| Project/Area Number |
15591431
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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 |
Digestive surgery
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| Research Institution | Nara Medical University |
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Principal Investigator |
KO Saiho Nara Medical University, School of Medicine, Research associate, 医学部, 助手 (80305713)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Yoshiyuki Nara Medical University, School of Medicine, Professor, 医学部, 教授 (00142381)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Hepatocellular carcinoma / Bone marrow transplantation / Mini-transplantation / Living-donor liver transplantation / Anti-tumor effect / Graft-versus-tumor effect / 生体肝移植 |
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| Research Abstract |
We established a bone marrow transplantation (BMT) model in mice. Preconditioning for BMT was performed with an anti-tumor agent, cyclophosphamide (CYP). BALB/c and C57BL/6 mice were used as recipients and donors. Donor-derived bone marrow cells were transplanted to the recipient after administration of CYP at a dose of 200mg/kg. Consequently, tumor-bearing mouse model was established with a BALB/c mouse-derived tumor cell line, colon 26 to evaluate graft-versus-tumor effect by BMT. Cells of colon 26 was injected subcutaneously to the recipient, and donor-derived bone marrow cells or splenocytes were transplanted alter CYP preconditioning. Allogeneic BMT exerted significant anti-tumor effect. However, many recipients died of systemic GVHD. Then we tried to develop new protocols to control GVHD in an allogeneic rat models in which serial blood monitoring of chimerism can be performed easily. A reduced dose of CYP (150mg/kg) was found to induce bone marrow chimerism without GVHD. Additionally transient use of FK506 inhibited GVHD even with a dose of 200mg/kg CYP. With this protocol donor-specific tolerance was established in a heart transplantation model and MLR. Because this protocol have anti-tumor effect and does not require chronic immunosuppression, it may be applied to liver transplantation for advanced hepatocellular carcinoma.
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