title: Inhibitors of Glioma Growth that Reveal the Tumour to the Immune System.
abstract: Treated glioblastoma patients survive from 6 to 14 months. In the first part of this review, we describe glioma origins, cancer stem cells and the genomic alterations that generate dysregulated cell division, with enhanced proliferation and diverse response to radiation and chemotherapy. We review the pathways that mediate tumour cell proliferation, neo-angiogenesis, tumor cell invasion, as well as necrotic and apoptotic cell death. Then, we examine the ability of gliomas to evade and suppress the host immune system, exhibited at the levels of antigen recognition and immune activation, limiting the effective signaling between glioma and host immune cells.The second part of the review presents current therapies and their drawbacks. This is followed by a summary of the work of our laboratory during the past 20 years, on oligosaccharide and glycosphingolipid inhibitors of astroblast and astrocytoma division. Neurostatins, the O-acetylated forms of gangliosides GD1b and GT1b naturally present in mammalian brain, are cytostatic for normal astroblasts, but cytotoxic for rat C6 glioma cells and human astrocytoma grades III and IV, with ID50 values ranging from 200 to 450 nM. The inhibitors do not affect neurons or fibroblasts up to concentrations of 4 μM or higher.At least four different neurostatin-activated, cell-mediated antitumoral processes, lead to tumor destruction: (i) inhibition of tumor neovascularization; (ii) activation of microglia; (iii) activation of natural killer (NK) cells; (iv) activation of cytotoxic lymphocytes (CTL). The enhanced antigenicity of neurostatin-treated glioma cells, could be related to their increased expression of connexin 43. Because neurostatins and their analogues show specific activity and no toxicity for normal cells, a clinical trial would be the logical next step.
authors.affiliation: Instituto Cajal de Neurobiología, CSIC, 28002 Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Nieto-Sampedro
authors.forename: Beatriz
authors.initials: B
authors.lastname: Valle-Argos
authors.forename: Diego
authors.initials: D
authors.lastname: Gómez-Nicola
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernández-Mayoralas
authors.forename: Manuel
authors.initials: M
authors.lastname: Nieto-Díaz
references.citation: J Med Chem. 1984 Feb;27(2):196-201
references.pmid: 6694168
references.citation: Science. 1990 Nov 30;250(4985):1233-8
references.pmid: 1978757
references.citation: Cancer Res. 2005 Feb 1;65(3):999-1006
references.pmid: 15705901
references.citation: Proc Natl Acad Sci U S A. 1990 Nov;87(21):8602-6
references.pmid: 2236070
references.citation: Chem Biol. 1997 Feb;4(2):97-104
references.pmid: 9190292
references.citation: Cancer Res. 2006 Dec 1;66(23):11502-13
references.pmid: 17114236
references.citation: J Biol Chem. 1998 May 29;273(22):13375-8
references.pmid: 9593664
references.citation: Clin Cancer Res. 2007 Feb 15;13(4):1253-9
references.pmid: 17317837
references.citation: Expert Rev Anticancer Ther. 2005 Oct;5(5):777-90
references.pmid: 16221048
references.citation: J Neurochem. 2000 Jun;74(6):2547-56
references.pmid: 10820217
references.citation: Nature. 2006 Dec 7;444(7120):756-60
references.pmid: 17051156
references.citation: Nat Rev Cancer. 2003 Oct;3(10):721-32
references.pmid: 13130303
references.citation: Oncogene. 2000 Nov 20;19(49):5614-9
references.pmid: 11114742
references.citation: Cancer Res. 2006 Nov 15;66(22):10815-23
references.pmid: 17090523
references.citation: Acta Neuropathol. 2009 Oct;118(4):469-74
references.pmid: 19554337
references.citation: Expert Rev Anticancer Ther. 2003 Oct;3(5):595-614
references.pmid: 14599084
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13944-9
references.pmid: 16166262
references.citation: Cancer Invest. 2004;22(3):417-34
references.pmid: 15493363
references.citation: Neurosurgery. 1998 Feb;42(2):341-6
references.pmid: 9482185
references.citation: Oncogene. 2007 Sep 20;26(43):6289-96
references.pmid: 17438529
references.citation: Brain Res. 1985 Sep 23;343(2):320-8
references.pmid: 3876863
references.citation: Oncogene. 1996 Oct 17;13(8):1615-9
references.pmid: 8895506
references.citation: Cancer Res. 2007 Apr 15;67(8):3691-7
references.pmid: 17440081
references.citation: Proc Natl Acad Sci U S A. 1972 Jul;69(7):1838-42
references.pmid: 4340161
references.citation: Glia. 1995 Nov;15(3):257-63
references.pmid: 8586462
references.citation: Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):241-9
references.pmid: 12787562
references.citation: BMC Cancer. 2010 Feb 21;10:49
references.pmid: 20170543
references.citation: Nature. 1990 Dec 20-27;348(6303):747-9
references.pmid: 2259385
references.citation: Eur J Immunol. 1987 Sep;17(9):1271-8
references.pmid: 3115791
references.citation: J Neuropathol Exp Neurol. 1996 Feb;55(2):169-77
references.pmid: 8786375
references.citation: Genome Biol. 2010;11(5):211
references.pmid: 20441611
