Targeted Peptide Selection and Validation

靶向肽选择和验证

• 批准号: 8555331
• 负责人: Thomas D Wang
• 金额: $ 21.31万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-21 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8555331
• 关键词: Adenocarcinoma; Barrett Esophagus; Binding; Biopsy; Cell surface; Cells; Clinical; Clinical Research; Cultured Cells; Detection; Dysplasia; Endoscopes; Endoscopy; Epidermal Growth Factor Receptor; Esophageal mucous membrane; Excision; Extracellular Domain; Fiber; Fluorescence; Future; Gene Amplification; Gene Targeting; Human Subject Research; Image; Individual; Investigation; Label; Microscope; Multi-Institutional Clinical Trial; Peptides; Performance; Pharmaceutical Preparations; Pharmacology and Toxicology; Phase; Proteins; Protocols documentation; Safety; Scanning; Screening for cancer; Specimen; Tissues; Validation; base; fluorophore; instrument; milligram; overexpression; phase 1 study; prototype; validation studies

A panel of 5 peptides will be developed that have specific binding activity to amplified and/or over expressed gene targets identified in Project 1. Validation of preferential binding will be performed to purified proteins and to cells in culture transfected with gene targets. Validation of selective binding will then be performed to high grade dysplasia and early adenocarcinoma in Barrett's esophagus on fresh endoscopic mucosal resection specimens and tissue biopsies in Core C using the multi-spectral scanning fiber endoscope (SFE) developed in Project 3. Rigorous statistical analysis will be performed by Core B. Phase 1 clinical studies of the individual peptides assigned to three fluorescent-labels will be performed to establish safety of this integrated imaging strategy for a future multi-center clinical validation study.

将开发一组 5 种肽，它们对扩增的肽具有特异性结合活性 和/或项目 1 中确定的过度表达基因目标。将进行优先结合验证 纯化的蛋白质和转染基因靶标的培养细胞。然后将验证选择性结合 新鲜内镜检查巴雷特食管高度不典型增生和早期腺癌 使用多光谱扫描纤维内窥镜在 Core C 中进行粘膜切除标本和组织活检 （SFE）在项目3中开发。严格的统计分析将由Core B进行。1期临床 将对分配给三个荧光标记的单个肽进行研究，以确定其安全性 这种综合成像策略适用于未来的多中心临床验证研究。