RESUMO
INTRODUCTION: Chordoma is a rare and a slow-growing tumor originating from the notochord and commonly localized in the skull base. Surgery and occasionally radiotherapy have emerged as the treatments of choice. In the relapsed situations available treatment options are strictly limited; however, recently molecularly targeted agents have been proposed to be of potential beneficial value. THE CASE: A 63-year-old male presenting with seizures and an extradural mass in the left brain hemisphere. An attempt to resect the tumor was followed by severe bradycardia when manipulating with the dura and therefore discontinued. It was considered too hazardous even to take a biopsy specimen. The tumor was considered radiologically and macroscopically as a chordoma. As the tumor progressed after radiotherapy, chemotherapy with erlotinib in combination with cetuximab was initiated. This treatment was interrupted due to progressive disease and toxicity. However, combination treatment with erlotinib and bevacizumab normalized the uptake of [11C]methionine PET signal and resulted in a slight tumor shrinkage on MRI. The patient is still (March 2011) free of symptoms, without cranial nerve deficits or seizures. DISCUSSION: This report shows that erlotinib and bevacizumab in combination may completely quench the transport of the essential amino acid methionine to a treatment refractory intracranial tumor bearing radiological and clinical characteristics of a chordoma. Further studies are necessary to establish this strategy as a treatment option for this indication.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cordoma/diagnóstico por imagem , Cordoma/tratamento farmacológico , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Terapia Combinada , Cloridrato de Erlotinib , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Quinazolinas/administração & dosagem , Radioterapia , Terapia de Salvação/métodosAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Cordoma/tratamento farmacológico , Quinazolinas/uso terapêutico , Neoplasias Cranianas/tratamento farmacológico , Adulto , Bevacizumab , Neoplasias Ósseas/cirurgia , Cordoma/cirurgia , Cloridrato de Erlotinib , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sacro/cirurgia , Resultado do TratamentoRESUMO
Human glioblastoma cell cultures were established and the expression of glial fibrillary acidic protein (GFAP) and the gap-junction protein connexin 43 (Cx43) was confirmed by Western blot. Following treatment with 4-phenylbutyrate (4-PB), increased concentrations of non-phosphorylated GFAP were seen, while phosphorylated isoforms remained intact. Immunocytochemical staining of glioblastoma cells revealed an intracellular redistribution of GFAP. In addition to cytoplasmic immunostaining, GFAP immunoreactivity was also associated with the nucleus and/or the nuclear membrane. Phosphorylated and non-phosphorylated Cx43 proteins were increased 2- to 5-fold following 4-PB treatment, and were redistributed to areas of the cell surface, participating in cell-to-cell contacts. In addition, functional gap-junction coupling was amplified, as indicated by increased fluorescent dye transfer, and elevated levels of Cx43 protein were detected in parallel with enhanced gap-junction communication. Induced cell differentiation, with improved functional coupling of tumour cells, may be of importance for therapeutic strategies involving intercellular transport of low molecular-weight compounds.