Inhibition of epidermal growth factor receptor by erlotinib: wound healing of experimental tympanic membrane perforations.
OBJECTIVE
Inhibition of epidermal growth factor receptor (EGFR) may arrest wound healing of experimental tympanic membrane perforation in rats.


BACKGROUND
An animal model of chronic tympanic membrane perforation is needed for experiments on supporting wound healing of tympanic membrane perforations. The EGFR has been implicated in the regulation of wound healing.


METHODS
Thirty animals were administered 80 or 40 mg/kg/d EGFR tyrosine kinase inhibitor, or vehicle only for 5 days. The right-sided tympanic membrane of each animal was perforated at Day 2. Rat ears were inspected repeatedly to analyze the status of perforation. Tympanic membranes were examined histologically.


RESULTS
Unfortunately, five animals in the 80-mg/kg group and four in the 40-mg/kg group died before they reached their scheduled endpoint. Taking into account the small sample sizes, we observed a delayed closure of perforations in the 80-mg/kg group and differences in the histologic parameters between treated groups and control group.


CONCLUSIONS
The inhibition of EGFR by systemic application of erlotinib seems not to be suitable to create a chronic tympanic membrane perforation in rat.
Kaftan
Holger
H
Department of Otorhinolaryngology and Head and Neck Surgery, University of Greifswald, Germany. h.kaftan@web.de
Vogelgesang
Silke
S
Lempas
Kathrin
K
Hosemann
Werner
W
Herzog
Michael
M
D000818:Animals; D002908:Chronic Disease; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D018058:Tympanic Membrane Perforation / Q000188:drug therapy* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors