title: Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.
abstract: OBJECTIVE
  Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options.
  
  
  METHODS
  A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse.
  
  
  RESULTS
  The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control.
  
  
  CONCLUSIONS
  We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis.
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Akpeng
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sara I
authors.initials: SI
authors.lastname: Pai
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, Maryland, USA sbest2@jhmi.edu.
authors.forename: Simon R A
authors.initials: SR
authors.lastname: Best
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D004353:Drug Evaluation, Preclinical / Q000379:methods; D052140:Human papillomavirus 11 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D023421:Models, Animal; D010212:Papilloma / Q000473:pathology* / Q000821:virology; D030361:Papillomavirus Infections / Q000188:drug therapy*; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D014134:Tracheal Neoplasms / Q000473:pathology* / Q000821:virology; D014183:Transplantation, Heterologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
keywords: bevacizumab; drug testing; laryngeal papilloma; larynx; papilloma; pulmonary papilloma; recurrent respiratory papillomatosis; xenograft