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Pesquisa : D02.241.081.844.562.668.050 [Categoria DeCS]
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[PMID]:28460336
[Au] Autor:Shashni B; Horiguchi Y; Kurosu K; Furusho H; Nagasaki Y
[Ad] Endereço:Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8573, Japan.
[Ti] Título:Application of surface enhanced Raman spectroscopy as a diagnostic system for hypersialylated metastatic cancers.
[So] Source:Biomaterials;134:143-153, 2017 Jul.
[Is] ISSN:1878-5905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Early diagnosis of metastatic cancers could greatly limit the number of cancer-associated deaths. Aberrant surface expression of sialic acid (hypersialylation) on tumors correlating with metastatic incidence and its involvement in tumorigenesis and progression is widely reported; hence detection of hypersialylated tumors may be an effective strategy to identify metastatic cancers. We herein report on the application of phenylboronic acid-installed PEGylated gold nanoparticles coupled with Toluidine blue O (T/BA-GNPs) as SERS probes to target surface sialic acid (N-acetylneuraminic acid, Neu5Ac). Strong SERS signals from metastatic cancer cell lines (breast cancer; MDA-MB231 and colon cancer; Colon-26) were observed, contrary to non-metastatic MCF-7 cells (breast cancer). The detected SERS signals from various cancer cell lines correlated with their reported metastatic potential, implying that our T/BA-GNP based SERS system was capable of distinguishing the metastaticity of cells based on the surface Neu5Ac density. T/BA-GNP based SERS system could also significantly differentiate between hypersialylated tumor tissues and healthy tissues with high SERS signal to noise ratio, due to plasmon coupling between the specifically aggregated functionalized GNPs. Furthermore, we also confirmed reduction in SERS signals from MDA-MB231 surface upon treatment with our original reactive oxygen species (ROS)-scavenging polymeric micelle, nitroxide-radical containing nanoparticles (RNPs). The ROS-mediated abrogation of sialylation by impairing the activation of NF-κB-sialyltransferase signaling cascade upon RNP treatment was confirmed by expression studies and the T/BA-GNPs based SERS system. The aforementioned findings thus, establish T/BA-GNPs based SERS as a potential cytodiagnostic system to detect hypersialylated metastatic tumors and RNPs as anti-metastatic cancer drug candidates.
[Mh] Termos MeSH primário: Ácidos Borônicos/uso terapêutico
Ácido N-Acetilneuramínico/metabolismo
Análise Espectral Raman/métodos
[Mh] Termos MeSH secundário: Animais
Western Blotting
Ácidos Borônicos/química
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/metabolismo
Linhagem Celular Tumoral
Cromatografia em Gel
Ouro/química
Seres Humanos
Células MCF-7
Nanopartículas Metálicas/química
Camundongos
NF-kappa B/metabolismo
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Boronic Acids); 0 (NF-kappa B); 0 (Reactive Oxygen Species); 7440-57-5 (Gold); GZP2782OP0 (N-Acetylneuraminic Acid); L12H7B02G5 (benzeneboronic acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:29188738
[Au] Autor:Hu JB; Song GL; Liu D; Li SJ; Wu JH; Kang XQ; Qi J; Jin FY; Wang XJ; Xu XL; Ying XY; Yu L; You J; Du YZ
[Ad] Endereço:a Institute of Pharmaceutics, College of Pharmaceutical Sciences , Zhejiang University , Hangzhou , China.
[Ti] Título:Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury.
[So] Source:Drug Deliv;24(1):1856-1867, 2017 Nov.
[Is] ISSN:1521-0464
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In an attempt to improve therapeutic efficacy of dexamethasone (DXM)-loaded solid lipid nanoparticles (NPs) for renal ischemia-reperfusion injury (IRI)-induced acute renal injury (AKI), sialic acid (SA) is used as a ligand to target the inflamed vascular endothelium. DXM-loaded SA-conjugated polyethylene glycol (PEG)ylated NPs (SA-NPs) are prepared via solvent diffusion method and show the good colloidal stability. SA-NPs reduce apoptotic human umbilical vein endothelial cells (HUVECs) via downregulating oxidative stress-induced Bax, upregulating Bcl-xL, and inhibiting Caspase-3 and Caspase-9 activation. Cellular uptake results suggest SA-NPs can be specifically internalized by the inflamed vascular endothelial cells (H O -pretreated HUVECs), and the mechanism is associated with the specific binding between SA and E-selectin receptor expressed on the inflamed vascular endothelial cells. Bio-distribution results further demonstrated the enhanced renal accumulation of DXM is achieved in AKI mice treated with SA-NPs, and its content is 2.70- and 5.88-fold higher than those treated with DXM and NPs at 6 h after intravenous administration, respectively. Pharmacodynamic studies demonstrate SA-NPs effectively ameliorate renal functions in AKI mice, as reflected by improved blood biochemical indexes, histopathological changes, oxidative stress levels and pro-inflammatory cytokines. Moreover, SA-NPs cause little negative effects on lymphocyte count and bone mineral density while DXM leads to severe osteoporosis. It is concluded that SA-NPs provide an efficient and targeted delivery of DXM for ischemia-reperfusion-induced injury-induced AKI, with improved therapeutic outcomes and reduced adverse effects.
[Mh] Termos MeSH primário: Lesão Renal Aguda/tratamento farmacológico
Portadores de Fármacos/química
Endotélio Vascular/efeitos dos fármacos
Lipídeos/química
Ácido N-Acetilneuramínico/química
Nanopartículas/química
Traumatismo por Reperfusão/tratamento farmacológico
[Mh] Termos MeSH secundário: Lesão Renal Aguda/metabolismo
Animais
Caspase 3/metabolismo
Linhagem Celular
Dexametasona/farmacologia
Selectina E/metabolismo
Endotélio Vascular/metabolismo
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Rim/efeitos dos fármacos
Rim/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos ICR
Nanopartículas/administração & dosagem
Estresse Oxidativo/efeitos dos fármacos
Polietilenoglicóis/química
Traumatismo por Reperfusão/metabolismo
Proteína X Associada a bcl-2/metabolismo
Proteína bcl-X/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (E-Selectin); 0 (Lipids); 0 (bcl-2-Associated X Protein); 0 (bcl-X Protein); 30IQX730WE (Polyethylene Glycols); 7S5I7G3JQL (Dexamethasone); EC 3.4.22.- (Caspase 3); GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.1080/10717544.2017.1410258


