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Pesquisa : D12.776.543.750.705.852.760.226 [Categoria DeCS]
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  1 / 195 MEDLINE  
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[PMID]:28323891
[Au] Autor:Granja AG; Holland JW; Pignatelli J; Secombes CJ; Tafalla C
[Ad] Endereço:Centro de Investigación en Sanidad Animal (CISA-INIA). Valdeolmos (Madrid), Spain.
[Ti] Título:Characterization of BAFF and APRIL subfamily receptors in rainbow trout (Oncorhynchus mykiss). Potential role of the BAFF / APRIL axis in the pathogenesis of proliferative kidney disease.
[So] Source:PLoS One;12(3):e0174249, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by hyper-secretion of immunoglobulins in response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In this context, we hypothesized that the BAFF/APRIL axis, known to play a major role in B cell differentiation and survival in mammals, could be affected by the parasite and consequently be involved in the apparent shift in normal B cell activity. To regulate B cell activity, BAFF and APRIL bind to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), whereas BAFF also binds to BAFF receptor (BAFF-R). In teleost fish, although some BAFF and APRIL sequences have been reported, their receptors have not been identified. Thus, as a first step in the current work, we have identified homologues to mammalian TACI, BCMA and BAFF-R in rainbow trout (Oncorhynchus mykiss), that constitute the first report of BAFF and APRIL receptor sequences in fish. Subsequently we studied the transcriptional modulation of BAFF, APRIL, and the fish-specific related cytokine, BALM and their putative receptors in fish naturally exposed to T. bryosalmonae. Finally, to gain further insights on the functional role that these cytokines play during the course of PKD, we have studied their effect on the survival of kidney IgM+ B cells and on immunoglobulin transcription. Our results support the premise that the BAFF / APRIL axis could play an important role during PKD, which may open the possibility of new therapeutic treatments against the disease.
[Mh] Termos MeSH primário: Receptor do Fator Ativador de Células B/metabolismo
Antígeno de Maturação de Linfócitos B/metabolismo
Doenças dos Peixes/patologia
Nefropatias/patologia
Oncorhynchus mykiss/parasitologia
Doenças Parasitárias em Animais/patologia
Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo
Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo
[Mh] Termos MeSH secundário: Animais
Linfócitos B/imunologia
Sequência de Bases
Doenças dos Peixes/parasitologia
Regulação da Expressão Gênica
Nefropatias/parasitologia
Myxozoa
Doenças Parasitárias em Animais/parasitologia
Análise de Sequência de DNA
Proteína Transmembrana Ativadora e Interagente do CAML/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B-Cell Activation Factor Receptor); 0 (B-Cell Maturation Antigen); 0 (Transmembrane Activator and CAML Interactor Protein); 0 (Tumor Necrosis Factor Ligand Superfamily Member 13)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174249


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[PMID]:28292432
[Au] Autor:Chesi M; Fonseca R
[Ad] Endereço:Mayo Clinic in Arizona, Phoenix, AZ 85054, USA.
[Ti] Título:Antibodies Create Killer Bonds in Myeloma.
[So] Source:Cancer Cell;31(3):305-307, 2017 03 13.
[Is] ISSN:1878-3686
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this issue of Cancer Cell, Li et al. and Seckinger et al. describe promising results of two T-cell-dependent bi-specific antibodies for the treatment of multiple myeloma: one targets FcRH5 expressed on B cells, whereas the other targets the B cell maturation antigen expressed on plasma cells.
[Mh] Termos MeSH primário: Antígeno de Maturação de Linfócitos B/imunologia
Mieloma Múltiplo/tratamento farmacológico
[Mh] Termos MeSH secundário: Anticorpos/imunologia
Anticorpos Monoclonais/imunologia
Linfócitos B
Seres Humanos
Plasmócitos
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Antibodies); 0 (Antibodies, Monoclonal); 0 (B-Cell Maturation Antigen)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170316
[St] Status:MEDLINE


  3 / 195 MEDLINE  
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[PMID]:28283566
[Au] Autor:Schuh E; Musumeci A; Thaler FS; Laurent S; Ellwart JW; Hohlfeld R; Krug A; Meinl E
[Ad] Endereço:Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, LMU Munich, 82152 Planegg-Martinsried, Germany.
[Ti] Título:Human Plasmacytoid Dendritic Cells Display and Shed B Cell Maturation Antigen upon TLR Engagement.
[So] Source:J Immunol;198(8):3081-3088, 2017 Apr 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The BAFF-APRIL system is best known for its control of B cell homeostasis, and it is a target of therapeutic intervention in autoimmune diseases and lymphoma. By analyzing the expression of the three receptors of this system, B cell maturation Ag (BCMA), transmembrane activator and CAML interactor, and BAFF receptor, in sorted human immune cell subsets, we found that BCMA was transcribed in plasmacytoid dendritic cells (pDCs) in both blood and lymphoid tissue. Circulating human pDCs contained BCMA protein without displaying it on the cell surface. After engagement of TLR7/8 or TLR9, BCMA was detected also on the cell surface of pDCs. The display of BCMA on the surface of human pDCs was accompanied by release of soluble BCMA (sBCMA); inhibition of γ-secretase enhanced surface expression of BCMA and reduced the release of sBCMA by pDCs. In contrast with human pDCs, murine pDCs did not express BCMA, not even after TLR9 activation. In this study, we extend the spectrum of BCMA expression to human pDCs. sBCMA derived from pDCs might determine local availability of its high-affinity ligand APRIL, because sBCMA has been shown to function as an APRIL-specific decoy. Further, therapeutic trials targeting BCMA in patients with multiple myeloma should consider possible effects on pDCs.
[Mh] Termos MeSH primário: Antígeno de Maturação de Linfócitos B/imunologia
Células Dendríticas/imunologia
Transdução de Sinais/imunologia
[Mh] Termos MeSH secundário: Animais
Receptor do Fator Ativador de Células B/imunologia
Antígeno de Maturação de Linfócitos B/biossíntese
Separação Celular
Células Dendríticas/metabolismo
Ensaio de Imunoadsorção Enzimática
Citometria de Fluxo
Seres Humanos
Camundongos
Reação em Cadeia da Polimerase
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B-Cell Activation Factor Receptor); 0 (B-Cell Maturation Antigen); 0 (TNFRSF13C protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170312
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601746


  4 / 195 MEDLINE  
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[PMID]:28267197
[Au] Autor:Tran NL; Schneider P; Santiago-Raber ML
[Ad] Endereço:Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
[Ti] Título:TACI-dependent APRIL signaling maintains autoreactive B cells in a mouse model of systemic lupus erythematosus.
[So] Source:Eur J Immunol;47(4):713-723, 2017 Apr.
[Is] ISSN:1521-4141
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Autoantibodies contribute to the development of systemic lupus erythematosus (SLE). APRIL (a proliferation-inducing ligand), a member of the TNF superfamily, regulates plasma-cell survival and binds to TACI (transmembrane activator CAML interactor) and BCMA (B-cell maturation antigen). We previously showed that APRIL blockade delayed disease onset in lupus-prone mice. In order to evaluate the role of APRIL receptors in the development of SLE, APRIL, TACI, BCMA, or double TACI.BCMA null mutations were introduced into the Nba2.Yaa (Y-linked autoimmune acceleration) spontaneous lupus mouse model. Mortality as a consequence of glomerulonephritis (GN) was reduced in Nba2.APRIL .Yaa, Nba2.TACI .Yaa and double-KO mice compared with Nba2.Yaa mice and correlated with lower levels of circulating antibodies, while splenic populations remained unchanged. In contrast, the appearance of symptoms was accelerated in BCMA-deficient mice, in which TACI signaling was increased. Finally, lupus-prone mice deficient for the APRIL-TACI axis produced less pathogenic antibodies and developed less GN. Disease reduction was attributed to impaired T-independent type 2 responses when the APRIL-TACI signaling axis was disrupted. Collectively, our results have identified and confirmed APRIL as a new target involved in B-cell activation, in the maintenance of plasma cell survival and subsequent increased autoantibody production that sustains lupus development in mice.
