title: Combined 4-hydroxy-ifosfamide and vinorelbine treatment in established and primary human breast cell cultures.
abstract: BACKGROUND
  Vinorelbine and ifosfamide are active drugs against breast cancer, but the best treatment schedule has yet to be defined by preclinical or clinical studies. The antitumor activity of 4-hydroxy-ifosfamide (4-OH-IF), the active form of ifosfamide, and vinorelbine (VNB) and their interaction were investigated in two established breast cancer cell lines (MCF-7 and BRC-230) and in 10 primary breast cancer cultures.
  
  
  METHODS
  Cytotoxic activity was evaluated by a highly efficient clonogenic assay (HECA). The median-effect principle was applied to evaluate synergistic and antagonistic interactions and the corresponding combination index values were calculated. Cell cycle perturbations were analysed by flow cytometry.
  
  
  RESULTS
  In MCF-7 and BRC-230 cell lines the sequence VNB for 4 hours followed by 4-OH-IF for 24 hours produced an antagonistic effect. Conversely, the inverse sequential scheme, 4-OH-IF-->VNB provided synergistic effects on both cell lines. The synergism was associated with a strong block in the G2-M phase. Synergistic activity of 4-OH-IF-->VNB sequence was confirmed in 7 of 10 primary breast cancer cultures.
  
  
  CONCLUSIONS
  In conclusion, the sequence 4-OH-IF-->VNB appeared to be the most effective scheme both in established cell lines and in primary breast cancer cultures.
authors.affiliation: Department of Medical Oncology, G. B. Morgagni-L. Pierantoni Hospital, Forli, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ricotti
authors.forename: F
authors.initials: F
authors.lastname: Barzanti
authors.forename: A
authors.initials: A
authors.lastname: Tesei
authors.forename: D
authors.initials: D
authors.lastname: Amadori
authors.forename: A
authors.initials: A
authors.lastname: Gasperi-Campani
authors.forename: G L
authors.initials: GL
authors.lastname: Frassineti
authors.forename: W
authors.initials: W
authors.lastname: Zoli
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine; D007069:Ifosfamide