119 results on '"Meléndez B"'
Search Results
2. Révision de quelques echinodermes (Cystoïdes, Crinoïdes), de I'Ordovicièn supérieur des Pyrénées
- Author
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Chauvel, J., Meléndez, B., Chauvel, J., and Meléndez, B.
- Abstract
This paper is a review of some Cystoidea specimens collected at Alp and Pardines, located in the Pyrenees (province of Gerona), by Dr. M. Faura i Sans 75 years ago. Now a days, they are located in the Paleontological Museum of the Seminario of Barcelona. As a result of this study, we have determined with certainty, the species Heliocrinites rouvillei v. Koenen and Corylocrinus sp., though in this case, it has not been possible to determine the species, since they are internal casts, There is also a Crinoid columnar plate, Conspectocrinus celticus Le Menn, attached to one of the specimens. The age of these fossils is upper Caradoc, being similar to the ordovician fauna of the Montagne Noire, the Armorican Massif and the South Aragon (Spain)., Comprende este trabajo la revisión de los ejemplares de Cistideos procedentes de Alp y Pardines, en el Pirineo de la provincia de Gerona, que fueron recogidos, en su mayor parte, por el Dr. M. Faura i Sans, y forman parte actualmente de la colección del Museo Paleontologico del Seminario Conciliar de Barcelona. El resultado del estudio ahora realizado, ha permitido determinar la especie Heliocrinites rouvillei v. Koenen y Corylocnnus sp., aunque por tratarse en este caso de moldes internos, no ha sido posible determinar la especie. En uno de los ejemplares aparece un artejo de un crinoide, Conspectocrinus celticus Le Menn. La edad geologica de estos fósiles, en su conjunto, corresponde al Caradoc superior, pudiendo compararse con las. faunas ordovicicas de la Montagne Noire, del Macizo Armoricano y del Sur de Aragon, Depto. de Geodinámica, Estratigrafía y Paleontología, Fac. de Ciencias Geológicas, TRUE, pub
- Published
- 2023
3. Sur quelques Cystoidees cites par les Drs. J. Almera et M. Faura dans I'Ordovicien de Barcelone
- Author
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Meléndez, B., Chauvel, J., Meléndez, B., and Chauvel, J.
- Abstract
This paper is a revision of Cystoidea specimens collected late in the XIX century, by Drs. J. Almera and M. Faura at several Ordovician outcrops near Barcelona, that are currently inaccessible. These Cystoidea were classified by Ch. Barrois in 189 1 as Echinosphaerites cf. balticus EICHW.a, nd belong to the paleontological collections of the Geological Museums of Barcelona (Museo Municipal & Museo del Seminario Conciliar). The main conciusion of the study is that none of the specimens belongs to Heliocrinites (Echinosphaerites) balticus, but that al1 of them should be referred to Caryocrinites: one specimcn has been clasiified as Caryocrinites aff. europaeus QUENST.a, nd the rest of them should be referred to as Caryocrinites rugatus (FORBES)A. s a result, the geological age of the outcrops must be Ashgil1 instead of Caradoc, as was supposed by M. Faura., Depto. de Geodinámica, Estratigrafía y Paleontología, Fac. de Ciencias Geológicas, TRUE, pub
- Published
- 2023
4. AB1270 RHEUMATOLOGY WORKFORCE IN LATIN AMERICA: TRAINING AND CURRENT STATUS
- Author
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Fernández-Ávila, D. G., primary, Patino-Hernandez, D., additional, Kowalski, S., additional, Vargas-Caselles, A., additional, Sapag Durán, A. M., additional, Cachafeiro Vilar, A., additional, Meléndez, B., additional, Pastelín, C. S., additional, Graf, C., additional, Rossetto, C., additional, Palleiro, D., additional, Trincado, D., additional, Fernández-Ávila, D., additional, Arrieta, D., additional, Reyes, G., additional, Then, J., additional, Ugarte-Gil, M. F., additional, Cardiel, M., additional, Colman, N., additional, Chávez, N., additional, Burgos, P., additional, Montufar, R., additional, Sandino, S., additional, Fuentes-Silva, Y., additional, and Soriano, E., additional
- Published
- 2020
- Full Text
- View/download PDF
5. Cystic trigeminal schwannoma with fluid-fluid levels
- Author
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Méndez, J. C., Saucedo, G., and Meléndez, B.
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- 2004
- Full Text
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6. 291P Prognosis of glioblastoma according to different TERT promoter mutations
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Hernandez Gonzalez, A., Sanz, C., Mariño Siancas, C.A., Domenech Vinolas, M., Parra, G., Esteve, A.M., Carrato, C., Melendez, B., Esteve Codina, A., Martinez-Cardús, A., Alameda, F., Pineda, E., Muñoz, A., Lopez, R., and Balana, C.
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- 2022
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7. The deployment scheduling analysis tool (DSAT)
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Hodgson, T.J, Melendez, B, Thoney, K.A, and Trainor, T
- Published
- 2004
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8. Panobinostat potentiates temozolomide effects and reverses epithelial-mesenchymal transition in glioblastoma cells
- Author
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Urdiciain-Ezpeleta, A. (Alejandro), Meléndez, B. (Bárbara), Rey, J.A. (Jorge Alberto), Idoate, M.A. (Miguel Ángel), and Saez-Castresana, J. (Javier)
- Subjects
Panobinostat ,Temozolomide ,Glioblastoma ,Epithelial-mesenchymal transition - Abstract
Glioblastoma is the most common form of glioma, as well as the most aggressive. Patients suffering from this disease have a very poor prognosis. Surgery, radiotherapy, and temozolomide are the only approved treatments nowadays. Panobinostat is a pan-inhibitor of histone deacetylases (HDACs) that has been shown to break some pathways which play an important role in cancer development. A global intention of using panobinostat as a therapeutic agent against glioblastoma is beginning to be a reality. We have treated the LN405 glioblastoma cell line with temozolomide, panobinostat, and combined treatment, in order to test apoptosis, colony formation, and a possible molecular reversion of the mesenchymal phenotype of the cells to an epithelial one. Our results show that panobinostat decreased N-cadherin levels in the LN405 glioblastoma cell line while it increased the expression of E-cadherin, which might be associated with a mesenchymal–epithelial transition in glioblastoma cells. Colony formation was reduced, and apoptosis was increased with treatments. Our research highlights the importance of panobinostat as a potential adjuvant therapy to be used with temozolomide to treat glioblastoma and the advantages of the combined treatment versus temozolomide alone, which is currently the first-line treatment used to treat this tumor
- Published
- 2018
9. Fulminant Septic Shock in AIDS Patients Caused by Disseminated Cryptococcosis
- Author
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Lozano, F., Gómez-Mateos, J., Irles, J. A., Meléndez, B., and Martin, E.
- Published
- 1999
- Full Text
- View/download PDF
10. 33P - Tumour mutational burden ring trial: Evaluation of targeted next-generation sequencing platforms for implementation in clinical practice
- Author
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Lambin, S., Lambrechts, D., De Rop, C., D'Haene, N., Froyen, G., Heukamp, L., Huijsmans, C., Maes, B., Melendez, B., Van Campenhout, C., Vanden Bempt, I., van den Brule, A., Vander Borght, S., Vannuffel, P., and Pauwels, P.
