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The insufficiently long RF saturation duration and relaxation delay in chemical exchange saturation transfer (CEST)-MRI experiments may result in underestimation of CEST measurements. To maintain the CEST effect without prolonging the saturation duration and reach quasi-steady state (QUASS), a deep learning method was developed to reconstruct a QUASS CEST image pixel by pixel from non-steady-state CEST acquired in experiments. In this work, we established a tumor-bearing rat model on a 7 T horizontal bore small-animal MRI scanner, allowing ground-truth generation, after which a bidirectional long short-term memory network was formulated and trained on simulated CEST Z-spectra to reconstruct the QUASS CEST; finally, the ground truth yielded by experiments was used to evaluate the performance of the reconstruction model by comparing the estimates with the ground truth. For quantitation evaluation, linear regression analysis, structural similarity index (SSIM) and peak signal-to-noise ratio (peak SNR) were used to assess the proposed model in the QUASS CEST reconstruction. In the linear regression analysis of in vivo data, the coefficient of determination for six different representative frequency offsets was at least R2 = 0.9521. Using the SSIM and peak SNR as evaluation metrics, the reconstruction accuracies of in vivo QUASS CEST were found to be 0.9991 and 46.7076, respectively. Experimental results demonstrate that the proposed model provides a robust and accurate solution for QUASS CEST reconstruction using a deep learning mechanism.
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Crystallization kinetics is the key factor in controlling the polymer crystallization process and affecting crystallinity and crystalline morphology, which determine the polymer's main properties. In this work, the non-isothermal crystallization kinetics of graphene/PA10T composites are investigated by the Jeziorny method and Mo method, and the crystallization activation energy is calculated by the Kissinger method. It is found that the addition of an appropriate amount of graphene to PA10T can significantly promote the crystallization of PA10T and accelerate its crystallization rate. The Jeziorny equation does not have a linear relationship across the whole crystallization range, while the Mo equation does a good linear fitting. In addition, the crystallization activation energy decreases when the graphene content is below 1 wt.%. TGA results indicate that the addition of graphene improves the thermal stability of PA10T.
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Birdstrikes are an important threat to aviation safety. A standardized, scientific process for assessing birdstrike risk could prevent accidents, thereby improving the flight safety and reducing economic losses. However, China currently lacks a unified birdstrike risk assessment system. Here, we propose and validate a new model for assessing birdstrike risk in order to fill that need. The model consists of two elements. First, empirical data are collected on the occurrence of birds at the airport and in a surrounding 8 km buffer. Second, each species is evaluated with a risk assessment matrix that takes into account the number of birds, weight, flight altitude, a tendency to cluster, and range of activity. These five factors allow each species to be divided into one of three risk levels: high danger (level 3), moderate danger (level 2) and low danger (level 1). We propose corresponding birdstrike prevention measures for each level. We apply this method to the civil aviation airport in Ordos, China. We found that 20 of the 118 species of birds in and around the airport were high danger birds (level 3). To validate this process, we compared these species with records of birdstrike accidents in a database maintained by the Civil Aviation Administration of China (CAAC) for 2007-2016. We found that 42% of the species we identified as high risk had been involved in at least one birdstrike accident, and that the remaining 58% belonged to families that appeared in the database. The high degree of overlap gives us high confidence in the practicality of our risk assessment model, which is based on the risk management concept of ISO 31000. Critically, this new model and method for predicting bird strike risk can be replicated at other airports around the world, even where no extensive records have been kept of past birdstrikes.
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Accidentes de Aviación/prevención & control , Accidentes de Aviación/estadística & datos numéricos , Aeropuertos/estadística & datos numéricos , Conducta Animal/fisiología , Aves , Vuelo Animal/fisiología , Modelos Estadísticos , Medición de Riesgo/métodos , Animales , Aves/clasificación , China , Bases de Datos como Asunto , Riesgo , Gestión de Riesgos , SeguridadRESUMEN
ABS/PA6-compatibilized blends were prepared by in situ reactive extrusion method. The main objective was to evaluate the influences of the morphology and blend composition on the rheological and nonisothermal crystallization properties. The morphology of submicron-sized ABS droplets evenly dispersed in PA6 led to dilatant fluid behavior and a transition from elastic to viscous behavior in the low-frequency region. The crystallization results indicated that reactive blends had elevated crystallization temperatures and crystallization rates, which were due to the heterogeneous nucleation of the submicron-sized ABS particles. In addition, it was observed that the theory by Mo suitably described the nonisothermal crystallization process. The activation energy slightly decreased for ABS contents of 5 and 15 wt % and then increased for a content of 25 wt %, indicating that the ABS promoted the crystallization of the blends at appropriate contents.
