The broad, long-term objective of this project is to develop a multi-institutional, multi-disciplinary translational Research Center to accelerate the clinical use of targeted imaging methodologies for the early detection and prevention of esophageal adenocarcinoma through the Barrett's Esophagus Translational Research Network (BETRNet). 3 inter-related Primary Research Projects and Shared Research Resources (Cores) will be established to develop advanced endoscopic imaging as an enabling technology for management of patients with Barrett's esophagus by visualizing molecular targets from amplified and overexpressed genes. In Project 1, genomic data will be analyzed to identify molecular targets based on properties of gene amplification and/or overexpression. These targets will be used to select highly specific peptides in Project 2 that will be fluorescent-labeled for detection on imaging. A multi-spectral scanning fiber endoscope will be developed in Project 3 to perform real time visualization of a panel of peptides in 3 fluorescence channels. The unique instrument design can pass through the working channel of a standard medical endoscope to allow for concurrent white light imaging. Future versions of this instrument may have 12 or more channels. Image processing algorithms will developed to """"""""red-flag"""""""" diseased regions on a panoramic view of the distal esophagus. This integrated imaging strategy aims to assist the physician in guiding tissue biopsy of high grade dysplasia and early adenocarcinoma that can not been seen otherwise. Phase 1 studies will be performed to prepare for a future multi-center clinical validation study. Future applications will allow for real time spatial visualization and monitoring of other targets, including those associated with stem cells or with biomarkers of cancer risk. Moreover, imaging of molecular targets can be performed in patients with Barrett's esophagus over time to better understand the molecular mechanisms of this disease. The 3 Cores will support the Primary Research Projects, Pilot Projects, and Cross-BETRNet Projects. The Administrative Core will provide support for grants and regulatory management, including budgets, financial reporting, progress reports, human subjects protocols, investigation of new drug (IND) applications, and Steering Committee representation. The Bioinformatics Core will provide support the Primary Projects for statistical evaluation of genomic, imaging, and clinical data and the BETRNet Network for data sharing and archiving of tissue specimens. The Validation &Pathology Core will provide support for validation of peptide binding activity to amplified and overexpressed gene targets in high-grade dysplasia and early adenocarcinoma.

Public Health Relevance

This research addresses the need for novel methodologies to improve early detection and prevention of esophageal adenocarcinoma in patients with Barrett's esophagus, a disease notable for having the fastest growing incidence of all cancers in the U.S. Targeted imaging provides an enabling technology to guide tissue biopsy and to study molecular mechanisms of cancer transformation over time. More effective cancer preventive measures will benefit not only affected individuals but also the public at large.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163059-04
Application #
8724430
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Richmond, Ellen S
Project Start
2011-09-21
Project End
2016-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Chen, Jing; Gao, Zhenghong; Li, Gaoming et al. (2018) Dual-modal in vivo fluorescence and photoacoustic imaging using a heterodimeric peptide. Chem Commun (Camb) 54:13196-13199
Joshi, Bishnu P; Wang, Thomas D (2018) Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications. Contrast Media Mol Imaging 2018:2015237
Rubenstein, Joel H; Waljee, Akbar K; Dwamena, Ben et al. (2018) Yield of Higher-Grade Neoplasia in Barrett's Esophagus With Low-Grade Dysplasia Is Double in the First Year Following Diagnosis. Clin Gastroenterol Hepatol 16:1529-1530
Tavakkoli, Anna; Appelman, Henry D; Beer, David G et al. (2018) Use of Appropriate Surveillance for Patients With Nondysplastic Barrett's Esophagus. Clin Gastroenterol Hepatol 16:862-869.e3
Stachler, Matthew D; Camarda, Nicholas D; Deitrick, Christopher et al. (2018) Detection of Mutations in Barrett's Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma. Gastroenterology 155:156-167
Jiang, Yang; Gong, Yuanzheng; Rubenstein, Joel H et al. (2017) Toward real-time quantification of fluorescence molecular probes using target/background ratio for guiding biopsy and endoscopic therapy of esophageal neoplasia. J Med Imaging (Bellingham) 4:024502
Savastano, Luis E; Seibel, Eric J (2017) Scanning Fiber Angioscopy: A Multimodal Intravascular Imaging Platform for Carotid Atherosclerosis. Neurosurgery 64:188-198
Zhou, Juan; He, Lei; Pang, Zhijun et al. (2017) Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia. Oncotarget 8:87095-87106
Savastano, Luis E; Zhou, Quan; Smith, Arlene et al. (2017) Multimodal laser-based angioscopy for structural, chemical and biological imaging of atherosclerosis. Nat Biomed Eng 1:
Ferrer-Torres, Daysha; Nancarrow, Derek J; Kuick, Rork et al. (2016) Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas. Oncotarget 7:54867-54882

Showing the most recent 10 out of 45 publications