中文摘要
肝癌严重危害人们健康,目前临床缺乏有效治疗方法,但早期肝癌病人可经手术切除获得较好预后。然而,早诊是肝癌临床检测面临的重要难题之一,亟需研发具有高特异性和灵敏度的肝癌检测新手段。本课题组在前期工作中,成功建立肝及肝癌组织活体切片平台,利用临床肝癌病人组织活体切片,进行噬菌体展示文库淘选,通过高通量测序,获得了多条特异性靶向肝癌的候选短肽。进而通过体外和体内原位癌模型试验,验证了候选靶向肽P47对肝癌细胞和肝癌组织的靶向性。基于前期结果,在本项目中拟对P47肝癌靶向肽在肝癌检测中的可行性及应用潜力展开系统的研究。通过对荧光标记P47肽在原位肝癌小鼠模型上的微型病灶、肝癌微转移及肝癌辅助手术切除等应用上的系统测试及对其作用机理的阐释,以期为肝癌临床检测提供一种更特异和更灵敏的检测新工具和思路。
英文摘要
Hepatocellular carcinoma (HCC) is a devastating disease with high frequency and there is no effective treatment available in clinic. Surgery is one of the most promising approaches for treating early-stage HCC patients, however the diagnosis or detection of early-stage HCC is challenging. Therefore it is urgent to develop more specific and sensitive tools for detecting early-stage HCC. In our previous work, we have successfully established the live slice platform for liver and HCC tissues and performed phage display screening with human HCC live slices. Through the high-throughput sequencing, we have obtained several candidate tumor-targeting peptides. Further evaluation in in vitro and orthotopic HCC mouse model revealed that the specific tumor-targeting property of candidate peptide –P47. Based on these findings, in this proposal we plan to investigate the feasibility and potential of the P47 peptide as a molecular beacon for the detection of micro-HCC, micrometastasis and peptide-aided surgery. Furthermore, we wish to elucidate the underlying mechanism for this peptide to provide guide for further optimization. We wish this study can open a novel avenue for the detection of early-stage HCC in clinic with a more specific and sensitive tool.
