Restoring mir122 in human stem-like hepatocarcinoma cells, prompts tumor dormancy through smad-independent TGF-β pathway.

miR122 is the prevalent miRNA in adult healthy liver and it is responsible for liver stem cell differentiation towards hepatocyte lineage. Its expression is frequently lost in hepatocellular carcinoma (HCC). We studied the effects of restoring miR122 expression in a distinctive cell line derived from human HCC-BCLC9 cells-with a solid stem-like cell profile, high tumor initiating ability and undetectable miR122 expression. We generated a stable BCLC9 cell line that expresses miR122 (BCLC9-miR122). Restitution of miR122 in BCLC9 cells, decreases cell proliferation rate and reduces significantly tumor size in vivo. BCLC9-miR122 cells down-regulate expression of MYC, KLF4, FOXM1, AKT2 and AKT3 genes and up-regulate FOXO1 and FOXO3A gene expression. In addition, miR122 transfected cells decreased AKT2 kinase activation while decreased FOXO1 and FOXO3A protein inactivation. Reduction in tumor size in BCLC9-miR122 associated with an increase in p38MAPK protein expression and activation leading to a low phospho-ERK1/2 to phospho-p38 ratio. Treatment of miR122 positive cells with an inhibitor of TGFBR1 activation, abolished tumor dormancy program and recovered cell proliferation rate through a Smad-independent TGF-β response.HCC stem-like cells can be directed towards cell differentiation and tumor dormancy by restoring miR122 expression. We demonstrate, for the first time, that dormancy program is achieved through a Smad-independent TGF-β pathway. Restablishing miR122 expression is a promising therapeutic strategy that would work concurrently reducing tumor aggressiveness and decreasing disease recurrence

Diseño de entornos telemáticos de formación para alumnos que cursan asignaturas de nuevas tecnologías

La teleenseñanza y la teleformación representan, servicios estratégicos ya que permiten, supe- rar las limitaciones territoriales y de distancia para acceder a los focos del conocimiento más avan- zados y/o actualizados en cada momento, y también permiten facilitar los procesos de formación continua fundamentales para mantener la capacidad competitiva de una sociedad. Este proyecto ha pretendido servir de punto de partida para acometer iniciativas más ambicio- sas como es la de impartir los contenidos de una asignatura a través de la red . Una última finali- dad que quisimos proponer perseguiría la adopción también de unas actitudes básicas del profeso- rado hacia las nuevas tecnologías, que estén fundamentadas en la reflexión crítica y creemos que lo hemos lograd

Análisis de la situación de los estudios agronómicos y forestales en Europa. Anexo III: análisis de los estudios europeos

El documento que se presenta es el resultado del análisis de la situación actual en estas ingenierías y del estudio del futuro de las mismas. Todas las propuestas que aquí se hacen se han consensuado en las sesiones del Plenario del grupo de trabajo. Por ello, es justo reconocer la aportación que este trabajo puede suponer a la futura Convergencia Europea en la Educación Superior

Molecular genetic heterogeneity in undifferentiated endometrial carcinomas

Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumors, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well-differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole-exome sequencing of the endometrioid and undifferentiated components, as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: (a) hypermutated tumors with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%); and (d) low copy number alterations (copy-number low) tumors with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group, whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumors. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumors, which may have prognostic value

Social/economic costs and health-related quality of life in patients with epidermolysis bullosa in Europe

Background The aim of this study was to determine the social/economic costs and health-related quality of life (HRQOL) of patients with epidermolysis bullosa (EB) in eight EU member states. Methods We conducted a cross-sectional study of patients with EB from Bulgaria, France, Germany, Hungary, Italy, Spain, Sweden and the United Kingdom. Data on demographic characteristics, health resource utilisation, informal care, labour productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. Results A total of 204 patients completed the questionnaire. Average annual costs varied from country to country, and ranged from €9509 to €49,233 (reference year 2012). Estimated direct healthcare costs ranged from €419 to €10,688; direct non-healthcare costs ranged from €7449 to €37,451 and labour productivity losses ranged from €0 to €7259. The average annual cost per patient across all countries was estimated at €31,390, out of which €5646 accounted for direct health costs (18.0 %), €23,483 accounted for direct non-healthcare costs (74.8 %), and €2261 accounted for indirect costs (7.2 %). Costs were shown to vary across patients with different disability but also between children and adults. The mean EQ-5D score for adult EB patients was estimated at between 0.49 and 0.71 and the mean EQ-5D visual analogue scale score was estimated at between 62 and 77. Conclusion In addition to its negative impact on patient HRQOL, our study indicates the substantial social/economic burden of EB in Europe, attributable mostly to high direct non-healthcare costs

Social/economic costs and health-related quality of life in patients with epidermolysis bullosa in Europe

BACKGROUND: The aim of this study was to determine the social/economic costs and health-related quality of life (HRQOL) of patients with epidermolysis bullosa (EB) in eight EU member states. METHODS: We conducted a cross-sectional study of patients with EB from Bulgaria, France, Germany, Hungary, Italy, Spain, Sweden and the United Kingdom. Data on demographic characteristics, health resource utilisation, informal care, labour productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. RESULTS: A total of 204 patients completed the questionnaire. Average annual costs varied from country to country, and ranged from euro9509 to euro49,233 (reference year 2012). Estimated direct healthcare costs ranged from euro419 to euro10,688; direct non-healthcare costs ranged from euro7449 to euro37,451 and labour productivity losses ranged from euro0 to euro7259. The average annual cost per patient across all countries was estimated at euro31,390, out of which euro5646 accounted for direct health costs (18.0 %), euro23,483 accounted for direct non-healthcare costs (74.8 %), and euro2261 accounted for indirect costs (7.2 %). Costs were shown to vary across patients with different disability but also between children and adults. The mean EQ-5D score for adult EB patients was estimated at between 0.49 and 0.71 and the mean EQ-5D visual analogue scale score was estimated at between 62 and 77. CONCLUSION: In addition to its negative impact on patient HRQOL, our study indicates the substantial social/economic burden of EB in Europe, attributable mostly to high direct non-healthcare costs.EU/A10120

Guia de contingut digital accessible

La guia de contingut digital accessible s'ha dissenyat per donar informació pas a pas sobre com estructurar, formatar i escriure un document amb contingut digital perquè sigui accessible. També es descriu com introduir contingut web de forma accessible.UdLxTothom UNIDISCA

Guia d'OpenCms

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/29018Aquesta guia mostra el procés de creació de contingut web de la forma més accessible possible d'acord amb les restriccions d'accessibilitat que presenta la plataforma OpenCms.UdLxTothom UNIDISCA