PURPOSE: We investigated the associations between hsMAD2 mRNA expression in tumor cells and sensitivity to paclitaxel or patient prognosis in neuroblastoma. METHODS: Fifty-one formalin-fixed paraffin-embedded tumor samples were manually microdissected to collect tumor cells, and RNA was purified. Nineteen clinical samples of advanced neuroblastoma showed appropriate quality of the isolated RNA for real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. The hsMAD2 expression levels were determined by real-time RT-PCR in 4 neuroblastoma cell lines and 19 clinical samples. The sensitivity to paclitaxel was assessed by WST-8 colorimetric assays and flow cytometry. HsMAD2 expression of the clinical samples was investigated for its association with prognosis in advanced neuroblastoma patients. RESULTS: There was a significant positive correlation between hsMAD2 mRNA expression and the sensitivity to paclitaxel in four neuroblastoma cell lines. High hsMAD2 expression may be correlated with paclitaxel-induced apoptosis. Kaplan-Meier survival curves were stratified by hsMAD2 expression using the median value as a cut-off point and analyzed for prognostic significance by the log-rank test (P = 0.0467). Furthermore, multivariate survival analysis revealed that only hsMAD2 expression had a significant impact on the overall survival rate. CONCLUSIONS: Our results may warrant clinical application of paclitaxel in neuroblastoma treatment for poor prognosis patients.
PURPOSE: We investigated the associations between hsMAD2 mRNA expression in tumor cells and sensitivity to paclitaxel or patient prognosis in neuroblastoma. METHODS: Fifty-one formalin-fixed paraffin-embedded tumor samples were manually microdissected to collect tumor cells, and RNA was purified. Nineteen clinical samples of advanced neuroblastoma showed appropriate quality of the isolated RNA for real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. The hsMAD2 expression levels were determined by real-time RT-PCR in 4 neuroblastoma cell lines and 19 clinical samples. The sensitivity to paclitaxel was assessed by WST-8 colorimetric assays and flow cytometry. HsMAD2 expression of the clinical samples was investigated for its association with prognosis in advanced neuroblastomapatients. RESULTS: There was a significant positive correlation between hsMAD2 mRNA expression and the sensitivity to paclitaxel in four neuroblastoma cell lines. High hsMAD2 expression may be correlated with paclitaxel-induced apoptosis. Kaplan-Meier survival curves were stratified by hsMAD2 expression using the median value as a cut-off point and analyzed for prognostic significance by the log-rank test (P = 0.0467). Furthermore, multivariate survival analysis revealed that only hsMAD2 expression had a significant impact on the overall survival rate. CONCLUSIONS: Our results may warrant clinical application of paclitaxel in neuroblastoma treatment for poor prognosis patients.
Authors: T Sugimoto; Y Horii; T Hino; J T Kemshead; H Kuroda; T Sawada; H Morioka; J Imanishi; H Inoko Journal: Cancer Res Date: 1989-04-01 Impact factor: 12.701