title: Caffeine dose-dependently potentiates the antitumor effect of cisplatin on osteosarcomas.
abstract: BACKGROUND
  Caffeine-assisted chemotherapy has been used in the treatment of osteosarcomas. However, there is little in vivo evidence for this treatment, and thus we sought to verify the dose and effect of caffeine in combination with cisplatin in osteosarcoma-bearing rats.
  
  
  METHODS
  Seven-week-old male Fischer rats were transplanted with chemical carcinogen-induced osteosarcoma, selected lung metastatic lesions tumor block. The osteosarcoma-bearing rats were treated with saline, caffeine, cisplatin or cisplatin and caffeine.
  
  
  RESULTS
  The most growth inhibition was observed in the co-administration group. When three different dosing schedules of caffeine were given, the extent of tumor inhibition was closely correlated with the average plasma concentration of caffeine. The cisplatin concentration in the tumor was significantly increased when caffeine was co-administered.
  
  
  CONCLUSIONS
  This study confirms that a high concentration of caffeine (about 0.4 mM) is effective in enhancing the antitumor effects of cisplatin.
authors.affiliation: Department of Hospital Pharmacy, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Kawahara
authors.forename: Yuri
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Kotaro
authors.initials: K
authors.lastname: Takazawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Katsuro
authors.initials: K
authors.lastname: Tomita
authors.forename: Koichi
authors.initials: K
authors.lastname: Yokogawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D012516:Osteosarcoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: D002110:Caffeine; D002945:Cisplatin