Lipids in Neural Tumors

  • J. R. Van Brocklyn
Reference work entry


It has long been appreciated that the formation of neural tumors is accompanied by profound changes in the composition of a wide variety of different lipids. Recent years have seen a major increase in knowledge of the molecular biological roles played by lipids in these tumors, which has led to the identification of lipids, the enzymes that metabolize them and the pathways they regulate as potential diagnostic and prognostic markers and as possible therapeutic targets for these devastating malignancies. This chapter will summarize the current knowledge in this field.


Brain Tumor Glioma Cell Cholesteryl Ester Glioma Cell Line Human Glioma Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations:


cyclin-dependent kinase




cyclicAMP response element binding protein


epidermal growth factor


extracellular signal-regulated kinase


glioblastoma multiforme


γ-linolenic acid




Jun N-terminal kinase




mitogen-activated protein


matrix metalloproteinase


natural killer cell


nonsteroidal anti-inflammatory drugs


platelet-derived growth factor




protein kinase C


primitive neural ectodermal tumor


proliferator activated receptor


phosphatase and tensin homolog deleted on chromosome 10


polyunsaturated fatty acids


reactive oxygen species




sphingosine kinase


vascular endothelial growth factor



The author thanks Dr. Hany Saqr for helpful recommendations regarding glycosphingolipids. Work in the author's laboratory was supported by Grant # R01 NS41517 from the National Institute of Neurological Disorders and Stroke (NINDS).


