| Project/Area Number |
15500345
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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 |
Medical systems
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| Research Institution | Nara Medical University |
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Principal Investigator |
NAKAMURA Shinobu Nara Medical University, Faculty of Medicine, Professor, 医学部, 教授 (20019946)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Shin-ichi Nara Medical University, Faculty of Medicine, Associate professor, 医学部, 助教授 (70209097)
KANNO Masatoshi Nara Medical University, Faculty of Medicine, Lecturer, 医学部, 講師 (30195185)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Ultrasound / Malignant tumor / Cell death / Cell proliferation / Anti-CD20 MoAb / Echo-contrast agent / Arsenic trioxide / 細胞膜透過性 / 亜砒酸 |
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| Research Abstract |
1.Objective :
To develop the new therapeutic strategy for malignant tumors using ultrasound in combination with low dose of anti-tumor agents.
2.Methods :
(1)Induction of cell death by ultrasonic exposure combined with anti-CD20 monoclonal antibody(MoAb) SU-DHL-4 cells expressing CD20 antigen on the cell membrane were employed. The cells were treated with low dose (0.1μl/ml) of anti-CD20 MoAb : rituximab, and exposed with ultrasound (0.25W or 0.5W, 1MHz) for 20 seconds. Then the cells were incubated for 4 days. The proliferation activity and cell death were observed using flow cytometer sequentially. Furthemore, in order to analyze the mechanism of the treatment-induced cell death, concentration of Ca^<2+> in the cells was measured by digital image analysis using Fura-2 AM before and after treatment.
(2)Enhancement of ultrasound-induced cell death by echo-contrast agents
Levovist, Optison and a new agent : YM454, were used for enhancing cell death.
(3)Induction of cell death by low dose of anti-tumor agents
Various cell lines : HL-60, RL,K562, were treated with low dose of arsenic trioxide inducing cell death in leukemia cell line, and the mechanism of cell death was investigated.
3.Results and Comments
(1)Ultrasound combined with low dose of rituximab induced SU-DHL-4 cell death effectively, but not synergistically. However the proliferation activity of the cells after the treatment was suppressed significantly. The effect of the combination on tumor cell death is controversial. Further investigation is needed.
(2)Optison and YM454 enhanced cell lysis.
(3)Low dose arsenic trioxide induced apoptosis or oncosis depending on cell line.
Based on these results, new drug transport system will be developed.
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