title: Modulation of radiation-induced oral mucositis (mouse) by selective inhibition of β1 integrin.
abstract: BACKGROUND
  Oral mucositis is a severe side effect of radio(chemo)therapy for head and neck tumors, for which β1 integrins have been proposed as potential therapeutic targets. The present study was initiated to determine the effect of selective inhibition of β1 integrin on the oral epithelial radiation response.
  
  
  METHODS
  Daily fractionated irradiation was given with 5 × 3 Gy/week over 1 or 2 weeks with/without the β1 integrin-inhibiting monoclonal antibody AIIB2 or an IgG control. Each protocol was terminated by graded test doses to generate full dose-effect curves for mucosal ulceration. The same technique was used for single dose irradiation.
  
  
  RESULTS
  Combined single dose irradiation plus AIIB2 resulted in a significant decrease of the ED50 compared to irradiation alone or control IgG. No effect of AIIB2 was found with fractionated irradiation over 1 week. With 2 weeks of fractionation, AIIB2 induced a significant increase in the ED50 for the terminating test irradiation when administered in week 2. The time course of the response was largely unaffected by β1 integrin inhibition.
  
  
  CONCLUSIONS
  A reduction of mucosal reactions by β1 integrin inhibition later in a course of fractionation was observed, i.e. when epithelial repopulation processes were active. Further mechanistic studies are required.
authors: Dept. of Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Germany.
authors: Maria
authors: M
authors: Albert
authors: Margret
authors: M
authors: Schmidt
authors: Nils
authors: N
authors: Cordes
authors: Wolfgang
authors: W
authors: Dörr
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D005455:Fluorescent Antibody Technique; D007274:Injections, Intraperitoneal; D019012:Integrin beta1 / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009061:Mouth Mucosa / Q000473:pathology / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D011897:Random Allocation; D012016:Reference Values; D013280:Stomatitis / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D019012:Integrin beta1