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[PMID]:29198893
[Au] Autor:Tsuji M; Sriwilaijaroen N; Inoue H; Miki K; Kinoshita K; Koyama K; Furuhata K; Suzuki Y; Takahashi K
[Ad] Endereço:Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose-shi, Tokyo 204-8588, Japan.
[Ti] Título:Synthesis and anti-influenza virus evaluation of triterpene-sialic acid conjugates.
[So] Source:Bioorg Med Chem;26(1):17-24, 2018 01 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We are interested in new non-natural glycosides with sialic acid conjugates and their biological activities. We report the synthesis of eleven non-natural occurring glycosides, which are triterpene (glycyrrhetinic acid and its derivatives)-sialic acid conjugates, and their inhibitory activities against influenza virus sialidases and influenza virus multiplication in MDCK host cells. Deoxoglycyrrhetol-sialic acid conjugates (6d and 6e) and oleanolic acid-sialic acid conjugates (7d and 7e) showed strong inhibitory activities against three subtypes of influenza virus sialidases. These four compounds (6d, 6e, 7d and 7e) showed clear inhibition to influenza virus multiplication but not to MDCK host cell survival.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Ácido N-Acetilneuramínico/farmacologia
Orthomyxoviridae/efeitos dos fármacos
Triterpenos/farmacologia
[Mh] Termos MeSH secundário: Animais
Antivirais/síntese química
Antivirais/química
Sobrevivência Celular/efeitos dos fármacos
Galinhas
Cães
Relação Dose-Resposta a Droga
Células Madin Darby de Rim Canino
Testes de Sensibilidade Microbiana
Estrutura Molecular
Ácido N-Acetilneuramínico/química
Relação Estrutura-Atividade
Triterpenos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Triterpenes); GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180106
[Lr] Data última revisão:
180106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE


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[PMID]:29072130
[Au] Autor:Chugh M; Piskarev V; Galanina O; Khasbiullina N; Kadam P; Shilova N; Pazynina G; Dobrochaeva K; Bhanushali P; Kozlov N; Tupitsin N; Bovin N
[Ad] Endereço:1 Agappe Diagnostics Ltd, Kochi, India.
[Ti] Título:Glycoprotein CA19.9-specific monoclonal antibodies recognize sialic acid-independent glycotope.
[So] Source:Tumour Biol;39(10):1010428317725434, 2017 Oct.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A repertoire of monoclonal antibodies was generated by immunization of mice with cancer-associated glycoprotein CA19.9, and two of them were selected as optimal capture and detecting counterparts for sandwich test system for detection of CA19.9. Fine epitope specificity of the antibodies was determined using printed glycan array, enzyme-linked immunosorbent assay, and inhibitory enzyme-linked immunosorbent assay. Unexpectedly, both immunoglobulins did not bind key epitope of CA19.9 glycoprotein, tetrasaccharide SiaLe , as well as its defucosylated form sialyl Le (known as CA-50 epitope). The antibodies were found to have different glycan-binding profiles; however, they recognized similar glycotopes with common motif Galß1-3GlcNAcß (Le ), thus resembling specificity of human natural cancer-associated anti-Le antibodies. We propose that cancer-specific glycopeptide epitope includes Galß1-3GlcNAcß fragment of a glycoprotein O-chain in combination with proximal hydrophobic amino acid(s) of the polypeptide chain.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Antígeno CA-19-9/imunologia
Epitopos/imunologia
Neoplasias/imunologia
Trissacarídeos/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/genética
Antígeno CA-19-9/genética
Epitopos/genética
Glicopeptídeos/genética
Glicopeptídeos/imunologia
Seres Humanos
Camundongos
Ácido N-Acetilneuramínico/genética
Ácido N-Acetilneuramínico/imunologia
Neoplasias/genética
Trissacarídeos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (CA-19-9 Antigen); 0 (Epitopes); 0 (Glycopeptides); 0 (Trisaccharides); 0 (galactosyl-beta(1-3)-N-acetylglucosaminyl-beta(1-3)galactose); GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171027
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317725434


  5 / 5311 MEDLINE  
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[PMID]:28916265
[Au] Autor:Andrabi R; Su CY; Liang CH; Shivatare SS; Briney B; Voss JE; Nawazi SK; Wu CY; Wong CH; Burton DR
[Ad] Endereço:Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripp
[Ti] Título:Glycans Function as Anchors for Antibodies and Help Drive HIV Broadly Neutralizing Antibody Development.
[So] Source:Immunity;47(3):524-537.e3, 2017 Sep 19.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Apex broadly neutralizing HIV antibodies (bnAbs) recognize glycans and protein surface close to the 3-fold axis of the envelope (Env) trimer and are among the most potent and broad Abs described. The evolution of apex bnAbs from one donor (CAP256) has been studied in detail and many Abs at different stages of maturation have been described. Using diverse engineering tools, we investigated the involvement of glycan recognition in the development of the CAP256.VRC26 Ab lineage. We found that sialic acid-bearing glycans were recognized by germline-encoded and somatically mutated residues on the Ab heavy chain. This recognition provided an "anchor" for the Abs as the core protein epitope varies, prevented complete neutralization escape, and eventually led to broadening of the response. These findings illustrate how glycan-specific maturation enables a human Ab to cope with pathogen escape mechanisms and will aid in optimization of immunization strategies to induce V2 apex bnAb responses.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/imunologia
Anticorpos Anti-HIV/imunologia
Infecções por HIV/imunologia
Infecções por HIV/metabolismo
HIV-1/imunologia
Polissacarídeos/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Afinidade de Anticorpos/imunologia
Formação de Anticorpos/imunologia
Sítios de Ligação
Epitopos/imunologia
Anticorpos Anti-HIV/química
Anticorpos Anti-HIV/classificação
Anticorpos Anti-HIV/genética
Proteína gp120 do Envelope de HIV/química
Proteína gp120 do Envelope de HIV/imunologia
Infecções por HIV/virologia
Seres Humanos
Cadeias Pesadas de Imunoglobulinas/genética
Modelos Moleculares
Ácido N-Acetilneuramínico/metabolismo
Testes de Neutralização
Fragmentos de Peptídeos/imunologia
Filogenia
Ligação Proteica/imunologia
Conformação Proteica
Multimerização Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Epitopes); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp120); 0 (Immunoglobulin Heavy Chains); 0 (Peptide Fragments); 0 (Polysaccharides); GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170917
[St] Status:MEDLINE


