Abstract
Therapeutic efforts for human glial tumors have over the past years been redirected towards a compartmental treatment concept. The diffusely infiltrative nature of the disease calls for therapeutic agents to reach single cells far beyond the focus of attention which present therapies like surgery and radiation are able to treat. Specific drug discovery approaches which seek to define targets which are specific for gliomas have generated therapeutic options which allow for a highly selective development of new reagents. Combined with new modalities for compartmental drug delivery, systemic complications might be reduced and advantage taken of a compartmental specificity of a target which otherwise in the context of systemic application would not be as specific or burdened with side effects. From the present status of therapeutic developments in neuro-oncology it can be expected that a sufficient number of drug targets emerge which can be exploited by means of interstitial or intracavitary delivery, which are not neurotoxic and which may even be imaged in their action with the new metabolic imaging modalities. Convection enhanced delivery, conditionally replicating oncolytic viruses and motile, genetically engineered neural stem cells all seem to fulfill the distribution requirements which an effective therapeutic for gliomas will need to overcome the very limited efficacy which surgery, conventional chemotherapy and radiation have to offer. Whereas the genomics based discovery approaches are not specific for neuro-oncology, the development of delivery strategies is highly specific for the central nervous system, thus creating a unique set of organ and disease specific therapies.
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Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785): 177–182, 1987
Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L et al.: Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3): 719–726, 2002
Sattler M, Griffin JD: Mechanisms of transformation by the BCR/ABL oncogene. Int J Hematol 73(3): 278–291, 2001
von Bubnoff N, Peschel C, Duyster J: Resistance of Philadelphia-chromosome positive leukemia towards the kinase inhibitor imatinib (STI571, Glivec): a targeted oncoprotein strikes back. Leukemia 17(5): 829–838, 2003
Lev S, Blechman JM, Givol D, Yarden Y: Steel factor and c-kit protooncogene: genetic lessons in signal transduction. Crit Rev Oncog 5(2–3): 141–168, 1994
Connolly EM, Gaffney E, Reynolds JV: Gastrointestinal stromal tumours. Br J Surg 90(10): 1178–1186, 2003
Kuppner MC, Van Meir E, Gauthier T, Hamou MF, de Tribolet N: Differential expression of the CD44 molecule in human brain tumours. Int J Cancer 50(4): 572–577, 1992
Zardi L, Carnemolla B, Siri A, Petersen TE, Paolella G, Sebastio G et al.: Transformed human cells produce a new fibronectin isoform by preferential alternative splicing of a previously unobserved exon. Embo J 6(8): 2337–2342, 1987
Herold-Mende C, Mueller MM, Bonsanto MM, Schmitt HP, Kunze S, Steiner HH. Clinical impact and functional aspects of tenascin-C expression during glioma progression. Int J Cancer 98(3): 362–369, 2002
Andressen C, Stacker E, Klinz FJ, Lenka N, Hescheler J, Fleischmann B et al.: Nestin-specific green fluorescent protein expression in embryonic stem cell-derived neural precursor cells used for transplantation. Stem Cells 19(5): 419–424, 2001
Jakobsson J, Ericson C, Jansson M, Bjork E, Lundberg C: Targeted transgene expression in rat brain using lentiviral vectors. J Neurosci Res 73(6): 876–885, 2003
Shi N, Zhang Y, Zhu C, Boado RJ, Pardridge WM: Brainspecific expression of an exogenous gene after i.v. administration. Proc Natl Acad Sci USA 98(22): 12754–12759, 2001
Steck PA, Saya H: Pathways of oncogenesis in primary brain tumors. Curr Opin Oncol 3(3): 476–484, 1991
Weber RG, Sabel M, Reifenberger J, Sommer C, Oberstrass J, Reifenberger G et al.: Characterization of genomic alterations associated with glioma progression by comparative genomic hybridization. Oncogene 13(5): 983–994, 1996
McKeever PE: Insights about brain tumors gained through immunohistochemistry and in situ hybridization of nuclear and phenotypic markers. J Histochem Cytochem 46(5): 585–594, 1998
Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H et al.: Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313(5998): 144–147, 1985
Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK et al.: Malignant glioma: genetics and biology of a grave matter. Genes Dev 15(11): 1311–1333, 2001
Smith JS, Alderete B, Minn Y, Borell TJ, Perry A, Mohapatra G et al.: Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 18(28): 4144–4152, 1999
Sallinen SL, Sallinen PK, Haapasalo HK, Helin HJ, Helen PT, Schraml P et al.: Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques. Cancer Res 60(23): 6617–6622, 2000
Muller S, Kunkel P, Lamszus K, Ulbricht U, Lorente GA, Nelson AM et al.: A role for receptor tyrosine phosphatase zeta in glioma cell migration. Oncogene 22(43): 6661–6668, 2003
Dong SM, Pang JC, Poon WS, Hu J, To KF, Chang AR et al.: Concurrent hypermethylation of multiple genes is associated with grade of oligodendroglial tumors. J Neuropathol Exp Neurol 60(8): 808–816, 2001
Gonzalez-Gomez P, Bello MJ, Arjona D, Lomas J, Alonso ME, De Campos JM et al.: Promoter hypermethylation of multiple genes in astrocytic gliomas. Int J Oncol 22(3): 601–608, 2003
Muller S, van den Boom D, Zirkel D, Koster H, Berthold F, Schwab M et al.: Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors. Hum Mol Genet 9(5): 757–763, 2000
Muller S, Zirkel D, Westphal M, Zumkeller W: Genomic imprinting of IGF2 and H19 in human meningiomas. Eur J Cancer 36(5): 651–655, 2000
Nakamura M, Watanabe T, Klangby U, Asker C, Wiman K, Yonekawa Y et al.: p14ARF deletion and methylation in genetic pathways to glioblastomas. Brain Pathol 11(2): 159–168, 2001
Watanabe T, Huang H, Nakamura M, Wischhusen J, Weller M, Kleihues P et al.: Methylation of the p73 gene in gliomas. Acta Neuropathol (Berl) 104(4): 357–362, 2002
Godard S, Getz G, Delorenzi M, Farmer P, Kobayashi H, Desbaillets I et al.: Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Cancer Res 63(20): 6613–6625, 2003
Mariani L, Beaudry C, McDonough WS, Hoelzinger DB, Demuth T, Ross KR et al.: Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes: a cDNA microarray analysis. J Neurooncol 53(2): 161–176, 2001
Mukasa A, Ueki K, Matsumoto S, Tsutsumi S, Nishikawa R, Fujimaki T et al.: Distinction in gene expression profiles of oligodendrogliomas with and without allelic loss of 1p. Oncogene 21(25): 3961–3968, 2002
Wang H, Shen W, Huang H, Hu L, Ramdas L, Zhou YH et al.: Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasionenhancing genes. Cancer Res 63(15): 4315–4321, 2003
Fuller GN, Hess KR, Rhee CH, Yung WK, Sawaya RA, Bruner JM et al.: Molecular classification of human diffuse gliomas by multidimensional scaling analysis of gene expression profiles parallels morphology-based classification, correlates with survival, and reveals clinically-relevant novel glioma subsets. Brain Pathol 12(1): 108–116, 2002
Hess KR, Fuller GN, Rhee CH, Zhang W: Statistical pattern analysis of gene expression profiles for glioblastoma tissues and cell lines. Int J Mol Med 8(2): 183–188, 2001
van den Boom J, Wolter M, Kuick R, Misek DE, Youkilis AS, Wechsler DS et al.: Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. Am J Pathol 163(3): 1033–1043, 2003
Shai R, Shi T, Kremen TJ, Horvath S, Liau LM, Cloughesy TF et al.: Gene expression profiling identifies molecular subtypes of gliomas. Oncogene 22(31): 4918–4923, 2003
Rhee CH, Hess K, Jabbur J, Ruiz M, Yang Y, Chen S et al.: cDNA expression array reveals heterogeneous gene expression profiles in three glioblastoma cell lines. Oncogene 18(17): 2711–2717, 1999
Huang H, Colella S, Kurrer M, Yonekawa Y, Kleihues P, Ohgaki H: Gene expression profiling of low-grade diffuse astrocytomas by cDNA arrays. Cancer Res 60(24): 6868–6874, 2000
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T: Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836): 494–498, 2001
Meng K, Rodriguez-Pena A, Dimitrov T, Chen W, Yamin M, Noda M et al.: Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta. Proc Natl Acad Sci USA 97(6): 2603–2608, 2000
Ulbricht U, Brockmann MA, Aigner A, Eckerich C, Muller S, Fillbrandt R et al.: Expression and function of the receptor protein tyrosine phosphatase zeta and its ligand pleiotrophin in human astrocytomas. J Neuropathol Exp Neurol 62(12): 1265–1275, 2003
Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P, Ohgaki H: Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6(3): 217–223, 1996; discussion 23–24
Brady LW, Markoe AM, Woo DV, Rackover MA, Koprowski H, Steplewski Z et al.: Iodine 125 labeled anti-epidermal growth factor receptor-425 in the treatment of malignant astrocytomas. A pilot study. J Neurosurg Sci 34(3–4): 243–249, 1990
Faillot T, Magdelenat H, Mady E, Stasiecki P, Fohanno D, Gropp P et al.: A phase I study of an anti-epidermal growth factor receptor monoclonal antibody for the treatment of malignant gliomas. Neurosurgery 39(3): 478–483, 1996
Westphal M, Hamel W, Zirkel D, Hermann HD, Bilzer T, Reifenberger G et al.: Epidermal growth factor receptor expression in human malignant glioma: in vitro and in vivo effects of application of monoclonal antibodies to the epidermal growth factor receptor. Recent Results Cancer Res 135: 171–184, 1994
Wersall P, Ohlsson I, Biberfeld P, Collins VP, von Krusenstjerna S, Larsson S et al.: Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma. Cancer Immunol Immunother 44(3): 157–164, 1997
Bier H, Hoffmann T, Hauser U, Wink M, Ochler M, Kovar A et al.: Clinical trial with escalating doses of the antiepidermal growth factor receptor humanized monoclonal antibody EMD 72 000 in patients with advanced squamous cell carcinoma of the larynx and hypopharynx. Cancer Chemother Pharmacol 47(6): 519–524, 2001
Crombet T, Torres O, Rodriguez V, Menendez A, Stevenson A, Ramos M et al.: Phase I clinical evaluation of a neutralizing monoclonal antibody against epidermal growth factor receptor in advanced brain tumor patients: preliminary study. Hybridoma 20(2): 131–136, 2001
Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG: Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 38(1): 17–23, 2001
Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG, Jakobovits A: Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Res 59(6): 1236–1243, 1999
Bigner SH, Humphrey PA, Wong AJ, Vogelstein B, Mark J, Friedman HS et al.: Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts. Cancer Res 50(24): 8017–8022, 1990
Kuan CT, Wikstrand CJ, Bigner DD: EGF mutant receptor vIII as a molecular target in cancer therapy. Endocr Relat Cancer 8(2): 83–96, 2001
Wikstrand CJ, McLendon RE, Friedman AH, Bigner DD. Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII. Cancer Res 57(18): 4130–4140, 1997
Humphrey PA, Wong AJ, Vogelstein B, Zalutsky MR, Fuller GN, Archer GE et al.: Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma. Proc Natl Acad Sci USA 87(11): 4207–4211, 1990
Wikstrand CJ, Cole VR, Crotty LE, Sampson JH, Bigner DD: Generation of anti-idiotypic reagents in the EGFRvIII tumor-associated antigen system. Cancer Immunol Immunother 50(12): 639–652, 2002
Wikstrand CJ, Fredman P, Svennerholm L, Humphrey PA, Bigner SH, Bigner DD: Monoclonal antibodies to malignant human gliomas. Mol Chem Neuropathol 17(2): 137–146, 1992
Sampson JH, Crotty LE, Lee S, Archer GE, Ashley DM, Wikstrand CJ et al.: Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors. Proc Natl Acad Sci USA 97(13): 7503–7508, 2000
Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY et al.: Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 21(12): 2237–2246, 2003
Rich JN, Reardon DA, Peery T, Dowell JM, Quinn JA, Penne KL et al.: Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol 22(1): 133–142, 2004
Sampson JH, Akabani G, Archer GE, Bigner DD, Berger MS, Friedman AH et al.: Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors. J Neurooncol 65(1): 27–35, 2003
Plate KH, Breier G, Weich HA, Risau W: Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359(6398): 845–848, 1992
Phillips HS, Armani MP, Stavrou D, Ferrara N, Westphal M: Intense focal expression of vascular endothelial growth factor mRNA in human intracranial neoplasms: association with regions of necrosis. Int J Oncol 2: 913–919, 1993
Kunkel P, Muller S, Schirmacher P, Stavrou D, Fillbrandt R, Westphal M et al.: Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas. Neuro-oncol 3(2): 82–88, 2001
Lamszus K, Laterra J, Westphal M, Rosen EM: Scatter factor/hepatocyte growth factor (SF/HGF) content and function in human gliomas. Int J Dev Neurosci 17(5–6): 517–530, 1999
Laterra J, Nam M, Rosen E, Rao JS, Lamszus K, Goldberg ID et al.: Scatter factor/hepatocyte growth factor gene transfer enhances glioma growth and angiogenesis in vivo. Lab Invest 76(4): 565–577, 1997
Schmidt NO, Westphal M, Hagel C, Ergun S, Stavrou D, Rosen EM et al.: Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis. Int J Cancer 84(1): 10–18, 1999
Bello L, Francolini M, Marthyn P, Zhang J, Carroll RS, Nikas DC et al.: Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery. Neurosurgery 49(2): 380–389; 2001; discussion 390
Bello L, Lucini V, Giussani C, Carrabba G, Pluderi M, Scaglione F et al.: IS20I, a specific alphavbeta3 integrin inhibitor, reduces glioma growth in vivo. Neurosurgery 52(1): 177–185; 2003; discussion 185–186
Fong TA, Shawver LK, Sun L, Tang C, App H, Powell TJ et al.: SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 59(1): 99–106, 1999
Laird AD, Vajkoczy P, Shawver LK, Thurnher A, Liang C, Mohammadi M et al.: SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res 60(15): 4152–4160, 2000
Garber K: Angiogenesis inhibitors suffer new setback. Nat Biotechnol 20(11): 1067–1068, 2002
Marshall E: Cancer therapy. Setbacks for endostatin. Science 295(5563): 2198–2199, 2002
Kunkel P, Ulbricht U, Bohlen P, Brockmann MA, Fillbrandt R, Stavrou D et al.: Inhibition of glioma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2. Cancer Res 61(18): 6624–6628, 2001
Rubenstein JL, Kirn J, Ozawa T, Zhang M, Westphal M, Deen DF et al.: Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption. Neoplasia 2(4): 306–314, 2000
Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D et al.: Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284(5422): 1994–1998, 1999
Lamszus K, Kunkel P, Westphal M: Invasion as limitation to anti-angiogenic glioma therapy. Acta Neurochir Suppl 88: 169–177, 2003
Brockmann MA, Papadimitriou A, Brandt M, Fillbrandt R, Westphal M, Lamszus K: Inhibition of intracerebral glioblastoma growth by local treatment with the scatter factor/hepatocyte growth factor-antagonist NK4. Clin Cancer Res 9(12): 4578–4585, 2003
Brockmann MA, Westphal M, Lamszus K: Improved method for the intracerebral engraftment of tumour cells and intratumoural treatment using a guide screw system in mice. Acta Neurochir (Wien) 145(9): 777–781, 2003
Engebraaten O, Hjortland GO, Hirschberg H, Fodstad O: Growth of precultured human glioma specimens in nude rat brain. J Neurosurg 90(1): 125–132, 1999
Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J et al.: Identification of a cancer stern cell in human brain tumors. Cancer Res 63(18): 5821–5828, 2003
Apuzzo ML, Liu CY: Things to come. Neurosurgery 49(4): 765–778, 2001
Dunn IF, Black PM: The neurosurgeon as local oncologist: cellular and molecular neu-rosurgery in malignant glioma therapy. Neurosurgery 52(6): 1411–1422; 2003; discussion 1422–1424.
Zlokovic BV, Apuzzo ML: Cellular and molecular neurosurgery: pathways from concept to reality – Part II: Vector systems and delivery methodologies for gene therapy of the central nervous system. Neurosurgery 40(4): 805–812, 1997; discussion 812–813
Zlokovic BV, Apuzzo ML: Cellular and molecular neurosurgery: pathways from concept to reality – Part I: Target disorders and concept approaches to gene therapy of the central nervous system. Neurosurgery 40(4): 789–803; 1997; discussion 803–804
Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC et al.: A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neurooncol 5(2): 79–88, 2003
Koepperi JA, H.-D. H, Giese A, H.-R. F, Raschdorff C, von Koschitzky H et al.: Lymphokine-activated killer cells, interleukin-2 and tumor necrosis factor alpha in malignant glioma: clinical and laboratory findings. Reg Cancer Treatm 3: 338–344, 1991
Kruse CA, Cepeda L, Owens B, Johnson SD, Stears J, Lillehei KO: Treatment of recurrent glioma with intracavitary alloreactive cytotoxic T lymphocytes and interleukin-2. Cancer Immunol Immunother 45(2): 77–87, 1997
Merchant RE, Ellison MD, Young HF: Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes. A review of preclinical and clinical investigations. J Neurooncol 8(2): 173–188, 1990
Quattrocchi KB, Miller CH, Cush S, Bernard SA, Dull ST, Smith M et al.: Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas. J Neurooncol 45(2): 141–157, 1999
Weller M, Fontana A: The failure of current immunotherapy for malignant glioma. Tumor-derived TGF-beta, T-cell apoptosis, and the immune privilege of the brain. Brain Res Rev 21(2): 128–151, 1995
Jachimczak P, Bogdahn U, Schneider J, Behl C, Meixensberger J, Apfel R et al.: The effect of transforming growth factor-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma. J Neurosurg 78(6): 944–951, 1993
Bigner DD, Brown M, Coleman RE, Friedman AH, Friedman HS, McLendon RE et al.: Phase I studies of treatment of malignant gliomas and neoplastic meningitis with 131I-radiolabeled monoclonal antibodies anti-tenascin 81C6 and anti-chondroitin proteoglycan sulfate Mel-14 F (ab¢)2 – a preliminary report. J Neurooncol 24(1): 109–122, 1995
Reardon DA, Akabani G, Coleman RE, Friedman AH, Friedman HS, Herndon JE, 2nd et al.: Phase II trial of murine (131)I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas. J Clin Oncol 20(5): 1389–1397, 2002
Riva P, Franceschi G, Arista A, Frattarelli M, Riva N, Cremonini AM et al.: Local application of radiolabeled monoclonal antibodies in the treatment of high grade malignant gliomas: a six-year clinical experience. Cancer 80(12 Suppl): 2733–2742, 1997
Paganelli G, Bartolomei M, Ferrari M, Cremonesi M, Broggi G, Maira G et al.: Pre-targeted locoregional radioimmunotherapy with 90Y-biotin in glioma patients: phase I study and preliminary therapeutic results. Cancer Biother Radiopharm 16(3): 227–235, 2001
Goetz C, Rachinger W, Poepperl G, Decker M, Gildehaus FJ, Stacker S et al.: Intralesional radioimmunotherapy in the treatment of malignant glioma: clinical and experimental findings. Acta Neurochir Suppl 88: 69–75, 2003
Goetz C, Riva P, Poepperl G, Gildehaus FJ, Hischa A, Tatsch K et al.: Locoregional radioimmunotherapy in selected patients with malignant glioma: experiences, side effects and survival times. J Neurooncol 62(3): 321–328, 2003
Ravic M: Intracavitary treatment of malignant gliomas: radioimmunotherapy targeting fibronectin. Acta Neurochir Suppl 88: 77–82, 2003
Breyer R, Hussein S, Radu DL, Putz KM, Gunia S, Hecker H et al.: Disruption of in-tracerebral progression of C6 rat glioblastoma by in vivo treatment with anti-CD44 monoclonal antibody. J Neurosurg 92(1): 140–149, 2000
Rainov NG: A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther 11(17): 2389–2401, 2000
Menei P, Benoit JP: Implantable drug-releasing biodegradable microspheres for local treatment of brain glioma. Acta Neurochir Suppl 88: 51–55, 2003
Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH: Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA 91(6): 2076–2080, 1994
Morrison PF, Laske DW, Bobo H, Oldfield EH, Dedrick RL: High-flow microinfusion: tissue penetration and Pharmacodynamics. Am J Physiol 266(1 Pt 2): R292–R305, 1994
Pardridge WM: Blood-brain barrier genomics and the use of endogenous transporters to cause drug penetration into the brain. Curr Opin Drug Discov Devel 6(5): 683–691, 2003
Laske DW, Youle RJ, Oldfield EH: Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med 3(12): 1362–1368, 1997
Puri RK, Hoon DS, Leland P, Snoy P, Rand RW, Pastan I et al.: Preclinical development of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma. Cancer Res 56(24): 5631–5637, 1996
Debinski W, Obiri NI, Pastan I, Puri RK: A novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4. J Biol Chem 270(28): 16775–16780, 1995
Husain SR, Behari N, Kreitman RJ, Pastan I, Puri RK: Complete regression of established human glioblastoma tumor xenograft by interleukin-4 toxin therapy. Cancer Res 58(16): 3649–3653, 1998
Weber F, Asher A, Bucholz R, Berger M, Prados M, Chang S et al.: Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. J Neurooncol 64(1–2): 125–137, 2003
Kunwar S: Convection enhanced delivery of IL13-PE38QQR for treatment of recurrent malignant glioma: presentation of interim findings from ongoing phase 1 studies. Acta Neurochir Suppl 88: 105–111, 2003
Filippi CG, Ulug AM, Ryan E, Ferrando SJ, van Gorp W: Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. AJNR Am J Neuroradiol 22(2): 277–283, 2001
Meade TJ, Taylor AK, Bull SR: New magnetic resonance contrast agents as biochemical reporters. Curr Opin Neurobiol 13(5): 597–602, 2003
Ichikawa T, Hogemann D, Saeki Y, Tyminski E, Terada K, Weissleder R et al.: MRI of transgene expression: correlation to therapeutic gene expression. Neoplasia 4(6): 523–530, 2002
Hamel W, Westphal M. Gene therapy of gliomas. Acta Neurochir Suppl 88: 125–135, 2003
Rainov NG, Ren H: Oncolytic viruses for treatment of malignant brain tumours. Acta Neurochir Suppl 88: 113–123, 2003
Ram Z, Culver KW, Oshiro EM, Viola JJ, DeVroom HL, Otto E et al.: Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nat Med 3(12): 1354–1361, 1997
Li Y, Pong RC, Bergelson JM, Hall MC, Sagalowsky AI, Tseng CP et al.: Loss of adenoviral receptor expression in human bladder cancer cells: a potential impact on the efficacy of gene therapy. Cancer Res 59(2): 325–330, 1999
Fuxe J, Liu L, Malin S, Philipson L, Collins VP, Pettersson RF: Expression of the cox-sackie and adenovirus receptor in human astrocytic tumors and xenografts. Int J Cancer 103(6): 723–739, 2003
Sandmair AM, Loimas S, Puranen P, Immonen A, Kossila M, Puranen M et al.: Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. Hum Gene Ther 11(16): 2197–2205, 2000
Anker L, Ohgaki H, Ludeke BI, Herrmann HD, Kleihues P, Westphal M: p53 protein accumulation and gene mutations in human glioma cell lines. Int J Cancer 55(6): 982–987, 1993
Rasheed BK, McLendon RE, Herndon JE, Friedman HS, Friedman AH, Bigner DD et al.: Alterations of the TP53 gene in human gliomas. Cancer Res 54(5): 1324–1330, 1994
Jen J, Harper JW, Bigner SH, Bigner DD, Papadopoulos N, Markowitz S et al.: Deletion of p16 and p15 genes in brain tumors. Cancer Res 54(24): 6353–6358, 1994
Abe T, Wakimoto H, Bookstein R, Maneval DC, Chiocca EA, Basilion JP: Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors. Cancer Gene Ther 9(3): 228–235, 2002
Kock H, Harris MP, Anderson SC, Machemer T, Hancock W, Sutjipto S et al.: Adeno virus-mediated p53 gene transfer suppresses growth of human glioblastoma cells in vitro and in vivo. Int J Cancer 67(6): 808–815, 1996
Lang FF, Bruner JM, Fuller GN, Aldape K, Prados MD, Chang S et al.: Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results. J Clin Oncol 21(13): 2508–2518, 2003
Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M et al.: An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274(5286): 373–376, 1996
Vecil GG, Lang FF: Clinical trials of adenoviruses in brain tumors: a review of Ad-p53 and oncolytic adenoviruses. J Neurooncol 65(3): 237–246, 2003
Fueyo J, Alemany R, Gomez-Manzano C, Fuller GN, Khan A, Conrad CA et al.: Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway. J Natl Cancer Inst 95(9): 652–660, 2003
Chiocca EA: Guided genes for tumor warfare. Nat Biotechnol 20(3): 235–236, 2002
Gromeier M, Lachmann S, Rosenfeld MR, Gutin PH, Wimmer E: Intergeneric poliovirus recombinants for the treatment of malignant glioma. Proc Natl Acad Sci USA 97(12): 6803–6808, 2000
Bernhardt G, Bibb JA, Bradley J, Wimmer E: Molecular characterization of the cellular receptor for poliovirus. Virology 199(1): 105–113, 1994
Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W et al.: Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci USA 97(23): 12846–12851, 2000
Gage FH. Mammalian neural stem cells. Science 287(5457): 1433–1438, 2000
Snyder EY, Deitcher DL, Walsh C, Arnold-Aldea S, Hartwieg EA, Cepko CL: Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell 68(1): 33–51, 1992
Kirsch M, Heese O, Westphal M, Schackert G. Stem cells in neuro-oncology – development, regeneration and treatment. Acta Neurochir Suppl 88: 143–151, 2003
Benedetti S, Pirola B, Polio B, Magrassi L, Bruzzone MG, Rigamonti D et al.: Gene therapy of experimental brain tumors using neural progenitor cells. Nat Med 6(4): 447–450, 2000
Ehtesham M, Kabos P, Gutierrez MA, Chung NH, Griffith TS, Black KL et al.: Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res 62(24): 7170–7174, 2002
Ehtesham M, Kabos P, Kabosova A, Neuman T, Black KL, Yu JS: The use of inter-leukin 12-secreting neural stem cells for the treatment of intracranial glioma. Cancer Res 62(20): 5657–5663, 2002
Brown AB, Yang W, Schmidt NO, Carroll R, Leishear KK, Rainov NG et al.: Intravascular delivery of neural stem cell lines to target intracranial and extracranial tumors of neural and non-neural origin. Hum Gene Ther 14(18): 1777–1785, 2003
Modo M, Cash D, Mellodew K, Williams SC, Fraser SE, Meade TJ et al.: Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging. Neuroimage 17(2): 803–811, 2002
Price SJ, Burnet NG, Donovan T, Green HA, Pena A, Antoun NM et al.: Diffusion tensor imaging of brain tumours at 3T: a potential tool for assessing white matter tract invasion? Clin Radiol 58(6): 455–462, 2003
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Westphal, M., Black, P.M. Perspectives of Cellular and Molecular Neurosurgery. J Neurooncol 70, 255–269 (2004). https://doi.org/10.1007/s11060-004-2754-3
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DOI: https://doi.org/10.1007/s11060-004-2754-3