| Project/Area Number |
17590291
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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 |
Human pathology
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| Research Institution | Hirosaki University |
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Principal Investigator |
KIJIMA Hiroshi Hirosaki University, School of Medicine, Professor, 医学部, 教授 (90204859)
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| Co-Investigator(Kenkyū-buntansha) |
KUSUMI Tomomi Hirosaki University, School of Medicine, Lecturer, 医学部, 講師 (90322932)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Cancer / Metastasis / Pancreas / Gene regulation |
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| Research Abstract |
Human pancreatic cancer is one of the most lethal malignancies because of rapid spread of the tumor, frequent incidence of metastasis and limitations of conventional therapy. Therefore, development of a new therapeutic strategy for pancreatic cancer such as molecular target therapy is one of the most pressing issues in current medicine. In this research projection, we designed ribozymes against K-ras gene and siRNA against claudin-1 gene, and examined growth suppression of human pancreatic cancer cells.
RESULTS in 2005
(1)Design of ribozymes. We designed anti-K-ras ribozyme against mutant K-ras gene transcripts, and generated a recombinant adenovirus to express the anti-K-ras ribozyme in the cells. However, we tried, but could not generate an adenovirus to express NF-kB gene transcripts.
(2)Transfection of anti-K-ras ribozyme into the pancreatic cancer cells. Human pancreatic cancer cells were infected with adenovirus/anti-K-ras ribozyme. The ribozyme suppressed the target K-ras gene expression.
RESULTS in 2006
(1)Efficacy of the transfected ribozyme in the pancreatic cancer cells. The transfected adenovirus/anti-K-ras ribozyme suppressed the target gene expression, and affected increase of apoptosis and inhibition of angiogenesis in the pancreatic cancer tissue, resulting in growth of the pancreatic cancer cells.
(2)Design of siRNA targeting claudin-1 gene. Claudin-1 plays a role in cell-to-cell attachment, and contributes cancer invasion. We designed anti-claudin-1 siRNA targeting claudin-1 gene transcripts. Anti-claudin-1 siRNA suppressed the target gene expression, as well as expression of matrix metalloproteinase-2 which is associated with cancer invasion in the stroma.
Our results indicated that high-efficiency adenovirus-mediated delivery of anti-K-ras ribozyme and/or anti-claudin-1 siRNA could become a molecular target therapy against human pancreatic cancer in the future.
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