  6 / 5311 MEDLINE  
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[PMID]:28880909
[Au] Autor:Mastrangeli R; Satwekar A; Cutillo F; Ciampolillo C; Palinsky W; Longobardi S
[Ad] Endereço:Biotech Development Programme, Merck Serono S.p.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Guidonia Montecelio, Rome, Italy.
[Ti] Título:In-vivo biological activity and glycosylation analysis of a biosimilar recombinant human follicle-stimulating hormone product (Bemfola) compared with its reference medicinal product (GONAL-f).
[So] Source:PLoS One;12(9):e0184139, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recombinant human follicle-stimulating hormone (r-hFSH) is widely used in fertility treatment. Although biosimilar versions of r-hFSH (follitropin alfa) are currently on the market, given their structural complexity and manufacturing process, it is important to thoroughly evaluate them in comparison with the reference product. This evaluation should focus on how they differ (e.g., active component molecular characteristics, impurities and potency), as this could be associated with clinical outcome. This study compared the site-specific glycosylation profile and batch-to-batch variability of the in-vivo bioactivity of Bemfola, a biosimilar follitropin alfa, with its reference medicinal product GONAL-f. The focus of this analysis was the site-specific glycosylation at asparagine (Asn) 52 of the α-subunit of FSH, owing to the pivotal role of Asn52 glycosylation in FSH receptor (FSHR) activation/signalling. Overall, Bemfola had bulkier glycan structures and greater sialylation than GONAL-f. The nominal specific activity for both Bemfola and GONAL-f is 13,636 IU/mg. Taking into account both the determined potency and the nominal amount the average specific activity of Bemfola was 14,522 IU/mg (105.6% of the nominal value), which was greater than the average specific activity observed for GONAL-f (13,159 IU/mg; 97.3% of the nominal value; p = 0.0048), although this was within the range stated in the product label. A higher batch-to-batch variability was also observed for Bemfola versus GONAL-f (coefficient of variation: 8.3% vs 5.8%). A different glycan profile was observed at Asn52 in Bemfola compared with GONAL-f (a lower proportion of bi-antennary structures [~53% vs ~77%], and a higher proportion of tri-antennary [~41% vs ~23%] and tetra-antennary structures [~5% vs <1%]). These differences in the Asn52 glycan profile might potentially lead to differences in FSHR activation. This, together with the greater bioactivity and higher batch-to-batch variability of Bemfola, could partly explain the reported differences in clinical outcomes. The clinical relevance of the differences observed between GONAL-f and Bemfola should be further investigated.
[Mh] Termos MeSH primário: Medicamentos Biossimilares/farmacologia
Hormônio Foliculoestimulante Humano/farmacologia
Hormônio Foliculoestimulante/farmacologia
Proteínas Recombinantes/farmacologia
[Mh] Termos MeSH secundário: Asparagina/metabolismo
Fucose/metabolismo
Glicopeptídeos/química
Glicosilação/efeitos dos fármacos
Seres Humanos
Ácido N-Acetilneuramínico/metabolismo
Mapeamento de Peptídeos
Polissacarídeos/metabolismo
Subunidades Proteicas/metabolismo
Padrões de Referência
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biosimilar Pharmaceuticals); 0 (Follicle Stimulating Hormone, Human); 0 (Glycopeptides); 0 (Polysaccharides); 0 (Protein Subunits); 0 (Recombinant Proteins); 0 (follitropin alfa); 28RYY2IV3F (Fucose); 7006-34-0 (Asparagine); 9002-68-0 (Follicle Stimulating Hormone); GZP2782OP0 (N-Acetylneuraminic Acid)
[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:170908
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184139


  7 / 5311 MEDLINE  
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[PMID]:28832645
[Au] Autor:Suptawiwat O; Ruangrung K; Boonarkart C; Puthavathana P; Maneechotesuwan K; Charngkaew K; Chomanee N; Auewarakul P
[Ad] Endereço:Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
[Ti] Título:Microparticle and anti-influenza activity in human respiratory secretion.
[So] Source:PLoS One;12(8):e0183717, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Respiratory secretions, such as saliva and bronchoalveolar fluid, contain anti-influenza activity. Multiple soluble factors have been described that exert anti-influenza activity and are believed to be responsible for the anti-influenza activity in respiratory secretions. It was previously shown that a bronchial epithelial cell culture could produce exosome-like particles with anti-influenza activity. Whether such extracellular vesicles in respiratory secretions have anti-influenza activity is unknown. Therefore, we characterized bronchoalveolar lavage fluid and found microparticles, which mostly stained positive for epithelial cell markers and both α2,3- and α2,6-linked sialic acid. Microparticles were purified from bronchoalveolar lavage fluid and shown to exhibit anti-influenza activity by a hemagglutination inhibition (HI) assay and a neutralization (NT) assay. In addition, physical binding between influenza virions and microparticles was demonstrated by electron microscopy. These findings indicate that respiratory microparticles containing viral receptors can exert anti-viral activity by probably trapping viral particles. This innate mechanism may play an important role in the defense against respiratory viruses.
[Mh] Termos MeSH primário: Líquido da Lavagem Broncoalveolar
Micropartículas Derivadas de Células/metabolismo
Vírus da Influenza A/fisiologia
Saliva
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Cães
Feminino
Seres Humanos
Células Madin Darby de Rim Canino
Masculino
Microscopia Eletrônica de Transmissão
Meia-Idade
Ácido N-Acetilneuramínico/metabolismo
Vírion/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183717


