Expresión de E-cadherina, laminina y colágeno IV en la evolución de displasia a carcinoma epidermoide oral

Objetivos: Estudiar la pérdida o reducción de la adhesión celular mediada por E-cadherina en leucoplasias, carcinomas epidermoides y metástasis ganglionares. Estudiar la pérdida de continuidad de la expresión de laminina y colágeno IV en la membrana basal epitelial en el desarrollo biológico de las leucoplasias y carcinomas orales. Material y metodo: Hemos estudiado 124 muestras de pacientes portadores de leucoplasias y carcinomas orales con diversos diagnósticos que abarcan desde epitelio normal (13 muestras), displasias leves (2), displasias moderadas (12), carcinomas in situ (13) carcinomas microinvasores (11) Carcinoma epidermoide oral (64 muestras) y metástasis ganglionar (9). Se construyeron 7 bloques de tissue microarrays con aguja de 2mm y se realizó un estudio mediante técnica inmunohistoquímica para E-cadherina (clona 36, T.D. ABD Company), Laminina (078P, Biogenex) y Colágeno IV (PHM12, Biogenex). Resultados: En Displasias Leves y Moderadas presentan pérdida de expresión de E-cadherina, Laminina, y Colágeno IV (20%). En Carcinomas in situ y Microinvasores, presentaron pérdida de expresión de E-cadherina (73%), y en Laminina y Colágeno IV (57%). En los carcinomas epidermoides, encontramos pérdida de expresión de E-cadherina (90%) y discontinuidad en la M. basal (70%). Todas las metástasis ganglionares presentaron pérdida de E-cadherina y discontinuidad en Laminina y Colágeno IV. Conclusiones: La pérdida de expresión de E-cadherina se incrementa al aumentar el grado de displasia de las lesiones. La perdida de continuidad en la expresión de laminina y Colágeno IV sigue una evolución paralela desde displasias a metástasis ganglionares. La disminución en la expresión de los tres marcadores ha sido significativa en la evolución de las lesiones orales.Objectives: Study the loss or reduction of the cellular adhesion mediated for E-cadherin in oral leukoplakias, oral squamous cell carcinomas and metastatic nodules. Study the loss of continuity of the laminin and collagen IV expression in the epithelial basal membrane from the biological development of the oral leukoplakias and oral carcinomas. Material and method: we have studied 124 samples of patient payees leukoplakias and oral carcinomas with diverse diagnosis that embrace from normal epithelium (13 samples), mild dysplasias (2), moderate dysplasias (12), 'in situ' carcinomas (13), microinvasive carcinomas (11) oral squamous cell carcinomas (64 samples) and metastatic nodules (9). 7 blocks of tissue microarrays were built with needle of 2mm and was carried out a study by means of immunohistochemical technique for E-cadherin (clone 36, Biogenex), Laminin (078P, Biogenex) and Collagen IV (PHM12, Biogenex). Results: In Mild and Moderate Dysplasias the results present loss of E-cadherin, Laminin, and Collagen IV (20%) expression. 'in situ' and microinvasive carcinomas, the results presented loss of E-cadherin expression (73%), and loss in Laminin and Collagen IV expression (57%). In the squamous cell carcinomas , we find E-cadherin underexpression (90%) and discontinuity in the Basal Membrane. (70%). All the metastatic nodules presented loss of E-cadherin expression and discontinuity in Laminin and Collagen IV expression. Conclusions: The loss of E-cadherin expression is increased when increasing the dysplasia grade of lesions. The loss of continuity in the laminin and Collagen IV expression follow a parallel evolution from dysplasias to metastatic nodules. The underexpression of the three markers has been significant in the evolution of the oral lesions

