title: Oncolytic Vaccinia virus and radiotherapy in head and neck cancer.
abstract: OBJECTIVE
  Oncolytic forms of attenuated Vaccinia virus are now in clinical development, assessing the compatibility of this novel treatment with radiotherapy may reveal exploitable synergistic relationships.
  
  
  METHODS
  In vitro analyses of cell killing, cell cycle effects and caspase activation were carried out on HN3, HN5, CAL27, Detroit, SIHN5B, and PJ41 cells. In vivo studies of the virus and X-radiation were performed on H&N xenografts in CD1 nude mice.
  
  
  RESULTS
  Cell killing in vitro was demonstrated to be dose- and time-dependent. Infection causes an increase in S-phase and sub-G1 cells. A dose dependent increase in active caspase-3 indicated induction of apoptosis. Xenografts injected with Vaccinia stabilised and frequently completely regressed. Combination with radiation generated additional cell death, induction of caspase activity and in vivo further improved long term regression rates.
  
  
  CONCLUSIONS
  These data support continued exploration of this therapy combination and indicates potential for clinical trials in head and neck cancer.
authors.affiliation: The Institute of Cancer Research, Divisions of Cancer Biology and Radiotherapy and Imaging, Targeted Therapy Team, London, UK. david.mansfield@icr.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Mansfield
authors.forename: T
authors.initials: T
authors.lastname: Pencavel
authors.forename: J N
authors.initials: JN
authors.lastname: Kyula
authors.forename: S
authors.initials: S
authors.lastname: Zaidi
authors.forename: V
authors.initials: V
authors.lastname: Roulstone
authors.forename: K
authors.initials: K
authors.lastname: Thway
authors.forename: L
authors.initials: L
authors.lastname: Karapanagiotou
authors.forename: A A
authors.initials: AA
authors.lastname: Khan
authors.forename: M
authors.initials: M
authors.lastname: McLaughlin
authors.forename: Y
authors.initials: Y
authors.lastname: Touchefeu
authors.forename: R
authors.initials: R
authors.lastname: Seth
authors.forename: A A
authors.initials: AA
authors.lastname: Melcher
authors.forename: R G
authors.initials: RG
authors.lastname: Vile
authors.forename: H S
authors.initials: HS
authors.lastname: Pandha
authors.forename: K J
authors.initials: KJ
authors.lastname: Harrington
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004789:Enzyme Activation; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D050130:Oncolytic Virotherapy; D014616:Vaccinia virus
chemical_list: D053148:Caspase 3; D053179:Caspase 7