- Published
- 2019
- Full Text
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11. Conformación de un portfolio eficiente de acciones IPSA, bajo efectos de la crisis subprime
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Arriagada O., Ximena, Meléndez B., Cristian, Fantóval C., Carolina, Toledo A., Rodrigo, Facultad de Economía y Negocios, and Escuela de Ingeniería Comercial
- Subjects
Índice de Precios Selectivo de Acciones ,Administración de Portfolio - Abstract
Tesis (Ingeniero Comercial) La incertidumbre en los mercados financieros, ha sido siempre el motor por el cual los inversionistas, buscan diferentes maneras de administrar el capital invertido. La importancia de este tema, se sitúa en el interés por parte de un inversor, en saber cual es el punto que le permitirla obtener un mayor retorno, asumiendo un nivel de riesgo determinado, puesto que el máximo nivel de rentabilidad que el inversionista espera obtener, está asociado al grado de tolerancia que este, tiene frente al riesgo, y justamente lo interesante de este estudio, radica en su principal propósito, el cual corresponde a encontrar la combinación óptima de un portfolio de acciones IPSA, que le permitan al inversor, obtener el mayor retorno posible, tomando en cuenta el nivel de riesgo que está dispuesto a asumir. Siendo este último punto de gran importancia, producto de la actual estado en el que se encuentran los mercados financieros internacionales. De este modo, tomando en consideración el propósito de este trabajo, la pregunta que servirá de guía en el presente estudio, se presenta a continuación: ¿Es posible conformar un Portfolio óptimo de acciones IPSA, que maximice la rentabilidad esperada en tiempos de crisis, asumiendo que se cumplen los supuestos de la Teoría de Carteras? Por lo tanto conforme a la pregunta antes formulada, la hipótesis supone que si se asumen los supuestos de Teoría de Carteras, entonces seria posible conformar un portfolio óptimo de acciones IPSA que maximice la rentabilidad esperada en tiempos de crisis.
- Published
- 2008
12. Stimulation of the midkine/ALK axis renders glioma cells resistant to cannabinoid antitumoral action
- Author
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Lorente, M, primary, Torres, S, additional, Salazar, M, additional, Carracedo, A, additional, Hernández-Tiedra, S, additional, Rodríguez-Fornés, F, additional, García-Taboada, E, additional, Meléndez, B, additional, Mollejo, M, additional, Campos-Martín, Y, additional, Lakatosh, S A, additional, Barcia, J, additional, Guzmán, M, additional, and Velasco, G, additional
- Published
- 2011
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13. Short Communication: Carora Cattle Show High Variability in αs1-Casein
- Author
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Caroli, A., primary, Chessa, S., additional, Chiatti, F., additional, Rignanese, D., additional, Meléndez, B., additional, Rizzi, R., additional, and Ceriotti, G., additional
- Published
- 2008
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14. Characterization of the A673 cell line (Ewing tumor) by molecular cytogenetic techniques
- Author
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Martı́nez-Ramı́rez, A, primary, Rodrı́guez-Perales, S, additional, Meléndez, B, additional, Martı́nez-Delgado, B, additional, Urioste, M, additional, Cigudosa, J.C, additional, and Benı́tez, J, additional
- Published
- 2003
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15. P189 Lung-free lymphomatoid granulomatosis and Crohn's disease: An unknown association
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Estepa, R., Medina, C., Piñero, A., Martin, E., Melendez, B., Castro, T., Ferrer, A., and Garcia, F.
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- 2014
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16. Instability of the D4Mit12 microsatellite marker in C57BL/6J × BALB/cJ F1 hybrid mice is independent of the tumor phenotype
- Author
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Herranz, M., primary, Santos, J., additional, Pérez de Castro, I., additional, Meléndez, B., additional, and Fernández-Piqueras, J.., additional
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- 1997
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17. 574 Methylation Profile in Oligodendroglial Tumours
- Author
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Mur, P., Perez-Magan, E., Mollejo, M., Fiano, C., Garcia, J.F., Rey, J.A., and Melendez, B.
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- 2012
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18. 477 Copy number alterations of glioma cell lines detected by array-based CGH show preferential loss of genetic material and no high-level EGFR amplification
- Author
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Garcia-Claver, A., Blesa, D., Velasco, G., Campos-Martín, Y., Ruano, Y., Perez-Magan, E., Rodriguez de Lope, A., Mollejo, M., and Melendez, B.
- Published
- 2010
- Full Text
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19. Arenig trace fossils from the Salamanca area, western Spain.
- Author
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Pickerill, R. K., Romano, M., and Meléndez, B.
- Published
- 1984
- Full Text
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20. Characterization of the murine p19(ARF) promoter CpG island and its methylation pattern in primary lymphomas.
- Author
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Meléndez, B, Malumbres, M, Pérez de Castro, I, Santos, J, Pellicer, A, and Fernández-Piqueras, J
- Abstract
The INK4a/ARF locus encodes two different proteins involved in cell cycle control. Both molecules, p16(INK4a) and p19(ARF), inhibit cell cycle progression and have been shown to act as tumor suppressors in a variety of models. Their expression is controlled by separate promoters responding to different stimuli and they therefore show independent transcriptional regulation. We have cloned and characterized a 2.5 kb region upstream of the murine p19(ARF) gene to determine the role of DNA methylation in suppressing p19(ARF) transcription in a wide panel of murine primary T cell lymphomas. This region contains a DNA fragment with the characteristics of a CpG island similar to those described for the murine p16(INK4a) and p15(INK4b) genes. Expression of p19(ARF) is decreased in a significant number (20%) of the murine lymphomas analyzed. Overexpression of the p19(ARF) transcript is also frequent, suggesting alterations in molecules of the retinoblastoma or p53 pathways that are involved in p19(ARF) regulation. Although hypermethylation of the INK4a and INK4b promoters is frequently involved in murine lymphomas, the p19(ARF) CpG island is infrequently methylated in the murine primary lymphomas studied in this work. Since loss of p19(ARF) expression cannot be explained as the result of homozygous deletions or hypermethylation of the ARF gene, other regulatory mechanisms seem to be altered in these malignancies.
- Published
- 2000
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21. Sur quelques Cystoidées cités par les Drs. J. Almera et M.Faura dans l'Ordovicien de Barcelone
- Author
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MELÉNDEZ, B. and CHAUVEL, J.
- Subjects
Barcelona ,Ordovício ,Cystoideos - Abstract
This paper is a revision of Cystoidea specimens collected late in the XIX century, by Drs. J. Almera and M. Faura at several Ordovician outcrops near Barcelona, that are currently inaccessible. These Cystoidea were classified by Ch. Barrois in 189 1 as Echinosphaerites cf. balticus EICHW.a, nd belong to the paleontological collections of the Geological Museums of Barcelona (Museo Municipal & Museo del Seminario Conciliar). The main conciusion of the study is that none of the specimens belongs to Heliocrinites (Echinosphaerites) balticus, but that al1 of them should be referred to Caryocrinites: one specimcn has been clasiified as Caryocrinites aff. europaeus QUENST.a, nd the rest of them should be referred to as Caryocrinites rugatus (FORBES)A. s a result, the geological age of the outcrops must be Ashgil1 instead of Caradoc, as was supposed by M. Faura.
