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Sökning: WFRF:(Morentin Gutierrez Pablo) > (2018) > Quantitation of End...

Quantitation of Endogenous Metabolites in Mouse Tumors Using Mass-Spectrometry Imaging

Swales, John G. (författare)
AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England;Sheffield Hallam Univ, Ctr Mass Spectrometry Imaging, Biomol Res Ctr, Sheffield S1 1WB, S Yorkshire, England
Dexter, Alex (författare)
Natl Ctr Excellence Mass Spectrometry Imaging NiC, Natl Phys Lab, Teddington TW11 0LW, Middx, England
Hamm, Gregory (författare)
AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England
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Nilsson, Anna (författare)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
Strittmatter, Nicole (författare)
AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England
Michopoulos, Filippos (författare)
AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England
Hardy, Christopher (författare)
AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England
Morentin-Gutierrez, Pablo (författare)
AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England
Mellor, Martine (författare)
AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England
Andrén, Per E. (författare)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
Clench, Malcolm R. (författare)
Sheffield Hallam Univ, Ctr Mass Spectrometry Imaging, Biomol Res Ctr, Sheffield S1 1WB, S Yorkshire, England
Bunch, Josephine (författare)
Natl Ctr Excellence Mass Spectrometry Imaging NiC, Natl Phys Lab, Teddington TW11 0LW, Middx, England
Critchlow, Susan E. (författare)
AstraZeneca, IMED Biotech Unit, Biosci, Oncol, Cambridge CB4 0WG, England
Goodwin, Richard J. A. (författare)
AstraZeneca, IMED Biotech Unit, Pathol Drug Safety & Metab, Darwin Bldg,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, Cambs, England
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 (creator_code:org_t)
2018-04-18
2018
Engelska.
Ingår i: Analytical Chemistry. - : AMER CHEMICAL SOC. - 0003-2700 .- 1520-6882. ; 90:10, s. 6051-6058
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Described is a quantitative-mass-spectrometry-imaging (qMSI) methodology for the analysis of lactate and glutamate distributions in order to delineate heterogeneity among mouse tumor models used to support drug-discovery efficacy testing. We evaluate and report on preanalysis-stabilization methods aimed at improving the reproducibility and efficiency of quantitative assessments of endogenous molecules in tissues. Stability experiments demonstrate that optimum stabilization protocols consist of frozen-tissue embedding, post-tissue-sectioning desiccation, and storage at -80 degrees C of tissue sections sealed in vacuum-tight containers. Optimized stabilization protocols are used in combination with qMSI methodology for the absolute quantitation of lactate and glutamate in tumors, incorporating the use of two different stable-isotope-labeled versions of each analyte and spectral-clustering performed on each tissue section using k-means clustering to allow region-specific, pixel-by-pixel quantitation. Region-specific qMSI was used to screen different tumor models and identify a phenotype that has low lactate heterogeneity, which will enable accurate measurements of lactate modulation in future drug-discovery studies. We conclude that using optimized qMSI protocols, it is possible to quantify endogenous metabolites within tumors, and region-specific quantitation can provide valuable insight into tissue heterogeneity and the tumor microenvironment.

Ämnesord

NATURVETENSKAP  -- Kemi -- Analytisk kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences -- Analytical Chemistry (hsv//eng)

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