| Project/Area Number |
13671294
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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 |
Digestive surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
KOUNO Hiroyuki Hamamatsu University School of Medicine, Dept. of Surgery II, Associate Professor, 医学部, 助教授 (00138033)
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| Co-Investigator(Kenkyū-buntansha) |
SA*ZUKA Yasuyuki University of Shizuoka, Pharmaceutical Science, Instructor, 薬学部, 助手 (90162403)
KAMIYA Kinji Hamamatsu University School of Medicine, University Hospital, Instructor, 医学部附属病院, 助手 (20324361)
TANAKA Tatsuo Hamamatsu University School of Medicine, University Hospital, Instructor, 医学部附属病院, 助手 (90273185)
藤瀬 裕 浜松医科大学, 医学部, 教授 (60004355)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Photfrin / PDT / liposome / gastric cancer / PEG / apoptosis / フォトフィリン / 血流量 |
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| Research Abstract |
Liposomal photofrin (LPF) was prepared with DMPC (100μmol), cholesterol (100μmol), DMPG (60μmol), and 30 mg of PF (10μmol) and PEG-LPF was prepared by polyethyleneglycol (PEG) modification of the surface of LPF, to enhance the therapeutic efficacy of photodynamic therapy (PDT). The entrapment rate of PF in both LPF and PEG-LPF was more than 80%, and both were stable for more than 3 months at room temperature. The human gastric cancer xenograft MT-2 was used in this study. At 8 h after *ection photofrin level in tumor tissue in the LPF group was significantly higher than that in the control group in which non-*osomal photfrin was injected, whereas the PF levels in PEG-LPF group was significantly higher at 24 and 48 h after injection than that in LPF group. The PF level in the liver were almost equal between PEG-LPF and control groups, although it was significantly higher in LPF group than that in the control group. Irradiation was performed with the Excimer Dye Laser at 8 h or 24 h after the injection. A significant reduction in the estimated tumor volume was observed in the LPF group compared with the control group, and the volume of necrotic tumor tissue and the apoptotic index were significantly higher in the LPF group at 8 h than in the PF group. A significant reduction in the estimated tumor volume and tumor blood flow were observed in the PEG-LPF group at 24 h compared with the LPF group, and the volume of necrotic tumor tissue and the apoptotic index were significantly higher in the PEG-LPF group at 24 h than in the LPF group. Repeated irradiation with PEG-LPF decreased tumor volume and increased survival rate significantly. In conclusion, the liposomalization of the photosensitizer increased the therapeutic effect of PDT and PEG modification of LPF enhanced vascular damage and increased apoptosis of the tumor. Repeated irradiation of PEG-LPF could eliminate the tumor completely, with a resulting improvement of survival rate.
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