504 research outputs found
STAT3 as a potential immunotherapy biomarker in oncogene-addicted non-small cell lung cancer
Immune checkpoint blockade has modified the treatment landscape for many types of tumors, including lung cancer. Still our knowledge on the biology of the interaction between tumor cells and the microenvironment is limited, preventing the optimal use of these new compounds and the maximum benefit that the patients can derive from them. We have actively worked on the role of STAT3, a transcriptional factor that causes innate resistance to targeted therapies in oncogene-addicted tumors. In this short review we take the opportunity to express our opinion and review existing knowledge on the immune role of STAT3 and the possible implications that this may have for the discovery of new biomarkers to predict response to immunotherapy, as well as new partners to combine with and increase the efficacy of immune checkpoint inhibitors
Carles Porta. 20 años de imagen gráfica del Animac
[EN] NIMAC celebrates its 20th anniversary, and from the beginning, Carles Porta signed the festival’s graphic image. From an interview with the author, we dive into in the evolution of the festival and the challenges it brought to his work. Carles Porta, author of the amazing posters and bumpers for the festival, talks about this project that has allowed him to reinvent himself at each edition.[ES] Animac cumple 20 años y, desde sus inicios, Carles Porta ha firmado la imagen gráfica del festival. A partir de una entrevista con el autor, nos sumergimos en la evolución del festival y en los retos que ha supuesto para su trabajo. Carles Porta, autor de los fantásticos carteles y cortinillas de la muestra, nos habla de este proyecto que le ha permitido reinventarse en cada edición.
Guardar / Salir Siguiente >Álvarez Sarrat, S. (2016). Carles Porta. 20 años de imagen gráfica del Animac. Con A de Animación. (6):22-28. https://doi.org/10.4995/caa.2016.4786SWORD2228
Don Francisco Codony de Paladella, coronel de los Reales Exercitos de S.M., Gobernador militar y político de esta ciudad de Manresa ... Con fecah de 9 del corriente me dice el señor fiscal de Real Sala del Crimen lo siguiente. ... En el dia 21 de este mes
A monoclonal antibody that specifically recognizes m6A nucleoside
A hybridoma against the nucleoside m6A has been obtained from mouse spleen. This hybridoma was named H65 and it secretes monoclonal antibodies anti-m6A. The competition assays showed that the monoclonal antibody was highly specific for m6A nucleoside.This work was supported by PGC grant no PB92-0004. C. Codony was recipient of a fellowship from PGC.Peer Reviewe
Carles Riba i la llengua literària durant el franquisme. Exercicis de simplicitat
Carles Riba escriptor de la simplicitat: un aspecte poc estudiat de l’autor de les Elegies de Bierville.
Ara que l’Institut d’Estudis Catalans ha publicat la nova Gramàtica de la llengua catalana, seguint encara la normativa fabriana tot i adequar-la a la situació actual, és important veure com un dels escriptors que més va voler seguir les prescripcions del mestre va posar-les en pràctica.
Per altra banda, calia analitzar de manera imparcial el paper rellevant de Riba per a la llengua i la cultura catalanes durant el franquisme, que fins ara ha estat vist només des de la perspectiva de l’absoluta admiració o al contrari des de la crítica més radical.
Carles Riba scrittore di semplicità: un aspetto poco studiato dell\u27autore delle Elegie di Bierville.
Ora che l\u27Institut d\u27Estudis Catalans ha pubblicato la nuova grammatica della lingua catalana, sempre seguendo la normativa fabriana ma adeguandola alla situazione attuale, è importante vedere come uno degli scrittori che più volevano seguire le prescrizioni del maestro le abbia messe in pratica.
D\u27altra parte, è stato necessario analizzare in modo imparziale l\u27importante ruolo di Riba per la lingua e la cultura catalana durante il regime di Franco, che fino ad ora è stato visto solo dal punto di vista dell\u27ammirazione assoluta o viceversa dalla critica più radicale.Carles Riba, one of the most relevant personalities in Catalan letters, not only as a poet but also as a linguist, has been considered a difficult writer. This book aims to examine how his theoretical preparation and his ideas in linguistics influenced his work in the particular case of some early stories in which he tries “uns utilíssims exercicis de simplicitat”. Carles Riba did not present his linguistic theories in a single text in a complete and articulated way but we can evaluate them in various papers he wrote and published up until his death in 1959. The first part of this work, after an introduction which sets the author in the context of European linguistics, is a review of the ideas that can be found in the collections of essays: Escolis i altres articles (1921), Els marges (1927), Per comprendre (1937), ... més els poemes (1957), and in a few other particularly interesting papers.
