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Anticancer Res ; 31(5): 1721-33, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21617231

RESUMO

BACKGROUND: Vincristine and lomustine are two important chemotherapeutic drugs used for the treatment of different types of neoplasms, including medulloblastomas. MATERIALS AND METHODS: We investigated the effects of vincristine and lomustine on 12 primary medulloblastoma cell cultures and the DAOY cell line using the annexinV-flow cytometry and immunoblotting techniques, following treatment of cells for different periods of time. RESULTS: Both drugs triggered apoptosis and cell cycle delay at the G(2)/M phase and also up-regulated p16. Furthermore, the expression of 8 different cancer-related genes were assessed and their mRNA and protein levels were found to be highly heterogeneous and did not correlate in several medulloblastoma cultures. Importantly, there was significant correlation between the level of cadherin-associated protein beta 1 (CTNNB1) and Aurora kinase A (STK15) proteins and neurotrophic tyrosine kinase receptor type 3 (TRKC) mRNA and the proportion of apoptosis induced by vincristine, the combination of both drugs, and lomustine, respectively. CONCLUSION: These genes could be of great importance as therapeutic biomarkers during the treatment of medulloblastoma patients with vincristine and lomustine.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Cerebelares/metabolismo , Meduloblastoma/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptor trkC/metabolismo , beta Catenina/metabolismo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Aurora Quinase A , Aurora Quinases , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Lomustina/administração & dosagem , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/patologia , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/genética , Receptor trkC/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Vincristina/administração & dosagem , beta Catenina/genética
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