Search

El motivo de mi trabajo está dirigido a buscar nuevas combinaciones de fármacos o sinergismos, que ayuden al tratamiento de las principales especies bacterianas implicadas en las infecciones pulmonares que padecen los pacientes con fibrosis quística. Entre estas especies bacterianas, que posteriormente especificaremos de forma detallada, se observa una tendencia hacia la formación biopelículas relacionadas con fenómenos de multiresistencia hacia los antibióticos clásicos empleados en el tratamiento de esta patología, lo cual dificulta enormemente la consecución del objetivo terapéutico deseado. Para ello hemos recurrido al empleo de los antibióticos “clásicos” destinados al tratamiento de estas especies bacterianas en los pacientes con fibrosis quística, junto con una serie de componentes que han sido extraídos de una librería de más de 700 moléculas proporcionadas por el NIHCC a la UGent.

Resumen tomado de la publicación El proyecto de acción tutorial se ha llevado a cabo en los cinco cursos de la titulación con un doble enfoque. Por una parte se han organizado grupos de tutoría de unos cinco alumnos en los que se han realizado actividades orientadas a mejorar el rendimiento académico, apoyo en la toma de decisiones, mejora del conocimiento que los alumnos tienen sobre la Universidad y los servicios y actividades que pueden realizar. Por otra parte, se han organizado actividades por cursos o varios cursos, para informar sobre temas generales de su interés, facilitar la realización de prácticas y apoyar a los alumnos de último curso en la incorporación al mercado laboral. Navarra Universidad Pública de Navarra. Biblioteca Universitaria; Campus de Arrosadia; 31006 Pamplona; Tel. +34948169060; Fax +34948169069; bupna@enavarra.es ESP

Simple Summary: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. Serrated adenocarcinoma (SAC) has been recently recognized by the WHO as a histological CRC with bad prognosis. Consistent with previous evidence, our group identified Fascin1 as a protein directly related to the invasiveness of tumor cells, overexpressed and positively correlated with worse survival in various carcinomas, including SAC. Therefore, Fascin1 has emerged as an ideal target for cancer treatment. In the present study, virtual screening has been carried out from a library of 9591 compounds, thus identifying the FDA-approved anti-retroviral raltegravir (RAL) as a potential Fascin1 blocker. In vitro and in vivo results show that RAL exhibits Fascin1-binding activity and Fascin1-dependent anti-invasive and anti-metastatic properties against CRC cells both in vitro and in vivo. Abstract: Background: Fascin1 is the key actin-bundling protein involved in cancer invasion and metastasis whose expression is associated with bad prognosis in tumor from different origins. Methods: In the present study, virtual screening (VS) was performed for the search of Fascin1 inhibitors and RAL, an FDA-approved inhibitor of human immunodeficiency virus-1 (HIV-1) integrase, was identified as a potential Fascin1 inhibitor. Biophysical techniques including nuclear magnetic resonance (NMR) and differential scanning fluorimetry (DSF) were carried out in order to confirm RAL as a Fascin1 blocker. The effect of RAL on actin-bundling activity Fascin1 was assessed by transmission electron microscopy (TEM), immunofluorescence, migration, and invasion assays on two human colorectal adenocarcinoma cell lines: HCT-116 and DLD-1. In addition, the anti-metastatic potential of RAL was in vivo evaluated by using the zebrafish animal model. Results: NMR and DSF confirmed in silico predictions and TEM demonstrated the RAL-induced disorganization of the actin structure compared to control conditions. The protrusion of lamellipodia in cancer cell line overexpressing Fascin1 (HCT-116) was abolished in the presence of this drug. By following the addition of RAL, migration of HCT-116 and DLD-1 cell lines was significantly inhibited. Finally, using endogenous and exogenous models of Fascin1 expression, the invasive capacity of colorectal tumor cells was notably impaired in the presence of RAL in vivo assays; without undesirable cytotoxic effects. Conclusion: The current data show the in vitro and in vivo efficacy of the antiretroviral drug RAL in inhibiting human colorectal cancer cells invasion and metastasis in a Fascin1-dependent manner., Instituto de Salud Carlos III Spanish Government, European Commission PI15/00626 PI18/00144, European Commission's Corbel Program PID-3630 2334 2428, Spanish Ministry of Economy and Competitiveness MINECO CTQ2017-87974-R, Fundación Seneca 20988/PI/18 20646/JLI/18, UCAM FPI05-UCAM/17, Junta Provincial Murcia Predoctoral Asociación Española contra el Cáncer (AECC) PRDMU19002