- Published
- 1979
22. Nouvelle interpretation des echinodermes de Collado de Tosas (Gerona, Espagne)
- Author
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Meléndez, B. and Le Menn, J.
- Subjects
QE1-996.5 ,lcsh:QE1-996.5 ,Ordovicico ,Ordovician ,Crinoides ,Geology ,Equinodermos ,lcsh:Geology ,Crinoids ,ordovicico ,equinodermos ,crinoides ,Echinoderms - Abstract
The revision of the echinoderms from Collado de Tosas, based on the original specimens and additional material, is undertaken. The study shows that the initial attribution to the genus Trochocystites belonging to the Homalozoa Cincta has been induced by the tectonic deformation and the presence of recristallization lamellae in the natural molds. New observations allow to conclude without ambiguity that these skeletal elements are isolated columnals with a broad lumen, of crinoids. The presence of Cambrian in the section, established exclusively on the initial determinations, cannot longer be maintained.Los fósiles de Equinodermos del Collado de Tosas fueron dados a conocer en 1911 por F. Azpeitia que los atribuyó a Trochocystites bohemicus Bar. Posteriormente, M. Faura (1912) hizo notar la presencia de fósiles ordovícicos en esta misma localidad, y propuso una interpretación estratigráfica que incluía un contacto anómalo con el supuesto Cámbrico determinado por los Trochocystites. Todo ello fue revisado por B. Meléndez en 1954, que creyó poder confirmar que los fósiles en cuestión (fig. 1), eran realmente Carpoideos. El estudio de nuevo material recogido in situ, así como de los ejemplares conservados en el Museo del Seminario Conciliar de Barcelona, nos ha llevado a la conclusión de que la atribución inicial de estos discutidos fósiles al género Trochocystites, fue debida a la deformación tectónica que les ha dado forma ovalada, y a la presencia de láminas de recristalización, en disposición radial, en los moldes (fig. 6, lám. 1), que dan la falsa apariencia de placas marginales. Las nuevas observaciones nos permiten afirmar que estos fósiles son placas columnales, aisladas, probablemente del pedúnculo de Crinoides, con cavidad central muy amplia (Iám. 1, figs. 15), aunque eventualmente, también podrían haber pertenecido a Cystideos. En consecuencia, la presencia del Cámbrico en esta localidad, basada únicamente en la determinación inicial, errónea, de estos fósiles, debe ser descartada. De acuerdo con el contexto estratigráfico y las características litológicas del material, los repetidos fósiles podrían pertenecer al Ordovícico, probablemente al Caradoc.
- Published
- 1988
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23. Los equinodermos (Cystoidea. Homalozoa. Stelleroidea. Crinoidea) del Paleozoico Inferior de los Montes de Toledo y Sierra Morena (España)
- Author
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Gutiérrez Marco, J. C., Chauvel, J., Meléndez, B., and Smith, A. B.
- Subjects
revisión ,review ,bioestratigrafía ,zona de Ossa Morena ,Stelleroidea ,Llandeilo ,zona Centro-ibérica ,Central-iberian zone ,«capas con Tristani» ,Stylophora ,biogeografía ,Ossa Morena zone ,new description ,Crinoidea ,biogeography ,Ordovícico ,Diploporita ,biostratigrapby ,España ,nueva descripción ,Homostelea ,Stylopbora ,Ordovician ,Cámbrico ,Llanvirn ,Cambrian ,«Tristani beds» ,Echinodermata ,Spain - Abstract
The presence of the cystoids Codiocystis and Phiyctocystis in the Llandeilo of Spain, associated to an undetermined Diploporite which may be a new genus, in confirmed. Several species of the genus Calix are described, some of them in open nomenclature, certain forms bearing a pentaradiated peristome. New samples of Homalozoa collected in the Middle Cambrian of Sierra Morena (Decacystis) and the Lower Llanvirn of the Toledo Mountains (Mitrocystites) are quotated, as well as an Asterozoa (Polaeura), found for the first time in Spain. The study of the echinoderm fauna collected in the "Tristani beds" (Llanvirn-Llandeilo) of the Spanish Central-iberian zone allow to establish conclusions of biostratigraphic and paleobiogeographic interest. Se confirma la presencia de los cistideos Codlocystis y Phlyctocystis en el Llandeilo de España, junto a un Diploporito indeterminado que quizá corresponda a un nuevo género. Se describen diversas especies del género Calix, alguna de ellas en nomenclatura abierta, observándose en ciertas formas la existencia de un peristoma pentarradiado. Se citan nuevos ejemplares de Homalozoos procedentes del Cámbrico medio de Sierra Morena (Decocystls) y del Llanvirn inferior de los Montes de Toledo (Mitrocystites), así como un Asterozoo, perteneciente al género Palaeura, descubierto por vez primera en España. El análisis de la fauna de equinodermos de las "capas con Tristani" (Llanvirn-Llandeilo) de la zona Centro-ibérica española, perm ite, además, establecer diversas conclusiones de interés bioestratigráfico y paleobiogeográfico.
- Published
- 1984
- Full Text
- View/download PDF
24. Nuevos hallazgos de Estilóforos (Homalozoos) en los materiales ordovícicos de la zona Centroibérica
- Author
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Gutiérrez-Marco, J. C. and Meléndez, B.
- Subjects
Zona Centroibérica ,Central Iberian Zone ,Spain ,Stylophora ,España ,Ordovician ,Estilóforos ,Homalozoos ,Homalozoa ,Ordovícico - Abstract
10 páginas, 6 figuras., [EN] The first determinable species of Ordovician Stylophora of the Hesperian Massif is described. The two specimens studied come from two localities of the Ciudad Real province, both of Dobrotivian (Llandeilian) age, and pertaining to the lower Guindo Shales (top of the Tournemini Biozone). Both are considered as Mitrocystella incipiens miloni CHAUVEL (Stylophora, Mitrata) a previously recorded species from three localities of the French Armorican Massif., [ES] Se describen los primeros restos de estilóforos ordovícicos determinables a nivel específico encontrados en el Macizo Hespérico. Los dos ejemplares estudiados proceden de sendas localidades de edad Dobrotiviense (Llandeilo) enclavadas en la provincia de Ciudad Real, que pertenecen a su vez a la parte inferior de las Pizarras Guindo (techo de la Biozona Tournemini) Ambos han sido determinados como Mítrocystella incipiens miloni, CHAUVEL (Stylophora, Mitrata), una forma conocida previamente en tres localidades del Macizo Armoricano francés., Este trabajo es una contribución al Proyecto núm. 2-454-2 (ID 456) financiado por la CAICYT y el CSIC a través del Instituto de Geología Económica (CSIC-UCM).
