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

We report on the use of 1H-NMR two-dimensional total correlated spectroscopy (2D TOCSY) at 600 MHz for an ex vivo analysis of fatty acyl chain lipid in normal smooth muscle and a series of primary retroperitoneal leiomyosarcomas. These TOCSY spectra were used to identify and quantitate the methylene protons situated between unsaturated site protons (D) to those bordered by only one unsaturated site proton (C). The D/C cross-peak volume ratios determined for oleic (18:1), linoleic (18:2), linolenic (18:3), and arachidonic (20:4) acids were 0.0, 1.3, 2.7, and 4.0, respectively, suggesting that this ratio can be a measure of the degree of unsaturation for fatty acyl chains of lipids. The D/C cross-peak volume ratio was found to be proportional to the mean mitotic activity (r = 0.94) in nine smooth muscle tissues. These results suggest, that for leiomyosarcoma, the degree of fatty acyl unsaturation may be an important determinant of the metastatic potential of these tumors. Furthermore, application of TOCSY for the ex vivo study of smooth muscle tumors would potentially serve as a pathologist-independent and quantitative method for assessment of leiomyosarcoma grade and mitotic activity thereby rendering a more accurate staging of patients.

[1]  D. Rose,et al.  Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cells in nude mice. , 1995, Journal of the National Cancer Institute.

[2]  K. Honn,et al.  Biological properties of 12(S)-HETE in cancer metastasis. , 1995, Advances in prostaglandin, thromboxane, and leukotriene research.

[3]  Ex vivo two-dimensional proton nuclear magnetic resonance spectroscopy of smooth muscle tumors: advantages of total correlated spectroscopy over homonuclear J-correlated spectroscopy. , 1994, Cancer research.

[4]  W. Mackinnon,et al.  Correlation of cellular differentiation in human colorectal carcinoma and adenoma cell lines with metabolite profiles determined by 1H magnetic resonance spectroscopy , 1994, International journal of cancer.

[5]  Takashi Ogino,et al.  Characterization of macromolecule resonances in the 1H NMR spectrum of rat brain , 1993, Magnetic resonance in medicine.

[6]  Charles J. Pouchert,et al.  The Aldrich library of [13]C and [1]H FT NMR spectra , 1993 .

[7]  W. Mackinnon,et al.  Cell-surface fucosylation and magnetic resonance spectroscopy characterization of human malignant colorectal cells. , 1992, Biochemistry.

[8]  R. Dahiya,et al.  Metastasis-associated alterations in phospholipids and fatty acids of human prostatic adenocarcinoma cell lines. , 1992, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[9]  O. Jardetzky,et al.  Characterization of lipid composition in stimulated human lymphocytes by 1H-NMR. , 1990, Biochimica et biophysica acta.

[10]  T. Alvegård,et al.  Histopathology peer review of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  M. Bárány,et al.  Quantitative and qualitative fat analysis in human leg muscle of neuromuscular diseases by 1H MR spectroscopy in vivo , 1989, Magnetic resonance in medicine.

[12]  W. J. Blitterswijk Structural basis and physiological control of membrane fluidity in normal and tumor cells. , 1988 .

[13]  C. Burns Membranes and cancer chemotherapy. , 1988, Cancer investigation.

[14]  Spector Aa,et al.  Biological and therapeutic potential of membrane lipid modification in tumors. , 1987 .

[15]  W. V. van Blitterswijk,et al.  Quantitative contributions of cholesterol and the individual classes of phospholipids and their degree of fatty acyl (un)saturation to membrane fluidity measured by fluorescence polarization. , 1987, Biochemistry.

[16]  A. A. Spector,et al.  Biological and therapeutic potential of membrane lipid modification in tumors. , 1987, Cancer research.

[17]  J. A. North,et al.  Adriamycin transport and sensitivity in fatty acid-modified leukemia cells. , 1986, Biochimica et biophysica acta.

[18]  J. Coindre,et al.  Reproducibility of a histopathologic grading system for adult soft tissue sarcoma , 1986, Cancer.

[19]  M. Bárány,et al.  Observation of the terminal methyl group in fatty acids of the linolenic series by a new 1H NMR pulse sequence providing spectral editing and solvent suppression. Application to excised frog muscle and rat brain. , 1986, Biochemistry.

[20]  P E Wright,et al.  Assignment of methylene proton resonances in NMR spectra of embryonic and transformed cells to plasma membrane triglyceride. , 1986, The Journal of biological chemistry.

[21]  J. A. North,et al.  Effect of cellular fatty acid alteration on adriamycin sensitivity in cultured L1210 murine leukemia cells. , 1984, Cancer research.

[22]  Richard R. Ernst,et al.  Coherence transfer by isotropic mixing: Application to proton correlation spectroscopy , 1983 .

[23]  C. Burns,et al.  Effect of cellular fatty acid alteration on hyperthermic sensitivity in cultured L1210 murine leukemia cells. , 1982, Cancer research.

[24]  A. A. Spector,et al.  Effect of modification of plasma membrane fatty acid composition on fluidity and methotrexate transport in L1210 murine leukemia cells. , 1979, Cancer research.

[25]  H. Suit,et al.  Sarcoma of soft tissue: Clinical and histopathologic parameters and response to treatment , 1975, Cancer.

[26]  W. D. Phillips,et al.  Proton magnetic resonance spectra of proteins in random-coil configurations. , 1969, Journal of the American Chemical Society.