Expresión proteica de p53 y proliferación celular en leucoplasias orales

Objetivos: Conocer la expresión proteica de las alteraciones genéticas que se producen en las etapas precoces de la cancerización del campo de cavidad oral en nuestro medio. Estudiar la proliferación celular mediante Ki-67 y la expresión de la proteína p53 para valorar si las alteraciones en la expresión proteica de estos marcadores suceden de forma secuencial a través de las distintas etapas en la cancerización del campo de la cavidad oral. Material y métodos: Se realizó un estudio mediante técnicas de inmunohistoquímica sobre 53 pacientes que presentaron lesiones de leucoplasia oral, atendidos por el Servicio de O.R.L del Hospital Universitario de Salamanca, desde 1.990 hasta 2000. Se incluyen en el estudio 11 muestras de epitelio normal, 15 displasias leves y moderadas, 15 carcinomas in situ, y 12 carcinomas microinvasores. Resultados: Encontramos la proliferación celular aumentada y sobreexpresión de p53 a medida que avanzamos en el grado de severidad histopatológica de las lesiones. Las alteraciones más precoces son el aumento significativo de la proliferación celular en displasias leves y moderadas y el aumento de expresión de p53. Conclusión: La leucoplasia oral es un estado precanceroso que constituye una lesión cancerizable debido a las alteraciones genéticas que intervienen en la evolución de la lesión. El estudio inmunohistoquímico y molecular de las lesiones es un medio rutinario que permite conocer la expresión proteica de las alteraciones genéticas, que puede ayudar en el diagnóstico precoz y tratamiento de esta patología, teniendo especial relevancia el estudio de Ki-67 en etapas iniciales y p53 en lesiones más avanzadas.OBJECTIVES: We intend to know the protein expression of genetic alterations that take place in the early stages in the field cancerization of oral cavity in our means as well as to study the cellular proliferation by means of Ki-67 and the protein product expression of p53 to value if the alterations in the protein products expression of these markers happen in a sequential pathway through the different stages in the field cancerization of oral cavity. MATERIALS AND METHODS: A study was made by immunohistochemistry on 53 patients that presented lesions of oral leukoplaquia, assisted by the ENT service at University Hospital of Salamanca, from 1.990 up to 2000. 11 samples of normal epithelium, 15 mild to moderate dysplasias, 15 in situ carcinomas and 12 microinvasive carcinomas are included in the study. RESULTS: we find an increased cellular proliferation and p53 over-expression as we advance in the grade of severity histopathologic of these lesions. The most early alterations are a significant increase of cell proliferation in mild and moderate dysplasias and an increased p53 over-expression. CONCLUSIONS: Oral leukoplaquia is a precancerous stage that constitutes a canzerisable lesion due to the genetic alterations that mediate in the evolution of lesion. Routine Immunohistochemical and molecular study of these lesions allow us to know the protein expression of genetic alterations that can help in the early diagnosis and treatment of this pathology, having special relevance the study of Ki-67 in early stages and p53 in advanced lesions

Immune system disorders, cancer and viral infections: A new treatment opportunity for the immune checkpoint inhibitors

Producción CientíficaThe relationship between viral infections and cancer is well known and has been established for decades. Multiple tumours are generated from alterations secondary to viral infections 2 resulting from a dysregulation of the immune system in many cases. Certain causal relationships, such as that between the Epstein–Barr virus (EBV) in nasopharyngeal cancer or hepatitis C and B viruses in hepatocarcinoma, have been clearly established, and their implications for the prognosis and treatment of solid tumours are currently unknown. Multiple studies have evaluated the role that these infections may have in the treatment of solid tumours using immunotherapy. A possible relationship between viral infections and an increased response to immune checkpoint inhibitors (ICIs) has been established at a theoretical level in solid neoplasms, such as EBV-positive cavum cancer and human papillomavirus (HPV)-positive and oropharyngeal cancer. These could yield a greater response associated with the activation of the immune system secondary to viral infection, the consequence of which is an increase in survival in these patients. That is why the objective of this review is to assess the different studies or clinical trials carried out in patients with solid tumours secondary to viral infections and their relationship to the response to ICIs

E-cadherin, laminin and collagen IV expression in the evolution from dysplasia to oral squamous cell carcinoma

