| Project/Area Number |
18591741
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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 |
Urology
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| Research Institution | University of Toyama |
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Principal Investigator |
NOZAKI Tetsuo University of Toyama, Graduate School of Medicine and Pharmaceutical Sciences for Research, assistant researcher (40303218)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,210,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | ultrasound / gene therapy / Bladder cancer / endoscopy / microbubble |
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| Research Abstract |
We have previously reported that cell membrane modification by lidocaine or heat can enhance ultrasound mediated transfection (USMT) in vitro. We investigated whether such enhancement could be observed using the T24 human bladder cancer cell line in vivo.
For in vitro transfection T24 cells were sonicated with 1 MHz ultrasound at 3.6 W/cm (ISATA) for 20 seconds. For in vivo transfection T24 cells in the bladder were transabdominally sonicated with 1 MHz ultrasound at 0.78 W/cm (ISATA) for 60 seconds. Transfection efficiency was evaluated by the luciferase assay standardized with protein contents of the samples. Lidocaine or heat treatment of T24 cells during sonication enhanced luciferase expression significantly. T24 cells were successfully transfected in the bladder. In addition, USMT enhancements were also observed when sonicated with lidocaine or heat. These results suggest that USMT and its enhancement with lidocaine or heat can be applied for gene therapy in the bladder.
Sonodynamic therapy (SDT), a novel and promising cancer therapy that uses a combination of ultrasound and hematoporphyrin, can induce cell death. Our experiments indicated that the ultrasonically induced cell damage rate was increased with 200-microg/mL hematoporphyrin, whereas no cell damage was observed with hematoporphyrin alone.
The bladder is considered to be one of the most favorable organs for ultrasound mediated gene therapy and sonodynamic therapy, because the inside of the bladder can be accumulated aqueous solutions and easily accessible through the trans-urethral rout. The further development of this new field will need many improvements, however, the recent successes in this method have positioned ultrasound as a highly safe modality for gene transfer in the future.
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