RESUMO
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia commonly affecting children with frequent somatic mutations in MAPK pathway genes including BRAFV600E and MAP2K1. Some studies suggest that LCH cells can recruit and modulate inflammatory cells, which could provide reciprocal survival signals. To characterize the immune profile of infiltrating inflammatory cells, and to clarify their participation in LCH pathogenesis, a detailed immunohistochemical analysis was performed. Fifteen (10 children, 5 adults) LCH cases were assessed through macrophage (CD68 and CD163), mature dendritic cell (mDC; CD83 and CD208), regulatory T cell (Treg; CD4, CD25 and FOXP3) and cytotoxic lymphocyte (CL; CD56, CD57, perforin and granzyme B) immunomarkers. Moreover, lymphocytic and LCH markers were also analysed. All cases were S100, CD1a, CD207 and CD4-positive. Bcl-2 and cyclin D1 expression was observed in 13 of 15 cases. In the immune microenvironment, M2-polarized macrophages and Tregs were the predominant cell populations, followed by significantly (P < .005) smaller levels of mDCs and CLs. Additionally, the number of CD3 + cells was significantly higher than that of CD20 + cells. In the CD3 + cell population, there were a significantly higher number of CD4 + cells than CD8 + cells. While there were no differences when comparing the paediatric and adult populations, FOXP3 + cells were significantly higher in patients with multisystem involvement and treated with chemotherapy, than single-site cases and those without chemotherapy. Our results suggest that M2-polarized macrophages and Treg infiltration can promote LCH development and survival, probably through pro-tumoral, immunosuppressive and/or cytokine-mediated mechanisms. This work highlights the need for further exploration of immune-targeted therapy for LCH.
Assuntos
Histiocitose de Células de Langerhans/metabolismo , Células de Langerhans/fisiologia , Macrófagos/metabolismo , Linfócitos T Reguladores/metabolismo , Adulto , Antígenos CD/metabolismo , Diferenciação Celular , Microambiente Celular , Criança , Pré-Escolar , Citocinas/metabolismo , Células Dendríticas/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imuno-Histoquímica/métodos , Lactente , Macrófagos/imunologia , Masculino , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Reguladores/imunologia , Células Th2/imunologiaRESUMO
The SET gene has four transcripts reported in NCBI, coding two isoforms of SET proteins. The most known function of SET protein is inhibiting protein phosphatase 2A, a tumor suppressor, which has been associated with different biological processes. In this review, our focus was on exploring the other SET functions related to epigenetic mechanisms, which impact cellular migration, cell cycle and apoptosis.
Assuntos
Apoptose , Epigênese Genética , Humanos , Processamento de Proteína Pós-Traducional , Isoformas de ProteínasRESUMO
Plasmablastic lymphoma (PBL) is a rare B-cell lymphoma occurring mainly in HIV patients. The tumor frequently involves extranodal sites such as the oral cavity, nasal cavity, gastrointestinal tract, skin, and lungs. The neoplastic cells are characterized by a plasmablastic appearance and typical immunophenotype that indicates plasma cell differentiation. Herein, we report a case of intraocular involvement by plasmablastic lymphoma in a HIV patient with a long history of cytomegalovirus retinitis and loss of vision. After an evisceration performed to control the blind, painful eye a diagnosis of PBL was made by examining the eye contents. Two months later, a biopsy of cervical lymph node revealed nodal lymphoma of the same type. To the best of our knowledge, this is the second case of intraocular PBL reported in English literature.
RESUMO
Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.
Assuntos
Periodontite Crônica/sangue , Mediadores da Inflamação/sangue , Biomarcadores/sangue , Quimiocina CCL2/sangue , Quimiocina CCL3/sangue , Quimiocina CCL4/sangue , Quimiocina CCL5/sangue , Quimiocina CXCL9/sangue , Quimiocinas CC/sangue , Citocinas/sangue , Proteína Ligante Fas/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Hemorragia Gengival/sangue , Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Humanos , Interferon gama/sangue , Interleucina-9/sangue , Interleucinas/sangue , Linfotoxina-alfa/sangue , Perda da Inserção Periodontal/sangue , Bolsa Periodontal/sangue , Fator de Crescimento Transformador beta/sangueRESUMO
Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.
Avanços no diagnóstico da doença periodontal levam a métodos nos quais o risco e atividade da doença periodontal podem ser identificados e quantificados por biomarcadores. Pacientes com periodontite podem apresentar elevados níveis circulatórios de marcadores inflamatórios específicos que podem ser correlacionados com a severidade da doença. Portanto, o objetivo desse estudo foi avaliar as diferenças nos níveis séricos de biomarcadores inflamatórios em pacientes saudáveis e com doença periodontal. Foram incluídos no estudo 25 pacientes (8 saudáveis e 17 com periodontite crônica). Uma amostra de 15 mL de sangue foi obtida para identificar os marcadores inflamatórios simultaneamente utilizando Array de proteínas através de citometria de fluxo. De 24 citocinas inflamatórias analisadas, apenas 3 (RANTES, MIG e Eotaxina) apresentaram diferenças estatisticamente significantes (p<0,05) entre os dois grupos. Conclui-se que alguns marcadores inflamatórios selecionados apresentam diferença de concentração em pacientes com periodontite e saudáveis. A análise do perfil de citocinas pode ser utilizada tanto para distinguir pacientes periodontais de pacientes saudáveis, como para medir o risco à doença. Contudo, mais estudos com número maior de amostras são necessários para validar os achados sobre os biomarcadores específicos.
Assuntos
Humanos , Periodontite Crônica/sangue , Mediadores da Inflamação/sangue , Biomarcadores/sangue , /sangue , /sangue , /sangue , /sangue , Quimiocina CXCL9/sangue , Quimiocinas CC/sangue , Citocinas/sangue , Proteína Ligante Fas/sangue , /sangue , Hemorragia Gengival/sangue , Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Interferon gama/sangue , Interleucina-9/sangue , Interleucinas/sangue , Linfotoxina-alfa/sangue , Perda da Inserção Periodontal/sangue , Bolsa Periodontal/sangue , Fator de Crescimento Transformador beta/sangueRESUMO
Neste trabalho, analisaram-se comparativamente as seqüências de nucleotídios dos genes das proteínas estruturais C, prM e E de todos os Flavivirus, incluindo, também, a regiäo 5' näo codificadora, de 21 Flavivirus. Utilizou-se para a análise o programa de microcomputador DNAsis (Hitachi, Japäo) e construiu-se uma árvore filogenética, incluindo os vinte e um (21) vírus, após alinhamento de suas seqüências de nucleotídios. Na árvore filogenética obtida, observou-se uma ramificaçäo inicial, separando os vírus transmitidos por carrapatos daqueles transmitidos por mosquitos. Também, agruparam-se, em diferentes ramos, os vírus do dengue, os da febre amarela, e os da encefalite japonesa. Observou-se uma evidente relaçäo entre a árvore filogenética e os subgrupos e tipos virais, reconhecidos com base em relacionamento antigênico.