RESUMO
PURPOSE: glioblastoma multiforme (GBM) still bears a very dismal prognosis even with complete resection followed by adjuvant chemoradiation. The aim of the current study was to evaluate in vitro the antitumor efficacy of arsenic trioxide (ATO) in combination with ionizing radiation plus temozolomide and bevacizumab against cultured glioblastoma stem-like cells, as possible way to increase the therapeutic index in patients diagnosed with recurrent, therapy-refractory GBM. METHODS: stem-like tumor cells isolated from a GBM biopsy were established by cell proliferation assays and upregulation of stem cell markers, as proven by reverse transcription - polymerase chain reaction (RT-PCR). Low concentrations of ATO were added prior to temozolomide, bevacizumab and ionizing irradiation. RESULTS: molecular analysis showed that cells expressed CXCR4, Oct-3/4 and GAPDH when compared to placental mesenchymal stem cells, as well as nestin, GFAP and neurofilament protein. Low concentrations of ATO led to morphologic differentiation, with fewer stem cells in Go state and differentiation-associated cytochemical features, like increased sensitivity to cytostatic drugs and radiotherapy. CONCLUSION: ATO exposure before conventional postoperative chemoradiotherapy for GBM might increase treatment efficacy. Further in vivo experiments on laboratory animals and analysis of absorption rate and side effects are required.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos da radiação , Radiossensibilizantes/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Trióxido de Arsênio , Arsenicais/administração & dosagem , Bevacizumab , Western Blotting , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Células Cultivadas , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Feminino , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Glioblastoma/patologia , Humanos , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos da radiação , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Nestina , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Óxidos/administração & dosagem , Placenta/citologia , Placenta/efeitos dos fármacos , Placenta/efeitos da radiação , Gravidez , RNA Mensageiro/genética , Tolerância a Radiação/efeitos dos fármacos , Radiação Ionizante , Receptores CXCR4 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TemozolomidaRESUMO
The sensitive nuclear analytical technique Instrumental Neutron Activation Analysis (INAA) has been applied on several types of metallic biomaterials (Heraenium CE, Ventura Nibon, Wiron 99 and Ducinox which are currently used for restoration in the dental clinics) to study its performance in elemental analysis and identify eventual limitations. The investigation has been performed by two NAA Laboratories and aimed at getting an answer to the question on how the biomaterials compositions influence the patients' health over the course of time, taking into account the EC Directive 94/27/EC recommendations concerning Ni toxicity.