Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells.

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.

Role of immune escape mechanisms in Hodgkin's lymphoma development and progression: a whole new world with therapeutic implications.

Hodgkin's lymphoma represents one of the most frequent lymphoproliferative syndromes, especially in young population. Although HL is considered one of the most curable tumors, a sizeable fraction of patients recur after successful upfront treatment or, less commonly, are primarily resistant. This work tries to summarize the data on clinical, histological, pathological, and biological factors in HL, with special emphasis on the improvement of prognosis and their impact on therapeutical strategies. The recent advances in our understanding of HL biology and immunology show that infiltrated immune cells and cytokines in the tumoral microenvironment may play different functions that seem tightly related with clinical outcomes. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of HL microenvironment. This new knowledge will probably translate into a change in the antineoplastic treatments in HL in the next future and hopefully will increase the curability rates of this disease.

New insights into the role of the immune microenvironment in breast carcinoma.

Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future.

Array-CGH in patients with a clinical diagnosis of Kabuki syndrome: identification of two cases with terminal 2q37 deletion and no other recurrent rearrangement

Background: Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. Methods: We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. Results: No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Conclusion: Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.

Els nens i nenes amb “Dictamen d’escolarització” i amb suport del CDIAP: estudi de les dimensions de l’atenció a les necessitats especials de l’alumnat, entre tres i sis anys, escolaritzat en un centre públic de la comarca d’Osona

La meva recerca ha tingut com a punt de partida “Els nens i nenes amb “Dictamen d’escolarització” i amb suport del CDIAP: estudi de les dimensions de l’atenció a les necessitats especials de l’alumnat, entre tres i sis anys, escolaritzat en un centre públic de la comarca d’Osona”. A partir d’aquí, s’ha elaborat un marc teòric a partir de les lleis d’educació, decrets que regulen els diferents serveis i un seguit de conceptes bàsics. Un cop elaborat aquest marc teòric per tal de recollir les dades dels alumnes, de tres a sis anys, d’una escola en concret s’ha dissenyat un instrument de recollida de dades que li diem full resum de serveis (FRS). El FRS és un instrument que ens ha servit per recollir totes les dades d’alumnes amb necessitats específiques i, sobretot, per saber quin suport reben per part de l’escola i per part d’altres serveis. A més a més, per recollir informació sobre els diferents serveis que atenen aquesta diversitat s’ha elaborat un guió d’entrevistes (GE). Aquest GE serveix per recollir els aspectes més importants de les entrevistes realitzades a l’EAP (Equip d’Assessorament i Orientació Psicopedagògica), CDIAP (Centre de Desenvolupament Infantil i Atenció Precoç) i CSMIJ (Centre de Salut Mental Infantil i Juvenil). A partir de la informació extreta dels dos instruments, s’han elaborat unes conclusions respecte els objectius plantejats en aquest projecte i la pregunta plantejada a l’inici.

Canvis neuropsicològics en el procés d’envelliment en les persones amb Síndrome de Down

La millora en la qualitat de vida ha afavorit considerablement l'augment de la longevitat de les persones amb discapacitat intel·lectual i amb síndrome de Down (SD) en particular i, per aquesta raó, és important descriure les característiques que presenta el seu procés d'envelliment. Per tant, és molt important aconseguir una major precisió en la detecció inicial dels canvis cognitius i emocionals, per tal de dur a terme una bona prevenció i/o intervenció ajustada a les necessitats de cada persona. És per tant, fonamental una bona prevenció i detecció de l’inici del deteriorament per així, millorar la intervenció en la seva qualitat de vida durant el procés d’envelliment. En aquest sentit i degut a què hi ha encara pocs estudis sobre el deteriorament cognitiu en l’envelliment de les persones amb SD, cal fomentar la realització d’estudis que permetin un millor coneixement del seu procés d’envelliment. Per aquest motiu, s’ha iniciat un estudi multicèntric amb diferents institucions que treballen amb persones amb SD, amb la finalitat de determinar si existeix un patró de deteriorament i l’evolució dels canvis cognitius i emocionals en el procés d’envelliment en les persones amb SD.

