Abstract
Chemotherapy has been relatively ineffective in the treatment of central nervous system (CNS) metastases of systemic cancers (i.e., breast cancer, small cell cancer of lung, lymphoma, and germ cell tumors), while clinical regression, even complete remission, of the tumor has occurred at the non-CNS systemic sites. The failure of response of such CNS metastatic tumors led us to focus on the issue of drug delivery to tumor. Besides the classic pharmacologic issues of drug delivery to tumors (i.e., blood flow, drug concentration, time of exposure, etc.), tumors within the CNS can be affected by problems of delivery because of the blood-brain barrier (BBB)1,2. The old concept that malignant tumors in the CNS have no effective barrier, as emphasized, for instance, by enhancement on computerized tomographic (CT) scan, has been shown to be incorrect. Numerous studies report variability in barrier permeability within malignant tumors. Even the well-vascularized, actively proliferating edge of the tumor, the brain adjacent to tumor (BAT), is known to be variable and complex in terms of barrier integrity.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
E. A. Neuwelt and P. Barnett, Blood-brain barrier disruption in the treatment of brain tumors: Animal studies, in: Implications of the blood-brain barrier and its manipulation: Vol II Clinical aspects, E.A. Neuwelt, ed., pp 107–194, Plenum Press, New York (1989).
S.I. Rapoport, Blood-brain Barrier in Physiology and Medicine, Raven Press, New York (1976).
N.H. Greig, Brain tumors and the blood-tumor barrier, in: Implications of the blood-brain barrier and its manipulation: Vol I Basic science aspects, E.A. Neuwelt ed., Plenum Press, New York (1989).
R.G. Blasberg, D. Groothuis, and P. Molnar, A review of hyperosmotic blood-brain barrier disruption in seven experimental brain tumor models, in: Pathophysiology of the Blood-brain Barrier, B.B. Johansson, C. Owman, and H. Widner, eds., Volume 14:197–220, Elsevier, New York, (1990).
P.A. Barnett, S. Roman-Goldstein, F. Ramsey, C. McCormick, G. Sexton, J. Szumowski, and E.A. Neuwelt, Differential permeability and quantitative MR imaging of a human lung carcinoma brain xenograft in the nude rat, Am. J. Path. 146:436 (1995).
M.K. Gumerlock and E.A. Neuwelt, The effects of anesthesia on osmotic blood-brain barrier disruption, Neurosurgery 26:268 (1990).
M.D. Walker, S.B. Green, D.P. Byar, E. Alexander, Jr., U. Batzdorf, W. H. Brooks, W.E. Hunt, C.S. MacCarty, M.D. Mahaley, Jr., J. Mealey, Jr., G. Owens, J. Ransohoff, J.T. Robertson, W.R. Shapiro, K.R. Smith, Jr., C.B. Wilson, and T.A. Strike, Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery, N. Engl. J. Med. 303:1323 (1980).
P.K. Duffner, M.E. Horowitz, J.P. Krischer, H.S. Friedman, P.C. Burger, M.E. Cohen, R.A. Sanford, R.K. Mulhern, H.E. James, C.R. Freeman, F.G. Seidel, and L.E. Kun, Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors, N. Engl. J. Med. 328:1725 (1993).
J.C. Allen, What we learn from infants with brain tumors, (Editorial), N Engl. J. Med. 328:1780 (1993).
J.R. Crossen, A. Garwood, E. Glatstein, and E.A. Neuwelt, Neurobehavioral sequelae of cranial irradiation in adults: A review of radiation induced encephalopathy, J. Clin. Oncol. 12:627 (1994).
E.A. Neuwelt, P.A. Barnett, K.E. Hellström, I Hellström, C.I. McCormick, and F.L. Ramsey, The effect of blood-brain barrier on intact and fragmented monoclonal antibody localization in intracerebral human carcinoma xenografts, J. Nuclear Medicine 35:1831 (1994).
E.A. Neuwelt, R. Weissleder, G. Nilaver, R.A. Kroll, S. Roman-Goldstein, J. Szumowski, M.A. Pagel, R.S. Jones, L.G. Remsen, C.I. McCormick, E.M. Shannon, and L.L. Muldoon, Delivery of virus-sized iron oxide particles to rodent CNS neurons, Neurosurgery 34:777 (1994).
J.M. Nazzaro, M. Pagel, L. Rosenbaum, and E.A. Neuwelt. A new model of systemic drug rescue based on permeability characteristics of the blood-brain barrier in intracerebral abscess-bearing rats, J. Neurosurg. 74:467 (1991).
R.A. Kroll, M.A. Pagel, J.J. Langone, G.J. Sexton, and E.A. Neuwelt, Differential permeability of the blood-tumor barrier in intracerebral tumor-bearing rats: Anti-drug antibody to achieve systemic drug rescue, Therapeutic Immunol. 1:333 (1995).
E.A. Neuwelt, M.A. Pagel, A.I. Geller, and L.L. Muldoon, Gene replacement therapy in the central nervous system; Viral vector mediated therapy of global neurodegenerative disease, Behav. Brain Sci. 18: 1 (1995).
E.A. Neuwelt, Blood-brain barrier disruption in the treatment of brain tumors: clinical implications, in: Implications of the blood-brain barrier and its manipulation: Vol. 2. Clinical implications, E.A. Neuwelt, ed., Plenum Press, New York, (1989).
E.A. Neuwelt, J. Howieson, E.P. Frenkel, D. Specht, R. Weigel, C.G. Buchan, and S.A. Hill, Therapeutic efficacy of multiagent chemotherapy with drug delivery enhancement by blood-brain barrier modification in glioblastoma, Neurosurgery 19:573 (1986).
E.A. Neuwelt, D. Goldman, S.A. Dahlborg, J. Crossen, F. Ramsey, S.M. Goldstein, R. Braziel, and B. Dana, Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: Prolonged survival and preservation of cognitive function, J. Clin. Oncol. 9:1580 (1991).
E.A. Neuwelt, H.D. Specht, and S.A. Hill, Permeability of human brain tumor to 99mTc-glucoheptonate and 99mTc-Albumin: Implications for monoclonal antibody therapy, J. Neurosurg. 65:194 (1986).
E.A. Neuwelt, D. Specht, S. Larson, K. Krohn, K. Hellström, I. Hellström, S.A. Dahlborg, and P. Barnett. Increased delivery of tumor-specific monoclonal antibodies to brain after osmotic blood-brain barrier modification in patients with melanoma metastatic to the CNS, Neurosurgery 20:885 (1987).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media New York
About this chapter
Cite this chapter
Neuwelt, E.A. (1995). Blood-Brain Barrier Manipulation: Current Status of Laboratory and Clinical Studies. In: Greenwood, J., Begley, D.J., Segal, M.B. (eds) New Concepts of a Blood—Brain Barrier. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1054-7_27
Download citation
DOI: https://doi.org/10.1007/978-1-4899-1054-7_27
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-1056-1
Online ISBN: 978-1-4899-1054-7
eBook Packages: Springer Book Archive