胃癌是發生在胃部黏膜的癌症，為全世界中癌症死亡原因之一。而有研究發現，胃幽門螺旋桿菌 (Helicobacter pylori, H. pylori) 為最主要影響胃癌的關鍵因素，當受到感染後，會造成慢性胃發炎，導致癌化的發生，形成胃癌。根據許多研究指出，胃上皮發炎和癌化過程中，H. pylori感染扮演重要的角色。 肝癌衍生生長因子(Hepatoma-Derived Growth Factor；HDGF) 是近期一種被關注的致癌因子，其在許多癌症惡化過程中皆有參與。過去研究指出，過度表現HDGF會促使胃癌細胞增生，並造成不良之預後。HDGF表現量增加亦與胃癌晚期患者存活率降低以及淋巴轉移相關。本研究旨在確定HDGF缺乏對H. pylori發病機制的影響以及HDGF調節H. pylori誘導促炎反應的機制。H. pylori感染刺激胃上皮細胞中HDGF的上調和分泌，並且HDGF缺乏消除了H. pylori促進胃中的炎症反應。HDGF可能是H. pylori誘導的胃炎甚至癌發生的病理因素。

Gastric carcinoma occurs in the mucosa of the stomach and it is one of the main causes of cancer death worldwide. Helicobacter pylori (H. pylori) was a leading factor in the occurrence of gastric cancer. When gastric was infected, it would cause chronic stomach inflammation and finally resulted in the occurrence of cancerous, the formation of gastric cancer. According to many studies, they indicated that H. pylori infection played a key role in the process of gastric epithelial inflammation and carcinogenesis. Hepatoma-derived growth factor (HDGF) is a novel growth factor involved in malignant progression of various types of cancer. Previous studies indicated that HDGF overexpression would cause the proliferation of gastric cancer cells. Moreover, HDGF upregulation was also correlated with the shorter survival in late-stage gastric cancer patients as well as the lymphe node metastasis. This study aimed to identify the consequences of HDGF deficiency on H. pylori pathogenesis and the mechanism by which HDGF modulates H. pylori -induced proinflammatory response. H. pylori infection stimulates the upregulation and secretion of HDGF in gastric epithelial cells, and HDGF deficiency abrogates H. pylori-promoted inflammatory response in stomach. HDGF is maybe a pathological factor in H. pylori-induced gastritis, even carcinogenesis.

論文審定書 i
誌謝 ii
中文摘要 iii
Abstract iv
Contents v
Figures and Legends Index vi
Abbreviation viii
Introduction 1
Specific Aims 10
Materials and methods 11
Discussion 28
Figures and legends 32
Appendix 63
Reference 68

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