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[PMID]:25027674
[Au] Autor:Tartaro K; VanVolkenburg M; Wilkie D; Coskran TM; Kreeger JM; Kawabata TT; Casinghino S
[Ad] Endereço:Pfizer Worldwide Research and Development, Drug Safety Research and Development , Groton, CT 06340 , USA.
[Ti] Título:Development of a fluorescence-based in vivo phagocytosis assay to measure mononuclear phagocyte system function in the rat.
[So] Source:J Immunotoxicol;12(3):239-46, 2015 Jul-Sep.
[Is] ISSN:1547-6901
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The mononuclear phagocyte system (MPS) which provides protection against infection is made up of phagocytic cells that engulf and digest bacteria or other foreign substances. Suppression of the MPS may lead to decreased clearance of pathogenic microbes. Drug delivery systems and immunomodulatory therapeutics that target phagocytes have a potential to inhibit MPS function. Available methods to measure inhibition of MPS function use uptake of radioactively-labeled cells or labor-intensive semi-quantitative histologic techniques. The objective of this work was to develop a non-radioactive quantitative method to measure MPS function in vivo by administering heat-killed E. coli conjugated to a pH-sensitive fluorescent dye (Bioparticles(®)). Fluorescence of the Bioparticles(®) is increased at low pH when they are in phagocytic lysosomes. The amount of Bioparticles(®) phagocytosed by MPS organs in rats was determined by measuring fluorescence intensity in livers and spleens ex vivo using an IVIS(®) Spectrum Pre-clinical In Vivo Imaging System. Phagocytosis of the particles by peripheral blood neutrophils was measured by flow cytometry. To assess method sensitivity, compounds likely to suppress the MPS [clodronate-containing liposomes, carboxylate-modified latex particles, maleic vinyl ether (MVE) polymer] were administered to rats prior to injection of the Bioparticles(®). The E. coli particles consistently co-localized with macrophage markers in the liver but not in the spleen. All of the compounds tested decreased phagocytosis in the liver, but had no consistent effects on phagocytic activity in the spleen. In addition, administration of clodronate liposomes and MVE polymer increased the percentage of peripheral blood neutrophils that phagocytosed the Bioparticles(®). In conclusion, an in vivo rat model was developed that measures phagocytosis of E. coli particles in the liver and may be used to assess the impact of test compounds on MPS function. Still, the detection of inhibition of splenic macrophage function will require further assay development.
[Mh] Termos MeSH primário: Escherichia coli/metabolismo
Fígado/citologia
Macrófagos/metabolismo
Sistema Fagocitário Mononuclear/metabolismo
Fagossomos/metabolismo
[Mh] Termos MeSH secundário: Animais
Bioensaio/métodos
Ácido Clodrônico/administração & dosagem
Escherichia coli/química
Corantes Fluorescentes/química
Temperatura Alta
Macrófagos/citologia
Masculino
Imagem Óptica
Fagocitose/efeitos dos fármacos
Copolímero de Pirano/administração & dosagem
Ratos
Ratos Wistar
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorescent Dyes); 0813BZ6866 (Clodronic Acid); 27100-68-1 (Pyran Copolymer)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150428
[Lr] Data última revisão:
150428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140717
[St] Status:MEDLINE
[do] DOI:10.3109/1547691X.2014.934976


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[PMID]:22044003
[Au] Autor:Perron-Sierra FM; Kucharkzyk N; Boucley C; Guyard-Daumas C; Sciberras S; Fouache C; Plantier S; Studeny A; Bossard C; Casara PJ; Golsteyn RM
[Ad] Endereço:Institut de Recherches Servier, Medicinal Chemistry, Surenses, France. francoise.perronsierra@fr.netgrs.com
[Ti] Título:Synthesis of Cis-fused pyran indolocarbazole derivatives that inhibit FLT3 kinase and the DNA damage kinase, checkpoint kinase 1.
[So] Source:Anticancer Agents Med Chem;12(3):194-201, 2012 Mar.
