Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth

BACKGROUND: Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment. METHODS: To investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties. RESULTS: In vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1. CONCLUSIONS: MTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment

Educación y cooperación para el desarrollo mediante estándares universales de accesibilidad

II FORO «IBEROAMÉRICA EN LA ESCENA ECONÓMICA INTERNACIONAL: INVERSIONES Y EDUCACIÓN PARA EL DESARROLLO». UNIVERSIDAD REY JUAN CARLOS, MADRID (ESPAÑA), 14 DE DICIEMBRE DE 200

Accesibilidad a Internet: requisitos para la calidad en la docencia e investigación

A good Internet platform for teaching and research must be accessible, independently of the computer platform used, language and other peculiarities (personal or external). This work analyzes the current limitations of Internet access, as well as the potentialities that would represent an access being truly independent of the computer platform, discapacities, availability and speed of access, language and legislation. Thus, the benefits for a more accesible network for lecturing and investigation, overcoming the geographic location or possible discapacity, would be immediate and would have a broad impact spectrum. A more accesible Internet would enhace not only the dissemination of the information, approaching us to the 'global village', but also others aspects like university principles and values that sould be considered: an improvement of the equality of opportunities and the access to the culture and the education, that are the basis of the progress and the individual and collective liberties.Una buena plataforma de docencia e investigación en la red debe ser accesible, independientemente del entorno informático, idioma y condicionantes( personales o externos). Es este trabajo se analizan, por una parte, las limitaciones actuales que se presentan en el acceso a Internet, y por otra las potencialidades que tendría un acceso un acceso independiente de las plataforma informáticas, discapacidades, disponibilidad y velocidad de acceso, idioma y legislación. Así, los beneficios para la docencia y la investigación de una red más accesible, por encima de la localización geográfica o posible discapacidad, serán inmediatos y redundaría en otros campos. Una Internet más accesible abriría una nueva vía no sólo para la difusión de la información, acercándonos a la 'aldea global', sino también para otros aspectos de lo que entenderemos como principios y valores universitarios y que deben ser considerados: una mejora en la igualdad de oportunidades y en el acceso a la cultura y la formación, que son las bases del progreso y de las libertades tanto individuales como colectivas

Atlas de las praderas marinas de España

Knowledge of the distribution and extent of seagrass habitats is currently the basis of management and conservation policies of the coastal zones in most European countries. This basic information is being requested through European directives for the establishment of monitoring programmes and the implementation of specific actions to preserve the marine environment. In addition, this information is crucial for the quantification of the ecological importance usually attributed to seagrass habitats due to, for instance, their involvement in biogeochemical cycles, marine biodiversity and quality of coastal waters or global carbon budgets. The seagrass atlas of Spain represents a huge collective effort performed by 84 authors across 30 Spanish institutions largely involved in the scientific research, management and conservation of seagrass habitats during the last three decades. They have contributed to the availability of the most precise and realistic seagrass maps for each region of the Spanish coast which have been integrated in a GIS to obtain the distribution and area of each seagrass species. Most of this information has independently originated at a regional level by regional governments, universities and public research organisations, which explain the elevated heterogeneity in criteria, scales, methods and objectives of the available information. On this basis, seagrass habitats in Spain occupy a total surface of 1,541,63 km2, 89% of which is concentrated in the Mediterranean regions; the rest is present in sheltered estuarine areas of the Atlantic peninsular regions and in the open coastal waters of the Canary Islands, which represents 50% of the Atlantic meadows. Of this surface, 71.5% corresponds to Posidonia oceanica, 19.5% to Cymodocea nodosa, 3.1% to Zostera noltii (=Nanozostera noltii), 0.3% to Zostera marina and 1.2% to Halophila decipiens. Species distribution maps are presented (including Ruppia spp.), together with maps of the main impacts and pressures that has affected or threatened their conservation status, as well as the management tools established for their protection and conservation. Despite this considerable effort, and the fact that Spain has mapped wide shelf areas, the information available is still incomplete and with weak precision in many regions, which will require an investment of major effort in the near future to complete the whole picture and respond to demands of EU directives.Versión del edito

Atlas de las praderas marinas de España

Knowledge of the distribution and extent of seagrass habitats is currently the basis of management and conservation policies of the coastal zones in most European countries. This basic information is being requested through European directives for the establishment of monitoring programmes and the implementation of specific actions to preserve the marine environment. In addition, this information is crucial for the quantification of the ecological importance usually attributed to seagrass habitats due to, for instance, their involvement in biogeochemical cycles, marine biodiversity and quality of coastal waters or global carbon budgets. The seagrass atlas of Spain represents a huge collective effort performed by 84 authors across 30 Spanish institutions largely involved in the scientific research, management and conservation of seagrass habitats during the last three decades. They have contributed to the availability of the most precise and realistic seagrass maps for each region of the Spanish coast which have been integrated in a GIS to obtain the distribution and area of each seagrass species. Most of this information has independently originated at a regional level by regional governments, universities and public research organisations, which explain the elevated heterogeneity in criteria, scales, methods and objectives of the available information. On this basis, seagrass habitats in Spain occupy a total surface of 1,541,63 km2, 89% of which is concentrated in the Mediterranean regions; the rest is present in sheltered estuarine areas of the Atlantic peninsular regions and in the open coastal waters of the Canary Islands, which represents 50% of the Atlantic meadows. Of this surface, 71.5% corresponds to Posidonia oceanica, 19.5% to Cymodocea nodosa, 3.1% to Zostera noltii (=Nanozostera noltii), 0.3% to Zostera marina and 1.2% to Halophila decipiens. Species distribution maps are presented (including Ruppia spp.), together with maps of the main impacts and pressures that has affected or threatened their conservation status, as well as the management tools established for their protection and conservation. Despite this considerable effort, and the fact that Spain has mapped wide shelf areas, the information available is still incomplete and with weak precision in many regions, which will require an investment of major effort in the near future to complete the whole picture and respond to demands of EU directives

