| Project/Area Number |
11670556
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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 |
Gastroenterology
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| Research Institution | Chiba Cancer Center Research Institute |
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Principal Investigator |
KAWAMURA Kiyoko Chiba Cancer Center Research Institute, Division of Pathology, Research Fellow, 研究局・病理研究部, 主任研究員 (80260248)
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| Co-Investigator(Kenkyū-buntansha) |
SAISHO Hiromitsu Chiba University, School of Medicine, Professor, 医学部・内科学第一講座, 教授 (10092058)
TAGAWA Masatoshi Chiba Cancer Center Research Institute, Division of Pathology, Head, 研究局・病理研究部, 部長 (20171572)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Gene therapy / Cyotokine / Suicide gene / Transcriptional regulation / IL-12 / IL-15 / IL-18 / HSV-TK / レトロウイルス |
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| Research Abstract |
(1)We explored possibility of gene therapy for gastrointestinal tumors using cytokine genes that direct Th-1 type T cells. Three cytokine genes, IL-12, IL-15 and IL-18 gene, were cloned with a RT-PCR method. These cytokines induces the differentiation of immature T cells into Th-1 type cells or are secreted from Th-1 type cells. Human pancreatic and murine colon carcinoma cells were retrovirally transduced with the cytokine genes and were inoculated into immunocompetent or immunocompromized mice. Syngeneic mice rejected the cytokine producers and the mice developed tumor-specific, T cell-dependent protective immunity. Anti-tumor effects were also produced in immunocompromized hosts and a number of mechanisms such as anti-angiogenesis were involved in the anti-tumor activity. (2)We took another approarch to express a suicide gene specifically in tumor cells. The promoter region of the midkine gene, whose expression was predominantly observed in a number of gastrointestinal tissues but not in normal tissues, should enable the tumor-specific gene expression. In fact we detected the midkine gene expression in 14 out 15 hepatocellular specimens and identified a 0.5-kb promoter region within the regulatory sequences, which was responsible for preferential expression of a fused foreign gene in tumor cells. Human pancreatic carcinoma cells transduced with the promoter-linked herpes simplex virus-thymidine kinase gene became sensitive to ganciclovir compared with untransduced parent cells.
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