RESUMO
The introduction of agents that inhibit tumor angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling has made a significant impact on the survival of patients with metastasized renal cell carcinoma (RCC). Sunitinib, a tyrosine kinase inhibitor of the VEGF receptor, has become the mainstay of treatment for these patients. Although treatment with sunitinib substantially improved patient outcome, the initial success is overshadowed by the occurrence of resistance. The mechanisms of resistance are poorly understood. Insight into the molecular mechanisms of resistance will help to better understand the biology of RCC and can ultimately aid the development of more effective therapies for patients with this infaust disease. In this review we comprehensively discuss molecular mechanisms of resistance to sunitinib and the involved biological processes, summarize potential biomarkers that predict response and resistance to treatment with sunitinib, and elaborate on future perspectives in the treatment of metastasized RCC.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Indóis/uso terapêutico , Neoplasias Renais/diagnóstico , Neoplasias Renais/tratamento farmacológico , Pirróis/uso terapêutico , Carcinoma de Células Renais/genética , Humanos , Neoplasias Renais/genética , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/genética , Prognóstico , Transdução de Sinais/genética , Sunitinibe , Microambiente Tumoral/genéticaRESUMO
The macroscale properties of polymer-matrix composites depend immensely on the quality of the interaction between the reinforcement phase and the bulk polymer. This work presents a method to improve the interfacial adhesion between metal-oxides and a polymer matrix by performing surface-initiated polymerization (SIP) by way of a biomimetic initiator. The initiator was modeled after 3,4-dihydroxy-L-phenylalanine (dopa), an amino acid that is highly concentrated in mussel foot adhesive proteins. Mechanical pull out tests of NiTi and Ti-6Al-4V wires from poly (methyl methacrylate) (PMMA) were performed to directly test the interfacial adhesion. These tests demonstrated improvements in maximum interfacial shear stress of 116% for SIP-modified NiTi wires and 60% for SIP-modified Ti-6Al-4V wires over unmodified specimens. Polymer chain growth from the metal oxides was validated using x-ray photoemission spectroscopy (XPS), ellipsometry, scanning electron microscopy (SEM), and contact angle analysis.
RESUMO
Myelopathy, a severe condition characterised by paraparesis, sensory deficits and sphincter dysfunction, is one of the neuropsychiatric manifestations that have been described in patients with systemic lupus erythematosus (SLE). SLE-associated myelopathy may confront clinicians with a challenging decision-making process due to the broad differential diagnosis, the lack of disease-specific findings, and the urgency to initiate immunosuppressive therapy early in the course of the disease to favourably affect outcome.