Differential chemosensitivity to antifolate drugs between RAS and BRAF melanoma cells.

BACKGROUND: The importance of the genetic background of cancer cells for the individual susceptibility to cancer treatments is increasingly apparent. In melanoma, the existence of a BRAF mutation is a main predictor for successful BRAF-targeted therapy. However, despite initial successes with these therapies, patients relapse within a year and have to move on to other therapies. Moreover, patients harbouring a wild type BRAF gene (including 25% with NRAS mutations) still require alternative treatment such as chemotherapy. Multiple genetic parameters have been associated with response to chemotherapy, but despite their high frequency in melanoma nothing is known about the impact of BRAF or NRAS mutations on the response to chemotherapeutic agents. METHODS: Using cell proliferation and DNA methylation assays, FACS analysis and quantitative-RT-PCR we have characterised the response of a panel of NRAS and BRAF mutant melanoma cell lines to various chemotherapy drugs, amongst them dacarbazine (DTIC) and temozolomide (TMZ) and DNA synthesis inhibitors. RESULTS: Although both, DTIC and TMZ act as alkylating agents through the same intermediate, NRAS and BRAF mutant cells responded differentially only to DTIC. Further analysis revealed that the growth-inhibitory effects mediated by DTIC were rather due to interference with nucleotide salvaging, and that NRAS mutant melanoma cells exhibit higher activity of the nucleotide synthesis enzymes IMPDH and TK1. Importantly, the enhanced ability of RAS mutant cells to use nucleotide salvaging resulted in resistance to DHFR inhibitors. CONCLUSION: In summary, our data suggest that the genetic background in melanoma cells influences the response to inhibitors blocking de novo DNA synthesis, and that defining the RAS mutation status could be used to stratify patients for the use of antifolate drugs

Hidrogenoaren ekoizpena hiri hondakin plastikoen pirolisi eta erreformatuaren bidez

Material plastikoen kontsumoak izugarri gora egin du azken mendean. Hori dela eta, material hauek erabiltzearen ondorioz sortutako hondakinak asko handitu dira. Europar Batasuneko herrialdeetan 250 milioi tona baino gehiago hiri - hondaki n solido ( RSU ) sortzen dira urtero, urteko %3ko hazkunt zarekin. K antitate honen %7a plastiko hondakinei dagokie, hots, 17.5 milioi tona. Itsasoko uretan ere aurki daitezke plastikoak, urtero sei milioi tona eta erdi botatzen baitira itsasora, mediterraneo itsasoa izanik munduko plastiko biltegirik handiena. Itsasoan 90 urteraino iraun dezake te eta urte hauetan zehar distantzia handiak egin ditzakete aldatu gabe. Horregatik esaten da plastikoak iraunkorrak direla. Egun, hondakin plastikoen portzentaia txiki bat bakarrik birziklatzen da eta bai biltegiratzea bai erreketa bidezko eliminazioak ingurumen arazoak dituzte . Gainera, plastiko gehienak degradaezi nak dira, urte luzez ingurugiro kalteak eraginez . Hori dela eta, material hauen balorizaziorako teknologia berrien sustapena beharrezkoa da, eskala handian eraginkorrak, ekonomikoki bideragarriak eta ingurugiroa errespetatuko dutenak. Hondakin plastikoetatik abiatuz hidrogenoa lortzeko prozesua interesgarria eta bideragarria da, hidrogenoaren kontsumoaren igoe ra kontuan hartuz. Gaur egun erregai fosilen prozesaketatik lortzen da hidrogenoa, CO 2 - a ren emisio handiak sortzen direlarik. Emisio hauen murrizketa beharrezkotzat hartu da. Hau guztiagatik, Gradu Amaierako Lan honen helburu nagusia plastikoen balorizazio a ikertzea da, konkretuki hiri - hondakin solidoetan aurkitzen diren plast ikoena . Pirolisi eta ur baporearen bidezko erreformatua erabili dira hidrogenoa lortzeko, azken hau balio handiko produktua izanik. Horretarako lehenengo etapa iturri ohantze konikoan, 500 ºC - tan, buruturiko pirolisia izan da eta bigarrenik ohantze fluidizatu batean ur baporearen bidezko erreformatua burutu da , 700 ºC - tan . Helburu nagusi hau betetzeko bestelako helburu zehatzak ezarri dira, hiri - hondakin solidoetan aurkitzen diren HDPE, PP, PS eta PET plastiko nahaste baten bideragarritasuna aztertu delarik aurrez aipatutako bi etapen bidez: Plastiko nahastearen pirolisian sorturiko konposatu hegazkorren erreformatua era jarraian burutzea. Zero denboran e rreakzio indizeak (konbertsioa et a etekinak) eta lortutako gasaren konposizioa determinatze a . Erreformatuan erabilitako katalizatzailearen desaktibatzeak erreakzioa ren konbertsio eta etekina n duen eragina aztertzea

A New Approach for the Study of the Coast Indentation Index

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Change detection of buildings from satellite imagery and lidar data

Geospatial objects change over time and this necessitates periodic updating of the cartography that represents them. Currently, this updating is done manually, by interpreting aerial photographs, but this is an expensive and time-consuming process. While several kinds of geospatial objects are recognized, this article focuses on buildings. Specifically, we propose a novel automatic approach for detecting buildings that uses satellite imagery and laser scanner data as a tool for updating buildings for a vector geospatial database. We apply the support vector machine (SVM) classification algorithm to a joint satellite and laser data set for the extraction of buildings. SVM training is automatically carried out from the vector geospatial database. For visualization purposes, the changes are presented using a variation of the traffic-light map. The different colours assist human operators in performing the final cartographic updating. Most of the important changes were detected by the proposed method. The method not only detects changes, but also identifies inaccuracies in the cartography of the vector database. Small houses and low buildings surrounded by high trees present significant problems with regard to automatic detection compared to large houses and taller buildings. In addition to visual evaluation, this study was checked for completeness and correctness using numerical evaluation and receiver operating characteristic curves. The high values obtained for these parameters confirmed the efficacy of the method

Eficacia de la coronariografía en el adulto mayor

Introduction: all people older than 60 years are included in the group of the elderly, although it is recognized that this approach does not take into account: the degenerative processes, chronic clinical conditions, disabilities and dependence.Objective: to determine the efficacy and safety of coronary angiography and percutaneous coronary approach in the elderly.Material and methods: A retrospective, descriptive study was conducted with 5715 patients. They underwent coronary angiography in the hemodynamic laboratory of the Cardiology Center referred from Pinar del Rio province during 2010 and 2013. The sample was comprised of 1933 patients over 60 years old. The information was obtained from the database ANGYCOR considering clinical and angiographic characteristics.Results: the most frequent diagnosis was stable angina (43.5%). The average age of 60-70 years prevailed, mainly group 60-69 years, male patients (77.2%) and hypertension (64.9%); 7.8% of the patients had a previous revascularization. In 98.0% the behavior was successful. It is concluded that the rate of complications and mortality in coronary angiography of the elderly is low, with high success rate, so that appears to be an effective and safe procedure.Conclusions: the rate of coronary angiography in patients older than 60 years is low. The study pointed out the presence of a multi-vessel disease and that major left coronary artery decreases as age increases. The frequency of complications along with mortality is null with high success rates.Introducción: se considera adulto mayor a toda persona cuya edad supere los 60 años, aunque se admite que este criterio no toma en cuenta: los procesos degenerativos, las alteraciones clínicas crónicas, la incapacidad y la dependencia.Objetivo: determinar la eficacia y seguridad de la coronariografía y el intervencionismo coronario percutáneo en el adulto mayor.Material y método: se realizó un estudio retrospectivo y descriptivo con los 5715 pacientes. A estos se les realizó una coronariografía en el laboratorio de hemodinámica del Cardiocentro procedente de Pinar del Río, entre 2010 y 2013. La muestra quedó formada por los 1933 mayores de 60 años. La información se obtuvo de la base de datos ANGYCOR, considerando las características clínico-angiográficas. Resultados: el diagnóstico más frecuente resultó la angina estable (43,5%). La edad promedio de 60 a 70 años, predominando el grupo de 60 a 69 años; la masculinidad (77,2%) y la hipertensión arterial (64,9%). El 7,8% de los enfermos tenían una revascularización anterior. En el 98,0% el proceder resultó exitoso. Se concluyó que el índice de complicaciones y la mortalidad en coronariografía del adulto mayor es bajo, con elevado porcentaje de éxito, por lo que parece proceder eficaz y seguro.Conclusiones: el índice de realización de coronariografía a pacientes mayores de 60 años es bajo. La indicación del estudio, la presencia de enfermedad multivasos y del tronco de coronaria izquierda disminuyen a medida que aumenta la edad. La frecuencia de complicaciones, la mortalidad es nula con elevado índice de éxito

Spatial control of Cdc42 signalling by a GM130-RasGRF complex regulates polarity and tumorigenesis

The small GTPase Cdc42 is a key regulator of polarity, but little is known in mammals about its spatial regulation and the relevance of spatial Cdc42 pools for polarity. Here we report the identification of a GM130-RasGRF complex as a regulator of Cdc42 at the Golgi. Silencing GM130 results in RasGRF-dependent inhibition of the Golgi pool of Cdc42, but does not affect Cdc42 at the cell surface. Furthermore, active Cdc42 at the Golgi is important to sustain asymmetric front-rear Cdc42-GTP distribution in directionally migrating cells. Concurrent to Cdc42 inhibition, silencing GM130 also results in RasGRF-dependent Ras-ERK pathway activation. Moreover, depletion of GM130 is sufficient to induce E-cadherin downregulation, indicative of a loss in cell polarity and epithelial identity. Accordingly, GM130 expression is frequently lost in colorectal and breast cancer patients. These findings establish a previously unrecognized role for a GM130-RasGRF-Cdc42 connection in regulating polarity and tumorigenesis