- Published
- 1987
25. Révision de quelques echinodermes (Cystoïdes, Crinoïdes), de l'Ordovicièn supérieur des Pyrénées
- Author
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CHAUVEL, J. and MELÉNDEZ, B.
- Abstract
This paper is a review of some Cystoidea specimens collected at Alp and Pardines, located in the Pyrenees (province of Gerona), by Dr. M. Faura i Sans 75 years ago. Now a days, they are located in the Paleontological Museum of the Seminario of Barcelona. As a result of this study, we have determined with certainty, the species Heliocrinites rouvillei v. Koenen and Corylocrinus sp., though in this case, it has not been possible to determine the species, since they are internal casts, There is also a Crinoid columnar plate, Conspectocrinus celticus Le Menn, attached to one of the specimens. The age of these fossils is upper Caradoc, being similar to the ordovician fauna of the Montagne Noire, the Armorican Massif and the South Aragon (Spain).
- Published
- 1981
26. Instability of the D4Mit12 microsatellite marker in C57BL/6J × BALB/cJ F1 hybrid mice is independent of the tumor phenotype.
- Author
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Herranz, M., Santos, J., Pérez de Castro, I., Meléndez, B., and Fernández-Piqueras, J..
- Published
- 1997
- Full Text
- View/download PDF
27. Los equinodermos (Cystoidea. Homalozoa. Stelleroidea. Crinoidea) del Paleozoico Inferior de los Montes de Toledo y Sierra Morena (España)
- Author
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Gutiérrez-Marco, J. C., Chauvel, J., Meléndez, B., Smith, A. B., Gutiérrez-Marco, J. C., Chauvel, J., Meléndez, B., and Smith, A. B.
- Abstract
[ES] Se confirma la presencia de los cistideos Codlocystis y Phlyctocystis en el Llandeilo de España, junto a un Diploporito indeterminado que quizá corresponda a un nuevo género. Se describen diversas especies del género Calix, alguna de ellas en nomenclatura abierta, observándose en ciertas formas la existencia de un peristoma pentarradiado. Se citan nuevos ejemplares de Homalozoos procedentes del Cámbrico medio de Sierra Morena (Decocystls) y del Llanvirn inferior de los Montes de Toledo (Mitrocystites), así como un Asterozoo, perteneciente al género Palaeura, descubierto por vez primera en España. El análisis de la fauna de equinodermos de las "capas con Tristani" (Llanvirn-Llandeilo) de la zona Centro-ibérica española, perm ite, además, establecer diversas conclusiones de interés bioestratigráfico y paleobiogeográfico., [EN] The presence of the cystoids Codiacystis and Phlyctocystis in the Llandeilo of Spain, associated to an undetermined Diploporite which may be a new genus, in confirmed. Several species of the genus Calix are described, some of them in open nomenclature, certain forms bearing a pentaradiated peristorne. New samples of Homalozoa collected in the Middle Cambrian of Sierra Morena (Decacystis) and the Lower Llanvirn of the Toledo Mountains (Mitrocystites) ara quotated, as well as an Asterozoa (Palaeura), found for the first time in Spain. The study of the echinoderm fauna collected in the "Tristani beds" (Llanvirn-Llandeilo) of the Spanish Central-iberian zone allow to establish conclusions of biostratigraphic and paleobiogeographic interest.
- Published
- 1984
28. Estudios paleontológicos en el Mioceno de la región bética
- Author
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Meléndez, B. and Meléndez, B.
- Abstract
Una de las conclusiones de la 2.ª Reunión del Comité del Neógeno del Mediterráneo, que tuvo lugar en España en 1961, aconsejaba realizar estudios paleontológicos con objeto de encontrar un nuevo "Estrato- tipo" y una nueva denominación para sustituir los términos estratigráficos "Mesiniense" y "Saheliense", que no se consideraron adecuados, por no reunir las condiciones impuestas por la Comisión de Estratigrafía del Congreso Geológico Internacional. A la vista de esta decision, la Sección de Paleontologia de Madrid del Instituto Lucas Mallada ha llevado a cabo una serie de trabajos paleontológicos relacionados con el Neógeno de Andalucía, con objeto de localizar una fauna fósil que fuese característica del Mioceno terminal.
- Published
- 1966
29. Microarray-based comparative genomic hybridization (array-CGH) as a useful tool for identifying genes involved in Glioblastoma (GB)
- Author
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Ruano, Y., Manuela Mollejo, Lope, A. R., Hernández-Moneo, J. L., Martínez, P., and Meléndez, B.
30. Multiplex-polymerase chain reaction assay for the detection of prognostically significant translocations in acute lymphoblastic leukemia
- Author
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Marín C, Martínez-Delgado B, Meléndez B, Mj, Larrayoz, Martínez-Ramírez A, Robledo M, Jc, Cigudosa, MJ Calasanz, and Benítez J
- Subjects
Humans ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Child ,Prognosis ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Translocation, Genetic - Abstract
The presence of specific chromosomal translocations in acute lymphoblastic leukemias (ALL) plays an important role in determining the prognosis of the patients. Our aim is to develop a highly sensitive and specific method to screen simultaneously for the four most frequent translocations in ALL: t(9;22), t(1;19), t(4;11), t(12;21).Our approach uses a multiplex-polymerase chain reaction (PCR) method, which involves two rounds of PCR using fluorescence-labeled nested primers. The chimeric transcripts resulting from these translocations can be identified by agarose gel electrophoresis or by fluorescence analysis. To validate this method we carried out the analysis in 42 pediatric ALL samples previously studied by cytogenetic and fluorescent in situ hybridization (FISH) techniques.In all samples with a known translocation detected by cytogenetic or FISH techniques, the same translocation was identified by the multiplex-PCR assay. Moreover, with this method we detected rearrangements in five patients in clinical remission and in two patients at diagnosis for whom karyotypes were normal and rearrangements had not been detected. The application of this multiplex-PCR assay was also useful in cases without cytogenetic results.These results show that the multiplex-PCR method allows reliable, sensitive and rapid detection of the prognostically significant translocations in ALL. We believe that this assay combined with cytogenetic analysis should be the strategy of choice for the initial diagnostic phase of acute lymphoblastic leukemia, and that it could be used not only at diagnosis but also to follow-up these alterations in remission samples without previous controls.
31. Estudios Geológicos
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Le Menn, J., primary and Meléndez, B., additional
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- 1988
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32. Note complementaire sur les echinodermes ordoviciens de Sierra Morena
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Chauvel, J., primary and Meléndez, B., additional
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- 1986
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33. Instability of the D4Mit12 microsatellite marker in C57BL/6J × BALB/cJ F1hybrid mice is independent of the tumor phenotype
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Herranz, M., Santos, J., Pérez de Castro, I., Meléndez, B., and Fernández-Piqueras, J..
