title: Clinical implications of CES2 RNA expression in neuroblastoma.
abstract: OBJECTIVE
  Human carboxylesterase 2 (CES2) is the key enzyme for metabolic activation of irinotecan (CPT-11). The aim was to evaluate the clinical implications of CES2 RNA expression in neuroblastoma cells.
  
  
  METHODS
  CES2 RNA expression was determined by real-time reverse transcription-polymerase chain reaction in five neuroblastoma cell lines and 42 clinical samples of untreated neuroblastoma. Sensitivity to CPT-11 was assessed by WST-8 colorimetric assays. Induction of apoptosis was evaluated by flow cytometry after CPT-11 exposure. Protein expression of CES2 was evaluated by Western blotting analysis. CES2 RNA expression in clinical samples was investigated for its associations with the clinicopathological characteristics.
  
  
  RESULTS
  CES2 RNA expression was observed in neuroblastoma cells, and its expression in neuroblastoma cell lines was positively correlated with sensitivity to CPT-11 and apoptosis after CPT-11 exposure in vitro. CES2 RNA expression was correlated with the protein levels of CES2 in vitro. CES2 RNA expression was significantly higher in patients with a characteristic related to advanced disease.
  
  
  CONCLUSIONS
  Our results suggest the potential of clinical application of CPT-11 in neuroblastoma treatment for patients with advanced disease.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. ucchie@clin.medic.mie-u.ac.jp
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Kohei
authors.initials: K
authors.lastname: Otake
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Kohei
authors.initials: K
authors.lastname: Matsushita
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Koike
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Motoko
authors.initials: M
authors.lastname: Ueeda
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D043182:Carboxylesterase / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077146:Irinotecan; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics*; D012313:RNA / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012313:RNA; D000077146:Irinotecan; C517204:CES2 protein, human; D043182:Carboxylesterase; D002166:Camptothecin