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Early Targets in Progression of Barrett's Esophagus to Esophageal Adenocarcinoma

巴雷特食管进展为食管腺癌的早期目标

基本信息

批准号：
9277831
负责人：
DAVID George BEER
金额：
$ 108.42万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-21 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9277831
关键词：
Accounting Address Adenocarcinoma Advisory Committees Appearance Barrett Esophagus Binding Biochemistry Budgets Candidate Disease Gene Cell surface Cells Center for Translational Science Activities Clinical Clinical Data Clinical Research Communication Contracts DNA DNA Sequence Alteration DNA copy number Dana-Farber Cancer Institute Data Databases Detection Developed Countries Developing Countries Dimerization Disease Endoscopes Endoscopy Esophageal Esophageal Adenocarcinoma Esophagogastric Junction Esophagus Excision Fiber Formalin Foundations Freezing Gene Expression Gene Expression Profiling Gene Targeting Genes Genomics Goals Grant Human Image Immunohistochemistry Incidence Individual Institution Investigational New Drug Application Label Lesion Ligands Light Longitudinal cohort Malignant Neoplasms Malignant neoplasm of esophagus Medical Methodology Michigan Mission Molecular Profiling Molecular Target Mutation Neoplasms Operative Surgical Procedures Outcome Paraffin Embedding Patient Recruitments Patients Peptides Performance Pharmacology and Toxicology Pilot Projects Plasma Premalignant Preventive measure Process Protocols documentation Research Research Personnel Research Project Grants Resources Reverse Transcriptase Polymerase Chain Reaction Risk Risk stratification Screening for cancer Sensitivity and Specificity Serum Spatial Distribution Specimen Survival Rate Telomerase Testing Therapeutic Intervention Time Tissue Microarray Tissues Translational Research Universities Update Variant Washington biobank clinical translation cohort dimer flexibility gastroesophageal junction adenocarcinoma genomic tools human subject imaging agent imaging modality improved in vivo innovation monomer novel overexpression patient registry programs sample collection spectrograph synergism transcriptome sequencing tumor heterogeneity virtual

项目摘要

- Project Summary/Abstract Recently, the incidence of esophageal (EAC) and gastro-esophageal junction (GEJAC) adenocarcinoma has increased dramatically, and have a poor 5-year survival rate of less than 15%. When detected early, these patients can have a good clinical outcome following surgery. These observations underscore the importance of early cancer detection. Patients with Barrett's esophagus (BE) are known to be at increased risk. Our overarching goal is to advance new methods of imaging to visualize the effects of spatial distribution of genetic alterations in BE by using novel imaging methods to evaluate tumor heterogeneity on the progression toward EAC. We propose a multi-institutional, trans-disciplinary, translational Research Center in the Barrett's Esophagus Translational Research Network (BETRNet). Our mission is to build on our expertise in genomic characterization, peptide biochemistry, and clinical translation to achieve our ultimate goal to perform early cancer detection at an early stage where therapeutic intervention can be most effective. We will identify a complementary panel of genes that are overexpressed on the cell surface and will be used to develop and validate new peptide imaging agents. The targets chosen will address 3 important clinical needs: 1) Real-time endoscopic identification of pre-malignant lesions and early stage cancer to guide endoscopic resection; 2) Risk stratification of BE patients for timing of endoscopic surveillance; and 3) Detection of gastro- esophageal junction adenocarcinomas in patients without endoscopic appearance of BE. We will use state-of-the-art genomic tools to to identify early overexpressed gene targets that arise in progression of BE to EAC by providing comprehensive analyses of gene expression alterations, DNA copy number variation, and genetic mutations. We will select candidate genes that are expressed on the cell surface where they can be endoscopically imaged in vivo. We will rigorously validate the panel of candidate targets with quantitative RT-PCR and immunohistochemistry on tissue microarrays using an independent cohort of human esophagus specimens. We will use these targets to first identify and validate monomer peptides that are highly specific. We will then arrange monomer peptides in a dimer configuration to produce multivalent ligand target interactions to improve binding performance and allow for early targets to be detected at low levels of expression. We will use a flexible fiber multi-spectral endoscope that can pass through the working channel of a standard medical endoscope to detect multiple targets at the same time. Successful completion of these aims will provide an integrated multi-spectral imaging methodology to longitudinally visualize overexpressed molecular targets that drive progression of Barrett's esophagus to esophageal adenocarcinoma. This innovative approach can serve as the foundation for validated preventive measures to improve patient management.

-项目摘要/摘要