RESUMO
OBJECTIVE: Despite an aggressive multimodal therapeutic regimen, glioblastoma (GBM) continues to portend a grave prognosis, which is driven in part by tumor heterogeneity at both the molecular and cellular levels. Accordingly, herein the authors sought to identify metabolic differences between GBM tumor core cells and edge cells and, in so doing, elucidate novel actionable therapeutic targets centered on tumor metabolism. METHODS: Comprehensive metabolic analyses were performed on 20 high-grade glioma (HGG) tissues and 30 glioma-initiating cell (GIC) sphere culture models. The results of the metabolic analyses were combined with the Ivy GBM data set. Differences in tumor metabolism between GBM tumor tissue derived from within the contrast-enhancing region (i.e., tumor core) and that from the peritumoral brain lesions (i.e., tumor edge) were sought and explored. Such changes were ultimately confirmed at the protein level via immunohistochemistry. RESULTS: Metabolic heterogeneity in both HGG tumor tissues and GBM sphere culture models was identified, and analyses suggested that tyrosine metabolism may serve as a possible therapeutic target in GBM, particularly in the tumor core. Furthermore, activation of the enzyme tyrosine aminotransferase (TAT) within the tyrosine metabolic pathway influenced the noted therapeutic resistance of the GBM core. CONCLUSIONS: Selective inhibition of the tyrosine metabolism pathway may prove highly beneficial as an adjuvant to multimodal GBM therapies.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Glioma/tratamento farmacológico , Glioma/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Tirosina/metabolismo , Sequência de Bases , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Células Cultivadas , Quimioterapia Adjuvante , Sistemas de Liberação de Medicamentos , Glioma/patologia , Humanos , Imuno-Histoquímica , Metabolômica , Nitrogênio/metabolismo , Tirosina Transaminase/metabolismoRESUMO
BACKGROUND: Pediatric pituitary adenomas are a rare medical entity that makes up a small portion of intracranial tumors in children and adolescents. Although benign, the majority of these lesions are secreting functional tumors with the potential for physiological sequela that can profoundly affect a child's development. FOCUS OF REVIEW: In this review, we discuss the medical and surgical management of these tumors with a focus on clinical presentation, diagnostic identification, surgical approach, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to treat these tumors. The management of pituitary tumors requires a multidisciplinary team of surgeons, endocrinologists, and neuroanesthesiologists as well as neurocritical care specialists to deliver comprehensive care.
Assuntos
Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Microcirurgia/métodos , Neuroendoscopia/métodos , Neoplasias Hipofisárias/terapia , Prolactinoma/terapia , Adenoma Hipofisário Secretor de ACT/diagnóstico por imagem , Adenoma Hipofisário Secretor de ACT/metabolismo , Adenoma Hipofisário Secretor de ACT/fisiopatologia , Adenoma/diagnóstico por imagem , Adenoma/metabolismo , Adenoma/fisiopatologia , Adenoma/cirurgia , Adolescente , Criança , Pré-Escolar , Craniotomia , Agonistas de Dopamina/uso terapêutico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/fisiopatologia , Humanos , Cavidade Nasal , Cirurgia Endoscópica por Orifício Natural/métodos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/fisiopatologia , Prolactinoma/diagnóstico por imagem , Prolactinoma/fisiopatologia , Osso EsfenoideRESUMO
INTRODUCTION: The field of neuromodulation continues to grow, especially in the area of pain management. Percutaneous nerve field stimulation continues to gain significant popularity for chronic, focal, and intractable neuropathic pain. MATERIALS AND METHODS: Tuohy needles have been traditionally used as the instrument of choice for subcutaneous implantation of peripheral field stimulators. The ON-Q® Tunneling System (Braun Melsungen AG, Melsungen, Germany) provides an adaptable option for subcutaneous implantation of electrodes, with a variety of lengths and gauges available. This system uses a disposable blunt needle and a peel-away sheath and is firm but malleable. Gentle curves can be applied to the stylet prior to implantation. The blunt, malleable nature of the needle and the soft Silastic sheath allow for applications in areas with greater curvature, such as the face, and ensure a subcutaneous placement. CONCLUSIONS: The great adaptability of this system allows for implantation of electrodes subcutaneously with efficacy and ease. Here we present a technical note on the use of this system for subcutaneous implantation of peripheral nerve field stimulators.