Benign and Atypical Meningioma Metabolic Signatures by High-Resolution Magic-Angle Spinning Molecular Profiling

Monleón, Daniel; Morales, José Manuel; González-Darder, José M.; Talamantes, F.; Cortés, O.; Gil-Benso, Rosario; López-Ginés, Concepción; Cerdá-Nicolás, Miguel; Celda, Bernardo

doi:10.1021/pr800110a

Cited by 58 publications

(48 citation statements)

References 40 publications

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“…NMR is one of the most efficient, robust, reproducible, and cheap methods for obtaining metabolic profiles in biological specimens without extensive sample preparation (11). High-resolution magic angle spinning (HR-MAS) NMR spectroscopy is a powerful technique for the investigation of metabolites within different intact tissues (12)(13)(14)(15)(16). The potential of HR-MAS applications to the study of biological tissues has been widely shown in the investigation of different cellular alterations.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Aggressiveness in Benign Meningiomas with Chromosomal Instabilities

et al. 2010

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Meningiomas are often considered benign tumors curable by surgery, but most recurrent meningiomas correspond to histologic benign tumors. Because alterations in chromosome 14 among others have suggested clinical aggressiveness and recurrence, determining both the molecular phenotype and the genetic profile may help distinguish tumors with aggressive metabolism. The aim of this study was to achieve higher specificity in the detection of meningioma subgroups by measuring chromosomal instabilities by fluorescence in situ hybridization and cytogenetics and metabolic phenotypes by high-resolution magic angle spinning spectroscopy. We studied 46 meningioma biopsies with these methodologies. Of these, 34 were of WHO grade 1 and 12 were of WHO grade 2. Genetic analysis showed a subgroup of histologic benign meningioma with chromosomal instabilities. The metabolic phenotype of this subgroup indicated an aggressive metabolism resembling that observed for atypical meningioma. According to the metabolic profiles, these tumors had increased energy demand, higher hypoxic conditions, increased membrane turnover and cell proliferation, and possibly increased resistance to apoptosis. Taken together, our results identify distinct metabolic phenotypes for otherwise benign meningiomas based on cytogenetic studies and global metabolic profiles of intact tumors. Measuring the metabolic phenotype of meningioma intact biopsies at the same time as histopathologic analysis may allow the early detection of clinically aggressive tumors. Cancer Res; 70(21); 8426-34. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

Metabolic Aggressiveness in Benign Meningiomas with Chromosomal Instabilities

et al. 2010

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“…High resolution magic angle spinning (HR-MAS) NMR spectroscopy is a powerful technique for the investigation of metabolites within different intact tissues (25)(26)(27)(28)(29)(30)(31). The precise determination of the biochemical and metabolic profiles in intact tissue promises to extend the possibilities of NMR as a medical diagnostic tool.…”

Section: Introductionmentioning

confidence: 99%

Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies

Monleνn

2010

Int J Mol Med

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Abstract. Among the different processes occurring during the evolution of liver disease, fibrosis has a predominant role. Liver fibrosis mechanisms are fairly constant irrespective of the underlying etiology. Cirrhosis is the end-stage of this reaction. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. The aim of this study was to demonstrate the applicability of 1 H high resolution magic angle spinning (HR-MAS) NMR spectroscopy in the biochemical profile determination of human liver needle biopsy samples for the characterization of metabolic alterations related to the severity of liver disease. We recorded and analyzed HR-MAS spectra of 68 liver tissue samples obtained by needle biopsy from patients with chronic liver disease. Multivariate analysis was applied to these data to obtain discrimination patterns and to reveal relevant metabolites. The metabolic characterization of liver tissue from needle biopsies by HR-MAS NMR spectroscopy provided differential patterns for cirrhotic and non-cirrhotic chronic liver disease tissue. Metabolites closely related to the liver metabolism such as some fatty acids, glucose and amino acids show differences between the two groups. Phospholipid precursors, which have been previously correlated with hepatic lesions also show differences. Furthermore, the correlation between histologically assessed liver disease stages and the levels of the most discriminative metabolites show that liver dysfunction is present at the initial stages of chronic hepatic lesions. Overall, this work suggests that the additional information obtained by NMR metabolomics applied to needle biopsies of human liver may be useful for assessing metabolic alterations and liver dysfunction in chronic liver disease. IntroductionThe liver is among the most metabolically diverse organs of the body and is involved in many critical metabolic processes (1). One of its major roles is storing endogenous fuels of the body. In addition, the liver acts as a major distribution center for exogenous energy supplies. The liver may be affected by many pathological aggressions. Liver dysfunction results in a variety of clinical signs and symptoms. However, some of these pathologies pose a diagnostic challenge as many different diseases show similar clinical signs (2-4). Moreover, liver biopsy assessment involves some degree of complication because of the proliferation of different grading and staging schemes (5-7). Metabolic alterations produced by liver disease may help clinicians better characterize the disease. Among the different processes occurring during the evolution of liver disease, fibrosis takes a predominant role. Liver fibrosis is characterized by the replacement of liver tissue by fibrous scar tissue as well as regenerative nodules, leading to progressive loss of liver function and to altered liver metabolism (8-11). Liver fibrosis induction mechanisms are fairly constant irrespectivel...

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“…Thus, for non-solid or highly viscous liquids, HR-MAS NMR spectroscopy allows the reduction of most of the line broadening associated with restricted molecular motion, chemical shift anisotropy, dipolar couplings and field inhomogeneity by high-rate spinning of the sample at the magic angle θ= 54.7˚ (14,15). The potential of HR-MAS applications to the study of cell cultures and biological tissues has been widely demonstrated in the investigation of different cellular alterations (16)(17)(18). In addition to the metabolites observed by conventional liquid NMR spectroscopy, HR-MAS provides information on the lipid content and other molecules that may be altered by extraction methods.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics of the effect of AMPK activation by AICAR on human umbilical vein endothelial cells

Martínez

Blas‐García²,

Morales³

et al. 2011

Int J Mol Med

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Abstract. AMP-activated protein kinase (AMPK) is a metabolic master switch expressed in a great number of cells and tissues. AMPK is thought to modulate the cellular response to different stresses that increase cellular AMP concentration. The adenosine analog, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an AMPK activator used in many studies to assess the effects of AMPK activation on cellular metabolism and function. However, the effect of AICAR on cell metabolism reaches many different pathways and metabolites, some of which do not seem to be fully related to AMPK activation. We have now for the first time used NMR metabolomics on human umbilical vein endothelial cells (HUVEC) for the study of the global metabolic impact of AMPK activation by AICAR. In our study, incubation with AICAR activates AMPK and is associated with, among others, broad metabolic alterations in energy metabolism and phospholipid biosynthesis. Using NMR spectroscopy and metabolic network tools, we analyzed the connections between the different metabolic switches activated by AICAR. Our approach reveals a strong interconnection between different phospholipid precursors and oxidation by-products. Metabolomics profiling is a useful tool for detecting major metabolic alterations, generating new hypotheses and provides some insight about the different molecular correlations in a complex system. The present study shows that AICAR induces metabolic effects in cell metabolism well beyond energy production pathways.

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Benign and Atypical Meningioma Metabolic Signatures by High-Resolution Magic-Angle Spinning Molecular Profiling

Cited by 58 publications

References 40 publications

Metabolic Aggressiveness in Benign Meningiomas with Chromosomal Instabilities

Metabolic Aggressiveness in Benign Meningiomas with Chromosomal Instabilities

Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies

Metabolomics of the effect of AMPK activation by AICAR on human umbilical vein endothelial cells

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