| Project/Area Number |
11671582
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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 | Keio University |
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Principal Investigator |
OHIGASHI Takashi Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (80185371)
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| Co-Investigator(Kenkyū-buntansha) |
NAKASHIMA Jun Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (10167546)
OYA Mototsugu Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (00213885)
YAZAKI Takahito Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (80200484)
MURAI Masaru Keio University, School of Medicine, Professor, 医学部, 教授 (90101956)
小山 政史 慶應義塾大学, 医学部, 助手 (70276351)
橘 政昭 慶應義塾大学, 医学部, 助教授 (70129526)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Bladder Neoplasm / Viral therapy / Mutant Virus / Targetting / ウイルス治療 / ヘルペスウイルス / 変異ウイルス |
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| Research Abstract |
G207 is a mutant herpes simplex virus (HSV) with a lacZ insertion in the ICP6 gene, which is essential for viral replication. Therefore, G207 is replication-competent only in highly proliferating cells such as cancer cells. In this study, we examined the antitumor activity of G207 to human bladder cancer cell lines in vitro and in vivo. Firstly, the susceptibility of human bladder cancer cell lines (KU19-19 and T24) to G207 was evaluated. The cytopathic effect appeared on day 1 post-infection in both of KU19-19 and T24, and the effective cytotoxicity with > 99% cell destruction was evident on day 6 (KU19-19) and day7 (T24). In order to evaluate the therapeutic potential of G207, we established a couple of in vivo models close to clinical situation. Intraneoplastic inoculation into subcutaneous (s.c.) tumor caused significant tumor growth inhibition. G207-treated tumors showed the extent of lacz expression. Intravesical inoculation of G207 also caused decreased tumor growth in an orthotopic human bladder cancer model. Furthermore, multiple intravenous inoculation markedly inhibited s.c. tumor growth/ Diffuse areas of lacZ expression were sporadically noted in the G207-treated tumors, while none was noted in liver, lung.
To create the bladder cancer-specific cytotoxic virus, we focused on Uroplakin 2 (UP2). The 3.6-kb DMA fragment including UP2 promoter was amplified from mouse genome library. When these segments were inoculated in the upstream of GFP expressing vector, the transfected mouse MBT-2 bladder cancer cells express GFP on the fluorescent microscope. The next step will be the completion of UP2 promotor-KP4 herpes virus.
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