title: Head and neck cancer radiosensitization by the novel poly(ADP-ribose) polymerase inhibitor GPI-15427.
abstract: BACKGROUND
  In this study, we tested the ability of a novel poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor, 10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]-anthracen-3-one (GPI-15427), to enhance the effect of radiotherapy in a xenograft model of human head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Human xenograft HNSCC tumors were established in female nude mice: animals were treated with orally administered GPI-15427 at varied doses prior to tumor irradiation. In vitro and in vivo apoptosis analyses and neutral single-cell gel electrophoresis (comet) assay were performed, with the "tail moment" calculated to evaluate DNA double-strand break damage.
  
  
  RESULTS
  Orally administered GPI-15427 given before radiation therapy significantly reduced tumor volume, and cells demonstrated significantly elevated mean tail moments (indicative of DNA damage) and enhanced apoptosis both in vitro and in vivo, compared with radiation-alone and control groups.
  
  
  CONCLUSIONS
  Use of the PARP-1 inhibitor GPI-15427 induced significant sensitization to radiotherapy, representing a promising new treatment in the management of HNSCC.
authors: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Khurram
authors: K
authors: Khan
authors: Koji
authors: K
authors: Araki
authors: Daiyou
authors: D
authors: Wang
authors: Guayan
authors: G
authors: Li
authors: Xin
authors: X
authors: Li
authors: Jie
authors: J
authors: Zhang
authors: Weizheng
authors: W
authors: Xu
authors: Randall K
authors: RK
authors: Hoover
authors: Susan
authors: S
authors: Lauter
authors: Bert
authors: B
authors: O'Malley
authors: Rena G
authors: RG
authors: Lapidus
authors: Daqing
authors: D
authors: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D020552:Comet Assay; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009930:Organic Chemicals / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D009930:Organic Chemicals; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents; C502278:GPI 15427