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‣ FoxP3, GATA-3 and T-bet expression in elderly asthma

Vale-Pereira, Sofia; Todo-Bom, Ana; Geraldes, Luisa; Schmidt-Weber, Carsten; Akdis, Cesmi; Mota-Pinto, Anabela
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica
Português
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Background Asthma is a chronic inflammatory disorder in which Th2, Th1 and suppressive T cells (Tregs) play a role. The transcription factor FoxP3 plays a role in Treg differentiation hile T-bet is important for Th1 and GATA-3 for Th2 differentiation from naïve T cells. Recent data show that age-related deregulation of Treg cells is a mechanism of senescence affecting several chronic diseases. It is crucial to understand the behaviour of these cell populations in asthma for elderly patients. Objective To evaluate FoxP3, GATA-3 and T-bet gene expression under basal conditions and after in vitro activation in a group of elderly asthmatic compared with age-matched healthy individuals. Methods Thirty-two elderly asthmatics and 17 healthy elderly individuals were selected. Serum total IgE was measured, and peripheral blood mononuclear cells (PBMCs) were isolated and stimulated in vitro with anti-CD3/anti-CD28, followed by mRNA isolation. After reverse transcription, real-time quantitative PCR was performed and relative quantification was determined 2 DDCt (2 DDCt method). Results The mean values and standard deviation of FoxP3, GATA-3 and T-bet relative expression for control vs. asthma were 10.2 6.8 vs. 4.8 3.8, 2.4 2.9 vs. 1.7 0.9 and 3.3 2.1 vs. 2.1 1.5...

‣ Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: A link to autoimmunity?

GENRE, J.; ERRANTE, P. R.; KOKRON, C. M.; TOLEDO-BARROS, M.; CAMARA, N. O. S.; RIZZO, L. V.
Fonte: ACADEMIC PRESS INC ELSEVIER SCIENCE Publicador: ACADEMIC PRESS INC ELSEVIER SCIENCE
Tipo: Artigo de Revista Científica
Português
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Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. In this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. In conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID. (C) 2009 Elsevier Inc. All rights reserved.; The Foundation for Support of Research in the State of Sao Paulo (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP)[04/15887-1]; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); The Foundation for Support of Research in the State of Sao Paulo (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP)[07/07139-3]; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); The National Council for Scientific and Technologic Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico -CNPq); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); The Brazilian Ministry of Science and Technology (MCT); Ministério da Ciência...

‣ Protection conferred by heterologous vaccination against tuberculosis is dependent on the ratio of CD4(+)/CD4(+) Foxp3(+) cells

Fedatto, Paola Fernanda; Sergio, Cassia Alves; Oliveira e Paula, Marina; Gembre, Ana Flavia; Franco, Luis Henrique; Wowk, Pryscilla Fanini; Ramos, Simone Gusmao; Horn, Cynthia; Marchal, Gilles; Turato, Walter Miguel; Silva, Celio Lopes; da Fonseca, Denise
Fonte: WILEY-BLACKWELL; HOBOKEN Publicador: WILEY-BLACKWELL; HOBOKEN
Tipo: Artigo de Revista Científica
Português
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CD4(+) Foxp3(+) regulatory T cells inhibit the production of interferon-?, which is the major mediator of protection against Mycobacterium tuberculosis infection. In this study, we evaluated whether the protection conferred by three different vaccines against tuberculosis was associated with the number of spleen and lung regulatory T cells. We observed that after homologous immunization with the 65 000 molecular weight heat-shock protein (hsp 65) DNA vaccine, there was a significantly higher number of spleen CD4(+) Foxp3(+) cells compared with non-immunized mice. Heterologous immunization using bacillus Calmette Guerin (BCG) to prime and DNA-hsp 65 to boost (BCG/DNA-hsp 65) or BCG to prime and culture filtrate proteins (CFP)-CpG to boost (BCG/CFP-CpG) induced a significantly higher ratio of spleen CD4(+)/CD4(+) Foxp3(+) cells compared with non-immunized mice. In addition, the protection conferred by either the BCG/DNA-hsp 65 or the BCG/CFP-CpG vaccines was significant compared with the DNA-hsp 65 vaccine. Despite the higher ratio of spleen CD4(+)/CD4(+) Foxp3(+) cells found in BCG/DNA-hsp 65-immunized or BCG/CFP-CpG-immunized mice, the lungs of both groups of mice were better preserved than those of DNA-hsp 65-immunized mice. These results confirm the protective efficacy of BCG/DNA-hsp 65 and BCG/CFP-CpG heterologous prime-boost vaccines and the DNA-hsp 65 homologous vaccine. Additionally...

