Skip to main content
SpringerLink
Log in

The effect of dexamethasone on the uptake of cisplatin in 9L glioma and the area of brain around tumor

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The negative influence of dexamethasone (Dex) on the uptake of cisplatin in brain tumors was investigated in rats bearing 9L glioma. Dex or saline was given intraperitoneally prior to intravenous administration of cisplatin 5 mg/kg. Total Platinum (Pt) concentration was quantified with atomic absorption spectroscopy (AAS) in tumor, brain around tumor (BAT), normal brain and plasma. In the second experiment DNA-adducts of cisplatin were determined in tumor and BAT by AAS. In tumor, there was no difference in the Pt concentration and in the DNA-adduct level between the two treatment groups. In BAT, the Pt level in the Dex group was 0.20 µg/g (SD = 0.10 µg/g), which was significantly lower than in the controls (0.53 µg/g (SD=0.21 µg/g); p < 0.001). In addition, the DNA-adduct level in BAT was 23% lower in the Dex treated rats (p=0.05). In normal brain the Pt concentration was 10-fold lower than in tumor tissue. Thus, Dex did not significantly limit the uptake of cisplatin in brain tumor nor did it influence the uptake in normal brain parenchyma. In contrast, in BAT that has a partially disrupted BBB, the concentrations of Pt and DNA-adduct formation were significantly decreased following pretreatment with Dex. The influence of Dex on limiting the effects of chemotherapy for brain tumors needs further study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Neuwelt EA, Barnett PA, Frenkel EP: Chemotherapeutic agent permeability to normal brain and delivery to avian sarcoma virus-induced brain tumors in the rodent: observation on problems of drug-delivery. Neurosurgery 14: 154–160, 1984

    Google Scholar 

  2. Donelli MG, Zucchetti M, D'Incalci M: Do anticancer agents reach the tumor target in the human brain? Cancer Chemother Pharmacol 30: 251–260, 1992

    Google Scholar 

  3. Gutin PH: Corticosteroid therapy in patients with cerebral tumors: benefits, mechanical problems, practicalities. Sem Oncol 2: 49–56, 1975

    Google Scholar 

  4. Reichman HR, Farrell CL, Del Maestro RF: Effects of steroids and nonsteroid anti-inflammatory agents on vascular permeability in a rat glioma model. J Neurosurg 65: 233–237, 1986

    Google Scholar 

  5. Yamada K, Ushio Y, Hayakawa T, Arita N, Yamada N, Mogami H: Effects of methylprednisolon on peritumoral brain edema: an autoradiographic study. J Neurosurg 59: 612–619, 1983

    Google Scholar 

  6. Nakagawa H, Groothuis DR, Owens ES, Fenstermacher JD, Patlak CS, Blasberg RG: Dexamethasone effects on [125I]Albumin distribution in experimental RG-2 gliomas and adjacent brain. J Cereb Blood Flow Metab 7: 687–700, 1987

    Google Scholar 

  7. Levin VA, Freeman-Dove M, Landahl HD: Permeability characteristics of brain adjacent to tumors in rats. Arch Neurol 32: 785–791, 1975

    Google Scholar 

  8. Ichimura K, Ohno K, Aoyagi M, Tamaki M, Suzuki R, Hirakawa K: Capillary permeability of experimental rat glioma and effects of intracarotid CDDP administration on tumor drug delivery. J Neuro-Oncol 16: 211–215, 1993

    Google Scholar 

  9. Stewart DJ, Leavens M, Maor M, Feun L, Luna M, Bonura J, Caprioli R, Loo TL, Benjamin RS: Human central nervous system distribution of cis-diamminedichloroplatinum and use as a radiosensitizer in malignant brain tumors. Cancer Res 42: 2474–2479, 1982

    Google Scholar 

  10. Nakagawa H, Fujita T, Izumoto S, Kubo S, Nakajima Y: Cisdiamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancer. J Neuro-Oncol 16: 61–67, 1993

    Google Scholar 

  11. Stewart DJ, Mikhael NZ, Nair RM, Kacew S, Montpetit V, Nanji A, Maroun JA, Howard K: Platinum concentrations in human autopsy tumor samples. Am J Clin Oncol 11: 152–158, 1988

    Google Scholar 

  12. Ma J, Verweij J, Planting AST, de Boer-Dennert M, van Ingen HE, van der Burg MEL, Stoter G, Schellens JHM: Current sample handling methods for measurements of platinum-DNA adducts in leucocytes in man lead to discrepant results in DNA adduct levels and DNA repair. Br J Cancer 71: 512–517, 1995

    Google Scholar 

  13. Weiszaecker M, Deen DF, Rosenblum ML, Hoshino T, Gutin PH, Barker M: The 9L rat brain tumor: Description and application of an animal model. J Neurol 224: 183–192, 1981

    Google Scholar 

  14. Ma J, Verweij J, Kolker HJ, Ingen van HE, Stoter G, Schellens JHM: Pharmacokinetic-dynamic relationship of cisplatin in vitro: simulation of an i.v. bolus and 3 h and 20 h infusion. Br J Cancer 69: 858–862, 1994

    Google Scholar 

  15. Grasso RJ, Johnson CE, Boler RK, Moore NA: Combined growth-inhibitory responses and ultrastructural alterations produced by 1,3-bis(2-chloroethyl)-1-nitrosourea and dexamethasone in rat glioma cell cultures. Cancer Res 37: 585–594, 1977

    Google Scholar 

  16. Wolff JEA, Guerin C, Laterra J, Bressler J, Indurti RR, Brem H, Goldstein GW: Dexamethasone reduces vascular density and plasminogen activator activity in 9L rat brain tumors. Brain Res 604: 79–85, 1993

    Google Scholar 

  17. Shapiro WR, Posner JB: Corticosteroid hormones – effects in an experimental brain tumor. Arch Neurol 30: 217–221, 1974

    Google Scholar 

  18. Tamargo RJ, Leong KW, Brem H: Growth inhibition of the 9L glioma using polymers to release heparin and cortison acetate. J Neuro-Oncol 9: 131–138, 1990

    Google Scholar 

  19. Neuwelt EA, Barnett PA, Bigner DD, Frenkel EP: Effects of adrenal cortical steroids and osmotic blood-brain barrier opening on methotrexate delivery to gliomas in the rodent: The factor of the blood-brain barrier. Proc Natl Acad Sci USA 79: 4420–4423, 1982 (Abstract)

    Google Scholar 

  20. Neuwelt EA, Horaczek A, Hagel MA: The effect of steroids on gentamicin delivery to brain after blood-brain-disruption. J Neurosurg 72: 123–126, 1990

    Google Scholar 

  21. Kourtopoulos H, Holm SE, Norrby SR: The influence F steroids on the penetration of antibiotics into brain tissue and brain abscesses. An experimental study in rats. J Antimicrobial Chemother 11: 245–249, 1983

    Google Scholar 

  22. Shapiro WR, Voorhies RM, Hiesinger EM, Sher PB, Basler GA, Lipschutz LE: Pharmacokinetics of tumor cell exposure to [14 C]methotrexate after intracarotid administration without and with hyperosmotic opening of the blood-brain barrier in rat brain tumors: A quantitative autoradiographic study. Cancer Res 48: 694–701, 1988

    Google Scholar 

  23. Shapiro WR, Hiesinger EM, Cooney GA, Basler GA, Lipschutz LE, Posner JB: Temporal effects of dexamethasone on blood-to-brain and blood-to-tumor transport of 14 Calpha-aminoisobutyric acid in rat C6 glioma. J Neuro-Oncol 8: 197–204, 1990

    Google Scholar 

  24. Warnke PC, Molnar P, Lapin GD, Kuruvilla A, Groothuis DR: The effect of dexamethasone on transcapillary transport in experimental brain tumors: II. canine brain tumors. J Neuro-Oncol 25: 29–38, 1995

    Google Scholar 

  25. Molnar P, Lapin GD, Groothuis DR: The effects of dexamethasone on experimental brain tumors: I. Transcapillary transport and blood flow in RG-2 rat gliomas. J Neuro-Oncol 25: 19–28, 1995

    Google Scholar 

  26. Jarden JO, Dhawan V, Moeller JR, Strother SC, Rottenberg DA: The time course of steroid action on blood-to-brain and blood-to-tumor transport of 82Rb: a position emission tomographic study. Ann Neurol 25: 239–245, 1989

    Google Scholar 

  27. Yeung WTI, Lee T-Y, Del Maestro RF, Kozak R, Bennett J, Brown T: Effects of steroids on iopamidol blood-brain transfer-constant and plasma volume in brain tumors measured with X-ray computed tomography. J Neuro-Oncol 18: 53–60, 1994

    Google Scholar 

  28. Watling CJ, MacDonald DR, Cairncross JG: Corticosteroid-induced magnetic resonance imaging changes in patients with recurrent malignant glioma. J Clin Oncol 12: 1886–1889, 1994

    Google Scholar 

  29. Groothuis DR, Fischer JM, Lapin G, Bigner DD, Vick NA: Permeability of different experimental brain tumor models to horseradish peroxidase, J Neuropathol Exp Neurol 41: 164–185, 1982

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuro-oncology, University Hospital Rotterdam, Rotterdam, The Netherlands

    C.S.M. Straathof (Dr. Daniel den Hoed Cancer Center and), M.J. van den Bent & Ch.J. Vecht

  2. Department of Medical Oncology, Dr. Daniel den Hoed Cancer Center and University Hospital Rotterdam, Rotterdam, The Netherlands

    C.S.M. Straathof (Dr. Daniel den Hoed Cancer Center and), J. Ma, G. Stoter & J.H.M. Schellens

  3. Department of Trials and Statistics, University Hospital Rotterdam, Rotterdam, The Netherlands

    P.I.M. Schmitz (Dr. Daniel den Hoed Cancer Center and)

  4. Department of Pathology, Dr. Daniel den Hoed Cancer Center, University Hospital Rotterdam, Rotterdam, The Netherlands

    J.M. Kros

Authors
  1. C.S.M. Straathof
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M.J. van den Bent
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P.I.M. Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J.M. Kros
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Stoter
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ch.J. Vecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J.H.M. Schellens
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Straathof, C., van den Bent, M., Ma, J. et al. The effect of dexamethasone on the uptake of cisplatin in 9L glioma and the area of brain around tumor. J Neurooncol 37, 1–8 (1998). https://doi.org/10.1023/A:1005835212246

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005835212246

Search

Navigation