Abstract
Since cytosine arabinoside (Ara-C) and etoposide (VP-16) are both important chemotherapeutic agents in the treatment of patients with acute leukemia, they are simultaneously applied in current treatmet schedules [1–3]. Cellular uptake of the prodrug Ara-C by nucleoside carrier-mediated facilitated diffusion [4, 5] and three step phosphorilation resulting in the active metabolite Ara-CTP [6] are the precondition of cytotoxic efficacy (Fig. 1). VP-16 inhibits cell growth primarily through its interaction with topoisomerase II [7]. By its ability to interact with membran lipids it inhibits this nucleosidcarrier [8, 9]. The inhibition of this carriermediated drug transport raises the possibility of an interaction between VP-16 and Ara-C.
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Refences
Ritter J (1989) Improved treatment results in the myelocytic sub types FAB M1-M4 of childhood AML by intensification of induction therapy: a report of the German AML-BFM-83 study. Proceedings of ASCO 8: 217
Reiter A (1991) Non-Hodgkin lymphomas (NHL) of childhood: treatment strategy and results in three multicenter trials of the BFM study group. Am J pediatr Hematol Oncol 13: 99
Crom W (1989) Targeted plasma concentration. A new therapeutic approach to relased AML in children. Haematol Bluttransfus 32: 82–87
White JC (1987) Membrane transport influences the rate of accumulation of cytosine arabinoside in human leukemia cells. J Clin Invest 79: 380–387
Wiley JS (1982) Cytosine influx and nucleosid transport sides in acute leukemia. J Clin Invest 69: 479–489
Kessel D (1967) Transport and phosporilation as factors in the antitumor action of cytosine arabinoside Science 156: 1240–41
Van Maanen JM (1988) Mechanism of action of the antitumor drug etoposide. J Natl Cancer Inst 80: 1526–31
Yalowich WC (1984) Analyses of the inhibitory effects of VP-16-213 and podophyllotoxin on thymidine transport and metabolism. Cancer Res 44: 984–989
White JC (1985) Inhibition of Ara-C transport and net accumulation by Teniposide and Etoposide in Ehrlich Ascites cells and human leukemia blasts. Cancer Res 45: 3070–75
Ehninger G (1991) Interaction of cytosine arabinoside uptake and cytosine triphosphate with various cytotoxic drugs. International Symposium Acute Leukemias II 1991 Meeting Abstract Nr 95
Boos J (1991) A single isocratic ion-pair highperformance- liquidchromatography determination of 1-β-arabinofuranosyl-cytosine-5-triphosphate for intracellular drug monitoring and in vitro incubation assays. J Pharm Biomed Anal 9: 47–52
Stewart F (1989) Altered protein binding of etoposide in patients with cancer. Clin Pharmacol Ther 45: 49–55
Stacher A (1984) Antineoplastische Chemotherapie In: Kümmerle, Klinische Pharmakologie S. 12
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© 1994 Springer-Verlag Berlin Heidelberg
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Menke, T., Pröbsting, B., Schultze-Westhoff, P., Ritter, J., Boos, J. (1994). Clinical Relevance of the Influence of Etoposide on Ara-CTP Formation in Leukemic Blast Cells. In: Büchner, T., Hiddemann, W., Wörmann, B., Schellong, G., Ritter, J. (eds) Acute Leukemias IV. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 36. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78350-0_46
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DOI: https://doi.org/10.1007/978-3-642-78350-0_46
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