| Project/Area Number |
14370382
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Gifu University |
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Principal Investigator |
SUGIYAMA Yasuyuki Gifu University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90211309)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAO Narutoshi Gifu University, Graduate School of Medicine, Reseach Associate, 大学院・医学系研究科, 助手 (80334944)
TAKAHASHI Takao Gifu University, University Hospital, Reseach Associate, 医学部附属病院, 助手 (90332684)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Dendritic cell / Antigen presentation / Gastroenterological cancer / Cancer immunotherapy / Activated lymphocyte transfusion |
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| Research Abstract |
1. Stimulation of dendritic cells with tumor antigen before maturation facilitated both activation of lymphocytes and attainment of high cytotoxicity. When tumor necrosis factor(TNF)-α was added to the culture medium before maturation of dendritic cells, the population of CD83 positive mature dendritic cells increased, followed by effective induction of activated killer lymphocytes against autologous tumor cells.
2. Two kinds of tumor antigens were prepared for the pulse of dendritic cells, one was prepared by treating the tumor cells with 5-fluorourcil plus cisplatin(FP treatment), the other was by freezing and thawing tumor cells(FT treatment). Thereafter the number of subG1-phase cells in the tumor antigen were measured by flow cytometry histogram. In the case of tumor cells with wild-type p53 gene status, FP treatment induced higher number of subG1-phase cells compared with FT treatment. To the contrary, as to the tumor cells with either mutant-type or deficient-type p53 gene status
… More
, FT treatment induced higher number of subG1-phase cells compared with FP treatment. It was noteworthy that the cytotoxic activity of killer lymphocytes pulsed by mature dendritic cells, increased in proportion to the number of subG1-phase cells in the tumor antigen, which was captured by dendritic cells. These results indicated that tumor cells with wild-type p53 gene status could be better candidate for FP treatment, while tumor cells with either mutant-type or deficient-type p53 gene status for FT treatment.
3. In BALB/c mice model, the production of TNF-α, interferon(IFN)-γ, and interleukin (IL)-4 and IL-10 by splenocytes increased by pulse with colon 26 tumor antigen prepared by FT treatment. Alternatively, polysaccharide-K treatment significantly reduced the production of IL-4 and IL-10, while the production of TNF-α and IFN-γ was slightly promoted. The same result was observed when human peripheral blood nuclear cells was pulsed with human gastic cancer antigen prepared by FT treatment. Above results may provide evidence to support the idea that immunopotentiator such as polysaccharide-K, could be one of the feasible agents to induce more professional antigen presenting dendritic cells. Less
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