title: Topical fluorouracil for actinic keratoses and photoaging: a clinical and molecular analysis.
abstract: OBJECTIVE
  To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses.
  
  
  METHODS
  Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation.
  
  
  METHODS
  Academic referral center.
  
  
  METHODS
  Twenty-one healthy volunteers, 56 to 85 years old, with actinic keratoses and photodamage. Interventions Twice-daily application of fluorouracil cream for 2 weeks and biopsies and clinical evaluation at baseline and periodically after treatment.
  
  
  METHODS
  Gene and protein expression of molecular effectors of epidermal injury, inflammation, and extracellular matrix remodeling 24 hours after fluorouracil treatment; clinical improvement measured by evaluators, photography, and patient questionnaires.
  
  
  RESULTS
  One day after the final fluorouracil treatment, gene expression of the effectors of epidermal injury (keratin 16), inflammation (interleukin 1beta), and extracellular matrix degradation (matrix metalloproteinases 1 and 3) was significantly increased. Types I and III procollagen messenger RNA were induced at week 4 (7-fold and 3-fold, respectively). Type I procollagen protein levels were increased 2-fold at week 24. Actinic keratoses and photoaging were statistically significantly improved. Most patients rated photoaging as improved and were willing to undergo the therapy again.
  
  
  CONCLUSIONS
  Topical fluorouracil causes epidermal injury, which stimulates wound healing and dermal remodeling resulting in improved appearance. The mechanism of topical fluorouracil in photoaged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photoaging.
authors.affiliation: Department of Dermatology, 1910 Taubman Center, University of Michigan Medical School, 1500 E Medical Center Dr, Ann Arbor, MI 48109-5314, USA. dsachs@med.umich.edu
authors.forename: Dana L
authors.initials: DL
authors.lastname: Sachs
authors.forename: Sewon
authors.initials: S
authors.lastname: Kang
authors.forename: Craig
authors.initials: C
authors.lastname: Hammerberg
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Helfrich
authors.forename: Darius
authors.initials: D
authors.lastname: Karimipour
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Orringer
authors.forename: Timothy
authors.initials: T
authors.lastname: Johnson
authors.forename: Ted A
authors.initials: TA
authors.lastname: Hamilton
authors.forename: Gary
authors.initials: G
authors.lastname: Fisher
authors.forename: John J
authors.initials: JJ
authors.lastname: Voorhees
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D055623:Keratosis, Actinic / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010781:Photography; D011336:Probability; D011446:Prospective Studies; D012333:RNA, Messenger / Q000187:drug effects; D018570:Risk Assessment; D012720:Severity of Illness Index; D015595:Skin Aging / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D012333:RNA, Messenger; D005472:Fluorouracil