Helicobacter Host Interactions in Animal Models

动物模型中螺杆菌与宿主的相互作用

基本信息

批准号：
7612068
负责人：
MANUEL R AMIEVA
金额：
$ 28.32万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-01 至 2010-10-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7612068
关键词：
Adenocarcinoma Adipocytes Animal Model Animals Antibiotic Therapy Antibiotics B-Lymphocytes Bacteria Bacterial Genes Bacterial Proteins Benign Cancer Etiology Cellular biology Cessation of life Characteristics Clonality Complement Development Disease Duodenal Ulcer Epithelial Cells Failure Funding Gastric Adenocarcinoma Gastric lymphoma Gastritis Genes Genetic Genetic Structures Helicobacter Helicobacter Infections Helicobacter pylori Human Immune Immune response Immune system Immunity Individual Infection Inflammation Inflammatory Integration Host Factors Laboratories Lasers Lymphocyte Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Methodology Methods Microbe Microdissection Modification Molecular Biology Mus Nature Omentum Organism Outcome Peptic Ulcer Phosphorylation Play Research Residual state Role Smoke Stomach T-Lymphocyte Technology Time Ulcer Work bacterial genetics cancer diagnosis cell type cytokine functional genomics in vivo malignant stomach neoplasm microbial host mouse model mucosa-associated lymphoid tissue mucosa-associated lymphoid tissue lymphoma prevent prophylactic tool

项目摘要

DESCRIPTION (provided by applicant): Gastric cancer is now the third most common diagnosed cancer of humans. It is the second most common cause of cancer-related deaths worldwide, only surpassed by smoking-related lung cancer. Infection with the bacterium Helicobacter pylori is causally associated with gastritis and peptic ulcer, as well as gastric adenocarcinoma and gastric lymphoma of mucosa-associated lymphoid tissue (MALT). Remarkably, a single bacterial protein called CagA is thought to play the principal role in the transition from simple inflammation to ulcer disease and adenocarcinoma. However, we don't understand why the vast majority of individuals infected by H. pylori remain free of serious disease even though often infected for a lifetime. Our work focuses on understanding what host factors, together with the genetic make-up of the infecting H. pylori, contribute to whether there is a relatively benign host-microbial relationship or the more devastating outcome of duodenal ulcer or gastric cancer. Using contemporary tools of bacterial genetics, molecular biology, cell biology and functional genomics, our proposed research will try to answer the following questions. How does Helicobacter pylori breach the gastric barrier to establish itself and to persist in the host? How does the organism manipulate the host immune system to persist for a lifetime? What is the failure of a natural infection to afford any immunity at all? Why, after we eradicate the microbe by antibiotic treatment, is re-infection even more deleterious for the host? What are the underlying features of the malignant transformation that are so intimately associated with the phosphorylation of the bacterial protein CagA? Our experimental approach to these questions makes use of animal models of infection and the study of the host response to infection, as well as what modifications of the genetic structure of the bacterium have on infectivity and it's ability to induce malignancy.

描述（由申请人提供）：胃癌目前是人类第三大最常见的诊断癌症。它是全球第二大癌症相关死亡原因，仅次于吸烟相关的肺癌。幽门螺杆菌感染与胃炎和消化性溃疡以及胃腺癌和胃粘膜相关淋巴组织（MALT）淋巴瘤有因果关系。值得注意的是，一种名为 CagA 的细菌蛋白被认为在从简单炎症到溃疡病和腺癌的转变中发挥着主要作用。然而，我们不明白为什么绝大多数感染幽门螺杆菌的人尽管经常感染终生，但仍然没有患上严重疾病。我们的工作重点是了解哪些宿主因素以及感染性幽门螺杆菌的基因组成，决定了宿主与微生物之间是否存在相对良性的关系，或者十二指肠溃疡或胃癌的破坏性结果。利用细菌遗传学、分子生物学、细胞生物学和功能基因组学的当代工具，我们提出的研究将尝试回答以下问题。幽门螺杆菌如何突破胃屏障在宿主体内建立并持续存在？生物体如何操纵宿主免疫系统使其持续一生？自然感染根本无法提供任何免疫力是什么原因？为什么在我们通过抗生素治疗消灭微生物后，再次感染对宿主的危害更大？与细菌蛋白 CagA 磷酸化密切相关的恶性转化的基本特征是什么？我们解决这些问题的实验方法利用了感染的动物模型和宿主对感染的反应的研究，以及细菌遗传结构的改变对感染性及其诱发恶性肿瘤的能力的影响。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chronic Helicobacter pylori infection with Sydney strain 1 and a newly identified mouse-adapted strain (Sydney strain 2000) in C57BL/6 and BALB/c mice.

C57BL/6 和 BALB/c 小鼠中悉尼菌株 1 和新鉴定的小鼠适应菌株（悉尼菌株 2000）的慢性幽门螺杆菌感染。

DOI：
发表时间：
2004-08
期刊：
影响因子：
0
作者：
Thompson, Lucinda J;Danon, Stephen J;Wilson, John E;O'Rourke, Jani L;Salama, Nina R;Falkow, Stanley;Mitchell, Hazel;Lee, Adrian
通讯作者：
Lee, Adrian

The role of bacterial pathogens in cancer.

细菌病原体在癌症中的作用。