title: Clinical implications of APEX1 and Jagged1 as chemoresistance factors in biliary tract cancer.
abstract: OBJECTIVE
  Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer.
  
  
  METHODS
  We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot. Alternately, the 10 patients of advanced biliary cancer consist of 2 group according to the chemotherapy response examined by immunohistochemistry using APEX1 and Jagged1 antibody, and protein expression level was scored for staining intensity and percent positive cell.
  
  
  RESULTS
  The result of MTT assay after APEX1 knockdown showed that strong coexpression of APEX1 and Jagged1 cell line (SNU-245, SNU-1079, and SNU-1196) showed a greater decrease in IC50of chemotherapeutic agent (5-fluorouracil, gemcitabine and cisplatin). The Western blot analysis of APEX1 and Jagged1 expression in biliary cancer cell lines after APEX1 knockdown definitively demonstrated decreased Jagged1 expression. The APEX1 and Jagged1expression level of immunohistochemistry represented that chemorefractory patients had higher than chemoresponsive patients.
  
  
  CONCLUSIONS
  These results demonstrate that simultaneous high expression of APEX1 and Jagged1 is associated with chemoresistance in biliary cancer and suggest that is a potential therapeutic target for chemoresistance in advanced biliary cancer.
authors.affiliation: Department of Premedical Course, Chosun University School of Medicine, Gwangju, Korea.
authors.forename: Hong-Beum
authors.initials: HB
authors.lastname: Kim
authors.affiliation: Department of Urology, Chosun University Hospital, Gwangju, Korea.
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Cho
authors.affiliation: Department of General Surgery, Chosun University Hospital, Gwangju, Korea.
authors.forename: Nam Gyu
authors.initials: NG
authors.lastname: Choi
authors.affiliation: Department of General Surgery, Chosun University Hospital, Gwangju, Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Chosun University Hospital, Gwangju, Korea.
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Hemato-Oncology, Department of Internal Medicine, Chosun University Hospital, Gwangju, Korea.
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Division of Hemato-Oncology, Department of Internal Medicine, Chosun University Hospital, Gwangju, Korea.
authors.forename: Sang Gon
authors.initials: SG
authors.lastname: Park
keywords: 5-FU; APEX1 protein; Cisplatin; Gemcitabine; Jagged1 protein