Cancer Treatment Reviews
Volume 30, Issue 5 , Pages 415-423 , August 2004

Modulation of the blood–brain barrier in oncology: therapeutic opportunities for the treatment of brain tumours?

  • E.Marleen Kemper

      Affiliations

    • Department of Clinical Chemistry, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    • ,
  • Willem Boogerd

      Affiliations

    • Department of Neurology, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
    • Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    • ,
  • Ingrid Thuis

      Affiliations

    • Department of Clinical Chemistry, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    • ,
  • Jos H Beijnen

      Affiliations

    • Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    • Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
    • Division of Drug Toxicology, Faculty of Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands
    • ,
  • Olaf van Tellingen

      Affiliations

    • Department of Clinical Chemistry, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    • Corresponding Author InformationCorresponding author. Tel.: +31-20-512-2792; fax: +31-20-512–2799

References 

  1. DeAngelis LM. Brain tumours. N. Engl. J. Med. 2001;344(2):114–123
  2. Legler JM, Ries LA, Smith MA, et al.  Cancer surveillance series [corrected]: brain and other central nervous system cancers: recent trends in incidence and mortality. J. Natl. Cancer Inst. 1999;91(16):1382–1390
  3. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer J. Clin. 1999;49(1):8–31 also p. 1
  4. Behin A, Hoang-Xuan K, Carpentier AF, Delattre JY. Primary brain tumours in adults. Lancet. 2003;361(9354):323–331
  5. Walker MD, Green SB, Byar DP, et al.  Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N. Engl. J. Med. 1980;303(23):1323–1329
  6. Silbergeld DL, Chicoine MR. Isolation and characterization of human malignant glioma cells from histologically normal brain. J. Neurosurg. 1997;86(3):525–531
  7. Plate KH, Risau W. Angiogenesis in malignant gliomas. Glia. 1995;15(3):339–347
  8. Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am. J. Pathol. 1995;146(5):1029–1039
  9. Zhang RD, Price JE, Fujimaki T, Bucana CD, Fidler IJ. Differential permeability of the blood–brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice. Am. J. Pathol. 1992;141(5):1115–1124
  10. Paterson AH, Agarwal M, Lees A, Hanson J, Szafran O. Brain metastases in breast cancer patients receiving adjuvant chemotherapy. Cancer. 1982;49(4):651–654
  11. Boogerd W, Vos VW, Hart AA, Baris G. Brain metastases in breast cancer: natural history, prognostic factors and outcome. J. Neurooncol. 1993;15(2):165–174
  12. Crivellari D, Pagani O, Veronesi A, et al.  High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel. Ann. Oncol. 2001;12(3):353–356
  13. Fine HA, Dear KB, Loeffler JS, Black PM, Canellos GP. Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer. 1993;71(8):2585–2597
  14. Cairncross JG, Macdonald DR. Successful chemotherapy for recurrent malignant oligodendroglioma. Ann. Neurol. 1988;23(4):360–364
  15. van den Bent MJ, Kros JM, Heimans JJ, et al.  Response rate and prognostic factors of recurrent oligodendroglioma treated with procarbazine, CCNU, and vincristine chemotherapy. Dutch Neuro-oncology Group. Neurology. 1998;51(4):1140–1145
  16. Nieder C, Grosu AL, Molls M. A comparison of treatment results for recurrent malignant gliomas. Cancer Treat Rev. 2000;26(6):397–409
  17. Rubin LL, Staddon JM. The cell biology of the blood–brain barrier. Annu. Rev. Neurosci. 1999;22:11–28
  18. Levin VA. Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J. Med. Chem. 1980;23(6):682–684
  19. Begley DJ. The blood–brain barrier: principles for targeting peptides and drugs to the central nervous system. J. Pharm. Pharmacol. 1996;48(2):136–146
  20. Banks WA, Kastin AJ, Barrera CM. Delivering peptides to the central nervous system: dilemmas and strategies. Pharm. Res. 1991;8(11):1345–1350
  21. Zlokovic BV. Cerebrovascular permeability to peptides: manipulations of transport systems at the blood–brain barrier. Pharm. Res. 1995;12(10):1395–1406
  22. Schinkel AH, Wagenaar E, Mol CAAM, Vandeemter L. P-glycoprotein in the blood–brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J. Clin. Invest. 1996;97:2517–2524
  23. de Boer AG, Sutanto W. Drug transport across the blood–brain barrier. In: In vitro and in vivo techniques. Amsterdam: Harwood Academic Publishers; 1997;
  24. Janzer RC, Raff MC. Astrocytes induce blood–brain barrier properties in endothelial cells. Nature. 1987;325(6101):253–257
  25. Gaillard PJ, Voorwinden LH, Nielsen JL, et al.  Establishment and functional characterization of an in vitro model of the blood–brain barrier, comprising a co-culture of brain capillary endothelial cells and astrocytes. Eur. J. Pharm. Sci. 2001;12(3):215–222
  26. Barrand MA, Robertson KJ, von Weikersthal SF. Comparisons of P-glycoprotein expression in isolated rat brain microvessels and in primary cultures of endothelial cells derived from microvasculature of rat brain, epididymal fat pad and from aorta. FEBS Lett. 1995;374(2):179–183
  27. Gutmann H, Torok M, Fricker G, Huwyler J, Beglinger C, Drewe J. Modulation of multidrug resistance protein expression in porcine brain capillary endothelial cells in vitro. Drug Metab. Dispos. 1999;27(8):937–941
  28. Smith QR, Allen DD. In situ brain perfusion technique. Methods Mol. Med. 2003;89:209–218
  29. de Lange EC, de Boer BA, Breimer DD. Microdialysis for pharmacokinetic analysis of drug transport to the brain. Adv. Drug Deliv. Rev. 1999;36(2–3):211–227
  30. Yan Q, Matheson C, Sun J, Radeke MJ, Feinstein SC, Miller JA. Distribution of intracerebral ventricularly administered neurotrophins in rat brain and its correlation with trk receptor expression. Exp. Neurol. 1994;127(1):23–36
  31. Brem H, Ewend MG, Piantadosi S, Greenhoot J, Burger PC, Sisti M. The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. J. Neurooncol. 1995;26(2):111–123
  32. Brem H, Piantadosi S, Burger PC, et al.  Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumour Treatment Group. Lancet. 1995;345(8956):1008–1012
  33. Westphal M, Hilt DC, Bortey E, et al.  A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncol. 2003;5(2):79–88
  34. Rapoport SI, Hori M, Klatzo I. Testing of a hypothesis for osmotic opening of the blood–brain barrier. Am. J. Physiol. 1972;223(2):323–331
  35. Brightman MW, Hori M, Rapoport SI, Reese TS, Westergaard E. Osmotic opening of tight junctions in cerebral endothelium. J. Comp. Neurol. 1973;152(4):317–325
  36. Rapoport SI. Effect of concentrated solutions on blood–brain barrier. Am. J. Physiol. 1970;219(1):270–274
  37. Kroll RA, Neuwelt EA. Outwitting the blood–brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery. 1998;42(5):1083–1099
  38. Nadal A, Fuentes E, Pastor J, McNaughton PA. Plasma albumin is a potent trigger of calcium signals and DNA synthesis in astrocytes. Proc. Natl. Acad. Sci. USA. 1995;92(5):1426–1430
  39. Siegal T, Rubinstein R, Bokstein F, et al.  In vivo assessment of the window of barrier opening after osmotic blood–brain barrier disruption in humans. J. Neurosurg. 2000;92(4):599–605
  40. Doolittle ND, Miner ME, Hall WA, et al.  Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood–brain barrier for the treatment of patients with malignant brain tumours. Cancer. 2000;88(3):637–647
  41. Mcallister LD, Doolittle ND, Guastadisegni PE, et al.  Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery. 2000;46(1):51–60
  42. Gumerlock MK, Belshe BD, Madsen R, Watts C. Osmotic blood–brain barrier disruption and chemotherapy in the treatment of high grade malignant glioma: patient series and literature review. J. Neurooncol. 1992;12(1):33–46
  43. Neuwelt EA, Howieson J, Frenkel EP, et al.  Therapeutic efficacy of multiagent chemotherapy with drug delivery enhancement by blood–brain barrier modification in glioblastoma. Neurosurgery. 1986;19(4):573–582
  44. Raymond JJ, Robertson DM, Dinsdale HB. Pharmacological modification of bradykinin induced breakdown of the blood–brain barrier. Can. J. Neurol. Sci. 1986;13(3):214–220
  45. Koga H, Inamura T, Ikezaki K, Nomura T, Samoto K, Fukui M. Increased delivery of a new cisplatin analogue (254-S) in a rat brain tumour by an intracarotid infusion of bradykinin. Neurol. Res. 1996;18(3):244–247
  46. Borlongan CV, Emerich DF. Facilitation of drug entry into the CNS via transient permeation of blood brain barrier: laboratory and preliminary clinical evidence from bradykinin receptor agonist, Cereport. Brain Res. Bull. 2003;60(3):297–306
  47. Bartus RT, Snodgrass P, Marsh J, Agostino M, Perkins A, Emerich DF. Intravenous cereport (RMP-7) modifies topographic uptake profile of carboplatin within rat glioma and brain surrounding tumour, elevates platinum levels, and enhances survival. J. Pharmacol. Exp. Ther. 2000;293(3):903–911
  48. Bartus RT, Elliott P, Hayward N, Dean R, McEwen EL, Fisher SK. Permeability of the blood brain barrier by the bradykinin agonist, RMP-7: evidence for a sensitive, auto-regulated, receptor-mediated system. Immunopharmacology. 1996;33(1-3):270–278
  49. Elliott PJ, Hayward NJ, Dean RL, Blunt DG, Bartus RT. Intravenous RMP-7 selectively increases uptake of carboplatin into rat brain tumours. Cancer Res. 1996;56(17):3998–4005
  50. Emerich DF, Snodgrass P, Dean R, et al.  Enhanced delivery of carboplatin into brain tumours with intravenous Cereport (RMP-7): dramatic differences and insight gained from dosing parameters. Br. J. Cancer. 1999;80(7):964–970
  51. Matsukado K, Inamura T, Nakano S, Fukui M, Bartus RT, Black KL. Enhanced tumour uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7. Neurosurgery. 1996;39(1):125–133 discussion 133–4
  52. Inamura T, Nomura T, Bartus RT, Black KL. Intracarotid infusion of RMP-7, a bradykinin analog: a method for selective drug delivery to brain tumours. J. Neurosurg. 1994;81(5):752–758
  53. Prados MD, Schold SC, Fine HA, et al.  A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma. Neuro-oncol. 2003;5(2):96–103
  54. Huai-Yun H, Secrest DT, Mark KS, et al.  Expression of multidrug resistance-associated protein (MRP) in brain microvessel endothelial cells. Biochem. Biophys. Res. Commun. 1998;243(3):816–820
  55. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta. 1976;455(1):152–162
  56. Kartner N, Riordan JR, Ling V. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science. 1983;221(4617):1285–1288
  57. O'Brien JP, Cordon-Cardo C. P-glycoprotein expression in normal human tissues. In:  Gupta S,  Tsuruo T editor. Multidrug resistance in cancer calls. New York: Wiley; 1996;p. 285–291
  58. Cordon-Cardo C, O'Brien JP, Boccia J, Casals D, Bertino JR, Melamed MR. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumour tissues. J. Histochem. Cytochem. 1990;38(9):1277–1287
  59. Pardridge WM, Golden PL, Kang YS, Bickel Y. Brain microvascular and astrocyte localization of P-glycoprotein. J. Neurochem. 1997;68:1278–1285
  60. Beaulieu E, Demeule M, Ghitescu L, Beliveau R. P-glycoprotein is strongly expressed in the luminal membranes of the endothelium of blood vessels in the brain. Biochem. J. 1997;326:539–544
  61. Schlachetzki F, Pardridge WM. P-glycoprotein and caveolin-1alpha in endothelium and astrocytes of primate brain. Neuroreport. 2003;14(16):2041–2046
  62. Seetharaman S, Barrand MA, Maskell L, Scheper RJ. Multidrug resistance-related transport proteins in isolated human brain microvessels and in cells cultured from these isolates. J. Neurochem. 1998;70:1151–1159
  63. Mayer U, Wagenaar E, Beijnen JH, et al.  Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr1a P-glycoprotein. Br. J. Pharmacol. 1996;119:1038–1044
  64. Schinkel AH, Smit JJ, van Tellingen O, et al.  Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood–brain barrier and to increased sensitivity to drugs. Cell. 1994;77(4):491–502
  65. Schinkel AH, Mayer U, Wagenaar E, et al.  Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc. Natl. Acad. Sci. USA. 1997;94:4028–4033
  66. van Asperen J, Schinkel AH, Beijnen JH, Nooijen WJ, Borst P, van Tellingen O. Altered pharmacokinetics of vinblastine in Mdr1a P-glycoprotein-deficient mice. J. Natl. Cancer Inst. 1996;88(14):994–999
  67. Kemper EM, van Zandbergen AE, Cleypool C, et al.  Increased penetration of paclitaxel into the brain by inhibition of P-glycoprotein. Clin. Cancer Res. 2003;9(7):2849–2855
  68. van Asperen J, van Tellingen O, Tijssen F, Schinkel AH, Beijnen JH. Increased accumulation of doxorubicin and doxorubicinol in cardiac tissue of mice lacking mdr1a P-glycoprotein. Br. J. Cancer. 1999;79(1):108–113
  69. Sawada T, Kato Y, Sakayori N, Takekawa Y, Kobayashi M. Expression of the multidrug-resistance P-glycoprotein (Pgp, MDR-1) by endothelial cells of the neovasculature in central nervous system tumours. Brain Tumour. Pathol. 1999;16(1):23–27
  70. Toth K, Vaughan MM, Peress NS, Slocum HK, Rustum YM. MDR1 P-glycoprotein is expressed by endothelial cells of newly formed capillaries in human gliomas but is not expressed in the neovasculature of other primary tumours. Am. J. Pathol. 1996;149(3):853–858
  71. Ashmore SM, Thomas DG, Darling JL. Does P-glycoprotein play a role in clinical resistance of malignant astrocytoma?. Anticancer Drugs. 1999;10(10):861–872
  72. Matsumoto T, Tani E, Kaba K, Shindo H, Miyaji K. Expression of P-glycoprotein in human glioma cell lines and surgical glioma specimens. J. Neurosurg. 1991;74(3):460–466
  73. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res. 1981;41(5):1967–1972
  74. Sikic BI, Fisher GA, Lum BL, Halsey J, Beketicoreskovic L, Chen G. Modulation and prevention of multidrug resistance by inhibitors of P-glycoprotein. Cancer Chemother. Pharmacol. 1997;40:S13–S19
  75. Huizing MT, Misser VH, Pieters RC, et al.  Taxanes: a new class of antitumour agents. Cancer Invest. 1995;13(4):381–404
  76. Chamberlain MC, Kormanik P. Salvage chemotherapy with taxol for recurrent anaplastic astrocytomas. J. Neurooncol. 1999;43(1):71–78
  77. Prados MD, Schold SC, Spence AM, et al.  Phase II study of paclitaxel in patients with recurrent malignant glioma. J. Clin. Oncol. 1996;14:2316–2321
  78. Kemper EM, Cleypool C, Boogerd W, Beijnen JH, van Tellingen O. The influence of the P-glycoprotein inhibitor zosuquidar trihydrochloride (LY335979) on the brain penetration of paclitaxel in mice. Cancer Chemother Pharmacol. 2004;53(2):173–178
  79. Fellner S, Bauer B, Miller DS, et al.  Transport of paclitaxel (Taxol) across the blood–brain barrier in vitro and in vivo. J. Clin. Invest. 2002;110(9):1309–1318
  80. Kemper EM, Verhey M, Boogerd W, Beijnen JH, van Tellingen O. Improved penetration of docetaxel into the brain by co-administration of inhibitors of P-glycoprotein. Eur. J. Cancer. 2004;40(8):1269–1274

PII: S0305-7372(04)00075-1

doi: 10.1016/j.ctrv.2004.04.001

Cancer Treatment Reviews
Volume 30, Issue 5 , Pages 415-423 , August 2004

Article Tools

* Image Usage & Resolution