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1.
Cureus ; 15(3): e36350, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37082496

RESUMO

Metastatic neuroblastoma to the bone and septic joint shares the same incidence in age and clinical symptomology. Here we discuss a three-year-old male who presented with anemia, persistent hip pain, and a refusal to bear weight. A thorough evaluation based on a broad differential diagnosis allowed for an expedient diagnosis of metastatic neuroblastoma. The timely diagnosis allowed for rapid enrolment in a children's oncology group (COG) clinical trial for advanced neuroblastoma. The patient tolerated the therapy without adverse events and remains in remission.

2.
J Neurooncol ; 126(3): 397-404, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26559543

RESUMO

Glioblastoma (GBM) is the most common primary tumor of the CNS and carries a dismal prognosis. The aggressive invasion of GBM cells into the surrounding normal brain makes complete resection impossible, significantly increases resistance to the standard therapy regimen, and virtually assures tumor recurrence. Median survival for newly diagnosed GBM is 14.6 months and declines to 8 months for patients with recurrent GBM. New therapeutic strategies that target the molecular drivers of invasion are required for improved clinical outcome. We have demonstrated that TROY (TNFRSF19), a member of the TNFR super-family, plays an important role in GBM invasion and resistance. Knockdown of TROY expression inhibits GBM cell invasion, increases sensitivity to temozolomide, and prolongs survival in an intracranial xenograft model. Propentofylline (PPF), an atypical synthetic methylxanthine compound, has been extensively studied in Phase II and Phase III clinical trials for Alzheimer's disease and vascular dementia where it has demonstrated blood-brain permeability and minimal adverse side effects. Here we showed that PPF decreased GBM cell expression of TROY, inhibited glioma cell invasion, and sensitized GBM cells to TMZ. Mechanistically, PPF decreased glioma cell invasion by modulating TROY expression and downstream signaling, including AKT, NF-κB, and Rac1 activation. Thus, PPF may provide a pharmacologic approach to target TROY, inhibit cell invasion, and reduce therapeutic resistance in GBM.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/prevenção & controle , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/prevenção & controle , Receptores do Fator de Necrose Tumoral/metabolismo , Xantinas/farmacologia , Western Blotting , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células/efeitos dos fármacos , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , NF-kappa B/metabolismo , Invasividade Neoplásica , Fármacos Neuroprotetores/farmacologia , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas
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