105 research outputs found

    Features of alterations of igneous rocks from Sierras of Guadarrama and Malagon (Spanish Central Range)

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    [Resumen] Se describen las características-de las alteraciones desarrolladas sobre las rocas ígneas de un sector del Sistema Central. Criterios geomorfológicos y su distinta composición mineralógica permiten suponer su origen a partir de distintas etapas de alteración. Se discuten las condiciones climáticas durante su formación, realizada siempre bajo climas poco agresivos.[Abstract] The main features of the alterations developped on igneous rocks of Central System are described. From geomorphological criteria as well as mineralogical data, different stages of weathering are been inferred. Although weathering processes have not been strong, different conditions are discussed for each stage

    Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide

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    The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) can cause resistance to the alkylating drug temozolomide (TMZ). The purpose of this study was to determine the relationship between the MGMT status, determined by means of several techniques and methods, and the cytotoxic response to TMZ in 11 glioblastoma multiforme (GBM) cell lines and 5 human tumour cell lines of other origins. Cell survival was analysed by clonogenic assay. The MGMT protein levels were assessed by western blot analysis. The MGMT promoter methylation levels were determined using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and quantitative real-time methylation-specific PCR (qMSP). On the basis of the results of these techniques, six GBM cell lines were selected and subjected to bisulphite sequencing. The MGMT protein was detected in all TMZ-resistant cell lines, whereas no MGMT protein could be detected in cell lines that were TMZ sensitive. The MS-MLPA results were able to predict TMZ sensitivity in 9 out of 16 cell lines (56%). The qMSP results matched well with TMZ sensitivity in 11 out of 12 (92%) glioma cell lines. In addition, methylation as detected by bisulphite sequencing seemed to be predictive of TMZ sensitivity in all six cell lines analysed (100%). The MGMT protein expression more than MGMT promoter methylation status predicts the response to TMZ in human tumour cell line

    Resultados del estudio geológico a escala 1/25.000 del término municipal de Madrid.

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    Se exponen de forma abreviada los rasgos en cuanto a metodología y conclusiones del estudio geológico a escala 1/25000 realizado en el Municipio de Madrid en los años 1982/83. Las diferentes unidades expresadas en la cartografiase describen en función de las pautas mayores observables en los materiales que forman cada una de ellas, analizándose sus relaciones estratigráficas. El Proyecto «Estudio Geológico a escala 1/25000 del Término Municipal de Madrid ha sido llevado a cabo a lo largo de los años 1982-83 como resultado de la colaboración científica entre diversos organismos de la Administración (Facultad de CC. Geológicas-Universidad Complutense, Instituto Geológico y Minero. Ayuntamiento de Madrid, Instituto de Geología de Madrid-CSIC, y otros). Constituye una de las áreas de actuación definidas dentro del Convenio de Colaboración Técnica y Cultural para el conocimiento de las Características del Suelo y Subsuelo de Madrid», propiciado y patrocinado por el Excmo. Ayuntamiento. La financiación del proyecto especifico de Geología ha sido realizada íntegramente por el IGME, organismo encargado además de su supervisión. El desarrollo del Proyecto tiene un marcado carácter interdisciplinar, fruto del trasvase de información entre los distintos grupos que abarca el Convenio general (aparte de los ya referidos, el SGOP, COPLACO, Laboratorio «José Luis Escario» siendo precisamente uno de los objetivos del trabajo el servir de apoyo a las restantes áreas de investigación. Los estudios geológicos realizados se plasman en un total de siete mapas a escala 1/25000 elaborados según la normativa Magna de cartografía geológica mapas que toman como referencia, aunque en algunos casos no las completan y en otros adosan porciones de hojas adyacentes, las hojas 1/25000 de Madrid, Alcorcón, El Pardo, San Femando de Henares, Pozuelo de Alarcón, Alcobendas y Castillo de Viñuelas

    Homogeneous MGMT Immunoreactivity Correlates with an Unmethylated MGMT Promoter Status in Brain Metastases of Various Solid Tumors

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    The O6-methylguanine-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical reports on treating brain metastases with temozolomide describe varying effects. This may be due to the fact that MGMT promoter methylation of brain metastases has not yet been explored in depth. Therefore, we assessed MGMT promoter methylation of various brain metastases including those derived from lung (n = 91), breast (n = 72) kidney (n = 49) and from malignant melanomas (n = 113) by methylation-specific polymerase chain reaction (MS-PCR) and MGMT immunoreactivity. Fifty-nine of 199 brain metastases (29.6%) revealed a methylated MGMT promoter. The methylation rate was the highest in brain metastases derived from lung carcinomas (46.5%) followed by those from breast carcinoma (28.8%), malignant melanoma (24.7%) and from renal carcinoma (20%). A significant correlation of homogeneous MGMT-immunoreactivity (>95% MGMT positive tumor cells) and an unmethylated MGMT promoter was found. Promoter methylation was detected in 26 of 61 (43%) tumors lacking MGMT immunoreactivity, in 17 of 63 (27%) metastases with heterogeneous MGMT expression, but only in 5 of 54 brain metastases (9%) showing a homogeneous MGMT immunoreactivity. Our results demonstrate that a significant number of brain metastases reveal a methylated MGMT-promoter. Based on an obvious correlation between homogeneous MGMT immunoreactivity and unmethylated MGMT promoter, we hypothesize that immunohistochemistry for MGMT may be a helpful diagnostic tool to identify those tumors that probably will not benefit from the use of alkylating agents. The discrepancy between promoter methylation and a lack of MGMT immunoreactivity argues for assessing MGMT promoter methylation both by immunohistochemical as well as by molecular approaches for diagnostic purposes

    O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

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    Background: The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. Methods A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Results Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Conclusions Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably
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