Análisis de las alteraciones genéticas y del microambiente inmune tumoral en pacientes con gliobastoma: impacto en el curso clínico del tumor

En el contexto en el que muchos de los genes alterados en el GB son diana de distintas vías de señalización celular estratégicas (p.ej. vías cuya alteración puede estar asociada con una pérdida del control del funcionamiento celular normal) con implicaciones, tanto en la interacción de la célula tumoral alterada con otras células, como en la creación de un microambiente tumoral específico que puede condicionar la evolución del tumor y la enfermedad, adquieren especial relevancia aquellos estudios que permiten combinar el análisis genético del tumor, con el conocimiento del microambiente inmune, para mejorar la comprensión de la patogenia de la enfermedad y de los criterios más relevantes que deben ser empleados para una mejor clasificación (pronóstica) de los pacientes con GB. Ante estos antecedentes, se plantea como objetivo general: Analizar las características genéticas y celulares del GB, incluido el microambiente del tumor y los componentes inmunes presentes en el mismo, con el fin de determinar su posible utilidad a la hora de estratificar a los pacientes en grupos pronósticos en función de dichas características genéticas e inmunes. Para ello, se definen tres objetivos específicos: 1. Identificar la presencia e incidencia de amplificaciones y/o deleciones génicas a nivel del genoma tumoral del GB y determinar su posible impacto en la supervivencia de los pacientes para ser utilizados en el futuro en la clasificación de los GB. 2. Analizar el perfil de expresión de aquellos genes amplificados con mayor frecuencia en GB, tanto en el tejido tumoral como en tejido cerebral no tumoral, y determinar su posible relación con el comportamiento clínico del tumor. 3. Diseñar e implementar una estrategia de análisis detallada de la composición celular de los GB y su microambiente inmune, mediante la técnica de CMF, y explorar su posible relación con las alteraciones genéticas subyacentes y el comportamiento clínico y pronóstico de la enfermedad

Voluntary or forced assignment to work groups in university students: effects on team roles

Póster 14.º Encontro da Associação Portuguesa de Psicologia Experimental. Universidade de Évora (Portugal), 3-4 mayo 2019[EN]The productivity of future professionals is usually conditioned by their ability to work in groups. Therefore, the EHEA has promoted various forms of teaching methodologies that require group activities by the university student. However, the consequences of a voluntary or forced assignment of students to such activities are still not well known. In addition to the type of assignment to the group, various variables intervene conditioning the proper functioning and didactic effectiveness of these activities. These variables can be of individual or collective type. The variables of individual type used in this study are: peer attachment, characterized by the person's way of bonding (Bowlby, 1969; Leiter, Day and Price, 2015); the expectation of self-efficacy, considered as confidence in one's ability to achieve the intended results (Ormrod, 2006); and the attitude toward collaborative learning, understood as the attitude towards working in small groups based on participation and positive interdependence. The collective variables selected are the team roles that make up the different work groups (Belbin, 2015). Each student can play several roles depending on the needs of the team and, also, according to their own interests. A team role is the commitment that the individual acquires to perform a certain function, adjusting their skills to the needs of the team. OBJETIVE Analyze the relationships between attachment, self-efficacy, attitude toward collaborative learning and team role, as well as the effect of voluntary or random training of work groups on team roles.Funded in the Call for Aid for Innovation Projects and Teacher Improvement 2018/19 (USAL

Mejora e innovación de los procedimientos para la evaluación continua y final de los estudiantes en Studium a través de formatos variados que propicien el aprendizaje significativo y la adquisición de competencias cognitivas específicas

Memoria ID-.004 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2021-2022

A Short Region of Connexin43 Reduces Human Glioma Stem Cell Migration, Invasion, and Survival through Src, PTEN, and FAK

[EN] Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects onmigration and invasion. Here,weshowthat a cell-penetrating peptide based onCX43(TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensinhomolog inglioma stem cells (GSCs) derived from patients. Consequently, TAT-Cx43266-283 reduced GSC motility, as analyzed by time-lapse microscopy, and strongly reduced their invasive ability. Interestingly, we investigated the effects of TAT-Cx43266-283 on freshly removed surgical specimens as undissociated glioblastoma blocks, which revealed a dramatic reduction in the growth, migration, and survival of these cells. In conclusion, a region of CX43 (amino acids 266–283) exerts an important anti-tumor effect in patient-derived glioblastoma models that includes impairment of GSC migration and invasion

Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles

[EN]everal classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using singlenucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region - either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p

Voluntary or forced assignment to work groups in university studies: effects on team roles

Memoria ID-005. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2018-2019

Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival.

Agradecimiento: el artículo está publicado en la revista Cancers [MDPI] y está disponible en: https://www.mdpi.com/2072-6694/12/1/231[EN]The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8-9 was found in only two tumors (2%). Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.Este estudio ha sido financiado por el Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación y Ministerio de Economía y Competitividad (RD12/0036/0048, AES PI16/00476-FONDOS FEDER y CB16/12/00400