Treatment of malignant gliomas: Radiotherapy, chemotherapy and integration of new targeted agents

Expert Review of Neurotherapeutics

Volumn 4, Issue 4, 2004, Pages 691-703

  Nieder, Carsten ^a   Grosu, Anca L ^a   Mehta, Minesh P ^b   Andratschke, Nicolaus ^a   Molls, Michael ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

Brain tumors; Chemotherapy; Glioma; Growth factors; Prognostic factors; Radiotherapy; Receptor tyrosine kinase inhibitor; Targeted therapy; Treatment

Indexed keywords

ANTIBODY; ANTISENSE OLIGONUCLEOTIDE; BROXURIDINE; BUCLADESINE; CARMULONIS; CARMUSTINE; CLADRIBINE; CYTARABINE; EFAPROXIRAL; EFLORNITHINE; EPIDERMAL GROWTH FACTOR; ETANIDAZOLE; GADOLINIUM; GADOLINIUM TEXAPHYRIN; HYDROXYUREA; IRINOTECAN; LEUSTAT; LOMUSTINE; MISONIDAZOLE; NITROSOUREA; OXYGEN; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PROCARBAZINE; RADIOSENSITIZING AGENT; TEMOZOLOMIDE; TENIPOSIDE; TIRAPAZAMINE; TOPOTECAN; TRANSFORMING GROWTH FACTOR BETA; UNINDEXED DRUG; VINCRISTINE;

BEAM THERAPY; BRACHYTHERAPY; CANCER GENETICS; CANCER GROWTH; GENE THERAPY; GLIOBLASTOMA; HUMAN; HYPERBARIC OXYGEN; IMMUNOTHERAPY; MULTIMODALITY CANCER THERAPY; ONCOGENE; POSTOPERATIVE CARE; PROGNOSIS; QUALITY OF LIFE; RADIATION DOSE; RADIATION DOSE FRACTIONATION; RADIATION NECROSIS; RADIOSURGERY; REVIEW; SCORING SYSTEM; SIGNAL TRANSDUCTION; STEREOTACTIC RADIOSURGERY; STEREOTAXIC SURGERY;

ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; DRUG DELIVERY SYSTEMS; GLIOMA; HUMANS; SIGNAL TRANSDUCTION;

EID: 3042783206     PISSN: 14737175     EISSN: None     Source Type: Journal    
DOI: 10.1586/14737175.4.4.691     Document Type: Review

References (98)

1. Thiessen B, Maguire JA, McNeil K et al. Loss of heterozygosity for loci on chromosome arms 1p and 10q in oligodendroglial tumors: relationship to outcome and chemosensitivity. J. Neurooncol. 64, 271-278 (2003).
2. Hashimoto N, Murakami M, Takahashi Y et al. Correlation between genetic alteration and long-term clinical outcome of patients with oligodendroglial tumors, with identification of a consistent region of deletion on chromosome arm 1p. Cancer 97, 2254-2261 (2003).
3. Laws ER, Parney IF, Huang W et al. Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J. Neurosurg. 99, 467-473 (2003).
4. Curran WJ, Scott CB, Horton J et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J. Natl Cancer Inst. 85, 704-710 (1993).
5. Guderson S, Lote K, Hannisdal E. Prognostic factors for glioblastoma multiforme. Acta Oncol. 35,123-127 (1996).
6. MRC Brain Tumour Working Party. Prognostic factors for high-grade malignant glioma: development of a prognostic index. J. Neuro-oncol. 9, 47-55 (1990).
7. Simpson JR, Horton J, Scott CB et al. Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive RTOG clinical trials. Int J. Radiat. Oncol. Biol. Phys. 26, 239-244 (1993).
8. Stemmer-Rachamimov AO, Louis DN. Histopathologic and immunohistochemical prognostic factors in malignant gliomas. Curr. Opin. Oncol. 9, 230-234 (1997).
9. Nieder C, Petersen S, Petersen C et al. The challenge of p53 as prognostic and predictive factor in gliomas. Cancer Treat. Rev. 26, 67-73 (2000).
10. Smith JS, Tachibana I, Passe SM et al. PTEN mutation, EGFR amplification and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J. Natl Cancer Inst. 93, 1246-1256 (2001).
11. Seiferheld W, Chakravarti A, Ang KK et al. Overexpression of the epidermal growth factor receptor (EGFR), as determined by EGFR immunostaining on tissue microarrays, fails to demonstrate independent prognostic value for patients with glioblastoma multiforme: a report from RTOG 7401, 7918, 8302, 8409, 9006, 9305, 9602 and 9806 (abstract 161). Int. J. Radiat. Oncol. Biol. Phys. 54, 96 (2002).
12. Simmons ML, Lamborn KR, Takahashi M et al. Analysis of complex relationships between age, p53, epidermal growth factor receptor and survival in glioblastoma patients. Cancer Res. 61, 1122-1128 (2001). Thoughtful analysis of emerging prognostic factors.
13. Schmidt MC, Antweiler S, Urban N et al. Impact of genotype and morphology on the prognosis of glioblastoma. J. Neuropathol. Exp. Neurol. 61, 321-328 (2002).
14. Brat DJ, Seiferheld W, Perry A et al. FISH analysis of genetic markers of prognosis for high grade astrocyotmas using tissue microarrays from RTOG clinical trials. Radiation Therapy Oncology Group Translational Research Program. Int. J. Radiat. Oncol. Biol. Phys. 57(Suppl), S135 (2003).
15. Nutt CL, Mani DR, Betensky RA et al. Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res. 63, 1602-1607 (2003). Valuable introduction to the field of modern classification methods.
16. Shai R, Shi T, Kremen TJ, et al. Gene expression profiling identifies molecular subtypes of gliomas. Oncogene 22, 4918-4923 (2003).
17. Mischel PS, Shai R, Shi T et al. Identification of molecular subtypes of glioblastoma by gene expression profiling. Oncogene 22, 2361-2373 (2003).
18. Kuznetsov YE, Caramanos Z, Antel SB et al. Proton magnetic resonance spectroscopic imaging can predict length of survival in patients with supratentorial gliomas. Neurosurgery 53, 565-574 (2003).
19. Zhu A, Shaeffer J, Leslie S et al. Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation. Int. J. Radiat. Oncol. Biol. Phys. 34, 809-815 (1996).
20. 6-methylguanine-DNA methyltransferase-deficient phenotype in human gliomas: frequency and time to tumor progression after alkylating agent-based chemotherapy. Clin. Cancer Res. 5, 807-814 (1999).
21. Friedman HS, McLendon RE, Kerby T et al. DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to temodal in newly diagnosed malignant glioma. J. Clin. Oncol. 16, 3851-3857 (1998).
22. Schiff D, Shaffrey ME. Role of resection for newly diagnosed malignant gliomas. Expert Rev. AntiCancer Ther. 3, 621-30 (2003).
23. Nieder C, Andratschke N, Wiedenmann N et al. Radiotherapy for high-grade gliomas: does altered fractionation improve the outcome? Strahlenther. Onkol. 180, (2004) (In Press). Summary of currently achievable results with standard treatments.
24. Fitzek MM, Thornton AF, Rabinov JD et al. Accelerated fractionated proton/ photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a Phase II prospective trial. J. Neurosurg. 91, 251-260 (1999).
25. Chan JL, Lee SW, Fraass BA et al. Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. J. Clin. Oncol. 20, 1635-1642 (2002).
26. Laperriere NJ, Leung PM, McKenzie S et al. Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma. Int. J. Radiat. Oncol. Biol. Phys. 41, 1005-1011 (1998).
27. Selker RG, Shapiro WR, Burger P et al. The Brain Tumor Co-operative Group NIH Trial 87-01: a randomised comparison of surgery, external radiotherapy and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy and carmustine. Neurosurgery 51, 343-355 (2002).
28. McDermott MW, Sneed PK, Gutin PH. Interstitial brachytherapy for malignant brain tumors. Semin. Surg. Oncol. 14, 79-87 (1998).
29. Sneed PK, Stauffer PR, McDermott MW et al. Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost ± hyperthermia for glioblastoma multiforme. Int. J. Radiat. Oncol. Biol. Phys. 40, 287-295 (1998).
30. Prados MD, Wara WM, Sneed PK et al. Phase III trial of accelerated hyperfractionation with or without difluromethylornithine (DFMO) versus standard fractionated radiotherapy with or without DFMO for newly diagnosed patients with glioblastoma multiforme. Int. J. Radiat. Oncol. Biol. Phys. 49, 71-77 (2001).
31. Shafman TD, Loeffler JS. Novel radiation technologies for malignant gliomas. Curr. Opin. Oncol. 11, 147-151 (1999).
32. Kleinberg L, Grossman SA, Carson K et al. Survival of patients with newly diagnosed glioblastoma multiforme treated with RSR13 and radiotherapy: results of a Phase II new approaches to brain tumor therapy CNS consortium safety and efficacy study. J. Clin. Oncol. 20, 3149-3155 (2002).
33. Williams JA, Williams JR, Yuan X et al. Protracted exposure radiosensitization of experimental human malignant glioma. Radiat. Oncol. Invest. 6, 255-263 (1998).
34. Fine HA, Dear KB, Loeffler JS et al. Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 71, 2585-2597 (1993).
35. Stewart LA. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359, 1011-1018 (2002). Most recent meta-analysis of chemotherapy in malignant gliomas.
36. Buckner JC, Schomberg PJ, McGinnis WL et al. A Phase III study of radiation therapy plus carmustine with or without recombinant interferon-α in the treatment of patients with newly diagnosed high-grade glioma. Cancer 92, 420-433 (2001).
37. Shapiro WR, Green SB, Burger PC et al. Randomized trial of three chemotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Co-operative Group Trial 8001. J. Neurosurg. 71, 1-9 (1989).
38. Grossman SA, O'Neill A, Grunnet M et al. Phase III study comparing three cycles of infusional carmustine and cisplatin followed by radiation therapy with radiation therapy and concurrent carmustine in patients with newly diagnosed supratentorial glioblastoma multiforme: Eastern Co-operative Oncology Group Trial 2394. J. Clin. Oncol. 21, 1485-1491 (2003).
39. Gilbert M, O'Neill A, Grossman S et al. A Phase II study of preradiation chemotherapy followed by external beam radiotherapy for the treatment of patients with newly diagnosed glioblastoma multiforme: an Eastern Co-operative Oncology Group study (E2393). J. Neurooncol. 47, 145-152 (2000).
40. Levin VA, Yung WK, Bruner J et al. Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas. Int. J. Radiat. Oncol. Biol. Phys. 53; 58-66 (2002).
41. Jeremic B, Shibamoto Y, Grujicic D et al. Concurrent accelerated hyperfractionated radiation therapy and carboplatin/ etoposide in patients with malignant glioma: long-term results of a Phase II study. J. Neuro-oncol. 51, 133-141 (2001).
42. Brandes AA, Rigon A, Zampieri P et al. Carboplatin and teniposide concurrent with radiotherapy in patients with glioblastoma multiforme: a Phase II study. Cancer 82, 355-361 (1998).
43. Levin VA, Silver P, Hannigan J et al. Superiority of postradiotherapy adjuvant chemotherapy with CCNU, procarbazine and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int. J. Radiat. Oncol. Biol. Phys. 18, 321-324 (1990).
44. Levin VA, Hess KR, Choucair A et al. Phase III randomised study of postradiotherapy chemotherapy with combination α-difluoromethylomithine- PCV versus PCV for anaplastic gliomas. Clin. Cancer Res. 9, 981-990 (2003).
45. Weller M, Muller B, Koch R et al. Neuro-Oncology Working Group 01 trial of nimustine plus teniposide versus nimustine plus cytarabine chemotherapy in addition to involved-field radiotherapy in the first-line treatment of malignant glioma. J. Clin. Oncol. 21, 3276-3284 (2003).
46. Durando X, Lemaire JJ, Tortochaux J et al. High-dose BCNU followed by autologous hematopoietic stem cell transplantation in supratentorial high-grade malignant gliomas: a retrospective analysis of 114 patients. Bone Marrow Transplant 31, 559-564 (2003).
47. Westphal M, Hilt DC, Bortey E et al. A Phase III trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. J. Neuro-oncol. 5, 79-88 (2003).
48. Degen JW, Walbridge S, Vortmeyer AO et al. Safety and efficacy of convection-enhanced delivery of gemcitabine or cathoplatin in a malignant glioma model in rats. J. Neurosurg. 99, 893-898 (2003).
49. Debinski W. Local treatment of brain tumors with targeted chimera cytotoxic proteins. Cancer Invest. 20, 801-809 (2002).
50. Kunwar S. Convection enhanced delivery of EL13-PE38QQR for treatment of recurrent malignant glioma: presentation of interim findings from ongoing Phase 1 studies. Acta Neurochir. Suppl. 88, 105-111 (2003).
51. Weber FW, Floeth F, Asher A et al. Local convection enhanced delivery of IL4-Pseudomonas exotoxin (NBI-3001) for treatment of patients with recurrent malignant glioma. Acta Neurochir. 88(Suppl.), 93-103 (2003).
52. Langer CJ, Ruffer J, Rhodes H et al. Phase II Radiation Therapy Oncology Group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme. Int. J. Radiat. Oncol. Biol. Phys. 51, 113-119 (2001).
53. Fisher B, Won M, Macdonald D, et al. Phase II study of topotecan plus cranial radiation for glioblastoma multiforme: results of Radiation Therapy Oncology Group 9513. Int. J. Radiat. Oncol. Biol. Phys. 53, 980-986 (2002).
54. Raymond E, Fabbro M, Boige V et al. Multicentre Phase II study and pharmacokinetic analysis of irinotecan in chemotherapy-naive patients with glioblastoma. Ann. Oncol. 14, 603-614 (2003).
55. Stupp R, Dietrich PY, Ostermann Kraljevic S et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J. Clin. Oncol. 20, 1375-1382 (2002).
56. Von Bossanyi P, Diete S, Dietzmann K et al. Immunohistochemical expression of P-glycoprotein and glutathione S-transferases in cerebral gliomas and response to chemotherapy. Acta Neuropathol. 94, 605-611 (1997).
57. Tuvesson H, Gunnarsson PO, Seidegard J. Measurement and characterization of the denitrosation of tauromustine and related nitrosoureas by glutathione transferases in liver cytosol from various species. Carcinogenesis 14, 1143-1147 (1993).
58. Wolff J, Denecke J, Jurgens H et al. Dexamethasone induces partial resistance to cisplatinum in C6 glioma cells. Anticancer Res. 16, 805-810 (1996).
59. Naumann U, Durka S, Weller M. Dexamethasone-mediated protection from drug cytotoxicity: association with p21WAF1/CIP1 protein accumulation. Oncogene 17, 1567-1575 (1998).
60. Belanich M, Pastor M, Randall T et al. Retrospective study of the correlation between DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res. 56, 783-788 (1996).
61. Ruan S, Okcu MF, Pong RC et al. Attenuation of WAF1/Cip1 expression by an antisense adenovirus expression vector sensitizes glioblastoma cells to apoptosis induced by chemotherapeutic agents 1,3-bis(2-chloroethyl)-1- nitrosourea and cisplatin. Clin. Cancer Res. 5, 197-202 (1999).
62. Choe G, Horvath S, Cloughesy TF et al. Analysis of the phosphatidylinositol 3-kinase signaling pathway in glioblastoma patients in vivo. Cancer Res. 63, 2742-2746 (2003).
63. Eshleman JS, Carlson BL, Mladek AC et al. Inhibition of the mammalian target of rapamycin sensitizes U87 xenografts to fractionated radiation therapy. Cancer Res. 62, 7291-7297 (2002).
64. Nakatani K, Yoshimi N, Mori H et al. The significance of the expression of tumor suppressor gene DCC in human gliomas. J. Neuro-oncol. 40, 237-242 (1998).
65. Kip1 is correlated with survival of patients with astrocytoma. Clin. Cancer Res. 5, 551-557 (1999).
66. Nieder C, Schlegel J, Andratschke N et al. The role of growth factors in central nervous system tumours. AntiCancer Res. 23, 1681-1686 (2003).
67. Barker FG II, Simmons ML, Chang SM et al. EGFR overexpression and radiation response in glioblastoma multiforme. Int. J. Radiat. Oncol. Biol. Phys. 51, 410-418 (2001).
68. Chakravarti A, Delaney MA, Noll E et al. Prognostic and pathologic significance of quantitative protein expression profiling in human gliomas. Clin. Cancer Res. 7, 2387-2395 (2001).
69. Muracciole X, Romain S, Dufour H et al. PAI-1 and EGFR expression in adult glioma tumors: toward a molecular prognostic classification. Int. J. Radiat. Oncol. Biol. Phys. 52, 592-598 (2002).
70. Lammering G, Valerie K, Lin PS et al. Radiosensitization of malignant glioma cells through overexpression of dominant-negative epidermal growth factor receptor. Clin. Cancer Res. 7, 682-690 (2001).
71. Lammering G, Hewit TH, Valerie K et al. AntierbB receptor strategy as a gene therapeutic intervention to improve radiotherapy in malignant human tumours. Int. J. Radiat. Biol. 79, 561-568 (2003). Valuable overview of antiepidermal growth factor (EGFR) strategies in conjunction with radiotherapy.
72. Li B, Chang CM, Yuan M et al. Resistance to small molecule inhibitors of epidermal growth factor receptor in malignant gliomas. Cancer Res. 63, 7443-7450 (2003).
73. Chakravarti A, Loeffler JS, Dyson NJ. Insulin-like growth factor receptor I mediates resistance to antiepidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositol 3-kinase signaling. Cancer Res. 62, 200-207 (2002).
74. Johns TG, Luwor RB, Murone C et al. Antitumor efficacy of cytotoxic drugs and the monoclonal antibody 806 is enhanced by the EGF receptor inhibitor AG1478. Proc. Natl. Acad. Sci. USA (2003). Intriguing data on combined antiEGFR strategies.
75. Chakravarti A, Chakladar A, Delaney MA, Latham DE, Loeffler JS. The epidermal receptor growth factor pathway mediates resistance to sequential administration of radiation and chemotherapy in primary human glioblastoma cells in a RAS-dependent manner. Cancer Res. 62, 4307-4315 (2002).
76. Rich JN, Reardon DA, Peery T et al. Phase II trial of gefitinib in recurrent glioblastoma. J. Clin. Oncol. 22, 133-142 (2004).
77. Jennings MT, Pietenpol JA. The role of transforming growth factor β in glioma progression. J. Neuro-oncol. 36, 123-140 (1998).
78. Wick W, Platten M, Weller M. Glioma cell invasion: regulation of metalloproteinase activity by TGF-β. J. Neuro-oncol. 53, 177-185 (2001).
79. Fakhrai H, Dorigo O, Shawler DL et al. Eradication of established intracranial rat gliomas by transforming growth factor β antisense gene therapy. Proc. Natl Acad. Sci. USA 93, 2909-2914 (1996).
80. Trojan J, Johnson TR, Rudin SD et al. Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor-1 RNA. Science 259, 94-97 (1993).
81. Andrews DW, Resnicoff M, Flanders AE et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor Type I receptor in malignant astrocytomas. J. Clin. Oncol. 19, 2189-2200 (2001).
82. Wen PY, Yung WK, Hess K et al. Phase I study of STI571 (Gleevec) for patients with recurrent malignant gliomas and meningiomas (NABTC 99-08, Abstract 288). Proc. Am. Soc. Clin. Oncol. 21, 73 (2002).
83. Schueneman AJ, Himmelfarb E, Geng L et al. SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models. Cancer Res. 63, 4009-4016 (2003). Good example of antiangiogenic receptor tyrosine kinases approaches.
84. Fukumura D, Xu L, Chen Y et al. Hypoxia and acidosis independently upregulate vascular endothelial growth factor transcription in brain tumours in vivo. Cancer Res. 61, 6020-6024 (2001).
85. Geng I, Donnelly E, McMahon G et al. Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy. Cancer Res. 61, 2413-2419 (2001).
86. Yung WA, Friedman H, Jackson E et al. A Phase I trial of PTK787/ZK 222584 (PTK/ ZK), a novel oral VEGFR TK inhibitor in recurrent glioblastoma (Abstract 315). Proc. Am. Soc. Clin. Oncol. 21, 79 (2002).
87. Auguste P, Gursel DB, Lemiere S et al. Inhibition of fibroblast growth factor/ fibroblast growth factor receptor activity in glioma cells impedes tumor growth by both angiogenesis-dependent and -independent mechanisms. Cancer Res. 61, 1717-1726 (2001).
88. Fine HA, Wen PY, Maher EA et al. Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas. J. Clin. Oncol. 21, 2299-2304 (2003).
89. Seiferheld W, Mehta MP, Delrowe J et al. 5 years of glioblastoma multiforme (GBM) Phase II trials at the Radiation Therapy Oncology Group (RTOG) (Abstract 281). Proc. Am. Soc. Clin. Oncol. 21, 71 (2002).
90. Kim JH, Kolozwary A, Rogulski K et al. Selective radiosensitization of 9L glioma in the brain transduced with double suicide fusion gene. Cancer J. Sci. Am. 4, 364-369 (1998).
91. Fulda S, Wick W, Weller M, Debatin KM. Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nature Med. 8, 808-815 (2002).
92. Emrich JG, Brady LW, Quang TS et al. Radioiodinated (I-125) monoclonal antibody 425 in the treatment of high grade glioma patients: ten-year synopsis of a novel treatment. Am. J. Clin. Oncol. 25, 541-546 (2002). Largest series of antibody-treated patients.
93. Reardon DA, Akabani G, Coleman RE 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, 1389-1397 (2002).
94. Mitchell DA, Fecci PE, Sampson JH. Adoptive immunotherapy for malignant glioma. Cancer J. 9, 157-166 (2003).
95. Yamanaka R, Abe T, Yajima N et al. Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical Phase I/II trial. Br. J. Cancer 89, 1172-1179 (2003).
96. Price A, Shi Q, Morris D et al. Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340. Clin. Cancer Res. 5, 845-854 (1999).
97. Delmas C, End D, Rochaix P et al. The farnesyltransferase inhibitor R115777 reduces hypoxia and matrix metalloproteinase 2 expression in human glioma xenograft. Clin. Cancer Res. 9, 6062-6068 (2003).
98. Komata T, Kanzawa T, Kondo Y et al. Telomerase as a therapeutic target for malignant gliomas. Oncogene 21, 656-663 (2002).