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ABSTRACT: Colorectal cancer is one of the most frequent and most lethal forms of cancer in the western world. The aim of this study
is to characterize by 1H high resolution magic angle spinning NMR spectroscopy (HRMAS) the metabolic fingerprint of both tumoral and healthy tissue
samples obtained from a cohort of patients affected by primary colorectal adenocarcinoma. By analyzing HRMAS data using multivariate
statistical analysis (PLS-DA), the two types of tissues could be discriminated with a high level of confidence. The identification
of the metabolites at the origin of this discrimination revealed that adenocarcinomas are richer in taurine, glutamate, aspartate,
and lactate whereas healthy tissues contain a higher amount of myo-inositol and β-glucose. The statistical model resulting
from the PLS-DA analysis was subsequently used to perform a blind test on tumoral and healthy colon biopsies. The results
of the classification showed that the HRMAS analysis has very high sensitivity and specificity.
Metabolomics 04/2012; 5(3):292-301. · 4.51 Impact Factor
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ABSTRACT: High resolution magic-angle spinning (HRMAS) NMR spectroscopy is a well established technique for ex vivo metabolite investigations but experimental factors such as ischemic delay or mechanical stress due to continuous spinning deserve further investigations. Cortical brain samples from rats that underwent ultrafast in vivo microwave irradiation (MWp group) were compared to similar samples that underwent standard nitrogen freezing with and without exposure to domestic microwaves (FN and FN+MWd groups). One dimensional (1)H HRMAS NMR spectra were acquired and 16 metabolites of interest were quantified. Within each group 3 samples underwent long lasting acquisition (up to 15 h). Statistically significant differences in metabolite concentrations were observed between groups for metabolites associated to post mortem biochemical changes and/or anaerobic glycolysis including several neurotransmitters. Spectral assessment over time showed a drastic reduction of biochemical variations in both MW groups. Only 2/16 metabolites exhibited significant signal variations after 15 h of continuous spinning and acquisition in the MWp group. This number increased to 10 in the FN group. We confirmed limited anaerobic metabolism and post mortem degradation after ultra fast in vivo MW irradiation. Furthermore, spectra obtained after MWp and MWd irradiation exhibited an extremely stable spectral pattern over extended periods of continuous acquisition.
Journal of neuroscience methods 07/2011; 201(1):89-97. · 2.30 Impact Factor
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ABSTRACT: Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i) discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii) generate statistical models capable of classifying borderline tumors and (iii) establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using (1)H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate) and mucinous (N-acetyl-lysine) carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients.
Journal of Oncology 01/2011; 2011:174019.
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IRBM. 01/2011; 32(5):279-283.
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ABSTRACT: High-resolution magic angle spinning (HRMAS) <sup>1</sup>H spectroscopy is playing an increasingly important role for diagnosis. This technique enables setting up metabolite profiles of ex vivo pathological and healthy tissue. Automatic quantitation of HRMAS signals provides reliable reference profiles to monitor diseases and pharmaceutical follow-up. Nevertheless, for several metabolites chemical shifts may slightly differ according to the micro-environment in the tissue or cells, in particular its pH. This hampers accurate estimation of the metabolite concentrations mainly when using quantitation algorithms based on a metabolite basis-set. In this work, we propose a user-friendly way to circumvent this problem based on stretching of the metabolite basis-set signals and maximization of the correlation between the HRMAS and basis-set spectra prior to quantitation.
Imaging Systems and Techniques (IST), 2010 IEEE International Conference on; 08/2010
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IEEE International Workshop on Imaging Systems and Techniques, IST. 01/2010;
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ABSTRACT: In spite of having been the object of considerable attention, the histopathological grading of oligodendrogliomas is still controversial. The determination of reliable biomarkers capable of improving the malignancy grading remains an essential step in working toward better therapeutic management of patients. Therefore the metabolome of 34 human brain biopsies, histopathologically classified as low-grade (LGO, N = 10) and high-grade (HGO, N = 24) oligodendrogliomas, was studied using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HRMAS NMR) and multivariate statistical analysis. The classification model obtained afforded a clear distinction between LGOs and HGOs and provided some useful insights into the different metabolic pathways that underlie malignancy grading. The analysis of the most discriminant metabolites in the model revealed the presence of tumoral hypoxia in HGOs. The statistical model was then used to study biopsy samples that were classified as intermediate oligodendrogliomas (N = 6) and glioblastomas (GBMs) (N = 30) by histopathology. The results revealed a gradient of tumoral hypoxia increasing in the following direction: LGOs, intermediate oligodendrogliomas, HGOs, and GBMs. Moreover upon analysis of the clinical evolution of the patients, the metabolic classification seems to provide a closer correlation with the actual patient evolution than the histopathological analysis.
Magnetic Resonance in Medicine 06/2008; 59(5):959-65. · 2.96 Impact Factor
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ABSTRACT: Accurate chemical shifts are now accessible with high field NMR spectrometers. After the recall of the basic formulae, methods are proposed to measure chemical shifts with a high precision. Using two coaxial rotors at the magic angle, the necessary parameters used for correction are measured. The influence of different factors on the precision of the NMR measurements is discussed. Some proposals are given for MAS experiments used with solid-state samples. © 2007 Wiley Periodicals, Inc. Concepts Magn Reson Part A 30A: 184–193, 2007.
Concepts in Magnetic Resonance Part A 07/2007; 30A(4):184 - 193. · 1.67 Impact Factor
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ABSTRACT: The structure of the 19-amino acid peptide epitope, corresponding to the 141-159 sequence of capsid viral protein VP1 of foot-and-mouth disease virus (FMDV), bound to three different resins, namely, polystyrene-MBHA, PEGA, and POEPOP, has been determined by high-resolution magic angle spinning (HRMAS) NMR spectroscopy. A combination of homonuclear and heteronuclear bidimensional experiments was used for the complete peptide resonance assignment and the qualitative characterization of the peptide folding. The influence of the chemicophysical nature of the different polymers on the secondary structure of the covalently attached FMDV peptide was studied in detail. In the case of polystyrene-MBHA and polyacrylamide-PEGA resins, the analysis of the 2D spectra was hampered by missing signals and extensive overlaps, and only a propensity toward a peptide secondary structure could be derived from the assigned NOE correlations. When the FMDV peptide was linked to the polyoxyethylene-based POEPOP resin, it was found to adopt in dimethylformamide a helical conformation encompassing the C-terminal domain from residues 152 to 159. This conformation is very close to that of the free peptide previously analyzed in 2,2,2-trifluoroethanol. Our study clearly demonstrates that a regular helical structure can be adopted by a resin-bound bioactive peptide. Moreover, a change in the folding was observed when the same peptide-POEPOP conjugate was swollen in aqueous solution, displaying the same conformational features as the free peptide in water. The possibility of studying solid-supported ordered secondary structures by the HRMAS NMR technique in a wide range of solvents can be extended either to other biologically relevant peptides and proteins or to new synthetic oligomers.
Journal of the American Chemical Society 06/2001; 123(18):4130-8. · 9.91 Impact Factor
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ABSTRACT: Solid-state nuclear magnetic resonance (NMR) techniques were used to characterize cyclomaltoheptaose (β-cyclodextrin, β-CD) polymers. These insoluble materials have been investigated by cross-polarization magic angle spinning with dipolar decoupling (CP/MAS), magic angle spinning without dipolar decoupling (MAS), and high-resolution magic angle spinning with gradients (HRMAS). These NMR spectra allow the assignment of the principal 1H and 13C signals. The presence of two distinct components (cross-linked β-CD and polymerized epichlorohydrin) in the materials was clearly demonstrated. These polymers were used as sorbents and the resulting NMR spectra are presented and discussed. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 1288–1295, 2000
Journal of Applied Polymer Science 02/2000; 75(10):1288 - 1295. · 1.29 Impact Factor
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ABSTRACT: SiO2 was thermally grown on arrays of silicon planes obtained from 〈110〉 substrates by means of micromachining. Blue photoluminescence was observed under pulsed-laser excitation from SiO2 grown on these planes. Experiments revealed that this emission was not affected by the Si/SiO2 interface properties or the silicon thickness, whereas its intensity and spectral features depended on the oxide thickness. Moreover, no detectable luminescence was observed from the oxide grown on unpatterned regions, where a smaller amount of oxide was excited by the laser beam. The photoluminescence disappeared when the oxide was removed. © 1999 American Institute of Physics.
Applied Physics Letters 07/1999; 75(4):489-491. · 3.84 Impact Factor
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ABSTRACT: The new concept of slaved pulses is evaluated in the context of the study of protein hydration. The inversion properties of these pulses are shown to be superior in quality to the previously published schemes. High-quality water selective homonuclear 2D 1H NOESY-NOESY and NOESY-TOCSY experiments were recorded on horse heart ferrocytochrome c.
Journal of Magnetic Resonance 06/1999; 138(1):107-14. · 2.14 Impact Factor
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ABSTRACT: The tetrapeptide Ala-lle-Gly-Met bound to a Wang resin via the methionine residue was studied by NMR under MAS conditions and compared to the same peptide in solution. The bound peptide exhibits average linewidths superior to those observed for the peptide in solution. The origin of the residual NMR linewidth observed for the bound form was investigated. The dynamics of the peptide is shown to be only marginally responsible for the increased linewidth; the major cause of the line broadening appears to be nonaveraged magnetic susceptibility differences.
Journal of Magnetic Resonance 02/1999; 136(1):127-9. · 2.14 Impact Factor
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ABSTRACT: The solid-phase synthesis of 2,5-diketopiperazines containing the trans-4-hydroxy-L-proline amino acid residue (Hyp) was performed on Ellman polystyrene, polyoxyethylene-polyoxypropylene (POEPOP), polystyrene-polyoxyethylene NovaSyn, and Wang resins, respectively. The reaction pathway allowed the introduction of different functional groups around the bicyclic scaffold in a combinatorial approach, and it generated mixtures of isomers. A detailed characterization of the single reaction steps by high resolution magic angle spinning (HRMAS) NMR spectroscopy was performed. The NMR spectral resolution of the resin-bound intermediates and final products was greatly influenced by the polymer matrix. The POEPOP resin permitted to obtain HRMAS NMR spectra with a resolution comparable with that of the spectra of the molecules in solution. Moreover, configurational and conformational isomers formed during the solid-phase reaction steps could be detected and easily assigned. Therefore, the combination of the HRMAS NMR technique with the use of nonaromatic resins may become an extremely powerful tool in solid-phase organic synthesis. This approach will allow the monitoring of multistep reactions and the conception of on-bead structural studies either on small molecules or on natural and/or synthetic oligomers.
Journal of Combinatorial Chemistry 2(6):681-90. · 3.41 Impact Factor
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ABSTRACT: Porous silicon (PoSi) LEDs are today under investigation for integration of optoelectronic silicon devices with standard microelectronic circuits. The electrical and optical properties of these devices depend on the anodization parameters (current density and time) of the PoSi formation process. However, a constant anodization current is generally used to fabricate the active PoSi layer of LEDs, and only few works exist in which a non-constant anodization current is reported. In this work, a study of the anodization current effects on the electroluminescence (EL) spectra of PoSi LEDs having around 0.1% of external quantum efficiency is presented. Several anodization current waveforms (constant, linear, triangular, and trapezoidal) were used to fabricate layers with different mechanical and optical properties. EL spectra of fabricated devices are reported and discussed. # 2003 Elsevier Science B.V. All rights reserved.
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ABSTRACT: High-resolution magic angle spinning (HRMAS) Nuclear magnetic resonance (NMR) 1H spectroscopy is playing an increasingly important role for diagnosis. This technique enables setting up metabolite profiles of ex vivo pathological and healthy tissue. Automatic quantitation of HRMAS signals provides reliable reference profiles useful to monitor diseases and pharmaceutical follow-up. However for several metabolites, the values of chemical shifts of proton groups may slightly differ according to the microenvironment in the tissue or cells, in particular to its pH. This hampers accurate estimation of the metabolite concentrations mainly when using quantitation algorithms based on a metabolite basis-set: the metabolite fingerprints are not correct anymore. In this work, we propose an accurate method based on quantum mechanical (QM) simulations. The proposed algorithm automatically corrects mismatches between the signal under analysis and the signals of the simulated basic-set by modifying the basis-set signals. In the optimization procedure, the basis-set signals are simulated again by varying the chemical shifts of metabolites in the QM procedure. Cross-correlation was used as cost function to measure how well the signals match each other. The proposed method, QM-QUEST, provides more robust fitting while limiting user involvement and respects the correct fingerprints of metabolites. Its efficiency is demonstrated by accurately quantitating signals from tissue samples of human brains with oligodendroglioma. (C) 2011 Elsevier Masson SAS. All rights reserved.
IRBM. 32(5):279-283.
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ABSTRACT: High-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) is playing an increasingly important role for diagnosis. This technique enables setting up metabolite profiles of ex vivo pathological and healthy tissue. The need to monitor diseases and pharmaceutical follow-up requires an automatic quantitation of HRMAS (1)H signals. However, for several metabolites, the values of chemical shifts of proton groups may slightly differ according to the micro-environment in the tissue or cells, in particular to its pH. This hampers the accurate estimation of the metabolite concentrations mainly when using quantitation algorithms based on a metabolite basis set: the metabolite fingerprints are not correct anymore. In this work, we propose an accurate method coupling quantum mechanical simulations and quantitation algorithms to handle basis-set changes. The proposed algorithm automatically corrects mismatches between the signals of the simulated basis set and the signal under analysis by maximizing the normalized cross-correlation between the mentioned signals. Optimized chemical shift values of the metabolites are obtained. This method, QM-QUEST, provides more robust fitting while limiting user involvement and respects the correct fingerprints of metabolites. Its efficiency is demonstrated by accurately quantitating 33 signals from tissue samples of human brains with oligodendroglioma, obtained at 11.7 tesla. The corresponding chemical shift changes of several metabolites within the series are also analyzed.
MEASUREMENT SCIENCE & TECHNOLOGY. 22(11).
