EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours

Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA and miRNA analyses demonstrated that metastases are associated with the early induction of epithelial-mesenchymal transition (EMT) and deregulated miRNA expression in primary tumours. Increased expression of miR-21 was observed in undifferentiated, prometastatic mouse tumours and in human tumours characterized by p53 mutations and distant metastasis. The augmented expression of miR-21, mediated by active mTOR and Stat3 signalling, conferred increased invasive properties to mouse keratinocytes in vitro and in vivo, whereas blockade of miR-21 in a metastatic spindle cell line inhibits metastasis development. Collectively these data identify novel molecular mechanisms leading to metastasis in vivo originated by p53 loss in epithelia

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

Expert consensus document:Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted

Economic valuation of the forest biodiversity in Mexico, a review

El deterioro creciente de los recursos naturales crea la necesidad de valorar los servicios ambientales, incluidos los de la biodiversidad. La valoración económica de ésta se ha focalizado en bienes y servicios sin mercado, lo cual es complicado. Se han desarrollado técnicas para medir estos valores cuya aceptación se ha incrementado últimamente. En este trabajo se hizo una búsqueda de las valoraciones económicas efectuadas en México. Casi la totalidad de estudios de valoración realizados en el país se restringen a los métodos de valoración contingente (MVC) y costo de viaje (MCV). El único nivel de biodiversidad explorado es el de ecosistema. No se conocen trabajos desarrollados en términos de los bienes y servicios sin mercado a nivel de gen y especie. El método de valoración contingente es el más utilizado (11 estudios), le sigue el método costo de viaje con un estudio realizado conjuntamente con el MVC. Ocho estudios no consideraron los sesgos más importantes (tiempo, sustitución, múltiples destinos, vehículo de pago, estratégico e hipotético) de estos métodos

Estimación del valor financiero de las existencias maderables de cedro rojo (Cedrela odorata L.) en México

One of the two large categories of economic valuation within the environmental services field associated to natural resources is the market valuation. As its name implies, this type of valuation uses information generated in the process of exchange of goods or services valued. This document contains a financial valuation effort of Spanish red cedar (Cedrela odorata L.) species in Mexico. In this exercise the market price method was applied in order to estimate the monetary value of its main use (timber), considering the standing wood volume of the species in natural forests, based on information generated from the national forest inventory database. The effect of wood volume, price and transportation cost on total value was evaluated through a sensitivity analysis. The estimated value for total standing timber was MXN$5 282 183 404 (USD$288 328 788 at May 2016 prices). The Gulf of Mexico region has the highest value representation among the three regions considered in this paper. According to the sensitivity analysis, the price of wood is the main factor affecting total timber value of the species.Uno de los dos grandes rubros de la valoración económica en el ámbito de los servicios ambientales asociados con recursos naturales es la valoración con mercado. Como su nombre lo indica, esta valoración utiliza información que se genera en el proceso de intercambio del bien o servicio valorado. El presente documento contiene un esfuerzo de este tipo de valoración, desde el punto de vista financiero, del cedro rojo (Cedrela odorata L.) en México. En este ejercicio se aplicó el método de precios de mercado para determinar el valor monetario de su principal uso (maderable), considerando el volumen de madera de la especie existente en los bosques naturales, con base en información generada a partir de las bases de datos del inventario nacional forestal. El efecto del volumen de madera, el precio y el costo del transporte sobre el valor total se evaluó mediante un análisis de sensibilidad. El valor maderable estimado de los árboles en pie asciende a la cantidad de MXN$5 282 183 404 (USD$288 328 788, a precios de mayo de 2016). De las tres regiones consideradas en esta valoración, la región Golfo de México es la de mayor aportación. De acuerdo con el análisis de sensibilidad realizado, el precio de la madera es el principal factor que afecta el valor maderable de la especie