Photodynamic therapy of intimal hyperplasia : Selective destruction by scavenger receptor mediated mechanism
| Project/Area Number |
09671255
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
NAGAE Tsuneyuki Tokyo Medical University, Department of Surgery, Staff, 医学部, 助手 (70217967)
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| Co-Investigator(Kenkyū-buntansha) |
AIZAWA Katsuo Tokyo Medical University, Department of Physiology, Professor, 医学部, 教授 (40074645)
ISHIMARU Shin Tokyo Medical University, Department of Surgery, Professor, 医学部, 教授 (50112785)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Photodynamic therapy / Intimal hyperplasia / Scavenger receptor / 光感受性物質 / スカベンジャー受容体 |
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| Research Abstract |
We have previously shown that maleylated-bovine serum albumin (mal-BSA) conjugated with a photosensitizer, chlorin e6, localizes higher in inner side of intimal hyperplasia (IH) and functions effectively as a photosensitizer for PDT. PDT as a treatment of IH using this scavenger-medicated delivery system shows effective in rat model of arterial wall injury. In this study, we tested the effect of a cylindrical fiber for intra-arterial radial irradiation using a second generation photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) in baloon injured arteries. A rabbit model was used to evaluate NPe6 uptake in abdominal and iliac (balloon injured) arteries. NPe6 was injected at the time of balloon injuries (5mg/kg). Three hours following injection, injured and non injured aorta (control) were retrieved and examined by fluorescence microscopy. Balloon injured arteries showed significantly higher fluorescence distribution in the media compared to non injured arteries. Laser irradiations were performed with a diode laser to emit 664 nm. Four days and 2 weeks after PDT, the arteries were excised and examined histologically. The results indicated that accellular arterial walls by cell depletion were observed radially at four days. Surrounding fibrovascular tissure and histiocytes ingrowth were limitted to penetrate to the acellular media and neointimal formation was suppressed at two and four weeks. Treatment of NPe6 sensitized, injured arteries with 664nm of light irradiation intraluminally is effective in limiting formation of intimal hyperplasia in this model of arterial wall injury. Future studies will explore the efficiency of mal-BSA photosensitizer conjugates using endovascular technique in vivo to develop clinically useful treatment for intimal hyperplasia.
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Report
(3 results)
Research Products
(3 results)
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[Publications] Nagae, T., Ishimaru, S., Aizawa, K., Uchimura, N., Yomo, T., Ebihara, Y.: "Photdynamic diagnosis and therapy using mono-L-aspartyl chlorin e6 in experimental atherosclerosis and injured arteries"J. Jpn. Coll. Angiol.. 39(2). 85-91 (1999)
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