title: Vitamin E analog, alpha-tocopherol ether-linked acetic acid analog, alone and in combination with celecoxib, reduces multiplicity of ultraviolet-induced skin cancers in mice.
abstract: The goals of this study were to determine whether alpha-tocopherol ether-linked acetic acid analog (alpha-TEA), a novel vitamin E analog, and celecoxib, alone or in combination, when administered as a late intervention can reduce the ultraviolet-induced nonmelanoma skin-tumor burden of established tumors, prevent additional tumors from developing, and prevent tumor recurrence once treatments are stopped. Hairless SKH-1 female mice were ultraviolet-irradiated for 24 weeks, divided into treatment groups so that each group had approximately 5.8 tumors/mouse, and then treated with 72 mug of liposome-formulated alpha-TEA by aerosol inhalation, 500 p.p.m. celecoxib in AIN-76 A diet, or a combination of alpha-TEA and celecoxib for 4 weeks. At the end of 4 weeks of treatment, each treatment group was subdivided, with one subgroup continuing to receive treatment and with treatment being stopped in the other. Skin-tumor development was monitored visually throughout the study and by histologic evaluation at the end. After 4 weeks of treatment, all treatments showed statistically significant reductions in tumor number when compared with controls. After termination of treatment, only alpha-TEA prevented a significant increase in tumor recurrence; however, continuous combination treatment resulted in the lowest total number of tumors. In conclusion alpha-TEA is an effective late-stage chemopreventive agent for nonmelanoma skin cancer that exhibits lasting benefits.
authors.affiliation: Section of Molecular Genetics and Microbiology, The University of Texas, Austin, TX 78712, USA.
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Riedel
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fischer
authors.forename: Bob G
authors.initials: BG
authors.lastname: Sanders
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kline
mesh_terms: D000085:Acetates / Q000737:chemistry; D000280:Administration, Inhalation; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D008081:Liposomes; D051379:Mice; D008812:Mice, Hairless; D009364:Neoplasm Recurrence, Local; D009381:Neoplasms, Radiation-Induced / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D011829:Radiation Dosage; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D024505:Tocopherols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000085:Acetates; D016861:Cyclooxygenase Inhibitors; D008081:Liposomes; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; C488288:2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid; D024505:Tocopherols