16 research outputs found
Aproximación a la caracterización morfológica y molecular por IRM y ERM de la respuesta a la terapia en modelos pre-clínicos de glioma
Descripció del recurs: el 01 setembre 2012La memoria del trabajo describe en detalle la estrategia seguida para mejorar a nivel preclínico la detección temprana de respuesta a la terapia en modelos animales de cáncer cerebral, más concretamente de tipo glioma. Así, la evolución de un tumor de tipo glioblastoma (glioma astrocítico de grado IV) inducible mediante inyección estereotáctica intracerebral a ratones C57BL/6 de células de la línea GL261 de ratón, ha sido caracterizada de manera no invasiva (mediante imágenes por RM, IRM) en cuanto a su aumento de volumen durante el tiempo de vida de los animales. Además, las curvas de supervivencia y la supervivencia promedio de estos ratones en ausencia de terapia han demostrado ser reproducibles y han permitido establecer el grupo control con el cual comparar el efecto de diversos agentes terapéuticos en la evolución del tumor. De los agentes y protocolos terapéuticos investigados, el más efectivo resultó ser, como era de esperar por la experiencia clínica previa, un agente alquilante del DNA, la Temozolomida (TMZ). La TMZ, en un protocolo de tres ciclos de administración, aumentó significativamente la supervivencia de los animales tratados, produciendo además una ralentización del crecimiento de los tumores durante una semana aproximadamente. Una vez establecido el modelo de respuesta a terapia, se investigó si alguna estrategia de imagen molecular basada en RM podía detectar dicha respuesta transitoria de los tumores a la terapia. Las dos principales estrategias de perturbación del metaboloma del tejido cerebral investigadas fueron la retención diferencial de dimetilsulfóxido (DMSO) y la variación del patrón espectral global tanto en condiciones de euglicemia como en hiperglicemia transitoria. En ambos casos se adquirieron imágenes moleculares de los tumores cerebrales antes, durante la respuesta a la terapia y al manifestarse la recidiva tumoral mediante imagen espectroscópica de RM (IERM). Finalmente, la información de las imágenes moleculares basadas en la perturbación con DMSO, aplicada a las imágenes moleculares previas a la perturbación en condiciones de euglicemia, permitió desarrollar un clasificador matemático que genera imágenes nosológicas de zonas que muestran respuesta a la terapia de tumores GL261. Este clasificador fue validado con éxito en un conjunto de datos independiente (tumores no utilizados para desarrollar el clasificador). Además, la tesis ha permitido avanzar en paralelo con la caracterización mediante IRM/ERM/IERM de otros modelos preclínicos de glioma (ratones modificados genéticamente que desarrollan oligodedndrogliomas de manera espontánea, y glioblastomas humanos desarrollados en animales inmunodeprimidos, nude mice), para poder aplicar en un futuro estrategias de predicción y seguimiento de la respuesta a la terapiaThis work describes in detail the strategy followed for improving the early response to therapy detection in brain tumors at preclinical level. Animal models of brain tumors, specifically glioma models, have been used for this purpose. The evolution of a high grade glioma model (glioblastoma (GBM), IV grade), induced by estereotatic injection of GL261 cells into the striatum of C57BL/6 WT mice, has been characterized using a non-invasive technique, consisting on MR images (MRI). Tumor volume growth rate and animal survival curves have been proved to be reproducible and have been used for establishing a control group for comparing the effect of different therapeutic agents on tumor evolution. Among all the agents investigated, the most effective was Temozolomide (TMZ), an oral alkylating agent commonly used in clinical trials for GBM treatment. A three cycle protocol using TMZ improves the survival rate of treated animals in comparison with the control group. This protocol also affects tumor growth rate, slowing down tumor evolution for a seven days period. After developing the appropriate response to therapy model, different molecular imaging strategies based on MR were investigated to determine if any of them could detect the transitory tumor response to therapy. The main strategies studied were the differential retention of dimethyl sulfoxide (DMSO) and global changes detected in the spectral pattern of tumors in euglicemia and after a hyperglicemic challenge. In both cases, molecular images from the tumors were acquired before, during the response to therapy and at tumor recurrence, using MR spectroscopic imaging (MRSI). Finally, the information obtained from molecular images based on DMSO perturbation (perturbation enhanced MRSI) was applied in euglicemic conditions for developing a mathematical classification system which generates nosologic images for GL261 tumors that show response to TMZ treatment. This classification system was successfully validated with an independent test set of data (tumors that were not used previously for developing the system). In addition, this work has also advanced in the characterization by MRI/MRS/MRSI of other preclinical glioma models (genetically engineered mice which spontaneously develop oligodendrogliomas, and immunosuppressed mice which develop human GBM) for a possible application in the future in tumor response to therapy prediction and follow up strategies
Aproximación a la caracterización morfológica y molecular por IRM y ERM de la respuesta a la terapia en modelos pre-clínicos de glioma
La memoria del trabajo describe en detalle la estrategia seguida para mejorar a nivel preclínico la detección temprana de respuesta a la terapia en modelos animales de cáncer cerebral, más concretamente de tipo glioma. Así, la evolución de un tumor de tipo glioblastoma (glioma astrocítico de grado IV) inducible mediante inyección estereotáctica intracerebral a ratones C57BL/6 de células de la línea GL261 de ratón, ha sido caracterizada de manera no invasiva (mediante imágenes por RM, IRM) en cuanto a su aumento de volumen durante el tiempo de vida de los animales. Además, las curvas de supervivencia y la supervivencia promedio de estos ratones en ausencia de terapia han demostrado ser reproducibles y han permitido establecer el grupo control con el cual comparar el efecto de diversos agentes terapéuticos en la evolución del tumor.