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To explore the impacts of future climate change on spring phenology stages (first leaf storey expansion stage, spring flowering stage) of rubber tree in Hainan Island, we established a rubber tree spring phenology simulation model based on the crop clock model and developed a computer software RubberSP. The model simulation accuracy was examined with experimental observed phenology data. Five global climate models (GCMs) from the Coupled Model Intercomparison Project Phase 5 (CMIP5) were integrated using Bayesian Model averaging method (BMA) to predict the impacts of climate change on the spring phenology of rubber tree in 2020-2099 (relative to 1986-2017) under climate scenarios of RCP2.6, RCP4.5 and RCP8.5, respectively. The results showed that the RubberSP model had good simulation accuracy, with the determination coefficient (R2) values ranging between 0.73-0.87, the root mean square error (RMSE) ranging from 3.26 to 4.15 d, and the normalized root mean square error (NRMSE) of 3.4%-7.4% between measured and simulated phenology stages. The uncertainty of a single GCM could be avoided by BMA method, which could better reflect the change trend of temperature. Temperature of Hainan Island in the end of 21 century, under the scenarios of RCP2.6, RCP4.5 and RCP8.5, would increase by more than 0.3, 1.0 and 2.5 â compared with the baseline, respectively. The spring phenology stages would appear earlier and yield would increase in the future climate scenario. The time isoline of spring phenology stages would move forward to northwest, which indicated that most suitable area for rubber tree plantation in Hainan Island would expand to the northwest. The spatial difference of the first leaf storey expansion stage would be more evident, but not for spring flowering stage. The amplitude of rubber tree spring phenology variations was closely related to the increases of temperature under different RCP scenarios, with the most apparent change under RCP8.5 scenario and most mild change under RCP2.6 scenario.
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Cambio Climático , Hevea , Teorema de Bayes , China , Estaciones del Año , TemperaturaRESUMEN
In this study, Fe3O4-nanoparticles-contained polyamide 6 (PA 6) microparticles (FP) were developed by a first dispersion of Fe3O4-nanoparticles in ε-caprolactam (CL) monomer in the presence of polystyrene (PS) and a subsequent in situ CL open polymerization into PA 6, followed by PS removal. The FP microparticles (as magnetic separation material) and nanochitin (n-CT, as an effective metal-cation natural adsorbent) were then in situ encapsulated into poly(vinyl alcohol)-enhanced chitosan hybrids (PVA/CTS) to form biodegradable nanocomposite hydrogels (FPCC) with magnetic separation ability. The FPCC hybridized hydrogels enabled about 1.7-fold Cu(II) adsorption capacity as compared to the pure PVA/CTS hydrogels with a Cu(II) adsorption value of 38.7 mg/g. More attractively, the adsorption equilibrium could be achieved within 10 min, which is quicker than many previous adsorbents. Furthermore, simulation results indicated that Cu(II) adsorption behaviors of the hybrid hydrogels conform to a pseudo-second-order kinetic model and a Langmuir isotherm model.
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Quitina/química , Cobre/química , Hidrogeles/química , Nanopartículas de Magnetita/química , Contaminantes Químicos del Agua/química , Adsorción , Caprolactama/análogos & derivados , Caprolactama/química , Fenómenos Magnéticos , Polímeros/química , Alcohol Polivinílico/química , Estireno/química , Purificación del Agua/métodosRESUMEN
In this study, nanochitin-contained magnetic chitosan (FPCC) microfibers were prepared successfully via continuous injection gelation method and employed to remove Ni(II) ion from aqueous solution. Firstly, Fe3O4-nanoparticles were encapsulated into ε-caprolactam (CL) monomer solution in the presence of polystyrene (PSE), followed by CL anionic ring-opening polymerization and PSE removal, and obtained magnetic polyamide 6 (PA 6) microparticles (FP). After that, the economical FPCC microfibers can be prepared by adding FP microparticles and nanochitin (n-CT) into poly(vinyl alcohol)/chitosan hybrids (PVA/CTS). The obtained FPCC microfibers had shown significant advantages in production, separation, and adsorption when compared to the hydrogel beads prepared by the traditional method (instantaneous gelation method). Within 10â¯h, 99.7% Ni(II) could be adsorbed by FPCC magnetic microfibers (adsorbent dosage: 1â¯g, pH: 4.1, and temperature: 293â¯K). More attractively, the hybridized microfibers could be easily separated from the aqueous solution through a magnetic separation method after Ni(II) adsorption. Ni(II) adsorption behaviors of the hybrid microfibers conform to the Langmuir isotherm model and pseudo-second-order kinetic model. Besides, the possible adsorption mechanism was also discussed.
