| Project/Area Number |
12670217
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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 |
KAIJIMA Hiroshi School of Medicine, Department of Pathology, Tokai University, Assistant Professe, 医学部, 講師 (90204859)
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| Co-Investigator(Kenkyū-buntansha) |
UEYAMA Yoshito Schoool of Medicine, Departemnt of Pathology, Tokai University, Associate Profssor, 医学部, 助教授 (30072408)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | ras oncogene / ribozyme / RNA enzyme / Gene modulation / pancreas cencer / colon cancer / apoptosis / angiogenesis / ras癌遺子 / 癌遺伝子 / ras遺伝子 / ウイルスベクター / 腫瘍性増殖 / 遺伝子治療 |
|---|
| Research Abstract |
The ras oncogene, especially activated K-ras gene, is thought to play an important role in progression of human cancer. For specific gene modulation, we designed an anti-K-ras ribozyme (anti-K-ras Rz) against activated K-ras mRNA (codon 12, GGT to GTT) and generated a recombinant adenovirus to express the ribozyme (rAd/anti-K-ras Rz). The virus, rAd/anti-K-ras Rz, significantly suppressed activated K-ras gene expression, and inhibited growth of human pancreatic carcinoma cells associated with apoptosis and decreased bcl-2 expression. Also, in a mice model system, rAd/anti-K-ras Rz reversed the malignant phenotype in human pancreatic tumors with K-ras gene mutation. The results indicated that the rAd/anti-K-ras Rz specifically down-regulated the K-ras/bcl-2 pathway, and induced apoptotic changes in pancreatic cancer. Anti-K-ras Rz inhibited not only in vitro cell growth of human colon cancer, but also in vivo tumor growth in mice. Anti-K-ras Rz suppressed VEGF gene expression, and enhanced TSP1 gene expression. The results suggested that the ribozyme-mediated inactivation of the activated K-ras mRNA induced growth suppression, apoptosis and alteration of angiogenic factor expression.
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