metabolomics research
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METABOLOMICS Fundamental, clinical & pre-clinical research
Genes
Cancer cells
Cancer tissue
DNA
RNA
Proteins
Metabolites
Dysfunction
Metabolomics research
Metabolomics for cancer research
CARMeN project2.7 millions €
METABOLOMICS Fundamental, clinical & pre-clinical research
University Hospitals of Strasbourg (I.J. Namer, J.P. Bellocq)University of Strasbourg / CNRS (K. Elbayed)Bruker France (M. Piotto)Regional Cancer Institute
Strasbourg’s Hautepierre Hospital11.7 T HRMAS-NMR System
January, 2008
54.7oB0
biological tissue(1-20 mg)
ppm6 4 2 0
HRMAS
withoutHRMAS
METABOLOMICS Fundamental, clinical & pre-clinical research
< 5 min
tumor surgery
dissectionof the tumor sample
tumor data bank
HRMAS-NMR
pathology
molecular biology
Clinical research
METABOLOMICS Fundamental, clinical & pre-clinical research
molecular biology
xenogreffs
HRMAS-NMRpathology
tumor surgery
Pre-clinical research
new traitement
( )Histopathology, molecular biology,
prognosis, medical imaging...Metabolomics data
NMR Metabolomics database in cancerology
( )Statistical models(PCA, PLS-DA)
METABOLOMICS Fundamental, clinical & pre-clinical research
HRMAS-NMR spectroscopy
13C
1H
2D
lactate
acetatebeta-glucosepyruvate
resolution : 10 microM
1D
Pretreatment of 1D spectra
normalization
sampling
Statistical treatmentPCA, PLS-DA
ref.
METABOLOMICS Fundamental, clinical & pre-clinical research
METABOLOMICS Fundamental, clinical & pre-clinical research
Publications:
G Erb, K Elbayed, M Piotto, J Raya, A Neuville, M Mohr, D Maitrot, P Kehrli, IJ Namer : Towards improved grading of malignancy in oligodendrogliomas using metabolomics. Magnetic Resonance in Medicine 59: 959-965, 2008.
M Piotto, FM Moussallieh, B Dillmann, A Imperiale, A Neuville, C Brigand, JP Bellocq, K Elbayed, IJ Namer : Metabolomic characterization of primary human colorectal cancers using high resolution magic angle spinning 1H magnetic resonance spectroscopy. Metabolomics 5: 292-301, 2009.
A Imperiale, K Elbayed, FM Moussallieh, A Neuville, M Piotto, JP Bellocq, P Lutz, IJ Namer : Metabolomic pattern of childhood neuroblastome obtained by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy. Pediatric Blood & Cancer (in press), 2010.
J Detour, K Elbayed, M Piotto, FM Moussallieh, A Nehlig, IJ Namer : Ultra fast in vivo microwave irradiation for inhanced metabolic stability of brain biopsy samples during HRMAS NMR analysis. Journal of Neurochemistry (submitted), 2010.
N Daci-Youcef, S Froeliech, FM Moussallieh, S Heikkinen, D Dembele, B Lhermitte, K Elbayed, C Koehl, IJ Namer, J Auwerx : Gene expression mapping of HDACs and co-factors correlates with metabolomic profile and helps to idendify human brain tumor subgroup signatures. In preparation for Cancer Research, 2010.
D Ben Sellem, K Elbayed, A Neuville, FM Moussallieh, M Piotto, JP Bellocq, IJ Namer : Metabolomic approach to ovarians cancers: HRMAS NMR investigation. In preparation for Gynecologic Oncology, 2010.
K Elbayed, FM Moussallieh, A Neuville, H Lang, M Piotto, JP Bellocq, IJ Namer : Metabolomic approach to renal cancers: HRMAS NMR investigation. In preparation for NMR in Biomedicine, 2010.
com
pone
nt 2
Metabolomic identification of biomarkers
METABOLOMICS Fundamental, clinical & pre-clinical research
Cancer vs. normal tissue
component 1
single i.v. injection of 20 mM [13C 2]-XXX
tumor resection HRMAS (1H-13C)Experimental nude mouse
model of human cancer
2D
Production of the [13C 2]-XXX
XXX
AlsaChim
HRMAS (1H-13C)
0
1
2
3
T 0 T +10 T +30 T +60
Times (mn)
XX
X (
mM
)
single i.v. injection of 20 mM [13C 2]-XXX
METABOLOMICS Fundamental, clinical & pre-clinical research
METABOLOMICS Fundamental, clinical & pre-clinical research
Major problem : sensitivity
1
104
0.0001
13Csignal intensity
1H signal intensity
CARMeN in vivo: 13C-NMR metabolic imaging in vivo
3T multinuclear NMR spectroscopy
METABOLOMICS Perspectives
9.4T multinuclear NMR spectroscopy
Bruker
Siemens
+cryo-probe
Bruker
13C-labelled metabolites
(GMP quality)
+
13C-labelled metabolites
+
AlsaChim
para-hydrogen induced polarization
+
Bruker
small animalimaging
medicalimaging technology transfer ?+
x6
x2
x100
x100
x4 x100
CARMeN in vivo: 13C-NMR metabolic imaging in vivo
13C-pyruvate
injected : metabolic products :
13C-lactate 13C-alanine
injected : 13C-urea
H13CO3- 13CO2
metabolic products :
http://www.imagnia.se
METABOLOMICS Perspectives
Real time metabolic imaging in vivo
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