title: Gene expression following exposure to celecoxib in humans: pathways of inflammation and carcinogenesis are activated in tumors but not normal tissues.
abstract: BACKGROUND
  The Cox-2 inhibitor, celecoxib (Pfizer Inc., N.Y., USA), is a promising chemopreventive agent [Arber et al.: N Engl J Med 2006;355:885-895; Bertagnolli et al.: N Engl J Med 2006;355:873-884]. This study aims to explore its mechanism by defining changes in gene expression between neoplastic and normal tissue samples before and after treatment.
  
  
  METHODS
  Patients with documented colorectal neoplasia in screening colonoscopy, destined to undergo surgical colectomy, were randomized for treatment with celecoxib (n = 11; 400 mg/day) or placebo (n = 3) for 30 days. Tissue samples were taken from the tumor and from normal adjacent mucosa during both colonoscopy and surgery. RNA was extracted and analyzed using Affymetrix Genechip®.
  
  
  RESULTS
  687 genes differentiated tumor samples before and after treatment, among which 310 genes did not show the same differential expression in the placebo group or normal samples. These genes were significantly related to pathways of cell cycle regulation and inflammation, and of note was the TGF-β pathway, which held a strong association with the list of genes formerly found to be associated with the colorectal cancer expression profile in microarray analyses, as summarized in a meta-analysis by Cardoso et al. [Biochim Biophys Acta 2007;1775:103-137].
  
  
  CONCLUSIONS
  Celecoxib selectively affects genes and pathways involved in inflammation and malignant transformation in tumor but not normal tissues, this may assist in the development of safer and more effective chemopreventive agents.
authors.affiliation: The Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Sagiv
authors.forename: Michal
authors.initials: M
authors.lastname: Sheffer
authors.forename: Diana
authors.initials: D
authors.lastname: Kazanov
authors.forename: Shiran
authors.initials: S
authors.lastname: Shapira
authors.forename: Inna
authors.initials: I
authors.lastname: Naumov
authors.forename: Sarah
authors.initials: S
authors.lastname: Kraus
authors.forename: Eytan
authors.initials: E
authors.lastname: Domany
authors.forename: Nadir
authors.initials: N
authors.lastname: Arber
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D003111:Colonic Polyps / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D046228:Microarray Analysis; D011720:Pyrazoles / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000032:analysis; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D012334:RNA, Neoplasm; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; D000068579:Celecoxib