- Abstract
We examined the stability of different types of DNA microsatellite markers in γ-radiation-induced thymic lymphomas as well as normal, nontumorous tissues of F
1 hybrid mice derived from the parental strains C57BL/6J, RF/J, and BALB/cJ. Surprisingly, the D4Mit12 microsatellite showed genomic instability in a significant fraction of DNAs of the (C57BL/6J × BALB/cJ) F1 hybrids with independence of the tumor phenotype. This instability was not found in the reciprocal F1 DNAs, in DNAs of the parental strains, or in DNAs of (C57BL/6J × RF/J) F1 hybrid mice. These results suggest that the instability of the D4Mitl2 microsatellite is dependent on its repeat length, the genetic background of F1 hybrids, and the maternal origin of the C57BL/6J allele.- Published
- 1997
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34. Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling
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Hernández-Moneo Jose-Luis, de Lope Angel, Gómez Elena, Camacho Francisca I, Fiaño Concepción, Ribalta Teresa, Mollejo Manuela, Ruano Yolanda, Martínez Pedro, and Meléndez Bárbara
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Conventional cytogenetic and comparative genomic hybridization (CGH) studies in brain malignancies have shown that glioblastoma multiforme (GBM) is characterized by complex structural and numerical alterations. However, the limited resolution of these techniques has precluded the precise identification of detailed specific gene copy number alterations. Results We performed a genome-wide survey of gene copy number changes in 20 primary GBMs by CGH on cDNA microarrays. A novel amplicon at 4p15, and previously uncharacterized amplicons at 13q32-34 and 1q32 were detected and are analyzed here. These amplicons contained amplified genes not previously reported. Other amplified regions containg well-known oncogenes in GBMs were also detected at 7p12 (EGFR), 7q21 (CDK6), 4q12 (PDGFRA), and 12q13-15 (MDM2 and CDK4). In order to identify the putative target genes of the amplifications, and to determine the changes in gene expression levels associated with copy number change events, we carried out parallel gene expression profiling analyses using the same cDNA microarrays. We detected overexpression of the novel amplified genes SLA/LP and STIM2 (4p15), and TNFSF13B and COL4A2 (13q32-34). Some of the candidate target genes of amplification (EGFR, CDK6, MDM2, CDK4, and TNFSF13B) were tested in an independent set of 111 primary GBMs by using FISH and immunohistological assays. The novel candidate 13q-amplification target TNFSF13B was amplified in 8% of the tumors, and showed protein expression in 20% of the GBMs. Conclusion This high-resolution analysis allowed us to propose novel candidate target genes such as STIM2 at 4p15, and TNFSF13B or COL4A2 at 13q32-34 that could potentially contribute to the pathogenesis of these tumors and which would require futher investigations. We showed that overexpression of the amplified genes could be attributable to gene dosage and speculate that deregulation of those genes could be important in the development and progression of GBM. Our findings highlight the important influence in GBM of signaling pathways such as the PI3K/AKT, consistent with the invasive features of this tumor.
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- 2006
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35. Identification of amplified and highly expressed genes in amplicons of the T-cell line huT78 detected by cDNA microarray CGH
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Díaz-Uriarte Ramón, Fernández Victoria, Cuadros Marta, Martínez-Delgado Beatriz, Meléndez Bárbara, and Benítez Javier
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Conventional Comparative Genomic Hybridization (CGH) has been widely used for detecting copy number alterations in cancer and for identifying regions containing candidate tumor responsible genes. Recently, several studies have shown the utility of cDNA microarray CGH for studing gene copy changes in various types of tumors. However, no such studies on T-cell lymphomas have been performed. To date T-cell lymphomas analyzed by the use of chromosome CGH have revealed only slight copy number alterations and not gene amplifications. Results In the present study, we describe the characterization of three amplicons of the T-cell line huT78 located at 2q34-q37, 8q23-q24 and 20p, where new amplified and overexpressed genes are found. The use of a cDNA microarray containing 7.657 transcripts allowed the identification of certain genes, such as BCLX, PCNA, FKBP1A, IGFBP2 and cMYC, that are amplified, highly expressed, and also contained in the amplicons on 20p and 2q. The expresion of these genes was analyzed in 39 T-cell lymphomas and 3 other T-cell lines. Conclusion By the use of conventional CGH and CGH and expression cDNA microarrays we defined three amplicons in the T-cell line huT78 and identified several novel gene amplifications (BCLX, PCNA, FKBP1A, IGFBP2 and cMYC). We showed that overexpression of the amplified genes could be attributable to gene dosage. We speculate that deregulation of those genes could be important in the development of T-cell lymphomas and/or in the maintenance of T-cell lines.
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- 2005
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36. P04.18 PROGNOSIS IMPACT OF THE REGIONAL DISTRIBUTION OF MGMT GENE METHYLATION ACCORDING TO THE CPGISLAND METHYLATOR PHENOTYPE AND AGE IN HIGH-GRADE GLIOMAS.
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Mur, P., de Lope, A. Rodriguez, Hernandez-Iglesias, T., Diaz, F., Ribalta, T., Fiaño, C., Garcia, J.F., Rey, J.A., Mollejo, M., and Meléndez, B.
- Published
- 2014
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37. MOLECULAR ANALYSIS OF EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) AND TP53 IN HUMAN GLIOMAS. A TISSUE MICROARRAY-BASED STUDY.
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Ruano, Y, Meléndez, B, Fiaño, C, Hernandez-Moneo, J L, Casado, A, Toscas, I, Martinez, P, Mollejo, M, and Ribalta, T
- Published
- 2004
38. Short Communication: Carora Cattle Show High Variability in αs1-Casein.
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Caroli, A., Chessa, S., Chiatti, F., Rignanese, D., Meléndez, B., Rizzi, R., and Ceriotti, G.
- Subjects
- *
MILK proteins , *CATTLE , *CASEINS , *GENES , *BREEDING - Abstract
The objective of this study was to analyze the genetic variability of milk proteins of the Carora, a shorthorned Bos taurus cattle breed in Venezuela and in other Southern American countries that is primarily used for milk production. A total of 184 individual milk samples were collected from Carora cattle in 5 herds in Venezuela. The milk protein genes αs1-casein (CN) (CSN1S1), β-CN (CSN2), κ-CN (CSN3), and β-lactoglobulin (LGB) were typed at the protein level by isoelectrofocusing. It was necessary to further analyze CSN1S1 at the DNA level by a PCR-based method to distinguish CSN1S1*G from B. Increased variation was found in particular at the CSN1S1 gene, where 4 variants were identified. The predominant variant was CSN1SI*B (frequency = 0.8). The second most common CSN1S1 variant was CSN1SI*G (0.101), followed by CSN1S1*C (0.082). Moreover, a new isoelectrofocusing pattern was identified, which may result from a novel CSN1S1 variant, named CSN1S1*I, migrating at an intermediate position between CSN1S1*B and CSN1S1*C. Six cows carried the variant at the heterozygous condition. For the other loci, predominance of CSN2*A² (0.764), CSN3*B (0.609), and LGB*B (0.592) was observed. Haplotype frequencies (AF) at the CSN1S1-CSN2-CSN3 complex were also estimated by taking association into account. Only 7 haplotypes showed AF values >0.05, accounting for a cumulative frequency of 0.944. The predominant haplotype was B-A²-B (frequency = 0.418), followed by B-A²-A (0.213). The occurrence of the G variant is at a rather high frequency, which is of interest for selection within the Carora breed because of the negative association of this variant with the synthesis of the specific protein. From a cheese-making point of view, this variant is associated with improved milk-clotting parameters but is negatively associated with cheese ripening. Thus, milk protein typing should be routinely carried out in the breed, with particular emphasis on using a DNA test to detect the CSN1IS*G variant. The CSN1S*G allele is likely to have descended from the Brown Swiss, which contributed to the Carora breed and also carries this allele. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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39. Genomic profile analysis of leiomyomas with bizarre nuclei and fumarate hydratase deficient leiomyomas: Strengths, weaknesses, and limitations of array-CGH interpretation.
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Fontanges Q, Dubos P, Lesluyes T, Laizet Y, Velasco V, Meléndez B, D'Haene N, Oliva E, Young RH, Mayeur L, Rebier F, Alamé M, Larmonier C, Devouassoux-Shisheboran M, Arnould L, Soubeyran I, Chakiba C, Floquet A, Babin G, Guyon F, Mery E, Le Guellec S, Noël JC, Croce S, and Chibon F
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- Female, Humans, Fumarate Hydratase genetics, Genes, p53, Genomics, Uterine Neoplasms genetics, Uterine Neoplasms pathology, Leiomyoma genetics, Leiomyoma pathology
- Abstract
A close relationship has been demonstrated between genomic complexity and clinical outcome in uterine smooth muscle tumors. We studied the genomic profiles by array-CGH of 28 fumarate hydratase deficient leiomyomas and 37 leiomyomas with bizarre nuclei (LMBN) from 64 patients. Follow-up was available for 46 patients (from three to 249 months, mean 87.3 months). All patients were alive without evidence of disease. For 51 array-CGH interpretable tumors the mean Genomic Index (GI) was 16.4 (median: 9.8; from 1 to 57.8), significantly lower than the mean GI in LMS (mean GI 51.8, p < 0.001). We described three groups: (1) a group with FH deletion (24/58) with low GI (mean GI: 11 vs. 22,4, p = 0.02), (2) a group with TP53 deletion (17/58) with higher GI (22.4 vs. 11 p = 0.02), and (3) a group without genomic events on FH or TP53 genes (17/58) (mean GI:18.3; from 1 to 57.8). Because none of these tumors recurred and none showed morphological features of LMS we concluded that GI at the cut-off of 10 was not applicable in these subtypes of LM. By integration of all those findings, a GI <10 in LMBN remains a valuable argument for benignity. Conversely, in LMBN a GI >10 or alteration in tumor suppressor genes, should not alone warrant a diagnosis of malignancy. Nine tumors were tested with Nanocind CINSARC® signature and all were classified in low risk of recurrence. We propose, based on our observations, a diagnostic approach of these challenging lesions., (© 2024 Wiley Periodicals LLC.)
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- 2024
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40. Glioblastoma Biology, Genetics and Possible Therapies.
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Castresana JS and Meléndez B
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- Humans, Drug Resistance, Neoplasm, Glioblastoma genetics, Glioblastoma pathology, Glioblastoma therapy, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms therapy
- Abstract
Glioblastoma is the most aggressive intracranial tumor [...].
- Published
- 2023
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41. An analysis of prognostic factors in a cohort of low-grade gliomas and degree of consistency between RTOG and EORTC scores.
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Pérez IF, Valverde D, Valverde CF, Iglesias JB, Silva MJV, Quintela ML, and Meléndez B
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- Adult, Humans, Isocitrate Dehydrogenase genetics, Mutation, Prognosis, Brain Neoplasms radiotherapy, Brain Neoplasms therapy, Glioma diagnosis, Glioma genetics, Glioma therapy
- Abstract
Due to their rarity and heterogeneity and despite the introduction of molecular features in the current WHO classification, clinical criteria such as those from the European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) are still being used to make treatment decisions in low-grade gliomas (LGG). Patients with diffuse low-grade glioma treated at our institution between 2002 and 2018 were analyzed, retrieving and assessing the degree of consistency between the EORTC and RTOG criteria, as well as the isocitrate dehydrogenase 1 and 2 (IDH) gene mutational status. Likewise, multivariate analyses were performed to ascertain the superiority of any of the factors over the others. One hundred and two patients were included. The degree of consistency between the RTOG and EORTC criteria was 71.6% (K = 0.426; p = 0.0001). Notably, 51.7% of those assigned to low risk by the EORTC were classified as high risk according to the RTOG classification. In multivariate analysis, only complete resection, age > 40 years, size and IDH mutation status were independently correlated with OS. When the RTOG and EORTC scores were entered into the model, only the EORTC model was independently associated with mortality. The degree of consistency between the EORT and RTOG criteria is low. Therefore, there is a need to integrate clinical-molecular scores to improve treatment decisions in LGG., (© 2022. The Author(s).)
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- 2022
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42. Rheumatology Training in Latin America: A Collaborative Study by the Pan American League of Associations for Rheumatology.
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Fernández-Ávila DG, Patino-Hernandez D, Kowalskii S, Vargas-Caselles A, Sapag AM, Cachafeiro-Vilar A, Meléndez B, Santiago-Pastelín C, Graf C, Rossetto C, Palleiro D, Trincado D, Fernández-Ávila DC, Arrieta D, Reyes G, Baez JT, Ugarte-Gil MF, Cardiel M, Colman N, Chávez N, Burgos PI, Montufar R, Sandino S, Fuentes-Silva Y, and Soriano ER
- Subjects
- Cross-Sectional Studies, Humans, Latin America epidemiology, Rheumatologists, Rheumatic Diseases epidemiology, Rheumatic Diseases therapy, Rheumatology
- Abstract
Background/objective: Demand for rheumatology care has steadily increased in recent years. The number of specialists in this field, however, seems insufficient. No recent studies have diagnosed the attributes of rheumatology training in Latin America., Methods: This is a descriptive cross-sectional study. We obtained data on each country through local rheumatologists of the Pan-American League Against Rheumatism, who acted as principal investigators for participating countries. Our sample was analyzed and described through means and standard deviations or through frequencies and percentages, depending on the variable., Results: Countries with the most rheumatology-training programs were Brazil (n = 50), Argentina (n = 18), and Mexico (n = 15). Ecuador, Honduras, and Nicaragua do not have rheumatology-training programs. The countries with the most available slots for rheumatology residents were Brazil (n = 126) and Argentina (n = 36). To be admitted into rheumatology training, candidates were required to have completed graduate studies in internal medicine in 42.1% of the programs. In 8 countries (42.1%), residents are not required to pay tuition; the median cost of tuition in the remaining countries is US $528 (interquartile range, US $2153)., Conclusions: Conditions associated with rheumatology training in Latin America vary. Significant differences exist in income and tuition fees for residents, for example, and 4 countries in Latin America do not currently offer programs. Information collected in this study will be useful when comparing the status of rheumatology services offered in Latin America with those in other countries. Most countries require a wider offering of rheumatology-training programs, as well as more available slots., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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43. Impact of COVID-19 pandemic on patients with rheumatic diseases in Latin America.
