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.

总结

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