‣ Efeito das células dendríticas na geração de células T CD4+CD25+Foxp3+.; Effect of dendritic cells on the generation of CD4+CD25+Foxp3+ T cells.

Marguti, Ivo
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 10/08/2007 Português
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As células dendríticas (DCs) são as principais células apresentadoras de antígeno do sistema imune. No entanto, trabalhos têm demonstrado seu envolvimento na manutenção da tolerância imunológica. As células T CD4+CD25+Foxp3+ possuem a capacidade de suprimir respostas imunes. Neste estudo avaliamos as alterações ocorridas na população de células T CD4+CD25+Foxp3+ após co-cultura de células de linfonodo com DCs. Nossos resultados demonstram que após a co-cultura há um aumento da população de células CD4+CD25+Foxp3+ de maneira independente do estado de ativação das DCs ou da presença de antígenos exógenos. No entanto, o aumento observado é maior quando DCs imaturas são incubadas com antígenos exógenos. Notamos ainda que há presença de TGF-ß em todas as condições experimentais em que observamos aumento da população de células CD4+CD25+Foxp3+. Nossos dados sugerem ainda que este aumento se deve à proliferação das células T CD4+CD25+Foxp3+.; Dendritic cells (DCs) are the most important antigen-presenting cells of the immune system. However, DCs have also been implicated in maintaining immunologic tolerance. CD4+CD25+Foxp3+ T lymphocytes are known as cells with regulatory properties. In this study we evaluated the changes in the CD4+CD25+Foxp3+ T cell population after co-culture of lymph-node cells with DCs. Our results show an increase in the CD4+CD25+Foxp3+ T cell population after co-culture and occurs regardless of the activation state of DCs and the presence of exogenous antigens; however it is greater when immature DCs are previously pulsed with exogenous antigen. We also noticed that TGF-? is present in all cultures conditions in which the CD4+CD25+Foxp3+ T cell population increases. Our data also suggests that the increase of the CD4+CD25+Foxp3+ T cell population may be due to the proliferation of these cells.

‣ Perfil imunoistoquímico de linfócitos T regulatórios no pênfico foliáceo endêmico através da expressão do marcador Foxp3; Immunohistochemical profile of regulatory T cell Foxp3 marker in endemic pemphigus foliaceus

Lago, Fernanda
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 31/08/2011 Português
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Introdução: Os linfócitos T regulatórios CD4+CD25+Foxp3+ (Tregs) desempenham um papel fundamental na manutenção da tolerância aos antígenos próprios e no controle da magnitude da resposta imunológica. Alterações quantitativas ou funcionais foram descritas em diversos distúbios auto-imunes. O pênfigo foliáceo endêmico (PFE) é uma doença bolhosa cutânea de natureza auto-imune, que compartilha características clínicas e imunopatológicas com o pênfigo foliáceo clássico, mas apresenta achados epidemiológicos próprios. Auto-anticorpos circulantes e teciduais da classe IgG dirigidos contra caderinas desmossômicas (desmogleína 1), levam à perda de adesão entre os queratinócitos. Objetivo: O objetivo deste estudo foi avaliar se a perda de tolerância é associada com alterações quantitativas nos linfócitos Tregs CD4+CD25+Foxp3+ na pele de pacientes com PFE. Métodos: Amostras de pele de 22 pacientes e 10 controles saudáveis foram submetidos à análise imunoistoquímica com anti-CD4, anti-CD25 e anti-Foxp3. Fotomicrografias foram obtidas de campos consecutivos ao longo de toda epiderme e derme. A seguir, foi realizada quantificação dos linfócitos Foxp3+, CD4+, CD25+, CD4+Foxp3+ e CD25+Foxp3+ em cada compartimento...

