RESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/efectos de la radiación , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Trióxido de Arsénico , Arsenicales/administración & dosificación , Bevacizumab , Western Blotting , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Células Cultivadas , Terapia Combinada , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Femenino , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Glioblastoma/patología , Humanos , Proteínas de Filamentos Intermediarios/genética , Proteínas de Filamentos Intermediarios/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de la radiación , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Nestina , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Óxidos/administración & dosificación , Placenta/citología , Placenta/efectos de los fármacos , Placenta/efectos de la radiación , Embarazo , ARN Mensajero/genética , Tolerancia a Radiación/efectos de los fármacos , Radiación Ionizante , Receptores CXCR4 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TemozolomidaRESUMEN
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.