| Project/Area Number |
16590746
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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 |
Respiratory organ internal medicine
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| Research Institution | Okayama University |
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Principal Investigator |
KIURA Katsuyuki Okayama University, Okayama Graduate School of Medicine, Dentistry and Pharmaceutica Sciences, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (10243502)
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| Co-Investigator(Kenkyū-buntansha) |
TBATA Masahiro Okayama University Hospital, Associate Professor, 医学部・歯学部附属病院, 助教授 (30243504)
AOE Motoi Okayama University Hospital, Assistant Prpfessor, 医学部・歯学部附属病院, 助手 (80260660)
YOSHINO Tadashi Okayama Graduate School of Medicine, Dentistry, and Pharmaceutica Sciences, Associate Professor, 大学院医歯薬学総合研究科, 教授 (70183704)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | AKT / MAPK / A / J mouse / NNK / cisplatin / ras / lung cancer / second malignancy |
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| Research Abstract |
The risks of secondary lung cancer in patients with early stage non-small and small cell lung cancers are estimated to be 1-2% and 2-10% per patient per year, respectively. Surprisingly, the incidence of second primary cancer in locally advanced non-small cell lung cancer at 10 years, following cisplatin-based chemotherapy with concurrent radiotherapy, increases to 61%. Those patients, on the road to being cured, cannot overlook the possibility of developing a second primary cancer. We developed a second primary lung cancer model using cisplatin as a carcinogen in A/J mice to screen for chemopreventive agents for a second malignancy. In the primary lung tumour model, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), benzo(a)pyrene (BaP), urethane induces specific K-ras mutations in codon 12, codon 13, and codon 61, respectively, in the A/J mice. In this study, we investigated the mechanisms of carcinogenicity by cisplatin in the A/J mice. In the cisplatin-induced tumours, we found no K-ras codon 12 mutation, which is the major mutation induced by NNK or BaP. K-ras gene mutations in codon 13 and codon 61 were found in one tumour (4%) and 5 tumours (17.8%), respectively. These findings suggest that cisplatin is partially related to K-ras codon 61 mutations, and that the mechanism of carcinogenicity by cisplatin is different from that by NNK or BaP
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