@article{ac2933a46056487385241e0d2435c282,
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-IL2Rgammanull (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. Conclusion: 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.",
keywords = "bevacizumab, drug testing, laryngeal papilloma, larynx, papilloma, pulmonary papilloma, recurrent respiratory papillomatosis, xenograft",
author = "Julie Ahn and Bishop, {Justin A.} and Belinda Akpeng and Pai, {Sara I.} and Best, {Simon R.A.}",
note = "Funding Information: This study revealed that bevacizumab treatment is able to elicit a significant therapeutic response in immunodeficient NSG mice with patient-derived papilloma. This finding and the stability of the human-derived papilloma through multiple xenograft passages direct attention to the importance of studying the pharmacodynamics of drugs in patient-originated in vivo tumors. We describe an animal model that replicates the molecular and histological characteristics of a human tracheal lesion and thus allows for personalized testing of therapeutic agents, which can then be clinically translatable to human trials. Authors{\textquoteright} Note This work was presented at the 94th annual meeting of the American Broncho-Esophagological Association, May 2014, Las Vegas, Nevada. This study was performed in accordance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals, the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the Animal Welfare Act (7 U.S.C. et seq.); the animal use protocol was approved by the Institutional Animal Care and Use Committee of Johns Hopkins Medical Institution. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. ",
year = "2015",
month = feb,
day = "1",
doi = "10.1177/0003489414546400",
language = "English (US)",
volume = "124",
pages = "110--115",
journal = "Annals of Otology, Rhinology and Laryngology",
issn = "0003-4894",
publisher = "Annals Publishing Company",
number = "2",
}