Identification of novel synthetic lethal vulnerability in non small cell lung cancer by co targeting TMPRSS4 and DDR1

Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4

Database of spatial distribution of non indigenous species in Spanish marine waters

Research in marine Spanish waters are focused on several actions to achieve an effectively management on protected areas, with the active participation of the stakeholders and research as basic tools for decision-making. Among these actions, there is one about the knowledge and control on NIS. One of its objectives is the creation of NIS factsheets, which are going to be added to the National Marine Biodiversity Geographical System (GIS) providing complementary information about taxonomic classification, common names, taxonomic synonyms, species illustrations, identification morphological characters, habitat in the native and introduced regions, biological and ecological traits, GenBank DNA sequences, world distribution, first record and evolution in the introduced areas, likely pathways of introduction, effects in the habitats and interaction with native species, and potential management measures to apply. The database will also provide data for (1) the European online platforms, (2) the environmental assessment for the Descriptor 2 (D2-NIS) of the EU Marine Strategy Framework Directive (MSFD), as well as (3) supporting decisions made by stakeholders. It is the result of extensive collaboration among scientist, manager’s and citizen science in the Spanish North-Atlantic, South-Atlantic, Gibraltar Strait-Alboran, Levantine-Balearic and Canary Islands marine divisions, providing an updated overview of the spatial distribution of relevant extended and invasive NIS of recent and established NIS introduced by maritime transport and aquaculture pathways, as well as on cryptogenic or native species in expansion due to the climatic water warming trend

Monographic consultation of onconephrology. Rationale and implementation

The increase in demand for medical care for renal complications associated with neoplastic diseases is a reality in most nephrology departments. In response to this overall situation, the creation of healthcare models such as monographic consultations and develop training programs in Onconephrology could improve the care of these patients.Through an exploratory and descriptive study, we identified current situation of kidney involvement in cancer patients. The objective of the present study is to establish the criteria for specific assistance in the field of Onconephrology. For this, we have reviewed key aspects and analyzed the current situation in our country, through a survey addressed to all nephrologists through the Spanish Society of Nephrology., together with the experience of two Spanish centers. From this information, we have established some requirements and recommendations for the start-up of these consultations. Resumen: El incremento de la demanda asistencial de patología renal asociada a enfermedades neoplásicas es una realidad en la mayoría de servicios de nefrología. Para dar respuesta a esta situación, debe considerarse la creación de modelos asistenciales como consultas monográficas y desarrollar programas de formación en Onconefrologia que permitan optimizar la atención de estos pacientes.A través de un estudio exploratorio y descriptivo, identificamos cual es la situación actual de la afectación renal en pacientes con cáncer. El objetivo del presente estudio es establecer los criterios para la asistencia específica en el ámbito de la Onconefrologia. Para ello hemos revisado aspectos clave y analizado la situación actual en nuestro entorno, mediante una encuesta dirigida a todos nefrólogos a través de la S.E.N., junto a la experiencia de dos centros españoles. A partir de esta información hemos establecido una serie de requisitos y recomendaciones para la puesta en marcha de estas consultas

El geólogo cartógrafo

La cartografía geológica es la disciplina que, empleando diversas técnicas, expresa mediante una representación gráfica la información geológica referida a un sector de la corteza terrestre. El producto resultante es el Mapa Geológico que es la figuración sobre un plano, de la naturaleza, distribución espacial y relaciones geométricas de los materiales que afloran en la superficie terrestre, observables tanto directa como indirectamente y representables, a una escala determinada, sobre una base topográfica o cualquier otro soporte de información geográfica.Instituto Geológico y Minero de España, Españ

Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference

Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects

Iron management in chronic kidney disease:Conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference

Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects

Children living with HIV in Europe: do migrants have worse treatment outcomes?

International audienceTo assess the effect of migrant status on treatment outcomes among children living with HIV in Europe