references.citation: Neurosurgery. 2002 Jul;51(1):2-12; discussion 12-3
references.pmid: 12182418
references.citation: J Neurosurg. 2004 Feb;100(2):310-9
references.pmid: 15086239
references.citation: Brain Res Dev Brain Res. 1994 Mar 18;78(1):17-24
references.pmid: 8004770
references.citation: Cancer Res. 1994 Aug 15;54(16):4299-303
references.pmid: 8044775
references.citation: Cancer Res. 1998 Dec 1;58(23):5275-9
references.pmid: 9850047
references.citation: J Biol Chem. 1996 Aug 23;271(34):20608-16
references.pmid: 8702807
references.citation: Neurosurg Clin N Am. 2010 Jan;21(1):31-42
references.pmid: 19944964
references.citation: J Neurosci Res. 1989 Jan;22(1):28-35
references.pmid: 2926839
references.citation: Cancer Res. 1992 Aug 1;52(15):4208-13
references.pmid: 1322238
references.citation: Oncogene. 2003 Feb 6;22(5):722-33
references.pmid: 12569364
references.citation: Cancer Res. 1999 Dec 15;59(24):6091-6
references.pmid: 10626796
references.citation: Nature. 1993 Dec 16;366(6456):704-7
references.pmid: 8259215
references.citation: Nature. 1985 Jan 10-18;313(5998):144-7
references.pmid: 2981413
references.citation: Nature. 1994 Dec 22-29;372(6508):786-91
references.pmid: 7997267
references.citation: Mol Cell Biol. 2002 Apr;22(7):2025-36
references.pmid: 11884591
references.citation: Neurosurgery. 2000 May;46(5):1169-77; discussion 1177-8
references.pmid: 10807250
references.citation: Oncologist. 2009 Nov;14(11):1131-8
references.pmid: 19897538
references.citation: Int J Cancer. 2001 Jul 15;93(2):243-51
references.pmid: 11410873
references.citation: Carbohydr Res. 1992 Jun 4;230(1):185-90
references.pmid: 1511452
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12867-72
references.pmid: 17646646
references.citation: Br J Cancer. 1999 Nov;81(6):1022-30
references.pmid: 10576660
references.citation: Nat Med. 2004 May;10(5):475-80
references.pmid: 15122249
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16466-71
references.pmid: 17056721
references.citation: Cell. 2007 Jan 26;128(2):309-23
references.pmid: 17254969
references.citation: Cancer Res. 2000 Feb 15;60(4):847-53
references.pmid: 10706092
references.citation: Cancer Cell. 2006 Aug;10(2):159-70
references.pmid: 16904613
references.citation: J Neurosurg. 2001 Sep;95(3):472-9
references.pmid: 11565870
references.citation: Biochem Soc Trans. 2006 Nov;34(Pt 5):647-62
references.pmid: 17052169
references.citation: Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7727-31
references.pmid: 8052651
references.citation: Cancer Res. 1996 Nov 1;56(21):5079-86
references.pmid: 8895767
references.citation: Prostate. 1999 Dec 1;41(4):275-80
references.pmid: 10544301
references.citation: Neuro Oncol. 2009 Dec;11(6):757-66
references.pmid: 19264916
references.citation: FEBS Lett. 1998 Dec 4;440(3):419-24
references.pmid: 9872414
references.citation: Oncogene. 2003 Apr 17;22(15):2361-73
references.pmid: 12700671
references.citation: J Exp Med. 2010 Feb 15;207(2):339-44
references.pmid: 20142433
references.citation: J Neurosci Res. 2006 Apr;83(5):754-62
references.pmid: 16477650
references.citation: Cancer Cell. 2005 Oct;8(4):323-35
references.pmid: 16226707
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: Oncogene. 1997 May 1;14(17):2005-13
references.pmid: 9160879
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1289-94
references.pmid: 16432180
references.citation: Nat Rev Cancer. 2006 Nov;6(11):876-85
references.pmid: 17036041
references.citation: EMBO J. 1998 Sep 1;17(17):5001-14
references.pmid: 9724636
references.citation: Cancer Res. 2003 Dec 15;63(24):8930-8
references.pmid: 14695210
references.citation: Cancer Manag Res. 2010 Jun 01;2:143-56
references.pmid: 21188105
references.citation: Int J Cancer. 2003 Feb 20;103(5):657-63
references.pmid: 12494475
references.citation: Cancer Res. 1994 Dec 15;54(24):6321-4
references.pmid: 7987821
references.citation: Am J Pathol. 2003 Apr;162(4):1037-42
references.pmid: 12651595
references.citation: Cancer Res. 2006 Mar 15;66(6):3294-302
references.pmid: 16540683
references.citation: Biochemistry. 1999 Jul 6;38(27):8762-9
references.pmid: 10393551
references.citation: Carcinogenesis. 1993 May;14(5):1073-5
references.pmid: 8389252
references.citation: Science. 2007 Oct 12;318(5848):287-90
references.pmid: 17872411
references.citation: Cancer Cell. 2002 Aug;2(2):103-12
references.pmid: 12204530
references.citation: Mol Cell. 2005 Apr 1;18(1):13-24
references.pmid: 15808505
references.citation: Cell. 1998 Mar 20;92(6):713-23
references.pmid: 9529248
references.citation: Neurosci Lett. 1991 May 13;126(1):33-6
references.pmid: 1650934
references.citation: Cancer Cell. 2004 Dec;6(6):553-63
references.pmid: 15607960
references.citation: Annu Rev Neurosci. 1999;22:511-39
references.pmid: 10202547
references.citation: J Natl Cancer Inst. 2005 Jun 15;97(12):880-7
references.pmid: 15956649
references.citation: Cancer Cell. 2002 Mar;1(2):157-68
references.pmid: 12086874
references.citation: Ann N Y Acad Sci. 2009 Sep;1174:18-23
references.pmid: 19769732
references.citation: Mol Cancer Res. 2005 Oct;3(10):541-51
references.pmid: 16254188
references.citation: Cancer Cell. 2010 Jan 19;17(1):98-110
references.pmid: 20129251
references.citation: Cancer Res. 2004 Oct 1;64(19):6892-9
references.pmid: 15466178
references.citation: Science. 2010 Mar 12;327(5971):1380-5
references.pmid: 20223987
references.citation: Cancer Res. 1991 Apr 15;51(8):2164-72
references.pmid: 2009534
references.citation: Clin Cancer Res. 2004 Oct 1;10(19):6732-43
references.pmid: 15475464
references.citation: Crit Rev Immunol. 2009;29(1):1-42
references.pmid: 19348609
references.citation: EMBO J. 1999 Jan 4;18(1):22-7
references.pmid: 9878046
references.citation: Nature. 2006 Dec 7;444(7120):761-5
references.pmid: 17151667
references.citation: Mol Cell Biol. 1997 Jul;17(7):3850-7
references.pmid: 9199319
references.citation: Science. 1997 Mar 28;275(5308):1943-7
references.pmid: 9072974
references.citation: Cancer Res. 1994 Feb 15;54(4):1105-8
references.pmid: 8313368
references.citation: Lab Invest. 2004 Aug;84(8):941-51
references.pmid: 15184909
references.citation: Brain Tumor Pathol. 2003;20(2):65-72
references.pmid: 14756443
references.citation: Cancer Immunol Immunother. 1997 Mar;44(1):55-63
references.pmid: 9111585
references.citation: Prog Nucleic Acid Res Mol Biol. 1995;51:167-223
references.pmid: 7659775
references.citation: Expert Rev Anticancer Ther. 2004 Oct;4(5):803-21
references.pmid: 15485315
references.citation: J Med Chem. 2003 Apr 10;46(8):1286-8
references.pmid: 12672228
references.citation: J Neurosci Res. 1991 Feb;28(2):254-60
references.pmid: 2033653
references.citation: J Biol Chem. 1995 Oct 6;270(40):23589-97
references.pmid: 7559524
references.citation: N Engl J Med. 2000 Nov 9;343(19):1350-4
references.pmid: 11070098
references.citation: Pathol Biol (Paris). 2003 Mar;51(2):74-5
references.pmid: 12801806
references.citation: Pathobiology. 1997;65(4):195-203
references.pmid: 9396043
references.citation: Adv Exp Med Biol. 1996;406:99-112
references.pmid: 8910675
references.citation: J Neurol Neurosurg Psychiatry. 1999 Dec;67(6):763-8
references.pmid: 10567494
references.citation: Oncogene. 2007 Jun 7;26(27):3930-40
references.pmid: 17213812
references.citation: Eur J Med Chem. 2010 May;45(5):2034-43
references.pmid: 20153569
references.citation: J Neurosurg. 2009 Mar;110(3):572-82
references.pmid: 19199469
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references.pmid: 12629218
references.citation: Mol Cell Biol. 2006 Sep;26(17):6425-34
references.pmid: 16914728
references.citation: Cancer Res. 1999 May 1;59(9):2217-22
references.pmid: 10232611
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14057-62
references.pmid: 15383658
references.citation: Cell Death Differ. 2006 Jun;13(6):1027-36
references.pmid: 16557269
references.citation: Cancer Res. 2004 Jun 1;64(11):3892-9
references.pmid: 15172999
references.citation: Cancer Res. 2006 Aug 15;66(16):7864-9
references.pmid: 16912159
references.citation: Cancer Res. 2003 Sep 15;63(18):5821-8
references.pmid: 14522905
references.citation: Cancer Cell. 2010 Mar 16;17(3):225-34
references.pmid: 20171147
references.citation: Eur J Immunol. 1988 Oct;18(10):1623-6
references.pmid: 3142781
references.citation: Nature. 1995 Nov 9;378(6553):203-6
references.pmid: 7477326
references.citation: Proc Natl Acad Sci U S A. 1998 May 12;95(10):5724-9
references.pmid: 9576951
references.citation: J Neurooncol. 2006 Jun;78(2):161-71
references.pmid: 16544055
references.citation: Science. 2002 Sep 13;297(5588):1867-70
references.pmid: 12228717
references.citation: Science. 2007 Dec 14;318(5857):1744-8
references.pmid: 18079394
references.citation: Curr Opin Neurol. 2004 Dec;17(6):655-62
references.pmid: 15542973
references.citation: Neurol Clin. 1995 Nov;13(4):795-812
references.pmid: 8583997
references.citation: Cell. 2007 Jan 12;128(1):141-56
references.pmid: 17218261
references.citation: J Neuroimmunol. 1986 May;11(3):205-14
references.pmid: 3958161
references.citation: Nature. 2007 Jan 4;445(7123):111-5
references.pmid: 17122771
references.citation: Nat Rev Neurol. 2009 Nov;5(11):610-20
references.pmid: 19826401
references.citation: N Engl J Med. 2005 Mar 10;352(10):997-1003
references.pmid: 15758010
references.citation: Cancer Res. 2005 Mar 15;65(6):2065-9
references.pmid: 15781613
references.citation: Cell. 2005 Mar 11;120(5):635-47
references.pmid: 15766527
references.citation: Cancer Res. 2005 Aug 15;65(16):7429-35
references.pmid: 16103096
references.citation: Anticancer Res. 2005 Jul-Aug;25(4):2943-50
references.pmid: 16080548
references.citation: J Mol Neurosci. 1999 Aug-Oct;13(1-2):177-85
references.pmid: 10691304
references.citation: J Med Chem. 1998 Nov 5;41(23):4599-606
references.pmid: 9804699
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12009-14
references.pmid: 14507994
references.citation: Science. 2008 Sep 26;321(5897):1807-12
references.pmid: 18772396
references.citation: J Neurosci. 1988 Feb;8(2):564-79
references.pmid: 2448434
references.citation: Nat Genet. 2007 May;39(5):582-3
references.pmid: 17460676
references.citation: J Neurochem. 2004 Dec;91(6):1275-83
references.pmid: 15584904
references.citation: EMBO J. 1999 Jan 15;18(2):353-62
references.pmid: 9889192
references.citation: Glia. 2001 Nov;36(2):118-24
references.pmid: 11596120
references.citation: Oncogene. 2004 Apr 12;23(16):2757-65
references.pmid: 15077139
references.citation: Hum Gene Ther. 2003 Sep 1;14(13):1235-46
references.pmid: 12952595
references.citation: Oncogene. 2000 Mar 9;19(11):1473-6
references.pmid: 10723139
references.citation: J Med Chem. 2004 Oct 7;47(21):4983-4
references.pmid: 15456241
references.citation: Cancer Res. 2000 Sep 15;60(18):5143-50
references.pmid: 11016641
references.citation: Cancer Gene Ther. 2001 Aug;8(8):589-98
references.pmid: 11571537
references.citation: Neoplasia. 2005 Apr;7(4):356-68
references.pmid: 15967113
references.citation: Nature. 1995 Nov 9;378(6553):206-8
references.pmid: 7477327
references.citation: J Clin Oncol. 2004 Jan 1;22(1):133-42
references.pmid: 14638850
references.citation: Acta Neuropathol. 2007 Aug;114(2):97-109
references.pmid: 17618441
references.citation: Cell. 2007 Feb 9;128(3):459-75
references.pmid: 17289567
references.citation: Nat Med. 2002 Aug;8(8):808-15
references.pmid: 12118245
references.citation: Nat Med. 1997 Jul;3(7):730-7
references.pmid: 9212098
references.citation: Cancer Res. 1994 Jul 15;54(14):3656-61
references.pmid: 8033079
references.citation: Mol Cell. 2001 Aug;8(2):317-25
references.pmid: 11545734
references.citation: Genomics. 2001 Mar 1;72(2):217-21
references.pmid: 11401436
references.citation: J Clin Invest. 1994 Sep;94(3):954-64
references.pmid: 7521890
references.citation: Science. 1997 Jun 20;276(5320):1848-50
references.pmid: 9188528
references.citation: Science. 2004 Jan 16;303(5656):359-63
references.pmid: 14671312
references.citation: Oncogene. 2005 Jan 27;24(5):829-37
references.pmid: 15580296
references.citation: Cancer Res. 2003 Nov 1;63(21):7462-7
references.pmid: 14612546
references.citation: Cancer Cell. 2002 Apr;1(3):269-77
references.pmid: 12086863
references.citation: Carbohydr Res. 1987 Sep 15;167:77-86
references.pmid: 3690578
references.citation: Cell. 1992 Jun 26;69(7):1237-45
references.pmid: 1535557
references.citation: Neurology. 2009 Oct 13;73(15):1200-6
references.pmid: 19822869
references.citation: Cancer Cell. 2007 Jan;11(1):83-95
references.pmid: 17222792
references.citation: Neuroscience. 2010 Jun 30;168(2):514-22
references.pmid: 20382206
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8904-9
references.pmid: 12861074
references.citation: J Neurooncol. 2004 Nov;70(2):217-28
references.pmid: 15674479
references.citation: Surg Neurol. 1976 Jan;5(1):19-23
references.pmid: 1265620
references.citation: Cancer Gene Ther. 2006 May;13(5):530-8
references.pmid: 16410821
references.citation: J Neurosci. 2009 Dec 2;29(48):15161-8
references.pmid: 19955368
references.citation: FEBS Lett. 1997 Dec 22;420(1):25-7
references.pmid: 9450543
references.citation: Cancer Cell. 2003 Mar;3(3):219-31
references.pmid: 12676581
references.citation: J Neurosci. 2008 Jan 2;28(1):264-78
references.pmid: 18171944
references.citation: Oncogene. 2002 Feb 21;21(9):1325-34
references.pmid: 11857076
references.citation: J Biol Chem. 1984 Jun 10;259(11):6818-25
references.pmid: 6327695
references.citation: Cancer Res. 1996 Jan 1;56(1):150-3
references.pmid: 8548755
references.citation: Curr Opin Cell Biol. 2005 Dec;17(6):596-603
references.pmid: 16226444
references.citation: J Neuropathol Exp Neurol. 1994 Jan;53(1):11-21
references.pmid: 8301315
references.citation: Oncology (Williston Park). 2001 Aug;15(8):1017, 1020, 1023-6
references.pmid: 11548974
references.citation: Nat Rev Immunol. 2004 May;4(5):336-47
references.pmid: 15122199
references.citation: Eur J Cancer. 1991;27(5):646-50
references.pmid: 1711354
references.citation: Nat Med. 1995 Jul;1(7):686-92
references.pmid: 7585152
references.citation: J Cell Sci. 2004 May 1;117(Pt 11):2173-81
references.pmid: 15126619
references.citation: Nature. 2000 Apr 13;404(6779):782-7
references.pmid: 10783894
references.citation: Cell. 2007 Jun 1;129(5):957-68
references.pmid: 17540175
references.citation: Nature. 2004 Nov 18;432(7015):396-401
references.pmid: 15549107
references.citation: Nat Rev Drug Discov. 2006 Sep;5(9):741-54
references.pmid: 16915232
references.citation: Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8292-7
references.pmid: 9653180
references.citation: Cancer Cell. 2009 Mar 3;15(3):220-31
references.pmid: 19249680
references.citation: Expert Opin Biol Ther. 2002 Jan;2(1):35-43
references.pmid: 11772338
references.citation: J Biol Chem. 1986 Feb 15;261(5):2434-40
references.pmid: 2418024
references.citation: Lancet Oncol. 2009 May;10(5):459-66
references.pmid: 19269895
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):973-8
references.pmid: 17210912
references.citation: Nature. 2009 Dec 10;462(7274):739-44
references.pmid: 19935646
references.citation: Nat Rev Immunol. 2002 Feb;2(2):116-26
references.pmid: 11910893
references.citation: Cell. 2008 May 30;133(5):775-87
references.pmid: 18510923
references.citation: Annu Rev Immunol. 1993;11:613-35
references.pmid: 8476574
references.citation: Science. 1981 Oct 30;214(4520):577-8
references.pmid: 7291999
references.citation: J Cell Biol. 2004 Jul 19;166(2):213-23
references.pmid: 15249583
references.citation: J Biol Chem. 2004 Aug 20;279(34):35510-7
references.pmid: 15169778
references.citation: J Biol Chem. 1997 Jan 31;272(5):2927-35
references.pmid: 9006938
references.citation: Melanoma Res. 2000 Oct;10(5):401-11
references.pmid: 11095400
references.citation: Nature. 1994 Nov 10;372(6502):150-7
references.pmid: 7969447
references.citation: Curr Top Microbiol Immunol. 2003;276:163-97
references.pmid: 12797448
references.citation: EMBO J. 1996 May 15;15(10):2442-51
references.pmid: 8665852
references.citation: J Med Chem. 2007 Jan 25;50(2):364-73
references.pmid: 17228879
references.citation: Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2965-9
references.pmid: 1557402
references.citation: Nat Cell Biol. 2001 Mar;3(3):245-52
references.pmid: 11231573
references.citation: Genes Dev. 1998 Dec 1;12(23):3644-9
references.pmid: 9851971
references.citation: Int J Hematol. 2003 Jun;77(5):439-43
references.pmid: 12841381
references.citation: Cancer Res. 2005 Jun 15;65(12):5172-80
references.pmid: 15958561
references.citation: Neuron. 2006 Jul 20;51(2):187-99
references.pmid: 16846854
references.citation: Am J Pathol. 2009 Apr;174(4):1149-53
references.pmid: 19246647
references.citation: Cancer Res. 2001 Aug 1;61(15):5843-9
references.pmid: 11479224
references.citation: Cancer Lett. 2003 Dec 8;202(1):43-51
references.pmid: 14643025
references.citation: Cancer Res. 1988 Oct 1;48(19):5546-51
references.pmid: 2901288
references.citation: Science. 2004 Apr 23;304(5670):554
references.pmid: 15016963
references.citation: Genes Dev. 2007 Nov 1;21(21):2683-710
references.pmid: 17974913
references.citation: EMBO J. 1996 Oct 1;15(19):5349-57
references.pmid: 8895579
references.citation: Nat Med. 2002 Oct;8(10):1145-52
references.pmid: 12244301
references.citation: Mol Immunol. 2002 Oct;39(3-4):217-33
references.pmid: 12200052
references.citation: Glia. 2005 Sep;51(4):279-85
references.pmid: 15818597
references.citation: Cancer Biol Ther. 2008 Jul;7(7):1098-103
references.pmid: 18443431
references.citation: Cancer Immunol Immunother. 2004 Mar;53(3):240-8
references.pmid: 14685779
references.citation: Lancet. 1984 Oct 6;2(8406):817-8
references.pmid: 6148561
references.citation: Cancer Res. 2007 May 1;67(9):4010-5
references.pmid: 17483311
references.citation: Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10218-21
references.pmid: 1332037
references.citation: Curr Opin Immunol. 2003 Apr;15(2):138-47
references.pmid: 12633662
references.citation: Cancer Res. 1996 May 15;56(10):2405-10
references.pmid: 8625319
references.citation: Cell. 1995 May 5;81(3):323-30
references.pmid: 7736585
references.citation: Eur J Immunol. 2003 Dec;33(12):3473-83
references.pmid: 14635058
references.citation: Science. 1990 Nov 23;250(4984):1132-5
references.pmid: 1701275
references.citation: Nat Rev Cancer. 2005 Nov;5(11):876-85
references.pmid: 16239906
references.citation: J Med Chem. 2009 Mar 12;52(5):1263-7
references.pmid: 19199478
references.citation: J Neurochem. 1999 Mar;72(3):954-61
references.pmid: 10037466
references.citation: Immunity. 2007 Jul;27(1):111-22
references.pmid: 17629517
references.citation: Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1138-42
references.pmid: 1705026
references.citation: J Cereb Blood Flow Metab. 2004 Aug;24(8):849-59
references.pmid: 15362715
references.citation: Ann Neurol. 1994 Nov;36(5):714-21
references.pmid: 7979217
references.citation: J Biol Chem. 2000 Feb 11;275(6):4215-9
references.pmid: 10660586
references.citation: J Exp Med. 1992 Sep 1;176(3):915-8
references.pmid: 1512552
references.citation: J Biol Chem. 1990 Nov 5;265(31):18713-6
references.pmid: 2229037
references.citation: J Natl Cancer Inst. 2004 Mar 17;96(6):483-6
references.pmid: 15026474
references.citation: Genes Dev. 1998 Dec 1;12(23):3675-85
references.pmid: 9851974
references.citation: Am J Physiol Lung Cell Mol Physiol. 2009 Nov;297(5):L856-63
references.pmid: 19684201
references.citation: J Immunol. 1987 Oct 1;139(7):2361-6
references.pmid: 3655365
references.citation: Cancer Res. 2001 May 1;61(9):3556-60
references.pmid: 11325817
references.citation: Science. 1988 Jun 24;240(4860):1784-6
references.pmid: 3289118
references.citation: Cancer Res. 2006 Aug 15;66(16):7843-8
references.pmid: 16912155
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8467-72
references.pmid: 12077306
references.citation: Cancer Res. 2003 Aug 1;63(15):4315-21
references.pmid: 12907597
references.citation: Neurosurg Clin N Am. 2010 Jan;21(1):17-29
references.pmid: 19944963
references.citation: Cancer Res. 2004 Jul 15;64(14):4783-9
references.pmid: 15256447
references.citation: Neurosurgery. 1992 Jun;30(6):891-6
references.pmid: 1614593
references.citation: Brain Pathol. 2003 Oct;13(4):507-18
references.pmid: 14655756
references.citation: Mol Cancer Res. 2006 Oct;4(10):709-14
references.pmid: 17050665
references.citation: J Neurooncol. 2004 Nov;70(2):229-43
references.pmid: 15674480
references.citation: Nature. 2009 Nov 5;462(7269):108-12
references.pmid: 19847166
references.citation: Genes Dev. 2006 Sep 15;20(18):2527-38
references.pmid: 16980582
references.citation: Nature. 1993 Apr 29;362(6423):857-60
references.pmid: 8479525
references.citation: PLoS Med. 2006 Dec;3(12):e485
references.pmid: 17177598
references.citation: J Biol Chem. 1985 Jan 10;260(1):315-9
references.pmid: 2578126
references.citation: J Immunother. 1997 May;20(3):165-77
references.pmid: 9181454
references.citation: Regul Pept. 1993 Oct 20;48(1-2):99-112
references.pmid: 7505471
references.citation: Neuropathol Appl Neurobiol. 1988 Mar-Apr;14(2):157-67
references.pmid: 3399024
references.citation: Glycoconj J. 2000 Jul-Sep;17(7-9):627-47
references.pmid: 11421354
references.citation: J Clin Oncol. 2002 Mar 1;20(5):1383-8
references.pmid: 11870183
references.citation: Genes Dev. 2001 Aug 1;15(15):1913-25
references.pmid: 11485986
references.citation: Oncogene. 2001 Jul 12;20(31):4128-37
references.pmid: 11464279
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9051-6
references.pmid: 16757565
references.citation: Biochem Biophys Res Commun. 1999 Nov 19;265(2):479-83
references.pmid: 10558893
references.citation: Annu Rev Biochem. 2001;70:535-602
references.pmid: 11395417
references.citation: Nature. 1994 Aug 18;370(6490):527-32
references.pmid: 8052307
references.citation: Oncogene. 2006 Aug 10;25(35):4913-22
references.pmid: 16547494
references.citation: Cell. 1993 Aug 27;74(4):609-19
references.pmid: 8358790
references.citation: J Immunol. 1985 Mar;134(3):1545-50
references.pmid: 3155771
references.citation: J Biol Chem. 2002 May 31;277(22):19251-4
references.pmid: 11953423
references.citation: Cancer Cell. 2006 Oct;10(4):269-80
references.pmid: 17045205
references.citation: Science. 2001 Nov 16;294(5546):1477-8
references.pmid: 11711663
references.citation: Nature. 2002 Oct 17;419(6908):729-34
references.pmid: 12384701
references.citation: Neuroreport. 2005 Jul 13;16(10):1081-5
references.pmid: 15973152
references.citation: Clin Cancer Res. 2004 Aug 1;10(15):5145-50
references.pmid: 15297418
references.citation: Cell. 2004 Dec 17;119(6):847-60
references.pmid: 15607980
references.citation: Cancer Res. 2007 Mar 15;67(6):2456-68
references.pmid: 17363563
references.citation: Nature. 1994 Feb 17;367(6464):645-8
references.pmid: 7509044
references.citation: J Immunol. 1984 Mar;132(3):1208-15
references.pmid: 6319491
references.citation: Oncogene. 1997 Dec 4;15(23):2755-65
references.pmid: 9419966
references.citation: Cancer Res. 2001 Mar 15;61(6):2759-65
references.pmid: 11289159
references.citation: Oncogene. 2000 Dec 7;19(52):6043-52
references.pmid: 11146556
references.citation: Am Fam Physician. 1994 Mar;49(4):787-97
references.pmid: 8116514
references.citation: J Neuroimmunol. 2000 Nov 1;111(1-2):177-85
references.pmid: 11063836
references.citation: Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1883-7
references.pmid: 1848013
references.citation: Clin Cancer Res. 2006 Aug 15;12(16):4899-907
references.pmid: 16914578
references.citation: Cancer Res. 1987 Nov 15;47(22):5846-52
references.pmid: 3664486
references.citation: Cancer Res. 2001 May 15;61(10):4190-6
references.pmid: 11358844
references.citation: Lab Invest. 1990 Feb;62(2):135-46
references.pmid: 2406502
references.citation: Biochem Biophys Res Commun. 1982 Jun 15;106(3):711-8
references.pmid: 6288031
references.citation: Nat Med. 2002 Mar;8(3):274-81
references.pmid: 11875499
references.citation: Semin Cell Dev Biol. 2004 Apr;15(2):161-70
references.pmid: 15209375
references.citation: Can J Neurol Sci. 1997 Feb;24(1):3-15
references.pmid: 9043741
references.citation: Cell. 2004 Apr 16;117(2):211-23
references.pmid: 15084259
references.citation: Cancer Immunol Immunother. 2003 Oct;52(10):583-91
references.pmid: 12827310
references.citation: Expert Rev Anticancer Ther. 2001 Oct;1(3):395-401
references.pmid: 12113106
references.citation: Cell. 1993 Nov 19;75(4):817-25
references.pmid: 8242752
references.citation: Cancer Res. 2004 Nov 1;64(21):7773-9
references.pmid: 15520182
references.citation: Cancer Res. 2003 Jun 1;63(11):2742-6
references.pmid: 12782577
references.citation: Aging (Albany NY). 2010 Nov;2(11):791-803
references.pmid: 21068464
references.citation: N Engl J Med. 2009 Sep 10;361(11):1058-66
references.pmid: 19657110
references.citation: J Neurooncol. 2009 Sep;94(3):299-312
references.pmid: 19381449
references.citation: Am J Pathol. 1997 Mar;150(3):805-14
references.pmid: 9060818
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15178-83
references.pmid: 14645703
references.citation: Nature. 2001 Nov 1;414(6859):105-11
references.pmid: 11689955
references.citation: Neurosurgery. 1995 Jan;36(1):124-32; discussion 132
references.pmid: 7708148
references.citation: Arch Neurol. 2010 Mar;67(3):279-83
references.pmid: 20212224
references.citation: Brain Pathol. 2003 Oct;13(4):539-53
references.pmid: 14655759
references.citation: J Neurosci. 2001 May 15;21(10):3360-8
references.pmid: 11331365
references.citation: Mol Cell. 2002 Sep;10(3):509-21
references.pmid: 12408820
references.citation: Sci STKE. 2002 Nov 26;2002(160):re15
references.pmid: 12454318
references.citation: Am J Respir Crit Care Med. 2005 May 15;171(10):1168-77
references.pmid: 15764728
references.citation: Genes Dev. 2001 Jun 1;15(11):1311-33
references.pmid: 11390353
references.citation: Mol Cell Biol. 1997 Mar;17(3):1702-13
references.pmid: 9032297
references.citation: J Immunol. 1997 Sep 1;159(5):2399-408
references.pmid: 9278331
references.citation: J Neuropathol Exp Neurol. 2004 Mar;63(3):210-22
references.pmid: 15055445
references.citation: Cancer Res. 2002 Aug 1;62(15):4307-15
references.pmid: 12154034
references.citation: Keio J Med. 2003 Dec;52(4):220-9
references.pmid: 14748474
references.citation: Curr Biol. 2004 Sep 21;14(18):1650-6
references.pmid: 15380067
references.citation: J Neurooncol. 2006 Jul;78(3):295-302
references.pmid: 16636750
references.citation: Cancer Res. 1992 Jun 1;52(11):3213-9
references.pmid: 1317261
references.citation: J Clin Oncol. 2005 Apr 1;23(10):2411-22
references.pmid: 15800333
references.citation: N Engl J Med. 2005 Aug 25;353(8):811-22
references.pmid: 16120861
references.citation: Cancer Res. 2001 Jul 1;61(13):4956-60
references.pmid: 11431323
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):639-44
references.pmid: 12515857
references.citation: Mol Cell Neurosci. 2011 Jan;46(1):89-100
references.pmid: 20801220
references.citation: Science. 2009 Apr 10;324(5924):261-5
references.pmid: 19359588
references.citation: Int J Dev Neurosci. 1999 Aug-Oct;17(5-6):547-56
references.pmid: 10571416
references.citation: Proc Natl Acad Sci U S A. 2004 May 4;101(18):6993-8
references.pmid: 15118108
references.citation: Hum Gene Ther. 1998 Sep 20;9(14):1983-93
references.pmid: 9759926
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11842-9
references.pmid: 14504387
references.citation: Cell. 2009 Dec 11;139(6):1096-108
references.pmid: 20005803
references.citation: J Exp Med. 1972 Dec 1;136(6):1631-47
references.pmid: 4345108
references.citation: Neuropathol Appl Neurobiol. 2006 Oct;32(5):532-8
references.pmid: 16972887
references.citation: Cancer Cell. 2005 Aug;8(2):119-30
references.pmid: 16098465
references.citation: Cancer Lett. 2006 Feb 8;232(2):139-47
references.pmid: 16139423
references.citation: J Clin Oncol. 2005 Dec 20;23(36):9359-68
references.pmid: 16361636
references.citation: Science. 2004 Jul 30;305(5684):626-9
references.pmid: 15286356
references.citation: Neuropathol Appl Neurobiol. 2005 Oct;31(5):486-90
references.pmid: 16150119
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13970-5
references.pmid: 14617774
references.citation: Microsc Res Tech. 1995 Nov 1;32(4):267-85
references.pmid: 8573777
references.citation: Cancer Metastasis Rev. 2007 Dec;26(3-4):373-400
references.pmid: 17717638
references.citation: Nat Rev Drug Discov. 2007 Apr;6(4):273-86
references.pmid: 17396134
references.citation: Cancer Res. 2002 Oct 1;62(19):5551-8
references.pmid: 12359767
references.citation: Cancer Res. 2002 Nov 15;62(22):6764-9
references.pmid: 12438278
references.citation: Cancer Res. 2001 Jul 15;61(14):5349-54
references.pmid: 11454673
references.citation: BMC Cancer. 2009 Dec 16;9:444
references.pmid: 20015387
references.citation: Nat Med. 2007 Jan;13(1):84-8
references.pmid: 17159987
references.citation: Cancer Res. 1994 Dec 15;54(24):6353-8
references.pmid: 7987828
references.citation: Nature. 2007 Jan 4;445(7123):106-10
references.pmid: 17122772
references.citation: Neurosurgery. 2000 Apr;46(4):778-91; discussion 791-2
references.pmid: 10764250
references.citation: Cancer Res. 1997 Apr 1;57(7):1250-4
references.pmid: 9102208
references.citation: J Clin Invest. 2005 Oct;115(10):2665-72
references.pmid: 16200200
references.citation: Mol Cancer Res. 2008 Dec;6(12):1795-806
references.pmid: 19074825
references.citation: Cancer Cell. 2006 May;9(5):341-9
references.pmid: 16697955
references.citation: J Biol Chem. 2004 Aug 6;279(32):33946-57
references.pmid: 15173171
references.citation: Cancer Res. 2001 Mar 1;61(5):2301-6
references.pmid: 11280802
references.citation: Biochim Biophys Acta. 1979 Feb 4;560(1):1-65
references.pmid: 216404
references.citation: Cancer. 1996 Jan 15;77(2):362-72
references.pmid: 8625246
references.citation: J Cell Sci. 1967 Sep;2(3):293-304
references.pmid: 4293083
references.citation: Oncogene. 2006 Mar 16;25(12):1696-708
references.pmid: 16449977
references.citation: Glia. 1998 Jun;23(2):156-68
references.pmid: 9600384
references.citation: Mol Cancer Ther. 2005 Jan;4(1):101-12
references.pmid: 15657358
references.citation: Cancer Cell. 2006 Dec;10(6):459-72
references.pmid: 17157787
references.citation: Cancer Res. 1994 Sep 15;54(18):5016-20
references.pmid: 8069869
references.citation: J Clin Invest. 1995 Jun;95(6):2633-43
references.pmid: 7539458
references.citation: J Clin Oncol. 2007 May 1;25(13):1651-7
references.pmid: 17470857
references.citation: Nat Genet. 1997 Apr;15(4):356-62
references.pmid: 9090379
references.citation: Lab Invest. 1992 Oct;67(4):529-34
references.pmid: 1434531
references.citation: N Engl J Med. 2005 Nov 10;353(19):2012-24
references.pmid: 16282176
references.citation: Genes Dev. 2002 Apr 15;16(8):984-93
references.pmid: 11959846
references.citation: Science. 1993 Jan 1;259(5091):94-7
references.pmid: 8418502
references.citation: J Neurochem. 2008 Dec;107(6):1741-52
references.pmid: 19014377
references.citation: Cancer Res. 2000 Mar 1;60(5):1383-7
references.pmid: 10728703
references.citation: J Immunol. 2002 Sep 1;169(5):2756-61
references.pmid: 12193750
references.citation: Surg Neurol. 2000 Apr;53(4):360-8; discussion 368-9
references.pmid: 10825522
references.citation: Biochim Biophys Acta. 2006 Feb;1762(2):191-201
references.pmid: 16055309
references.citation: Cell. 1993 Nov 19;75(4):805-16
references.pmid: 8242751
references.citation: N Engl J Med. 2009 Feb 19;360(8):765-73
references.pmid: 19228619
references.citation: J Biochem. 2000 Jun;127(6):1021-31
references.pmid: 10833270
references.citation: Genes Dev. 2007 Jan 1;21(1):98-111
references.pmid: 17210792
references.citation: Am J Pathol. 2003 Apr;162(4):1083-93
references.pmid: 12651601
references.citation: J Neuropathol Exp Neurol. 2004 Aug;63(8):841-55
references.pmid: 15330339
references.citation: Cancer Res. 2007 Feb 1;67(3):1030-7
references.pmid: 17283135
references.citation: Ann N Y Acad Sci. 2003 Apr;987:180-7
references.pmid: 12727638
references.citation: Expert Opin Ther Targets. 2001 Aug;5(4):491-506
references.pmid: 12540262
references.citation: J Cell Biol. 2001 Dec 24;155(7):1129-35
references.pmid: 11756467
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10399-404
references.pmid: 8816812
references.citation: Tumour Biol. 2007;28(3):165-72
references.pmid: 17519535
references.citation: Nat Rev Cancer. 2006 Nov;6(11):857-66
references.pmid: 17060945
references.citation: Cancer Res. 2004 Apr 15;64(8):2751-8
references.pmid: 15087390
references.citation: Clin Cancer Res. 1995 Aug;1(8):859-64
references.pmid: 9816055
references.citation: J Neurosurg. 1977 Apr;46(4):467-76
references.pmid: 191575
references.citation: PLoS One. 2011 Jan 14;6(1):e16264
references.pmid: 21264258
references.citation: Science. 1989 Dec 8;246(4935):1303-6
references.pmid: 2588007
references.citation: Cancer Res. 1984 Feb;44(2):753-60
references.pmid: 6318976
references.citation: Nat Rev Cancer. 2002 Aug;2(8):594-604
references.pmid: 12154352
references.citation: Brain. 2010 Jul;133(Pt 7):1961-72
references.pmid: 20513660
references.citation: J Cell Sci. 2003 Nov 1;116(Pt 21):4409-17
references.pmid: 13130092
references.citation: Cancer Res. 2006 Jun 1;66(11):5618-23
references.pmid: 16740698
references.citation: Cancer Res. 1984 Nov;44(11):5279-85
references.pmid: 6386148
references.citation: Clin Cancer Res. 2005 Nov 1;11(21):7841-50
references.pmid: 16278407
references.citation: EMBO J. 1991 Jun;10(6):1565-9
references.pmid: 2026149
references.citation: J Neurosci Res. 1999 Aug 1;57(3):371-80
references.pmid: 10412028
references.citation: Clin Cancer Res. 2005 Dec 1;11(23):8304-11
references.pmid: 16322289
references.citation: J Immunol. 2001 Aug 1;167(3):1137-40
references.pmid: 11466326
references.citation: Proc Natl Acad Sci U S A. 1987 Apr;84(7):2082-6
references.pmid: 3550805
references.citation: Nature. 1956 Mar 17;177(4507):524-5
references.pmid: 13321892
references.citation: Nature. 2006 Sep 28;443(7110):448-52
references.pmid: 16957738
references.citation: Science. 2001 Oct 12;294(5541):374-80
references.pmid: 11598301
references.citation: J Neuroimmunol. 2001 Jan 1;112(1-2):15-27
references.pmid: 11108929
references.citation: J Neurochem. 1980 Jul;35(1):266-9
references.pmid: 7452256
references.citation: Cell. 1995 Dec 15;83(6):993-1000
references.pmid: 8521522
references.citation: Cancer Res. 2002 Jul 1;62(13):3729-35
references.pmid: 12097282
references.citation: Cancer Res. 2005 May 15;65(10):3967-79
references.pmid: 15899784
references.citation: J Biol Chem. 2000 Mar 24;275(12):8945-51
references.pmid: 10722742
references.citation: Cancer Cell. 2006 Jun;9(6):425-34
references.pmid: 16766262
references.citation: Neuropathol Appl Neurobiol. 1993 Apr;19(2):146-51
references.pmid: 8316334
references.citation: J Biol Chem. 1997 May 16;272(20):13189-95
references.pmid: 9148935
references.citation: Lab Invest. 2004 Apr;84(4):397-405
references.pmid: 14990981
references.citation: Cancer Res. 2006 Dec 15;66(24):11520-39
references.pmid: 17178843