907 resultados para Glioblastoma,. ABC transporters, hypoxia, Doxorubicin, Temozolomide, Pgp
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The overall goal of this assessment was to evaluate the effects of nutrient-source reductions that may be implemented in the Mississippi River Basin (MRB) to reduce the problem of low oxygen conditions (hypoxia) in the nearshore Gulf of Mexico. Such source reductions would affect the quality of surface waters—streams, rivers, and reservoirs—in the drainage basin itself, as well as nearshore Gulf waters. The task group’s work was divided into addressing the effects of nutrient-source reductions on: (1) surface waters in the MRB and (2) hypoxia in the Gulf of Mexico.
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Ths report addresses the following two questions: 1) What are the loads (flux) of nutrients transported from the Mississippi-Atchafalaya River Basin to the Gulf of Mexico, and where do they come from within the basin? 2) What is the relative importance of specific human activities, such as agriculture, point-source discharges, and atmospheric deposition in contributing to these loads? These questions were addressed by first estimating the flux of nutrients from the Mississippi-Atchafalaya River Basin and about 50 interior basins in the Mississippi River system using measured historical streamflow and water quality data. Annual nutrient inputs and outputs to each basin were estimated using data from the National Agricultural Statistics Service, National Atmospheric Deposition Program, and point-source data provided by the USEPA. Next, a nitrogen mass balance was developed using agricultural statistics, estimates of nutrient cycling in agricultural systems, and a geographic information system. Finally, multiple regression models were developed to estimate the relative contributions of the major input sources to the flux of nitrogen and phosphorus to the Gulf of Mexico.
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In this report we have attempted to evaluate the ecological and economic consequences of hypoxia in the northern Gulf of Mexico. Although our initial approach was to rely on published accounts, we quickly realized that the body of published literature deahng with hypoxia was limited, and we would have to conduct our own exploratory analysis of existing Gulf data, or rely on published accounts from other systems to infer possible or potential effects of hypoxia. For the economic analysis, we developed a conceptual model of how hypoxia-related impacts could affect fisheries. Our model included both supply and demand components. The supply model had two components: (1) a physical production function for fish or shrimp, and (2) the cost of fishing. If hypoxia causes the cost of a unit of fishing effort to change, then this will result in a shift in supply. The demand model considered how hypoxia might affect the quality of landed fish or shrimp. In particular, the market value per pound is lower for small shrimp than for large shrimp. Given the limitations of the ecological assessment, the shallow continental shelf area affected by hypoxia does show signs of hypoxia-related stress. While current ecological conditions are a response to a variety of stressors, the effects of hypoxia are most obvious in the benthos that experience mortality, elimination of larger long-lived species, and a shifting of productivity to nonhypoxic periods (energy pulsing). What is not known is whether hypoxia leads to higher productivity during productive periods, or simply to a reduction of productivity during oxygen-stressed periods. The economic assessment based on fisheries data, however, failed to detect effects attributable to hypoxia. Overall, fisheries landings statistics for at least the last few decades have been relatively constant. The failure to identify clear hypoxic effects in the fisheries statistics does not necessarily mean that they are absent. There are several possibilities: (1) hypoxic effects are small relative to the overall variability in the data sets evaluated; (2) the data and the power of the analyses are not adequate; and (3) currently there are no hypoxic effects on fisheries. Lack of identified hypoxic effects in available fisheries data does not imply that effects would not occur should conditions worsen. Experience with other hypoxic zones around the globe shows that both ecological and fisheries effects become progressively more severe as hypoxia increases. Several large systems around the globe have suffered serious ecological and economic consequences from seasonal summertime hypoxia; most notable are the Kattegat and Black Sea. The consequences range from localized loss of catch and recruitment failure to complete system-wide loss of fishery species. If experiences in other systems are applicable to the Gulf of Mexico, then in the face of worsening hypoxic conditions, at some point fisheries and other species will decline, perhaps precipitously.
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Nutrient overenrichment from human activities is one of the major stresses affecting coastal ecosystems. There is increasing concern in many areas around the world that an oversupply of nutrients from multiple sources is having pervasive ecological effects on shallow coastal and estuarine areas. These effects include reduced light penetration, loss of aquatic habitat, harmfid algal blooms, a decrease in dissolved oxygen (or hypoxia), and impacts on living resources. The largest zone of oxygen-depleted coastal waters in the United States, and the entire western Atlantic Ocean, is found in the northern Gulf of Mexico on the Louisiana-Texas continental shelf. This zone is influenced by the freshwater discharge and nutrient flux of the Mississippi River system. This report describes the seasonal, interannual, and long-term variability in hypoxia in the northern Gulf of Mexico and its relationship to nutrient loading. It also documents the relative roles of natural and human-induced factors in determining the size and duration of the hypoxic zone.
