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1H NMR Ganglioside Ceramide Resonance Region on the Differential Diagnosis of Low and High Malignancy of Brain Gliomas
Authors:V. Lombardi  L. Valko  M. Valko  A. Scozzafava  H. Morris  M. Melnik  J. Svitel  M. Budešinský  J. Pelnár  J. Steno  T. Liptaj  L. Zalibera  J. Budinská  J. Zlatoš  A. Giuliani  L. Mascolo  D. Leibfritz
Affiliation:(1) Department of Pathological Anatomy, Oncology Center of Bari, I-701 26 Bari, Italy;(2) Department of Physical Chemistry, Slovak Technical University, SK-812 37 Bratislava, Slovak Republic;(3) Department of Chemistry, University of Firenze, I-501 44 Florence, Italy;(4) School of Pharmacy and Chemistry, John Moores University, Liverpool, L3 3AF, U.K;(5) Department of Inorganic Chemistry, Slovak Technical University, SK-812 37 Bratislava, Slovak, Republic;(6) Department of Biochemical Technology, Slovak Technical University, SK-812 37 Bratislava, Slovak Republic;(7) Department of NMR Spectroscopy, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ-166 10 Prague 6, Czech Republic;(8) Department of Neurosurgery, Faculty of Medicine, Comenius University, SK-833 05 Bratislava, Slovak Republic;(9) Department of Neurology, Litomerice Medical Center, CZ-412 01 Litomerice, Czech Republic;(10) Department of Histology, Faculty of Medicine, Comenius University, SK-811 08 Bratislava, Slovak Republic;(11) Department of Chemistry and Medical Biochemistry, University of Milano, I-201 33 Milano, Italy;(12) Inst. of Organic Chemistry, University of Bremen, Bremen, Germany
Abstract:1. The high-resolution 1H NMR (MRS) spectra of human brain tumor homogenates revealed a broad resonance at 5.3–5.4 ppm in glioblastoma multiforme (N = 16) and brain metastases (N = 2). The broad resonance was identified as ceramide, a sphingosine–fatty acid combination portion of ganglioside, indicating an elevated abundance of monounsaturated fatty acids. GLC analysis of gangliosides in the highly malignant glioblastoma multiforme revealed that the elevated monounsaturated fatty acid is oleic acid (C18:1). The resonance at 5.3–5.4 ppm region was not detectable in normal human brain (N = 2), in meningiomas (N = 2), or in low-grade astrocytomas (N = 12). In normal human brain the abundance of monounsaturated fatty acid is minimal.2. This investigation was made possible because the method of producing homogenate resulted in (i) no loss of lipids during the process and (ii) a well-homogenised sample, with (iii) no loss in chemical integrity.3. The properties of tumor gangliosides include antigenic specificity and immunosuppresive activity and the ceramide, a sphingosine–fatty acid combination, noticeably influences the ganglioside immunosuppressive activity.4. The observation of 1H NMR ceramide resonance in high-malignant brain tumors emphasizes the dramatic role of aberrant gangliosides and ceramide precursors on the grade of malignancy and invasiveness.5. Further insight into the specific nature of the ceramide portion of gangliosides in grading the malignancy of brain tumors should be investigated further.
Keywords:brain gliomas  ceramide  ganglioside  malignancy  1H NMR spectroscopy
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