Infrequent loss of luminal differentiation in ductal breast cancer metastasis

Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and -positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes

SPARC mediates metastatic cooperation between CSC and non-CSC prostate cancer cell subpopulations

Background Tumor cell subpopulations can either compete with each other for nutrients and physical space within the tumor niche, or co-operate for enhanced survival, or replicative or metastatic capacities. Recently, we have described co-operative interactions between two clonal subpopulations derived from the PC-3 prostate cancer cell line, in which the invasiveness of a cancer stem cell (CSC)-enriched subpopulation (PC-3M, or M) is enhanced by a non-CSC subpopulation (PC-3S, or S), resulting in their accelerated metastatic dissemination. Methods M and S secretomes were compared by SILAC (Stable Isotope Labeling by Aminoacids in Cell Culture). Invasive potential in vitro of M cells was analyzed by Transwell-Matrigel assays. M cells were co-injected with S cells in the dorsal prostate of immunodeficient mice and monitored by bioluminescence for tumor growth and metastatic dissemination. SPARC levels were determined by immunohistochemistry and real-time RT-PCR in tumors and by ELISA in plasma from patients with metastatic or non-metastatic prostate cancer. Results Comparative secretome analysis yielded 213 proteins differentially secreted between M and S cells. Of these, the protein most abundantly secreted in S relative to M cells was SPARC. Immunodepletion of SPARC inhibited the enhanced invasiveness of M induced by S conditioned medium. Knock down of SPARC in S cells abrogated the capacity of its conditioned medium to enhance the in vitro invasiveness of M cells and compromised their potential to boost the metastatic behavior of M cells in vivo. In most primary human prostate cancer samples, SPARC was expressed in the epithelial tumoral compartment of metastatic cases. Conclusions The matricellular protein SPARC, secreted by a prostate cancer clonal tumor cell subpopulation displaying non-CSC properties, is a critical mediator of paracrine effects exerted on a distinct tumor cell subpopulation enriched in CSC. This paracrine interaction results in an enhanced metastatic behavior of the CSC-enriched tumor subpopulation. SPARC is expressed in the neoplastic cells of primary prostate cancer samples from metastatic cases, and could thus constitute a tumor progression biomarker and a therapeutic target in advanced prostate cancer

El uso de ecuaciones específicas de conversión TS-Talla para la estima de la biomasa de peces en balsas de acuicultura someras mediante métodos acústicos

La acuicultura es un sector con demanda creciente en nuestro país y se encuentra en una etapa donde los procesos de producción y comercialización están consolidados. Actualmente, las empresas acuícolas buscan la mejora en la optimización de gastos y el control de la trazabilidad del producto. Para mejorar estos parámetros, es fundamental tener un control exhaustivo sobre el número de peces que se crían en las balsas de cultivo y la biomasa de estas. En primer lugar, para ajustar la dosis de pienso (gasto más relevante en la producción) y en segundo lugar, para mejorar la trazabilidad y el control de la producción final. La hidroacústica ha demostrado ser una técnica eficaz para la determinación de densidad y biomasa de peces, tanto en sistemas de agua dulce como salada. Con este método no intrusivo, se pretende mejorar la fiabilidad de las estimas de densidad y biomasa y reducir el estrés que provocan a los peces los muestreos convencionales. Este trabajo tiene como objetivo la aplicación de esta técnica para la estima de biomasa de peces en balsas de doradas (Sparusaurata) y lubinas (Dicentrarchuslabrax) en esteros. Para ello, se han elaborado ecuaciones que relacionan el TS (dB), cantidad de sonido que devuelve el pez, con la longitud (mm) de los peces, validándose la eficiencia del uso específico de dichas ecuaciones para la estima de la biomasa de peces en sistemas someros

MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells

MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Formación de los tutores de las prácticas externas como herramienta eficaz en la mejora del aprendizaje del estudiante y su inserción laboral

El objetivo del proyecto es mejorar la calidad de la tutorización de las prácticas externas y fomentar las buenas prácticas que garanticen el proceso de enseñanza-aprendizaje. Están implicados tutores académicos, externos, instituciones y estudiante

