title: Recombinant human granulocyte colony-stimulating factor enhanced cytotoxicity of Ara-C in Ara-C-resistant leukemic cells from a patient with biphenotypic leukemia in cell kinetic quiescence.
abstract: In vitro preincubation with recombinant granulocyte colony-stimulating factor(rhG-CSF, 100 ng/ml) enhanced the cytotoxicity of 1-beta-D-arabinofuranosylcytosine(Ara-C) in leukemic cells resistant to Ara-C from a patient with biphenotypic leukemia. Treatment of the cells with rhG-CSF resulted in a 17-fold increase in DNA synthesis, 4.6-fold increase in percentage of S-phase, and a two-fold increase in Ara-CTP formation. Maximal effect was observed at 72 h of incubation. Combination chemotherapy with rhG-CSF and Ara-C to the patient showed remarkable cytoreduction. These results indicate that recruitment of resistant leukemic cells in cell kinetic quiescence is inducible by rhG-CSF and that it is possible enhancement of the cytotoxicity to cell cycle-specific drugs such as Ara-C.
authors.affiliation: Department of Pediatrics, Mie University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Higashigawa
authors.forename: Y
authors.initials: Y
authors.lastname: Komada
authors.forename: N
authors.initials: N
authors.lastname: Washio
authors.forename: H
authors.initials: H
authors.lastname: Kuwabara
authors.forename: H
authors.initials: H
authors.lastname: Hori
authors.forename: M
authors.initials: M
authors.lastname: Ido
authors.forename: M
authors.initials: M
authors.lastname: Sakurai
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002648:Child; D003561:Cytarabine / Q000494:pharmacology*; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D014316:Tritium; D014407:Tumor Cells, Cultured
chemical_list: D011994:Recombinant Proteins; D003561:Cytarabine; D014316:Tritium; D016179:Granulocyte Colony-Stimulating Factor; D004247:DNA