Toward improved grading of malignancy in oligodendrogliomas using metabolomics

Erb, Gilles; Elbayed, Karim; Piotto, Martial; Raya, Jésus; Neuville, Agnès; Mohr, Michel; Maitrot, D; Kehrli, P.; Namer, Izzie Jacques

doi:10.1002/mrm.21486

Cited by 64 publications

(63 citation statements)

References 29 publications

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“…A number of HR-MAS MRS approaches have demonstrated altered tumor metabolic profiles for treated tumors, in conjunction with subsequent histopathology of the same tumor specimen, which supports histopathological examination and improves the accuracy in the diagnosis, characterization, and evaluation of tumor progression in different tumors (12,16,17). In this study, 1 H HR-MAS MRS was used to investigate how brivanib treatment influences the metabolic profiles of Hep3B xenografts.…”

Section: Discussionmentioning

confidence: 85%

“…Due to its closer and realistic insights, the application of the HR-MAS MRS technique has increasingly been utilized for the analysis of intact tissues, predominantly in cancer research (13). Previous studies have shown that the quantification of tumor metabolic changes with 1 H HR-MAS MRS, in conjunction with subsequent histopathology of the same tumor specimen, supplements histopathological examination and improves the accuracy in the diagnosis, characterization, and evaluation of tumor progression in different tumors, including prostate (14,15), brain (16), lung (17), breast (12), hepatic (10) and cervical tumors (18). Therefore, this study was designed to investigate whether 1 H HR-MAS MRS supplements histopathological examination and provides quantitative metabolite information for the analysis of the efficacy of brivanib treatment in Hep3B tumor xenografts.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology

Yang

Song

Kim

et al. 2013

Molecular Medicine Reports

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Abstract. Angiogenesis inhibition is an attractive therapeutic strategy in the management of solid tumors. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) are key factors in growth and neovascularization of hepatocellular carcinoma (HCC). Brivanib is a novel, orally available dual tyrosine kinase inhibitor that selectively targets the key angiogenesis receptors VEGF-R2, FGF-R1 and FGF-R2. Recently, high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) has provided the opportunity to investigate more detailed metabolic profiles from intact tissue specimens that are correlated with histopathology and is thus, a promising tool for monitoring changes induced by treatment. In the present study, 1 H HR-MAS MRS and immunohistochemistry were used to investigate the antitumor efficacy of brivanib in HCC xenograft models. Tumor growth was significantly suppressed in brivanib-treated mice compared with the controls and treatment was associated with the inhibition of angiogenesis, increased apoptosis and inhibition of cell proliferation. Furthermore, HR-MAS techniques showed altered metabolic profiles between the two groups. HR-MAS spectra demonstrated a significant decrease in choline metabolite levels in the treated groups, concurrent with decreased cell proliferation and increased apoptosis. The results showed that 1 H HR-MAS MRS provides quantitative metabolite information that may be used to analyze the efficacy of brivanib treatment in Hep3B tumor xenografts. Thus, the HR-MAS MRS technique may be a complementary method to support histopathological results and increase its potential for use in the clinic.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology

Yang

Song

Kim

et al. 2013

Molecular Medicine Reports

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“…to obtain detailed metabolic profiles of human brain tumours [1][2][3][4][5][6]. There is a widespread use of 1 H 1D spectra to quantify the metabolites [1-3, 6, 7].…”

Section: High-resolution Magic Angle Spinning (Hrmas) Nmr Has Become mentioning

confidence: 99%

“…There is a widespread use of 1 H 1D spectra to quantify the metabolites [1-3, 6, 7]. 2D 1 H -1 H homonuclear or 1 H - 13 C heteronuclear experiments have improved the assignments in HRMAS spectra [3][4][5]8] but the quantitative metabolic information comes mainly from the 1 H 1D spectra. The use of 31 P NMR spectroscopy has also been demonstrated to be useful in the metabolomic study of brain cancer since there are 31 P-containing metabolites that can provide valuable information complementary to 1 H NMR in metabolic studies [9][10][11].…”

Section: High-resolution Magic Angle Spinning (Hrmas) Nmr Has Become mentioning

confidence: 99%

Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies

2012

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“…Simultaneously, proline, glutamate, glutamine, gamma amino butyric acid, and NAA, which are related to the Krebs pathway, are decreased. This metabolic shift toward fermentative metabolism may indicate hypoxia in HGOs (19). In breast cancer patients without lymphatic spread, an important factor influencing further treatment decisions is breast cancer grade.…”

Section: Histopathologic Gradingmentioning

confidence: 99%

Magnetic Resonance Metabolomics of Intact Tissue: A Biotechnological Tool in Cancer Diagnostics and Treatment Evaluation

et al. 2010

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Personalized medicine is increasingly important in cancer treatment for its role in staging and its potential to improve stratification of patients. Different types of molecules, genes, proteins, and metabolites are being extensively explored as potential biomarkers. This review discusses the major findings and potential of tissue metabolites determined by high-resolution magic angle spinning magnetic resonance spectroscopy for cancer detection, characterization, and treatment monitoring. Cancer Res; 70(17); 6692-6. ©2010 AACR. The Concept of MetabolomicsThe metabolome is the complete set of small-molecule metabolites in an organism and the final downstream product of the preceding gene expression and protein activity. Disease and influences from environmental factors, such as diet and drugs, are important factors in shaping the dynamic composition of the metabolome. The purpose of using metabolomics is to monitor the metabolic state at a certain time point and thereby understand more complex biological interactions, or to define biomarkers related to specific conditions. Compared with the more well-established "omics" technologies (genomics, transcriptomics, and proteomics), metabolomics is a relatively new and emerging field. Metabolomics contributes to the diversity of technologies within systems biology, thus enabling a more holistic picture of the chosen biological system. Magnetic resonance spectroscopy (MRS) offers safe, nondestructive, and quantitative metabolite identification in an automated and high-throughput fashion. Its sensitivity is substantially lower than for mass spectrometry (microgram compared with picogram level), but MRS enables investigation of tissue samples by high-resolution magic angle spinning (HR-MAS) MRS with minimal sample preparation, keeping the sample intact after analysis (1). This review focuses on the use of HR-MAS in cancer detection, characterization, and treatment evaluation, in which several studies show that MR metabolomics has promise. Patients with identical clinical and morphologic cancer diagnosis may have very different outcomes. Moreover, the metabolic state in cancer compared with control tissue, or metabolic changes following response and/or resistance to therapy, usually involves multiple metabolites. Multivariate analysis, which handles interactions between multiple variables (metabolites), has, thus, become a commonly used strategy for analysis of large spectral data sets. Statistical methods, such as principal component analysis (PCA) and partial least squares regression (PLS), are then applied to matrices of spectral data for exploration and model building to establish classifiers that enable predictions and classifications related to the biological problem in question. Proper validation of the classifiers, preferably using separate data for training and testing, is of great importance. By this means, MR metabolomics can establish a more detailed tumor portrait by defining specific fingerprints reflecting diagnostic status or therapeutic response. O...

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Toward improved grading of malignancy in oligodendrogliomas using metabolomics

Cited by 64 publications

References 29 publications

Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology

Characterization of brivanib therapy response in hepatocellular carcinoma xenografts using 1H HR-MAS spectroscopy and histopathology

Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies

Magnetic Resonance Metabolomics of Intact Tissue: A Biotechnological Tool in Cancer Diagnostics and Treatment Evaluation

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