‣ Expressão de Foxp3, IL-17 e IL-23 na Leishmaniose Tegumentar Americana causada por Leishmania (Leishmania) amazonensis e Leishmania (Viannia) braziliensis; Expression of Foxp3, IL-17 and IL-23 in American cutaneous leishmaniasis due Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis

Menezes, Joyce Prieto Bezerra de
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 13/09/2013 Português
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A leishmaniose tegumentar americana (LTA) apresenta um amplo espectro de manifestações clínicas e imunopatológicas resultante da interação entre as diferentes espécies de Leishmania e os mecanismos de resposta imune do hospedeiro. Leishmania (Viannia) braziliensis e Leishmania (Leishmania) amazonensis são as espécies de maior potencial patogênico para o homem e de importância médica no Brasil. As células TCD4, quando ativadas por antígenos via MHC II podem se diferenciar em linhagens de células efetoras como Th1, Th2, Th17 e células T reguladoras (Treg). IL-23 é indispensável para as funções efetoras e manutenção de células Th17. O objetivo deste trabalho foi avaliar a expressão de Foxp3, IL-17 e IL-23 em lesões cutâneas de pacientes com diferentes formas clínicas da LTA. Biópsias parafinadas de 44 pacientes foram submetidas à imunoistoquímica, sendo 6 casos de leishmaniose cutânea anérgica difusa (LCADIDRM-) e leishmaniose cutânea disseminada borderline (LCDBIDRM-), ambas causadas por L.(L) amazonensis e 16 casos de leishmaniose cutânea localizada (LCLIDRM+) também causada por L.(L.) amazonensis; 9 casos de LCLIDRM+, 2 casos de LCDBIDRM- e 5 casos de leishmaniose cutâneo-mucosa (LCMIDRM+), todos causados por L.(V.) braziliensis. A densidade de células Tregs Foxp3+ no espectro clínico da LTA mostrou um aumento progressivo partindo das formas centrais LCL causadas por L.(V.) braziliensis (170mm2) e L.(L) amazonensis (140mm2) para as formas polares...

‣ Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas

Cunha, Lucas Leite; Morari, Elaine Cristina; Nonogaki, Suely; Soares, Fernando Augusto; Vassallo, Jose; Ward, Laura Sterian
Fonte: Hospital Clinicas, Univ Sao Paulo; Sao Paulo Publicador: Hospital Clinicas, Univ Sao Paulo; Sao Paulo
Tipo: Artigo de Revista Científica
Português
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OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3(+) lymphocyte infiltration in differentiated thyroid carcinoma cells. METHODS: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues. RESULTS: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3+ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion...

‣ Impact of Foxp3+ regulatory invariant NKT cells in the allergic airways disease