De los agentes y protocolos terapéuticos investigados, el más efectivo resultó ser, como era de esperar por la experiencia clínica previa, un agente alquilante del DNA, la Temozolomida (TMZ). La TMZ, en un protocolo de tres ciclos de administración, aumentó significativamente la supervivencia de los animales tratados, produciendo además una ralentización del crecimiento de los tumores durante una semana aproximadamente. Una vez establecido el modelo de respuesta a terapia, se investigó si alguna estrategia de imagen molecular basada en RM podía detectar dicha respuesta transitoria de los tumores a la terapia. Las dos principales estrategias de perturbación del metaboloma del tejido cerebral investigadas fueron la retención diferencial de dimetilsulfóxido (DMSO) y la variación del patrón espectral global tanto en condiciones de euglicemia como en hiperglicemia transitoria. En ambos casos se adquirieron imágenes moleculares de los tumores cerebrales antes, durante la respuesta a la terapia y al manifestarse la recidiva tumoral mediante imagen espectroscópica de RM (IERM). Finalmente, la información de las imágenes moleculares basadas en la perturbación con DMSO, aplicada a las imágenes moleculares previas a la perturbación en condiciones de euglicemia, permitió desarrollar un clasificador matemático que genera imágenes nosológicas de zonas que muestran respuesta a la terapia de tumores GL261. Este clasificador fue validado con éxito en un conjunto de datos independiente (tumores no utilizados para desarrollar el clasificador).
Además, la tesis ha permitido avanzar en paralelo con la caracterización mediante IRM/ERM/IERM de otros modelos preclínicos de glioma (ratones modificados genéticamente que desarrollan oligodedndrogliomas de manera espontánea, y glioblastomas humanos desarrollados en animales inmunodeprimidos, nude mice), para poder aplicar en un futuro estrategias de predicción y seguimiento de la respuesta a la terapia.This work describes in detail the strategy followed for improving the early response to therapy detection in brain tumors at preclinical level. Animal models of brain tumors, specifically glioma models, have been used for this purpose. The evolution of a high grade glioma model (glioblastoma (GBM), IV grade), induced by estereotatic injection of GL261 cells into the striatum of C57BL/6 WT mice, has been characterized using a non-invasive technique, consisting on MR images (MRI). Tumor volume growth rate and animal survival curves have been proved to be reproducible and have been used for establishing a control group for comparing the effect of different therapeutic agents on tumor evolution.
Among all the agents investigated, the most effective was Temozolomide (TMZ), an oral alkylating agent commonly used in clinical trials for GBM treatment. A three cycle protocol using TMZ improves the survival rate of treated animals in comparison with the control group. This protocol also affects tumor growth rate, slowing down tumor evolution for a seven days period. After developing the appropriate response to therapy model, different molecular imaging strategies based on MR were investigated to determine if any of them could detect the transitory tumor response to therapy. The main strategies studied were the differential retention of dimethyl sulfoxide (DMSO) and global changes detected in the spectral pattern of tumors in euglicemia and after a hyperglicemic challenge. In both cases, molecular images from the tumors were acquired before, during the response to therapy and at tumor recurrence, using MR spectroscopic imaging (MRSI). Finally, the information obtained from molecular images based on DMSO perturbation (perturbation enhanced MRSI) was applied in euglicemic conditions for developing a mathematical classification system which generates nosologic images for GL261 tumors that show response to TMZ treatment. This classification system was successfully validated with an independent test set of data (tumors that were not used previously for developing the system).
