| Project/Area Number |
12213164
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
TATEMATSU Masae Aichi Cancer Center, Diviswn of Oncological Pathology, Chief, 腫瘍病理学部, 副所長兼部長 (70117836)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAMOTO Tetsuya Aichi Cancer Center, Division of Oncological Pathology, Section head, 腫瘍病理学部, 室長 (00236861)
IKEHARA Yuzuru Aichi Cancer Center, Division of Oncological Pathology, Researcher, 腫瘍病理学部, 研究員 (10311440)
MIZOSHITA Tsutomu Aichi Cancer Center, Division of Oncological Pathology, Researcher, 腫瘍病理学部, 研究員 (40347414)
稲田 健一 愛知県がんセンター, 腫瘍病理学部, 主任研究員 (70246081)
中西 速夫 愛知県がんセンター研究所, 腫瘍病理学部, 室長 (20207830)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥51,200,000 (Direct Cost: ¥51,200,000)
Fiscal Year 2004: ¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2003: ¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2002: ¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2001: ¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2000: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | Helicobacter pylori / Mongolian gerbil / promoter / salt / NF-kB / CagE / heterotopic proliferative gland / Intestinal metaplasia / IL-1β / β-catenin / スナネズミ腺胃発がんモデル / microdissection / mutation / H. pylori / 若年感染 / 炎症 / Updated Sydney System / 胃がん / スナネズミ腺胃発癌モデル / 可逆性病変 / スナネズミホモログ遺伝子 / 細胞分化マーカー |
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| Research Abstract |
Helicobacter pylori (Hp) infection is well accepted to be a very important factor for gastric carcinogenesis in die human stomach. In Mongolian gerbils (MG) treated with chemical carcinogens, Hp infection enhances glandular stomach carcinogenesis, and eradication of infection results in curtailment of enhancing effects, particularly at early stages of associated inflammation. A high-salt diet exacerbates the effects of Hp infection on gastric carcinogenesis, and these two factors act synergistically to promote the development of gastric cancers in this animal model. However, the bacterium exerts the greater effects. Early acquisition significantly increases gastric chemical carcinogenesis in MGs, as compared to later infection. While heterotopic proliferative glands (HPGs), hyperplastic and dilated glands localized beneath the muscularis mucosae, frequently develop with Hp infection alone in this animal model, they obviously regress on eradication, suggesting a relation to severe gastritis, rather than a malignant character. In conclusion, Hp is not an initiator, but rather a strong promoter of gastric carcinogenesis, whose eradication, together with reduction in salt intake, might effectively prevent gastric cancer development. Intestinal metaplasia (IM) has been considered to be premalignant condition in stomach carcinogenesis. However, adenocarcinomas developed in MG consisted most of those containing gastric phenotype (92%), suggesting IM rather an innocent bystander. Considering NF-kB pathway, expression of IkB and its phosphorylation was observed especially through CagE protein. p-Catenin was found to be highly conserved among mammals including MG. It is mutated at one of 43 cases (2.1%) of stomach adenocarcinomas with its nuclear accumulation. For the chemopreventive approach, concentrate of Japanese apricot was administered to MG with Hp infection and showed alleviation of inflammation and carcinogenesis.
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