Gomes, Marta Isabel de Carvalho Ferreira
Fonte: Universidade de Lisboa Publicador: Universidade de Lisboa
Tipo: Dissertação de Mestrado
Publicado em //2013 Português
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Tese de mestrado em Bioquímica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2013; As células NKT invariantes Foxp3+ demonstram propriedades imunossupressoras após indução da expressão de Foxp3, tendo por isso sido designadas “células NKT reguladoras Foxp3+”. Estas células partilham vários marcadores fenotípicos com as células T reguladoras, tais como a expressão de CD25, GITR e CTLA-4, não perdendo, contudo, as suas características de células iNKT, nomeadamente a expressão de PLZF. Muito embora estas células tenham sido identificadas in vivo em nódulos linfáticos cervicais de ratinhos protegidos de encefalomielite autoimune experimentalmente induzida (EAE), após administração de α-galactosilceramida, o seu estudo tem sido feito recorrendo à conversão in vitro de células iNKT. Assim sendo, para que se verifique a conversão para células que expressem Foxp3, as células iNKT são isoladas por citometria de fluxo e colocadas em cultura com TGF-β, IL-2 e anti-CD28, na presença de anti-CD3 imobilizado em placa de cultura. Apesar do facto das células iNKT Foxp3+ terem já sido caracterizadas, várias características fenotípicas permanecem ainda por estudar. Além disso...

‣ In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

Cartier,L.; Rodriguez,L.; Alberti,C.; Valenzuela,M.A.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2010 Português
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HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4+CD25+ T-regulatory cells (Treg). For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-β, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years). The control group consisted of 23 non-infected subjects (12 women and 11 men) with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4+CD25+ T cells). Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively) than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31). Both groups had similar levels of TGF-β and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway...

‣ Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas

Cunha,Lucas Leite; Morari,Elaine Cristina; Nonogaki,Suely; Soares,Fernando Augusto; Vassallo,José; Ward,Laura Sterian
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2012 Português
Relevância na Pesquisa
37.207002%
OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3+ lymphocyte infiltration in differentiated thyroid carcinoma cells. METHODS: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues. RESULTS: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3+ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion...

‣ Comparative Genomics Reveals Key Gain-of-Function Events in Foxp3 during Regulatory T Cell Evolution

Nissen, Jesper K.; Betz, Alexander G.; Andersen, Kristian G
Fonte: Frontiers Research Foundation Publicador: Frontiers Research Foundation
Tipo: Artigo de Revista Científica
Português
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The immune system has the ability to suppress undesirable responses, such as those against commensal bacteria, food, and paternal antigens in placenta pregnancy. The lineage-specific transcription factor Foxp3 orchestrates the development and function of regulatory T cells underlying this immunological tolerance. Despite the crucial role of Foxp3 in supporting immune homeostasis, little is known about its origin, evolution, and species conservation. We explore these questions using comparative genomics, structural modeling, and functional analyses. Our data reveal that key gain-of-function events occurred during the evolution of Foxp3 in higher vertebrates. We identify key conserved residues in its forkhead domain and show a detailed analysis of the N-terminal region of Foxp3, which is only conserved in mammals. These components are under purifying selection, and our mutational analyses demonstrate that they are essential for Foxp3 function. Our study points to critical functional adaptations in immune tolerance among higher vertebrates, and suggests that Foxp3-mediated transcriptional mechanisms emerged during mammalian evolution as a stepwise gain of functional domains that enabled Foxp3 to interact with a multitude of interaction partners.; Organismic and Evolutionary Biology

‣ Análise de células t regulatórias foxp3+no líquen plano oral

Pereira, Joabe dos Santos
Fonte: Universidade Federal do Rio Grande do Norte; BR; UFRN; Programa de Pós-Graduação em Patologia Oral; Odontologia Publicador: Universidade Federal do Rio Grande do Norte; BR; UFRN; Programa de Pós-Graduação em Patologia Oral; Odontologia
Tipo: Dissertação Formato: application/pdf
Português
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T regulatory cells have the function of controlling immune responses and maintaining self-tolerance. The FoxP3 has been considered the most specific marker for Treg cells. The aiming of this paper was to evaluate the immunoexpression of FoxP3 in the inflammatory infiltrate from oral lichen planus (OLP) and to compare it with the infiltrate in fibrous inflammatory hyperplasia (FIH) and then, between reticular and erosive forms of OLP. The samples were composed by 32 cases of OLP (17 reticular and 15 erosive) beyond 10 cases of FIH that were submitted to immunohistochemistry staining for FoxP3. Localization of the staining was classified in underepithelial and intraepithelial and the amount of FoxP3+ cells was evaluated through cells counting in 10 consecutive fields, at 400x power magnification. The values were expressed in mean ± standart deviation, and submitted to statistical tests with 5% of significance level. It was observed a statistical significant difference in the amount of FoxP3+ Treg cells between the two combined forms of OLP (1,6 ± 2,2) and the FIH (0,5 ±0,4) (P<0,05). This maybe could be explained by immunological mechanism of OLP, which involves a permanent antigenic induction likely with consequent perpetuation of lesion...

