title: Telomerase-specific oncolytic adenovirus: antitumor effects on radiation-resistant head and neck squamous cell carcinoma cells.
abstract: BACKGROUND
  Radioresistance remains a critical issue in the use of radiotherapy for the treatment of head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy of combination treatment with OBP-301, a telomerase-specific replication-selective adenovirus, and radiotherapy in overcoming radioresistance by examining its effect on radiation-resistant HNSCC cells.
  
  
  METHODS
  Radiation-resistant HNSCC cells were treated with OBP-301 and radiation in vitro and in an orthotopic nude mouse model in vivo and synergism was assessed. Apoptosis and expression of MRN complex, which plays a key role in DNA repair machinery, were also analyzed.
  
  
  RESULTS
  Infection with OBP-301 was found to enhance the antitumor efficacy of radiation both in vitro and in vivo by inhibiting MRN complex expression and increasing apoptosis induction.
  
  
  CONCLUSIONS
  Combined OBP-301 and radiation therapy seems to overcome radioresistance in HNSCC cells by inhibiting DNA repair machinery, and may thus be a novel therapeutic strategy for treating HNSCC.
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hyakusoku
authors.forename: Chihiro
authors.initials: C
authors.lastname: Horii
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takahashi
authors.forename: Goshi
authors.initials: G
authors.lastname: Nishimura
authors.forename: Takahide
authors.initials: T
authors.lastname: Taguchi
authors.forename: Norio
authors.initials: N
authors.lastname: Kondo
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sakakibara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Urata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sano
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy / Q000628:therapy*; D004260:DNA Repair / Q000502:physiology / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009360:Neoplastic Cells, Circulating; D050130:Oncolytic Virotherapy / Q000379:methods*; D011839:Radiation, Ionizing; D011879:Radiotherapy Dosage; D000077195:Squamous Cell Carcinoma of Head and Neck; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D019098:Telomerase
keywords: OBP-301; head and neck squamous cell carcinoma; radiation sensitivity; telomerase; virotherapy