H. Pylori Relationship to Digestive Diseases and Cancer

幽门螺杆菌与消化系统疾病和癌症的关系

• 批准号: 10846242
• 负责人: RICHARD M. PEEK
• 金额: $ 12.5万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10846242
• 关键词: Academic Medical Centers; African; Binding; Biopsy; Cancer Etiology; Cessation of life; Development; Digestive System Disorders; Ensure; Freezing; Funding; Gastric Tissue; Gastritis; Goals; Helicobacter Infections; Helicobacter pylori; Helicobacter pylori induced gastric cancer; Immune response; Infection; Interleukin-9; Malignant Neoplasms; Mentors; Molecular; Molecular Epidemiology of Cancer; Nucleotides; Paraffin Embedding; Parents; Pathogenesis; Pathogenicity; Pathology; Pathway interactions; Population; Process; Research; Research Activity; Research Personnel; Research Priority; Research Project Grants; Risk Factors; Sampling; Signal Transduction; Stomach; Training; Viola; Zambia; anticancer research; carcinogenesis; carcinogenicity; career development; gastric carcinogenesis; interest; low and middle-income countries; malignant stomach neoplasm; neglect; novel; parent grant; pathogen; response

Summary This application is being submitted in response to the Notice of Special Interest (NOSI) NOT-CA-23-038 with a goal to support mentored cancer research career development for Dr. Violet Kayamba, an early-stage low- and middle-income country (LMIC) investigator (ESLI) from Zambia. It is a supplement to our ongoing funded study focused on Helicobacter pylori (H. pylori) pathogenesis and cancer (R01 CA077955, PI: Dr Richard Peek), and will be guided by a mentoring team at Vanderbilt University Medical Center. The overarching goal of the proposed research is to strengthen Dr Kayamba’s capacity to conduct world-class, high-impact research while defining molecular mechanisms underlying H. pylori-associated gastric carcinogenesis. Gastric cancer (GC) is one of the leading causes of cancer death in Zambia, but it is relatively neglected in terms of being a research priority. H. pylori infection is the single most important risk factor for GC, and this pathogen utilizes multiple strategies to manipulate the host immune response, ensuring persistence and ultimately triggering carcinogenesis. In this supplement, we will investigate the same molecules being studied in the parent grant, but using samples from a novel sub-Saharan African population. The proposed research is consistent with the theme of the parent study, i.e. to define molecular pathways manipulated by pathogenic H. pylori that drive immune responses with carcinogenic potential, particularly Interleukin-9 (IL-9) and Nucleotide-binding and oligomerization domain containing 1 (NOD1) signaling. We hypothesize that as H. pylori-induced gastric pathology progresses from non-atrophic gastritis through various stages to GC, levels of NOD1 decrease with a corresponding increase in IL-9 expression and that these changes can be reversed by eradicating the infection. Thus, immunostaining of gastric tissue at various stages of the carcinogenic process will not only provide great training and career development to a high promising ESLI, but also strengthen the scientific rigor of the parent study. In this supplement, Aim 1 will examine IL-9 and NOD1 activation levels in paraffin-embedded and frozen gastric biopsies at different steps along the Correa pathway. Aim 2 will compare levels of IL-9 and NOD1 activation before and after successful eradication of H. pylori infection. The research activities proposed in this supplement research project will be carried out by Dr. Kayamba and her team in Zambia, using approaches being employed by the parent study. We are confident that this mentored research will prepare her to become an independent investigator and leader in the field of GC molecular epidemiology.

概括 该申请是为了响应特殊利益通知（NOSI）非CA-23-038 一个支持指导的癌症研究职业发展的目标，紫罗兰（Violet Kayamba）博士， 来自赞比亚的中等收入国家（LMIC）调查员（ESLI）。 研究重点是幽门螺杆菌（H. Pylori）发病机理和癌症（R01 CA077955，PI：Richard博士 Peek），并将在范德比尔医学中心的指导团队中进行指导 拟议的研究是加强博士。 同时定义了幽门螺杆菌的胃癌发生的分子机制。 胃癌（GC）是赞比亚癌症死亡的主要原因之一，但在 作为研究宗教的条款。 病原体利用多种策略来操纵宿主免疫反应，确保持久性和 最终触发癌变。 在父母的赠款中，但使用了新型非洲人口的样本 与父母研究一致，即定义通过致病性操纵的分子途径 幽门螺杆菌以致癌潜力驱动免疫反应，尤其是白介素9（IL-9）和 核苷酸结合和寡聚结构域的贡献1（NOD1）信号传导。 我们假设随着幽门螺杆菌诱导的胃病理病理学从非养生胃炎throlth脚牙发展 到GC的各个阶段，NOD1的水平随着CorressPond的增加而降低IL-9表达，然后 这些变化可以通过消除各种组织来逆转 致癌过程的阶段不仅可以为晶粒和职业发展提供高度 有希望的ESLI，但也加强了父母研究的科学严谨性。 在不同步骤中检查石蜡包埋和冷冻胃活检中的IL-9和NOD1激活水平 沿着Correa途径2比较成功之前和之后的IL-9和NOD1的水平 根除幽门螺杆菌感染。 此补充研究项目中支撑的研究活动将由Kayamba博士和 她在赞比亚的团队使用父母研究的Apploaches。 与她的指导研究使她成为GC领域的独立调查员和领导者 分子流行病学。

项目成果

CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions.

• DOI: 10.1111/j.1469-0691.2009.02811.x
• 发表时间: 2010-04
• 期刊: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
• 作者: Sicinschi LA;Correa P;Peek RM;Camargo MC;Piazuelo MB;Romero-Gallo J;Hobbs SS;Krishna U;Delgado A;Mera R;Bravo LE;Schneider BG
• 通讯作者: Schneider BG

Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells.

• DOI: 10.1111/j.1574-695x.2008.00439.x
• 发表时间: 2008-08
• 期刊: FEMS immunology and medical microbiology
• 作者: Ding SZ;Olekhnovich IN;Cover TL;Peek RM Jr;Smith MF Jr;Goldberg JB
• 通讯作者: Goldberg JB

Endoscopy for Gastric Cancer Screening Is Cost Effective for Asian Americans in the United States.

• DOI: 10.1016/j.cgh.2020.07.031
• 发表时间: 2020-12
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 作者: Shah SC;Canakis A;Peek RM Jr;Saumoy M
• 通讯作者: Saumoy M

Quantitative detection of Helicobacter pylori gene expression in vivo and relationship to gastric pathology.

体内幽门螺杆菌基因表达的定量检测及其与胃病理的关系。

• DOI: 10.1128/iai.68.10.5488-5495.2000
• 发表时间: 2000
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: PeekJr,RM;vanDoorn,LJ;Donahue,JP;Tham,KT;Figueiredo,C;Blaser,MJ;Miller,GG
• 通讯作者: Miller,GG

Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle.

• 发表时间: 1999-12
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: R. Peek;M. Blaser;D. Mays;M. H. Forsyth;T. Cover;S. Song;U. Krishna;J. Pietenpol