Base de dados : MEDLINE
Pesquisa : D12.776.395.550.014 [Categoria DeCS]
Referências encontradas : 685 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 69 ir para página                         

  1 / 685 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28465453
[Au] Autor:Kaufman HL
[Ad] Endereço:Departments of Surgery and Medicine, Rutgers University, New Brunswick, New Jersey. howard.kaufman@rutgers.edu.
[Ti] Título:Rational Combination Immunotherapy: Understand the Biology.
[So] Source:Cancer Immunol Res;5(5):355-356, 2017 May.
[Is] ISSN:2326-6074
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Selecting rational treatment combinations remains a major challenge for improving immunotherapy outcomes. In this issue of , Zhang and colleagues reduced tumors by inhibiting CD47 in a lung carcinoma model, a treatment that inadvertently induced autophagy through inhibition of the Akt/mTOR pathway. By also targeting autophagy, the therapeutic response improved, highlighting the importance of understanding the biology beneath antitumor immunity.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/terapia
Imunoterapia
Neoplasias Pulmonares/terapia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos Imunológicos/uso terapêutico
Autofagia/efeitos dos fármacos
Antígeno CD47/antagonistas & inibidores
Antígeno CD47/imunologia
Carcinoma Pulmonar de Células não Pequenas/imunologia
Cloroquina/uso terapêutico
Quimioterapia Combinada
Seres Humanos
Neoplasias Pulmonares/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Immunological); 0 (CD47 Antigen); 886U3H6UFF (Chloroquine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1158/2326-6066.CIR-17-0128


  2 / 685 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28801234
[Au] Autor:Xu MM; Pu Y; Han D; Shi Y; Cao X; Liang H; Chen X; Li XD; Deng L; Chen ZJ; Weichselbaum RR; Fu YX
[Ad] Endereço:Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; Department of Radiation and Cellular Oncology, The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA.
[Ti] Título:Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling.
[So] Source:Immunity;47(2):363-373.e5, 2017 Aug 15.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion, but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA, increase of DNA sensing by blocking the interaction of SIRPα with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically, CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs, which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs. mtDNA was recognized by cyclic-GMP-AMP synthase (cGAS) in the DC cytosol, contributing to type I interferon (IFN) production and antitumor adaptive immunity. Thus, our findings have demonstrated how tumor cells inhibit innate sensing in DCs and suggested that the CD47-SIRPα axis is critical for DC-driven antitumor immunity.
[Mh] Termos MeSH primário: Antígenos de Diferenciação/metabolismo
Neoplasias do Colo/imunologia
DNA Mitocondrial/imunologia
Células Dendríticas/imunologia
Proteínas de Membrana/metabolismo
Receptores Imunológicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Anticorpos Bloqueadores/uso terapêutico
Antígeno CD47/imunologia
Antígeno CD47/metabolismo
Células Cultivadas
Neoplasias do Colo/genética
Neoplasias do Colo/terapia
Apresentação Cruzada
Modelos Animais de Doenças
Seres Humanos
Interferon Tipo I/metabolismo
Macrófagos/imunologia
Glicoproteínas de Membrana/metabolismo
Proteínas de Membrana/genética
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
NADPH Oxidase 2
NADPH Oxidases/metabolismo
Nucleotidiltransferases/metabolismo
Transdução de Sinais
Evasão Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Blocking); 0 (Antigens, Differentiation); 0 (CD47 Antigen); 0 (DNA, Mitochondrial); 0 (Interferon Type I); 0 (MPYS protein, mouse); 0 (Membrane Glycoproteins); 0 (Membrane Proteins); 0 (Ptpns1 protein, mouse); 0 (Receptors, Immunologic); 0 (SIRPA protein, human); EC 1.6.3.- (CYBB protein, human); EC 1.6.3.- (NADPH Oxidase 2); EC 1.6.3.- (NADPH Oxidases); EC 2.7.7.- (MB21D1 protein, mouse); EC 2.7.7.- (Nucleotidyltransferases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170813
[St] Status:MEDLINE


