Gene expression analysis of aberrant signaling pathways in meningiomas

Examining aberrant pathway alterations is one method for understanding the abnormal signals that are involved in tumorigenesis and tumor progression. In the present study, expression arrays were performed on tumor-related genes in meningiomas. The GE Array Q Series HS-006 was used to determine the expression levels of 96 genes that corresponded to six primary biological regulatory pathways in a series of 42 meningiomas, including 32 grade I, four recurrent grade I and six grade II tumors, in addition to three normal tissue controls. Results showed that 25 genes that were primarily associated with apoptosis and angiogenesis functions were downregulated and 13 genes frequently involving DNA damage repair functions were upregulated. In addition to the inactivation of the neurofibromin gene, NF2, which is considered to be an early step in tumorigenesis, variations of other biological regulatory pathways may play a significant role in the development of meningiomaThis study was partially supported by Fondo de Investigaciones Sanitarias, Ministerio de Ciencia e Innovación, Spain, Grants PI‑08/1849 and PI‑10/1972; and by grant PI‑10‑045 from the Fundación Sociosanitaria de Castilla‑La Mancha, Spai

Aprendizaje basado en competencias en la enseñanza de la psiquiatría para estudiantes de medicina

A lo largo de los años, la enseñanza de la psiquiatría para estudiantes de medicina se ha transformado a través de las metodologías implementadas en el proceso. Los cambios en el perfil del trabajo del docente, el rol del estudiante, las estrategias de enseñanza y las actividades que se utilizan, responden a las propuestas de los diversos modelos de aprendizaje que se han puesto en práctica. El objetivo del presente análisis se fundamenta en la descripción de los diferentes enfoques pedagógicos que existen a través de la revisión bibliográfica y la interpretación correspondiente. Mediante esta consideración se planteó una propuesta de trabajo basada en competencias, la cual se pueda implementar en el curso de Psiquiatría que forma parte de la malla curricular en la carrera de medicina de la Universidad de Ciencias Médicas.Over the years, the teaching of psychiatry for medical students has been transformed through the methodologies implemented in the process. The changes in the profile of the teacher's work, the role of the student, the teaching strategies and the activities that are used, respond to the proposals of the various learning models that have been put into practice. The objective of this analysis is based on the description of the different pedagogical approaches that exist through bibliographic review and the corresponding interpretation. Through this consideration, a work proposal based on competencies was proposed, which can be implemented in the Psychiatry course that is part of the curricular mesh in the medical career of the University of Medical Sciences.Universidad Nacional, Costa RicaDivisión de Educologí

Microarray analysis of gene expression in vestibular schwannomas reveals SPP1/MET signaling pathway and androgen receptor deregulation

Vestibular schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of neurofibromin 2 (NF2). Transcriptomic alterations, such as the neuregulin 1 (NRG1)/ErbB2 pathway, have been described in schwannomas. In this study, we performed a whole transcriptome analysis in 31 vestibular schwannomas and 9 control nerves in the Affymetrix Gene 1.0 ST platform, validated by quantitative real-time PCR (qRT-PCR) using TaqMan Low Density arrays. We performed a mutational analysis of NF2 by PCR̸denaturing high-performance liquid chromatography (dHPLC) and multiplex ligation-dependent probe amplification (MLPA), as well as a microsatellite marker analysis of the loss of heterozygosity (LOH) of chromosome 22q. The microarray analysis demonstrated that 1,516 genes were deregulated and 48 of the genes were validated by qRT-PCR. At least 2 genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed 1 hit and 8 tumors showed no NF2 alteration. MET and associated genes, such as integrin, alpha 4 (ITGA4)̸B6, PLEXNB3/SEMA5 and caveolin-1 (CAV1) showed a clear deregulation in vestibular schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in schwannoma merlin depletion. Finally, no major differences were observed among tumors of different size, histological type or NF2 status, which suggests that, at the mRNA level, all schwannomas, regardless of their molecular and clinical characteristics, may share common features that can be used in their treatmentThis study was supported by grants PI07/0577, PI08/1849 and PI10/1972 from Fondo de Investigaciones Sanitarias, Ministerio de Ciencia e Innovación, Spain and PI10-045, and from the Fundación Sociosanitaria de Castilla-La Mancha, Spai

Genomic deletions at 1p and 14q are associated with an abnormal cDNA microarray gene expression pattern in meningiomas but not in schwannomas