[Mh] Termos MeSH primário: Antígeno de Maturação de Linfócitos B/metabolismo
Linfócitos B/imunologia
Lúpus Eritematoso Sistêmico/imunologia
Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo
Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo
[Mh] Termos MeSH secundário: Animais
Autoanticorpos/metabolismo
Autoantígenos/imunologia
Antígeno de Maturação de Linfócitos B/genética
Células Cultivadas
Modelos Animais de Doenças
Suscetibilidade a Doenças
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Camundongos Mutantes
Transdução de Sinais/genética
Proteína Transmembrana Ativadora e Interagente do CAML/genética
Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Autoantigens); 0 (B-Cell Maturation Antigen); 0 (Tnfrsf13b protein, mouse); 0 (Tnfrsf17 protein, mouse); 0 (Transmembrane Activator and CAML Interactor Protein); 0 (Tumor Necrosis Factor Ligand Superfamily Member 13)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170308
[St] Status:MEDLINE
[do] DOI:10.1002/eji.201646630


  5 / 195 MEDLINE  
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[PMID]:28262554
[Au] Autor:Seckinger A; Delgado JA; Moser S; Moreno L; Neuber B; Grab A; Lipp S; Merino J; Prosper F; Emde M; Delon C; Latzko M; Gianotti R; Lüoend R; Murr R; Hosse RJ; Harnisch LJ; Bacac M; Fauti T; Klein C; Zabaleta A; Hillengass J; Cavalcanti-Adam EA; Ho AD; Hundemer M; San Miguel JF; Strein K; Umaña P; Hose D; Paiva B; Vu MD
[Ad] Endereço:Universitätsklinikum Heidelberg, Labor für Myelomforschung and Medizinische Klinik V, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
[Ti] Título:Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment.
[So] Source:Cancer Cell;31(3):396-410, 2017 Mar 13.
[Is] ISSN:1878-3686
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We identified B cell maturation antigen (BCMA) as a potential therapeutic target in 778 newly diagnosed and relapsed myeloma patients. We constructed an IgG-based BCMA-T cell bispecific antibody (EM801) and showed that it increased CD3 T cell/myeloma cell crosslinking, followed by CD4 /CD8 T cell activation, and secretion of interferon-γ, granzyme B, and perforin. This effect is CD4 and CD8 T cell mediated. EM801 induced, at nanomolar concentrations, myeloma cell death by autologous T cells in 34 of 43 bone marrow aspirates, including those from high-risk patients and patients after multiple lines of treatment, tumor regression in six of nine mice in a myeloma xenograft model, and depletion of BCMA cells in cynomolgus monkeys. Pharmacokinetics and pharmacodynamics indicate weekly intravenous/subcutaneous administration.
[Mh] Termos MeSH primário: Anticorpos Biespecíficos/uso terapêutico
Antígeno de Maturação de Linfócitos B/imunologia
Mieloma Múltiplo/tratamento farmacológico
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Biespecíficos/biossíntese
Anticorpos Biespecíficos/farmacocinética
Anticorpos Biespecíficos/farmacologia
Seres Humanos
Ativação Linfocitária
Macaca fascicularis
Camundongos
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bispecific); 0 (B-Cell Maturation Antigen)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170629
[Lr] Data última revisão:
170629
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE


  6 / 195 MEDLINE  
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[PMID]:28260502
[Au] Autor:Zheng C; Zhang X; Zhao Z; Hao X; Wei J; Sun J
[Ad] Endereço:Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
[Ti] Título:Selective Binding BAFF/APRIL by the In and Outside Conservative Region of BCMA.
[So] Source:Protein Pept Lett;24(6):489-494, 2017.
[Is] ISSN:1875-5305
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: BAFF and APRIL are members of TNF superfamily. They play vital roles in the pathogenesis of autoimmune diseases. BCMA, a receptor, shows higher affinity for APRIL than for BAFF. Previous studies found that ligand binding specificity of BCMA may be determined by sequence outside DxL motif. OBJECTIVE: Investigate the contribution of a segment outside the DxL motif of BCMA for binding with ligands. METHOD: In this study, the conservative region of BCMA was divided into two segments: BCMA1 (NEYFDSLLHACIPC), a segment of the DXL motif and BCMA2 (QLRCSSNTPPLT), a segment outside of the DXL motif. Two peptides corresponding to the two segments were synthesized and their contribution to the ligands binding were detected by competitive ELISA. BCMA1-Fc fusion protein was also constructed, purified and analyzed by indirect and competitive ELISA. RESULTS: BCMA2 had no inhibiting effect on the interaction of BCMA-Fc and BCMA1-Fc with BAFF, but, it inhibited 22.5% and 15.2% of the interaction of BCMA-Fc and BCMA1-Fc with mAPRIL respectively. The binding rates of BCMA1-Fc for BAFF were 91.7%, but 80.6% for mAPRIL, suggesting that BCMA1-Fc without BCMA2, bound BAFF well and less efficiently to mAPRIL. CONCLUSION: These results suggest that BCMA2 outside of the conservative DxL motif of BCMA may play an important role in the binding selectivity to its ligands.