  3 / 685 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28632731
[Au] Autor:Barrera L; Montes-Servín E; Hernandez-Martinez JM; García-Vicente MLÁ; Montes-Servín E; Herrera-Martínez M; Crispín JC; Borbolla-Escoboza JR; Arrieta O
[Ad] Endereço:Functional Unit of Thoracic Oncology and Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico City, Mexico.
[Ti] Título:CD47 overexpression is associated with decreased neutrophil apoptosis/phagocytosis and poor prognosis in non-small-cell lung cancer patients.
[So] Source:Br J Cancer;117(3):385-397, 2017 Jul 25.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Non-small-cell lung cancer (NSCLC) patients often exhibit neutrophilia, which has been associated with poor clinical outcomes. However, the mechanisms that lead to neutrophilia have not been fully established. CD47 is an antiphagocytic molecule that promotes neutrophil recruitment. METHODS: Blood was collected from 50 treatment-naive patients with advanced NSCLC and from 25 healthy subjects. The frequency of CD66b cells and the expression of CD47 were determined by flow cytometry. Neutrophil apoptosis was determined by 7-amino-actinomycin D/Annexin V-APC staining. Phagocytosis was assessed by flow cytometry. Reactive oxygen species production after phorbol 12-myristate 13-acetate treatment was quantified by 2',7'-dichlorofluorescein fluorescence. Pro-inflammatory plasma cytokines were quantified using a cytometric bead array assay. RESULTS: The percentage of circulating neutrophils was significantly higher in patients than in controls (P<0.001). Patient-derived neutrophils had a higher oxidative potential than those of controls (P=0.0286). The number of neutrophils in late apoptosis/necrosis was lower in patients than in controls (P=0.0317). Caspase 3/7 activation was also lower in patients than in controls (P=0.0079). CD47 expression in whole-blood samples and in the neutrophil fraction was higher in NSCLC patients than in controls (P=0.0408 and P<0.001). Patient-derived neutrophils were phagocytosed at a lower rate than those of controls (P=0.0445). CD47 expression in neutrophils negatively correlated with their ingestion by macrophages (P=0.0039). High CD47 expression was associated with a lower overall survival. CONCLUSIONS: Increased CD47 expression on the surface of neutrophils was associated with a delay in neutrophil apoptosis and with an impairment in their phagocytic clearance by macrophages, suggesting that CD47 overexpression may be one of the underlying mechanisms leading to neutrophilia in NSCLC patients.
[Mh] Termos MeSH primário: Antígeno CD47/sangue
Carcinoma Pulmonar de Células não Pequenas/sangue
Neoplasias Pulmonares/sangue
Neutrófilos/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Antígenos CD/análise
Apoptose
Estudos de Casos e Controles
Caspase 3/metabolismo
Caspase 7/metabolismo
Moléculas de Adesão Celular/análise
Citocinas/sangue
Feminino
Proteínas Ligadas por GPI/análise
Seres Humanos
Contagem de Leucócitos
Masculino
Meia-Idade
Neutrófilos/química
Neutrófilos/fisiologia
Fagocitose
Prognóstico
Espécies Reativas de Oxigênio/metabolismo
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD47 Antigen); 0 (CEACAM8 protein, human); 0 (Cell Adhesion Molecules); 0 (Cytokines); 0 (GPI-Linked Proteins); 0 (Reactive Oxygen Species); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 7)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.173


  4 / 685 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28607485
[Au] Autor:Kamerkar S; LeBleu VS; Sugimoto H; Yang S; Ruivo CF; Melo SA; Lee JJ; Kalluri R
[Ad] Endereço:Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77005, USA.
[Ti] Título:Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer.
[So] Source:Nature;546(7659):498-503, 2017 06 22.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic Kras , a common mutation in pancreatic cancer. Compared to liposomes, the engineered exosomes (known as iExosomes) target oncogenic KRAS with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. Treatment with iExosomes suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival. Our results demonstrate an approach for direct and specific targeting of oncogenic KRAS in tumours using iExosomes.
[Mh] Termos MeSH primário: Exossomos/metabolismo
Inativação Gênica
Neoplasias Pancreáticas/genética
Neoplasias Pancreáticas/terapia
Proteínas Proto-Oncogênicas p21(ras)/genética
RNA Interferente Pequeno/administração & dosagem
RNA Interferente Pequeno/genética
[Mh] Termos MeSH secundário: Animais
Antígeno CD47/metabolismo
Modelos Animais de Doenças
Exossomos/imunologia
Feminino
Terapia Genética
Lipossomos/imunologia
Camundongos
Monócitos/citologia
Monócitos/imunologia
Metástase Neoplásica/prevenção & controle
Neoplasias Pancreáticas/sangue
Neoplasias Pancreáticas/patologia
Pinocitose
Proteínas Proto-Oncogênicas p21(ras)/metabolismo
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CD47 Antigen); 0 (Cd47 protein, mouse); 0 (Liposomes); 0 (RNA, Small Interfering); EC 3.6.5.2 (Kras2 protein, mouse); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.1038/nature22341