This part focuses also on some of the controversies in which Carles Riba is involved as a linguist during the spanish dictatorship: especially his role on the publication of the second edition of Pompeu Fabra’s dictionary in 1954 and the consequences of the prologue he wrote for the volume. Joan Coromines considers an attack on the linguist Pompeu Fabra the negative comparison Riba proposes with the honnête homme: in our research we re-evaluate this consideration and analyse the historical and semantic value of this expression belonging to 17th-century French culture.
The second part of this paper is a strictly linguistic analysis of three texts, chosen among Carles Riba’s works for children. The interest of those texts is in the author’s deliberate intent of using the most simple language, which enables us to determine what he considers the basic aspects of linguistic quality. Furthermore, the existence of different editions of those texts permits a philological analysis of those versions showing Carles Riba’s ‘simple’ language in three very representative moments, from the beginning of his career as a writer to the difficult situation during the dictatorship
Carles Salvador i la modernització literària valenciana
Through a critical examination of the Valencian literary circles at the end of the nineteenth century (during the Renaixença), the author situates the decisive role Carles Salvador played in the renovation of literary form and content, especially in the temporal option of the Avant-garde, in poetry and theatre
Un col·loqui poc conegut de Carles Ros
This paper deals with the philological edition of a literary text by the 18th c. Valencian grammarian and poet Carles Ros i Hebrera, “Paper graciós, discursiu, enfàtic, alusiu i sentenciós per a desfresar-se de llaurador a les carnistoltes”. This text is part of a group of humorous “col∙loquis” which Ros wrote on the occasion of the carnival. This edition is important since this dialogue has not been recorded in any of the compilations and studies of Ros’ works so far, despite belonging to one of the most popular groups of his works. Moreover, it has lately been listed within the lost or impossible to find works by the famous Valencian author. Finally this edition of the text, which entails several variations when compared to the other editions, is different from those mentioned by the bibliographers. The paper also encloses a study on the importance of the literary and linguistic works by Carles Ros, as well as a philological and literary analysis of the text we are editing.Keywords: Literature, 18th century, València, Carles Ros
Abstract 3077: Tumor cells with acquired resistance to EGFR inhibitors and overexpression or activation of AXL, MET and FGFR1 are insensitive to single-agent treatment targeting AXL, MET or FGFR
Abstract
Background: Aberrant activity of the MET, FGFR1 and AXL receptors has been associated with the development of resistance to first, second and third generation EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutated non-small cell lung cancer (NSCLC) patients.
Methods: We obtained 6 resistant lines by treating EGFR-mutated (exon 19), TKI sensitive PC9 cells with increasing concentrations of gefitinib or erlotinib. The p.T790M resistance mutation emerged in two cell lines (GR1, GR4), which remained sensitive to osimertinib, a third generation EGFR TKI. Six new cell lines to resistant to “second line” osimertinib were generated from GR1 and GR4 by exposure to increasing concentrations of the inhibitor. Finally, six more cell lines resistant to “first line” osimertinib were derived from the PC9 parental cells. All resistant cell lines were genotyped for selected genes (including EGFR) and characterized for AXL, MET and FGFR1 expression and activation by Q-RT-PCR, immunohistochemistry and Western blotting. The effects of AXL (BGB324), MET (crizotinib, capmatinib) and FGFR1 (nindetanib) inhibitors on the parental and the 18 resistant cell lines were analyzed by MTT and, in some cases, by colony formation. AXL was stably silenced in some of the resistant cell lines.
Results: All cell lines resistant to “first line” gefitinib, erlotinib and osimertinib maintained the exon 19 EGFR sensitizing mutation. In contrast, three of the resistant cell lines to “second line” osimertinib lost the exon 19 and the p.T790M mutations. In two more, the p.T790M dropped to low allelic fractions (1% and 0.03%). Regardless of the EGFR status, AXL overexpression was the most common event related to EGFR TKI resistance in our panel of 18 cell lines, with FGFR1 and MET overexpression or activation as less frequent events. In proliferation assays, the IC50 of the EGFR TKI resistant cell lines for BGB324 (AXL inhibitor) was indistinguishable from the IC50 of the parental, EGFR TKI sensitive cell line. Similar results were obtained in the case of capmatinib, crizotinib (MET inhibitors) and nintedanib (FGFR inhibitor). Stable silencing of AXL on some of the AXL-overexpressing resistant cell lines had no effects in terms of doubling times, morphology of cells or sensitivity to EGFR TKIs. In combination experiments, the effect of BGB and MET inhibitors was found to be additive.