[Mh] Termos MeSH primário: Fator Ativador de Células B/genética
Antígeno de Maturação de Linfócitos B/genética
Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Fator Ativador de Células B/química
Antígeno de Maturação de Linfócitos B/química
Sequência Conservada/genética
Ensaio de Imunoadsorção Enzimática
Seres Humanos
Ligantes
Ligação Proteica
Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B-Cell Activating Factor); 0 (B-Cell Maturation Antigen); 0 (Ligands); 0 (TNFRSF17 protein, human); 0 (TNFSF13B protein, human); 0 (Tumor Necrosis Factor Ligand Superfamily Member 13)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE
[do] DOI:10.2174/0929866524666170301115209


  7 / 195 MEDLINE  
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[PMID]:28034989
[Au] Autor:Ghermezi M; Li M; Vardanyan S; Harutyunyan NM; Gottlieb J; Berenson A; Spektor TM; Andreu-Vieyra C; Petraki S; Sanchez E; Udd K; Wang CS; Swift RA; Chen H; Berenson JR
[Ad] Endereço:Institute for Myeloma & Bone Cancer Research, West Hollywood, CA, USA.
[Ti] Título:Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients.
[So] Source:Haematologica;102(4):785-795, 2017 Apr.
[Is] ISSN:1592-8721
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:B-cell maturation antigen is expressed on plasma cells. In this study, we have identified serum B-cell maturation antigen as a novel biomarker that can monitor and predict outcomes for multiple myeloma patients. Compared to healthy donors, patients with multiple myeloma showed elevated serum B-cell maturation antigen levels ( <0.0001). Serum B-cell maturation antigen levels correlated with the proportion of plasma cells in bone marrow biopsies (Spearman's rho = 0.710; <0.001), clinical status (complete response partial response, =0.0374; complete response progressive disease, <0.0001), and tracked with changes in M-protein levels. Among patients with non-secretory disease, serum B-cell maturation antigen levels correlated with bone marrow plasma cell levels and findings from positron emission tomography scans. Kaplan-Meier analysis demonstrated that serum B-cell maturation antigen levels above the median levels were predictive of a shorter progression-free survival ( =0.0006) and overall survival ( =0.0108) among multiple myeloma patients (n=243). Specifically, patients with serum B-cell maturation antigen levels above the median level at the time of starting front-line ( =0.0043) or a new salvage therapy ( =0.0044) were found to have shorter progression-free survival. Importantly, serum B-cell maturation antigen levels did not show any dependence on renal function and maintained independent significance when tested against other known prognostic markers for multiple myeloma such as age, serum ß2 microglobulin, hemoglobin, and bone disease. These data identify serum B-cell maturation antigen as a new biomarker to manage multiple myeloma patients.
[Mh] Termos MeSH primário: Antígeno de Maturação de Linfócitos B/sangue
Biomarcadores Tumorais
Mieloma Múltiplo/sangue
Mieloma Múltiplo/mortalidade
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Biomarcadores
Medula Óssea/metabolismo
Medula Óssea/patologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Mieloma Múltiplo/diagnóstico
Mieloma Múltiplo/tratamento farmacológico
Estadiamento de Neoplasias
Plasmócitos/metabolismo
Plasmócitos/patologia
Prognóstico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B-Cell Maturation Antigen); 0 (Biomarkers); 0 (Biomarkers, Tumor)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170707
[Lr] Data última revisão:
170707
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161231
[St] Status:MEDLINE
[do] DOI:10.3324/haematol.2016.150896


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[PMID]:28025583
[Au] Autor:Hipp S; Tai YT; Blanset D; Deegen P; Wahl J; Thomas O; Rattel B; Adam PJ; Anderson KC; Friedrich M
[Ad] Endereço:Immune-Modulation and Biotherapeutics Discovery, Boehringer Ingelheim RCV GmbH &Co KG, Vienna, Austria.
[Ti] Título:A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo.
[So] Source:Leukemia;31(8):1743-1751, 2017 Aug.
[Is] ISSN:1476-5551
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T-cell redirecting therapies. We developed a bispecific T-cell engager (BiTE) targeting BCMA and CD3É› (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA-negative cells were not affected. Activity of BI 836909 was not influenced by the presence of bone marrow stromal cells, soluble BCMA or a proliferation-inducing ligand (APRIL). In ex vivo assays, BI 836909 induced potent autologous MM cell lysis in both, newly diagnosed and relapsed/refractory patient samples. In mouse xenograft studies, BI 836909 induced tumor cell depletion in a subcutaneous NCI-H929 xenograft model and prolonged survival in an orthotopic L-363 xenograft model. In a cynomolgus monkey study, administration of BI 836909 led to depletion of BCMA-positive plasma cells in the bone marrow. Taken together, these results show that BI 836909 is a highly potent and efficacious approach to selectively deplete BCMA-positive MM cells and represents a novel immunotherapeutic for the treatment of MM.
[Mh] Termos MeSH primário: Anticorpos Biespecíficos/uso terapêutico
Antígeno de Maturação de Linfócitos B/imunologia
Complexo CD3/imunologia
Mieloma Múltiplo/terapia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Apoptose
Células Cultivadas
Citocinas/secreção
Feminino
Seres Humanos
Ativação Linfocitária
Macaca fascicularis
Camundongos
Mieloma Múltiplo/imunologia
Mieloma Múltiplo/patologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bispecific); 0 (B-Cell Maturation Antigen); 0 (CD3 Complex); 0 (Cytokines)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161228
[St] Status:MEDLINE
[do] DOI:10.1038/leu.2016.388


  9 / 195 MEDLINE  
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[PMID]:28028945
[Au] Autor:Shen X; Wang M; Guo Y; Ju S
[Ad] Endereço:Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, China.
[Ti] Título:The Correlation Between Non-Hodgkin Lymphoma and Expression Levels of B-Cell Activating Factor and Its Receptors.
[So] Source:Adv Clin Exp Med;25(5):837-844, 2016 Sep-Oct.
[Is] ISSN:1899-5276
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Lymphoma is a malignant tumor of the immune system originating from lymph nodes and extralymphatic tissues. Its occurrence is believed to be associated with various immune cells due to the proliferation and differentiation of lymphocytes during the immune response. It has been found in many studies that B-cell activating factor (BAFF), as a member of the tumor necrosis factor (TNF) superfamily, could specifically activate B lymphocytes and promote their proliferation. OBJECTIVES: To explore correlations between non-Hodgkin lymphoma (NHL) and the expression of BAFF and its receptors in NHL patients. MATERIAL AND METHODS: The protein expression of BAFF and its receptors in serum and BAFF mRNA expression in peripheral blood mononuclear cells (PBMCs) of 47 NHL patients and 20 healthy subjects were detected by ELISA and RFQ-PCR and compared with LDH and ß2M levels. RESULTS: BAFF mRNA expression in the PBMCs of NHL patients was significantly higher than in healthy controls. The expression levels of serum BAFF and the three receptors (TACI, BCMA and BAFF-R) in NHL patients were significantly higher than in healthy controls, and were not significantly correlated with ß2M and LDH levels. CONCLUSIONS: The serum protein concentration of BAFF and the expression level of BAFF mRNA in PBMCs of NHL patients underwent abnormal changes, indicating that BAFF and its receptors may play some role in the pathogenesis of NHL.
[Mh] Termos MeSH primário: Fator Ativador de Células B/metabolismo
Receptor do Fator Ativador de Células B/metabolismo
Antígeno de Maturação de Linfócitos B/metabolismo
Linfoma não Hodgkin/metabolismo
Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Fator Ativador de Células B/sangue
Fator Ativador de Células B/genética
Antígeno de Maturação de Linfócitos B/sangue
Estudos de Casos e Controles
Feminino
Seres Humanos
L-Lactato Desidrogenase/metabolismo
Linfoma não Hodgkin/sangue
Linfoma não Hodgkin/genética
Linfoma não Hodgkin/patologia
Masculino
Meia-Idade
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Proteína Transmembrana Ativadora e Interagente do CAML/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B-Cell Activating Factor); 0 (B-Cell Activation Factor Receptor); 0 (B-Cell Maturation Antigen); 0 (RNA, Messenger); 0 (TNFRSF13B protein, human); 0 (TNFRSF13C protein, human); 0 (TNFRSF17 protein, human); 0 (TNFSF13B protein, human); 0 (Transmembrane Activator and CAML Interactor Protein); EC 1.1.1.27 (L-Lactate Dehydrogenase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161229
[St] Status:MEDLINE
[do] DOI:10.17219/acem/29182


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Fotocópia
[PMID]:27655102
[Au] Autor:Uzzan M; Colombel JF; Cerutti A; Treton X; Mehandru S
[Ad] Endereço:Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. mathieuuzzan@gmail.com.
[Ti] Título:B Cell-Activating Factor (BAFF)-Targeted B Cell Therapies in Inflammatory Bowel Diseases.
[So] Source:Dig Dis Sci;61(12):3407-3424, 2016 Dec.
[Is] ISSN:1573-2568
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inflammatory bowel diseases (IBD) involve dysregulated immune responses to gut antigens in genetically predisposed individuals. While a better elucidation of IBD pathophysiology has considerably increased the number of treatment options, the need for more effective therapeutic strategies remains a pressing priority. Defects of both non-hematopoietic (epithelial and stromal) and hematopoietic (lymphoid and myeloid) cells have been described in patients with IBD. Within the lymphoid system, alterations of the T cell compartment are viewed as essential in the pathogenesis of IBD. However, growing evidence points to the additional perturbations of the B cell compartment. Indeed, the intestinal lamina propria from IBD patients shows an increased presence of antibody-secreting plasma cells, which correlates with enhanced pro-inflammatory immunoglobulin G production and changes in the quality of non-inflammatory IgA responses. These B cell abnormalities are compounded by the emergence of systemic antibody responses to various autologous and microbial antigens, which predates the clinical diagnosis of IBD and identifies patients with complicated disease. It is presently unclear whether such antibody responses play a pathogenetic role, as B cell depletion with the CD20-targeting monoclonal antibody rituximab did not ameliorate ulcerative colitis in a clinical trial. However, it must be noted that unresponsiveness to rituximab is also observed also in some patients with autoimmune disorders usually responsive to B cell-depleting therapies. In this review, we discussed mechanistic aspects of B cell-based therapies and their potential role in IBD with a special interest on BAFF and BAFF-targeting therapies buoyed by the success of anti-BAFF treatments in rheumatologic disorders.
[Mh] Termos MeSH primário: Fator Ativador de Células B/imunologia
Linfócitos B/imunologia
Fatores Imunológicos/uso terapêutico
Imunossupressores/uso terapêutico
Doenças Inflamatórias Intestinais/tratamento farmacológico
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/uso terapêutico
Anticorpos Monoclonais Humanizados/uso terapêutico
Fator Ativador de Células B/antagonistas & inibidores
Receptor do Fator Ativador de Células B/imunologia
Antígeno de Maturação de Linfócitos B/imunologia
Células Dendríticas/imunologia
Seres Humanos
Imunidade Humoral/imunologia
Switching de Imunoglobulina/imunologia
Imunoglobulina G/imunologia
Doenças Inflamatórias Intestinais/imunologia
Terapia de Alvo Molecular
Monócitos/imunologia
Plasmócitos/imunologia
Proteínas Recombinantes de Fusão/uso terapêutico
Rituximab/uso terapêutico
Linfócitos T/imunologia
Células Th1/imunologia
Células Th17/imunologia
Proteína Transmembrana Ativadora e Interagente do CAML/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antibodies, Monoclonal, Humanized); 0 (B-Cell Activating Factor); 0 (B-Cell Activation Factor Receptor); 0 (B-Cell Maturation Antigen); 0 (Immunoglobulin G); 0 (Immunologic Factors); 0 (Immunosuppressive Agents); 0 (Recombinant Fusion Proteins); 0 (TACI receptor-IgG Fc fragment fusion protein); 0 (Transmembrane Activator and CAML Interactor Protein); 4F4X42SYQ6 (Rituximab); 73B0K5S26A (belimumab); PQP8VH3MJW (tabalumab)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160923
[St] Status:MEDLINE



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