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Fernández-Ávila DG, Barahona-Correa J, Romero-Alvernia D, Kowalski S, Sapag A, Cachafeiro-Vilar A, Meléndez B, Pastelín C, Palleiro D, Arrieta D, Reyes G, Pons-Estel GJ, Then-Báez J, Ugarte-Gil MF, Cardiel MH, Colman N, Chávez N, Burgos PI, Montufar R, Sandino S, Fuentes-Silva YJ, and Soriano ER
- Subjects
- Cross-Sectional Studies, Humans, Latin America, Pandemics, Antirheumatic Agents therapeutic use, COVID-19, Health Knowledge, Attitudes, Practice, Rheumatic Diseases drug therapy
- Abstract
The objective of our study was to describe knowledge, attitudes and practices of Latin-American rheumatology patients regarding management and follow-up of their disease during COVID-19 pandemic. A cross-sectional observational study was conducted using a digital anonymous survey. Rheumatic patients ≥ 18 years from non-English-speaking PANLAR countries were included. Our survey included 3502 rheumatic patients living in more than 19 Latin-American countries. Median age of patients was 45.8(36-55) years and the majority (88.9%) was female. Most frequently self-reported disease was rheumatoid arthritis (48.4%). At least one anti-rheumatic treatment was suspended by 23.4% of patients. Fear of contracting SARS-Cov2 (27.7%) and economic issues (25%) were the most common reasons for drug discontinuation. Self-rated disease activity increased from 30 (7-50) to 45 (10-70) points during the pandemic. Communication with their rheumatologist during the pandemic was required by 55.6% of patients, mainly by telephone calls (50.2%) and social network messages (47.8%). An adequate knowledge about COVID-19 was observed in 43% of patients. Patients with rheumatic diseases in Latin America were negatively affected by the COVID-19 pandemic. An increase in self-rated disease activity, a reduction in medication adherence, and hurdles for medical follow-up were reported. Teleconsultation was perceived as a valid alternative to in-person visits during the pandemic., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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44. Impact of COVID-19 Pandemic on Rheumatology Practice in Latin America.
- Author
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Fernández-Ávila DG, Barahona-Correa J, Romero-Alvernia D, Kowalski S, Sapag A, Cachafeiro-Vilar A, Meléndez B, Santiago-Pastelín C, Palleiro D, Arrieta D, Reyes G, Pons-Estel GJ, Then-Báez J, Ugarte-Gil MF, Cardiel MH, Colman N, Chávez N, Burgos PI, Montúfar R, Sandino S, Fuentes-Silva YJ, and Soriano ER
- Subjects
- COVID-19 Testing, Cross-Sectional Studies, Female, Humans, Latin America epidemiology, Middle Aged, Pandemics, SARS-CoV-2, Surveys and Questionnaires, COVID-19, Rheumatology
- Abstract
Objective: To describe the effect of the coronavirus disease 2019 (COVID-19) pandemic on Latin American rheumatologists from a professional, economic, and occupational point of view., Methods: We conducted an observational cross-sectional study using an online survey sent to rheumatologists of each non-English-speaking country member of the Pan American League of Rheumatology Associations (PANLAR). A specific questionnaire was developed., Results: Our survey included 1097 rheumatologists from 19 Latin American countries. Median (IQR) age of respondents was 48 (40-59) years and 618 (56.3%) were female. Duration of practice since graduation as a rheumatologist was 17 years, and 585 (53.3%) were aged < 50 years. Most rheumatologists worked in private practice (81.8%) and almost half worked in institutional outpatient centers (55%) and inpatient care (49.9%). The median number of weekly hours (IQR) of face-to-face practice before the pandemic was 27 (15-40) hours, but was reduced to 10 (5-20) hours during the pandemic. Telehealth was used by 866 (78.9%) respondents during the pandemic. Most common methods of communication were video calls (555; 50.6%), telephone calls (499; 45.5%), and WhatsApp voice calls (423; 38.6%). A reduction in monthly wages was reported by 946 (86.2%) respondents. Consultation fees also were reduced and 88 (8%) rheumatologists stated they had lost their jobs. A reduction in patient adherence to medication was reported by nearly 50% of respondents. Eighty-one (7.4%) rheumatologists received a COVID-19 diagnosis and 7 (8.6%) of them were hospitalized., Conclusion: The COVID-19 pandemic has reshaped rheumatology practice in Latin America and has had a profound effect on rheumatologists' behaviors and clinical practice., (© 2021 The Journal of Rheumatology.)
- Published
- 2021
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45. Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma.
- Author
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López V, Tejedor JR, Carella A, García MG, Santamarina-Ojeda P, Pérez RF, Mangas C, Urdinguio RG, Aranburu A, de la Nava D, Corte-Torres MD, Astudillo A, Mollejo M, Meléndez B, Fernández AF, and Fraga MF
- Abstract
Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in adulthood. Epigenetic mechanisms are known to play a key role in GBM although the involvement of histone methyltransferase KMT5B and its mark H4K20me2 has remained largely unexplored. The present study shows that DNA hypermethylation and loss of DNA hydroxymethylation is associated with KMT5B downregulation and genome-wide reduction of H4K20me2 levels in a set of human GBM samples and cell lines as compared with non-tumoral specimens. Ectopic overexpression of KMT5B induced tumor suppressor-like features in vitro and in a mouse tumor xenograft model, as well as changes in the expression of several glioblastoma-related genes. H4K20me2 enrichment was found immediately upstream of the promoter regions of a subset of deregulated genes, thus suggesting a possible role for KMT5B in GBM through the epigenetic modulation of key target cancer genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 López, Tejedor, Carella, García, Santamarina-Ojeda, Pérez, Mangas, Urdinguio, Aranburu, de la Nava, Corte-Torres, Astudillo, Mollejo, Meléndez, Fernández and Fraga.)
- Published
- 2021
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46. Molecular and Cellular Mechanisms of Glioblastoma.
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Castresana JS and Meléndez B
- Subjects
- Animals, Humans, Brain Neoplasms, Glioblastoma
- Abstract
Glioblastoma is the most malignant primary brain tumor [...].
- Published
- 2021
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47. Silencing of Histone Deacetylase 6 Decreases Cellular Malignancy and Contributes to Primary Cilium Restoration, Epithelial-to-Mesenchymal Transition Reversion, and Autophagy Inhibition in Glioblastoma Cell Lines.
