Xenograft Model for Therapeutic Drug Testing in Recurrent Respiratory Papillomatosis
| Autor: | Justin A. Bishop, Julie Ahn, Sara I. Pai, Simon R. Best, Belinda Akpeng |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Larynx
Drug medicine.medical_specialty Pathology Bevacizumab media_common.quotation_subject Transplantation Heterologous Drug Evaluation Preclinical Angiogenesis Inhibitors Papillomatosis Antibodies Monoclonal Humanized Mice Mice Inbred NOD medicine Animals Humans Effective treatment Respiratory Tract Infections media_common Papilloma Human papillomavirus 11 business.industry Papillomavirus Infections General Medicine medicine.disease Dermatology Treatment Outcome medicine.anatomical_structure Otorhinolaryngology Models Animal Tracheal Neoplasms Recurrent Respiratory Papillomatosis medicine.symptom business medicine.drug |
| Zdroj: | Annals of Otology, Rhinology & Laryngology. 124:110-115 |
| ISSN: | 1943-572X 0003-4894 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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