title: Combination effects of Ara-C and 5-fluorodeoxyuridine against leukemia cells in vitro and in mice.
abstract: BACKGROUND
  Ara-C (1-beta-D-arabinofuranosylcytosine) is widely used for treatment of human leukemia. However, due to emergence of resistance, new drug combinations need to be developed.
  
  
  METHODS
  We tested the combination of Ara-C with 5-FdUrd (5-fluorodeoxyuridine) in L1210 and P388D1 mouse leukemia cells in vitro and in vivo by growth inhibition and recovery assay in leukemia-bearing mice.
  
  
  RESULTS
  Simultaneous incubation of cells with Ara-C and 5-FdUrd yielded more than additive effects for most combinations in both cell lines; synergy was seen in P388D1 cells. P388D1 cells showed delayed growth after treatment with Ara-C or 5-FdUrd in a growth recovery assay. In animal studies, simultaneous subcutaneous administration of the compounds did not show any significant beneficial effects as compared with monotherapy. Intraperitoneal administration of both compounds, however, significantly prolonged the survival of P388D1 animals.
  
  
  CONCLUSIONS
  Depending on cell type and route of drug administration, the combination of Ara-C and 5-FdUrd might offer a promising additional treatment option for leukemia.
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Rauko
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bauer
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Horvath
authors.forename: Thomas
authors.initials: T
authors.lastname: Höchtl
authors.forename: Philipp
authors.initials: P
authors.lastname: Saiko
authors.forename: Doris
authors.initials: D
authors.lastname: Karl
authors.forename: Herbert
authors.initials: H
authors.lastname: Schott
authors.forename: Monika
authors.initials: M
authors.lastname: Fritzer-Szekeres
authors.forename: Ladislav
authors.initials: L
authors.lastname: Novotny
authors.forename: Thomas
authors.initials: T
authors.lastname: Szekeres
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D007941:Leukemia P388 / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
chemical_list: D005467:Floxuridine; D003561:Cytarabine