title: Detection of esophageal squamous cell carcinoma by cathepsin B activity in nude mice.
abstract: OBJECTIVE
  Despite great progress in treatment, the prognosis for patients with esophageal squamous cell carcinoma (ESCC) remains poor, highlighting the importance of early detection. Although upper endoscopy can be used for the screening of esophagus, it has limited sensitivity for early stage disease. Thus, development of new diagnosis approach to improve diagnostic capabilities for early detection of ESCC is an important need. The aim of this study was to assess the feasibility of using cathepsin B (CB) as a novel imaging target for the detection of human ESCC by near-infrared optical imaging in nude mice.
  
  
  METHODS
  Initially, we examined specimens from normal human esophageal tissue, intraepithelial neoplasia lesions, tumor in situ, ESCC and two cell lines including one human ESCC cell line (Eca-109) and one normal human esophageal epithelial cell line (HET-1A) for CB expression by immunohistochemistry and western blot, respectively. Next, the ability of a novel CB activatable near-infrared fluorescence (NIRF) probe detecting CB activity presented in Eca-109 cells was confirmed by immunocytochemistry. We also performed in vivo imaging of tumor bearing mice injected with the CB probe and ex vivo imaging of resected tumor xenografts and visceral organs using a living imaging system. Finally, the sources of fluorescence signals in tumor tissue and CB expression in visceral organs were identified by histology.
  
  
  RESULTS
  CB was absent in normal human esophageal mucosa, but it was overexpressed in ESCC and its precursor lesions. The novel probe for CB activity specifically detected ESCC xenografts in vivo and in vitro.
  
  
  CONCLUSIONS
  CB was highly upregulated in human ESCC and its precursor lesions. The elevated CB expression in ESCC allowed in vivo and in vitro detection of ESCC xenografts in nude mice. Our results support the usefulness of CB activity as a potential imaging target for the detection of human ESCC.
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China; Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Cardiovascular and Cerebrovascular Disease Hospital, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhe
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Cihang
authors.initials: C
authors.lastname: Bao
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Wang
authors.affiliation: Digestive System Department, General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Shaoqi
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Oncology, Wendeng Center Hospital, Weihai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Oncology, Liaocheng People's Hospital, Liaocheng, China.
authors.forename: Fangli
authors.initials: F
authors.lastname: Cao
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging; D061848:Optical Imaging / Q000379:methods; D009928:Organ Specificity / Q000235:genetics; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D002401:Cathepsin B