title: Prevention of mouse lung tumors by combinations of chemopreventive agents using concurrent and sequential administration.
abstract: BACKGROUND
  Concurrent and sequential administration of combinations of budesonide, bexarotene, suberoylanilide hydroxamic acid (SAHA) and atorvastatin were evaluated in A/J mice for prevention of lung tumors initiated by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol, NNK).
  
  
  METHODS
  Individual drugs and their combinations were administered for 26 weeks after NNK initiation. For sequential administration, budesonide was given for 21 weeks followed by a second drug.
  
  
  RESULTS
  Alone, budesonide, bexarotene, and SAHA caused a significant decrease in total and large tumors at 21 and 26 weeks. Concurrent treatment with budesonide and bexarotene or SAHA caused a significantly greater decrease in total tumors and large tumors than either drug administered alone. Sequential administration of all combinations (except budesonide/atorvastatin) gave a significant reduction in total and large tumors. Budesonide followed by SAHA and SAHA with atorvastatin yielded a greater reduction in large tumors.
  
  
  CONCLUSIONS
  Combinations of drugs demonstrated a greater efficacy in preventing mouse lung tumors than did the individual agents.
authors.affiliation: College of Public Health, The Ohio State University, Columbus, OH 43210, U.S.A. casto.44@osu.edu
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Casto
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pereira
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D000077610:Bexarotene; D001835:Body Weight / Q000187:drug effects; D019819:Budesonide / Q000494:pharmacology / Q000627:therapeutic use; D018890:Chemoprevention; D005260:Female; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D051379:Mice; D013764:Tetrahydronaphthalenes / Q000494:pharmacology / Q000627:therapeutic use; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D013764:Tetrahydronaphthalenes; D019819:Budesonide; D000077337:Vorinostat; D000077610:Bexarotene