Pritchard D M, Przemeck S M C
Department of Medicine, University of Liverpool, Liverpool, UK.
Aliment Pharmacol Ther. 2004 Apr 15;19(8):841-59. doi: 10.1111/j.1365-2036.2004.01911.x.
Gastric cancer is the second most common cause of cancer-related mortality world-wide. In most cases, it develops via the pre-malignant stages of atrophic gastritis, intestinal metaplasia and dysplasia, following Helicobacter pylori infection of susceptible individuals. A number of rodent models have recently provided valuable insights into the host, bacterial and environmental factors involved in gastric carcinogenesis. Wild-type rodents do not develop gastric adenocarcinoma, but early studies showed that the disease could be induced in several rodent species by chemical carcinogens. More recently, it has been demonstrated that gastric adenocarcinoma can be induced in Mongolian gerbils by H. pylori infection and in C57BL/6 mice by long-term H. felis infection. These models have allowed the importance of Helicobacter virulence genes, host factors, such as gender, strain and immune response, and environmental factors, such as dietary salt, to be explored. A number of transgenic mice with alterations in various pathways, including the immune response, gastrin biosynthesis, parietal cell development, growth factors and tumour suppressors, have also provided models of various stages of gastric carcinogenesis. One model that has proved to be particularly valuable is the hypergastrinaemic INS-GAS mouse, in which gastric carcinoma develops spontaneously in old animals, but the process is greatly accelerated by Helicobacter infection.
胃癌是全球癌症相关死亡的第二大常见原因。在大多数情况下，它是在易感个体感染幽门螺杆菌后，通过萎缩性胃炎、肠化生和发育异常等癌前阶段发展而来的。最近，一些啮齿动物模型为胃癌发生过程中涉及的宿主、细菌和环境因素提供了有价值的见解。野生型啮齿动物不会发生胃腺癌，但早期研究表明，化学致癌物可在几种啮齿动物物种中诱发这种疾病。最近，已经证明幽门螺杆菌感染可在蒙古沙鼠中诱发胃腺癌，长期感染猫螺杆菌可在C57BL/6小鼠中诱发胃腺癌。这些模型有助于探讨幽门螺杆菌毒力基因、宿主因素（如性别、品系和免疫反应）以及环境因素（如饮食中的盐）的重要性。一些在包括免疫反应、胃泌素生物合成、壁细胞发育、生长因子和肿瘤抑制因子等各种途径发生改变的转基因小鼠，也为胃癌发生的各个阶段提供了模型。一种已被证明特别有价值的模型是高胃泌素血症INS-GAS小鼠，在老年动物中会自发发生胃癌，但幽门螺杆菌感染会大大加速这一过程。