  1. Adamczyk M, Scherrer E, Kupferberg A, Malviya AN, Mersel M. 1998. Inhibition of p42/p44 mitogen-activated protein kinase by oxysterols in rat astrocyte primary cultures and C6 glioma cell lines. J Neurosci Res 53: 38–50.PubMedGoogle Scholar
  2. Altomare DA, Testa JR. 2005. Perturbations of the AKT signaling pathway in human cancer. Oncogene 24: 7455–7464.PubMedGoogle Scholar
  3. Anelli V, Bassi R, Tettamanti G, Viani P, Riboni L. 2005. Extracellular release of newly synthesized sphingosine-1-phosphate by cerebellar granule cells and astrocytes. J Neurochem 92: 1204–1215.PubMedGoogle Scholar
  4. Arico S, Pattingre S, Bauvy C, Gane P, Barbat A, et al. 2002. Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. J Biol Chem 277: 27613–27321.PubMedGoogle Scholar
  5. Arikawa K, Takuwa N, Yamaguchi H, Sugimoto N, Kitayama J, et al. 2003. Ligand-dependent inhibition of B16 melanoma cell migration and invasion via endogenous S1P2 G protein-coupled receptor requirement of inhibition of cellular Rac activity. J Biol Chem 278: 32841–32851.PubMedGoogle Scholar
  6. Badie B, Schartner JM, Hagar AR, Prabakaran S, Peebles TR, et al. 2003. Microglia cyclooxygenase-2 activity in experimental gliomas: Possible role in cerebral edema formation. Clin Cancer Res 9: 872–877.PubMedGoogle Scholar
  7. Bassi R, Anelli V, Giussani P, Tettamanti G, Viani P, et al. 2006. Sphingosine-1-phosphate is released by cerebellar astrocytes in response to bFGF and induces astrocyte proliferation through Gi-protein-coupled receptors. Glia 53: 621–630.PubMedGoogle Scholar
  8. Becker R, Rohlfs J, Jennemann R, Wiegandt H, Mennel HD, et al. 2000. Glycosphingolipid component profiles or human gliomas – correlation to survival time and histopathological malignancy grading. Clin Neuropathol 19: 119–125.PubMedGoogle Scholar
  9. Berra B, Gaini SM, Riboni L. 1985. Correlation between ganglioside distribution and histological grading of human astrocytomas. Int J Cancer 36: 363–366.PubMedGoogle Scholar
  10. Bitton RJ, Guthmann MD, Gabri MR, Carnero AJ, Alonso DF, et al. 2002. Cancer vaccines: An update with special focus on ganglioside antigens. Oncol Rep 9: 267–276.PubMedGoogle Scholar
  11. Black KL, Hoff JT, McGillicuddy JE, Gebarski SS. 1986. Increased leukotriene C4 and vasogenic edema surrounding brain tumors in humans. Ann Neurol 19: 592–595.PubMedGoogle Scholar
  12. Black KL, King WA, Ikezaki K. 1990. Selective opening of the blood–tumor barrier by intracarotid infusion of leukotriene C4. J Neurosurg 72: 912–919.PubMedGoogle Scholar
  13. Black P, Hand CM, Vender JR, Finkelstein SD. 1998. Chemotherapy in experimental brain tumor, Part 2. Pretreatment with leukotriene C4 prolongs survival. J Neurooncol 36: 7–19.PubMedGoogle Scholar
  14. Blazquez C, Casanova ML, Planas A, Del Pulgar TG, Villanueva C, et al. 2003. Inhibition of tumor angiogenesis by cannabinoids. FASEB J 17: 529–531.PubMedGoogle Scholar
  15. Blazquez C, Gonzalez-Feria L, Alvarez L, Haro A, Casanova ML, et al. 2004. Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas. Cancer Res 64: 5617–5623.PubMedGoogle Scholar
  16. Blomgren H, Kling-Andersson G. 1992. Growth inhibition of human malignant glioma cells in vitro by agents which interfere with biosynthesis of eicosanoids. Anticancer Res 12: 981–986.PubMedGoogle Scholar
  17. Bouterfa HL, Sattelmeyer V, Czub S, Vordermark D, Roosen K, et al. 2000. Inhibition of Ras farnesylation by lovastatin leads to downregulation of proliferation and migration in primary cultured human glioblastoma cells. Anticancer Res 20: 2761–2771.PubMedGoogle Scholar
  18. Brante G. 1949. Studies on lipids in the nervous system; with special reference to quatitative chemical determination and topical distribution. Acta Physiol Scand (18 suppl): 63.Google Scholar
  19. Bremer EG, Hakomori S. 1982. GM3 ganglioside induces hamster fibroblast growth inhibition in chemically-defined medium: Gangliosides may regulate growth factor receptor function. Biochem Biophys Res Commun 106: 711–718.PubMedGoogle Scholar
  20. Bremer EG, Hakomori S, Bowen-Pope DF, Raines E, Ross R. 1984. Ganglioside-mediated modulation of cell growth, growth factor binding, and receptor phosphorylation. J Biol Chem 259: 6818–6825.PubMedGoogle Scholar
  21. Bremer EG, Schlessinger J, Hakomori S. 1986. Ganglioside-mediated modulation of cell growth. Specific effects of GM3 on tyrosine phosphorylation of the epidermal growth factor receptor. J Biol Chem 261: 2434–2440.PubMedGoogle Scholar
  22. Bui T, Kuo C, Rotwein P, Straus DS. 1997. Prostaglandin A2 specifically represses insulin-like growth factor-I gene expression in C6 rat glioma cells. Endocrinology 138: 985–993.PubMedGoogle Scholar
  23. Carine K, Schengrund CL. 1984. Effects of exogenous GM1 and GD1a on S20Y neuroblastoma cells. J Neurosci Res 12: 59–69.PubMedGoogle Scholar
  24. Castelli MG, Chiabrando C, Fanelli R, Martelli L, Butti G, et al. 1989. Prostaglandin and thromboxane synthesis by human intracranial tumors. Cancer Res 49: 1505–1508.PubMedGoogle Scholar
  25. Castilla EA, Prayson RA, Kanner AA, Rybicki LA, Tubbs RR, et al. 2003. Cyclooxygenase-2 in oligodendroglial neoplasms. Cancer 98: 1465–1472.PubMedGoogle Scholar
  26. Cechin SR, Dunkley PR, Rodnight R. 2005. Signal transduction mechanisms involved in the proliferation of C6 glioma cells induced by lysophosphatidic acid. Neurochem Res 30: 603–611.PubMedGoogle Scholar
  27. Chahlavi A, Rayman P, Richmond AL, Biswas K, Zhang R, et al. 2005. Glioblastomas induce T-lymphocyte death by two distinct pathways involving gangliosides and CD70. Cancer Res 65: 5428–5438.PubMedGoogle Scholar
  28. Chang F, Li R, Ladisch S. 1997. Shedding of gangliosides by human medulloblastoma cells. Exp Cell Res 234: 341–346.PubMedGoogle Scholar
  29. Chio CC, Lin SJ, Lin MT. 1995. Leukotriene E4 selectively increase the delivery of methotrexate to the C6 gliomas in rats. J Neurooncol 25: 89–95.PubMedGoogle Scholar
  30. Choi BO, Yamaki T, Tatewaki K, Ibayashi Y, Hashi K. 1997. Deletion of complex gangliosides of human glioma cells during mitotic cell division. J Neurooncol 34: 211–219.PubMedGoogle Scholar
  31. Chun J. 1999. Lysophospholipid receptors: Implications for neural signaling. Crit Rev Neurobiol 13: 151–168.PubMedGoogle Scholar
  32. Chun J. 2005. Lysophospholipids in the nervous system. Prostaglandins Other Lipid Mediat 77: 46–51.PubMedGoogle Scholar
  33. Cimini A, Cristiano L, Colafarina S, Benedetti E, Di Loreto S, et al. 2005. PPARγ-dependent effects of conjugated linoleic acid on the human glioblastoma cell line (ADF). Int J Cancer 117: 923–933.PubMedGoogle Scholar
  34. Comas TC, Tai T, Kimmel D, Scheithauer BW, Burger PC, et al. 1999. Immunohistochemical staining for ganglioside GD1b as a diagnostic and prognostic marker for primary human brain tumors. Neuro Oncol 1: 261–267.PubMedGoogle Scholar
  35. Conde B, Tejedor M, Sinues E, Alcala A. 1991. Modulation of cell growth and differentiation induced by prostaglandin D2 in the glioma cell line C6. Anticancer Res 11: 289–295.PubMedGoogle Scholar
  36. Constantini S, Tamir J, Gomori MJ, Shohami E. 1993. Tumor prostaglandin levels correlate with edema around supratentorial meningiomas. Neurosurgery 33: 204–211.PubMedGoogle Scholar
  37. Corcoran RB, Scott MP. 2006. Oxysterols stimulate Sonic hedgehog signal transduction and proliferation of medulloblastoma cells. Proc Natl Acad Sci USA 103: 8408–8413.PubMedGoogle Scholar
  38. Cully M, You H, Levine AJ, Mak TW. 2006. Beyond PTEN mutations: The PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 6: 184–192.PubMedGoogle Scholar
  39. Cuvillier O, Levade T. 2003. Enzymes of sphingosine metabolism as potential pharmacological targets for therapeutic intervention in cancer. Pharmacol Res 47: 439–445.PubMedGoogle Scholar
  40. Daido S, Kanzawa T, Yamamoto A, Takeuchi H, Kondo Y, et al. 2004. Pivotal role of the cell death factor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells. Cancer Res 64: 4286–4293.PubMedGoogle Scholar
  41. Das UN, Prasad VV, Reddy DR. 1995. Local application of γ-linolenic acid in the treatment of human gliomas. Cancer Lett 94: 147–155.PubMedGoogle Scholar
  42. Das UN. 2004. From bench to the clinic: Gamma-linolenic acid therapy of human gliomas. Prostaglandins Leukot Essent Fatty Acids 70: 539–552.PubMedGoogle Scholar
  43. Davidsson P, Fredman P, Collins VP, von Holst H, Mansson JE, et al. 1989. Ganglioside composition in human meningiomas. J Neurochem 53: 705–709.PubMedGoogle Scholar
  44. De Petrocellis L, Cascio MG, Di Marzo V. 2004. The endocannabinoid system: A general view and latest additions. Br J Pharmacol 141: 765–774.PubMedGoogle Scholar
  45. Deininger MH, Weller M, Streffer J, Mittelbronn M, Meyermann R. 1999. Patterns of cyclooxygenase-1 and -2 expression in human gliomas in vivo. Acta Neuropathol (Berl) 98: 240–244.Google Scholar
  46. Deininger MH, Meyermann R, Trautmann K, Morgalla M, Duffner F, et al. 2000. Cyclooxygenase (COX)-1 expressing macrophages/microglial cells and COX-2 expressing astrocytes accumulate during oligodendroglioma progression. Brain Res 885: 111–116.PubMedGoogle Scholar
  47. Deng QJ, Mao BY, Zhang SF, Tang J, Wang ER. 2004. Expression and clinical significance of cyclooxygenase-2 in medulloblastoma. Sichuan Da Xue Xue Bao Yi Xue Ban 35: 641–643.PubMedGoogle Scholar
  48. Dennis J, Nogaroli L, Fuss B. 2005. Phosphodiesterase-Ialpha/autotaxin (PD-Ialpha/ATX): A multifunctional protein involved in central nervous system development and disease. J Neurosci Res 82: 737–742.PubMedGoogle Scholar
  49. Dobrowsky R, Werner M, Castellino A, Chao M, Hannun Y. 1994. Activation of the sphingomyelin cycle through the low affinity neurotrophin receptor. Science 265: 1596–1599.PubMedGoogle Scholar
  50. Dufner-Beattie J, Lemons RS, Thorburn A. 2001. Retinoic acid-induced expression of autotaxin in N-myc-amplified neuroblastoma cells. Mol Carcinog 30: 181–189.PubMedGoogle Scholar
  51. Duntsch C, Divi MK, Jones T, Zhou Q, Krishnamurthy M, et al. 2005. Safety and efficacy of a novel cannabinoid chemotherapeutic, KM-233, for the treatment of high-grade glioma. J Neurooncol 77: 1–10.Google Scholar
  52. Edsall LC, Cuvillier O, Twitty S, Spiegel S, Milstien S. 2001. Sphingosine kinase expression regulates apoptosis and caspase activation in PC12 cells. J Neurochem 76: 1573–1584.PubMedGoogle Scholar
  53. Ellert-Miklaszewska A, Kaminska B, Konarska L. 2005. Cannabinoids down-regulate PI3K/Akt and Erk signalling pathways and activate proapoptotic function of Bad protein. Cell Signal 17: 25–37.PubMedGoogle Scholar
  54. English D, Welch Z, Kovala AT, Harvey K, Volpert OV, et al. 2000. Sphingosine 1-phosphate released from platelets during clotting accounts for the potent endothelial cell chemotactic activity of blood serum and provides a novel link between hemostasis and angiogenesis. FASEB J 14: 2255–2265.PubMedGoogle Scholar
  55. Farooqui T, Franklin T, Pearl DK, Yates AJ. 1997. Ganglioside GM1 enhances induction by nerve growth factor of a putative dimer of TrkA. J Neurochem 68: 2348–2355.PubMedGoogle Scholar
  56. Feizi T. 1985. Demonstration by monoclonal antibodies that carbohydrate structures of glycoproteins and glycolipids are onco-developmental antigens. Nature 314: 53–57.PubMedGoogle Scholar
  57. Fiebich BL, Hull M, Lieb K, Gyufko K, Berger M, et al. 1997. Prostaglandin E2 induces interleukin-6 synthesis in human astrocytoma cells. J Neurochem 68: 704–709.PubMedGoogle Scholar
  58. Fischer I, Gagner JP, Law M, Newcomb EW, Zagzag D. 2005. Angiogenesis in gliomas: Biology and molecular pathophysiology. Brain Pathol 15: 297–310.PubMedGoogle Scholar
  59. Fowler CJ, Jonsson KO, Andersson A, Juntunen J, Jarvinen T, et al. 2003. Inhibition of C6 glioma cell proliferation by anandamide, 1-arachidonoylglycerol, and by a water soluble phosphate ester of anandamide: Variability in response and involvement of arachidonic acid. Biochem Pharmacol 66: 757–767.PubMedGoogle Scholar
  60. Fredman P, von Holst H, Collins VP, Ammar A, Dellheden B, et al. 1986. Potential ganglioside antigens associated with human gliomas. Neurol Res 8: 123–126.PubMedGoogle Scholar
  61. Fredman P, von Holst H, Collins VP, Granholm L, Svennerholm L. 1988. Sialyllactotetraosylceramide, a ganglioside marker for human malignant gliomas. J Neurochem 50: 912–919.PubMedGoogle Scholar
  62. Fredman P, Mansson JE, Bigner SH, Wikstrand CJ, Bigner DD, et al. 1990. Gangliosides in the human glioma cell line U-118 MG grown in culture or as xenografts in nude mice. Biochim Biophys Acta 1045: 239–244.PubMedGoogle Scholar
  63. Fredman P. 1994. Gangliosides associated with primary brain tumors and their expression in cell lines established from these tumors. Prog Brain Res 101: 225–240.PubMedGoogle Scholar
  64. Fredman P, Wikstrand CJ, Mansson JE, Reifenberger G, Bigner SH, et al. 1996. In vivo growth conditions suppress the expression of ganglioside GM2 and favour that of lacto series gangliosides in the human glioma D-54MG cell line. Glycoconj J 13: 391–399.PubMedGoogle Scholar
  65. French KJ, Schrecengost RS, Lee BD, Zhuang Y, Smith SN, et al. 2003. Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res 63: 5962–2969.PubMedGoogle Scholar
  66. Fujimoto Y, Izumoto S, Suzuki T, Kinoshita M, Kagawa N, et al. 2005. Ganglioside GM3 inhibits proliferation and invasion of glioma. J Neurooncol 71: 99–106.PubMedGoogle Scholar
  67. Gaini SM, Riboni L, Cerri C, Grimoldi N, Sganzerla EP, et al. 1988. Ganglioside content and composition in human gliomas. Acta Neurochir Suppl (Wien) 43: 126–129.Google Scholar
  68. Galve-Roperh I, Sanchez C, Cortes ML, del Pulgar TG, Izquierdo M, et al. 2000. Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat Med 6: 313–319.PubMedGoogle Scholar
  69. Giese A, Hagel C, Kim EL, Zapf S, Djawaheri J, et al. 1999. Thromboxane synthase regulates the migratory phenotype of human glioma cells. Neuro Oncol 1: 3–13.PubMedGoogle Scholar
  70. Goddard DH, Bomalaski JS, Lipper S, Shorr RG, Clark MA. 1996. Phospholipase A2-mediated inflammation induces regression of malignant gliomas. Cancer Lett 102: 1–6.PubMedGoogle Scholar
  71. Gomez Del Pulgar T, De Ceballos ML, Guzman M, Velasco G. 2002. Cannabinoids protect astrocytes from ceramide-induced apoptosis through the phosphatidylinositol 3-kinase/protein kinase B pathway. J Biol Chem 277: 36527–36533.PubMedGoogle Scholar
  72. Gopal K, Grossi E, Paoletti P, Usardi M. 1963. Lipid composition of human intracranial tumors: A biochemical study. Acta Neurochir (Wien) 11: 333–347.Google Scholar
  73. Goswami R, Singh D, Phillips G, Kilkus J, Dawson G. 2005. Ceramide regulation of the tumor suppressor phosphatase PTEN in rafts isolated from neurotumor cell lines. J Neurosci Res 81: 541–550.PubMedGoogle Scholar
  74. Goswami S, Gupta A, Sharma SK. 1998. Interleukin-6-mediated autocrine growth promotion in human glioblastoma multiforme cell line U87MG. J Neurochem 71: 1837–1845.PubMedGoogle Scholar
  75. Gottfries J, Fredman P, Mansson JE, Collins VP, von Holst H, et al. 1990. Determination of gangliosides in six human primary medulloblastomas. J Neurochem 55: 1322–1326.PubMedGoogle Scholar
  76. Gottfries J, Percy AK, Mansson JE, Fredman P, Wikstrand CJ, et al. 1991. Glycolipids and glycosyltransferases in permanent cell lines established from human medulloblastomas. Biochim Biophys Acta 1081: 253–261.PubMedGoogle Scholar
  77. Gratsa A, Rooprai HK, Rogers JP, Martin KK, Pilkington GJ. 1997. Correlation of expression of NCAM and GD3 ganglioside to motile behaviour in neoplastic glia. Anticancer Res 17: 4111–4117.PubMedGoogle Scholar
  78. Grayson G, Ladisch S. 1992. Immunosuppression by human gangliosides. II. Carbohydrate structure and inhibition of human NK activity. Cell Immunol 139: 18–29.PubMedGoogle Scholar
  79. Grieb P, Ryba MS, Jagielski J, Gackowski W, Paczkowski P, et al. 1999. Serum cholesterol in cerebral malignancies. J Neurooncol 41: 175–180.PubMedGoogle Scholar
  80. Hakomori S. 1984. Tumor-associated carbohydrate antigens. Annu Rev Immunol 2: 103–126.PubMedGoogle Scholar
  81. Hallak A, Alon-Baron L, Shamir R, Moshkowitz M, Bulvik B, et al. 2003. Rofecoxib reduces polyp recurrence in familial polyposis. Dig Dis Sci 48: 1998–2002.PubMedGoogle Scholar
  82. Hama K, Aoki J, Fukaya M, Kishi Y, Sakai T, et al. 2004. Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. J Biol Chem 279: 17634–17639.PubMedGoogle Scholar
  83. Hara A, Okayasu I. 2004. Cyclooxygenase-2 and inducible nitric oxide synthase expression in human astrocytic gliomas: Correlation with angiogenesis and prognostic significance. Acta Neuropathol (Berl) 108: 43–48.Google Scholar
  84. Hara S, Nakashima S, Kiyono T, Sawada M, Yoshimura S, et al. 2004. p53-Independent ceramide formation in human glioma cells during gamma-radiation-induced apoptosis. Cell Death Differ 11: 853–861.PubMedGoogle Scholar
  85. Hart S, Fischer OM, Ullrich A. 2004. Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res 64: 1943–1950.PubMedGoogle Scholar
  86. Hashizume K, Black KL. 2002. Increased endothelial vesicular transport correlates with increased blood–tumor barrier permeability induced by bradykinin and leukotriene C4. J Neuropathol Exp Neurol 61: 725–735.PubMedGoogle Scholar
  87. Hatano M, Mizuno M, Yoshida J. 2004. Enhancement of C2-ceramide antitumor activity by small interfering RNA on X chromosome-linked inhibitor of apoptosis protein in resistant human glioma cells. J Neurosurg 101: 119–127.PubMedGoogle Scholar
  88. Hay N. 2005. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8: 179–183.PubMedGoogle Scholar
  89. Hedberg KM, Dellheden B, Wikstrand CJ, Fredman P. 2000. Monoclonal anti-GD3 antibodies selectively inhibit the proliferation of human malignant glioma cells in vitro. Glycoconj J 17: 717–726.PubMedGoogle Scholar
  90. Hedberg KM, Mahesparan R, Read TA, Tysnes BB, Thorsen F, et al. 2001. The glioma-associated gangliosides 3′-isoLM1, GD3 and GM2 show selective area expression in human glioblastoma xenografts in nude rat brains. Neuropathol Appl Neurobiol 27: 451–464.PubMedGoogle Scholar
  91. Higuchi T, Iwama T, Yoshinaga K, Toyooka M, Taketo MM, et al. 2003. A randomized, double-blind, placebo-controlled trial of the effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous polyposis patients. Clin Cancer Res 9: 4756–4760.PubMedGoogle Scholar
  92. Hildebrandt JP, Hildebrandt P. 1997. Lysophosphatidic acid depletes intracellular calcium stores different from those mediating capacitative calcium entry in C6 rat glioma cells. Glia 19: 67–73.PubMedGoogle Scholar
  93. Hinz B, Ramer R, Eichele K, Weinzierl U, Brune K. 2004. Up-regulation of cyclooxygenase-2 expression is involved in R(+)-methanandamide-induced apoptotic death of human neuroglioma cells. Mol Pharmacol 66: 1643–1651.PubMedGoogle Scholar
  94. Hla T. 2004. Physiological and pathological actions of sphingosine 1-phosphate. Semin Cell Dev Biol 15: 513–520.PubMedGoogle Scholar
  95. Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ, et al. 2005. Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia 7: 7–16.PubMedGoogle Scholar
  96. Hull MA. 2005. Cyclooxygenase-2: How good is it as a target for cancer chemoprevention? Eur J Cancer 41: 1854–1863.PubMedGoogle Scholar
  97. Icard-Liepkalns C, Liepkalns VA, Yates AJ, Rodriguez ZR, Stephens RE. 1982. Effect of exogenous gangliosides on human neural cell division. J Cell Physiol 113: 186–191.PubMedGoogle Scholar
  98. Ishihara S, Rumi MA, Okuyama T, Kinoshita Y. 2004. Effect of prostaglandins on the regulation of tumor growth. Curr Med Chem Anticancer Agents 4: 379–387.PubMedGoogle Scholar
  99. Ishii I, Fukushima N, Ye X, Chun J. 2004. Lysophospholipid receptors: Signaling and biology. Annu Rev Biochem 73: 321–354.PubMedGoogle Scholar
  100. Jakobisiak M, Golab J. 2003. Potential antitumor effects of statins (Review). Int J Oncol 23: 1055–1069.PubMedGoogle Scholar
  101. Jantke J, Ladehoff M, Kurzel F, Zapf S, Kim E, et al. 2004. Inhibition of the arachidonic acid metabolism blocks endothelial cell migration and induces apoptosis. Acta Neurochir (Wien) 146: 483–494.Google Scholar
  102. Jennemann R, Rodden A, Bauer BL, Mennel HD, Wiegandt H. 1990. Glycosphingolipids of human gliomas. Cancer Res 50: 7444–7449.PubMedGoogle Scholar
  103. Johnsen JI, Lindskog M, Ponthan F, Pettersen I, Elfman L, et al. 2005. NSAIDs in neuroblastoma therapy. Cancer Lett 228: 195–201.PubMedGoogle Scholar
  104. Joki T, Heese O, Nikas DC, Bello L, Zhang J, et al. 2000. Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Cancer Res 60: 4926–4931.PubMedGoogle Scholar
  105. Kaplan S, Novikov I, Modan B. 1997. Nutritional factors in the etiology of brain tumors: Potential role of nitrosamines, fat, and cholesterol. Am J Epidemiol 146: 832–841.PubMedGoogle Scholar
  106. Kardosh A, Blumenthal M, Wang WJ, Chen TC, Schonthal AH. 2004. Differential effects of selective COX-2 inhibitors on cell cycle regulation and proliferation of glioblastoma cell lines. Cancer Biol Ther 3: 55–62.PubMedGoogle Scholar
  107. Karim A, McCarthy K, Jawahar A, Smith D, Willis B, et al. 2005. Differential cyclooxygenase-2 enzyme expression in radiosensitive versus radioresistant glioblastoma multiforme cell lines. Anticancer Res 25: 675–679.PubMedGoogle Scholar
  108. Kato M, Nagaya T, Fujieda M, Saito K, Yoshida J, et al. 2002. Expression of PPARγ and its ligand-dependent growth inhibition in human brain tumor cell lines. Jpn J Cancer Res 93: 660–666.PubMedGoogle Scholar
  109. Kawagoe H, Stracke ML, Nakamura H, Sano K. 1997. Expression and transcriptional regulation of the PD-Ialpha/autotaxin gene in neuroblastoma. Cancer Res 57: 2516–2521.PubMedGoogle Scholar
  110. Kawamori T, Osta W, Johnson KR, Pettus BJ, Bielawski J, et al. 2005. Sphingosine kinase 1 is up-regulated in colon carcinogenesis. FASEB J: doi10.1096/fj.05-4331fje.Google Scholar
  111. Khan RB, Krasin MJ, Kasow K, Leung W. 2004. Cyclooxygenase-2 inhibition to treat radiation-induced brain necrosis and edema. J Pediatr Hematol Oncol 26: 253–255.PubMedGoogle Scholar
  112. Kikuchi T, Nagata Y, Abe T. 1997. In vitro and in vivo antiproliferative effects of simvastatin, an HMG-CoA reductase inhibitor, on human glioma cells. J Neurooncol 34: 233–239.PubMedGoogle Scholar
  113. Kilkus J, Goswami R, Testai FD, Dawson G. 2003. Ceramide in rafts (detergent-insoluble fraction) mediates cell death in neurotumor cell lines. J Neurosci Res 72: 65–75.PubMedGoogle Scholar
  114. Kim JA, Chung YJ, Lee YS. 1998. Intracellular Ca2+ mediates lipoxygenase-induced proliferation of U-373 MG human astrocytoma cells. Arch Pharm Res 21: 664–670.PubMedGoogle Scholar
  115. Kim SK, Lim SY, Wang KC, Kim YY, Chi JG, et al. 2004. Overexpression of cyclooxygenase-2 in childhood ependymomas: Role of COX-2 inhibitor in growth and multi-drug resistance in vitro. Oncol Rep 12: 403–409.PubMedGoogle Scholar
  116. Kim WH, Choi CH, Kang SK, Kwon CH, Kim YK. 2005. Ceramide induces non-apoptotic cell death in human glioma cells. Neurochem Res 30: 969–979.PubMedGoogle Scholar
  117. Kishi Y, Okudaira S, Kishi M, Hama K, Shida D, et al. 2006. Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcoholine to lysophosphatidic acid. J Biol Chem 281: 17492–17500.PubMedGoogle Scholar
  118. Knobbe CB, Merlo A, Reifenberger G. 2002. Pten signaling in gliomas. Neuro Oncol 4: 196–211.PubMedGoogle Scholar
  119. Koh E, Clair T, Woodhouse EC, Schiffmann E, Liotta L, et al. 2003. Site-directed mutations in the tumor-associated cytokine, autotaxin, eliminate nucleotide phosphodiesterase, lysophospholipase D, and motogenic activities. Cancer Res 63: 2042–2045.PubMedGoogle Scholar
  120. Kökoglu E, Tüter Y, Sandikçi KS, Yazici Z, Ulakoglu EZ, et al. 1998. Prostaglandin E2 levels in human brain tumor tissues and arachidonic acid levels in the plasma membrane of human brain tumors. Cancer Lett 132: 17–21.PubMedGoogle Scholar
  121. Koochekpour S, Merzak A, Pilkington GJ. 1995. Growth factors and gangliosides stimulate laminin production by human glioma cells in vitro. Neurosci Lett 186: 53–56.PubMedGoogle Scholar
  122. Koochekpour S, Merzak A, Pilkington GJ. 1996. Vascular endothelial growth factor production is stimulated by gangliosides and TGF-beta isoforms in human glioma cells in vitro. Cancer Lett 102: 209–215.PubMedGoogle Scholar
  123. Koochekpour S, Pilkington GJ. 1996. Vascular and perivascular GD3 expression in human glioma. Cancer Lett 104: 97–102.PubMedGoogle Scholar
  124. Kostic D, Buchheit F. 1970. Gangliosides in human brain tumors. Life Sci 9: 589–596.Google Scholar
  125. Koyuturk M, Ersoz M, Altiok N. 2004. Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via c-jun N-terminal kinase. Neurosci Lett 370: 212–217.PubMedGoogle Scholar
  126. Kulp SK, Yang YT, Hung CC, Chen KF, Lai JP, et al. 2004. 3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major cyclooxygenase-2-independent target for celecoxib in prostate cancer cells. Cancer Res 64: 1444–1451.PubMedGoogle Scholar
  127. Kurpad SN, Zhao XG, Wikstrand CJ, Batra SK, McLendon RE, et al. 1995. Tumor antigens in astrocytic gliomas. Glia 15: 244–256.PubMedGoogle Scholar
  128. Kurzel F, Hagel C, Zapf S, Meissner H, Westphal M, et al. 2002. Cyclo-oxygenase inhibitors and thromboxane synthase inhibitors differentially regulate migration arrest, growth inhibition and apoptosis in human glioma cells. Acta Neurochir (Wien) 144: 71–87.Google Scholar
  129. Ladisch S, Gillard B, Wong C, Ulsh L. 1983. Shedding and immunoregulatory activity of YAC-1 lymphoma cell gangliosides. Cancer Res 43: 3808–3813.PubMedGoogle Scholar
  130. Ladisch S, Chang F, Li R, Cogen P, Johnson D. 1997. Detection of medulloblastoma and astrocytoma-associated ganglioside GD3 in cerebrospinal fluid. Cancer Lett 120: 71–78.PubMedGoogle Scholar
  131. Larner J, Jane J, Laws E, Packer R, Myers C, et al. 1998. A phase I-II trial of lovastatin for anaplastic astrocytoma and glioblastoma multiforme. Am J Clin Oncol 21: 579–583.PubMedGoogle Scholar
  132. Lauc G, Heffer-Lauc M. 2006. Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins. Biochim Biophys Acta 1760: 584–602.PubMedGoogle Scholar
  133. Le Scolan E, Pchejetski D, Banno Y, Denis N, Mayeux P, et al. 2005. Overexpression of sphingosine kinase 1 is an oncogenic event in erythroleukemic progression. Blood 106: 1808–1816.PubMedGoogle Scholar
  134. Le Stunff H, Milstien S, Spiegel S. 2004. Generation and metabolism of bioactive sphingosine-1-phosphate. J Cell Biochem 92: 882–899.PubMedGoogle Scholar
  135. Leaver HA, Bell HS, Rizzo MT, Ironside JW, Gregor A, et al. 2002a. Antitumour and pro-apoptotic actions of highly unsaturated fatty acids in glioma. Prostaglandins Leukot Essent Fatty Acids 66: 19–29.PubMedGoogle Scholar
  136. Leaver HA, Wharton SB, Bell HS, Leaver-Yap IM, Whittle IR. 2002b. Highly unsaturated fatty acid induced tumour regression in glioma pharmacodynamics and bioavailability of gamma linolenic acid in an implantation glioma model: Effects on tumour biomass, apoptosis and neuronal tissue histology. Prostaglandins Leukot Essent Fatty Acids 67: 283–292.PubMedGoogle Scholar
  137. Leaver HA, Williams JR, Smith C, Whittle IR. 2004. Intracellular oxidation by human glioma cell populations: Effect of arachidonic acid. Prostaglandins Leukot Essent Fatty Acids 70: 449–453.PubMedGoogle Scholar
  138. Ledwozyw A, Lutnicki K. 1992. Phospholipids and fatty acids in human brain tumors. Acta Physiol Hung 79: 381–387.PubMedGoogle Scholar
  139. Lee MJ, Thangada S, Claffey KP, Ancellin N, Liu CH, et al. 1999a. Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell 99: 301–312.PubMedGoogle Scholar
  140. Lee OH, Kim YM, Lee YM, Moon EJ, Lee DJ, et al. 1999b. Sphingosine 1-phosphate induces angiogenesis: Its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. Biochem Biophys Res Commun 264: 743–750.PubMedGoogle Scholar
  141. Lehnhardt FG, Rohn G, Ernestus RI, Grune M, Hoehn M. 2001. 1H- and 31P-MR spectroscopy of primary and recurrent human brain tumors in vitro: Malignancy-characteristic profiles of water soluble and lipophilic spectral components. NMR Biomed 14: 307–317.PubMedGoogle Scholar
  142. Lepley D, Paik JH, Hla T, Ferrer F. 2005. The G protein-coupled receptor S1P2 regulates Rho/Rho kinase pathway to inhibit tumor cell migration. Cancer Res 65: 3788–3795.PubMedGoogle Scholar
  143. Li J, Yen C, Liaw D, Podsypanina K, Bose S, et al. 1997. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943–1947.PubMedGoogle Scholar
  144. Li RX, Ladisch S. 1991. Shedding of human neuroblastoma gangliosides. Biochim Biophys Acta 1083: 57–64.PubMedGoogle Scholar
  145. Lo HS, Hogan EL, Koontz DA, Traylor TD. 1980. Serum gangliosides in cerebral astrocytoma. Ann Neurol 8: 534–538.PubMedGoogle Scholar
  146. Loeffler S, Fayard B, Weis J, Weissenberger J. 2005. Interleukin-6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1. Int J Cancer 115: 202–213.PubMedGoogle Scholar
  147. Loh JK, Hwang SL, Lieu AS, Huang TY, Howng SL. 2002. The alteration of prostaglandin E2 levels in patients with brain tumors before and after tumor removal. J Neurooncol 57: 147–150.PubMedGoogle Scholar
  148. Lombardi V, Valko L, Valko M, Scozzafava A, Morris H, et al. 1997. 1H NMR ganglioside ceramide resonance region on the differential diagnosis of low and high malignancy of brain gliomas. Cell Mol Neurobiol 17: 521–535.PubMedGoogle Scholar
  149. Lopez-Aguilar E, Sepulveda-Vildosola AC, Rivera-Marquez H, Cerecedo-Diaz F, Valdez-Sanchez M, et al. 1999. Security and maximal tolerated doses of fluvastatin in pediatric cancer patients. Arch Med Res 30: 128–131.PubMedGoogle Scholar
  150. Lou HO, Clausen J, Bierring F. 1965. Phospholipids and glycolipids of tumours in the central nervous system. J Neurochem 12: 619–627.PubMedGoogle Scholar
  151. Maccarrone M, Attina M, Cartoni A, Bari M, Finazzi-Agro A. 2001. Gas chromatography-mass spectrometry analysis of endogenous cannabinoids in healthy and tumoral human brain and human cells in culture. J Neurochem 76: 594–601.PubMedGoogle Scholar
  152. Maccarrone M, Pauselli R, Di Rienzo M, Finazzi-Agro A. 2002. Binding, degradation and apoptotic activity of stearoylethanolamide in rat C6 glioma cells. Biochem J 366: 137–144.PubMedGoogle Scholar
  153. Maceyka M, Payne SG, Milstien S, Spiegel S. 2002. Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. Biochim Biophys Acta 1585: 193–201.PubMedGoogle Scholar
  154. Maeda Y, Yamaki T, Yoshikawa J, Tatewaki K, Piao H, et al. 1998. Chemical, metabolic and immunological characterization of gangliosides of human glioma cells. Cancer Biochem Biophys 16: 313–332.PubMedGoogle Scholar
  155. Magrassi L, Adorni L, Montorfano G, Rapelli S, Butti G, et al. 1998. Vitamin D metabolites activate the sphingomyelin pathway and induce death of glioblastoma cells. Acta Neurochir (Wien) 140: 707–713.Google Scholar
  156. Maidment SL, Merzak A, Koochekpour S, Rooprai HK, Rucklidge GJ, et al. 1996. The effect of exogenous gangliosides on matrix metalloproteinase secretion by human glioma cells in vitro. Eur J Cancer 32A: 868–871.PubMedGoogle Scholar
  157. Malchinkhuu E, Sato K, Muraki T, Ishikawa K, Kuwabara A, et al. 2003. Assessment of the role of sphingosine 1-phosphate and its receptors in high-density lipoprotein-induced stimulation of astroglial cell function. Biochem J 370: 817–827.PubMedGoogle Scholar
  158. Malchinkhuu E, Sato K, Horiuchi Y, Mogi C, Ohwada S, et al. 2005. Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells. Oncogene 24: 6676–6688.PubMedGoogle Scholar
  159. Malek RL, Toman RE, Edsall LC, Wong S, Chiu J, et al. 2001. Nrg-1 belongs to the endothelial differentiation gene family of G protein-coupled sphingosine-1-phosphate receptors. J Biol Chem 276: 5692–5699.PubMedGoogle Scholar
  160. Maltese WA, Defendini R, Green RA, Sheridan KM, Donley DK. 1985. Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Clin Invest 76: 1748–1754.PubMedGoogle Scholar
  161. Manfredi MG, Lim S, Claffey KP, Seyfried TN. 1999. Gangliosides influence angiogenesis in an experimental mouse brain tumor. Cancer Res 59: 5392–5397.PubMedGoogle Scholar
  162. Manning TJ Jr, Parker JC, Sontheimer H. 2000. Role of lysophosphatidic acid and rho in glioma cell motility. Cell Motil Cytoskeleton 45: 185–199.PubMedGoogle Scholar
  163. Martin DD, Robbins ME, Spector AA, Wen BC, Hussey DH. 1996. The fatty acid composition of human gliomas differs from that found in nonmalignant brain tissue. Lipids 31: 1283–1288.PubMedGoogle Scholar
  164. Massi P, Vaccani A, Ceruti S, Colombo A, Abbracchio MP, et al. 2004. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. J Pharmacol Exp Ther 308: 838–845.PubMedGoogle Scholar
  165. Matsuo M, Yonemitsu N, Zaitsu M, Ishii K, Hamasaki Y, et al. 2001. Expression of prostaglandin H synthase-2 in human brain tumors. Acta Neuropathol (Berl) 102: 181–187.Google Scholar
  166. Matsuo M, Yoshida N, Zaitsu M, Ishii K, Hamasaki Y. 2004. Inhibition of human glioma cell growth by a PHS-2 inhibitor, NS398, and a prostaglandin E receptor subtype EP1-selective antagonist, SC51089. J Neurooncol 66: 285–292.PubMedGoogle Scholar
  167. Mazhar D, Gillmore R, Waxman J. 2005. COX and cancer. QJM 98: 711–718.PubMedGoogle Scholar
  168. McAllister SD, Chan C, Taft RJ, Luu T, Abood ME, et al. 2005. Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. J Neurooncol 74: 31–40.PubMedGoogle Scholar
  169. Merzak A, Koochekpour S, Pilkington GJ. 1994. Cell surface gangliosides are involved in the control of human glioma cell invasion in vitro. Neurosci Lett 177: 44–46.PubMedGoogle Scholar
  170. Merzak A, Koochekpour S, Pilkington GJ. 1995. Adhesion of human glioma cell lines to fibronectin, laminin, vitronectin and collagen I is modulated by gangliosides in vitro. Cell Adhes Commun 3: 27–43.PubMedGoogle Scholar
  171. Mitsuda T, Furukawa K, Fukumoto S, Miyazaki H, Urano T, et al. 2002. Overexpression of ganglioside GM1 results in the dispersion of platelet-derived growth factor receptor from glycolipid-enriched microdomains and in the suppression of cell growth signals. J Biol Chem 277: 11239–11246.PubMedGoogle Scholar
  172. Mochizuki T, Asai A, Saito N, Tanaka S, Katagiri H, et al. 2002. Akt protein kinase inhibits non-apoptotic programmed cell death induced by ceramide. J Biol Chem 277: 2790–2797.PubMedGoogle Scholar
  173. Morosetti R, Servidei T, Mirabella M, Rutella S, Mangiola A, et al. 2004. The PPARγ ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines. Int J Oncol 25: 493–502.PubMedGoogle Scholar
  174. Murakami M, Goto T, Saito Y, Goto S, Kochi M, et al. 2001. The inhibitory effect of simvastatin on growth in malignant gliomas–with special reference to its local application with fibrin glue spray in vivo. Int J Oncol 19: 525–531.PubMedGoogle Scholar
  175. Murata J, Lee HY, Clair T, Krutzsch HC, Arestad AA, et al. 1994. cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. J Biol Chem 269: 30479–30484.PubMedGoogle Scholar
  176. Naidu MR, Das UN, Kishan A. 1992. Intratumoral gamma-linoleic acid therapy of human gliomas. Prostaglandins Leukot Essent Fatty Acids 45: 181–184.PubMedGoogle Scholar
  177. Nakamura O, Iwamori M, Matsutani M, Takakura K. 1991. Ganglioside GD3 shedding by human gliomas. Acta Neurochir (Wien) 109: 34–36.Google Scholar
  178. Nam DH, Park K, Park C, Im YH, Kim MH, et al. 2004. Intracranial inhibition of glioma cell growth by cyclooxygenase-2 inhibitor celecoxib. Oncol Rep 11: 263–268.PubMedGoogle Scholar
  179. Nathoo N, Barnett GH, Golubic M. 2004. The eicosanoid cascade: Possible role in gliomas and meningiomas. J Clin Pathol 57: 6–13.PubMedGoogle Scholar
  180. Nathoo N, Prayson RA, Bondar J, Vargo L, Arrigain S, et al. 2006. Increased expression of 5-lipoxygenase in high-grade astrocytomas. Neurosurgery 58: 347–354.PubMedGoogle Scholar
  181. Noda S, Yoshimura S, Sawada M, Naganawa T, Iwama T, et al. 2001. Role of ceramide during cisplatin-induced apoptosis in C6 glioma cells. J Neurooncol 52: 11–21.PubMedGoogle Scholar
  182. Noll EN, Lin J, Nakatsuji Y, Miller RH, Black PM. 2001. GM3 as a novel growth regulator for human gliomas. Exp Neurol 168: 300–309.PubMedGoogle Scholar
  183. Nygren C, von Holst H, Mansson JE, Fredman P. 1997. Increased levels of cholesterol esters in glioma tissue and surrounding areas of human brain. Br J Neurosurg 11: 216–220.PubMedGoogle Scholar
  184. Obara Y, Kurose H, Nakahata N. 2005. Thromboxane A2 promotes interleukin-6 biosynthesis mediated by an activation of cyclic AMP-response element-binding protein in 1321N1 human astrocytoma cells. Mol Pharmacol 68: 670–679.PubMedGoogle Scholar
  185. Ohgaki H. 2005. Genetic pathways to glioblastomas. Neuropathology 25: 1–7.PubMedGoogle Scholar
  186. Okamoto H, Takuwa N, Yokomizo T, Sugimoto N, Sakurada S, et al. 2000. Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3. Mol Cell Biol 20: 9247–9261.PubMedGoogle Scholar
  187. Pan XL, Izumi T, Yamada H, Akiyoshi K, Suenobu S, et al. 2000. Ganglioside patterns in neuroepithelial tumors of childhood. Brain Dev 22: 196–198.PubMedGoogle Scholar
  188. Patti R, Gumired K, Reddanna P, Sutton LN, Phillips PC, et al. 2002. Overexpression of cyclooxygenase-2 (COX-2) in human primitive neuroectodermal tumors: Effect of celecoxib and rofecoxib. Cancer Lett 180: 13–21.PubMedGoogle Scholar
  189. Petersen C, Petersen S, Milas L, Lang FF, Tofilon PJ. 2000. Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor. Clin Cancer Res 6: 2513–2520.PubMedGoogle Scholar
  190. Petersen G, Moesgaard B, Schmid PC, Schmid HH, Broholm H, et al. 2005. Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non-tumour brain tissue. J Neurochem 93: 299–309.PubMedGoogle Scholar
  191. Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, et al. 2002. A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50: 857–860.PubMedGoogle Scholar
  192. Pilorget A, Annabi B, Bouzeghrane F, Marvaldi J, Luis J, et al. 2005. Inhibition of angiogenic properties of brain endothelial cells by platelet-derived sphingosine-1-phosphate. J Cereb Blood Flow Metab 25: 1171–1182.PubMedGoogle Scholar
  193. Popko B, Pearl DK, Walker DM, Comas TC, Baerwald KD, et al. 2002. Molecular markers that identify human astrocytomas and oligodendrogliomas. J Neuropathol Exp Neurol 61: 329–338.PubMedGoogle Scholar
  194. Poppe M, Reimertz C, Munstermann G, Kogel D, Prehn JH. 2002. Ceramide-induced apoptosis of D283 medulloblastoma cells requires mitochondrial respiratory chain activity but occurs independently of caspases and is not sensitive to Bcl-xL overexpression. J Neurochem 82: 482–494.PubMedGoogle Scholar
  195. Portnow J, Suleman S, Grossman SA, Eller S, Carson K. 2002. A cyclooxygenase-2 (COX-2) inhibitor compared with dexamethasone in a survival study of rats with intracerebral 9L gliosarcomas. Neuro Oncol 4: 22–25.PubMedGoogle Scholar
  196. Prayson RA, Castilla EA, Vogelbaum MA, Barnett GH. 2002. Cyclooxygenase-2 (COX-2) expression by immunohistochemistry in glioblastoma multiforme. Ann Diagn Pathol 6: 148–153.PubMedGoogle Scholar
  197. Rabin SJ, Mocchetti I. 1995. GM1 ganglioside activates the high-affinity nerve growth factor receptor trkA. J Neurochem 65: 347–354.PubMedGoogle Scholar
  198. Raffaghello L, Marimpietri D, Pagnan G, Pastorino F, Cosimo E, et al. 2003. Anti-GD2 monoclonal antibody immunotherapy: A promising strategy in the prevention of neuroblastoma relapse. Cancer Lett 197: 205–209.PubMedGoogle Scholar
  199. Rampersaud AA, Van Brocklyn JR, Yates AJ. 1998. GM1 activates the MAP kinase cascade through a novel wortmannin-sensitive step upstream from c-Raf. Ann N Y Acad Sci 845: 424.PubMedGoogle Scholar
  200. Recht LD, Salmonsen R, Rosetti R, Jang T, Pipia G, et al. 2001. Antitumor effects of ajulemic acid (CT3), a synthetic non-psychoactive cannabinoid. Biochem Pharmacol 62: 755–763.PubMedGoogle Scholar
  201. Reynolds LM, Dalton CF, Reynolds GP. 2001. Phospholipid fatty acids and neurotoxicity in human neuroblastoma SH-SY5Y cells. Neurosci Lett 309: 193–196.PubMedGoogle Scholar
  202. Riboni L, Campanella R, Bassi R, Villani R, Gaini SM, et al. 2002. Ceramide levels are inversely associated with malignant progression of human glial tumors. Glia 39: 105–113.PubMedGoogle Scholar
  203. Rolhion C, Penault-Llorca F, Kemeny JL, Lemaire JJ, Jullien C, et al. 2001. Interleukin-6 overexpression as a marker of malignancy in human gliomas. J Neurosurg 94: 97–101.PubMedGoogle Scholar
  204. Rudra PK, Krokan HE. 2001. Cell-specific enhancement of doxorubicin toxicity in human tumour cells by docosahexaenoic acid. Anticancer Res 21: 29–38.PubMedGoogle Scholar
  205. Ryu Y, Takuwa N, Sugimoto N, Sakurada S, Usui S, et al. 2002. Sphingosine-1-phosphate, a platelet-derived lysophospholipid mediator, negatively regulates cellular Rac activity and cell migration in vascular smooth muscle cells. Circ Res 90: 325–332.PubMedGoogle Scholar
  206. Salhia B, Rutten F, Nakada M, Beaudry C, Berens M, et al. 2005. Inhibition of Rho-kinase affects astrocytoma morphology, motility, and invasion through activation of Rac1. Cancer Res 65: 8792–8800.PubMedGoogle Scholar
  207. Sanai N, Alvarez-Buylla A, Berger MS. 2005. Neural stem cells and the origin of gliomas. N Engl J Med 353: 811–822.PubMedGoogle Scholar
  208. Sanchez C, Galve-Roperh I, Canova C, Brachet P, Guzman M. 1998. Δ9-tetrahydrocannabinol induces apoptosis in C6 glioma cells. FEBS Lett 436: 6–10.PubMedGoogle Scholar
  209. Sanchez C, de Ceballos ML, del Pulgar TG, Rueda D, Corbacho C, et al. 2001. Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res 61: 5784–5789.PubMedGoogle Scholar
  210. Saqr HE, Lee MC, Burkman AM, Yates AJ. 1995. Gangliosides have a bimodal effect on DNA synthesis in U-1242 MG human glioma cells. J Neurosci Res 41: 491–500.PubMedGoogle Scholar
  211. Saqr HE, Omran O, Dasgupta S, Yu RK, Oblinger JL, et al. 2006. Endogenous GD3 ganglioside induces apoptosis in U-1242 MG glioma cells. J Neurochem 96: 1301–1314.PubMedGoogle Scholar
  212. Sato K, Ishikawa K, Ui M, Okajima F. 1999a. Sphingosine 1-phosphate induces expression of early growth response-1 and fibroblast growth factor-2 through mechanism involving extracellular signal-regulated kinase in astroglial cells. Brain Res Mol Brain Res 74: 182–189.PubMedGoogle Scholar
  213. Sato K, Tomura H, Igarashi Y, Ui M, Okajima F. 1999b. Possible involvement of cell surface receptors in sphingosine 1-phosphate-induced activation of extracellular signal-regulated kinase in C6 glioma cells. Mol Pharmacol 55: 126–133.PubMedGoogle Scholar
  214. Sato K, Ui M, Okajima F. 2000. Differential roles of Edg-1 and Edg-5, sphingosine 1-phosphate receptors, in the signaling pathways in C6 glioma cells. Brain Res Mol Brain Res 85: 151–160.PubMedGoogle Scholar
  215. Sawada M, Nakashima S, Banno Y, Yamakawa H, Hayashi K, et al. 2000. Ordering of ceramide formation, caspase activation, and Bax/Bcl-2 expression during etoposide-induced apoptosis in C6 glioma cells. Cell Death Differ 7: 761–772.PubMedGoogle Scholar
  216. Sawada M, Nakashima S, Kiyono T, Nakagawa M, Yamada J, et al. 2001. p53 regulates ceramide formation by neutral sphingomyelinase through reactive oxygen species in human glioma cells. Oncogene 20: 1368–1378.PubMedGoogle Scholar
  217. Sawada M, Nakashima S, Kiyono T, Yamada J, Hara S, et al. 2002. Acid sphingomyelinase activation requires caspase-8 but not p53 nor reactive oxygen species during Fas-induced apoptosis in human glioma cells. Exp Cell Res 273: 157–168.PubMedGoogle Scholar
  218. Sawada M, Kiyono T, Nakashima S, Shinoda J, Naganawa T, et al. 2004. Molecular mechanisms of TNF-alpha-induced ceramide formation in human glioma cells: P53-mediated oxidant stress-dependent and -independent pathways. Cell Death Differ 11: 997–1008.PubMedGoogle Scholar
  219. Schulz G, Cheresh DA, Varki NM, Yu A, Staffileno LK, et al. 1984. Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma patients. Cancer Res 44: 5914–5920.PubMedGoogle Scholar
  220. Seasholtz TM, Radeff-Huang J, Sagi SA, Matteo R, Weems JM, et al. 2004. Rho-mediated cytoskeletal rearrangement in response to LPA is functionally antagonized by Rac1 and PIP2. J Neurochem 91: 501–512.PubMedGoogle Scholar
  221. Segura BJ, Zhang W, Xiao L, Logsdon CD, Mulholland MW. 2005. Sphingosine-1-phosphate induces early response gene expression in C6 glioma cells. Brain Res Mol Brain Res 133: 325–328.PubMedGoogle Scholar
  222. Seyfried TN, el-Abbadi M, Ecsedy JA, Bai HW, Yohe HC. 1996. Influence of host cell infiltration on the glycolipid content of mouse brain tumors. J Neurochem 66: 2026–2033.PubMedGoogle Scholar
  223. Seyfried TN, el-Abbadi M, Ecsedy JA, Griffin ME, Yohe HC. 1998. Ganglioside composition of a mouse brain tumor grown in the severe combined immunodeficiency (SCID) mouse. Mol Chem Neuropathol 33: 27–37.PubMedGoogle Scholar
  224. Shinoura N, Dohi T, Kondo T, Yoshioka M, Takakura K, et al. 1992. Ganglioside composition and its relation to clinical data in brain tumors. Neurosurgery 31: 541–549.PubMedGoogle Scholar
  225. Shono T, Tofilon PJ, Bruner JM, Owolabi O, Lang FF. 2001. Cyclooxygenase-2 expression in human gliomas: Prognostic significance and molecular correlations. Cancer Res 61: 4375–4381.PubMedGoogle Scholar
  226. Singh LP, Pearl DK, Franklin TK, Spring PM, Scheithauer BW, et al. 1994. Neutral glycolipid composition of primary human brain tumors. Mol Chem Neuropathol 21: 241–257.PubMedGoogle Scholar
  227. Sminia P, Stoter TR, van der Valk P, Elkhuizen PH, Tadema TM, et al. 2005. Expression of cyclooxygenase-2 and epidermal growth factor receptor in primary and recurrent glioblastoma multiforme. J Cancer Res Clin Oncol 131: 653–661.PubMedGoogle Scholar
  228. Smith GD, Neaton JD, Ben-Shlomo Y, Shipley M, Wentworth D. 1992. Serum cholesterol concentration and primary malignant brain tumors: A prospective study. Am J Epidemiol 135: 259–265.PubMedGoogle Scholar
  229. Soma MR, Pagliarini P, Butti G, Paoletti R, Paoletti P, et al. 1992. Simvastatin, an inhibitor of cholesterol biosynthesis, shows a synergistic effect with N,N′-bis(2-chloroethyl)-N-nitrosourea and β-interferon on human glioma cells. Cancer Res 52: 4348–4355.PubMedGoogle Scholar
  230. Soma MR, Baetta R, De Renzis MR, Mazzini G, Davegna C, et al. 1995. In vivo enhanced antitumor activity of carmustine [N,N′-bis(2-chloroethyl)-N-nitrosourea] by simvastatin. Cancer Res 55: 597–602.PubMedGoogle Scholar
  231. Sottocornola E, Colombo I, Vergani V, Taraboletti G, Berra B. 1999. Increased tumorigenicity and invasiveness of C6 rat glioma cells transfected with the human α-2,8 scDNA. Invasion Metastasis 18: 142–154.Google Scholar
  232. Spiegel S, Milstien S. 2003. Sphingosine-1-phosphate: An enigmatic signalling lipid. Nat Rev Mol Cell Biol 4: 397–407.PubMedGoogle Scholar
  233. Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, et al. 1998. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95: 29–39.PubMedGoogle Scholar
  234. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, et al. 2000. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342: 1946–1952.PubMedGoogle Scholar
  235. Steiner MR, Urso JR, Klein J, Steiner SM. 2002. Multiple astrocyte responses to lysophosphatidic acids. Biochim Biophys Acta 1582: 154–160.PubMedGoogle Scholar
  236. Sullards MC, Wang E, Peng Q, Merrill AH Jr. 2003. Metabolomic profiling of sphingolipids in human glioma cell lines by liquid chromatography tandem mass spectrometry. Cell Mol Biol (Noisy-le-grand) 49: 789–797.Google Scholar
  237. Sung CC, Pearl DK, Coons SW, Scheithauer BW, Johnson PC, et al. 1994. Gangliosides as diagnostic markers of human astrocytomas and primitive neuroectodermal tumors. Cancer 74: 3010–3022.PubMedGoogle Scholar
  238. Sung CC, Pearl DK, Coons SW, Scheithauer BW, Johnson PC, et al. 1995. Correlation of ganglioside patterns of primary brain tumors with survival. Cancer 75: 851–859.PubMedGoogle Scholar
  239. Sung CC, Collins R, Li J, Pearl DK, Coons SW, et al. 1996. Glycolipids and myelin proteins in human oligodendrogliomas. Glycoconj J 13: 433–443.PubMedGoogle Scholar
  240. Sung CC, O'Toole EA, Lannutti BJ, Hunt J, O'Gorman M, et al. 1998. Integrin α5 β1 expression is required for inhibition of keratinocyte migration by ganglioside GT1b. Exp Cell Res 239: 311–319.PubMedGoogle Scholar
  241. Svennerholm L. 1980. Ganglioside designation. Adv Exp Med Biol 125: 11.PubMedGoogle Scholar
  242. Taha TA, Argraves KM, Obeid LM. 2004. Sphingosine-1-phosphate receptors: Receptor specificity versus functional redundancy. Biochim Biophys Acta 1682: 48–55.PubMedGoogle Scholar
  243. Tas PW, Koschel K. 1998. Sphingosine-1-phosphate induces a Ca2+ signal in primary rat astrocytes and a Ca2+ signal and shape changes in C6 rat glioma cells. J Neurosci Res 52: 427–434.PubMedGoogle Scholar
  244. Testai FD, Landek MA, Dawson G. 2004. Regulation of sphingomyelinases in cells of the oligodendrocyte lineage. J Neurosci Res 75: 66–74.PubMedGoogle Scholar
  245. Thibault A, Samid D, Tompkins AC, Figg WD, Cooper MR, et al. 1996. Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clin Cancer Res 2: 483–491.PubMedGoogle Scholar
  246. Thornton MV, Kudo D, Rayman P, Horton C, Molto L, et al. 2004. Degradation of NF-kappa B in T cells by gangliosides expressed on renal cell carcinomas. J Immunol 172: 3480–3490.PubMedGoogle Scholar
  247. Thun MJ, Henley SJ, Patrono C. 2002. Nonsteroidal anti-inflammatory drugs as anticancer agents: Mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 94: 252–266.PubMedGoogle Scholar
  248. Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, et al. 2002. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem 277: 39436–39442.PubMedGoogle Scholar
  249. Tosi MR, Bottura G, Lucchi P, Reggiani A, Trinchero A, et al. 2003. Cholesteryl esters in human malignant neoplasms. Int J Mol Med 11: 95–98.PubMedGoogle Scholar
  250. Traylor TD, Hogan EL. 1980. Gangliosides of human cerebral astrocytomas. J Neurochem 34: 126–131.PubMedGoogle Scholar
  251. Traynelis VC, Ryken TC, Cornelius AS. 1995. Cytotoxicity of cis-parinaric acid in cultured malignant gliomas. Neurosurgery 37: 484–489.PubMedGoogle Scholar
  252. Tuettenberg J, Grobholz R, Korn T, Wenz F, Erber R, et al. 2005. Continuous low-dose chemotherapy plus inhibition of cyclooxygenase-2 as an antiangiogenic therapy of glioblastoma multiforme. J Cancer Res Clin Oncol 131: 31–40.PubMedGoogle Scholar
  253. Tugnoli V, Tosi MR, Tinti A, Trinchero A, Bottura G, et al. 2001. Characterization of lipids from human brain tissues by multinuclear magnetic resonance spectroscopy. Biopolymers 62: 297–306.PubMedGoogle Scholar
  254. Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, et al. 2002. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol 158: 227–233.PubMedGoogle Scholar
  255. Umezu-Goto M, Tanyi J, Lahad J, Liu S, Yu S, et al. 2004. Lysophosphatidic acid production and action: Validated targets in cancer? J Cell Biochem 92: 1115–1140.PubMedGoogle Scholar
  256. Vaccani A, Massi P, Colombo A, Rubino T, Parolaro D. 2005. Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism. Br J Pharmacol 144: 1032–1036.PubMedGoogle Scholar
  257. Van Brocklyn J, Bremer EG, Yates AJ. 1993. Gangliosides inhibit platelet-derived growth factor-stimulated receptor dimerization in human glioma U-1242 MG and Swiss 3T3 cells. J Neurochem 61: 371–374.PubMedGoogle Scholar
  258. Van Brocklyn JR, Vandenheede JR, Fertel R, Yates AJ, Rampersaud AA. 1997. Ganglioside GM1 activates the mitogen-activated protein kinase Erk2 and p70 S6 kinase in U-1242 MG human glioma cells. J Neurochem 69: 116–125.PubMedGoogle Scholar
  259. Van Brocklyn JR, Letterle CA, Snyder PJ, Prior TW. 2002. Sphingosine-1-phosphate stimulates human glioma cell proliferation through Gi-coupled receptors: Role of ERK MAP kinase and phosphatidylinositol 3-kinase β. Cancer Lett 181: 195–204.PubMedGoogle Scholar
  260. Van Brocklyn JR, Young N, Roof R. 2003. Sphingosine-1-phosphate stimulates motility and invasiveness of human glioblastoma multiforme cells. Cancer Lett 199: 53–60.PubMedGoogle Scholar
  261. Van Brocklyn JR, Jackson CA, Pearl DK, Kotur MS, Snyder PJ, et al. 2005. Sphingosine kinase-1 expression correlates with poor survival of patients with glioblastoma multiforme. Roles of sphingosine kinase isoforms in growth of glioblastoma cell lines. J Neuropathol Exp Neurol 64: 695–705.PubMedGoogle Scholar
  262. Vann LR, Payne SG, Edsall LC, Twitty S, Spiegel S, et al. 2002. Involvement of sphingosine kinase in TNF-α stimulated tetrahydrobiopterin biosynthesis in C6 glioma cells. J Biol Chem 277: 12649–12656.PubMedGoogle Scholar
  263. Vartak S, Robbins ME, Spector AA. 1997. Polyunsaturated fatty acids increase the sensitivity of 36B10 rat astrocytoma cells to radiation-induced cell kill. Lipids 32: 283–292.PubMedGoogle Scholar
  264. Vartak S, McCaw R, Davis CS, Robbins ME, Spector AA. 1998. Gamma-linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to ‘normal’ rat astrocytes. Br J Cancer 77: 1612–1620.PubMedGoogle Scholar
  265. Velasco G, Galve-Roperh I, Sanchez C, Blazquez C, Guzman M. 2004. Hypothesis: Cannabinoid therapy for the treatment of gliomas? Neuropharmacology 47: 315–323PubMedGoogle Scholar
  266. Vescovi AL, Galli R, Reynolds BA. 2006. Brain tumour stem cells. Nat Rev Cancer 6: 425–436.PubMedGoogle Scholar
  267. Viani P, Giussani P, Brioschi L, Bassi R, Anelli V, et al. 2003. Ceramide in nitric oxide inhibition of glioma cell growth. Evidence for the involvement of ceramide traffic. J Biol Chem 278: 9592–9601.PubMedGoogle Scholar
  268. Visentin B, Vekich JA, Sibbald BJ, Cavalli AL, Moreno KM, et al. 2006. Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell 9: 225–238.PubMedGoogle Scholar
  269. Wagenknecht B, Gulbins E, Lang F, Dichgans J, Weller M. 1997. Lipoxygenase inhibitors block CD95 ligand-mediated apoptosis of human malignant glioma cells. FEBS Lett 409: 17–23.PubMedGoogle Scholar
  270. Wagenknecht B, Roth W, Gulbins E, Wolburg H, Weller M. 2001. C2-ceramide signaling in glioma cells: Synergistic enhancement of CD95-mediated, caspase-dependent apoptosis. Cell Death Differ 8: 595–602.PubMedGoogle Scholar
  271. Wang W, Macaulay RJ. 2003. Cell-cycle gene expression in lovastatin-induced medulloblastoma apoptosis. Can J Neurol Sci 30: 349–357.PubMedGoogle Scholar
  272. Wang XQ, Sun P, Paller AS. 2003. Ganglioside GM3 inhibits matrix metalloproteinase-9 activation and disrupts its association with integrin. J Biol Chem 278: 25591–25599.PubMedGoogle Scholar
  273. Weissenberger J, Loeffler S, Kappeler A, Kopf M, Lukes A, et al. 2004. IL-6 is required for glioma development in a mouse model. Oncogene 23: 3308–3316.PubMedGoogle Scholar
  274. Werthle M, Bochelen D, Adamczyk M, Kupferberg A, Poulet P, et al. 1994. Local administration of 7 β-hydroxycholesteryl-3-oleate inhibits growth of experimental rat C6 glioblastoma. Cancer Res 54: 998–1003.PubMedGoogle Scholar
  275. Wikstrand CJ, He XM, Fuller GN, Bigner SH, Fredman P, et al. 1991. Occurrence of lacto series gangliosides 3′-isoLM1 and 3′,6′-isoLD1 in human gliomas in vitro and in vivo. J Neuropathol Exp Neurol 50: 756–769.PubMedGoogle Scholar
  276. Wikstrand CJ, Longee DC, McLendon RE, Fuller GN, Friedman HS, et al. 1993. Lactotetraose series ganglioside 3′,6′-isoLD1 in tumors of central nervous and other systems in vitro and in vivo. Cancer Res 53: 120–126.PubMedGoogle Scholar
  277. Wikstrand CJ, Fredman P, McLendon RR, Svennerholm L, Bigner DD. 1994. Altered expression of ganglioside phenotypes of human gliomas in vivo and in vitro. Mol Chem Neuropathol 21: 129–138.PubMedGoogle Scholar
  278. Williams JR, Leaver HA, Ironside JW, Miller EP, Whittle IR, et al. 1998. Apoptosis in human primary brain tumours: Actions of arachidonic acid. Prostaglandins Leukot Essent Fatty Acids 58: 193–200.PubMedGoogle Scholar
  279. Windh RT, Lee MJ, Hla T, An S, Barr AJ, et al. 1999. Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the Gi, Gq, and G12 families of heterotrimeric G proteins. J Biol Chem 274: 27351–27358.PubMedGoogle Scholar
  280. Yates AJ, Thompson DK, Boesel CP, Albrightson C, Hart RW. 1979. Lipid composition of human neural tumors. J Lipid Res 20: 428–436.PubMedGoogle Scholar
  281. Yates AJ, Agudelo JD, Sung CC. 1992. Glycolipids of a human glioma cell line bearing receptors for platelet-derived growth factor (PDGF). Lipids 27: 308–310.PubMedGoogle Scholar
  282. Yates AJ, Van Brocklyn J, Saqr HE, Guan Z, Stokes BT, et al. 1993. Mechanisms through which gangliosides inhibit PDGF-stimulated mitogenesis in intact Swiss 3T3 cells: Receptor tyrosine phosphorylation, intracellular calcium, and receptor binding. Exp Cell Res 204: 38–45.PubMedGoogle Scholar
  283. Yates AJ, Comas T, Scheithauer BW, Burger PC, Pearl DK. 1999a. Glycolipid markers of astrocytomas and oligodendrogliomas. J Neuropathol Exp Neurol 58: 1250–1262.PubMedGoogle Scholar
  284. Yates AJ, Franklin TK, McKinney P, Collins R, Comas T, et al. 1999b. Gangliosides and neutral glycolipids in ependymal, neuronal and primitive neuroectodermal tumors. J Mol Neurosci 12: 111–121.PubMedGoogle Scholar
  285. Young N, Van Brocklyn JR. 2007. Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness. Exp Cell Res 313: 1615–1627.PubMedGoogle Scholar
  286. Zander T, Kraus JA, Grommes C, Schlegel U, Feinstein D, et al. 2002. Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARgamma. J Neurochem 81: 1052–1060.PubMedGoogle Scholar
  287. Zha S, Yegnasubramanian V, Nelson WG, Isaacs WB, De Marzo AM. 2004. Cyclooxygenases in cancer: Progress and perspective. Cancer Lett 215: 1–20.PubMedGoogle Scholar
  288. Zhao S, Jiang X, Xue D, Chen D. 1998. Glioma prostaglandin levels correlate with brain edema. J Tongji Med Univ 18: 115–118.PubMedGoogle Scholar
  289. Zinda MJ, Vlahos CJ, Lai MT. 2001. Ceramide induces the dephosphorylation and inhibition of constitutively activated Akt in PTEN negative U87MG cells. Biochem Biophys Res Commun 280: 1107–1115.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

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  • J. R. Van Brocklyn

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