  5 / 685 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28537232
[Au] Autor:Ratnikova NM; Lezhnin YN; Frolova EI; Kravchenko JE; Chumakov SP
[Ad] Endereço:Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia.
[Ti] Título:[CD47 receptor as a primary target for cancer therapy].
[So] Source:Mol Biol (Mosk);51(2):251-261, 2017 Mar-Apr.
[Is] ISSN:0026-8984
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Recently, a number of new highly efficient antibody-based anticancer therapeutics have emerged. These receptor-binding antibodies have beneficial toxicity profiles associated with relatively mild side effects. Therefore, the search for novel surface proteins that are present on cancer cells and play important metabolic or defensive roles has intensified. Additionally, the therapeutic stimulation of patient's immune system in order to aim its components, specifically, phagocytes and cytotoxic T-lymphocytes, at tumor cells is gaining traction. This review is focused on the CD47 surface receptor, a ubiquitously expressed molecule, which could nevertheless serve as a therapeutic target due to its ability to simultaneously stimulate both natural and adaptive immune response.
[Mh] Termos MeSH primário: Antígenos de Neoplasias/imunologia
Antígeno CD47/imunologia
Imunidade Celular
Imunidade Inata
Neoplasias
Fagócitos/imunologia
Linfócitos T Citotóxicos/imunologia
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Neoplasias/imunologia
Neoplasias/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (CD47 Antigen); 0 (CD47 protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.7868/S0026898417010153


  6 / 685 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28522599
[Au] Autor:Alvey C; Discher DE
[Ad] Endereço:Systems Pharmacology and Translational Therapeutics Graduate Group, Physical Sciences Oncology Center at Penn, Molecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
[Ti] Título:Engineering macrophages to eat cancer: from "marker of self" CD47 and phagocytosis to differentiation.
[So] Source:J Leukoc Biol;102(1):31-40, 2017 Jul.
[Is] ISSN:1938-3673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The ability of a macrophage to engulf and break down invading cells and other targets provides a first line of immune defense in nearly all tissues. This defining ability to "phagos" or devour can subsequently activate the entire immune system against foreign and diseased cells, and progress is now being made on a decades-old idea of directing macrophages to phagocytose specific targets, such as cancer cells. Engineered T cells provide precedence with recent clinical successes against liquid tumors, but solid tumors remain a challenge, and a handful of clinical trials seek to exploit the abundance of tumor-associated macrophages instead. Although macrophage differentiation into such phenotypes with deficiencies in phagocytic ability can raise challenges, newly recognized features of cancer cells that might be manipulated to increase the phagocytosis of those cells include ≥1 membrane protein, CD47, which broadly inhibits phagocytosis and is abundantly expressed on all healthy cells. Physical properties of the target also influence phagocytosis and again relate-via cytoskeleton forces-to differentiation pathways in solid tumors. Such pathways extend to mechanosensing by the nuclear lamina, which is known to influence signaling by soluble retinoids that can regulate the macrophage SIRPα, the receptor for CD47. Here, we highlight some of those past, present, and rapidly emerging efforts to understand and control macrophages for cancer therapy.
[Mh] Termos MeSH primário: Biomarcadores Tumorais
Antígeno CD47
Citofagocitose/genética
Engenharia Genética
Macrófagos/imunologia
Neoplasias
[Mh] Termos MeSH secundário: Animais
Antígenos de Diferenciação/genética
Antígenos de Diferenciação/imunologia
Biomarcadores Tumorais/genética
Biomarcadores Tumorais/imunologia
Antígeno CD47/genética
Antígeno CD47/imunologia
Seres Humanos
Neoplasias/genética
Neoplasias/imunologia
Neoplasias/terapia
Receptores Imunológicos/genética
Receptores Imunológicos/imunologia
Transdução de Sinais/genética
Transdução de Sinais/imunologia
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, Differentiation); 0 (Biomarkers, Tumor); 0 (CD47 Antigen); 0 (Receptors, Immunologic); 0 (SIRPA protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1189/jlb.4RI1216-516R


