title: Topical application of 5-fluorouracil on attic cholesteatoma results in downregulation of keratinocyte growth factor and reduction of proliferative activity.
abstract: To investigate the cell-biological effect of topically applied 5-fluorouracil (5-FU) on middle ear cholesteatoma, 12 attic cholesteatomas were treated with topical application of 5-FU cream, two to five times with an interval of 2 weeks (5-FU group). The control group comprised 65 cholesteatoma that were not treated with 5-FU. All lesions were later excised surgically and processed for immunohistochemical analyses of Ki-67, keratinocyte growth factor (KGF) and its receptor (KGFR). 5-FU significantly reduced the expression of KGF, did not change KGFR expression, and significantly reduced the Ki-67 labeling index, relative to the control group. The effect of 5-FU on cholesteatoma seems to be mediated, at least in part, through downregulation of KGF in stromal cells and reduction of the proliferative activity of epithelial cells.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. tomomiYF@net.nagasaki-u.ac.jp
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamamoto-Fukuda
authors.forename: Mariko
authors.initials: M
authors.lastname: Terakado
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hishikawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.forename: Haruo
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D018424:Cholesteatoma, Middle Ear / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis / Q000187:drug effects; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D019394:Ki-67 Antigen; D005346:Fibroblast Growth Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor; D005472:Fluorouracil