The molecular pathology of meningiomas and shwannomas involve the inactivation of the NF2 gene to generate grade I tumors. Genomic losses at 1p and 14q are observed in both neoplasms, although more frequently in meningiomas. The inactivation of unidentified genes located in these regions appears associated with tumor progression in meningiomas, but no clues to its molecular/clinical meaning are available in schwannomas. Recent microarray gene expression studies have demonstrated the existence of molecular subgroups in both entities. In the present study, we correlated the presence of genomic deletions at 1p, 14q, and 22q with the expression patterns of 96 tumor-related genes obtained by cDNA low-density microarrays in a series of 65 tumors including 42 meningiomas and 23 schwannomas. Two expression pattern groups were identified by cDNA mycroarray analysis when compared to the expression pattern in normal control RNA in both meningiomas and schwannomas, each one with patterns similar and different from the normal control. Meningioma and schwannoma subgroups differed in the expression of 38 and 16 genes, respectively. Using MLPA and microsatellites, we identified genomic losses at 1p, 14q, and 22q at nonrandom frequencies (12.5-69%) in meningiomas and schwannomas. Losses at 22q were almost equally frequent in both molecular expression subgroups in both neoplasms. However, deletions at 1p and 14q accumulated in meningiomas with a gene expression pattern different from the normal pattern, whereas the inverse situation occurred in schwannomas. Those anomalies characterized the schwannomas with expression pattern similar to the normal control. These findings suggest that deletions at 1p and 14q enhance the development of an abnormal tumor-related gene expression pattern in meningiomas, but this fact is not corroborated in schwannomas. (C) 2010 Elsevier Inc. All rights reserved.Fondo de Investigaciones Sanitarias, Ministerio de Sanidad[PI-05-0829]Fondo de Investigaciones Sanitarias, Ministerio de Sanidad[PI-07-0577]Fundacion para la Investigacion Bio-medica del Hospital Universitario La Pa

Pedagogía universitaria: Convergencias interdisciplinarias

La presente edición “Pedagogía Universitaria: Convergencias Interdisciplinarias” contiene una recopilación de ensayos redactados por egresadas y egresados de la Maestría en Educación con Énfasis en Docencia Universitaria de la Universidad Nacional de Costa Rica. En ella, convergen pensamientos divergentes y prospectivos sobre el camino para darle continuidad y perseverancia al acto educativo que transcurre en las aulas universitarias y en todas las modalidades conocidas antes, en, durante y post pandemia COVID-19. Estos docentes nos presentan sus preocupaciones, dudas, pensamientos, inquietudes y proposiciones plasmadas en las líneas de cada de uno de estos ensayos, en diversos temas y conectados con el quehacer pedagógico universitario en una gama de disciplinas como: arte, medicina, matemáticas, psiquiatría, química, administración, docencia, lenguas, diseño ambiental, diseño gráfico, o en temas específicos como el fraude académico, la pedagogía saludable, el Diseño Universal de Aprendizaje (DUA) y los cursos de capacitación para el profesorado en materia pedagógica, entre otros. Es un libro lleno de experiencias pedagógicas y planteamientos conceptuales y metodológicos para compartir entre colegas, y hace una llamada a la reflexión permanente de nuestro ejercicio profesional. Los y las invito a disfrutar de esta lectura.Universidad Nacional, Costa RicaDivisión de Educologí

Global Profiling in Vestibular Schwannomas Shows Critical Deregulation of MicroRNAs and Upregulation in Those Included in Chromosomal Region 14q32

<div><p>Background</p><p>Vestibular schwannomas are benign tumors that arise from Schwann cells in the VIII cranial pair and usually present <i>NF2</i> gene mutations and/or loss of heterozygosity on chromosome 22q. Deregulation has also been found in several genes, such as ERBB2 and NRG1. MicroRNAs are non-coding RNAs approximately 21 to 23 nucleotides in length that regulate mRNAs, usually by degradation at the post-transcriptional level.</p><p>Methods</p><p>We used microarray technology to test the deregulation of miRNAs and other non-coding RNAs present in GeneChip miRNA 1.0 (Affymetrix) over 16 vestibular schwannomas and 3 control-nerves, validating 10 of them by qRT-PCR.</p><p>Findings</p><p>Our results showed the deregulation of 174 miRNAs, including miR-10b, miR-206, miR-183 and miR-204, and the upregulation of miR-431, miR-221, miR-21 and miR-720, among others. The results also showed an aberrant expression of other non-coding RNAs. We also found a general upregulation of the miRNA cluster located at chromosome 14q32.</p><p>Conclusion</p><p>Our results suggest that several miRNAs are involved in tumor formation and/or maintenance and that global upregulation of the 14q32 chromosomal site contains miRNAs that may represent a therapeutic target for this neoplasm.</p></div

Three dimensional representation of the Principal Component Analysis of the 16 schwannomas (blue dots corresponding to sporadical and red dot to the NF2 patient) and the 3 control nerves (green dots).

<p>Three dimensional representation of the Principal Component Analysis of the 16 schwannomas (blue dots corresponding to sporadical and red dot to the NF2 patient) and the 3 control nerves (green dots).</p

The top 30 deregulated non-miRNAs present in the arrays.

<p>The top 30 deregulated non-miRNAs present in the arrays.</p

Available miRNAs correspond to those miRNAs tested in the microarray.

<p>Up or downregulation was obtained from those with at least a 2-fold change and p>0.05 when schwannomas and control nerves were compared. Other non-coding RNAs were not considered in this table.</p