Department of Medicine, National University Health System, Singapore; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut; Genome Institute of Singapore, A-STAR, Singapore; Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut.
Department of Medicine, National University Health System, Singapore.
Clin Gastroenterol Hepatol. 2014 Jan;12(1):126-9. doi: 10.1016/j.cgh.2013.08.033. Epub 2013 Aug 23.
The best means to improve gastrointestinal cancer survival is screening and treatment of early lesions. In esophageal adenocarcinoma, it is believed that low-grade dysplasia and perhaps even high-risk Barrett's esophagus represent the most attractive targets for achieving a cure. An issue with Barrett's esophagus is that endoscopy alone cannot distinguish Barrett's esophagus from columnar-lined epithelium or from areas of low-grade dysplasia. Much effort, therefore, has been devoted to discover molecular biomarkers of high-risk states and to develop imaging tools for detecting these biomarkers in a manner that could assist real-time in vivo targeting of sites for biopsy. The strategy we have used is to generate stem cell clones from Barrett's esophagus biopsy specimens and to compare their gene expression profiles with patient-matched stem cell clones of the esophageal squamous epithelia and gastric cardia. It is anticipated that by mining the expression data sets of these Barrett's stem cell clones, we will be able to identify unique cell surface markers of the Barrett's stem cells against which cytotoxic antibodies or aptamers can be developed and used to aid the endoscopist in identifying regions of atypia for biopsy, perform a real-time diagnosis, stratify patients during the examination, and, ultimately, direct therapy in a preemptive manner.
提高胃肠道癌生存率的最佳方法是筛查和治疗早期病变。在食管腺癌中，人们认为低级别上皮内瘤变，甚至高危的 Barrett 食管，代表了实现治愈的最有吸引力的目标。Barrett 食管的一个问题是，仅凭内镜无法将 Barrett 食管与柱状上皮或低级别上皮内瘤变区分开来。因此，人们付出了很多努力来发现高危状态的分子生物标志物，并开发用于以可实时辅助活检目标部位靶向的方式检测这些生物标志物的成像工具。我们使用的策略是从 Barrett 食管活检标本中生成干细胞克隆，并将其基因表达谱与患者匹配的食管鳞状上皮和胃贲门的干细胞克隆进行比较。预计通过挖掘这些 Barrett 干细胞克隆的表达数据集，我们将能够识别 Barrett 干细胞的独特细胞表面标志物，针对这些标志物可以开发细胞毒性抗体或适体，并用于帮助内镜医生识别活检的异型区域，进行实时诊断，在检查过程中对患者进行分层，并最终以先发制人的方式指导治疗。
