Protein-loss of SWI/SNF-complex core subunits influences prognosis dependent on histological subtypes of intra- and extrahepatic cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive malignancy with a 5-year-survival rate of <10%, mainly due to diagnosis in advanced stages and limited therapeutic options in case of progressive disease. Recently, evidence has indicated that alterations in the SWI/SNF-complex (SWI/SNF) may have an important role in the tumorigenesis of CCA. SWI/SNF-related chromatin remodeling has been reported to be crucial for differentiation and tumor suppression, and loss-of-function mutations of SWI/SNF are present in 20% of human malignancies; however, at present, little is known about its relevance in CCA. In the present study, a cohort of 52 patients with the diagnosis of primary CCA was retrospectively collected. All patients underwent surgery with curative intent. Tissue microarray analysis was performed on each tumor for immunohistochemical loss-of-protein analysis of the SWI/SNF core subunits ARID1A, INI-1, BRG1, PBRM-1 and BRM, corresponding to the following CCA subtypes: Extrahepatic CCA (ECCA), small duct or large duct intrahepatic CCA (ICCA). Kaplan-Meier analysis was used to determine survival distribution and survival differences were evaluated by log-rank test. In total, 14 of 52 patients (~35%) exhibited protein-loss of any tested SWI/SNF core subunit. Notably, 17% of patients exhibited a loss of ARID1a; this was the protein loss with the highest frequency. Patients with small and large duct ICCA with protein-loss of any tested SWI/SNF subunit exhibited significantly worse survival compared with the wild-type cohort with proficient protein expression (P=0.013 and P=0.002), whereas no significant survival difference was detected for patients with ECCA. SWI/SNF and its core subunits may be considered promising predictive and therapeutic targets, and require further investigation in patients with CCA.

Detection of circulating tumor DNA by digital droplet PCR in resectable lung cancer as a predictive tool for recurrence.

Lung cancer is the leading cause of cancer-related mortality worldwide due to difficulties in early detection and high postsurgical recurrence rate. Current European Guidelines recommend follow-up via computerized tomography (CT) scans on regular basis within the first 2 years after radical surgical resection. Despite these efforts, recurrence rates remain high with 30-70 %. Therefore, it is imperative to develop predictive markers for metastases and postsurgical recurrence using minimally invasive methods. This prospective study aims at defining the feasibility of detecting circulating tumor DNA (ctDNA) in presurgical plasma samples of patients with lung cancer by digital droplet PCR. Resected tumor tissue and simultaneous blood samples were collected from 24 patients with lung cancer in stage I-IIIA (12 stage I, 8 stage II, 4 stage III). Genomic DNA from the tumor tissue samples were analyzed for hotspot mutations using a 17 gene panel next-generation sequencing (NGS) assay. CtDNA from corresponding plasma samples were analyzed using digital droplet PCR (ddPCR). Additionally, DNA sequencing results were correlated with patients' outcome. At least one somatic mutation was detected by NGS (96 %) in 23 of the tested tissue samples. DdPCR detected mutations in circulating cell-free DNA (ccfDNA) of nine patients' samples (9/23, 39 %). Postsurgical outcome analysis was performed for those patients who had received complete tumor resection (n = 21). Four of them suffered from an early relapse within the first two years after surgery, including two with detectable somatic mutations in ccfDNA during primary staging. Taken together, we showed that the 17 gene panel assay revealed in 23 of 24 patients at least one somatic mutation in the primary tumor by NGS. Tumor-specific mutation was detectable in 39 % from the blood of early stage lung cancer patients by ddPCR.

Dynamiques identitaires dans le cinéma cubain Le "Nous cubain" entre construction idéologique et appartenance culturelle / Dinâmicas identitárias no cinema cubano O “Nós cubano” entre a construção ideológica e o pertencimento cultural / Identity dynamics in the cuban cinema The “Cuban We” between ideological construction and cultural belonging / Dinámicas de identidad en el cine cubano El "Nosotros cubano" entre la construcción ideológica y la pertenencia cultural

Cet article retrace, grâce à une analyse de l’imaginaire fictionnel de films de fiction cubains, l’évolution de la définition du Nous cubain, à partir de la Révolution en 1959 jusqu’au début des années 2000. Marquée par une frontière nette entre le Nous et les Autres, fondée sur une opposition idéologique et une séparation géographique, le concept du Nous a été remis en question avec l’arrivée des nouvelles générations nées au sein même du Nous révolutionnaire, puis avec les bouleversements provoqués par l’ébranlement de l’URSS. Dans les intrigues fictionnelles, la possibilité de reprendre contact avec les personnes émigrées ainsi que les nouvelles données migratoires stimulent les protagonistes à mettre en avant leurs références communes au-delà de la distance. Ainsi, la frontière délimitant le Nous à partir de critères idéologiques perd son importance au profit d’une conception d’un Nous plus ouvert et dynamique, fondé davantage sur un sentiment d’appartenance culturelle et affective. (AU)

Através da análise do imaginário ficcional coletivo encontrado nos filmes de ficção cubanos, este artigo retraça a evolução da ideia do Nós cubano desde o início da Revolução Cubana em 1959 até o começo dos anos 2000. O conceito de Nós, primeiramente sendo marcado pela fronteira entre o Nós e os Outros, baseado numa oposição ideológica e numa separação geográfica, foi questionado pela chegada de uma nova geração nascida sob o Nós revolucionário e, após, pelas mudanças causadas pelo desaparecimento da URSS. Nos filmes de ficção, a possibilidade de retomar contato com emigrados e, com novas regras sobre a migração, estimulou os protagonistas a realçarem referências comuns, apesar da distância. As fronteiras do Nós, definidas ideologicamente, perderam sua importância favorecendo um Nós cubano mais aberto e dinâmico, baseado num senso de pertencimento cultural e emocional. (AU)

Through the analysis of the fictional imaginary of Cuban fiction films, this article retraces the evolution of the idea of the Cuban We from the beginnings of the Revolution in 1959 to the beginning of the XXI century. The WE concept, first being marked by a clear frontier between the We and the Others, based on an ideological opposition and geographical separation, was questioned by the arrival of the new generations born within the revolutionary We and, later, by the changes caused by the breakdown of the Soviet Union. In the plots of fiction films, the possibility of regaining contact with emigrants and the new migratory patterns stimulate the protagonists to concentrate on their common references despite the distance. The frontiers of the We, defined along ideological lines, lose their importance in favor of a more open and dynamic We, one based on a sense of cultural and emotional belonging. (AU)

A través de un análisis del imaginario ficcional de las películas de ficción cubanas, ese artículo reconstituye la evolución de la definición del Nosotros cubano, a partir de la Revolución en 1959 hasta los años 2000. El concepto del Nosotros, marcado por una frontera fundada en una oposición ideológica y una separación geográfica, fue cuestionado con la llegada de las nuevas generaciones nacidos adentro del Nosotros revolucionario y con los cambios provocados por el derrumbe de la Unión soviética. En las historias ficcionales, la posibilidad de contactar personas de afuera y las nuevas condiciones migratorias estimulan los protagonistas a concentrarse en sus referencias comunes más allá de la distancia. La frontera delimitando el Nosotros a partir de criterios ideológicos pierde su importancia en favor de una concepción del Nosotros más abierto y dinámico, fundado en un sentimiento de pertenencia cultural y afectiva. (AU)

Dynamiques identitaires dans le cinéma cubain Le "Nous cubain" entre construction idéologique et appartenance culturelle / Dinâmicas identitárias no cinema cubano O “Nós cubano” entre a construção ideológica e o pertencimento cultural / Identity dynamics in the cuban cinema The “Cuban We” between ideological construction and cultural belonging / Dinámicas de identidad en el cine cubano El "Nosotros cubano" entre la construcción ideológica y la pertenencia cultural

Cet article retrace, grâce à une analyse de l’imaginaire fictionnel de films de fiction cubains, l’évolution de la définition du Nous cubain, à partir de la Révolution en 1959 jusqu’au début des années 2000. Marquée par une frontière nette entre le Nous et les Autres, fondée sur une opposition idéologique et une séparation géographique, le concept du Nous a été remis en question avec l’arrivée des nouvelles générations nées au sein même du Nous révolutionnaire, puis avec les bouleversements provoqués par l’ébranlement de l’URSS. Dans les intrigues fictionnelles, la possibilité de reprendre contact avec les personnes émigrées ainsi que les nouvelles données migratoires stimulent les protagonistes à mettre en avant leurs références communes au-delà de la distance. Ainsi, la frontière délimitant le Nous à partir de critères idéologiques perd son importance au profit d’une conception d’un Nous plus ouvert et dynamique, fondé davantage sur un sentiment d’appartenance culturelle et affective.

Através da análise do imaginário ficcional coletivo encontrado nos filmes de ficção cubanos, este artigo retraça a evolução da ideia do Nós cubano desde o início da Revolução Cubana em 1959 até o começo dos anos 2000. O conceito de Nós, primeiramente sendo marcado pela fronteira entre o Nós e os Outros, baseado numa oposição ideológica e numa separação geográfica, foi questionado pela chegada de uma nova geração nascida sob o Nós revolucionário e, após, pelas mudanças causadas pelo desaparecimento da URSS. Nos filmes de ficção, a possibilidade de retomar contato com emigrados e, com novas regras sobre a migração, estimulou os protagonistas a realçarem referências comuns, apesar da distância. As fronteiras do Nós, definidas ideologicamente, perderam sua importância favorecendo um Nós cubano mais aberto e dinâmico, baseado num senso de pertencimento cultural e emocional.

Through the analysis of the fictional imaginary of Cuban fiction films, this article retraces the evolution of the idea of the Cuban We from the beginnings of the Revolution in 1959 to the beginning of the XXI century. The WE concept, first being marked by a clear frontier between the We and the Others, based on an ideological opposition and geographical separation, was questioned by the arrival of the new generations born within the revolutionary We and, later, by the changes caused by the breakdown of the Soviet Union. In the plots of fiction films, the possibility of regaining contact with emigrants and the new migratory patterns stimulate the protagonists to concentrate on their common references despite the distance. The frontiers of the We, defined along ideological lines, lose their importance in favor of a more open and dynamic We, one based on a sense of cultural and emotional belonging.

A través de un análisis del imaginario ficcional de las películas de ficción cubanas, ese artículo reconstituye la evolución de la definición del Nosotros cubano, a partir de la Revolución en 1959 hasta los años 2000. El concepto del Nosotros, marcado por una frontera fundada en una oposición ideológica y una separación geográfica, fue cuestionado con la llegada de las nuevas generaciones nacidos adentro del Nosotros revolucionario y con los cambios provocados por el derrumbe de la Unión soviética. En las historias ficcionales, la posibilidad de contactar personas de afuera y las nuevas condiciones migratorias estimulan los protagonistas a concentrarse en sus referencias comunes más allá de la distancia. La frontera delimitando el Nosotros a partir de criterios ideológicos pierde su importancia en favor de una concepción del Nosotros más abierto y dinámico, fundado en un sentimiento de pertenencia cultural y afectiva.