[Is] ISSN:1875-5992
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Protein kinases are important enzymes in solid tumour and leukaemia pathologies. Their structures are well understood at the atomic level and their key role in the progression of certain cancers makes them valuable targets for anti-cancer therapy. Through medicinal chemical approaches, we developed an efficient preparative stereospecific synthesis of N12, N13 pyran-bridged indolocarbazoles that opens access to functional diversity within this previously challenging series. We focused upon the indolocarbazole class of chemical inhibitors, which includes S27888, an inhibitor we previously identified. We used biochemical and cell-based assays to identify small molecule inhibitors of Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase that is activated when cancer cells are treated with genotoxic agents. These compounds show a promising inhibitory profile on Chk1. Furthermore, these compounds are active against FLT3, which is a tyrosine kinase that is frequently activated in human leukaemias. These data suggest that this chemical class may provide a source of therapeutic compounds for a broad range of human cancers.
[Mh] Termos MeSH primário: Carbazóis/síntese química
Dano ao DNA
Indóis/síntese química
Inibidores de Proteínas Quinases/síntese química
Proteínas Quinases/metabolismo
Copolímero de Pirano/química
Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores
[Mh] Termos MeSH secundário: Carbazóis/química
Carbazóis/uso terapêutico
Quinase do Ponto de Checagem 1
Dano ao DNA/efeitos dos fármacos
Células HT29
Seres Humanos
Indóis/farmacologia
Neoplasias/tratamento farmacológico
Neoplasias/enzimologia
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/farmacologia
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Proteínas Serina-Treonina Quinases/metabolismo
Copolímero de Pirano/farmacologia
Tirosina Quinase 3 Semelhante a fms/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carbazoles); 0 (Indoles); 0 (Protein Kinase Inhibitors); 27100-68-1 (Pyran Copolymer); EC 2.7.- (Protein Kinases); EC 2.7.10.1 (FLT3 protein, human); EC 2.7.10.1 (fms-Like Tyrosine Kinase 3); EC 2.7.11.1 (CHEK1 protein, human); EC 2.7.11.1 (Checkpoint Kinase 1); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1209
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:111103
[St] Status:MEDLINE


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[PMID]:20079705
[Au] Autor:El Khoury G; Laurenceau E; Chevolot Y; Mérieux Y; Desbos A; Fabien N; Rigal D; Souteyrand E; Cloarec JP
[Ad] Endereço:Institut des Nanotechnologies de Lyon-INL, UMR CNRS 5270, Université de Lyon, 69134 Ecully, France.
[Ti] Título:Development of miniaturized immunoassay: influence of surface chemistry and comparison with enzyme-linked immunosorbent assay and Western blot.
[So] Source:Anal Biochem;400(1):10-8, 2010 May 01.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Protein microarray technology provides a useful approach for the simultaneous serodetection of various antibodies in low sample volumes. To implement functional protein microarrays, appropriate surface chemistry must be designed so that both the protein structure and the biological activity can be retained. In the current study, two surface chemistries for protein microarrays and immunofluorescent assays were developed. Glass slides were functionalized with N-hydroxysuccinimide (NHS) ester via a monofunctional silane or maleic anhydride-alt-methyl vinyl ether (MAMVE) copolymer to allow covalent grafting of histone proteins. Analytical performance of these microarrays was then evaluated for the detection of anti-histone autoantibodies present in the sera of patients suffering from a systemic autoimmune disease, namely systemic lupus erythematosus (SLE), and the results were compared with those of the classical enzyme-linked immunosorbent assay (ELISA) and Western blot. The detection limit of our MAMVE copolymer microarrays was 50-fold lower than that of the classical ELISA. Furthermore, 100-fold less volume of biological samples was required with these miniaturized immunoassays.
[Mh] Termos MeSH primário: Imunoensaio/métodos
Análise Serial de Proteínas/métodos
[Mh] Termos MeSH secundário: Autoanticorpos/sangue
Western Blotting/métodos
Ensaio de Imunoadsorção Enzimática/métodos
Histonas/química
Histonas/imunologia
Histonas/metabolismo
Seres Humanos
Proteínas Imobilizadas/química
Proteínas Imobilizadas/imunologia
Proteínas Imobilizadas/metabolismo
Lúpus Eritematoso Sistêmico/metabolismo
Miniaturização
Copolímero de Pirano/química
Silanos/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Histones); 0 (Immobilized Proteins); 0 (Silanes); 27100-68-1 (Pyran Copolymer)
[Em] Mês de entrada:1006
[Cu] Atualização por classe:100309
[Lr] Data última revisão:
100309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100119
[St] Status:MEDLINE
[do] DOI:10.1016/j.ab.2010.01.013


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[PMID]:14598476
[Au] Autor:Kozeletskaia KN; Stotskaia LL; Serbin AV; Munshi K; Sominina AA; Kiselev OI
[Ti] Título:[Structure and antiviral activity of adamantane-containing polymer preparation].
[Ti] Título:Struktura i antivirusnaia aktivnost' adamantansoderzhashchikh polimernykh preparatov..
[So] Source:Vopr Virusol;48(5):19-26, 2003 Sep-Oct.
[Is] ISSN:0507-4088
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:New water-soluble antiviral chemical agents, containing 10 to 30% of adamantane derivatives (amino-, aminopropyl-adamantane-, aminomethyl- and rimantadine), which were conjugated with polycarboxylic matrixes of the divinyl ether and maleic anhydride copolymers (DIVEMA), were developed. The polymeric drugs exhibited a low cytotoxicity (4 to 10 times less than rimantadine) and a wide spectrum of antiviral activity against influenza viruses, including both the remantadine-resistant strains of A/PR/8/34 (H1N1) and the B/Saint-Petersburg strain/71/77 as well as against herpes viruses of type 1, parainfluenza viruses of types 1 and 3 and RS-virus. A reduction of the viral infection titer in their reproduction in sensitive cells' cultures was more than 2.0 Ig ID50. Complete inhibition of viral-specific syntheses, registered by immune-enzyme assay (IEA) and by hemagglutination test was observed at low infection doses ranging from 1 to 100 ID50. The efficiency of the antiviral effect depends on a drug's molecular weight and a structure of chemical bonds between the adamantane nucleus and the polymeric matrix.
[Mh] Termos MeSH primário: Adamantano/análogos & derivados
Antivirais/farmacologia
Polímeros/farmacologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Efeito Citopatogênico Viral/efeitos dos fármacos
Cães
Relação Dose-Resposta a Droga
Farmacorresistência Viral
Herpesviridae/efeitos dos fármacos
Seres Humanos
Peso Molecular
Orthomyxoviridae/efeitos dos fármacos
Orthomyxoviridae/imunologia
Polímeros/síntese química
Copolímero de Pirano/síntese química
Copolímero de Pirano/farmacologia
Vírus Sinciciais Respiratórios/efeitos dos fármacos
Respirovirus/efeitos dos fármacos
Respirovirus/imunologia
Rimantadina/farmacologia
Relação Estrutura-Atividade
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:COMPARATIVE STUDY; ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Polymers); 0T2EF4JQTU (Rimantadine); 27100-68-1 (Pyran Copolymer); PJY633525U (Adamantane)
[Em] Mês de entrada:0403
[Cu] Atualização por classe:161109
[Lr] Data última revisão:
161109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:031106
[St] Status:MEDLINE


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[PMID]:11091363
[Au] Autor:Holladay SD; Sharova L; Smith BJ; Gogal RM; Ward DL; Blaylock BL
[Ad] Endereço:Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0442, USA. holladay@vt.edu
[Ti] Título:Nonspecific stimulation of the maternal immune system. I. Effects On teratogen-induced fetal malformations.
[So] Source:Teratology;62(6):413-9, 2000 Dec.