Conclusions: In tumor cell line models of acquired resistance to EGFR TKIs, overexpression or activation of AXL, MET and FGFR1 was not associated to sensitivity to single-agent treatment with AXL, MET or FGFR inhibitors. Multitargeted approaches might be more effective in this setting.
Citation Format: Jordi Bertran-Alamillo, Miguel Angel Molina-VIla, Cristina Teixidó, Jordi Codony-Servat, Ana Giménez-Capitán, Carles Codony-Servat, Silvia García-Román, Erika Aldeguer, Sonia Rodríguez, Rafael Rosell. Tumor cells with acquired resistance to EGFR inhibitors and overexpression or activation of AXL, MET and FGFR1 are insensitive to single-agent treatment targeting AXL, MET or FGFR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3077. doi:10.1158/1538-7445.AM2017-3077</jats:p
A second-step splicing activity is conserved from yeast to human
We describe a defective HeLa nuclear extract which is particularly deficient in step 2 of splicing reaction. With this extract we have studied the conservation of a second-step activity from yeast to human cells. We detected a S. cerevisiae second-step splicing activity that allows restoration of step 2 of the defective HeLa nuclear extract, which indicates that yeast purified fraction has a second-step activity that is conserved from yeast to human cells. The activity is a yeast UsnRNP protein(s) since it is purified with anti-tri-methylguanosine by immunoaffinity columns.This work was supported by PGC Grant No. PB92-0004 and an Alexander von Humboldt Foundation grant. C. Codony was the recipient of a fellowship from PGC; R.B. Cicarelli was the recipient from a fellowship from CAPES and Spanish MEC; A. Khaouja was the recipient of a fellowship from the Moroccan government.Peer Reviewe
Les revenus dans l'exploitation agricole : définitions et mesure
[fre] Les revenus dans l'exploitation agricole : définitions et mesures par Roland CARLES Devant la grande variété des concepts utilisés pour présenter les résultats économiques des entreprises agricoles, une mise au point est apparue nécessaire. L'auteur montre à quelles optiques se rattachent les principaux d'entre eux en distinguant entre «constatation des revenus » et «gestion des entreprises ». Le calcul des revenus du travail qui se rattache à l'option «gestion des entreprises », rencontre certaines difficultés parce qu'il suppose l'introduction de charges forfaitaires ou supplétives (valeur locative des terres en propriété, intérêt du capital d'exploitation) dans les charges globales de l'entreprise. L'auteur analyse ensuite les résultats de calcul portant sur les exploitations agricoles, suivies en 1972 dans le cadre du réseau d'information comptable agricole, et note l'importance des disparités liées à l'échelle des entreprises, leurs orientations de production et leur localisation. [eng] Farming incomes: Definitions and measure by Roland CARLES . In view of the great variety of concepts used in the presentation of agricultural enterprises economic results, it became a necessity to perfect them. The author points out to which perspective the leading ones are connected with, by distinguishing «incomes establishment» from « enterprises management ». The computation of labour incomes, connected with the option « enterprises management » meets with various difficulties since it assumes the insertion of contractual or additional charges (rental value of land properties, interest of farming capital) within the global charges of the enterprise. . The author analyses afterwards the results of a calculation bearing on farms, followed up in 1972 within the framework of the information system of farming accounting and notes the importance of disparities connected with the size of enterprises, their productive orientation and their localization. [spa] Los ingresos en la explotación agricola : Definiciones y medida por Roland CARLES Ante la gran variedad de conceptos que se utilizan para presentar resultados económicos de empresas agrícolas era menester enfocarlos. El autor muestra los aspectos bajo los cuales pueden considerarse los principales, distinguiendo entre « comprebación de los ingresos » y «administración empresarial ». El cálculo de ingresos del trabajo, vinculado con la opción « administración empresarial » tropieza con algunas dificultades ya que presupone la introducción de cargas a tanto alzado o supletorias (valor en alquiler de las tierras de propiedad, interés del capital de explotación) en las cargas globales de la empresa. . El autor analiza luego los resultados de un cálculo referente a las explotaciones agricolas observadas durante al ano 1972 en el cuadro de la red de información contable agricola y atestigua la importancia de las desemejanzas vinculadas con el tamano de las empresas, su orientación productiva y su localización.
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