La patogenia del Sarcoma de Ewing. Implicaciones de las Células Madre Mesenquimales y Nuevas Estrategias Terapéuticas

[ES]El Sarcoma de Ewing (SE) es un tumor maligno que afecta mayoritariamente a niños o adultos jóvenes. Dentro del grupo de sarcomas, después del osteosarcoma, es el que tiene peor pronóstico con una media de supervivencia del 30% en los casos metastásicos. A nivel molecular el SE se caracteriza por la presencia de una fusión génica entre el gen EWS y genes de la familia ETS principalmente FLI 1 (>90% casos) y ERG (5-10% casos . El producto de esta fusión es una proteína quimérica que actúa como factor de transcripción aberrante, desregulando ciertos genes tales como CD99 y genes relacionados con la ruta de IGF1R, entre otros genes. A nivel morfológico, las células de SE se caracterizan por la presencia de una elevada expresión del receptor de superficie CD99 en el 99% de las células. El tratamiento de primera línea se basa por regímenes multi-terapéuticos incluyendo quimioterapia con combinaciones de doxorubicina, vincristina, ifosfamida y etopósido, combinada con radioterapia y/o cirugía. Además en pacientes con tumores de mal pronóstico se han realizado varios ensayos clínicos con inhibidores de PARP, inhibidores de IGF1R y trasplante autólogo de células stem combinado con radioterapia, entre otros tratamientos. Todos estos estudios reflejan que la mejor estrategia terapéutica es el uso de de multi-tratamientos. En este sentido, estudios preclínicos, in vitro e in vivo han mostrado varias estrategias terapéuticas que podrían ser eficaces en el tratamiento de pacientes con SE de entre los cuales hay que destacar el bloqueo de las dianas clave en SE: la fusión génica, el eje IGF1-IGF1R y en segundo plano la sobre expresión de CD99.Este proyecto de tesis ha sido financiado por: - La Fundação para a Ciência e Tecnologia, Governo de Portugal, con el Proyecto: “The pathogenesis of Ewing Sarcoma: implications for novel treatment strategies” (SFRH/BD/69318/2010). - La Red de Excelencia de la Comunidad Europea EUROBONET, con el Proyecto Europeo “Molecular Pathology of Bone Tumors” (FP6-2004-Lifescihealth-5, 018814). - European Clinical trials in Rare Sarcomas within an integrated translational trial network (EUROSARC) FP7-HEALTH-2011-two-stage (Project ID 278742 Comisión Europea) - El Ministerio de Ciencia e Innovación, a través del Instituto de Salud Carlos III (RD12/0036/0017, RD06/0020/0059, PI1203102, PI1100018, PI081828, PI052524) -La Fundación Asociación Española Contra el Cáncer (AECC), con el proyecto “Búsqueda, validación y traslación clínica de nuevas dianas terapéuticas a partir de estudios de genómica y epigenómica integrativa en sarcoma de Ewing”. (GCB13131578DE Á

Characterisation of polyphenols by HPLC-PAD-ESI/MS and antioxidant activity in Equisetum telmateia

The antioxidant activity of an aqueous extract (infusion) and respective ethyl acetate fraction of Equisetum telmateia Ehrh. (Equisetaceae), a plant used in traditional medicine for its anti-inflammatory and diuretic properties, has been evaluated by DPPH, TEAC and TBARS assays. A high and significant antioxidant activity was detected in the ethyl acetate fraction. Analysis of the aqueous extract and the ethyl acetate fraction by HPLC-PAD-ESI/MS allowed the identification of the major phenolic compounds as flavan-3-ol, kaempferol and phenolic acid derivatives. Among the flavan-3-ols, A-type proanthocyanidins and afzelechin derivatives were detected as well as the more common B-type procyanidins, B2 and C1, whose identification was further confirmed by HPLC using detection involving chemical reaction with p-dimethylamino-cinnamaldehyde. The results suggest that the anti-inflammatory activity of E. telmateia could be due, at least in part, to the presence of compounds with antioxidant activity. Copyright © 2005 John Wiley & Sons, Ltd

Undernutrition and associated factors among hospitalized patients

Background & aims: The identification of modifiable risk factors associated with disease-related undernutrition at hospital admission will contribute to the development of integrated intervention and control strategies for a timely primary prevention. This study aim was to quantify the association between functional autonomy and undernutrition. Methods: A multicentric cross-sectional study was developed in six public hospitals in Portugal. Undernutrition risk was assessed using Nutritional Risk Screening 2002, undernutrition status was classified from anthropometry and functional autonomy was evaluated using the Katz Index. Results: In this sample of 1144 patients, 36% were at undernutrition risk and 9.7% undernourished. In logistic regression analysis, dependent patients were at an increased risk of undernutrition (OR ¼ 1.69, 95% confidence interval (CI) ¼ 1.20e2.39). The following parameters: illiteracy (OR ¼ 2.45, CI ¼ 1.52e3.96), age (one year increment) (OR ¼ 1.03, CI ¼ 1.02e1.04), male (OR ¼ 1.61, CI ¼ 1.19e2.16), single/divorced/widowed (OR ¼ 1.83, CI ¼ 1.34e2.51) and smoker (OR ¼ 1.55, CI ¼ 1.02e2.35) also increased the undernutrition risk. The impaired functional status, being single, divorced or widowed and be a smoker were also associated with anthropometric undernutrition. Conclusions: Functional impairment is related with undernutrition risk and with anthropometrical undernutrition at hospital admission. We also conclude that little extra information is gained by using anthropometrical indices compared to NRS 2002 when assessing the factors associated with undernutrition.info:eu-repo/semantics/publishedVersio

Estratégias a adotar pelos enfermeiros para a prevenção e redução de flebites associadas ao cateter venoso periférico: revisão sistemática da literatura

info:eu-repo/semantics/publishedVersio

Estratégias a adotar pelos enfermeiros para a prevenção e redução de flebites associadas ao cateter venoso periférico: revisão sistemática da literatura

info:eu-repo/semantics/publishedVersio

Characterization of human mesenchymal stem cells from Ewing sarcoma patients. Pathogenetic implications

Amaral, Ana Teresa et al.[Background] Ewing Sarcoma (EWS) is a mesenchymal-derived tumor that generally arises in bone and soft tissue. Intensive research regarding the pathogenesis of EWS has been insufficient to pinpoint the early events of Ewing sarcomagenesis. However, the Mesenchymal Stem Cell (MSC) is currently accepted as the most probable cell of origin.[Materials and Methods] In an initial study regarding a deep characterization of MSC obtained specifically from EWS patients (MSC-P), we compared them with MSC derived from healthy donors (MSC-HD) and EWS cell lines. We evaluated the presence of the EWS-FLI1 gene fusion and EWSR1 gene rearrangements in MSC-P. The presence of the EWS transcript was confirmed by q-RT-PCR. In order to determine early events possibly involved in malignant transformation, we used a multiparameter quantitative strategy that included both MSC immunophenotypic negative/positive markers, and EWS intrinsic phenotypical features. Markers CD105, CD90, CD34 and CD45 were confirmed in EWS samples.[Results] We determined that MSC-P lack the most prevalent gene fusion, EWSR1-FLI1 as well as EWSR1 gene rearrangements. Our study also revealed that MSC-P are more alike to MSC-HD than to EWS cells. Nonetheless, we also observed that EWS cells had a few overlapping features with MSC. As a relevant example, also MSC showed CD99 expression, hallmark of EWS diagnosis. However, we observed that, in contrast to EWS cells, MSC were not sensitive to the inhibition of CD99. [Conclusions] In conclusion, our results suggest that MSC from EWS patients behave like MSC-HD and are phenotypically different from EWS cells, thus raising important questions regarding MSC role in sarcomagenesis. © 2014 Amaral et al.Enrique de Álava's lab is also sourced by the Red Temática de investigación del cáncer (RTICC, Spain). Katia Scotlandi's lab is also sourced by the Italian Association for cancer research (AIRC IG10452).Peer Reviewe