RESUMEN
Glioblastoma (GBM) is the most aggressive malignant glioma, with a very poor prognosis; as such, efforts to explore new treatments and GBM's etiology are a priority. We previously described human GBM cells (R2J-GS) as exhibiting the properties of cancer stem cells (growing in serum-free medium and proliferating into nude mice when orthotopically grafted). Sodium selenite (SS)-an in vitro attractive agent for cancer therapy against GBM-was evaluated in R2J-GS cells. To go further, we launched a preclinical study: SS was given orally, in an escalation-dose study (2.25 to 10.125 mg/kg/day, 5 days on, 2 days off, and 5 days on), to evaluate (1) the absorption of selenium in plasma and organs (brain, kidney, liver, and lung) and (2) the SS toxicity. A 6.75 mg/kg SS dose was chosen to perform a tumor regression assay, followed by MRI, in R2J-GS cells orthotopically implanted in nude mice, as this dose was nontoxic and increased brain selenium concentration. A group receiving TMZ (5 mg/kg) was led in parallel. Although not reaching statistical significance, the group of mice treated with SS showed a slower tumor growth vs. the control group (p = 0.08). No difference was observed between the TMZ and control groups. We provide new insights of the mechanisms of SS and its possible use in chemotherapy.
Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Cuerpo Estriado/cirugía , Glioblastoma/tratamiento farmacológico , Células Madre Neoplásicas/trasplante , Selenito de Sodio/efectos adversos , Oligoelementos/efectos adversos , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Animales , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cuerpo Estriado/metabolismo , Glioblastoma/patología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Selenio/metabolismo , Selenito de Sodio/administración & dosificación , Temozolomida/administración & dosificación , Oligoelementos/administración & dosificación , Resultado del TratamientoRESUMEN
Reasons for signal suppression during the analysis of light petroleum matrices by inductively coupled plasma mass spectrometry (ICP MS) were examined. A decrease of the ionization efficiency of the plasma was found to be the principal factor responsible for this loss of sensitivity. Consequently, an interface based on a total consumption micronebulizer and a heated spray chamber was constructed to alleviate this problem. A method based on flow-injection ICP MS using this interface was developed for the direct multielement analysis of undiluted fuels (gasoline, kerosene) and gas condensates offering an increase in sensitivity by at least a factor of 3-4 in comparison with the existing setups.