Objetivos: Estudiar la pérdida o reducción de la adhesión celular mediada por E-cadherina en leucoplasias, carcinomas epidermoides y metástasis ganglionares. Estudiar la pérdida de continuidad de la expresión de laminina y colágeno IV en la membrana basal epitelial en el desarrollo biológico de las leucoplasias y carcinomas orales. Material y metodo: Hemos estudiado 124 muestras de pacientes portadores de leucoplasias y carcinomas orales con diversos diagnósticos que abarcan desde epitelio normal (13 muestras), displasias leves (2), displasias moderadas (12), carcinomas in situ (13) carcinomas microinvasores (11) Carcinoma epidermoide oral (64 muestras) y metástasis ganglionar (9). Se construyeron 7 bloques de tissue microarrays con aguja de 2mm y se realizó un estudio mediante técnica inmunohistoquímica para E-cadherina (clona 36, T.D. ABD Company), Laminina (078P, Biogenex) y Colágeno IV (PHM12, Biogenex). Resultados: En Displasias Leves y Moderadas presentan pérdida de expresión de E-cadherina, Laminina, y Colágeno IV (20%). En Carcinomas in situ y Microinvasores, presentaron pérdida de expresión de E-cadherina (73%), y en Laminina y Colágeno IV (57%). En los carcinomas epidermoides, encontramos pérdida de expresión de E-cadherina (90%) y discontinuidad en la M. basal (70%). Todas las metástasis ganglionares presentaron pérdida de E-cadherina y discontinuidad en Laminina y Colágeno IV. Conclusiones: La pérdida de expresión de E-cadherina se incrementa al aumentar el grado de displasia de las lesiones. La perdida de continuidad en la expresión de laminina y Colágeno IV sigue una evolución paralela desde displasias a metástasis ganglionares. La disminución en la expresión de los tres marcadores ha sido significativa en la evolución de las lesiones orales

Interactiva mediante el sistema responseware en el master universitario en tratamiento de soporte y cuidados paliativos en el enfermo oncológico.

Memoria ID-052. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2013-2014

Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence

Marijuana consumption during adolescence has been proposed to be a stepping stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance (fourteen 2 h daily sessions) of cocaine self administration (1 mg/kg), food reinforced operant learning under conditions of normal (ad libitum access to food), and high motivation (food restriction schedule) were measured. Additionally, brain metabolic activity was analyzed by means of [18F] fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP treated rats showed a higher rate of cocaine self administration as compared to vehicle treated females and males; no differences were found between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in the food reinforced operant task, pointing to the cocaine specific nature of the effect seen in self administration rather than a general change in reward processing. Basal brain metabolic activity also changed in CP treated females when compared to their vehicle treated counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a hypo activation of the amygdalo entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters the susceptibility to acquire cocaine self administration, in a sex specific fashion. This increased susceptibility could be related to thechanges in brain metabolic activity induced by cannabinoids during adolescenceThis work was supported by Grants FIS G03/05 (Red de Trastornos Adictivos), BSO2001-1099, FIS 01-05-01, Plan Nacional sobre Drogas (PNSD) 2001–2003, PNSD 2004–2007, GR-SAL/0260/2004 to EA and Grants INT/2012/ 2002, CB06/01/0079, and CENIT (2006–2009) to MDPublicad

Aproximación multidisciplinar a la supervisión del practicum en las carreras de educación, medicina, odontología, informática, comunicación y documentación

Memoria ID-035. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2013-2014

Artesãos, cartografia e império. A produção social de um instrumento náutico no mundo ibérico, 1500-1650

