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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 110-115 |
| Number of pages | 6 |
| Journal | Annals of Otology, Rhinology and Laryngology |
| Volume | 124 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2015 |
Fingerprint
Keywords
- bevacizumab
- drug testing
- laryngeal papilloma
- larynx
- papilloma
- pulmonary papilloma
- recurrent respiratory papillomatosis
- xenograft
ASJC Scopus subject areas
- Otorhinolaryngology
- Medicine(all)
Cite this
Xenograft Model for Therapeutic Drug Testing in Recurrent Respiratory Papillomatosis. / Ahn, Julie; Bishop, Justin A.; Akpeng, Belinda; Pai, Sara I.; Best, Simon R.
In: Annals of Otology, Rhinology and Laryngology, Vol. 124, No. 2, 01.02.2015, p. 110-115.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Xenograft Model for Therapeutic Drug Testing in Recurrent Respiratory Papillomatosis
AU - Ahn, Julie
AU - Bishop, Justin A.
AU - Akpeng, Belinda
AU - Pai, Sara I.
AU - Best, Simon R
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - bevacizumab
KW - drug testing
KW - laryngeal papilloma
KW - larynx
KW - papilloma
KW - pulmonary papilloma
KW - recurrent respiratory papillomatosis
KW - xenograft
UR - http://www.scopus.com/inward/record.url?scp=84925286832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925286832&partnerID=8YFLogxK
U2 - 10.1177/0003489414546400
DO - 10.1177/0003489414546400
M3 - Article
C2 - 25124839
AN - SCOPUS:84925286832
VL - 124
SP - 110
EP - 115
JO - Annals of Otology, Rhinology and Laryngology
JF - Annals of Otology, Rhinology and Laryngology
SN - 0003-4894
IS - 2
ER -