title: KGFR as a possible therapeutic target in middle ear cholesteatoma.
abstract: CONCLUSIONS
  We demonstrated that repression of keratinocyte growth factor (KGF) receptor (KGFR) could be a potentially useful strategy in the conservative treatment of middle ear cholesteatoma.
  
  
  OBJECTIVE
  Recently, the use of a selective inhibitor of the KGFR, SU5402, in an in vitro experiment resulted in the inhibition of the differentiation and proliferation of epithelial cells through KGF secretion by fibroblasts isolated from the cholesteatoma. In this study, we investigated the effects of the KGFR inhibitor during middle ear cholesteatoma formation in vivo.
  
  
  METHODS
  Based on the role of KGF in the development of cholesteatoma, Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal of rats five times on every fourth day. Ears transfected with empty vector were used as controls. KGFR selective inhibitor (SU5402) or MEK inhibitor (PD0325901) was administered in the right ear of five rats after vector transfection. In the control, 2% DMSO in PBS was administered in the other ears after vector transfection.
  
  
  RESULTS
  The use of a selective KGFR inhibitor, SU5402, completely prevented middle ear cholesteatoma formation in the rats.
authors.affiliation: Department of Histology and Cell Biology.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamamoto-Fukuda
authors.forename: Naotaro
authors.initials: N
authors.lastname: Akiyama
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shibata
authors.forename: Haruo
authors.initials: H
authors.lastname: Takahashi
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikeda
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kohno
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
mesh_terms: D000818:Animals; D001549:Benzamides; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism / Q000517:prevention & control*; D004159:Diphenylamine / Q000031:analogs & derivatives; D004353:Drug Evaluation, Preclinical; D004424:Ear Canal / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005822:Genetic Vectors; D008297:Male; D011758:Pyrroles / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014162:Transfection
chemical_list: D001549:Benzamides; D011758:Pyrroles; C105686:SU 5402; C506614:mirdametinib; D004159:Diphenylamine; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: KGF; KGF receptor inhibitor; Keratinocyte growth factor; electroporation; in vivo model