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1.
Rev Bras Ortop (Sao Paulo) ; 59(1): e119-e124, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38524721

RESUMO

Objective: To quantify the use of social media platforms by orthopedic traumatologists with an emphasis on demographic, practice-based, and regional differences. Materials and Methods: Using the Orthopaedic Trauma Association (OTA) membership database, online searches were performed to identify professional profiles on numerous social media platforms. This presence was then quantified by a cumulative social media score which was correlated to the demographic information collected. Results: In total, 1,262 active fellowship-trained orthopedic traumatologists were identified. Surgeons practicing in an academic setting were found to be more likely to use numerous social media platforms and to present an overall greater social media score than those in private practices. No significant differences in use were found based on practice region. Conclusion: Social media platforms are currently underused by orthopedic traumatologists. Level of Evidence: IV.

2.
J Mater Chem B ; 10(2): 224-235, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34846443

RESUMO

To alter the immunosuppressive tumor microenvironment (TME), we developed an immunostimulatory nanoparticle (NP) to reprogram a tumor's dysfunctional and inhibitory antigen-presenting cells (APCs) into properly activated APCs that stimulate tumor-reactive cytotoxic T cells. Importantly, systemic delivery allowed NPs to efficiently utilize the entire microvasculature and gain access into the majority of the perivascular TME, which coincided with the APC-rich tumor areas leading to uptake of the NPs predominantly by APCs. In this work, a 60 nm NP was loaded with a STING agonist, which triggered robust production of interferon ß, resulting in activation of APCs. In addition to untargeted NPs, we employed 'mainstream' ligands targeting fibronectin, αvß3 integrin and P-selectin that are commonly used to direct nanoparticles to tumors. Using the 4T1 mouse model, we assessed the microdistribution of the four NP variants in the tumor immune microenvironment in three different breast cancer landscapes, including primary tumor, early metastasis, and late metastasis. The different NP variants resulted in variable uptake by immune cell subsets depending on the organ and tumor stage. Among the NP variants, therapeutic studies indicated that the untargeted NPs and the integrin-targeting NPs exhibited a remarkable short- and long-term immune response and long-lasting antitumor effect.


Assuntos
Neoplasias da Mama/terapia , GMP Cíclico/análogos & derivados , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Nanopartículas/química , 1,2-Dipalmitoilfosfatidilcolina/química , Animais , Linhagem Celular Tumoral , GMP Cíclico/uso terapêutico , Células Dendríticas/efeitos dos fármacos , Ligantes , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Peptídeos/química , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Linfócitos T/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
3.
Rev. bras. ortop ; 59(1): 119-124, 2024. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1559597

RESUMO

Abstract Objective: To quantify the use of social media platforms by orthopedic traumatologists with an emphasis on demographic, practice-based, and regional differences. Materials and Methods: Using the Orthopaedic Trauma Association (OTA) membership database, online searches were performed to identify professional profiles on numerous social media platforms. This presence was then quantified by a cumulative social media score which was correlated to the demographic information collected. Results: In total, 1,262 active fellowship-trained orthopedic traumatologists were identified. Surgeons practicing in an academic setting were found to be more likely to use numerous social media platforms and to present an overall greater social media score than those in private practices. No significant differences in use were found based on practice region. Conclusion: Social media platforms are currently underused by orthopedic traumatologists. Level of Evidence: IV.


Resumo Objetivo: Quantificar o uso de plataformas de rede social por traumato-ortopedistas, com ênfase nas diferenças demográficas, regionais e de tipo de prática clínica. Materiais e Métodos: Utilizando o banco de dados de membros da Orthopaedic Trauma Association (OTA), foram realizadas pesquisas on-line para identificar perfis de profissionais em diversas plataformas de rede social. Esta presença foi quantificada por uma pontuação cumulativa de redes sociais, que foi correlacionada com as informações demográficas coletadas. Resultados: Foram identificados 1.262 profissionais com treinamento especializado em trauma ortopédico. Observou-se que os cirurgiões que atuam em ambiente acadêmico têm maior probabilidade de usar diversas plataformas de rede social e apresentam pontuação geral maior em redes sociais do que aqueles que atuam em consultório particular. Não foram encontradas diferenças significativas quanto ao uso de redes sociais com base na região de atuação. Conclusão: Atualmente, as plataformas de rede social são subutilizadas pelos traumato-ortopedistas. Nível de Evidência: IV.

4.
Cancer Res ; 79(20): 5394-5406, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31431457

RESUMO

Effective cancer immunotherapy depends on the robust activation of tumor-specific antigen-presenting cells (APC). Immune agonists encapsulated within nanoparticles (NP) can be delivered to tumor sites to generate powerful antitumor immune responses with minimal off-target dissemination. Systemic delivery enables widespread access to the microvasculature and draining to the APC-rich perivasculature. We developed an immuno-nanoparticle (immuno-NP) coloaded with cyclic diguanylate monophosphate, an agonist of the stimulator of interferon genes pathway, and monophosphoryl lipid A, and a Toll-like receptor 4 agonist, which synergize to produce high levels of type I IFNß. Using a murine model of metastatic triple-negative breast cancer, systemic delivery of these immuno-NPs resulted in significant therapeutic outcomes due to extensive upregulation of APCs and natural killer cells in the blood and tumor compared with control treatments. These results indicate that NPs can facilitate systemic delivery of multiple immune-potentiating cargoes for effective APC-driven local and systemic antitumor immunity. SIGNIFICANCE: Systemic administration of an immuno-nanoparticle in a murine breast tumor model drives a robust tumor site-specific APC response by delivering two synergistic immune-potentiating molecules, highlighting the potential of nanoparticles for immunotherapy.


Assuntos
Células Apresentadoras de Antígenos/imunologia , GMP Cíclico/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Interferon beta/fisiologia , Lipídeo A/análogos & derivados , Neoplasias Mamárias Experimentais/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Nanocápsulas/administração & dosagem , Receptor 4 Toll-Like/agonistas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , GMP Cíclico/administração & dosagem , GMP Cíclico/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Feminino , Células Matadoras Naturais/imunologia , Lipídeo A/administração & dosagem , Lipídeo A/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/patologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microcirculação , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia
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