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

幽门螺杆菌（Helicobacter pylori, Hp）感染是人类胃内发生胃癌的重要因素。在用化学致癌物治疗的蒙古沙鼠（MG）中，Hp感染增强了腺性胃癌的发生，根除感染导致增强作用的减弱，特别是在相关炎症的早期阶段。高盐饮食加剧了Hp感染对胃癌的影响，这两个因素协同作用，促进了该动物模型中胃癌的发展。然而，细菌的影响更大。与晚期感染相比，早期感染显著增加mg患者的胃化学癌变。而异位增生腺（hpg），位于粘膜肌层下方的增生和扩张腺体，在该动物模型中经常与Hp感染单独发生，但它们在根除后明显消退，提示与严重胃炎有关，而不是恶性特征。综上所述，Hp不是胃癌发生的引发剂，而是胃癌发生的强促进剂，根除Hp并减少盐的摄入可以有效预防胃癌的发生。肠上皮化生（IM）一直被认为是胃癌发生的恶性前病变。然而，MG中发生的腺癌大部分是胃表型的腺癌（92%），这表明IM是一个无辜的旁观者。考虑NF-kB通路，主要通过CagE蛋白观察IkB的表达及其磷酸化。发现p-Catenin在包括MG在内的哺乳动物中高度保守。43例（2.1%）胃腺癌中有1例发生突变，伴有核积聚。在化学预防方面，用杏浓缩液治疗Hp感染的MG，可减轻炎症和癌变。

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.