Explicar cómo y en qué condiciones fueron construidos algunos de los instrumentos científicos más emblemáticos del mundo moderno sigue siendo un desafío para los historiadores de la ciencia y de la tecnología. Este principio afecta también a los instrumentos náuticos. Así, el objetivo del presente artículo es considerar el “cómo” y el “en qué condiciones”, en un sentido amplio, analizando uno de estos artefactos: las cartas náuticas construidas durante la expansión marítima europea. Originalidad: La originalidad del texto no reside únicamente en llevar a cabo una reconstrucción de este instrumento en Portugal y España que aporte nuevos datos sobre su proceso de fabricación y sus fabricantes, sino también en arrojar luz sobre antiguos debates historiográficos que subyacen a la génesis de la ciencia moderna, tales como la difícil colaboración entre hombres prácticos y hombres teóricos; la aportación de comunidades de artesanos al mundo del conocimiento; el papel que los saberes prácticos tuvieron en el establecimiento de nuevas formas de estandarización en ciencia; la adopción de una metodología empírica para el dominio del mundo o la construcción de grandes imperios globales cimentados sobre la base del trabajo manual. Metodología: El análisis de estos debates requiere una aproximación metodológica que atienda a las categorías y los conceptos principales puestos en circulación tanto por la historia como por la filosofía de la ciencia más reciente. En definitiva, se trata de atender a las condiciones que permitieron el establecimiento de acuerdos (y también de controversias) epistemológicos entre diferentes comunidades de conocimiento tomando un instrumento náutico como “mediador”. Conclusiones: El artículo concluye que la consideración de las culturas empíricas del conocimiento y sus realizaciones materiales son una condición sine qua non para entender la génesis de la modernidad científica europea y la construcción de un mundo globalExplaining how and under what conditions some of the most emblematic scientific instruments of the modern world were built remains a challenge for historians of science and technology. This principle also affects nautical instruments. Thus, the objective of this article is to consider the “how” and the “under what conditions”, in a broad sense, by examining one of these devices: the nautical charts developed during the European maritime expansion. Originality: The originality of this article lies not only in the reconstruction of this instrument in Portugal and Spain, providing new information about its development process and its manufacturers, but also in shedding light on old historiographical debates that underlie the genesis of modern science, such as the difficult collaboration between practical men and theoretical men; the contribution of artisan communities to the world of knowledge; the role that practical knowledge played in the establishment of new forms of standardization in science; the adoption of an empirical methodology for achieving mastery of the world or the construction of large global empires founded upon manual labor. Methodology: Analyzing these debates requires a methodological approach that addresses the main categories and concepts put into circulation by the most recent history and philosophy of science. In short, unveiling the conditions that enabled the establishment of epistemological agreements (and also disputes) between different knowledge communities by taking a nautical instrument as “mediator.” Conclusions: The article concludes that examining empirical knowledge cultures and their material achievements are a sine qua non condition to understand the genesis of European scientific modernity and the construction of a global worldExplicar como e em que condições foram construídos alguns dos instrumentos científicos mais emblemáticos do mundo moderno continua sendo um desafio para os historiadores da ciência e da tecnologia. Esse princípio afeta também os instrumentos náuticos. Assim, o objetivo do presente artigo é considerar o “como” e o “em que condições”, em um sentido amplo, e analisar um desses artefatos: as cartas náuticas construídas durante a expansão marítima europeia. Originalidade: A originalidade do texto não reside unicamente na realização de uma reconstrução desse instrumento em Portugal e na Espanha de forma que traga novos dados sobre seu processo de fabricação e de seus fabricantes, mas também em lançar luz sobre antigos debates historiográficos que subjazem à gênese da ciência moderna, tais como a difícil colaboração entre homens práticos e homens teóricos, a contribuição de comunidades de artesãos ao mundo do conhecimento; o papel que os saberes práticos tiveram no estabelecimento de novas formas de padronização na ciência, a adoção de uma metodologia empírica para o domínio do mundo ou a construção de grandes impérios globais cimentados sobre a base do trabalho manual. Metodologia: A análise desses debates requer uma aproximação metodológica que atenda às categorias e aos principais conceitos colocados em circulação tanto pela história quanto pela filosofia da ciência mais recente. Definitivamente, trata-se de atender às condições que permitiram o estabelecimento de acordos (e também de controvérsias) epistemológicos entre diferentes comunidades de conhecimento tomando o instrumento náutico como “mediador”. Conclusões: O artigo conclui que a consideração das culturas empíricas do conhecimento e suas realizações materiais são uma condição sine qua non para entender a gênese da modernidade científica europeia e a construção de um mundo globa

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio