SEOM clinical guidelines for the treatment of non‑small cell lung cancer (2018)

Non-small cell lung cancer (NSCLC) accounts for up to 85% of all lung cancers. The last few years have seen the development of a new staging system, diagnostic procedures such as liquid biopsy, treatments like immunotherapy, as well as deeper molecular knowledge; so, more options can be offered to patients with driver mutations. Groups with specific treatments account for around 25% and demonstrate significant increases in overall survival, and in some subgroups, it is important to evaluate each treatment alternative in accordance with scientific evidence, and even more so with immunotherapy. New treatments similarly mean that we must reconsider what should be done in oligometastatic disease where local treatment attains greater valu

La contrapráctica como herramienta educativa innovadora para favorecer la evolución del aprendizaje de los estudiantes de Derecho

In view of the growing need to reinforce the students’ learning process, the counter-practice is projected as an innovative educational tool capable of achieving an evolution in learning. Through this activity, which has already been implemented in the course unit of Law and Religion at the Jaume I University of Castellón (Spain), the student is granted the possibility of studying in depth a highly topical issue to prepare a legal reflection. Their previous autonomous work will be complemented and perfected with a rigorously updated legal-practical exposition by the teacher after which she will propose to the student an experimental practice with the aim of contrasting it with the legal reality. The learning evolution will take place when students are able to carry out an analysis of factual and legal basis, but enriched with the empirical contrast based on personal or third-party experiences that can lead to a major debate in relation to possible mismatches between law and social reality.Ante la creciente necesidad de reforzar el proceso de aprendizaje de los alumnos, la contrapráctica se proyecta como una herramienta educativa innovadora capaz de lograr una evolución en el aprendizaje. A través de esta actividad, que ya se ha implantado en la unidad de curso de Derecho y Religión de la Universidad Jaume I de Castellón (España), se concede al alumno la posibilidad de profundizar en un tema de gran actualidad para elaborar una reflexión jurídica. Su trabajo autónomo previo será complementado y perfeccionado con una exposición jurídico-práctica rigurosamente actualizada por parte de la profesora tras la cual propondrá al alumno una práctica experimental con el fin de contrastarla con la realidad jurídica. La evolución del aprendizaje se producirá cuando el alumno sea capaz de realizar un análisis de base fáctica y jurídica, pero enriquecido con el contraste empírico basado en experiencias personales o de terceros que puede dar lugar a un importante debate en relación con los posibles desajustes entre el derecho y la realidad social

Heterotypic paracrine signaling drives fibroblast senescence and tumor progression of large cell carcinoma of the lung

Senescence in cancer cells acts as a tumor suppressor, whereas in fibroblasts enhances tumor growth. Senescence has been reported in tumor associated fibroblasts (TAFs) from a growing list of cancer subtypes. However, the presence of senescent TAFs in lung cancer remains undefined. We examined senescence in TAFs from primary lung cancer and paired control fibroblasts from unaffected tissue in three major histologic subtypes: adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC). Three independent senescence markers (senescence-associated beta-galactosidase, permanent growth arrest and spreading) were consistently observed in cultured LCC-TAFs only, revealing a selective premature senescence. Intriguingly, SCC-TAFs exhibited a poor growth response in the absence of senescence markers, indicating a dysfunctional phenotype rather than senescence. Co-culturing normal fibroblasts with LCC (but not ADC or SCC) cancer cells was sufficient to render fibroblasts senescent through oxidative stress, indicating that senescence in LCC-TAFs is driven by heterotypic signaling. In addition, senescent fibroblasts provided selective growth and invasive advantages to LCC cells in culture compared to normal fibroblasts. Likewise, senescent fibroblasts enhanced tumor growth and lung dissemination of tumor cells when co-injected with LCC cells in nude mice beyond the effects induced by control fibroblasts. These results define the subtype-specific aberrant phenotypes of lung TAFs, thereby challenging the common assumption that lung TAFs are a heterogeneous myofibroblast-like cell population regardless of their subtype. Importantly, because LCC often distinguishes itself in the clinic by its aggressive nature, we argue that senescent TAFs may contribute to the selective aggressive behavior of LCC tumors

Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts

Epigenetic changes through altered DNA methylation have been implicated in critical aspects of tumor progression, and have been extensively studied in a variety of cancer types. In contrast, our current knowledge of the aberrant genomic DNA methylation in tumor-associated fibroblasts (TAFs) or other stromal cells that act as critical coconspirators of tumor progression is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer patients using the HumanMethylation450 microarray. We found widespread DNA hypomethylation concomitant with focal gain of DNA methylation in TAFs compared to CFs. The aberrant DNA methylation landscape of TAFs had a global impact on gene expression and a selective impact on the TGF-β pathway. The latter included promoter hypermethylation-associated SMAD3 silencing, which was associated with hyperresponsiveness to exogenous TGF-β1 in terms of contractility and extracellular matrix deposition. In turn, activation of CFs with exogenous TGF-β1 partially mimicked the epigenetic alterations observed in TAFs, suggesting that TGF-β1 may be necessary but not sufficient to elicit such alterations. Moreover, integrated pathway-enrichment analyses of the DNA methylation alterations revealed that a fraction of TAFs may be bone marrow-derived fibrocytes. Finally, survival analyses using DNA methylation and gene expression datasets identified aberrant DNA methylation on the EDARADD promoter sequence as a prognostic factor in non-small cell lung cancer patients. Our findings shed light on the unique origin and molecular alterations underlying the aberrant phenotype of lung TAFs, and identify a stromal biomarker with potential clinical relevance

Accurate Identification of ALK Positive Lung Carcinoma Patients: Novel FDA-Cleared Automated Fluorescence In Situ Hybridization Scanning System and Ultrasensitive Immunohistochemistry

Background: Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples. Methods: Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system. Results: All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively. Conclusions: The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situation

Rethinking environmental constitutionalism in Ecuador and Bolivia from an indigenous peoples’ religious freedom perspective

La radical importancia de la espiritualidad y de los sistemas de creencias para los pueblos indígenas se refleja no solo en sus formas de vida en armonía con la naturaleza y en la profunda vinculación religiosa que comparten con sus territorios tradicionales, sino que sobrepasa este ámbito comunitario hasta llegar a impactar en la propia configuración de los Estados en que estos pueblos habitan. El presente estudio examina la especial repercusión de la religiosidad indígena en el constitucionalismo ambiental de Ecuador y Bolivia, así como el papel clave que ambos países han desempeñado en la articulación internacional de los derechos de la naturaleza como consecuencia directa de la integración de las cosmovisiones indígenas en sus respectivos sistemas.The critical importance of spirituality and belief systems for indigenous peoples is reflected not only in their ways of life in harmony with nature and in the deep religious attachment they share with their traditional territories, but it rather expands beyond this community level in such a way as to have an impact on the very configuration of the States in which these peoples inhabit. The present study examines the special impact of indigenous spirituality on the environmental constitutionalism of Ecuador and Bolivia, as well as the key role both states have played in the international articulation of the rights of nature as a direct consequence of the integration of indigenous worldviews in their respective systems

El papel decisivo de los pueblos indígenas en la mitigación y adaptación al cambio climático: Evolución y retos pendientes

Los conocimientos ecológicos tradicionales que los pueblos indígenas, a partir de sus más profundas convicciones religiosas y sistemas de creencias, han ido desarrollando sobre sus territorios y transmitiendo de generación en generación, desde tiempos inmemoriales, están demostrando ser de vital importancia en la lucha contra el cambio climático. Si bien, hace no tantos años, la tendencia imperante dentro de la comunidad científica era la de denigrar e infravalorar el potencial que estos conocimientos poseían, de un tiempo a esta parte estos pueblos están empezando a ver formalmente reconocido su papel decisivo en la mitigación y adaptación a este fenómeno ambiental. Esta investigación analiza la evolución, tanto en el plano científico como en el normativo, que ha experimentado el reconocimiento del rol de estos pueblos en la consecución de los objetivos fijados en materia ambiental y climática, al tiempo que plantea los retos pendientes que todavía están por afrontarThe traditional ecological knowledge indigenous peoples, based on their deepest religious convictions and beliefs systems, have been developing on their territories and gathering over generations since time immemorial is proving to be of vital importance in the fight against climate change. While, not so long ago, the prevailing trend within the scientific community was to denigrate and undervalue the potential this knowledge had, for some time now these peoples are beginning to see how their key role in the mitigation and adaptation to this environmental phenomenon is being formally recognized. This research analyzes the evolution, both at the scientific and normative fields, of the recognition of these peoples’ role in the fulfillment of environmental and climatic goals, while raising the challenges that remain to be tackle

Las competiciones de juicio simulado desde la perspectiva del coach: a propósito de la primera edición de la Moot Court AEDEUR

Un dels principals punts febles dels actuals plans d'estudis del Grau en Dret en la immensa majoria d'universitats espanyoles és la falta de desenvolupament pràctic de les competències bàsiques que l'alumnat haurà de dominar una vegada doni principi a la seva carrera professional. Com a eina didàctica encaminada a tractar de pal·liar aquesta acusada manca, s'ha proposat la participació d'un reduït grup d'estudiants en una competició de judici simulat. Aquest article parteix de l'experiència educativa de l'equip de la Universitat Jaume I en la primera edició de la Moot Court AEDEUR, projectada des del punt de vista de l'entrenador, per a analitzar les estratègies didàctiques emprades en la preparació de cadascuna de les fases de la competició i corroborar la seva efectivitat en l'adquisició de les competències previstes. D'aquesta manera, es podrà concloure que la participació en competicions de judici simulat complementa adequadament la formació integral com a juristes de l'estudiantat del Grau en Dret, en preparar-los eficaçment per a situacions quotidianes de la pràctica professional.One of the main pending tasks of the current Law Degree syllabus in the vast majority of Spanish universities is precisely the lack of practice of the basic skills students will have to master once they get started with their professional careers. The participation in moot court competitions appears as an effective tool to overcome this acute deficiency, largely due to the mandatory credit limitation. This paper arises from the learning experience of the Jaume I University team in the first edition of the AEDEUR Moot Court, projected from the viewpoint of the coach, in order to analyze the teaching methodology used in the preparation of each of the competition phases and corroborate its effectiveness in the acquisition of the expected skills in each of them. Thus, the conclusion extracted is that the participation in moot court competitions adequately complements Law Degree students’ general training as jurists, as it successfully prepares them for day-to-day situations of the professional practice.Una de las principales tareas pendientes de los actuales planes de estudios del Grado en Derecho en la inmensa mayoría de universidades españolas es precisamente la falta de puesta en práctica de las habilidades básicas que el alumnado deberá dominar una vez dé comienzo a su carrera profesional. La participación en competiciones de juicio simulado se plantea como una herramienta efectiva para suplir esta acusada carencia, debida, en gran medida, a la preceptiva limitación de créditos. Este artículo parte de la experiencia educativa del equipo de la Universitat Jaume I en la primera edición de la Moot Court AEDEUR, proyectada desde el punto de vista del entrenador, para analizar la metodología docente empleada en la preparación de cada una de las fases de la competición y corroborar su efectividad en la adquisición de las competencias esperadas en cada una de ellas. De este modo, se podrá concluir que la participación en competiciones de juicio simulado complementa adecuadamente la formación general como juristas del estudiantado del Grado en Derecho, al prepararlos eficazmente para situaciones cotidianas de la práctica profesional