  7 / 685 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28424516
[Au] Autor:Chen J; Zhong MC; Guo H; Davidson D; Mishel S; Lu Y; Rhee I; Pérez-Quintero LA; Zhang S; Cruz-Munoz ME; Wu N; Vinh DC; Sinha M; Calderon V; Lowell CA; Danska JS; Veillette A
[Ad] Endereço:Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec H2W 1R7, Canada.
[Ti] Título:SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin.
[So] Source:Nature;544(7651):493-497, 2017 04 27.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα-CD47 checkpoint could be useful in treating human cancer. However, the pro-phagocytic receptor(s) responsible for tumour cell phagocytosis is(are) largely unknown. Here we find that macrophages are much more efficient at phagocytosis of haematopoietic tumour cells, compared with non-haematopoietic tumour cells, in response to SIRPα-CD47 blockade. Using a mouse lacking the signalling lymphocytic activation molecule (SLAM) family of homotypic haematopoietic cell-specific receptors, we determined that phagocytosis of haematopoietic tumour cells during SIRPα-CD47 blockade was strictly dependent on SLAM family receptors in vitro and in vivo. In both mouse and human cells, this function required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319), expressed on macrophages and tumour cell targets. In contrast to most SLAM receptor functions, SLAMF7-mediated phagocytosis was independent of signalling lymphocyte activation molecule-associated protein (SAP) adaptors. Instead, it depended on the ability of SLAMF7 to interact with integrin Mac-1 (refs 18, 19, 20) and utilize signals involving immunoreceptor tyrosine-based activation motifs. These findings elucidate the mechanism by which macrophages engulf and destroy haematopoietic tumour cells. They also reveal a novel SAP adaptor-independent function for a SLAM receptor. Lastly, they suggest that patients with tumours expressing SLAMF7 are more likely to respond to SIRPα-CD47 blockade therapy.
[Mh] Termos MeSH primário: Neoplasias Hematológicas/imunologia
Neoplasias Hematológicas/patologia
Antígeno de Macrófago 1/metabolismo
Macrófagos/imunologia
Fagocitose/imunologia
Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo
[Mh] Termos MeSH secundário: Actinas/metabolismo
Animais
Antígenos de Diferenciação/imunologia
Antígenos de Diferenciação/metabolismo
Antígeno CD47/imunologia
Antígeno CD47/metabolismo
Feminino
Neoplasias Hematológicas/tratamento farmacológico
Seres Humanos
Macrófagos/citologia
Macrófagos/metabolismo
Masculino
Camundongos
Camundongos Knockout
Receptores Imunológicos/antagonistas & inibidores
Receptores Imunológicos/imunologia
Receptores Imunológicos/metabolismo
Família de Moléculas de Sinalização da Ativação Linfocitária/deficiência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Actins); 0 (Antigens, Differentiation); 0 (CD47 Antigen); 0 (CD47 protein, human); 0 (Macrophage-1 Antigen); 0 (Receptors, Immunologic); 0 (SIRPA protein, human); 0 (SLAMF7 protein, human); 0 (Signaling Lymphocytic Activation Molecule Family); 0 (Slamf7 protein, mouse)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1038/nature22076


