Identification of oxidative stress related proteins as biomarkers for lung cancer and chronic obstructive pulmonary disease in bronchoalveolar lavage

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis. © 2013 by the authors; licensee MDPI, Basel, Switzerland.LPA is funded by Fondo de Investigación Sanitaria (PI081156) and Fondo de Investigación Sanitaria (PI1102688). MDP is funded by Fondo de Investigación Sanitaria (CD 09/00148). AN is funded by the Portuguese Ministry of Science, Technology and Superior Education—FCT (Fundação para a Ciência e para a Tecnologia: SFRH/BD/48341/2008). SMP is funded by Fondo de Investigación Sanitaria (CD 11/00153).Peer Reviewe

Identification of proteomic signatures associated with lung cancer and COPD

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. The aim of this study was to identify distinct proteomic profiles able to discriminate these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC without COPD, and control with neither COPD nor LC. Proteins were separated into spots by bidimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 40 proteins were differentially expressed in the LC and/or COPD groups as compared with the control group. Distinct protein profiles were identified and validated for each pathological entity (LC and COPD). The main networks involved were related to inflammatory signalling, free radical scavenging and oxidative stress response, and glycolysis and gluconeogenesis pathways. The most relevant signalling link between LC and COPD was through the NF-κB pathway.In conclusion, the protein profiles identified contribute to elucidate the underlying pathogenic pathways of both diseases, and provide new tools of potential use as biomarkers for the early diagnosis of LC. Biological significance: Sequence coverage. The protein sequence coverage (95%) was estimated for specific proteins by the percentage of matching amino acids from the identified peptides having confidence greater than or equal to 95% divided by the total number of amino acids in the sequence.Ingenuity Pathways Analysis. Mapping of our proteins onto biological pathways and disease networks demonstrated that 22 proteins were linked to inflammatory signalling (p-value: 1.35*10-08-1.42*10-02), 15 proteins were associated with free radical scavenging and oxidative stress response (p-value: 4.93*10-11-1.27*10-02), and 9 proteins were related with glycolysis and gluconeogenesis pathways (p-value: 7.39*10-09-1.58*10-02). © 2013 Elsevier B.V.The present study was partially financed by the Fondo de Investigación Sanitaria (PI081156, PI1102688). MDP is funded by the Fondo de Investigación Sanitaria (CD 09/00148). AN is funded by the Portuguese Ministry of Science, Technology and Superior Education — FCT (Fundação para a Ciência e para a Tecnologia: SFRH/BD/48341/2008). SMP is funded by the Fondo de Investigación Sanitaria (CD 11/00153).Peer Reviewe

Papel de la proteína de adhesión sináptica neurexina 1 en autismo

1 página. IX Jornadas Andaluzas Salud Investiga. Cádiz 20-22 octubre, 2010.El Trastorno del Espectro Autista (TEA) es un conjunto de síndromes del desarrollo que se caracterizan por déficit en la interacción social, comunicación restringida y comportamientos estereotipados. Hasta un 70% de los casos están asociados a retraso mental. La mayor parte de los casos de TEA se enmarcan dentro de las enfermedades complejas, causadas por la combinación de alelos de susceptibilidad y factores ambientales. Se han identificado mutaciones y variaciones estructurales en genes que codifican proteínas sinápticas, como las neurexinas, que podrían incrementar el riesgo a desarrollar la enfermedad. Los objetivos de nuestro estudio son entender el mecanismo de acción de neurexina-1 beta (NRXN1β) en el desarrollo del TEA.Peer reviewe

MicroRNAs as potential predictors of extreme response to tyrosine kinase inhibitors in renal cell cancer

Background: MicroRNAs play an important role as modulators of gene expression in several biological processes and are closely related to development and cell differentiation regulation. Previous works have revealed a potential predictive role for miRNAs in different tumor types. This study aims to analyze the ability of miRNAs in segregating metastatic renal cell carcinoma patients according to their responses to tyrosine kinase inhibitors (TKIs). Methods: Extreme responders were considered in the study and were defined as those patients that either had a long-term response (LR) (progression-free survival ˃11 months) or those that were primary refractory (PR) (progression as best response). The expression of 754 miRNAs was analyzed in tumor tissue of these 2 sets of patients. Results: In a study cohort (n = 15) 4 miRNAs were significantly associated with patient response and differentially expressed in PR vs. LR (up-regulated in PR vs. LR: miR-425-5p, down-regulated in PR vs. LR: miR-139-3p, let-7d and let-7e). Further analysis in a validation cohort (n = 36) revealed similar results. Conclusion: The present data strength the potential role of miRNAs as a tool to predict treatment outcomes in patients with metastatic renal cell carcinoma treated with TKIs