In addition, this work has also advanced in the characterization by MRI/MRS/MRSI of other preclinical glioma models (genetically engineered mice which spontaneously develop oligodendrogliomas, and immunosuppressed mice which develop human GBM) for a possible application in the future in tumor response to therapy prediction and follow up strategies
Assessment of a 1H high-resolution magic angle spinning NMR spectroscopy procedure for free sugars quantification in intact plant tissue
In most plants, sucrose is the primary product of photosynthesis, the transport form of assimilated carbon, and also one of the main factors determining sweetness in fresh fruits. Traditional methods for sugar quantification (mainly sucrose, glucose and fructose) require obtaining crude plant extracts, which sometimes involve substantial sample manipulation, making the process time-consuming and increasing the risk of sample degradation. Here, we describe and validate a fast method to determine sugar content in intact plant tissue by using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS NMR). The HR-MAS NMR method was used for quantifying sucrose, glucose and fructose in mesocarp tissues from melon fruits (Cucumis melo var. reticulatus and Cucumis melo var. cantalupensis). The resulting sugar content varied among individual melons, ranging from 1.4 to 7.3 g of sucrose, 0.4–2.5 g of glucose; and 0.73–2.83 g of fructose (values per 100 g fw). These values were in agreement with those described in the literature for melon fruit tissue, and no significant differences were found when comparing them with those obtained using the traditional, enzymatic procedure, on melon tissue extracts. The HR-MAS NMR method offers a fast (usually <30 min) and sensitive method for sugar quantification in intact plant tissues, it requires a small amount of tissue (typically 50 mg fw) and avoids the interferences and risks associated with obtaining plant extracts. Furthermore, this method might also allow the quantification of additional metabolites detectable in the plant tissue NMR spectrum.This work was funded by grants from the Spanish Ministerio de Ciencia e Innovación (SAF2008-03323 and SAF2011-23870 to CA) and the Ministerio de Economia y Competitividad (BIO2009-08719 and BIO2012-32838 to BSS). CIBER-BBN is an initiative of Instituto de Salud Carlos III, Spain, which is co-funded with EU-funds.Peer reviewe
III Jornadas de experiencias docentes EGB y EEMM
En la Cub.: Ministerio de Educación y Ciencia. Centros de Profesores de Aragón, La Rioja y NavarraComunicaciones sobre diversas experiencias docentes en educación primaria y secundaria presentadas a las III Jornadas de Experiencias Docentes EGB y EEMM celebradas en Ezcaray (La Rioja) los días 10, 11 y 12 de septiembre de 1990. Las comunicaciones presentadas abarcan los distintos niveles y ciclos de la educación infantil, primaria y secundaria, así como educación especial; y en las mismas se exponen distintas experiencias llevadas a cabo por los docentes en las diferentes áreas y temas transversales.La RiojaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]
Improving the classification of brain tumors in mice with perturbation enhanced (PE)-MRSI
P1382: CIRCULATING CAR-T CELLS MONITORING OF KINETICS AND EXHAUSTION MARKERS AS PREDICTIVE FACTORS IN B-CELL MALIGNANCIES
Down syndrome as risk factor for respiratory syncytial virus hospitalization : A prospective multicenter epidemiological study
Respiratory syncytial virus (RSV) infection in childhood, particularly in premature infants, is associated with significant morbidity and mortality. To compare the hospitalization rates due to RSV infection and severity of disease between infants with and without Down syndrome (DS) born at term and without other associated risk factors for severe RSV infection. In a prospective multicentre epidemiological study, 93 infants were included in the DS cohort and 68 matched by sex and data of birth (±1 week) and were followed up to 1 year of age and during a complete RSV season. The hospitalization rate for all acute respiratory infection was significantly higher in the DS cohort than in the non-DS cohort (44.1% vs 7.7%, P<.0001). Hospitalizations due to RSV were significantly more frequent in the DH cohort than in the non-DS cohort (9.7% vs 1.5%, P=.03). RSV prophylaxis was recorded in 33 (35.5%) infants with DS. The rate of hospitalization according to presence or absence of RSV immunoprophylaxis was 3.0% vs 15%, respectively. Infants with DS showed a higher rate of hospitalization due to acute lower respiratory tract infection and RSV infection compared to non-DS infants. Including DS infants in recommendations for immunoprophylaxis of RSV disease should be considered