[Is] ISSN:0040-3709
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Maternal immune stimulation has reported, but unconfirmed, efficacy for reducing chemical-induced morphologic defects in mice. METHODS: Teratogenic chemicals (2,3,7, 8-tetrachlorodibenzo-p-dioxin [TCDD], ethyl carbamate [urethane], methylnitrosourea [MNU], or valproic acid [VA]) were given to pregnant mice to induce cleft palate (TCDD, urethane), digital defects (urethane, MNU), or exencephaly (VA). Before teratogen administration, the immune system of female mice was stimulated by intraperitoneal (IP) administration of pyran copolymer or attenuated bacillus Calmette Guérin (BCG), or by footpad injection with Freund's complete adjuvant (FCA). RESULTS: Fetal defects caused by all four chemicals studied were reduced by maternal immunostimulation, sometimes dramatically. In addition to reducing VA-induced exencephaly, immunostimulation with FCA resulted in fetal mice displaying anury (absence of tails). Activated maternal immune cells could not be detected in fetal circulation using flow cytometry and a fluorescent cell-tracking probe. CONCLUSIONS: For the chemicals tested, maternal immune stimulation has efficacy in reducing fetal defects. Immune protection against teratogenesis may be an indirect effect of maternal immune cell activation.
[Mh] Termos MeSH primário: Anormalidades Induzidas por Medicamentos/prevenção & controle
Anormalidades Múltiplas/prevenção & controle
Adjuvantes Imunológicos/uso terapêutico
Vacina BCG/uso terapêutico
Adjuvante de Freund/uso terapêutico
Metilnitrosoureia/toxicidade
Dibenzodioxinas Policloradas/toxicidade
Gravidez/imunologia
Copolímero de Pirano/uso terapêutico
Teratogênios/toxicidade
Uretana/toxicidade
Ácido Valproico/toxicidade
[Mh] Termos MeSH secundário: Anormalidades Induzidas por Medicamentos/embriologia
Anormalidades Induzidas por Medicamentos/etiologia
Anormalidades Múltiplas/embriologia
Anormalidades Múltiplas/etiologia
Adjuvantes Imunológicos/administração & dosagem
Animais
Vacina BCG/administração & dosagem
Vacina BCG/imunologia
Fissura Palatina/induzido quimicamente
Fissura Palatina/prevenção & controle
Cruzamentos Genéticos
Feminino
Sangue Fetal/citologia
Citometria de Fluxo

Adjuvante de Freund/administração & dosagem
Adjuvante de Freund/imunologia
Injeções
Injeções Intraperitoneais
Deformidades Congênitas dos Membros/induzido quimicamente
Deformidades Congênitas dos Membros/prevenção & controle
Troca Materno-Fetal
Camundongos
Camundongos Endogâmicos C3H
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos ICR
Defeitos do Tubo Neural/induzido quimicamente
Defeitos do Tubo Neural/prevenção & controle
Copolímero de Pirano/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (BCG Vaccine); 0 (Polychlorinated Dibenzodioxins); 0 (Teratogens); 27100-68-1 (Pyran Copolymer); 3IN71E75Z5 (Urethane); 614OI1Z5WI (Valproic Acid); 684-93-5 (Methylnitrosourea); 9007-81-2 (Freund's Adjuvant)
[Em] Mês de entrada:0101
[Cu] Atualização por classe:161124
[Lr] Data última revisão:
161124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:001125
[St] Status:MEDLINE


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[PMID]:10595742
[Au] Autor:Novakovic S; Ihan A; Jezersek B
[Ad] Endereço:Department of Tumor Biology, Institute of Oncology, Ljubljana, Slovenia. snovakovic@onko-i.si
[Ti] Título:Effectiveness of a simply designed tumor vaccine in prevention of malignant melanoma development.
[So] Source:Jpn J Cancer Res;90(10):1130-8, 1999 Oct.
[Is] ISSN:0910-5050
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:We investigated the efficacy of a simple syngeneic tumor vaccine to induce specific antitumor immunity in female C57Bl/6 mice. Tumor vaccine was prepared by mixing irradiated B-16 melanoma tumor cells with the pleiotropic biological response modifier-maleic anhydride divinyl ether (MVE-2). Experimental animals were pretreated with the vaccine in order to prevent the development of intraperitoneal (i.p.) B-16 melanoma tumors after inoculation of viable tumor cells. More than 40% of prevaccinated animals challenged i.p. with 5 x 10(5) viable tumor cells were completely protected from tumor development and remained tumor-free 100 days after tumor cell inoculation. The percentage of tumor-free animals (survivors) rose to as much as 90% when the application of tumor vaccine was repeated two weeks after the first vaccination (i.e. one week after the inoculation of viable tumor cells). The induced antitumor response depended predominantly upon macrophage function, since vaccinated animals which were depleted of peritoneal macrophages died within the same time range as animals in the control group. Also, tumor-type specificity of the vaccine was confirmed by the fact that the animals vaccinated with B-16 melanoma vaccine were not protected from the development of another type of tumor. In conclusion, comparison of the experimental data with the data from the literature suggests that our simple tumor vaccine may be as effective as genetically engineered tumor vaccines. At the same time, this kind of vaccine is easier to control and thus safer to apply in humans when compared to genetically engineered vaccines.
[Mh] Termos MeSH primário: Vacinas Anticâncer
Macrófagos Peritoneais/imunologia
Melanoma Experimental/imunologia
Melanoma Experimental/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Antígenos de Diferenciação/análise
Esquema de Medicação
Feminino
Citometria de Fluxo
Fatores Imunológicos
Contagem de Linfócitos
Camundongos
Camundongos Endogâmicos C57BL
Copolímero de Pirano
Fatores de Tempo
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Differentiation); 0 (Cancer Vaccines); 0 (Immunologic Factors); 27100-68-1 (Pyran Copolymer)
[Em] Mês de entrada:0001
[Cu] Atualização por classe:071115
[Lr] Data última revisão:
071115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:991214
[St] Status:MEDLINE


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[PMID]:10383834
[Au] Autor:Kondo T; Terajima H; Todoroki T; Hirano T; Ito Y; Usia T; Messmer K
[Ad] Endereço:Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Munich, D-81377, Germany.
[Ti] Título:Prevention of hepatic ischemia-reperfusion injury by SOD-DIVEMA conjugate.
[So] Source:J Surg Res;85(1):26-36, 1999 Jul.
[Is] ISSN:0022-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A protective effect of the SOD (superoxide dismutase)-DIVEMA (divinyl ether and maleic anhydride) conjugate on I-R (ischemia-reperfusion) liver injury was demonstrated. Twenty minutes of normothermic hepatic ischemia was induced by clamping the portal triad of Sprague-Dawley rats. Five minutes before the end of ischemia, SOD, SOD-DIVEMA, or NaCl (0.9%) was given intravenously. Using intravital fluorescence microscopy, hepatic microvascular perfusion was analyzed before ischemia and repeatedly during the 120-min reperfusion period. SOD-DIVEMA significantly restored the sinusoidal perfusion rate (control, 98.0 +/- 0.5; NaCl, 65.5 +/- 7. 7; SOD, 81.5 +/- 8.2; SOD-DIVEMA, 95.8 +/- 0.7%) and reduced the number of leukocytes stagnant in acini (control, 4.4 +/- 0.9; NaCl, 36.6 +/- 6.3; SOD, 27.7 +/- 6.8; SOD-DIVEMA, 12.3 +/- 3.3 cells/lobule) and adherent in postsinusoidal venules (control, 55.0 +/- 24; NaCl, 417 +/- 63; SOD, 253 +/- 58; SOD-DIVEMA, 40.0 +/- 14 cells/mm2). In addition, SOD-DIVEMA maintained postischemic hepatocellular integrity. The SOD-DIVEMA-treated group revealed higher serum SOD enzyme activity compared to the SOD group after 120 min of reperfusion (SOD-DIVEMA, 33.0 +/- 5.9; SOD, 8.6 +/- 3.1 U/ml). The beneficial effect of SOD-DIVEMA was most prominent after 120 min of reperfusion, indicating a longer intravascular half-life of SOD-DIVEMA.