Registro Español de Trasplante Cardiaco. XXXI Informe Oficial de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología

Introducción y objetivos Se presentan las características clínicas y los resultados de los trasplantes cardiacos realizados en España con la actualización correspondiente a 2019. Métodos Se describen las características clínicas y los resultados de los trasplantes cardiacos realizados en 2019, así como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a años previos, los cambios más llamativos son el descenso hasta el 38% de los trasplantes realizados en código urgente, y la consolidación en el cambio de asistencia circulatoria pretrasplante, con la práctica desaparición del balón de contrapulsación (0, 7%), la estabilización del uso del oxigenador extracorpóreo de membrana (9, 6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0, 34), y ambas mejores que la del trienio 2010-2012 (p = 0, 002 y p = 0, 01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en España como los resultados en supervivencia en los últimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoría con dispositivos de asistencia ventricular. Introduction and objectives: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. Methods: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. Results: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P = .34). Survival in both these periods was better than that from 2010 to 2012 (P = .002 and P = .01, respectively). Conclusions: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant

Identity between the PCPH proto-oncogene and the CD39L4 (ENTPD5) ectonucleoside triphosphate diphosphohydrolase gene

PCPH was initially defined as a proto-oncogene on the basis of its frequent detection as an activated oncogene in tumorigenic Syrian hamster embryo fibroblast cell lines converted to the neoplastic state by a single treatment with the carcinogen 3-methylcholanthrene (MC). Further studies identified the translation product of the PCPH gene as a ribonucleotide-binding protein with special affinity for ribonucleoside diphosphates. Later, we showed that the PCPH protein was homologous to the product of the yeast GDA1 gene and demonstrated that it had intrinsic guanosine diphosphatase activity, although it did not complement the disrupted phenotype when expressed in gda1 null Saccharomyces cerevisiae strains. These results indicated that the primary function of PCPH was unlikely to be related to the ribonucleotide recycling function that its yeast counterpart performs in the Golgi during the process of protein glycosylation. However, taken together, our data strongly suggested that the normal cellular function of PCPH was related to ribonucleotide metabolism. We now report that PCPH is structurally and functionally identical to the mammalian ectonucleoside triphosphate diphosphohydrolase CD39L4 (ENTPD5), recently described as a member of the lymphoid activation antigen () CD39 protein family. These results may help to establish the normal cellular function of the PCPH proto-oncogene product and its role in neoplastic development during carcinogenesis

Identity between the PCPH proto-oncogene and the CD39L4 (ENTPD5) ectonucleoside triphosphate diphosphohydrolase gene

PCPH was initially defined as a proto-oncogene on the basis of its frequent detection as an activated oncogene in tumorigenic Syrian hamster embryo fibroblast cell lines converted to the neoplastic state by a single treatment with the carcinogen 3-methylcholanthrene (MC). Further studies identified the translation product of the PCPH gene as a ribonucleotide-binding protein with special affinity for ribonucleoside diphosphates. Later, we showed that the PCPH protein was homologous to the product of the yeast GDA1 gene and demonstrated that it had intrinsic guanosine diphosphatase activity, although it did not complement the disrupted phenotype when expressed in gda1 null Saccharomyces cerevisiae strains. These results indicated that the primary function of PCPH was unlikely to be related to the ribonucleotide recycling function that its yeast counterpart performs in the Golgi during the process of protein glycosylation. However, taken together, our data strongly suggested that the normal cellular function of PCPH was related to ribonucleotide metabolism. We now report that PCPH is structurally and functionally identical to the mammalian ectonucleoside triphosphate diphosphohydrolase CD39L4 (ENTPD5), recently described as a member of the lymphoid activation antigen () CD39 protein family. These results may help to establish the normal cellular function of the PCPH proto-oncogene product and its role in neoplastic development during carcinogenesis

Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth

BACKGROUND: Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment. METHODS: To investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties. RESULTS: In vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1. CONCLUSIONS: MTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment

Early evolutionary divergence between papillary and anaplastic thyroid cancers

Background: Papillary thyroid cancer (PTC) is the most common thyroid carcinoma and exhibits an almost uniformly good prognosis, while anaplastic thyroid cancer (ATC) is less frequent and is one of the most aggressive cancers usually resistant to conventional treatment. Current hypothesis posits that ATC derives from PTC through the progressive acquisition of a discrete number of genomic alterations and implies that the mutational landscape of ATC resembles that of PTC. However, the clinical behaviour of ATC and PTC is radically different. We decided to address the disconnection between the clinical behaviour of ATC and PTC and the proposed model of the progressive development of ATC from PTC. Patients and methods: We carried out exome sequencing of DNA from 14 ATC specimens including three cases of concomitant ATC and PTC as well as their corresponding normal DNA from 14 patients. The sequencing results were validated using droplet digital PCR. We carried out immunohistochemistry and immunofluorescence studies of the concomitant ATC and PTC cases. In addition, we integrated our sequencing results with the existing TCGA data. Results: Most of the somatic mutations identified in the ATC component differed from the ones in PTC in the cases of concomitant ATC and PTC. The trunks of the phylogenetic trees representing the somatic mutations were short with long branches. In one case of concomitant PTC and ATC specimens, we observed an infiltration of PTC cells within the ATC component. Moreover, we integrated our results with data obtained from TCGA and observed that the most frequent mutations found in ATC presented high cancer cell fraction values and were significantly different from the PTC ones. Conclusion: ATC diverge from PTC early in tumour development and both tumour types evolve independently. Our work allows the understanding of the relationship between ATC and PTC facilitating the clinical management of these malignancies