Effect of Adenomatous Polyposis Coli Loss on Tumorigenic Potential in Pancreatic Ductal Adenocarcinoma

Loss of the Adenomatous Polyposis Coli (APC) tumor suppressor in colorectal cancer elicits rapid signaling through the Wnt/β-catenin signaling pathway. In contrast to this well-established role of APC, recent studies from our laboratory demonstrated that APC functions through Wnt-independent pathways to mediate in vitro and in vivo models of breast tumorigenesis. Pancreatic ductal adenocarcinoma (PDAC) has an overall median survival of less than one year with a 5-year survival rate of 7.2%. APC is lost in a subset of pancreatic cancers, but the impact on Wnt signaling or tumor development is unclear. Given the lack of effective treatment strategies for pancreatic cancer, it is important to understand the functional implications of APC loss in pancreatic cancer cell lines. Therefore, the goal of this project is to study how APC loss affects Wnt pathway activation and in vitro tumor phenotypes. Using lentiviral shRNA, we successfully knocked down APC expression in six pancreatic cancer cell lines (AsPC-1, BxPC3, L3.6pl, HPAF-II, Hs 766T, MIA PaCa-2). No changes were observed in localization of β-catenin or reporter assays to assess β-catenin/TCF interaction. Despite this lack of Wnt/β-catenin pathway activation, the majority of APC knockdown cell lines exhibit an increase in cell proliferation. Cell migration assays showed that the BxPC-3 and L3.6pl cells were impacted by APC knockdown, showing faster wound healing in scratch wound assays. Interestingly, APC knockdown had no effect on gemcitabine treatment, which is the standard care for pancreatic cancer. It is important to understand the functional implications of APC loss in pancreatic cancer cells lines, which could be used as a target for therapeutics

DAMA/NaI results

The DAMA/NaI set-up of the DAMA experiment has been operative during seven annual cycles and has investigated several rare processes. In particular, it has been realised in order to investigate the model independent annual modulation signature for Dark Matter particles in the galactic halo. With the total exposure collected in the seven annual cycles (107731 kg day) a model independent evidence for the presence of a Dark Matter particle component in the galactic halo has been pointed out at 6.3 sigma C.L.. Some of the many possible corollary model dependent quests for the candidate particle have been presented as well.Comment: Contributed paper to the Rencontres de Moriond "Electroweak Interactions and Unified Theories", La Thuile, Aosta Valley, Italy, March 200

Evaluación de la participación de las comunidades de Tortí e Higueronal en la construcción del acueducto rural.

Objetivos Este trabajo pretende contribuir a la definición y precisión de los conceptos, y proveer la información necesaria sobre la participación de la comunidad en los programas de salud, específicamente en aquellos destinados a la dotación de agua potable, mediante el análisis del estudio de familias, proporcionar conocimientos en tres áreas básicas: La índole y la magnitud de la participación de la comunidad en el campo de la salud. La razón por la cual existe o falta la participación de la comunidad. El modo en que la participación de la comunidad ha ayudado a mejorar los servicios, la cobertura y las condiciones de salud. Por otro lado, pretendemos en el presente estudio, señalar dos diferentes grados de participación por parte de nuestras gentes, a saber: La utilización de los servicios e instalaciones de salud, como requisito previo, casi indispensable para que se dé una verdadera participación. La cooperación con las iniciativas planificadas por un organismo externo, lo cual incluye el aporte de trabajo, fondos y materiales, junto a la ayuda para llevar a cabo proyectos y actividades

β-Catenin is required for the tumorigenic behavior of triple-negative breast cancer cells

Our previous data illustrated that activation of the canonical Wnt signaling pathway was enriched in triple-negative breast cancer and associated with reduced overall survival in all patients. To determine whether Wnt signaling may be a promising therapeutic target for triple-negative breast cancer, we investigated whether β-catenin was necessary for tumorigenic behaviors in vivo and in vitro. β-catenin expression level was significantly reduced in two human triple-negative breast cancer cell lines, MDA-MB-231 and HCC38, using lentiviral delivery of β-catenin-specific small hairpin RNAs (shRNAs). Upon implantation of the cells in the mammary fat pad of immunocompromised mice, we found that β-catenin shRNA HCC38 cells formed markedly smaller tumors than control cells and grew much more slowly. In in vitro assays, β-catenin silencing significantly reduced the percentage of Aldefluor-positive cells, a read-out of the stem-like cell population, as well as the expression of stem cell-related target genes including Bmi-1 and c-Myc. β-catenin-knockdown cells were also significantly impaired in their ability to migrate in wound-filling assays and form anchorage-independent colonies in soft agar. β-catenin-knockdown cells were more sensitive to chemotherapeutic agents doxorubicin and cisplatin. Collectively, these data suggest that β-catenin is required for triple-negative breast cancer development by controlling numerous tumor-associated properties, such as migration, stemness, anchorage-independent growth and chemosensitivity