2001 Fiscal Year Final Research Report Summary
Tumor Specific Gene Therapy Using Mutant Herpes Simplex Virus for Bladder Cancer
| 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)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Bladder Neoplasm / Viral therapy / Mutant Virus / Targetting |
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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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[Publications] Ohigashi, T., Ueno, M., Nonaka, S., Nakanoma, T., Furukawa Y., Deguchi, N. and Murai, M.: "Tyrosine kinase inhibitors reduce bcl-2 expression and induce apoptosis in androgen-dependent cells"Am. J. Physiol. (Cell Physiol.). 278. C66-C72 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ueno, M., Ban, S, 0higashi, T., Nakanoma, T., Nonaka, S., Hirata, R., Iida, M. and Deguchi, N.: "Simultaneous production of granulocyte colony-stimulating factor and parathyroid hormone-related protein in bladder cancer"Int. J. Urol.. 7. 72-75 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Oyama, M., Yazaki, T., Ohigashi, T., Hoshi, M., Horiguchi, Y., Oya, M., Asakura, H., Nakashima, J., Tacnibana, M., Uyemura, K., Murai, M.: "Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms"Molecular Urol.. 4. 83-87 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakashima, J., Tachibana, M., Horiguchi, Y., Oya M., Ohigashi, T., Asakura, H. and Murai, M.: "Serum interleukin 6 as a prognostic factor in patients with prostate cancer"Clin. Cancer Res.. 6. 2702-2706 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Oyama, M., Ohigashi, T., Hoshi, M., Nakashima, J., Tachibana, M., Murai, M., Uyemura, K. and Yazaki, T.: "Intra-vesical and intravenous therapy of human bladder cancer by the herpes vector G207"Hum. Gene Ther.. 11. 1683-1693 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakashima, J, Ozu, C., Nishiyama, T., Oya, M., Ohigashi, T., Asakura, H., Tachibana, M. and Murai, M.: "Prognosis value of alkaline phosphatase flare in patients with metastatic prostate cancer treated with endocrine therapy"Urology. 56. 843-847 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Oyama, M., Ohigashi, T., Hoshi, M., Murai, M., Uyemura, K. and Yazaki, T.: "Oncolytic viral therapy for human prostate cancer, by conditionally replicating herpes simplex virus vector G207"Jpn. J. Cancer Res.. 91. 1339-1344 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Ueno, M., Nakashima, J., Ohigashi, T., Deguchi, N., Ban, S., Akita, M., Murai, M.: "Establishment of testicular carcinoma cell line producing a-fetoprotein"BJU Int.. 88. 661-621 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Ueno, M., Akita, M., Ban, S., Ohigashi, T., Yanagida, S., lida, M., Deguchi, N.: "Production of parathyroid hormone-related protein in two new cell lines of renal cell carcinoma"Int J Urol. 8. 549-556 (2001)
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「研究成果報告書概要(欧文)」より
