title: Celecoxib decreases Ki-67 proliferative index in active smokers.
abstract: OBJECTIVE
  This study evaluated the feasibility of cyclooxygenase-2 (COX-2) inhibition for lung cancer chemoprevention. We hypothesized that treatment with oral Celecoxib, a selective COX-2 inhibitor, would favorably alter the biomarkers of lung cancer risk as measured by the Ki-67 proliferative labeling index (Ki-67 LI).
  
  
  METHODS
  Twenty active heavy smokers were enrolled into a pilot study and treated with Celecoxib for 6 months. Bronchoscopies with bronchial biopsies were done before and after 6 months of Celecoxib treatment. H&E stain for histologic grading and immunohistochemical examination for Ki-67 LI, COX-2, and survivin were carried out on serially matched biopsy samples to determine responses to treatment.
  
  
  RESULTS
  Treatment with Celecoxib significantly reduced Ki-67 LI in smokers by 35% (P = 0.016), and increased the expression of nuclear survivin by 23% (P = 0.036) without significantly changing that of cytoplasmic survivin.
  
  
  CONCLUSIONS
  Our findings suggest that oral Celecoxib may be capable of modulating the proliferation indices and apoptotic balance in bronchial tissue of active smokers.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1690, USA. jmao@mednet.ucla.edu
authors.forename: Jenny T
authors.initials: JT
authors.lastname: Mao
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.forename: Bradley
authors.initials: B
authors.lastname: Adams
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roth
authors.forename: Lee
authors.initials: L
authors.lastname: Goodglick
authors.forename: Longsheng
authors.initials: L
authors.lastname: Hong
authors.forename: Marie
authors.initials: M
authors.lastname: Burdick
authors.forename: E Robert M
authors.initials: ER
authors.lastname: Strieter
authors.forename: Carmack
authors.initials: C
authors.lastname: Holmes
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
mesh_terms: D000368:Aged; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000187:drug effects; D008175:Lung Neoplasms / Q000517:prevention & control*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000187:drug effects; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000187:drug effects; D010865:Pilot Projects; D011720:Pyrazoles / Q000627:therapeutic use*; D012907:Smoking / Q000009:adverse effects*; D013449:Sulfonamides / Q000627:therapeutic use*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D052246:Cyclooxygenase 2 Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D000077022:Survivin; D051546:Cyclooxygenase 2; D000068579:Celecoxib