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Cyclooxygenase 2 Promoter–Based Replication-Selective Adenoviral Vector for Hypopharyngeal Cancer
Takahiro Nakagawa, MD;
Hironori Tanaka, MD, PhD;
Toshiro Shirakawa, MD, PhD;
Akinobu Gotoh, MD, PhD;
Yoshitake Hayashi, MD, PhD;
Katsuyuki Hamada, MD, PhD;
Mamoru Tsukuda, MD, PhD;
Ken-ichi Nibu, MD, PhD
Arch Otolaryngol Head Neck Surg. 2009;135(3):282-286.
Objective To explore the potential clinical application of the oncolytic activity of cyclooxygenase 2 (COX-2) promoter–based, conditional, replication-selective adenovirus vector for hypopharyngeal squamous cell carcinoma.
Design In vivo study and retrospective study.
Setting Kobe University Hospital, Kobe, Japan.
Subjects Expression of COX-2 in hypopharyngeal cancers treated at Kobe University Hospital was immunohistochemically investigated. In addition, nude mice bearing human hypopharyngeal cancer cells (H891) were used to analyze oncolytic activity of a conditional replication-selective adenovirus vector in which the expression of E1a, required for viral replication, is controlled by the COX-2 promoter Ad-COX2-E1a.
Results In vivo assays showed significant growth suppression in the murine hypopharyngeal model. Cyclooxygenase 2 expression was observed in 75.3% of hypopharyngeal cancers, especially in differentiated tumor cells (P = .001; r = 0.433).
Conclusion In this study, we demonstrated the potential of oncolytic therapy using the COX-2–promoter based, conditional, replication-selective adenovirus for COX-2–expressing hypopharyngeal squamous cell carcinomas.
Author Affiliations: Department of Otolaryngology–Head and Neck Surgery (Drs Nakagawa, Tanaka, and Nibu) and International Center for Medical Research and Treatment (Drs Shirakawa and Hayashi), Kobe University Graduate School of Medicine, Kobe, Japan; Laboratory of Cell and Gene Therapy, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo, Japan (Dr Gotoh); Department of Gynecology, Ehime University School of Medicine, Ehime, Japan (Dr Hamada); and Department of Otolaryngology–Head and Neck Surgery, Yokohama City University School of Medicine, Yokohama, Japan (Dr Tsukuda).
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