Trabajo para la obtención del título de Piloto de Segunda de la Marina Mercante Española

Para la elección del contenido del trabajo he seguido el mismo esquema utilizado para la presentación de las memorias de las prácticas académicas realizadas para la obtención de la diplomatura en navegación marítima y de la licenciatura en náutica y transporte marítimo. El modelo se basa en realizar un análisis de todos los equipamientos e instrumentación que podemos encontrar a bordo. Si nos fijamos en lo que establece la Orden del Ministerio de Transporte, Turismo y Comunicaciones de 18 de octubre de 1989 podríamos afirmar que la temática del presente trabajo se enmarcará dentro de los epígrafes “Seguridad a bordo, contra incendios, emergencias, supervivencia y salvamento” y “Equipamiento e instrumentación de a bordo”.El trabajo que les presento a continuación analiza el equipamiento del buque Nura Nova. El último de los tres buques en los que he estado embarcado como alumno de puente. El trabajo está dividido en varios apartados principales: Equipos de navegación, protección, comunicación, salvamento, contra incendios, carga y descarga y lucha contra la contaminación. Además de los apartados anteriores que forman el cuerpo central del trabajo, hay otros capítulos secundarios que ayudan a completarlo, como el capítulo que abre el trabajo y que narra brevemente la historia del Nura Nova.

Expression of Glycogen Phosphorylase Isoforms in Cultured Muscle from Patients with McArdle´s Disease Carrying the p.R771PfsX33 PYGM Mutation

Mutations in the PYGM gene encoding skeletal muscle glycogen phosphorylase (GP) cause a metabolic disorder known as McArdle's disease. Previous studies in muscle biopsies and cultured muscle cells from McArdle patients have shown that PYGM mutations abolish GP activity in skeletal muscle, but that the enzyme activity reappears when muscle cells are in culture. The identification of the GP isoenzyme that accounts for this activity remains controversial.

Pilot study about the effect of rt-PA administration on the excitotoxicity mediated brain damage and its repercussion on the functional prognosis of patients with ischaemic stroke: research protocol

Fibrinolytic therapy with Recombinant Tissue-Plasminogen Activator (rt-PA) is currently the only effective treatment for ischaemic stroke in its acute phase. Even though its use generally improves the prognosis of those patients likely to receive it, rt-PA administration is associated to several risks, such as haemorrhagic transformation ofthe ischaemic lesion and activation of excitotoxic mechanisms that may contribute to an increase in mortality or to a poor outcome in certain occasions, specially when arterial recanalization is not achieved or the rt-PA is lately administrated. Since in the last few years the role of glutamate in the neurotoxicity associated toischaemia has been widely studied and it is known that high plasma glutamate levels are predictors of ischaemic lesion growth and poor neurological outcome, it is necessary to find out which factors can contribute to glutamate release in the brain. The aim of this study is to determine if rt-PA administration is related to an increase in plasma glutamate levels, as well as to define if higher plasma glutamate levels at admission are related to different evolution and prognosis of our patients, both in those in which recanalisation is achieved and not. A series of cases of patients with hemispheric cerebral infarction admitted in our hospital during a year will be studied, and the data obtained from them will be compared to the data obtained from a control group, the samples of wich were takenyears ago, before rt-PA was routinely used

A vueltas con la Crónica del rey don Rodrigo

The paper discusses the problem of the literary genre of the Crónica sarracina from a peninsular and european points of view. It is considerer through the prism of a new kind of fiction, related to history and an incipient realism, which grows up along the 15th century. Moreover, it reveals new fragments inspired by Pedro de Corral from the catalan version of Seneca’s tragedies and from the Libro de los doce sabios

De Francisco a Marco Antonio Aldana pasando por Gaspar

It is traditionally considered that the «Aldana», whom Gaspar Gil Polo praises at the end of his «Canto de Turia» (1564), was Francisco de Aldana, the «divino». It is nonetheless more probable that it was in fact rather the Valencian poet, Marco Antonio Aldana, almost forgotten today, but very much in the public eye within the cultivated circles of the end of the sixteenth century Valencia

El Cancionero del Barón de Claret: fama de Lope de Vega y Calderón de la Barca en la Cataluña de la segunda mitad del siglo XVII

Comentari del llibre Cancionero del Barón de Claret, compilat a Catalunya. El comentari es centra en la influència de Lope de Vega i de Calderón de la Barca sobre aquesta obra. Resulta més influent Lope de Vega, malgrat que en el moment de la compilació de la obra ja no estava de moda, que Calderón de la Barca

De Heródoto a Lope : nota a El mejor alcade, el rey

Article sobre les al·lusions i anècdotes tradicionals que fa servir Lópe de Vega a les seves obres. Concretament es tracta un episodi del llibre El mejor alcalde, el rey

Lope de Vega en "Cancionero del Barón de Claret": una antología personal de poesía y teatro

Presentació del Cancionero del Barón de Claret. Compilat durant el triomf de la mal dita “escola calderoniana”, demostra un interès molt gran per la poesia i el teatre de Lope, fins el punt que és d’aquest autor de qui es recullen més composicions

Recull de literatura jove. 'Recopilación de literatura joven'.

El presente material se dirige al alumnado de educación secundaria, en el marco de la Fiesta del Libro, y forma parte del programa del Departamento de Dinámica Educativa del Ayuntamiento de Palma de Mallorca