1998 Fiscal Year Final Research Report Summary
Anti-oncogene hammerhead ribozymes (RNA enzymes) specifically inhibit oncogens in a mice model system.
| Project/Area Number |
09670239
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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 |
Experimental pathology
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| Research Institution | Tokai University |
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Principal Investigator |
KIJIMA Hiroshi Tokai University School of Medicine Assistant Professor, 医学部, 講師 (90204859)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Hitoshi Tokai University School of Medicine Assistant Professor, 医学部, 講師 (20191273)
NAKAMURA Masato Tokai University School of Medicine Assistant Professor, 医学部, 講師 (00164335)
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| Project Period (FY) |
1997 – 1998
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| Keywords | ribozyme / RNA enzyme / gene modulation / pancreatic cancer / ras oncogene / mice model |
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| Research Abstract |
Pancreatic cancer is one on lethal human cancers, and development of its new therapeutic strategy is eagerly required today. Point mutation in the K-ras gene is observed at a high incidence in human pancreatic carcinomas. These alterations can be used as potential targets for specific ribozyme-mediated reversal of the malignant phenotype. We have demonstrated the efficacy of a hammerhead ribozyme directed against codon 12 of the activated K-ras gene in a Capan-1 human pancreatic carcinoma cell line. To develop this strategy into a therapeutic application, we designed a recombinant adenovirus encoding a gene cassette for the anti-K-ras ribozyme. By using this recombinant adenovirus in a mice model system, it was possible to accomplish efficient reversion of the malignant phenotype in human pancreatic tumors with K- ras gene mutation. The high efficiency adenoviral-mediated delivery of anti-oncogene ribozyme could emerge as a significant gene therapy strategy against human malignancies.
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[Publications] Ryuji Suto, Yoshiyuki Abe, MasatoNakamura, Yasuyuki Onishi, Masumi Yoshimura, Yoon Hwan Lee, Takashi Imanishi, Hitoshi Yamazaki, Hiroshi Kijima, Testuji Tokunaga, Yoshiro Oshika, Nobuyoshi Hiraoka, Norikazu Tamaoki, Hiroaki Fukuda, Yoshito Ueyama.: "Multidrug resistance mediated by overexpression of P-glycoprotein in human osteosarcoma in vivo." Int J Oncol. 12. 287-291 (1998)
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[Publications] Tetsuji Tokunaga, Yoshiro Oshika, Yoshiyuki Abe, Yuichi Ozeki, Sotaro Sadahiro, Hiroshi Kijima, Takashi Tsuchida, Hitoshi Yamazaki, Yoshito Ueyama, Norikazu Tamaoki, Masato Nakamura.: "Vascular endothelial growth factor (VFGF) mRNA isoform expression pattern is correlated with liver metastasisand poor prognosis in colon cancer." Br J Cancer. 77. 998-1002 (1998)
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