157 research outputs found
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Rapalink-1 Targets Glioblastoma Stem Cells and Acts Synergistically with Tumor Treating Fields to Reduce Resistance against Temozolomide.
Temporal stability of soil moisture and radar backscatter observed by the advanced Synthetic Aperture Radar (ASAR)
The high spatio-temporal variability of soil moisture is the result of atmospheric forcing and redistribution processes related to terrain, soil, and vegetation characteristics. Despite this high variability, many field studies have shown that in the temporal domain soil moisture measured at specific locations is correlated to the mean soil moisture content over an area. Since the measurements taken by Synthetic Aperture Radar (SAR) instruments are very sensitive to soil moisture it is hypothesized that the temporally stable soil moisture patterns are reflected in the radar backscatter measurements. To verify this hypothesis 73 Wide Swath (WS) images have been acquired by the ENVISAT Advanced Synthetic Aperture Radar (ASAR) over the REMEDHUS soil moisture network located in the Duero basin, Spain. It is found that a time-invariant linear relationship is well suited for relating local scale (pixel) and regional scale (50 km) backscatter. The observed linear model coefficients can be estimated by considering the scattering properties of the terrain and vegetation and the soil moisture scaling properties. For both linear model coefficients, the relative error between observed and modelled values is less than 5 % and the coefficient of determination (R-2) is 86 %. The results are of relevance for interpreting and downscaling coarse resolution soil moisture data retrieved from active (METOP ASCAT) and passive (SMOS, AMSR-E) instruments
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Rapalink-1 Targets Glioblastoma Stem Cells and Acts Synergistically with Tumor Treating Fields to Reduce Resistance against Temozolomide.
Glioblastoma (GBM) is a lethal disease with limited clinical treatment options available. Recently, a new inhibitor targeting the prominent cancer signaling pathway mTOR was discovered (Rapalink-1), but its therapeutic potential on stem cell populations of GBM is unknown. We applied a collection of physiological relevant organoid-like stem cell models of GBM and studied the effect of RL1 exposure on various cellular features as well as on the expression of mTOR signaling targets and stem cell molecules. We also undertook combination treatments with this agent and clinical GBM treatments tumor treating fields (TTFields) and the standard-of-care drug temozolomide, TMZ. Low nanomolar (nM) RL1 treatment significantly reduced cell growth, proliferation, migration, and clonogenic potential of our stem cell models. It acted synergistically to reduce cell growth when applied in combination with TMZ and TTFields. We performed an in silico analysis from the molecular data of diverse patient samples to probe for a relationship between the expression of mTOR genes, and mesenchymal markers in different GBM cohorts. We supported the in silico results with correlative protein data retrieved from tumor specimens. Our study further validates mTOR signaling as a druggable target in GBM and supports RL1, representing a promising therapeutic target in brain oncology
Data mashups: potential contribution to decision support on climate change and health.
notes: PMCID: PMC3945564This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Linking environmental, socioeconomic and health datasets provides new insights into the potential associations between climate change and human health and wellbeing, and underpins the development of decision support tools that will promote resilience to climate change, and thus enable more effective adaptation. This paper outlines the challenges and opportunities presented by advances in data collection, storage, analysis, and access, particularly focusing on "data mashups". These data mashups are integrations of different types and sources of data, frequently using open application programming interfaces and data sources, to produce enriched results that were not necessarily the original reason for assembling the raw source data. As an illustration of this potential, this paper describes a recently funded initiative to create such a facility in the UK for use in decision support around climate change and health, and provides examples of suitable sources of data and the purposes to which they can be directed, particularly for policy makers and public health decision makers.UK Medical Research CouncilUK Natural Environment Research CouncilEuropean Regional Development Fund Programme 2007 to 2013European Social Fund Convergence Programme for Cornwall and the Isles of Scill
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A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity
Abstract: Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply of macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy in cancer therapy. Several tumors excessively metabolize glutamine to generate precursors for nonessential amino acids, nucleotides, and lipids, in a process called glutaminolysis. Here we show that pharmacological inhibition of glutaminase (GLS) eradicates glioblastoma stem-like cells (GSCs), a small cell subpopulation in glioblastoma (GBM) responsible for therapy resistance and tumor recurrence. Treatment with small molecule inhibitors compound 968 and CB839 effectively diminished cell growth and in vitro clonogenicity of GSC neurosphere cultures. However, our pharmaco-metabolic studies revealed that only CB839 inhibited GLS enzymatic activity thereby limiting the influx of glutamine derivates into the TCA cycle. Nevertheless, the effects of both inhibitors were highly GLS specific, since treatment sensitivity markedly correlated with GLS protein expression. Strikingly, we found GLS overexpressed in in vitro GSC models as compared with neural stem cells (NSC). Moreover, our study demonstrates the usefulness of in vitro pharmaco-metabolomics to score target specificity of compounds thereby refining drug development and risk assessment
A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity
Abstract: Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply of macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy in cancer therapy. Several tumors excessively metabolize glutamine to generate precursors for nonessential amino acids, nucleotides, and lipids, in a process called glutaminolysis. Here we show that pharmacological inhibition of glutaminase (GLS) eradicates glioblastoma stem-like cells (GSCs), a small cell subpopulation in glioblastoma (GBM) responsible for therapy resistance and tumor recurrence. Treatment with small molecule inhibitors compound 968 and CB839 effectively diminished cell growth and in vitro clonogenicity of GSC neurosphere cultures. However, our pharmaco-metabolic studies revealed that only CB839 inhibited GLS enzymatic activity thereby limiting the influx of glutamine derivates into the TCA cycle. Nevertheless, the effects of both inhibitors were highly GLS specific, since treatment sensitivity markedly correlated with GLS protein expression. Strikingly, we found GLS overexpressed in in vitro GSC models as compared with neural stem cells (NSC). Moreover, our study demonstrates the usefulness of in vitro pharmaco-metabolomics to score target specificity of compounds thereby refining drug development and risk assessment
Melanoma Patients with Positive Sentinel Nodes Who Did Not Undergo Completion Lymphadenectomy: A Multi-Institutional Study
Completion lymph node dissection (CLND) is considered the standard of care in melanoma patients found to have sentinel lymph node (SLN) metastasis. However, the therapeutic utility of CLND is not known. The natural history of patients with positive SLNs who do not undergo CLND is undefined. This multi-institutional study was undertaken to characterize patterns of failure and survival rates in these patients and to compare results with those of positive-SLN patients who underwent CLND.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45875/1/10434_2006_Article_10237.pd
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radica en discutir sobre la crisis de la âciudadâ o
de la âurbanidadâ que se manifiesta con mĂĄs fuerza en
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