  8 / 685 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28403150
[Au] Autor:Martinez-Marin D; Jarvis C; Nelius T; de Riese W; Volpert OV; Filleur S
[Ad] Endereço:Department of Urology, Texas Tech University-Health Sciences Center, Lubbock, Texas, United States of America.
[Ti] Título:PEDF increases the tumoricidal activity of macrophages towards prostate cancer cells in vitro.
[So] Source:PLoS One;12(4):e0174968, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Although inflammation and prostate cancer (PCa) have been linked, the molecular interactions between macrophages and PCa cells are poorly explored. Pigment Epithelium-Derived Factor (PEDF) is an anti-angiogenic and anti-tumor factor. We previously showed that PEDF induces macrophages recruitment in vitro, correlates with macrophages density in human prostate, and stimulates macrophages polarization towards the classically activated pathway. Here, we demonstrate that PEDF modulates the interaction between macrophages and PCa cells through a bidirectional signalling leading to tumor cell apoptosis and phagocytosis. METHODS: RAW 264.7 and THP-1 cells, and BMDMs were grown in vitro as mono- or co-cultures with PC3 or CL1 tumor cells. The effects of PEDF and its derived P18 peptide were measured on macrophages differentiation, migration, and superoxide production, and tumor cell apoptosis and phagocytosis. PEDF receptors (ATP5B, PNPLA2, and LRP6) and CD47 mRNA and protein expression were quantified in macrophages and tumor cells by quantitative RT-PCR, western blot, immunofluorescence and flow cytometry. RESULTS: We found that PEDF induced the migration of macrophages towards tumor 3D spheroids and 2D cultures. In co-culture, PEDF increased PCa cells phagocytosis through an indirect apoptosis-dependent mechanism. Moreover, PEDF stimulated the production of superoxide by macrophages. Conditioned media from macrophages exposed to PEDF induced tumor cells apoptosis in contrast to control conditioned media suggesting that ROS may be involved in tumor cells apoptosis. ATP5B and PNPLA2 PEDF receptors on macrophages and CD47 on tumor cells were respectively up- and down-regulated by PEDF. As PEDF, blocking CD47 induced phagocytosis. Inhibiting ATP5B reduced phagocytosis. Inversely, PNPLA2 inhibition blocks differentiation but maintains phagocytosis. CD47-induced phagocytosis was partially reverted by ATP5B inhibition suggesting a complementary action. Similar effects were observed with P18 PEDF-derived peptide. CONCLUSIONS: These data established that modulating the molecular interactions between macrophages and PCa cells using PEDF may be a promising strategy for PCa treatment.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Proteínas do Olho/farmacologia
Macrófagos/fisiologia
Fatores de Crescimento Neural/farmacologia
Neoplasias da Próstata/tratamento farmacológico
Serpinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Antígeno CD47/metabolismo
Linhagem Celular Tumoral
Movimento Celular
Técnicas de Cocultura
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Lipase/metabolismo
Macrófagos/efeitos dos fármacos
Masculino
Camundongos
ATPases Mitocondriais Próton-Translocadoras/metabolismo
Fagocitose
Compostos de Fenilureia/farmacologia
Células RAW 264.7
Esferoides Celulares/efeitos dos fármacos
Esferoides Celulares/metabolismo
Superóxidos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (CD47 Antigen); 0 (Eye Proteins); 0 (Nerve Growth Factors); 0 (Phenylurea Compounds); 0 (Serpins); 0 (atglistatin); 0 (pigment epithelium-derived factor); 11062-77-4 (Superoxides); EC 3.1.1.3 (Lipase); EC 3.1.1.3 (PNPLA2 protein, mouse); EC 3.6.3.- (ATP5b protein, mouse); EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174968


  9 / 685 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28289091
[Au] Autor:Lopes FB; Bálint S; Valvo S; Felce JH; Hessel EM; Dustin ML; Davis DM
[Ad] Endereço:Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9NT, England, UK.
[Ti] Título:Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages.
[So] Source:J Cell Biol;216(4):1123-1141, 2017 Apr 03.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Signal integration between activating Fc receptors and inhibitory signal regulatory protein α (SIRPα) controls macrophage phagocytosis. Here, using dual-color direct stochastic optical reconstruction microscopy, we report that Fcγ receptor I (FcγRI), FcγRII, and SIRPα are not homogeneously distributed at macrophage surfaces but are organized in discrete nanoclusters, with a mean radius of 71 ± 11 nm, 60 ± 6 nm, and 48 ± 3 nm, respectively. Nanoclusters of FcγRI, but not FcγRII, are constitutively associated with nanoclusters of SIRPα, within 62 ± 5 nm, mediated by the actin cytoskeleton. Upon Fc receptor activation, Src-family kinase signaling leads to segregation of FcγRI and SIRPα nanoclusters to be 197 ± 3 nm apart. Co-ligation of SIRPα with CD47 abrogates nanocluster segregation. If the balance of signals favors activation, FcγRI nanoclusters reorganize into periodically spaced concentric rings. Thus, a nanometer- and micron-scale reorganization of activating and inhibitory receptors occurs at the surface of human macrophages concurrent with signal integration.
[Mh] Termos MeSH primário: Macrófagos/metabolismo
Membranas/metabolismo
Receptores de IgG/metabolismo
Receptores Imunológicos/metabolismo
[Mh] Termos MeSH secundário: Citoesqueleto de Actina/metabolismo
Antígeno CD47/metabolismo
Proteínas de Transporte/metabolismo
Seres Humanos
Leucócitos Mononucleares/metabolismo
Fagocitose/fisiologia
Ligação Proteica/fisiologia
Transdução de Sinais/fisiologia
Quinases da Família src/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD47 Antigen); 0 (CD47 protein, human); 0 (Carrier Proteins); 0 (Receptors, IgG); 0 (Receptors, Immunologic); EC 2.7.10.2 (src-Family Kinases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171123
[Lr] Data última revisão:
171123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201608094


