RESUMEN
This trial is based on the strategy of reversing O6-methylguanine-DNA methyltransferase (MGMT)-mediated nimustine resistance by depleting MGMT activity with streptozotocin (STZ) pretreatment. Eight patients with recurrent malignant gliomas refractory to previous nimustine chemotherapy were entered in this study. Patients received STZ (2g/m2) followed one hour with nimustine (2-3 mg/Kg) via the ipsilateral carotid artery. After 1-2 cycles of therapy, 3 patients responded, 4 stabilized, and 1 failed. Toxic effects were generally tolerated. The preliminary results indicated that nimustine-resistant tumor cells in vivo could also be sensitized by modulation of MGMT activity.
Asunto(s)
Astrocitoma/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Metiltransferasas/antagonistas & inhibidores , Proteínas de Neoplasias/antagonistas & inhibidores , Nimustina/farmacología , Estreptozocina/farmacología , Adulto , Astrocitoma/enzimología , Astrocitoma/patología , Astrocitoma/radioterapia , Astrocitoma/cirugía , Neoplasias Encefálicas/enzimología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Terapia Combinada , Irradiación Craneana , Resistencia a Medicamentos , Femenino , Glioblastoma/enzimología , Glioblastoma/patología , Glioblastoma/radioterapia , Glioblastoma/cirugía , Humanos , Inyecciones Intraarteriales , Masculino , Metiltransferasas/fisiología , Proteínas de Neoplasias/fisiología , Recurrencia Local de Neoplasia , Nimustina/administración & dosificación , Nimustina/uso terapéutico , O(6)-Metilguanina-ADN Metiltransferasa , Inducción de Remisión , Estreptozocina/administración & dosificación , Estreptozocina/uso terapéutico , Resultado del TratamientoRESUMEN
STUDY DESIGN: An experimental animal model was used to assess spinal cord injury following lateral hemitransection at thoracic spinal cord level. OBJECTIVE: To determine whether extract of Ginkgo biloba (EGb) could have a neuroprotective effect in spinal cord injury (SCI) in rats. SETTING: Department of Biological Sciences and Biotechnology, Tsinghua University, China. METHODS: A total of 72 adult rats were divided randomly into three groups: the EGb group, normal saline (NS) group, and sham operation group (sham group). After thoracic spinal cord hemitransection was performed at the level of the 9th thoracic vertebra (T9), rats in the EGb group were given 100 mg/kg EGb 761 daily, while rats in the NS group received NS. The rats in the sham group only underwent laminectomy without spinal cord hemitransection. At various time points after surgery, thoracic spinal cords were sampled and sliced for histochemistry, immunohistochemistry of inducible nitric oxide synthase (iNOS), and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) of apoptotic cells. RESULTS: Myelin staining showed that the area of cavities was small and the demyelinated zones were limited at and around the injury site of the spinal cord in the EGb group, while the area of cavities was large and the demyelinated zones were serious in the NS group. Nissl staining showed that the ratio of bilateral ventral horn neurons (transection side/uninjured side) in the EGb group was higher than that in the NS group (P<0.05). The apoptotic index and the percentage of iNOS-positive cells were lower in the EGb group than in the NS group. Furthermore, the percentage of iNOS-positive cells positively correlated with the apoptotic index (r( 2)=0.729, P<0.01) after SCI. CONCLUSION: This study demonstrated that EGb 761 could inhibit iNOS expression and have neuroprotective effect by preventing nerve cells from apoptosis after SCI in rats.