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A Replication-Selective Adenoviral Vector for Head and Neck Cancers
Hironori Tanaka, MD;
Toshiro Shirakawa, MD, PhD;
Zhujun Zhang, MD, PhD;
Katsuyuki Hamada, MD, PhD;
Akinobu Gotoh, MD, PhD;
Ken-ichi Nibu, MD, PhD
Arch Otolaryngol Head Neck Surg. 2005;131:630-634.
Objective To test the oncolytic activity of cyclo-oxygenase 2 (COX-2) promoterbased conditional replication-selective adenovirus vector for squamous cell carcinoma cells of the head and neck.
Design In vitro study.
Subjects None.
Interventions 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, was generated. Its oncolytic activity according to the levels of COX-2 and of Coxsackie and adenovirus receptor expression was tested in a series of human head and neck squamous cell carcinoma cell lines.
Results The respective COX-2 messenger RNA expression ratios of KB, H891, T891, T892, and L871 were 1.5, 60.0, 1.0, 14.6, and 1.3. The corresponding Coxsackie and adenovirus receptor messenger RNA expression ratios were 1, 1, 5, 3, and 1. In vitro assays showed significant growth suppression of cancer cell lines with strong expressions of COX-2.
Conclusion This study demonstrated the possibility of oncolytic therapy using the COX-2 promoterbased conditional replication-selective adenovirus for head and neck squamous cell carcinoma expressing COX-2.
Author Affiliations: Department of OtolaryngologyHead and Neck Surgery (Drs Tanaka and Nibu) and International Center for Medical Research and Treatment (Drs Shirakawa, Zhang, and Gotoh), Kobe University Graduate School of Medicine, Kobe, Japan; and Department of Gynecology, Ehime University School of Medicine, Ehime, Japan (Dr Hamada).
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ABSTRACT
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