RESUMEN
OBJECTIVE: To assess the relative contribution of ictal subtraction single-photon emission computed tomography (ISSPECT) and 18 F-fluorodeoxyglucose positron emission tomography computed tomography (PET) in epilepsy surgery decision making. MATERIALS AND METHODS: A retrospective 3-year study of consecutive patients with resistant focal epilepsy who underwent ISSPECT and PET to evaluate to what extent these modalities influence decisions in epilepsy surgery and outcomes. ISSPECT imaging was performed in 106 patients and 58 (55%) had PET also. The clinical consensus (ClinC) was the final arbiter for decisions. Post-surgical outcomes were collected from follow-up clinics. Non-parametric statistics were used to assess association and logistic regression to evaluate prediction of outcomes. RESULTS: Of 106 patients, 60 were males (57%). MRI was non-lesional in 46 (43%). Concordance with ClinC was seen in 80 patients (76%) for ISSPECT, in 46 patients (79%) for PET, and in 37 patients (64%) for ISSPECT + PET. Fifty-six patients (53%) were planned for intracranial video-electroencephalography monitoring (IVEM). Those with ClinC-PET concordance were likely to proceed to IVEM (p = 0.02). ClinC-PET concordance and ClinC-ISSPECT concordance did not predict decision to proceed to surgery, but VEM-MRI concordance did in lesional cases (p = 0.018). Forty-five (42%) underwent surgery of which 29 had minimum follow-up for 1 year (mean, 20 months; SD, 8) and 22 (76%) had Engel class I outcomes. ClinC-ISSPECT concordance (p = 0.024) and VEM-MRI concordance (p = 0.016) predicted Engel class I outcomes. CONCLUSION: Those with ClinC-PET concordance were more likely to proceed with IVEM. ClinC-ISSPECT concordance and VEM-MRI concordance predicted good surgical outcomes.
Asunto(s)
Epilepsia Refractaria/diagnóstico por imagen , Epilepsias Parciales/diagnóstico por imagen , Neuroimagen/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adolescente , Adulto , Epilepsia Refractaria/cirugía , Electroencefalografía/métodos , Epilepsias Parciales/cirugía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Monitorización Neurofisiológica Intraoperatoria , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Cirugía Asistida por ComputadorRESUMEN
Abundant levels of the hyperactive low molecular weight (LMW) forms of cyclin E contribute to deregulation of Cdk2 in breast tumors, but the mechanism through which they arise is not fully understood. Here, we explored the hypothesis that post-translational processing by a protease generates the LMW forms of cyclin E in breast tumors. In ZR75 tumor cell lysates, calcium-induced cyclin E truncation into peptides corresponding in size with LMW forms of cyclin E in tumor tissues. Calpeptin inhibited calcium-stimulated cyclin E truncation, indicating that cleavage resulted from activity of the calcium-dependent protease, calpain. Consistently, calcium+calpain caused truncation of cyclin E immunoprecipitated from tumor cells and tissues. Calcium also caused truncation of the calpain regulatory subunit in tumor cell lysates, indicating that elevated calpain activity accompanies cyclin E truncation. Increased levels of the calpain small subunit were also observed in breast tumors, and significant amounts of its proteolyzed forms indicated increased calpain activity. While elastase also caused cyclin E truncation, the cleavage pattern was distinct from that generated by calpain, suggesting discrete mechanisms in regulating the formation of LMW cyclin E in breast tumors. Treatment of ZR75 cultures with calcium+A23187 recapitulated the formation of the calcium/calpain-induced LMW forms of cyclin E. Altered calcium homeostasis and/or inability of the endogenous calpain inhibitor to control the activity of high levels of the calpain small subunit may contribute to increased calpain activity in breast tumors, causing abundant levels of LMW cyclin E.