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Quitosano/química , Hidrogeles/química , Nanopartículas/química , Níquel/química , Soluciones/química , Contaminantes Químicos del Agua/química , Adsorción , Caprolactama/química , Concentración de Iones de Hidrógeno , Cinética , Magnetismo/métodos , Poliestirenos/química , Temperatura , Agua/química , Purificación del Agua/métodosRESUMEN
Multifunctional probes are needed to characterize individual cells simultaneously by different techniques to provide complementary information. A preparative method and an in vitro demonstration of function are presented for a dual-function dark field microscopy/surface-enhanced Raman scattering (SERS) liposome probe for cancer. Liposomes composed of zwitterionic lipids are valuable both to limit biofouling and to serve as a modular matrix to incorporate a variety of functional molecules and hence are used here as vehicles for SERS-active materials. Dark field microscopy and SERS represent new combined functionalities for targeted liposomal probes. Two methods of antibody conjugation to SERS liposomes are demonstrated: (i) direct conjugation to functional groups on the SERS liposome surface and (ii) postinsertion of lipid-functionalized antibody fragments (Fabs) into preformed SERS liposomes. In vitro experiments targeting both lymphoma cell line LY10 and primary human chronic lymphocytic leukemia (CLL) cells demonstrate the usefulness of these probes as optical contrast agents in both dark field and Raman microscopy.
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Leucemia de Células B/diagnóstico por imagen , Liposomas/química , Linfoma/diagnóstico por imagen , Animales , Anticuerpos/inmunología , Línea Celular Tumoral , Colesterol/química , Cabras , Oro/química , Humanos , Leucemia de Células B/inmunología , Linfoma/inmunología , Nanopartículas del Metal/química , Fosfatidilcolinas/química , Ovinos , Espectrometría Raman/métodos , Esfingomielinas/químicaRESUMEN
In this work, Ni particles/PA12 powders (Ni/PA12) and graphite oxide (GO)-encapsulated Ni particles/PA12 powders (GO-Ni/PA12) composite powders were prepared by defect-included electroless plating technique, and its laser sintered behaviour was investigated. Results showed that a lot of defects could formed on the surface of CH3COOH etched PA12 powders. The defects would induce Ni and GO-Ni particles independently plated on the PA12 surface. Adding GO in the plating solution would facilitate the deposition of Ni particles, GO, and NiO on the PA 12 surface, but inhibit the growth and the crystallinity of the Ni particles. The SLS process involved the contact of PA12 powders, the formation of sintering neck, the growth of sintering neck and the formation of fused solid. Sintering process could facilitate the re-arrangement of Ni particles due to surface tension and the growth of sintering neck. The Ni particles had well wettability, and the interfaces between Ni particles and PA 12 were contacted soundly. The tensile strength and bending strength of the 10 W-sintered Ni/PA12 specimen were 50 MPa and 60 MPa. But SLS process caused the serious aggregation of GO-Ni particles due to higher concentration, activity and surface area of GO-Ni particles.
