| Project/Area Number |
13470246
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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 |
General surgery
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| Research Institution | THE TAZUKEKOFUKAI MEDICAL RESEARCH INSTITUTE |
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Principal Investigator |
TAKABAYASHI Arimichi The Tazuke-Kofukai ,Medical Research Institute Associate Director, 医学研究所, 副所長 (00226911)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Hajime Kyoto University, Institute for Virus Research Associate Professor, ウイルス研究所, 助教授 (70303914)
SASADA Teturo The Tazuke-Kofukai, Medical Research Institute Chief Researcher, 医学研究所・第2研究部, 研究員 (70293967)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥9,600,000 (Direct Cost: ¥9,600,000)
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| Keywords | Surgical Stress / Mitochondrial Membrane Potential / Peripheral Blood Lymphocytes / Natural Killer Cell / Thioredxin / Chemotherapy / Drug Resistance / Surgical Stress / CD4^+CD25^+T cell / 腫瘍増殖 / 消化器癌 |
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| Research Abstract |
(1) There are accumulating evidences that surgical stresses cause impairment of systemic immune responses, which may promote susceptibility to infection as well as growth of remnant cancer cells in cancer patients. The decrease of mitochondria! membrane potential (Δψ_m) is an early event of apoptotic cell death. The Δψ_m in peripheral blood lymphocytes (PBL), especially in natural kilfer (NK) cell population, was reduced after major surgery and this reduction appeared to be proportional to the severity of the surgical procedures and reflected the impairment of cellular function. The Δψ_m in NK cells was also negatively correlated with the level of plasma noradrenaline after major surgery, suggesting that the reduction of Δψ_m in NK cells induced by surgical stresses may be, at least in some part, mediated by neuroendocrine system. Collectively, monitoring of Δψ_m in PBL after surgery may be one of the useful markers for estimating the magnitude of surgical stresses on the immune system.
(2) NOG18, a nitric oxide donor induced a decrease in the Δψ_m of the PBL in a dose-dependent fashion, which suggests that abundant NO at an inflammatory site may impair NK cell function. Trolox, a vitamin E analog, partially reversed the NO-induced decrease in the Δψ_m of the PBL.
(3) Thioredoxin (TRX) has various kinds of biological action as a redox regulator. The plasma levels of TRX increased after major surgery. The changes in the TRX levels tended to show an inverse relationship with the changes in the Δψ_m in PBL, suggesting that TRX may be a good parameter for estimating the extent of surgical stress.
(4) The function of retinoblastoma gene product and transcriptional factor E2F might relate with the mechanism of the acquisition of 5-FU resistance by human colon cancer cell line.
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