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Published on: April 7, 2017
Clinical implications of CES2 RNA expression in neuroblastoma
Keiichi Uchida1, Kohei Otake, Koji Tanaka
1Department 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
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.
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