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Bird species richness is mediated by local, regional, and historical factors, for example, competition, environmental heterogeneity, contemporary, and historical climate. Here, we related bird species richness with phylogenetic relatedness of bird assemblages, plant species richness, topography, contemporary climate, and glacial-interglacial climate change to investigate the relative importance of these factors. This study was conducted in Inner Mongolia, an arid and semiarid region with diverse vegetation types and strong species richness gradients. The following associated variables were included as follows: phylogenetic relatedness of bird assemblages (Net Relatedness Index, NRI), plant species richness, altitudinal range, contemporary climate (mean annual temperature and precipitation, MAT and MAP), and contemporary-Last Glacial Maximum (LGM) change in climate (change in MAT and change in MAP). Ordinary least squares linear, simultaneous autoregressive linear, and Random Forest models were used to assess the associations between these variables and bird species richness across this region. We found that bird species richness was correlated negatively with NRI and positively with plant species richness and altitudinal range, with no significant correlations with contemporary climate and glacial-interglacial climate change. The six best combinations of variables ranked by Random Forest models consistently included NRI, plant species richness, and contemporary-LGM change in MAT. Our results suggest important roles of local ecological factors in shaping the distribution of bird species richness across this semiarid region. Our findings highlight the potential importance of these local ecological factors, for example, environmental heterogeneity, habitat filtering, and biotic interactions, in biodiversity maintenance.
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Polyamide-6 (PA6) submicron-sized spheres are prepared by two steps: (1) anionic ring-opening polymerization of ε-caprolactam in the presence of poly(ethylene glycol)-block-poly-(propylene glycol)-block-poly(ethylene glycol)(PEG-b-PPG-b-PEG) and (2) separation of PA6 spheres by dissolving PEG-b-PPG-b-PEG from the prepared blends. The PA6 microspheres obtained are regular spherical, with diameter ranging from 200 nm to 2 µm and narrow size distribution, as confirmed by scanning electron microscopy. By comparison with PA6/PS and PA6/PEG systems, it is denominated that the PEG blocks in PEG-b-PPG-b-PEG can effectively reduce the surface tension of PA6 droplets and further decrease the diameter of the PA6 microspheres. The PPG block in PEG-b-PPG-b-PEG can prevent the PA6 droplets coalescing with each other, and isolated spherical particles can be obtained finally. The phase inversion of the PA6/PEG-b-PPG-b-PEG blends occurs at very low PEG-b-PPG-b-PEG content; the PEG-b-PPG-b-PEG phase can be removed by water easily. The whole experiment can be finished in a short time (approximately in half an hour) without using any organic solvents; it is an efficient strategy for the preparation of submicron-sized PA6 microspheres.
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Caprolactama/análogos & derivados , Caprolactama/química , Microesferas , Nylons/síntesis química , Polietilenglicoles/química , Polímeros/síntesis química , Glicoles de Propileno/química , Caprolactama/síntesis química , Tecnología Química Verde , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Polimerizacion , Tensión SuperficialRESUMEN
AIMS: Clonal expansion of lymphocytes may account for asymptomatic lymphocytosis. Unlike monoclonal B lymphocytosis, the detection of T-cell clones is difficult using immunophenotype-based assays. This study aimed to evaluate PCR-based clonality assays for the identification of T-cell clones among patients with unexplained lymphocytosis. METHODS: We incorporated the BIOMED-2 multiplex PCR into the investigation of peripheral lymphocytosis. Clonality analysis was performed with three reactions for TCRß and two reactions for TCRγ gene rearrangements. The analysis was performed with blood specimens from a total of 150 adult patients who presented with incidental lymphocytosis. RESULTS: PCR assays were validated using confirmed T-cell malignancies and the detection sensitivity was determined at a level of 2%. Using the TCRß and TCRγ combination, 25 (16.6%) of 150 patients were found to have clonal TCR arrangement. Patients who harboured clonal T cells presented with a mild to moderate absolute lymphocytosis, with a median lymphocyte count of 4.5 × 10(9)/l (range 3.7-9.8 × 10(9)) and the absence of other haematological abnormalities. Immunophenotyping confirmed T-cell lymphocytosis with an increase in CD8 T cells in the majority of patients. CONCLUSIONS: This study demonstrated the use of PCR assays for the effective detection of clonal T lymphocytosis. Our data indicate a high prevalence of silent T-cell clones among patients with peripheral lymphocytosis.
