Clinical implications of CES2 RNA expression in neuroblastoma

Keiichi Uchida, Kohei Otake, Koji Tanaka, Kiyoshi Hashimoto, Susumu Saigusa, Kohei Matsushita, Yuhki Koike, Mikihiro Inoue, Motoko Ueeda, Yoshinaga Okugawa, Yasuhiro Inoue, Yasuhiko Mohri, Masato Kusunoki

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Background/Purpose: 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.

Original languageEnglish
Pages (from-to)502-509
Number of pages8
JournalJournal of Pediatric Surgery
Volume48
Issue number3
DOIs
Publication statusPublished - 03-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Surgery

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