Project/Area Number |
14370543
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Otorhinolaryngology
|
Research Institution | Kobe University |
Principal Investigator |
NIBU Ken-ichi Kobe University, Graduate School of Medicine Department of Otolaryngology-Head and Neck Surgery, Professor, 大学院・医学系研究科, 教授 (20251283)
|
Co-Investigator(Kenkyū-buntansha) |
OTSUKI Naoki Kobe University, Hospital, Associate Professor, 医学部附属病院, 講師 (40343264)
志水 賢一郎 神戸大学, 医学部附属病院, 助手 (00335431)
遠藤 壮平 日本大学, 医学部, 講師 (80246876)
俣野 哲朗 東京大学, 大学院・医学系研究科, 助教授 (00270653)
|
Project Period (FY) |
2002 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥5,400,000 (Direct Cost: ¥5,400,000)
|
Keywords | head and neck cancer / gene therapy / adenoviral vector / COX-2 / adenoviral vector / head and neck cancer / repication-selective / gene therpay / oncolysis / 頭頚部癌 / 増殖型アデノウイルスベクター / CAR |
Research Abstract |
Objective : To teat the oncolytic activity of COX2-promoter based conditional replication-selective adenovirus vector for squamous cell carcinoma cells of head and neck. Subjects : A conditional replication-selective adenovirus vector in which the expression of Ela, required for viral replication, is controlled by the COX-2 promoter, Ad-COX2-Ela, was generated. Its oncolytic activity according to the levels of COX-2 and CAR (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 mRNA expression ratios of KB, H891, T891, T892, and L871 were 1.5, 60, 1, 14.6, and 1.3. The corresponding CAR mRNA expression ratios were 1, 1, 5, 4, and 3. In vitro assays showed significant growth suppression of cancer cell lines with strong expressions of COX-2. In addition, Ad-COX2-Ela showed significant growth suppression of COX-2 expressing tumors in vivo model. Cenclusions In this study, we demonstrated the possibility of oncolytic therapy using the COX-2 promoter based conditional replication-selective adenovirus for head dnd neck squamous cell carcinoma expressing COX-2.
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