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[PMID]:28724773
[Au] Autor:Bar-On Y; Charpak-Amikam Y; Glasner A; Isaacson B; Duev-Cohen A; Tsukerman P; Varvak A; Mandelboim M; Mandelboim O
[Ad] Endereço:The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel.
[Ti] Título:NKp46 Recognizes the Sigma1 Protein of Reovirus: Implications for Reovirus-Based Cancer Therapy.
[So] Source:J Virol;91(19), 2017 Oct 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The recent approval of oncolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK cell-activating receptor NKp46 and the orthologous mouse protein NCR1 recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify sites of NKp46/NCR1 binding to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy Collectively, we have identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed both for clearance of reovirus infection and for reovirus-based tumor therapy. Reovirus infects much of the population during childhood, causing mild disease, and hence is considered to be efficiently controlled by the immune system. Reovirus also specifically infects tumor cells, leading to tumor death, and is currently being tested in human clinical trials for cancer therapy. The mechanisms by which our immune system controls reovirus infection and tumor killing are not well understood. We report here that natural killer (NK) cells recognize a viral protein named sigma1 through the NK cell-activating receptor NKp46. Using several mouse tumor models, we demonstrate the importance of NK cells in protection from reovirus infection and in reovirus killing of tumors Collectively, we identify a new ligand for the NKp46 receptor and provide evidence for the importance of NKp46 in the control of reovirus infections and in reovirus-based cancer therapy.
[Mh] Termos MeSH primário: Antígenos Ly/metabolismo
Células Matadoras Naturais/imunologia
Orthoreovirus Mamífero 3/metabolismo
Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo
Terapia Viral Oncolítica/métodos
Vírus Oncolíticos/metabolismo
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Cercopithecus aethiops
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
Seres Humanos
Ativação Linfocitária/imunologia
Melanoma/terapia
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Camundongos Knockout
Ácido N-Acetilneuramínico/metabolismo
Células Vero
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Ly); 0 (Natural Cytotoxicity Triggering Receptor 1); 0 (Ncr1 protein, mouse); 0 (Viral Proteins); GZP2782OP0 (N-Acetylneuraminic Acid)
[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:170721
[St] Status:MEDLINE


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[PMID]:28687873
[Au] Autor:Li Q; Wei D; Feng F; Wang XL; Li C; Chen ZN; Bian H
[Ad] Endereço:Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, 710032, China.
[Ti] Título:α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
[So] Source:J Cancer Res Clin Oncol;143(11):2171-2181, 2017 Nov.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property. In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated. METHODS: Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor. Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels. RESULTS: We demonstrated that sialic acid was essential for NDV binding and infection of tumor cells. α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect. More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo. CONCLUSIONS: The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
[Mh] Termos MeSH primário: Neoplasias do Colo/terapia
Ácido N-Acetilneuramínico/metabolismo
Vírus da Doença de Newcastle/genética
Terapia Viral Oncolítica
Sialiltransferases/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose
Células CHO
Proliferação Celular
Neoplasias do Colo/metabolismo
Neoplasias do Colo/patologia
Cricetinae
Cricetulus
Seres Humanos
Camundongos
Camundongos Nus
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.4.99.- (Sialyltransferases); EC 2.4.99.1 (beta-D-galactoside alpha 2-6-sialyltransferase); EC 2.4.99.6 (N-acetyllactosaminide alpha-2,3-sialyltransferase); GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170709
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2470-y


  10 / 5311 MEDLINE  
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[PMID]:28668296
[Au] Autor:Lemmers RFH; Vilaj M; Urda D; Agakov F; Simurina M; Klaric L; Rudan I; Campbell H; Hayward C; Wilson JF; Lieverse AG; Gornik O; Sijbrands EJG; Lauc G; van Hoek M
[Ad] Endereço:Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, The Netherlands; Department of Internal Medicine, Maxima Medical Center, Eindhoven, The Netherlands.
[Ti] Título:IgG glycan patterns are associated with type 2 diabetes in independent European populations.
[So] Source:Biochim Biophys Acta;1861(9):2240-2249, 2017 09.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects. METHODS: In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination. RESULTS: After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729. CONCLUSIONS: Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology. GENERAL SIGNIFICANCE: This work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/etiologia
Imunoglobulina G/metabolismo
[Mh] Termos MeSH secundário: Idoso
Área Sob a Curva
Feminino
Galactose/metabolismo
Glicosilação
Seres Humanos
Masculino
Meia-Idade
Ácido N-Acetilneuramínico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Immunoglobulin G); GZP2782OP0 (N-Acetylneuraminic Acid); X2RN3Q8DNE (Galactose)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE



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