Factors regulating initiation, progression and submucosal invasion in gastric cancer.

胃癌是人类第二常见的死亡原因。它与幽门螺杆菌密切相关，幽门螺杆菌是一种常见的、容易传播的细菌，感染了世界上大约一半的人口。幽门螺杆菌(HP)是如何致癌的，为什么只有一小部分感染者会致癌，目前尚不清楚。然而，很明显，在宿主中产生强烈炎症反应并拥有完整的致病(疾病相关)基因的螺杆菌物种在长期感染后与癌症的发展比其他物种更强。我们最近开发了一种转基因小鼠，它在控制肠道炎症的某些方面的调控途径中存在微小缺陷。令人惊讶的是，这些小鼠中有100%迅速发展为胃癌，这与人类疾病有许多相似之处，包括炎症、胃壁结构丧失以及癌细胞渗透到下面的肌肉层。这个项目的目标是弄清楚Hp是否会引起正常胃细胞的类似变化，就像我们定义的胃癌小鼠模型一样。具体地说，我们将确定HP是否干扰了特定的炎症介质的工作方式，如果是的话，那么它对检测癌细胞和防止肿瘤生长的某些胃基因的影响方式。

Gastric cancer is the second most common cause of death in humans. It is strongly associated with Helicobacter pylori, a common and easily transmitted bacterium which infects about half the world's population. Exactly how Helicobacter pylori (HP) causes cancer, and why it does so in only a small percentage of those infected is unknown. It is clear however that Helicobacter species that produce a strong inflammatory response in the host and possess a full complement of pathogenic (disease-associated) genes are more strongly associated with cancer development after long-term infection than others. We have recently developed a genetically modified mouse which has a minor defect in a regulatory pathway which controls some aspects of gut inflammation. Surprisingly 100% of these mice rapidly develop gastric cancer which has many similarities with the human disease, including inflammation, loss of structure of the stomach lining and penetration of cancerous cells into the muscle layers below. The objectives of this project are to work out whether HP induces similar changes in normal stomach cells as occurs in our defined mouse model of gastric cancer. Specifically we will determine if HP disturbs the way a particular mediator of inflammation works, and if so the way this impacts on certain stomach genes which detect cancerous cells and prevent tumor growth.