- Author
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Urdiciain A, Erausquin E, Zelaya MV, Zazpe I, Lanciego JL, Meléndez B, Rey JA, Idoate MA, Riobo-Del Galdo NA, and Castresana JS
- Abstract
Glioblastoma multiforme, the most common type of malignant brain tumor as well as the most aggressive one, lacks an effective therapy. Glioblastoma presents overexpression of mesenchymal markers Snail, Slug, and N-Cadherin and of the autophagic marker p62. Glioblastoma cell lines also present increased autophagy, overexpression of mesenchymal markers, Shh pathway activation, and lack of primary cilia. In this study, we aimed to evaluate the role of HDAC6 in the pathogenesis of glioblastoma, as HDAC6 is the most overexpressed of all HDACs isoforms in this tumor. We treated glioblastoma cell lines with siHDAC6. HDAC6 silencing inhibited proliferation, migration, and clonogenicity of glioblastoma cell lines. They also reversed the mesenchymal phenotype, decreased autophagy, inhibited Shh pathway, and recovered the expression of primary cilia in glioblastoma cell lines. These results demonstrate that HDAC6 might be a good target for glioblastoma treatment.
- Published
- 2021
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48. APR-246 combined with 3-deazaneplanocin A, panobinostat or temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells.
- Author
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De La Rosa J, Urdiciain A, Zelaya MV, Zazpe I, Meléndez B, Rey JA, Idoate MA, and Castresana JS
- Subjects
- Adenosine analogs & derivatives, Adenosine pharmacology, Adenosine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Apoptosis drug effects, Brain Neoplasms genetics, Brain Neoplasms pathology, Cell Line, Tumor, Cell Proliferation drug effects, Colony-Forming Units Assay, Drug Screening Assays, Antitumor, Drug Synergism, Epigenesis, Genetic drug effects, Gene Expression Regulation, Neoplastic drug effects, Glioblastoma genetics, Glioblastoma pathology, Humans, Mutation, Panobinostat pharmacology, Panobinostat therapeutic use, Quinuclidines therapeutic use, Temozolomide pharmacology, Temozolomide therapeutic use, Tumor Suppressor Protein p53 genetics, Antineoplastic Combined Chemotherapy Protocols pharmacology, Brain Neoplasms drug therapy, Glioblastoma drug therapy, Quinuclidines pharmacology, Tumor Suppressor Protein p53 metabolism
- Abstract
Glioblastoma is the most malignant brain tumor and presents high resistance to chemotherapy and radiotherapy. Surgery, radiotherapy and chemotherapy with temozolomide are the only treatments against this tumor. New targeted therapies, including epigenetic modulators such as 3‑deazaneplanocin A (DZ‑Nep; an EZH2 inhibitor) and panobinostat (a histone deacetylase inhibitor) are being tested in vitro, together with temozolomide. The present study combined APR‑246 with DZ‑Nep, panobinostat and teomozolomide in order to explore the possibility of restoring p53 function in mutated cases of glioblastoma. Following the Chou‑Talalay method it was demonstrated that APR‑246 acts in an additive manner together with the other compounds, reducing clonogenicity and inducing apoptosis in glioblastoma cells independently of p53 status.
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- 2021
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49. Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).
- Author
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Moreno-Torres B, Campos-Martín Y, Meléndez B, Garcia Martin RM, Vicente A, Rodríguez de Lope Á, Alen JF, Mollejo M, and Hernández-Laín A
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Cohort Studies, Craniopharyngioma mortality, Female, Humans, Infant, Male, Middle Aged, Mutation, Pituitary Neoplasms mortality, Prognosis, Spain, Survival Rate, Young Adult, Craniopharyngioma diagnosis, Craniopharyngioma genetics, Pituitary Neoplasms diagnosis, Pituitary Neoplasms genetics, Proto-Oncogene Proteins B-raf genetics, beta Catenin genetics
- Abstract
Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in BRAF (V600E) and CTNNB1 genes characterize PCP and ACP, respectively. Recently, both variants have been shown to express elevated PD-L1 protein expression, but ACP also exhibited tumor cell-intrinsic PD-1 expression. In this study we analyze these molecular alterations in 52 cases with a long follow-up and examine their associations with immunohistochemical and clinical characteristics. ACPs comprise 73.1% of cases, while 21.2% are PCPs. Aberrant nuclear immunoreactivity for β-catenin was observed in all ACPs. BRAF p.V600E mutations were observed in 90.9% of PCPs. Only one ACP case featured both alterations. Both types of CP exhibited strong nuclear staining for p63 with diffuse and basal distribution. ACP and PCP consistently expressed PD-L1, most in a substantial percentage of tumor cells, with a distinctive spatial distribution of expression in each subtype; only ACP demonstrated PD-1 expression. There was no evidence of differences in clinical prognosis between ACPs and PCPs. The identification of hallmark molecular signatures in the two CP variants is useful for sub-categorization in routine histopathology reporting. It is also pertinent to personalized therapy and for the development of improved non-invasive therapeutic strategies in this disease.
- Published
- 2021
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50. Clinical, radiological and molecular characterization of intramedullary astrocytomas.
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Lebrun L, Meléndez B, Blanchard O, De Nève N, Van Campenhout C, Lelotte J, Balériaux D, Riva M, Brotchi J, Bruneau M, De Witte O, Decaestecker C, D'Haene N, and Salmon I
- Subjects
- Adolescent, Adult, Aged, Astrocytoma mortality, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Progression-Free Survival, Spinal Cord Neoplasms mortality, Young Adult, Astrocytoma genetics, Astrocytoma pathology, Spinal Cord Neoplasms genetics, Spinal Cord Neoplasms pathology
- Abstract
Intramedullary astrocytomas (IMAs) are rare tumors, and few studies specific to the molecular alterations of IMAs have been performed. Recently, KIAA1549-BRAF fusions and the H3F3A p.K27M mutation have been described in low-grade (LG) and high-grade (HG) IMAs, respectively. In the present study, we collected clinico-radiological data and performed targeted next-generation sequencing for 61 IMAs (26 grade I pilocytic, 17 grade II diffuse, 3 LG, 3 grade III and 12 grade IV) to identify KIAA1549-BRAF fusions and mutations in 33 genes commonly implicated in gliomas and the 1p/19q regions. One hundred seventeen brain astrocytomas were analyzed for comparison. While we did not observe a difference in clinico-radiological features between LG and HG IMAs, we observed significantly different overall survival (OS) and event-free survival (EFS). Multivariate analysis showed that the tumor grade was associated with better OS while EFS was strongly impacted by tumor grade and surgery, with higher rates of disease progression in cases in which only biopsy could be performed. For LG IMAs, EFS was only impacted by surgery and not by grade. The most common mutations found in IMAs involved TP53, H3F3A p.K27M and ATRX. As in the brain, grade I pilocytic IMAs frequently harbored KIAA1549-BRAF fusions but with different fusion types. Non-canonical IDH mutations were observed in only 2 grade II diffuse IMAs. No EGFR or TERT promoter alterations were found in IDH wild-type grade II diffuse IMAs. These latter tumors seem to have a good prognosis, and only 2 cases underwent anaplastic evolution. All of the HG IMAs presented at least one molecular alteration, with the most frequent one being the H3F3A p.K27M mutation. The H3F3A p.K27M mutation showed significant associations with OS and EFS after multivariate analysis. This study emphasizes that IMAs have distinct clinico-radiological, natural evolution and molecular landscapes from brain astrocytomas.
- Published
- 2020
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