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

基本信息

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
项目类别：
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

项目摘要

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.

概括本申请是为了响应特殊利益通知 (NOSI) NOT-CA-23-038 而提交的，其中包含目标是支持 Violet Kayamba 博士指导的癌症研究职业发展，她是一位早期低水平癌症患者来自赞比亚的中等收入国家 (LMIC) 调查员 (ESLI) 这是对我们持续资助的补充。研究重点是幽门螺杆菌 (H. pylori) 发病机制和癌症（R01 CA077955，PI：Richard 博士） Peek），并将由范德比尔特大学医学中心的指导团队指导。拟议研究的目的是加强 Kayamba 博士进行世界级、高影响力研究的能力同时定义幽门螺杆菌相关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，但在赞比亚相对被忽视。幽门螺杆菌感染是 GC 的一个最重要的危险因素，这是一个研究重点。病原体利用多种策略来操纵宿主免疫反应，确保持久性和最终引发致癌作用在本补充材料中，我们将研究正在研究的相同分子。拟议的研究使用了来自撒哈拉以南非洲新人口的样本。与母研究的主题一致，即定义致病性操纵的分子途径幽门螺杆菌驱动具有致癌潜力的免疫反应，特别是白细胞介素 9 (IL-9) 和含有 1 (NOD1) 信号传导的核苷酸结合和寡聚化结构域。我们研究发现，幽门螺杆菌引起的胃部病理学从非萎缩性胃炎发展到 GC 的各个阶段，NOD1 水平下降，IL-9 表达相应增加，并且这些变化可以通过根除感染来逆转，因此，对胃组织进行不同部位的免疫染色。致癌过程的各个阶段不仅会为高级人员提供良好的培训和职业发展 ESLI，但也有望加强母体研究的科学性在本补充中，目标 1 将。在不同步骤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，目标 2 将比较成功前后的 IL-9 和 NOD1 激活水平。根除幽门螺杆菌感染。本补充研究项目中提出的研究活动将由 Kayamba 博士和她在赞比亚的团队使用了家长研究所采用的方法，我们对此充满信心。指导性研究将使她成为 GC 领域的独立研究者和领导者分子流行病学。

项目成果

期刊论文数量（48）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The biological impact of Helicobacter pylori colonization.

幽门螺杆菌定植的生物学影响。

DOI：
发表时间：
2001-07
期刊：
影响因子：
0
作者：
Peek Jr; R M
通讯作者：
R M

Local and systemic immune and inflammatory responses to Helicobacter pylori strains.

对幽门螺杆菌菌株的局部和全身免疫和炎症反应。

DOI：
发表时间：
2005-12
期刊：
影响因子：
0
作者：
Bhat, Niranjan;Gaensbauer, James;Peek, Richard M;Bloch, Karen;Tham, Kyi;Blaser, Martin J;Perez
通讯作者：
Perez

Role of Helicobacter pylori CagA molecular variations in induction of host phenotypes with carcinogenic potential.

幽门螺杆菌 CagA 分子变异在诱导具有致癌潜力的宿主表型中的作用。

DOI：
发表时间：
2009-04-15
期刊：
影响因子：
0
作者：
Schneider, Natasha;Krishna, Uma;Romero;Israel, Dawn A;Piazuelo, M Blanca;Camargo, M Constanza;Sicinschi, Liviu A;Schneider, Barbara G;Correa, Pelayo;Peek Jr, Richard M
通讯作者：
Peek Jr, Richard M

Helicobacter pylori infection stimulates plasminogen activator inhibitor 1 production by gastric epithelial cells.

幽门螺杆菌感染刺激胃上皮细胞产生纤溶酶原激活剂抑制剂 1。

DOI：
发表时间：
2008-09
期刊：
影响因子：
3.1
作者：
Keates, A C;Tummala, S;Peek Jr, R M;Csizmadia, E;Kunzli, B;Becker, K;Correa, P;Romero;Piazuelo, M B;Sheth, S;Kelly, C P;Robson, S C;Keates, S
通讯作者：
Keates, S

Helicobacter pylori perturbs iron trafficking in the epithelium to grow on the cell surface.

幽门螺杆菌会扰乱上皮细胞表面铁的运输。