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Genes Codificadores de la Cadena beta de los Receptores de Linfocito T/genética , Linfocitosis/inmunología , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T/inmunología , Adulto , Reordenamiento Génico , Humanos , Linfocitosis/genética , Linfocitosis/patología , Reacción en Cadena de la Polimerasa , Linfocitos T/patologíaRESUMEN
The labeling of cell surface receptors by fluorescent markers is an established method for the identification of cell phenotype in both research and clinical settings. Fluorescence dye labeling has inherent constraints, most notably the upper limit of labels per cell that may be probed using a single excitation source, in addition to a physical limit to the number of broad emission spectra that can be distinctly collected within the visible wavelength region. SERS labeling has the potential to mitigate these shortfalls. Herein, antibody-targeted, PEG-coated surface-enhanced Raman scattering (SERS) Au nanoparticles are used simultaneously to label three cell surface markers of interest on malignant B cells from the LY10 lymphoma cell line. The SERS probes were characterized by multiple methods to confirm their monodispersity and functionalization with both PEG and monoclonal antibodies. The specificity of the particles' cell labeling was demonstrated on both primary chronic lymphocytic leukemia and LY10 cells using SERS from cell suspensions and confocal Raman mapping, respectively. Fluorescence flow cytometry was employed to confirm the binding of SERS probes to LY10 over large cell populations, and the particles' SERS was collected directly from labeled cells using a commercial flow cytometer. To the best of our knowledge, this is the first demonstration of SERS flow cytometry from cells tagged with targeted SERS probes.
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Citometría de Flujo/métodos , Colorantes Fluorescentes/química , Oro/química , Leucemia/patología , Linfoma/patología , Nanopartículas del Metal/química , Espectrometría Raman/métodos , Animales , Anticuerpos Monoclonales/inmunología , Antígenos CD/inmunología , Antígenos CD/metabolismo , Linfocitos B/metabolismo , Línea Celular Tumoral , Regulación de la Expresión Génica , Humanos , Especificidad por Sustrato , Propiedades de SuperficieRESUMEN
The extensive reclamation of marshland into cropland has tremendously impacted the ecological environment of the Sanjiang Plain in northeast China. To understand the impacts of marshland reclamation and restoration on soil properties, we investigated the labile organic carbon fractions and the soil enzyme activities in an undisturbed marshland, a cultivated marshland and three marshlands that had been restored for 3, 6 and 12 years. Soil samples collected from the different management systems at a depth of 0-20 cm in July 2009 were analyzed for soil organic carbon (SOC), dissolved organic carbon (DOC), microbial biomass carbon (MBC) and easily degradable organic carbon. In addition, the activities of the invertase, ß-glucosidase, urease and acid phosphatase were determined. These enzymes are involved in C, N and P cycling, respectively. Long-term cultivation resulted in decreased SOC, DOC, MBC, microbial quotient and C (invertase, ß-glucosidase) and N-transforming (urease) enzyme activities compared with undisturbed marshland. After marshland restoration, the MBC and DOC concentrations and the soil invertase, ß-glucosidase and urease activities increased. Soil DOC and MBC concentrations are probably the main factors responsible for the different invertase, ß-glucosidase and urease activities. In addition, marshland restoration caused a significant increase in the microbial quotient, which reflects enhanced efficiency of organic substrate use by microbial biomass. Our observations demonstrated that soil quality recovered following marshland restoration. DOC, MBC and invertase, ß-glucosidase and urease activities were sensitive for discriminating soil ecosystems under the different types of land use. Thus, these parameters should be considered to be indicators for detecting changes in soil quality and environmental impacts in marshlands.
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Carbono/metabolismo , Conservación de los Recursos Naturales , Microbiología del Suelo , Suelo/química , Humedales , Agricultura , Biomasa , China , Enzimas/metabolismoRESUMEN
Plant aboveground biomass, total organic carbon( TOC), microbial biomass carbon( MBC), basal respiration( BR), microbial quotient (Cmic/Corg) and metabolic quotient (qCO2) in 0-15 cm and 15-50 cm marsh soil of Calamagrostis angustifolia under different water levels were investigated with controlled experiment. The result showed that water level exerted significant effect on plant biomass, which was the highest under 10 cm waterlogged level and of higher productivity under 0-20 cm waterlogged level. TOC, MBC, BR, Cmic/Corg and qCO2 differed significantly under different water levels. BR and TOC responded to different waterlogged levels in the same way. BR and TOC of 0-15 cm marsh soil were the highest under 0 cm waterlogged level, however, BR and TOC of 15-50 cm marsh soil decreased respectively with increasing water, which was corresponding with soil MBC and Cmic/Corg and qCO2 increased with increasing water. As a result, microbial community is altered and microbial activity is decreasing by increasing waterlogged level, and microbial activity is the lowest under 30 cm waterlogged level, which affects organic carbon accumulation and decomposition.
