Project/Area Number |
16300173
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Medical systems
|
Research Institution | SAPPORO MEDICAL UNIVERSITY |
Principal Investigator |
KOITO Kazumitsu SAPPORO MEDICAL UNIVERSITY, DEPARTMENT of RADIOLOGY, ASSISTANT PROFESSOR, 医学部, 講師 (90153460)
|
Co-Investigator(Kenkyū-buntansha) |
HAREYAMA Masato SAPPORO MEDICAL UNIVERSITY, PROFESSOR, 医学部, 教授 (10173098)
SAKATA Koich SAPPORO MEDICAL UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (10235153)
|
Project Period (FY) |
2004 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥7,000,000 (Direct Cost: ¥7,000,000)
|
Keywords | ultrasound / HIFU / microbubble / apoptosis / 抗腫瘍効果 / カスペース活性 |
Research Abstract |
[Analysis of apoptosis manifestation due to high intensity focused ultrasound (HIFU)] We investigated the anticancer efficacy of HIFU and the apoptosis activity confirmed by caspase to find other possible mechanisms of cell damage under several exposure conditions of HIFU. The subcutaneous KDH-8 tumors of WKAH/HKm rats were reduced by HIFU treatment, and these rats survived significantly longer without complications than the non-treatment rats. Apoptosis (Hoechst 33258 staining) was significantly more induced at the low power exposures (10Wx0.1sec-30Wx1.0sec) than at the high power exposures in cultured KDH-8 cells. Caspase 8 and 9/6 were significantly more elicited at low power exposure than at high exposure. Caspase 3 activity had two peaks, with one peak forming at around 10Wx0.4sec and the other at around 60Wx1.0sec. The activity of caspase 3, 8 and 9/6 was respectively increased 2.5-, 2.0- and 1.5-fold beyond the baseline activity of non-exposed cells in 10Wx0.4sec. These results indicated that the death receptor dependent pathway was more induced than the mitochondria dependent pathway. From these results, we concluded that the anticancer mechanism of HIFU was not only due to thermal coagulation, but also apoptosis mediated by several caspases. [Study of anticancer effect induced by HIFU and microbubbles] We compared the anticancer effect of HIFU with intravenous administration of microbubbles by using subcutaneous VX_2 tumor. The necrosis areas of the tumor adding Optison (4.8μm/ml) and Levovist (300mg/ml) were wider than control (without Microbubbles). Those results indicate that HIFU with microbubbles could obtain more effective tumor ablation safely.
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