title: Tumor local chemohyperthermia using docetaxel-embedded magnetoliposomes: Interaction of chemotherapy and hyperthermia.
abstract: OBJECTIVE
  We have studied and reported the usefulness of tumor local chemohyperthermia at a low-grade temperature below 43°C with docetaxel-embedded magnetoliposome (DML) and an applied alternating current magnetic field. However, the mechanisms of this treatment and the dynamics of the injected docetaxel were not investigated in our previous study. Thus, we investigated the interaction of chemotherapy and hyperthermia in the treated tumor.
  
  
  METHODS
  Human MKN45 gastric cancer cells were implanted in the hind limbs of Balb-c/nu/nu mice. DML, magnetite-loaded liposome, and docetaxel were injected into the tumors with or without being exposed to an alternating current magnetic field. Docetaxel and tumor necrosis factor-α concentrations, the cell cycle, and cell death rates in the tumor were examined.
  
  
  RESULTS
  Docetaxel concentrations were significantly higher in the DML-injected group than in the docetaxel-injected group 3 days after injection. A G2/M peak was observed 1 day after treatment in the DML-injected and exposed group and the docetaxel-injected group, while it was observed 3 days after treatment in the DML-injected without heating group and the magnetite-loaded liposome group. The tumor cell death rate gradually increased in the DML-injected group, with or without being exposed, while it gradually decreased after its peak in other groups. The tumor necrosis factor-α concentration in the tumor treated with DML with heating remained at a high level on the 7th day after treatment, while it decreased after its peak in other groups.
  
  
  CONCLUSIONS
  The antitumor effect of this treatment derives from a combination of hyperthermia and chemotherapy locally in the tumor.
authors.affiliation: Department of Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. myoshida@m.ehime-u.ac.jp
authors.forename: Motohira
authors.initials: M
authors.lastname: Yoshida
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Maehara
authors.forename: Takashi
authors.initials: T
authors.lastname: Naohara
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Aono
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sugishita
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D006979:Hyperthermia, Induced; D015552:Injections, Intralesional; D008081:Liposomes; D008280:Magnetics; D058185:Magnetite Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D043823:Taxoids / Q000008:administration & dosage* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D058185:Magnetite Nanoparticles; D043823:Taxoids; D014409:Tumor Necrosis Factor-alpha; D000077143:Docetaxel