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Variables psicológicas implicadas en la actitud e iniciativa emprendedora

Identificar variables individuales relacionadas con la iniciativa emprendedora y el fomento de competencias transversales relacionadas con la misma, supone un desafío en la investigación actual sobre emprendimiento. El proyecto titulado Variables psicológicas implicadas en la actitud e iniciativa emprendedora, realizado bajo el programa Innova Docencia promovido por el Vicerrectorado de Calidad de la UCM en la convocatoria 2016-2017, ha tenido por objetivo analizar y evaluar variables psicológicas relacionadas con emprendimiento que presentan una muestra de estudiantes de la Universidad Complutense de Madrid. En dicho estudio han participado 1222 estudiantes de la UCM correspondientes a 27 titulaciones: 14 de Grado, 2 de Dobles Grados, y 11 de Máster. El 28,6% de la muestra fueron hombres y el 71% fueron mujeres. La media de edad fue de 20,43 años. El equipo investigador estuvo compuesto por 40 personas: 25 PDI de la UCM, 2 PAS, 8 alumnos y alumnas, 1 técnico, y 4 PDI de las universidades de Castilla-La Mancha (UCLM), UNED, Carlos III de Madrid (UC3M), y Alcalá de Henares (UAH). El PDI de la UCM correspondía a las siguientes facultades: Psicología (7), Ciencias de la Documentación (3), Ciencias Económicas y Empresariales (6), Ciencias Políticas y Sociología (3), Comercio (1), Trabajo Social (1), Ciencias Biológicas (2), Informática (1), y Bellas Artes (1). Un equipo UCM perteneciente a 9 facultades, que representó a 13 departamentos y a todas las áreas de conocimiento. La metodología empleada consistió en un cuestionario que evaluaba los siguientes aspectos: datos sociodemográficos, actitud emprendedora, y las variables psicológicas: personalidad, inteligencia emocional, resolución de problemas y tolerancia a la ambigüedad. Se optó por instrumentos estandarizados, con buenas características psicométricas de fiabilidad y validez que permitieran obtener resultados robustos, con amplia evidencia empírica y que evaluaban adecuadamente variables que la literatura ha relacionado con la actitud e iniciativa emprendedora. Además todos ellos se han utilizado en investigaciones relacionadas con emprendimiento, lo que aumentó la validez externa. Se ha analizado la iniciativa emprendedora desde el punto de vista de los estudiantes y también teniendo en cuenta variables del entorno familiar y personal. Los resultados nos muestran que son las variables psicológicas de extraversión, reparación emocional y estrategias de resolución de problemas las que predicen la iniciativa emprendedora. Los estudiante que compaginan estudios y trabajo tienen una mayor iniciativa emprendedora, y aquellos cuyos padres y/o pareja desarrollan su actividad laboral como autónomos. Se presentan datos por titulación académica, sexo, actividad laboral de los padres y compaginar estudios y trabajo. Se muestran datos de todas las variables psicológicas por titulación académica, y una comparativa de dichas variables entre los universitarios, un grupo de estudiantes de Formación Profesional (FP) y una muestra de emprendedores reales. Los resultados obtenidos son relevantes para tomar decisiones orientadas a la mejora de la actitud, iniciativa y comportamiento emprendedor. Permitirán el diseño y ejecución de actividades académicas para sensibilizar a los estudiantes en la cultura emprendedora, y formar en competencias transversales, cada vez más demandadas, para mejorar la empleabilidad y competitividad como claves para el crecimiento de nuestra sociedad

Variables psicológicas implicadas en la actitud e iniciativa emprendedora (II): personalidad, cognición y emoción

El proyecto titulado: Variables implicadas en la actitud e iniciativa emprendedora (II): personalidad, cognición y emoción, es la continuidad de otro presentado en la convocatoria anterior (2016-2017) cuyo objetivo era evaluar variables psicológicas en la actitud emprendedora de los estudiantes universitarios de la Universidad Complutense de Madrid (UCM). Este segundo proyecto ha tenido por objetivo principal ampliar la evaluación a otras facultades y áreas de conocimiento de nuestra universidad a fin de obtener el mapa y perfil de la iniciativa emprendedora del universitario UCM