The Role of the Microenvironment in Barrett's Esophagus

微环境在巴雷特食管中的作用

• 批准号: 10607819
• 负责人: Julian Abrams
• 金额: $ 44.2万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10607819
• 关键词: 3-Dimensional; Ablation; Antibiotics; Barrett Esophagus; Bile Acids; Bile Reflux; Breath Tests; Cells; Chronic; Clinic; Clinical Research; Cross-Sectional Studies; Dana-Farber Cancer Institute; Development; Disease; Epithelial; Esophageal Adenocarcinoma; Genomics; Germ-Free; Goals; Housing; Human; Immune; Inflammation; Interleukin-6; Intervention; Knowledge; Lead; Malignant Neoplasms; Microbe; Microbiology; Modeling; Mutation; Myeloid Cells; Organoids; Patients; Pennsylvania; Porifera; Regulatory T-Lymphocyte; Research; Role; Saliva; Site; TP53 gene; Testing; Transgenic Organisms; Universities; biomarker signature; capsule; esophageal carcinogenesis; experimental study; genetic signature; immune activation; innovation; metabolomics; microbiome; microbiome research; microbiota; minimally invasive; mouse model; novel; novel marker; predictive marker; programs; response; screening; surveillance strategy; translational applications; translational research program; tumor microenvironment; tumorigenic

PROJECT SUMMARY Barrett’s esophagus is an increasingly prevalent, preneoplastic disorder resulting from acid/bile reflux and chronic inflammation at the GE junction. The BETRNet Research Center 1 represents a translational research program from Columbia University, the University of Pennsylvania and the Mayo Clinic. The team, which has been highly productive, has been focused on the role of microbiota and the tumor microenvironment in the development and progression of Barrett’s esophagus and esophageal adenocarcinoma. The group also includes additional collaborative sites at MIT, the Dana Farber Cancer Institute and Munich Technical University, and utilizes heavily a Microbiome and Metabolomics Core at Penn-CHOP. Thus, the team comprises broad and unique expertise in mouse models, genomics, microbiology and clinical research. Our research program is built around the hypothesis that the inflammation-dependent tumor microenvironment, modulated by the GE junction microbiome, is critical for early progression of esophageal carcinogenesis. The proposal utilizes both the novel transgenic (L2-ILB) and innovative 3D organoid models, along with a cross-sectional study of 150 Barrett’s and non-Barrett’s patients. Project 1 studied the role of microbiota and myeloid cells in the L2-ILB mouse model of Barrett’s esophagus. This project incorporated germ-free housing, antibiotic eradication, colonization with defined flora, myeloid cell ablation and correlative human studies. Project 2 focused on the characterization of microenvironment drivers in BE, and included FACS/IHC analysis of CAFs and immune cells (MDSCs/Tregs) in BE patients, along with 3D organoids in culture, as well as defining the role of IL-6 in response to epithelial TP53 mutations and immune cell activation. Finally, Project 3 seeks to identify novel biomarkers and gene signatures related to the microbiome and microenvironment. The study analyzed bile acids, a product of microbes, and minimally invasive tests such as saliva/breath test/tethered capsule sponge to analyze microbes to develop screening/surveillance strategies. Overall, these projects will advance the science of the microbiome and microenvironment in BE that will hopefully lead to translational applications. For the extension period, we propose to continue and complete experiments and analyses related to the three Projects.

项目总结

项目成果

Update on ablation for Barrett's esophagus.

巴雷特食管消融的最新进展。

• DOI: 10.1007/s11894-013-0368-7
• 发表时间: 2014
• 期刊: Current gastroenterology reports
• 作者: Falk,GaryW

Endoscopic evaluation and advanced imaging of Barrett's esophagus.

• DOI: 10.1016/j.giec.2010.09.013
• 发表时间: 2011-01
• 期刊: Gastrointestinal endoscopy clinics of North America
• 作者: Wang, Kenneth K;Okoro, Ngozi;Prasad, Ganapathy;WongKeeSong, Michel;Buttar, Navtej S;Tian, Jianmin
• 通讯作者: Tian, Jianmin

Barrett's esophagus: genetic and cell changes.

巴雷特食管：遗传和细胞变化。

• DOI: 10.1111/j.1749-6632.2011.06043.x
• 发表时间: 2011
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Souza,RhondaF;Freschi,Giancarlo;Taddei,Antonio;Ringressi,MariaNovella;Bechi,Paolo;Castiglione,Francesca;RossiDegl'Innocenti,Duccio;Triadafilopoulos,George;Wang,JeanS;Chang,AndrewC;Barr,Hugh;Bajpai,Manisha;Das,KironM;Schneid
• 通讯作者: Schneid

Emerging Insights into the Esophageal Microbiome.

• DOI: 10.1007/s11938-018-0171-5
• 发表时间: 2018-03
• 期刊: Current treatment options in gastroenterology
• 作者: May M;Abrams JA
• 通讯作者: Abrams JA

Goblet Cell Ratio in Combination with Differentiation and Stem Cell Markers in Barrett Esophagus Allow Distinction of Patients with and without Esophageal Adenocarcinoma.

• DOI: 10.1158/1940-6207.capr-16-0117
• 发表时间: 2017-01
• 期刊: Cancer prevention research (Philadelphia, Pa.)
• 作者: Schellnegger R;Quante A;Rospleszcz S;Schernhammer M;Höhl B;Tobiasch M;Pastula A;Brandtner A;Abrams JA;Strauch K;Schmid RM;Vieth M;Wang TC;Quante M
• 通讯作者: Quante M