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Biomasa , Poaceae/metabolismo , Microbiología del Suelo , Agua/análisis , Humedales , Carbono/análisis , China , Poaceae/clasificación , Poaceae/crecimiento & desarrollo , Suelo/análisisRESUMEN
By the soil respiration system of Li-6400, the characteristics of soil respiration with and without litter were investigated to explore the litter's contributions to soil respiration and its correlations with the input of litter and environmental factors under different land-use types in Sanjiang Plain. Results demonstrated that the average contribution of litter to soil respiration ranged from - 0.21 to 0.64 micromol/(m2 x s) in the growing season under the four land-use types. The contribution rate showed in the following order: wetland (14%) > artificial forest (12%) > soybean field (8%) > abandoned land (- 5%). As to abandoned land, the value was negative, and the litter inhibited soil respiration. The litter' s contributions to soil respiration may depend on the balance between the decomposition of litter and its shielding effects on soil respiration. There were highly significant correlations between litter's contributions to soil respiration and soil temperature at 10cm depth except for soybean field. Moreover, the influence of rainfall associated with the input of litter, which suggested that besides decomposition litter may take part in the ecological effect of climate changes in the future.
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Dióxido de Carbono/análisis , Glycine max/crecimiento & desarrollo , Suelo/análisis , Árboles/genética , Humedales , China , Monitoreo del Ambiente , Hojas de la Planta/metabolismo , Lluvia , TemperaturaRESUMEN
OBJECTIVE: To evaluate the biological safety of continuous carbon-fiber reinforced polyolefin as hard tissue repair material. METHODS: Biocompatibility of the material was evaluated through hemolysis test, pyrogen test, skin irritation test, cytotoxicity test, ames test, in vitro chromosome aberration test, and bone marrow cells Micronuclei test. RESULTS: No obvious hemolysis, pyrogenic characteristics, sensitivity, cytotoxicity, and mutagenicity were observed. CONCLUSION: The continuous carbon-fiber reinforced polyolefin composite material is of good biological safety. It meets all the demand made by biological safety as hard tissue repair material.
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Materiales Biocompatibles/toxicidad , Carbono/toxicidad , Polienos/toxicidad , Animales , Materiales Biocompatibles/química , Carbono/química , Fibra de Carbono , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cricetinae , Cobayas , Hemólisis/efectos de los fármacos , Ensayo de Materiales , Ratones , Polienos/química , Conejos , Ratas , Pruebas de ToxicidadRESUMEN
BACKGROUND: Fewer than 30 cases of oligodendroglioma or anaplastic oligodendroglioma metastatic to bone are reported in the literature. Prolonged survival even with therapy is uncommon. METHODS: We report a case of anaplastic oligodendroglioma metastatic to bone with a dramatic and durable response to temozolomide therapy. A retrospective case review, molecular analysis, and literature search were performed. RESULTS: The patient presented with a right frontal mass in 1990. Progression led to resection of the lesion in 1995. Histology revealed an anaplastic oligodendroglioma and the tumour was found to have allelic loss of heterozygosity (LOH) of chromosome 1p (1p-). He received standard radiation therapy. In 2000 he developed hip and pelvic pain. A bone scan showed multiple skeletal lesions. Magnetic resonance imaging of the brain showed stability of intracranial disease. Resection of one lesion found metastatic anaplastic oligodendroglioma with identical morphology to the patient's original tumour, including glial fibrillary acidic protein expression. The patient was started on standard temozolomide chemotherapy and celecoxib with prompt pain relief, and rapid normalization of serum alkaline phosphatase. He received a total of 12 cycles of combined therapy with no toxicity and no evidence of progression until increasing pain marked disease recurrence. The patient underwent palliative chemo- and radiation therapy but eventually succumbed. DISCUSSION: Loss of heterozygosity 1p- is associated with prolonged survival in anaplastic oligodendroglioma and may increase the cumulative risk for development of systemic metastases. We speculate that metastases from oligodendroglioma harbouring loss of heterozygosity at chromosome 1p- retain the chemosensitivity of the initial lesion.