  10 / 685 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28286286
[Au] Autor:Weiskopf K
[Ad] Endereço:Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: kweiskopf@bwh.harvard.edu.
[Ti] Título:Cancer immunotherapy targeting the CD47/SIRPα axis.
[So] Source:Eur J Cancer;76:100-109, 2017 May.
[Is] ISSN:1879-0852
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The success of cancer immunotherapy has generated tremendous interest in identifying new immunotherapeutic targets. To date, the majority of therapies have focussed on stimulating the adaptive immune system to attack cancer, including agents targeting CTLA-4 and the PD-1/PD-L1 axis. However, macrophages and other myeloid immune cells offer much promise as effectors of cancer immunotherapy. The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint. CD47 is highly expressed on many different types of cancer, and it transduces inhibitory signals through SIRPα on macrophages and other myeloid cells. In a diverse range of preclinical models, therapies that block the CD47/SIRPα axis stimulate phagocytosis of cancer cells in vitro and anti-tumour immune responses in vivo. A number of therapeutics that target the CD47/SIRPα axis are under preclinical and clinical investigation. These include anti-CD47 antibodies, engineered receptor decoys, anti-SIRPα antibodies and bispecific agents. These therapeutics differ in their pharmacodynamic, pharmacokinetic and toxicological properties. Clinical trials are underway for both solid and haematologic malignancies using anti-CD47 antibodies and recombinant SIRPα proteins. Since the CD47/SIRPα axis also limits the efficacy of tumour-opsonising antibodies, additional trials will examine their potential synergy with agents such as rituximab, cetuximab and trastuzumab. Phagocytosis in response to CD47/SIRPα-blocking agents results in antigen uptake and presentation, thereby linking the innate and adaptive immune systems. CD47/SIRPα blocking therapies may therefore synergise with immune checkpoint inhibitors that target the adaptive immune system. As a critical regulator of macrophage phagocytosis and activation, the potential applications of CD47/SIRPα blocking therapies extend beyond human cancer. They may be useful for the treatment of infectious disease, conditioning for stem cell transplant, and many other clinical indications.
[Mh] Termos MeSH primário: Anticorpos Antineoplásicos/efeitos dos fármacos
Antígeno CD47/imunologia
Imunoterapia/métodos
Macrófagos/efeitos dos fármacos
Neoplasias/tratamento farmacológico
Fagocitose/efeitos dos fármacos
Receptores Imunológicos/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Anticorpos Antineoplásicos/imunologia
Apresentação do Antígeno/efeitos dos fármacos
Apresentação do Antígeno/imunologia
Antígenos de Diferenciação/imunologia
Seres Humanos
Macrófagos/imunologia
Camundongos
Terapia de Alvo Molecular
Células Mieloides/efeitos dos fármacos
Células Mieloides/imunologia
Neoplasias/imunologia
Fagocitose/imunologia
Receptores Imunológicos/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Neoplasm); 0 (Antigens, Differentiation); 0 (CD47 Antigen); 0 (Ptpns1 protein, mouse); 0 (Receptors, Immunologic); 0 (SIRPA protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170314
[St] Status:MEDLINE



página 1 de 69 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde