title: Effect of combined therapy with the antiestrogen agent toremifene and local hyperthermia on breast cancer cells implanted in nude mice.
abstract: OBJECTIVE
  We evaluated the effects of combined treatment with the antiestrogen agent toremifene (TOR) and local hyperthermia (LHT) on the MCF-7 breast cancer cell line.
  
  
  METHODS
  BALB/c mice implanted with MCF-7 cells were divided into six treatment groups: a control group, a TOR30 group (given 30 mg/kg/day), a TOR120 group (given 120 mg/kg/day), an LHT group (43.5 degrees C), a TOR30 + LHT group, and a TOR120 + LHT group. The effects of the treatments on tumor cells, estrogen receptor (ER) expression, and cell cycle kinetics were measured after 21 days. We calculated the apoptotic index and vascular density inside the tumors and evaluated the efficacy of the transmigration of TOR into the tumors.
  
  
  RESULTS
  The antitumor effects were significantly greater in both combined therapy groups than in any of the single therapy groups. Estrogen receptor expression was weaker in the combined therapy groups than in the single therapy groups, and there were more G0/G1-phase cells and fewer S-phase cells in both combined therapy groups than in the single therapy groups. The apoptotic index was increased and the tumor vascular density was decreased in the combined therapy groups.
  
  
  CONCLUSIONS
  We attributed the effects of this combined therapy to the induction of apoptosis, the decrease in vascular density, and the increase and decrease in G0/G1-phase and S-phase cells, respectively, in the tumors.
authors.affiliation: Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kanaya
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Doihara
authors.forename: Kouji
authors.initials: K
authors.lastname: Shiroma
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ogasawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D003131:Combined Modality Therapy; D005260:Female; D005434:Flow Cytometry; D006979:Hyperthermia, Induced; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017312:Toremifene / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017312:Toremifene