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- Mörén, Lina, et al.
(author)
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Metabolomic profiling identifies distinct phenotypes for ASS1 positive and negative GBM
- 2018
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In: BMC Cancer. - : BioMed Central. - 1471-2407. ; 18
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Journal article (peer-reviewed)abstract
- Background: Tumour cells have a high demand for arginine. However, a subset of glioblastomas has a defect in the arginine biosynthetic pathway due to epigenetic silencing of the rate limiting enzyme argininosuccinate synthetase (ASS1). These tumours are auxotrophic for arginine and susceptible to the arginine degrading enzyme, pegylated arginine deiminase (ADI-PEG20). Moreover, ASS1 deficient GBM have a worse prognosis compared to ASS1 positive tumours. Since altered tumour metabolism is one of the hallmarks of cancer we were interested to determine if these two subtypes exhibited different metabolic profiles that could allow for their non-invasive detection as well as unveil additional novel therapeutic opportunities.Methods: We looked for basal metabolic differences using one and two-dimensional gas chromatography-time-of-flight mass spectrometry (1D/2DGC-TOFMS) followed by targeted analysis of 29 amino acids using liquid chromatography-time-of-flight mass spectrometry (LC-TOFMS). We also looked for differences upon arginine deprivation in a single ASS1 negative and positive cell line (SNB19 and U87 respectively). The acquired data was evaluated by chemometric based bioinformatic methods.Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) of both the 1D and 2D GC-TOFMS data revealed significant systematic difference in metabolites between the two subgroups with ASS1 positive cells generally exhibiting an overall elevation of identified metabolites, including those involved in the arginine biosynthetic pathway. Pathway and network analysis of the metabolite profile show that ASS1 negative cells have altered arginine and citrulline metabolism as well as altered amino acid metabolism. As expected, we observed significant metabolite perturbations in ASS negative cells in response to ADI-PEG20 treatment.Conclusions: This study has highlighted significant differences in the metabolome of ASS1 negative and positive GBM which warrants further study to determine their diagnostic and therapeutic potential for the treatment of this devastating disease.
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| 2. |
- Richard, M. S., et al.
(author)
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An empirical approach to modeling ion production rates in Titan's ionosphere I : Ion production rates on the dayside and globally
- 2015
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In: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 120:2, s. 1264-1280
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Journal article (peer-reviewed)abstract
- Titan's ionosphere is created when solar photons, energetic magnetospheric electrons or ions, and cosmic rays ionize the neutral atmosphere. Electron densities generated by current theoretical models are much larger than densities measured by instruments on board the Cassini orbiter. This model density overabundance must result either from overproduction or from insufficient loss of ions. This is the first of two papers that examines ion production rates in Titan's ionosphere, for the dayside and nightside ionosphere, respectively. The first (current) paper focuses on dayside ion production rates which are computed using solar ionization sources (photoionization and electron impact ionization by photoelectrons) between 1000 and 1400km. In addition to theoretical ion production rates, empirical ion production rates are derived from CH4, CH3+, and CH4+ densities measured by the INMS (Ion Neutral Mass Spectrometer) for many Titan passes. The modeled and empirical production rate profiles from measured densities of N-2(+) and CH4+ are found to be in good agreement (to within 20%) for solar zenith angles between 15 and 90 degrees. This suggests that the overabundance of electrons in theoretical models of Titan's dayside ionosphere is not due to overproduction but to insufficient ion losses.
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