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The occurrence of hypoxia, or low dissolved oxygen, is increasing in coastal waters worldwide and represents a significant threat to the health and economy of our Nation’s coasts and Great Lakes. This trend is exemplified most dramatically off the coast of Louisiana and Texas, where the second largest eutrophication-related hypoxic zone in the world is associated with the nutrient pollutant load discharged by the Mississippi and Atchafalaya Rivers. Aquatic organisms require adequate dissolved oxygen to survive. The term “dead zone” is often used in reference to the absence of life (other than bacteria) from habitats that are devoid of oxygen. The inability to escape low oxygen areas makes immobile species, such as oysters and mussels, particularly vulnerable to hypoxia. These organisms can become stressed and may die due to hypoxia, resulting in significant impacts on marine food webs and the economy. Mobile organisms can flee the affected area when dissolved oxygen becomes too low. Nevertheless, fish kills can result from hypoxia, especially when the concentration of dissolved oxygen drops rapidly. New research is clarifying when hypoxia will cause fish kills as opposed to triggering avoidance behavior by fish. Further, new studies are better illustrating how habitat loss associated with hypoxia avoidance can impose ecological and economic costs, such as reduced growth in commercially harvested species and loss of biodiversity, habitat, and biomass. Transient or “diel-cycling” hypoxia, where conditions cycle from supersaturation of oxygen late in the afternoon to hypoxia or anoxia near dawn, most often occurs in shallow, eutrophic systems (e.g., nursery ground habitats) and may have pervasive impacts on living resources because of both its location and frequency of occurrence.
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目的 探讨大蹼铃蟾抗菌肽22 (Maximin22) 对膀胱癌 细胞株HLA2DR 及HLA2ABC 表达的影响, 并与TNF2α、 IFN2α进行比较。方法 采用肿瘤细胞培养方法,流式细胞 仪检测各实验样品对膀胱癌细胞株T24 、BIU287 、SCaBER 的HLA2DR 及HLA2ABC 表达的影响。结果 Maximin22 对 不同的膀胱癌细胞株在小剂量下即有抑制作用,并呈剂量相 关性,各实验样品未见对各膀胱癌细胞株的HLA2DR 表达 有影响,Maximin22 、TNF2α对HLA2ABC 的表达均无影响; IFN2α则对HLA2ABC 的表达有上调作用。结论 Maximin2 2 、TNF2α抗癌机制与提高肿瘤细胞HLA2DR、ABC 的表达无 关, IFN2α可通过提高肿瘤细胞HLA2ABC 的表达提高T 细 胞对膀胱肿瘤的识别杀伤能力。
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ABC转运蛋白主要包括P-糖蛋白、多药耐药相关蛋白和乳腺癌耐药蛋白,它们属于同一家族,具有保守的功能结构域和多样化的生物学功能。ABC转运蛋白部分成员的过表达与肿瘤细胞的多药耐药性(MDR)密切相关,是导致化疗失败的主要原因。随着对MDR机制认识的深入,针对多药耐药蛋白的特异结构域已设计出多种形式的MDR逆转药物。近年来发现,ABC转运蛋白广泛存在于多种正常的组织和器官,参与药物和内、外源毒素的吸收、分布和排泄,行使解毒和防御保护的作用。因此,通过转植ABC转运蛋白基因有可能降低经济鱼类、虾等水产品中有毒
Identifying cancer subtypes in glioblastoma by combining genomic, transcriptomic and epigenomic data
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We present a nonparametric Bayesian method for disease subtype discovery in multi-dimensional cancer data. Our method can simultaneously analyse a wide range of data types, allowing for both agreement and disagreement between their underlying clustering structure. It includes feature selection and infers the most likely number of disease subtypes, given the data. We apply the method to 277 glioblastoma samples from The Cancer Genome Atlas, for which there are gene expression, copy number variation, methylation and microRNA data. We identify 8 distinct consensus subtypes and study their prognostic value for death, new tumour events, progression and recurrence. The consensus subtypes are prognostic of tumour recurrence (log-rank p-value of $3.6 \times 10^{-4}$ after correction for multiple hypothesis tests). This is driven principally by the methylation data (log-rank p-value of $2.0 \times 10^{-3}$) but the effect is strengthened by the other 3 data types, demonstrating the value of integrating multiple data types. Of particular note is a subtype of 47 patients characterised by very low levels of methylation. This subtype has very low rates of tumour recurrence and no new events in 10 years of follow up. We also identify a small gene expression subtype of 6 patients that shows particularly poor survival outcomes. Additionally, we note a consensus subtype that showly a highly distinctive data signature and suggest that it is therefore a biologically distinct subtype of glioblastoma. The code is available from https://sites.google.com/site/multipledatafusion/
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Organisms living in water are inevitably exposed to periods of hypoxia. Environmental hypoxia has been an important stressor having manifold effects on aquatic life. Many fish species have evolved behavioral, physiological, biochemical and molecular adaptations that enable them to cope with hypoxia. However, the molecular mechanisms of hypoxia tolerance in fish, remain unknown. in this study, we used suppression subtractive hybridization to examine the differential gene expression in CAB cells (Carassius auratus blastulae embryonic cells) exposed to hypoxia for 24 h. We isolated 2100 clones and identified 211 differentially expressed genes (e-value <= 5e-3; Identity > 45%). Among the genes whose expression is modified in cells, a vast majority involved in metabolism, signal transduction, cell defense, angiogenesis, cell growth and proliferation. Twelve genes encoding for ERO1-L, p53, CPO, HO-1, MKP2, PFK-2, cystatin B, GLUT1, BTG1, TGF beta 1, PGAM1, hypothetical protein F1508, were selected and identified to be hypoxia-induced using semi-quantitive RT-PCR and real-time PCR. Among the identified genes, two open reading frames (ORFs) encoding for CaBTG1 and Cacystatin B were obtained. The deduced amino acid sequence of CaBTG1 had 94.1%, 72.8%, 72.8%, 72.8%, 68.6% identity with that of DrBTG1, HsBTG1, BtBTG1, MmBTG1 and XIBTG1. Comparison of Cacystatin B with known cystatin B, the molecules exhibited 49.5 to 76.0% identity overall. These results may provide significant information for further understanding of the adaptive mechanism by which C. auratus responds to hypoxia. (c) 2008 Elsevier Inc. All rights reserved.
