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ID 30286
フルテキストURL
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著者
Umeoka, Tatsuo Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
Kawashima, Takeshi Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
Kagawa, Shunsuke Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
Teraishi, Fuminori Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
Taki, Masaki Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
Nishizaki, Masahiko Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
Kyo, Satoru Department of Obstetrics and Gynecology, Kanazawa University School of Medicine
Nagai, Katsuyuki Oncolys BioPharma, Inc.
Urata, Yasuo Oncolys BioPharma, Inc.
Tanaka, Noriaki Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
Fujiwara, Toshiyoshi Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry
抄録
Currently available methods for detection of tumors in vivo such as X-ray, computed tomography, and ultrasonography are noninvasive and have been well studied; the images, however, are not specific for tumors. Direct optical imaging of tumor cells in vivo that can clearly distinguish them from surrounding normal tissues may be clinically useful. Here, we describe a new approach to visualizing tumors whose fluorescence can be detected using tumor-specific replication-competent adenovirus (OBP-301, Telomelysin) in combination with Ad-GFP, a replication-deficient adenovirus expressing green fluorescent protein (GFP). Human telomerase reverse transcriptase is the catalytic subunit of telomerase, which is highly active in cancer cells but quiescent in most normal somatic cells. We constructed an adenovirus 5 vector in which the human telomerase reverse transcriptase promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site and showed that OBP-301 replicated efficiently in human cancer cells, but not in normal cells such as human fibroblasts. When the human lung and colon cancer cell lines were infected with Ad-GFP at a low multiplicity of infection, GFP expression could not be detected under a fluorescence microscope; in the presence of OBP-301, however, Ad-GFP replicated in these tumor cells and showed strong green signals. In contrast, coinfection with OBP-301 and Ad-GFP did not show any signals in normal cells such as fibroblasts and vascular endothelial cells. We also found that established subcutaneous tumors could be visualized after intraturnoral injection of OBP-301 and Ad-GFP. A549 human lung tumors and SW620 human colon tumors transplanted into BALB/c nu/nu mice were intraturnorally injected with 8 X 10(5) plaque-forming units of Ad-GFP in combination with 8 X 106 plaque-forming units of OBP-301. Within 3 days of treatment, the fluorescence of the expressed GFP became visible by a three-chip color cooled charged-coupled device camera in these tumors, whereas intraturnoral injection of Ad-GFP alone could not induce GFP fluorescence. Moreover, intrathoracic administration of Ad-GFP and OBP-301 could visualize disseminated A549 tumor nodules in mice after intrathoracic implantation. Our results indicate that intratumoral or intrathoracic injection of Ad-GFP in combination with OBP-301 might be a useful diagnostic method that provides a foundation for future clinical application.
キーワード
GFP
adenovirus
telomerase
replication
gene therapy
備考
Published with permission from the copyright holder. This is the author's copy, as published in Cancer Research, September 2004, Volume 64, Issue 17, Pages 6259-6265.
Direct access to Thomson Web of Science record
Copyright © 2004 American Association for Cancer Research. All rights reserved.
発行日
2004-09-01
出版物タイトル
Cancer Research
64巻
17号
出版者
American Association for Cancer Research
開始ページ
6259
終了ページ
6265
ISSN
0008-5472
NCID
AA00598557
資料タイプ
学術雑誌論文
オフィシャル URL
http://cancerres.aacrjournals.org/content/64/17/6259
言語
English
OAI-PMH Set
岡山大学
著作権者
American Association for Cancer Research
論文のバージョン
author
査読
有り
PubMed ID
Web of Sience KeyUT
Submission Path
oncology/4