Gene alterations during stomach carciro genesis in H. pyrori infected Mongolian gerbik

幽门螺杆菌感染蒙古沙鼠胃癌发生过程中的基因改变

• 批准号: 12213164
• 负责人: TATEMATSU Masae
• 金额: $ 32.77万
• 依托单位: Aichi Cancer Center
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12213164/
• 关键词: 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

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.

幽门螺杆菌（Helicobacter pylori，Hp）感染是胃癌发生的重要因素。在蒙古沙鼠（MG）与化学致癌剂治疗，Hp感染增强腺胃癌变，根除感染的结果在削减增强效果，特别是在早期阶段的相关炎症。高盐饮食加剧了Hp感染对胃癌发生的影响，这两个因素协同作用，以促进胃癌的发展，在这个动物模型。然而，细菌发挥更大的作用。早期收购显着增加胃化学致癌MG相比，后来的感染。虽然异位增殖腺（HPGs），粘膜肌层下的增生和扩张的腺体，经常发展与Hp感染单独在这个动物模型中，他们明显消退根除，这表明与严重胃炎，而不是恶性特征。总之，Hp不是胃癌发生的启动子，而是胃癌发生的强促进剂，根除Hp并减少盐的摄入，可能有效地预防胃癌的发生。肠上皮化生（IM）被认为是胃癌发生过程中的癌前状态。然而，腺癌的发展在MG包括那些包含胃表型（92%），而不是一个无辜的旁观者，这表明IM。考虑到NF-kB通路，尤其通过CagE蛋白观察到IkB的表达及其磷酸化。发现β-连环蛋白在包括MG在内的哺乳动物中高度保守。在43例胃腺癌中有1例（2.1%）发生突变，并伴有细胞核积聚。对于化学预防方法，日本杏浓缩物被给予MG与Hp感染，并表现出减轻炎症和致癌作用。

项目成果

Synergistic promoting effects of Helicobacter pylori infection and high-salt diet on gastric carcinogenesis in Mongolian gerbils.

• DOI: 10.1111/j.1349-7006.2002.tb01209.x
• 发表时间: 2002-10
• 期刊: Japanese journal of cancer research : Gann
• 作者: Nozaki K;Shimizu N;Inada K;Tsukamoto T;Inoue M;Kumagai T;Sugiyama A;Mizoshita T;Kaminishi M;Tatematsu M
• 通讯作者: Tatematsu M

Effect of early eradication on Helicobacter pylori-related gastric carcinogenesis in Mongolian gerbils

• DOI: 10.1111/j.1349-7006.2003.tb01426.x
• 发表时间: 2003-03-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Nozaki, K;Shimizu, N;Tatematsu, M
• 通讯作者: Tatematsu, M

Polymorphisms of two fucosyltransferase genes (Lewis and Secretor genes) involving type 1 Lewis antigens are associated with the presence of anti-Helicobacter pylori lgG antibody.

涉及 1 型 Lewis 抗原的两个岩藻糖基转移酶基因（Lewis 和 Secretor 基因）的多态性与抗幽门螺杆菌 IgG 抗体的存在相关。

• 发表时间: 2001
• 期刊: Cancer Epidemiol. Biomarkers Prev. 10
• 作者: Ikehara Y;Nishihara S;Yasutomi H;Kitamura T;Matsuo K;Shimizu N;Inada K;Kodera Y;Yamamura Y;Narimatsu H;Hamajima N;Tatematsu M
• 通讯作者: Tatematsu M

Yuasa, H., et al.: "A phenotypic shift from gastric-intestinal to solely intestinal cell types in intestinal metaplasia in rat stomach following treatment with X-rays"J. Toxicol. Pathol. 5. 85-93 (2002)

Yuasa, H., et al.：“X 射线治疗后大鼠胃肠化生的表型从胃肠细胞类型转变为单纯肠细胞类型”J.

Earlier Helicobacter pylori infection increases the risk for the N-methyl-N-nitrosourea-induced stomach carcinogenesis in Mongolian gerbils.

• DOI: 10.1111/j.1349-7006.2002.tb01237.x
• 发表时间: 2002-12
• 期刊: Japanese journal of cancer research : Gann
• 作者: Cao X;Tsukamoto T;Nozaki K;Tanaka H;Shimizu N;Kaminishi M;Kumagai T;Tatematsu M
• 通讯作者: Tatematsu M