| Project/Area Number |
15380211
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Clinical veterinary science
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
FUJINAGA Toru Hokkaido Univ., Grad.School.of Vet.Med., Prof, 大学院・獣医学研究科, 教授 (50181376)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Masahiro Hokkaido Univ., Grad.School.of Vet.Med., Asso.Prof., 大学院・獣医学研究科, 助教授 (80260397)
廉澤 剛 北海道大学, 大学院・獣医学研究科, 講師 (70214418)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | BPD-MA / dog / laser beam / mouse model bearing with tumor / photodynamic therapy / photosensitizer / tumor / veterinary medicine / 蛍光色素 / マウス担癌モデル / イヌ / マウス胆癌モデル / BPD-HA / 扁平状皮癌 |
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| Research Abstract |
In this study, we used BPD-MA (benzoporphyrin derivative monoacid ring A) which is a second generation photosensitizer with a rapid body clearance and strong light absorption at a wavelength of approximately 690 nm ; this wavelength allows considerably high light penetration into the tissue. Basic and clinical studies on photodynamic therapy using BPD-MA for the treatment of animal tumor were performed.
In vitro, it was suggested that photosensitivity of cells induced by PDT was dependent on several factors. In vivo, antiangiogenic PDT using BPD-MA induced a significant tumor vascular damage and a superior antitumor effect comparing with cellular-targeting PDT. By considering the pharmacokinetic parameters of BPD-MA, antiangiogenic PDT using BPD-MA could be completed within a short time period and be performed repeatedly because BPD-MA can be rapidly cleared from the tissues, and hence, shows low accumulation. Therefore, PDT using BPD-MA is suggested to be an effective form of treatment
… More
for canine malignant solid tumors.
Finally, the efficacy of antiangiogenic PDT using BPD-MA in 19 dogs with head tumors was assesse. Each tumor was irradiated with 690-nm laser light at 15 minutes after initiating the intravenous infusion of 0.5 mg/kg BPD-MA. In cases that were followed-up for more than 1 year after PDT, the median survival time of 6 dogs with oral tumors was found to be 423 days (range, 300-743 days) and a 1-year survival rate was observed in 67% of the dogs. In 5 dogs with nasal cavity tumors, the values were 533 days (range, 129-694 days) and 60%, respectively. The computed tomography (CT) enhancement values before and after PDT were significantly different (p < 0.001) and were 54.3 ± 25.8 Hounsfield units (HU) (21 treatments in 15 dogs) and 5.5 ± 5.7 HU (18 treatments in 11 dogs). The mean CT enhancement value of the tumors in which 19 treatments were effective was 57.2 HU and that for tumors in which 2 treatments were ineffective was 27.5 HU. The major side effect was temporary edema around the treated area for 1 week after PDT ; however, it did not require any specific treatment. Moreover, antiangiogenic PDT using BPD-MA can be performed repeatedly because BPD-MA is rapidly cleared from the tissues and hence shows low accumulation. Antiangiogenic PDT might be a promising method for treating canine solid malignant tumors without causing any serious side effects. Angiographic CT might play a useful role in selecting antiangiogenic PDT cases and in determining the therapeutic effect after antiangiogenic PDT.
In clinical application study, it was thought that the light irradiation to the tumor must be finished at short times after the administration of BPD-MA because of the rapid decrease of the BPD-MA concentration in the blood. Conversely, antiangiogenic PDT using BPD-MA could be finished at short times and performed repeatedly because of BPD-MA rapid clearance and low accumulation in tissues.
It is concluded that antiangiogenic PDT was effectively able to treat locally solid tumors without any serious side effects. Less
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