‣ Natural occurring regulatory T cells: role of transcription factor FOXP3 and new approaches improving Treg-cell based therapy

FANELLI, GIORGIA
Fonte: La Sapienza Universidade de Roma Publicador: La Sapienza Universidade de Roma
Tipo: Tese de Doutorado
Português
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The immune system requires a network of regulatory mechanisms that enable the host to maintain immune regulation, homeostasis and tolerance. A functionally committed CD4+CD25+FOXP3+ T cells subset (Treg cells) have a key role in determining the outcomes of protective immunity to a spectrum of foreign antigens while maintaining tolerance to self-antigens and suppressing excessive inflammation that can cause pathology. The transcription factor forkhead P3 (FOXP3) is highly expressed in Treg cells and it is critical for their suppressive function. The importance of FOXP3 is demonstrated in humans with a severe autoimmunity disease called immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) caused by mutations in FOXP3 gene. Therefore, there is an increasing interest in manipulating FOXP3 function and/or using CD4+CD25+FOXP3+ Treg cells as cell therapy to modify immune responses in cancer, autoimmunity and transplantation. The transcription factor FOXP3 has been shown to regulate negatively some genes such as Il2 and positively others, such as Cd25 and Ctla4. To better understand the function of FOXP3 as transcriptional activator, the regulation of CD25, the IL-2Rα chain, by FOXP3 was investigated (Part I). Analyzing a regulatory region of Cd25 promoter...

‣ Expresión de foxp3 en células tumorales y su implicación en el pronóstico del cáncer

Espinosa Sandoval, Adriana Lucía
Fonte: Pontifícia Universidade Javeriana Publicador: Pontifícia Universidade Javeriana
Tipo: bachelorThesis; Trabajo de Grado Pregrado Formato: Pdf
Português
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El factor de transcripción FOXP3, característico de las células T reguladoras (Tregs), se ha encontrado recientemente expresado por células tumorales de diferentes tipos de cáncer. Distintos estudios han reportado que la expresión de FOXP3 en células tumorales se ha asociado a un mal pronóstico de la enfermedad. Sin embargo, la importancia pronostica que posee la expresión de FOXP3 en células tumorales y su relación con las células Tregs sigue sin estar clara. Con el fin de describir la relación entre la expresión del factor de transcripción FOXP3 en células tumorales y parámetros clínicos y biológicos de valor pronóstico de la enfermedad, se realizó una revisión bibliográfica de la literatura reciente sobre la expresión de FOXP3 en células tumorales, en artículos científicos publicados en revistas de alto impacto.; FOXP3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in regulatory T lymphocytes. Its expression was first considered as specific of this cell type, but recent data indicate that FOXP3 is also expressed in human tumor cells, with a variety of different tumors including pancreatic adenocarcinoma, breast cancer, gastric cancer, ovarian cancer and adult T-cell leukemia/lymphoma (ATLL). In addition the FOXP3 expression in tumor cells is associated with a less favorable prognosis and others studies presented evidences that support the role of FOXP3 up-regulation as anti-tumor and ante-metastatic mechanisms.

‣ Expresión de foxp3 en células tumorales y su implicación en el pronóstico del cáncer.

Espinosa Sandoval, Adriana Licía
Fonte: Pontifícia Universidade Javeriana Publicador: Pontifícia Universidade Javeriana
Formato: PDF
Português
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El factor de transcripción FOXP3, característico de las células T reguladoras (Tregs), se ha encontrado recientemente expresado por células tumorales de distintos tipos de cáncer. Distintos estudios han reportado que la expresión de FOXP3 en células tumorales se ha asociado a un mal pronóstico de la enfermedad. Sin embargo, la importancia pronostica que posee la expresión de FOXP3 en células tumorales y su relación con las células Tregs sigue sin estar clara. Con el fin de describir la relación entre la expresión del factor de transcripción FOXP3 en células tumorales y parámetros clínicos y biológicos de valor pronóstico de la enfermedad, se realizó una revisión bibliográfica de la literatura reciente sobre la expresión de FOXP3 en células tumorales, en artículos científicos publicados en revistas de alto impacto. En esta revisión se observó la expresión de FOXP3, en células tumorales de cáncer de seno, cáncer de páncreas, cáncer gástrico, cáncer de ovario y en leucemia/linfoma T del adulto (LLTA), con distintos patrones de expresión e implicación en el pronóstico de la enfermedad. Además se evidenció el papel dual de FOXP3 como un mecanismo adicional de evasión inmune en cáncer de páncreas y su papel como un represor de oncogenes en algunos estudios en cáncer seno.

‣ FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells

McInnes, N.; Sadlon, T.; Brown, C.; Pederson, S.; Beyer, M.; Schultze, J.; McColl, S.; Goodall, G.; Barry, S.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
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The transcription factor FOXP3 has been identified as a tumour suppressor in the breast and prostate epithelia, but little is known about its specific mechanism of action. We have identified a feed-forward regulatory loop in which FOXP3 suppresses the expression of the oncogene SATB1. In particular, we demonstrate that SATB1 is not only a direct target of FOXP3 repression, but that FOXP3 also induces two miRs, miR-7 and miR-155, which specifically target the 3′-UTR of SATB1 to further regulate its expression. We conclude that FOXP3-regulated miRs form part of the mechanism by which FOXP3 prevents the transformation of the healthy breast epithelium to a cancerous phenotype. Approaches aimed at restoring FOXP3 function and the miRs it regulates could help provide new approaches to target breast cancer.; N McInnes, TJ Sadlon, CY Brown, S Pederson, M Beyer, JL Schultze, S McColl, GJ Goodall and SC Barry

‣ FOXP3 over-expression inhibits melanoma tumorigenesis via effects on proliferation and apoptosis

Tan, B.; Anaka, M.; Deb, S.; Freyer, C.; Ebert, L.M.; Chueh, A.C.; Al-Obaidi, S.; Behren, A.; Jayachandran, A.; Cebon, J.; Chen, W.; Mariadason, J.M.
Fonte: Impact Journals Publicador: Impact Journals
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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The Forkhead box P3 (FOXP3) transcription factor is the key driver of regulatory T cell (Treg cells) differentiation and immunosuppressive function. In addition, FOXP3 has been reported to be expressed in many tumors, including melanoma. However, its role in tumorigenesis is conflicting, with both tumor suppressive and tumor promoting functions described. The aim of the current study was to characterize the expression and function of FOXP3 in melanoma. FOXP3 expression was detected by immunohistochemistry (IHC) in 12% (18/146) of stage III and IV melanomas. However expression was confined to fewer than 1% of cells in these tumors. Stable over-expression of FOXP3 in the SK-MEL-28 melanoma cell line reduced cell proliferation and clonogenicity in vitro, and reduced xenograft growth in vivo. FOXP3 over-expression also increased pigmentation and the rate of apoptosis of SK-MEL-28 cells. Based on its infrequent expression in human melanoma, and its growth inhibitory and pro-apoptotic effect in over-expressing melanoma cells, we conclude that FOXP3 is not likely to be a key tumor suppressor or promoter in melanoma.; BeeShin Tan, Matthew Anaka, Siddhartha Deb, Claudia Freyer, Lisa M. Ebert, Anderly C. Chueh, Sheren Al-Obaidi, Andreas Behren...

