibles encabezados por la serenidad, el paisaje y, por ende, la identidad territorial. La revisión de la literatura referida a marcas de territorio, el análisis de la producción documental vinculada a Territoris serens y la organización de un grupo focal de discusión permitirá dirimir el proceso de transformación de territorios en marcas, en aras de conseguir, en nombre de la competitividad, un renovado y posmoderno «sentido de lugar».

Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of a2b1 Integrin and E-Cadherin Function

In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLex) along with a concomitant decrease in α2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, α2β1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLex and lower α2,6-sialic acid content on the glycans of their α2β1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLex and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion