The Effects of Induced Hypertension on the Uptake of ACNU in Experimental Brain Tumor

  • Y. Tsurumi


There have been improvements in chemotherapy for malignant brain tumors in recent years, but there still remain many problems and limitations in such therapy when considered from the perspective of therapeutic effectiveness. Not only must the sensitivity of tumor tissues to various anticancer drugs be tested, but also studies must be made of the in vivo pharmacokinetics of such drugs, including their uptake by tumor cells. In other words, no matter how large the administered dose of a drug is, if the effective volume entering the tumor tissue is insufficient, then satisfactory therapeutic results cannot be expected. From this perspective, the development of new techniques for the administration of such drugs that would result in increased uptake achieved selectively by the brain tumor tissue without an increase in systemic side effects would be desirable.


Brain Tumor Normal Brain Tissue Malignant Brain Tumor Hypertension Group Brain Tumor Model 


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  1. 1.
    Blasberg RG, Kobayashi T, Horowitz M, Rice JM, Groothuis D, Molnar P, Fenstermacher JD (1983) Regional blood flow in ethylnitrosourea-induced brain tumors. Ann Neurol 14:189–201PubMedCrossRefGoogle Scholar
  2. 2.
    Endo H, Larsen B, Lassen NA (1977) Regional cerebral blood flow alterations remote from the site of intracranial tumors. J Neurosurg 46:271–281PubMedCrossRefGoogle Scholar
  3. 3.
    Hara M, Takeuchi K (1979) Pharmacokinetic analysis of ACNU in brain tumors. Brain and Nerve 31:1279–1289 (in Japanese)Google Scholar
  4. 4.
    Kaneko S, Abe H, Aida T, Tsuru M, Kodama T, Kobayashi H (1980) Experimental study of immunochemotherapy of brain tumors—experimental brain tumor model and immunochemotherapy by a combination of PSK and ACNU. Neurol Med Chir (Tokyo) 20:997–1005 (in Japanese)CrossRefGoogle Scholar
  5. 5.
    Kitahara M, Katakura R, Mori T, Suzuki J, Sasaki T (1984) Combined effect of ACNU and 5-fluorouracil on spheroids of rat glioma cells. Neurol Med Chir (Tokyo) 24:747–757 (in Japanese)CrossRefGoogle Scholar
  6. 6.
    Levin VA, Hoffman W, Weinkam RJ (1978) Pharmacokinetics of BCNU in man: a preliminary study of 20 patients. Cancer Treat Rep 62:1305–1312PubMedGoogle Scholar
  7. 7.
    Mineura K, Mori T, Katakura R, Suzuki J, Sasaki T (1981) Therapeutic effects of l-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and radiation on the rat glioma. Neurol Surg (Tokyo) 9:257–265 (in Japanese)Google Scholar
  8. 8.
    Mori T, Mineura K, Katakura R (1979) Chemotherapy of malignant brain tumors by a water-soluble anti-tumor nitrosourea, ACNU. Neurol Med Chir (Tokyo) 19:1157–1171 (in Japanese)CrossRefGoogle Scholar
  9. 9.
    Rail DP, Zubrod CG (1962) Mechanism of drug absorption and excretion: passage of drugs in and out of the central nervous system. Ann Rev Pharmacol 2:109–128CrossRefGoogle Scholar
  10. 10.
    Schabel FM (1974) New experimental drug combination with potential clinical utility. Biochem Pharmacol (Suppl 2) 23:163–176Google Scholar
  11. 11.
    Schabel FM (1975) Synergism and antagonism among antitumor agents. In: Pharmacological basis of cancer chemotherapy. Williams and Wilkins, Baltimore, pp 595–623Google Scholar
  12. 12.
    Suzuki M, Hori K, Abe I, Saito S, Sato H (1981) A new approach to cancer chemotherapy: Selective enhancement of tumor blood flow with angiotensin II. J Nat Cancer Inst 67:663–669PubMedGoogle Scholar
  13. 13.
    Suzuki M, Hori K, Abe I, Saito S, Sato H (1984) Functional characterization of the microcirculation in tumors. Cancer Metastasis Rev 3:115–126PubMedCrossRefGoogle Scholar
  14. 14.
    Tanaka M, Nishigaki T, Nakajima E, Totsuka S, Nakamura K (1980) Distribution, excretion, and metabolism of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1 (2-chloro-ethyl)-l-nitrosourea (ACNU) in rats and mice after iv administration. Cancer Treat Rep 64:575–580PubMedGoogle Scholar

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© Springer-Verlag Tokyo 1988

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  • Y. Tsurumi

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