‣ A tumour suppressor role for FOXP3 and FOXP3-regulated microRNAs in breast cancer cells.

McInnes, Natasha Jacqueline
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2013 Português
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During their lifetime, 1 in 9 Australian women will be diagnosed with breast cancer, a disease that arises due to mutations and epigenetic modifications to tumour suppressor genes and cancer-promoting oncogenes. This thesis investigates the tumour suppressive role of a transcription factor called Forkhead box Protein 3 (FOXP3) in breast cancer. Little is known regarding its role in the breast and therefore identification of FOXP3-sensitive pathways has the potential to highlight novel targets for breast cancer diagnosis and therapy. FOXP3 is a “master regulator‟ in immunosuppressive T regulatory cells, where it is essential for both cell development and function. It was previously thought that FOXP3 expression was restricted to these immune cells, however recent studies have identified FOXP3 expression in breast epithelia, where it has potential tumour suppressor properties. FOXP3 is mutated or has reduced expression in a significant proportion of human breast cancer samples, and loss of FOXP3 has been linked to increased mammary tumour formation in animal models. Few targets of FOXP3 in the breast have been identified, but it is known to directly repress the HER2 and SKP2 oncogenes while maintaining expression of the p21 tumour suppressor gene. A number of groups have shown that in T regulatory cells...

‣ FOXP3 expression in papillary thyroid carcinoma with and without Hashimoto's thyroiditis

Neves Junior,Murilo Pedreira; Carvalho Filho,Edgar Marcelino de; Camandaroba,Marcos Pedro Guedes; Mascarenhas,Milena Brachmans; Correia,Thaizza Cavalcante; Neves,Yuri Costa Sarno
Fonte: Sociedade Brasileira de Patologia Clínica; Sociedade Brasileira de Patologia; Sociedade Brasileira de Citopatologia Publicador: Sociedade Brasileira de Patologia Clínica; Sociedade Brasileira de Patologia; Sociedade Brasileira de Citopatologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2013 Português
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INTRODUCTION: The forkhead box P3 (FOXP3) plays a role in cell development and control. In the presence of abnormal FOXP3 expression, tumor cells may evade the immunosurveillance of lymphoid cells, the first step for the maintenance of cancer cells in the thyroid tissue. OBJECTIVE: To identify the presence of FOXP3 in papillary thyroid carcinoma (PTC) with and without Hashimoto's Thyroiditis (HT). METHODS: We conducted a series study of cases collected from 2000 to 2008, when 1,438 thyroidectomies were performed. We selected those diagnosed with PTC, comprising 466 cases. 30 patients were randomly selected for purposes of immunohistochemistry with antibodies against FOXP3. RESULT: FOXP3 revealed high positivity for PTC and positive immunostaining was present in 21 (72.4%) from all analyzed cases. There was no difference regarding coexistent HT or not. DISCUSSION AND CONCLUSION: In the present study, it was evidenced that the focal or diffuse FOXP3 expression was commonly observed in neoplastic cells from PTC, hence indicating that the assessment of this molecule expression in suspected cases of thyroid cancer may contribute to its diagnosis.

‣ Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas

Cunha, Lucas Leite; Morari, Elaine Cristina; Nonogaki, Suely; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian
Fonte: Universidade de São Paulo. Faculdade de Medicina Publicador: Universidade de São Paulo. Faculdade de Medicina
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; Formato: application/pdf
Publicado em 01/01/2012 Português
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OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3+ lymphocyte infiltration in differentiated thyroid carcinoma cells. METHODS: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues. RESULTS: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3+ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion...