2000 Fiscal Year Final Research Report Summary
ANALYSIS OF CANCER GROWTH MECHANISM DUE TO SURGICAL STRESS
| Project/Area Number |
11470251
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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 | Tazuke Kofukai Medical Institute |
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Principal Investigator |
TAKABAYASHI Arimichi Tazuke Kofukai Medical Institute Associate Director, 医学研究所, 副所長 (00226911)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Hajime Institute for Virus Research, Kyoto University Associate Professor, ウイルス研究所, 助手 (70303914)
KAWAI Yasuhiro Tazuke Kofukai Medical Institute II Staff Scientist, 医学研究所・第2研究部, 研究員 (20311285)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Surgical stress / Thioredoxin / Redox regulation / Drug resistance / Biological response / Nitric oxide / Apoptosis |
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| Research Abstract |
1. TRX is over expressed in pancreatic cancers and plasma TRX levels were elevated in pancreatic cancer patients. CDDP resistant Hela cell line also over expressed TRX.(Nakamura, et al Caner Detect Prev.2000 ; 24(1) : 53-60)
2. In mice, elevated plasma TRX efficiently blocks lipopolysaccharide-induced chemotaxis, an innate immune mechanism that might be involved in the mechanism of cancer metastasis. (Nakamura, et al. Proc Natl Acad Sci U S A.2001 Feb 27 ; 98(5) : 2688-2693)
3. In 100 primary breast cancer cases, TRX positive cases were 89% in mutant p53 positive cases. CDDP treatment or irradiation augmented expression of TRX and p53 in MCF-7 cells. Confocal microscopy analysis showed that CDDP treatment induced translocation of TRX into nuclei. These results suggest the possible association of TRX with p53-dependent function including DNA repair in breast cancer. (Ueno, et al. Immunol Lett. 2000 Dec 1 ; 75(1) : 15-20)
4. The ΔΨm of the peripheral lymphocytes (PBL), especially natural ki
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ller cells significantly decreased after major surgery such as esophageal resection and liver resection. The decreased ΔΨm in the PBL correlates with the increased plasma noradrenaline level. Continuous stimuli with noradrenaline lead NK cells to undergo apoptosis.
5. Nitric oxide (NO) induced a decrease in the ΔΨm of the PBL in a dose-dependent fashion and also induced an increase in the levels of reactive oxygen species (ROS), which caused these cells to undergo apoptosis. Dual-color staining of the ΔΨm and lymphocyte surface markers demonstrated that CD3^-CD56^+ natural killer cells were responsive to NO.Trolox, a vitamin E analog, partially reversed the NO-induced decrease in the ΔΨm of the PBL.(Takabayashi, et al. Antioxid Redox Signal. 2000 winter ; 2(4) : 673-80)
6. Tumor DPD activity was found to correlate well with tumor DPD mRNA expression. Advanced gastric cancer patients who responded to preoperative chemotherapy had lower DPD mRNA levels. (Takabayashi, et al. Int J Oncol. 2000 Nov ; 17(5) : 889-95)
7. In the cases with the normal plasma TRX level, the plasma TRX level increased after major surgery and correlated with the decrease of the ΔΨm of the PBL. Less
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