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Photodynamic therapy and diagnosis of5-aminolevulinic acid for gastrointestinal cancer

5-氨基乙酰丙酸治疗消化道肿瘤的光动力治疗及诊断

基本信息

批准号：
16591309
负责人：
TANAKA Tatsuo
金额：
$ 2.24万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Photofrin is the most commonly used photosensitizer for photodynamic therapy (PDT). The major side effect of Photofrin is cutaneous photosensitivity. 5-aminolevulinic acid (5-ALA) is potentially exploitable for PDT and does not cause the side effect of prolonged normal skin photosensitization. We investigated the anti-tumor effects and safety of 5-ALA in patients with gastrointestinal cancer. 5-ALA(30 mg/kg) was administrated orally. At 4 h after administration, laser beam was irradiated to the tumor site endscopically using a directional quartz fiber (energy level : 100 J/cm^2). The antitumor effects of 5-ALA PDT according to patients were one PR and two SD. We investigated antitumor effects of 5-ALA PDT for human gastric cancer by animal model. Nude mice were implanted subcutaneously MT2 tumor (human gastric cancer line) and 5-ALA PDT was done. The rates of tumor shrinkage after PDT were 0.40 (5-ALA) and 0.16 (Photofrin). Judging from these results, anti-tumor effect of 5-ALA PDT is not satisfaction in the clinical and basic research.Next, we investigated antitumor effects of PDT using a fractionated dosing of mono-L-aspartyl chlorine e6 (NPe6) in a murine tumor. Eight nude mice with MT2 tumor were given 10 mg/kg NPe6 intravenously. Two hours later PDT was performed using a laser diode at a light dose of 100 J/ cm^2 and wavelength of 664 nm. Histological changes in tumors were examined 3 weeks after PDT. The CR rate was 87.5 % and the overall response rate was 100 %. The anti-tumor efficacy of NPe6 for human gastric cancer is very excellent correspond to it of Photofrin.

Photofrin是光动力学治疗（PDT）中最常用的光敏剂。Photofrin的主要副作用是皮肤光敏性。5-氨基乙酰丙酸（5-ALA）是潜在的可开发的PDT和不引起延长正常皮肤光敏化的副作用。我们研究了5-ALA在胃肠道肿瘤患者中的抗肿瘤作用和安全性。经口给予5-ALA（30 mg/kg）。给药后4 h，使用定向石英纤维（能量水平：100 J/cm ^2），经内窥镜向肿瘤部位照射激光束。5-ALA光动力疗法的抗肿瘤效果按患者分类为PR 1例，SD 2例。本实验通过动物模型研究了5-ALA光动力疗法对人胃癌的抗肿瘤作用。裸鼠皮下移植MT 2肿瘤（人胃癌细胞系），进行5-ALA PDT。PDT后肿瘤缩小率分别为0.40（5-ALA）和0.16（Photofrin）。从这些结果来看，5-ALA PDT的抗肿瘤作用在临床和基础研究中并不令人满意。接下来，我们使用分次剂量的单-L-乙酰氯e6（NPe 6）在小鼠肿瘤中研究PDT的抗肿瘤作用。8只移植有MT 2肿瘤的裸鼠静脉注射10 mg/kg NPe 6。两小时后，使用激光二极管以100 J/cm ^2的光剂量和664 nm的波长进行PDT。光动力治疗后3周观察肿瘤组织学变化。CR率87.5%，总有效率100%. NPe 6对人胃癌的抗肿瘤效果与Photofrin相当。