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.
BACKGROUND/ PURPOSE:Humancarboxylesterase 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: Michela Capello; Minhee Lee; Hong Wang; Ingrid Babel; Matthew H Katz; Jason B Fleming; Anirban Maitra; Huamin Wang; Weihua Tian; Ayumu Taguchi; Samir M Hanash Journal: J Natl Cancer Inst Date: 2015-05-29 Impact factor: 13.506
Authors: Yihui Chen; Michela Capello; Mayrim V Rios Perez; Jody V Vykoukal; David Roife; Ya'an Kang; Laura R Prakash; Hiroyuki Katayama; Ehsan Irajizad; Alia Fleury; Sammy Ferri-Borgogno; Dodge L Baluya; Jennifer B Dennison; Kim-Anh Do; Oliver Fiehn; Anirban Maitra; Huamin Wang; Paul J Chiao; Matthew H G Katz; Jason B Fleming; Samir M Hanash; Johannes F Fahrmann Journal: Mol Metab Date: 2021-12-28 Impact factor: 7.422