1H-NMR detectable fatty acyl chain unsaturation in excised leiomyosarcoma correlate with grade and mitotic activity.

Singer, Samuel; Sivaraja, M.; Souza, Kerry; Millis, Kevin K.; Corson, Joseph M.

doi:10.1172/jci118785

Cited by 31 publications

(41 citation statements)

References 20 publications

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“…33 The degree of fatty acyl unsaturation is believed to be an important determinant of the metastatic potential of soft tissue sarcomas. 17 The signi cantly higher 0.9/1.3 ratio (P = 0.0001) found for tumors in our study is consistent with this. The reduction of creatine, indicative of increased energy metabolism, is also observed in both brain tumors and malignant prostate tissue.…”

Section: Discussionsupporting

confidence: 91%

“…Recently, Singer et al have shown that a signi cant correlation exists between the degree of unsaturation of fatty acyl chains, obtained from two-dimensional MRS, and the mitotic activity, indicator of grade or degree of differentiation, in soft tissue sarcomas. 17 However, such two-dimensional experiments require long acquisition times and are complicated to perform. Millis et al in their recent work used both one-and twodimensional approaches, but they limited their study to liposarcomas.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Statistical Classification Strategy for Proton Magnetic ResonanceSpectra of Soft Tissue Sarcoma: An Exploratory Study withPotential Clinical Utility

Bezabeh

El‐Sayed

Patel

et al. 2002

Sarcoma

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Statistical Classification Strategy for Proton Magnetic ResonanceSpectra of Soft Tissue Sarcoma: An Exploratory Study withPotential Clinical Utility

Bezabeh

El‐Sayed

Patel

et al. 2002

Sarcoma

View full text Add to dashboard Cite

show abstract

“…Changes in lipid composition in mdx skeletal muscle have previously been identified in vivo and in intact biopsy samples. 68,69 Given the extensive use of genetically-modified mice, it is important to be aware of the strain background in order to fully characterize the changes induced by genetic deletion or modification. 70,71 For instance, the Fcer1g mouse comes on both a Balbc and C57BL/6J background.…”

Section: Metabonomic Studies Of Physiological Variationmentioning

confidence: 99%

NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

et al. 2004

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Strategies such as genomics, proteomics and metabonomics are being applied with increasing frequency in the pharmaceutical industry. For each of these approaches, toxicological response can be measured by terms of deviation from control or baseline status. However, in order to accurately define drug-induced response, it is necessary to characterize the normal degree of physiological variation in the absence of stimuli. Here, 1 H NMR spectroscopic-based analyses of the metabolic composition of urine in experimental animals under various normal physiological conditions are reviewed. In particular, the effects of inter-animal and diurnal variation, gender, age, diet, species, strain, hormonal status and stress on the biochemical composition of urine are explored. Pattern recognition methods facilitate the comparison of urine NMR spectra over a given time-course, enabling the establishment of changes in profile and highlighting the dynamic metabolic status of an organism. Thus metabonomic approaches based on information-rich spectroscopic data sets can be used to evaluate normal physiological variation and for investigation of drug safety issues.

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“…Quantitative TOCSY was used to obtain a GPC:Cho ratio that was found to be increased in leiomyosarcomas in comparison with leiomyomas (21). It has also been used to perform lipid group analysis, showing increased fatty acyl unsaturation in leiomyosarcomas according to their mitotic activity (23), and increased fatty acyl saturation of cholesteryl ester and triglyceride in multidrug-resistant carcinoma cell lines (24). In the present study there were moderate differences in the slopes of calibration curves from one Plp derivative to another, which indicates that caution should be used when making between-derivative quantitative comparisons.…”

Section: Hrmas Proton Tocsy As a Quantitative Tool: Validation And LImentioning

confidence: 99%

Quantitative HRMAS proton total correlation spectroscopy applied to cultured melanoma cells treated by chloroethyl nitrosourea: Demonstration of phospholipid metabolism alterations

Morvan

Demidem

Papon

et al. 2003

Magnetic Resonance in Med

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The ability to follow phospholipid (Plp) metabolism is of paramount importance in many circumstances in which cell survival and cell proliferation are of concern-for example in neurological disorders and cancer (1,2). NMR spectroscopy has long been known to be important tool for exploring Plp metabolism (3-6). Novel NMR developments, such as high-resolution magic angle spinning (HRMAS) probes, have provided improved spectra of cultured cells (7) and normal (8,9) and cancer (10 -12) tissues. Recently, using HRMAS together with proton total correlation spectroscopy (TOCSY), we showed that a mousebearing B16 melanoma tumor responded to chloroethyl nitrosourea (CENU) treatment in vivo by altering its Plp metabolism (12).The first purpose of the present study was to demonstrate on cultured B16 melanoma cells in vitro that HRMAS proton TOCSY cross-peak signal variations of Plp derivatives reflected concentration variations. The second purpose was to determine the Plp metabolism response of cultured B16 melanoma cells to CENU treatment in vitro, as a model for Plp metabolism alterations previously observed in vivo.The Plp derivatives that were simultaneously observed using proton TOCSY were choline (Cho), phosphocholine (PC), cytidyl-diphosphate-choline (CDP-Cho), ethanolamine (Eth), phosphoethanolamine (PE), CDP-ethanolamine (CDP-Eth) (all of which are derivatives of the phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEth) biosynthetic pathways), and glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) (derivatives of PtdCho and PtdEth hydrolysis) (1-3).As regards the most expressed Plp derivatives in cultured B16 melanoma cells, HRMAS proton TOCSY signals revealed linearity with 1D saturation recovery signals, the NMR spectroscopy reference for quantifying concentrations. Therefore, HRMAS proton TOCSY was used to quantify concentration changes of water-soluble Plp derivatives in CENU-treated cultured melanoma cells. The response of cultured B16 melanoma cells to CENU treatment involved a transient accumulation of GPC and GPE, a down-regulation of PC and increase of CDP-Eth during cell proliferation inhibition, and a dramatic and irreversible rise of PE during and after cell proliferation inhibition. These data are discussed in relation to mouse-bearing B16 melanoma tumor response to CENU in vivo, and to Plp metabolism enzymatic involvement. METHODS ChemicalsNЈ-[2-chloroethyl]-N[2-(methylsulfonyl)ethyl]-NЈ-nitrosourea (cystemustine) is a CENU antineoplastic agent (13) that has been proposed for the treatment of human malignant melanoma and glioma. Cystemustine (Orphachem, Clermont-Ferrand, France) was supplied as a 5-mM solution in 0.9% NaCl. D 2 O (SDS, Peypin, France) was used to lock the spectrometer. Cell CulturesTransplantable B16 melanoma cells originating from C57BL6/6J Ico mice (ICIG, Villejuif, France) were adapted

show abstract

1H-NMR detectable fatty acyl chain unsaturation in excised leiomyosarcoma correlate with grade and mitotic activity.

Cited by 31 publications

References 20 publications

Statistical Classification Strategy for Proton Magnetic ResonanceSpectra of Soft Tissue Sarcoma: An Exploratory Study withPotential Clinical Utility

Statistical Classification Strategy for Proton Magnetic ResonanceSpectra of Soft Tissue Sarcoma: An Exploratory Study withPotential Clinical Utility

NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

Quantitative HRMAS proton total correlation spectroscopy applied to cultured melanoma cells treated by chloroethyl nitrosourea: Demonstration of phospholipid metabolism alterations

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