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:
- 金额:$ 12.5万
- 依托单位:
- 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:
- 关键词:Academic Medical CentersAfricanBindingBiopsyCancer EtiologyCessation of lifeDevelopmentDigestive System DisordersEnsureFreezingFundingGastric TissueGastritisGoalsHelicobacter InfectionsHelicobacter pyloriHelicobacter pylori induced gastric cancerImmune responseInfectionInterleukin-9Malignant NeoplasmsMentorsMolecularMolecular Epidemiology of CancerNucleotidesParaffin EmbeddingParentsPathogenesisPathogenicityPathologyPathway interactionsPopulationProcessResearchResearch ActivityResearch PersonnelResearch PriorityResearch Project GrantsRisk FactorsSamplingSignal TransductionStomachTrainingViolaZambiaanticancer researchcarcinogenesiscarcinogenicitycareer developmentgastric carcinogenesisinterestlow and middle-income countriesmalignant stomach neoplasmneglectnovelparent grantpathogenresponse
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
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)。这是我们正在进行的资助的补充
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),并将由范德比尔特大学医学中心的心理团队指导。总体目标
拟议的研究是为了增强Kayamba博士进行世界一流的高影响力研究的能力
同时定义了幽门螺杆菌相关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
作为研究重点的条款。幽门螺杆菌感染是GC的最重要危险因素,这是
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。在此补充中,我们将研究研究的相同分子
在父母的赠款中,但使用来自新型撒哈拉以南非洲人口的样本。拟议的研究
与父母研究的主题一致,即定义通过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复杂,尤其是白介素-9(IL-9)和
包含1(NOD1)信号传导的核苷酸结合和寡聚结构域。
我们假设,随着幽门螺杆菌诱导的胃病理学从非营养性胃炎进行
GC的各个阶段,NOD1的水平随着IL-9表达的相应增加而降低,并且
这些变化可以通过消除感染来逆转。那,在各种
致癌过程的阶段不仅可以为高度提供良好的培训和职业发展
有希望的ESLI,但也加强了父母研究的科学严谨性。在此补充中,AIM 1将
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
AIM 2将在成功之前和之后比较IL-9和NOD1激活的水平
根除幽门螺杆菌感染。
该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父母研究聘用的方法。我们有信心这
Menored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)
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:
- 影响因子:0
- 作者:Ding SZ;Olekhnovich IN;Cover TL;Peek RM Jr;Smith MF Jr;Goldberg JB
- 通讯作者:Goldberg JB
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:
- 影响因子:0
- 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
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:
- 影响因子:0
- 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:
- 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.
- DOI:
- 发表时间:1999-12
- 期刊:
- 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
- 通讯作者:R. Peek;M. Blaser;D. Mays;M. H. Forsyth;T. Cover;S. Song;U. Krishna;J. Pietenpol
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RICHARD M. PEEK其他文献
RICHARD M. PEEK的其他文献
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{{ truncateString('RICHARD M. PEEK', 18)}}的其他基金
Mechanisms that Regulate Helicobacter pylori-Induced beta-catenin Activation
调节幽门螺杆菌诱导的 β-连环蛋白激活的机制
- 批准号:
8413057 - 财政年份:2013
- 资助金额:
$ 12.5万 - 项目类别:
Role of Iron and B-Catenin Activation in Gastric Carcinogenesis
铁和 B-连环蛋白激活在胃癌发生中的作用
- 批准号:
9274160 - 财政年份:2009
- 资助金额:
$ 12.5万 - 项目类别:
H. Pylori-Induced Inflammation and Gastric Cancer
幽门螺杆菌引起的炎症和胃癌
- 批准号:
8011208 - 财政年份:2009
- 资助金额:
$ 12.5万 - 项目类别:
H. Pylori-Induced Inflammation and Gastric Cancer
幽门螺杆菌引起的炎症和胃癌
- 批准号:
7753610 - 财政年份:2009
- 资助金额:
$ 12.5万 - 项目类别:
H. pylori-Induced Inflammation and gastric cancer
幽门螺杆菌引起的炎症和胃癌
- 批准号:
9203563 - 财政年份:2009
- 资助金额:
$ 12.5万 - 项目类别:
H. Pylori-Induced Inflammation and Gastric Cancer
幽门螺杆菌引起的炎症和胃癌
- 批准号:
8212343 - 财政年份:2009
- 资助金额:
$ 12.5万 - 项目类别:
H. pylori-Induced Inflammation and gastric cancer
幽门螺杆菌引起的炎症和胃癌
- 批准号:
8821584 - 财政年份:2009
- 资助金额:
$ 12.5万 - 项目类别:
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