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The dependence of the Raman spectrum on the excitation energy has been investigated for ABA-and ABC- stacked few-layer graphene in order to establish the fingerprint of the stacking order and the number of layers, which affect the transport and optical properties of few-layer graphene. Five different excitation sources with energies of 1.96, 2.33, 2.41, 2.54 and 2.81â €...eV were used. The position and the line shape of the Raman 2D, G*, N, M, and other combination modes show dependence on the excitation energy as well as the stacking order and the thickness. One can unambiguously determine the stacking order and the thickness by comparing the 2D band spectra measured with 2 different excitation energies or by carefully comparing weaker combination Raman modes such as N, M, or LOLA modes. The criteria for unambiguous determination of the stacking order and the number of layers up to 5 layers are established.
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BACKGROUND: Hypoxia and ischemia induce neuronal damage, decreased neuronal numbers and synaptophysin levels, and deficits in learning and memory functions. Previous studies have shown that lycium barbarum polysaccharide, the most effective component of barbary wolfberry fruit, has protective effects on neural cells in hypoxia-ischemia. OBJECTIVE: To investigate the effects of Naotan Pill on glutamate-treated neural cells and on cognitive function in juvenile rats following hypoxia-ischemia. DESIGN, TIME AND SETTING: The randomized, controlled, in vivo study was performed at the Cell Laboratory of Lanzhou University, Lanzhou Institute of Modern Physics of Chinese Academy of Sciences, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from December 2005 to August 2006. The cellular neurobiology, in vitro experiment was conducted at the Institute of Human Anatomy, Histology, Embryology and Neuroscience, School of Basic Medical Sciences, Lanzhou University, and Department of Traditional Chinese Medicine of Gansu Provincial Rehabilitation Center Hospital, China from March 2007 to January 2008. MATERIALS: Naotan Pill, composed of barbary wolfberry fruit, danshen root, grassleaf sweetflag rhizome, and glossy privet fruit, was prepared by Gansu Provincial Rehabilitation Center, China. Rabbit anti-synaptophysin, choline acetyl transferase polyclonal antibody, streptavidin-biotin complex kit and diaminobenzidine kit (Boster, Wuhan, China), as well as glutamate (Hualian, Shanghai, China) were used in this study. METHODS: Cortical neural cells were isolated from neonatal Wistar rats. Neural cell damage models were induced using glutamate, and administered Naotan Pill prior to and following damage. A total of 54 juvenile Wistar rats were equally and randomly assigned into model, Naotan Pill, and sham operation groups. The left common carotid artery was ligated, and then rat models of hypoxic-ischemic injury were assigned to the model and Naotan Pill groups. At 2 days following model induction, rats in the Naotan Pill group were administered Naotan Pill suspension for 21 days. In the model and sham operation groups, rats received an equal volume of saline. MAIN OUTCOME MEASURES: Neural cell morphology was observed using an inverted phase contrast microscope. Survival rate of neural cells was measured by MTT assay. Synaptophysin and choline acetyl transferase expression was observed in the hippocampal CA1 region of juvenile rats using immunohistochemistry. Cognitive function was tested by the Morris water maze. RESULTS: Pathological changes were detected in glutamate-treated neural cells. Neural cell morphology remained normal after Naotan Pill intervention. Absorbance and survival rate of neural cells were significantly greater following Naotan Pill intervention, compared to glutamate-treated neural cells (P < 0.05). Synaptophysin and choline acetyl transferase expression was lowest in the hippocampal CA1 region in the model group and highest in the sham operation group. Significant differences among groups were observed (P < 0.05). Escape latency and swimming distance were significantly longer in the model group compared to the Naotan Pill group (P < 0.05). CONCLUSION: Naotan Pill exhibited protective and repair effects on glutamate-treated neural cells. Naotan Pill upregulated synaptophysin and choline acetyl transferase expression in the hippocampus and improved cognitive function in rats following hypoxia-ischemia.