[Mh] Termos MeSH primário: Isquemia/prevenção & controle
Circulação Hepática/fisiologia
Copolímero de Pirano/uso terapêutico
Traumatismo por Reperfusão/prevenção & controle
Superóxido Dismutase/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Combinação de Medicamentos
Fígado/efeitos dos fármacos
Fígado/patologia
Circulação Hepática/efeitos dos fármacos
Masculino
Microcirculação/efeitos dos fármacos
Microcirculação/fisiologia
Microscopia de Fluorescência
Ratos
Ratos Sprague-Dawley
Superóxido Dismutase/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Drug Combinations); 27100-68-1 (Pyran Copolymer); EC 1.15.1.1 (Superoxide Dismutase)
[Em] Mês de entrada:9907
[Cu] Atualização por classe:061115
[Lr] Data última revisão:
061115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:990629
[St] Status:MEDLINE


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[PMID]:9864393
[Au] Autor:Novakovic S; Ihan A; Wraber B; Jezersek B
[Ad] Endereço:Department of Tumor Biology, Institute of Oncology, 1105 Ljubljana, Slovenia.
[Ti] Título:An effective tumor vaccine against malignant melanoma: irradiated autologous tumor cells admixed with MVE-2.
[So] Source:Int J Mol Med;3(1):95-102, 1999 Jan.
[Is] ISSN:1107-3756
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to develop as effective as possible autologous tumor vaccine which would be at the same time easy to produce, highly controllable, and without undesired side effects on normal tissue. Therefore, irradiated autologous - syngeneic B-16 tumor cells admixed with a non-specific immunomodulator MVE-2 (a polymer fraction of 1,2-co-polymer of divinyl ether and maleic anhydride) were used for subcutaneous (s.c.). or intraperitoneal (i.p.) prevaccination of experimental mice. Compared to the control mice, a statistically significant delay in tumor development of s.c. tumors was achieved in prevaccinated mice (p<0.05). An even better effect was observed in mice challenged i.p. with viable tumor cells. Using a single prevaccination complete protection was obtained in between 40-85% of the experimental mice. When the survivors from the groups injected once with the tumor vaccine were rechallenged with viable tumor cells (101 day after the first tumor challenge, no additional prevaccination), 15.7% remained free of tumor, while the survivors from the groups injected with the tumor vaccine twice and 101 day later rechallenged with viable tumor cells remained free of tumor in 60% of the cases. Based on these results we can postulate that our vaccine is effective for prevention of tumor development. The achieved protection can be augmented with serial vaccinations and can be maintained for a longer period of time.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Vacinas Anticâncer/administração & dosagem
Melanoma/prevenção & controle
Copolímero de Pirano/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Apoptose/imunologia
Vacinas Anticâncer/uso terapêutico
Citocinas/sangue
Citocinas/efeitos dos fármacos
Citocinas/imunologia
Relação Dose-Resposta a Droga
Feminino
Injeções Intraperitoneais
Injeções Subcutâneas
Melanoma/imunologia
Camundongos
Camundongos Endogâmicos C57BL
Copolímero de Pirano/uso terapêutico
Fatores de Tempo
Resultado do Tratamento
Células Tumorais Cultivadas/efeitos da radiação
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cancer Vaccines); 0 (Cytokines); 27100-68-1 (Pyran Copolymer)
[Em] Mês de entrada:9902
[Cu] Atualização por classe:061115
[Lr] Data última revisão:
061115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:981229
[St] Status:MEDLINE


  9 / 153 MEDLINE  
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Fotocópia
[PMID]:9345288
[Au] Autor:Kaneda Y; Yamamoto Y; Tsunoda S; Kamada H; Tsutsumi Y; Hirano T; Mayumi T
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Osaka University, Japan.
[Ti] Título:Bioconjugation of tumor necrosis factor-alpha with the copolymer of divinyl ether and maleic anhydride increasing its antitumor potency.
[So] Source:Biochem Biophys Res Commun;239(1):160-5, 1997 Oct 09.
[Is] ISSN:0006-291X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To enhance the therapeutic usefulness of antitumor cytokines in vivo, we synthesized bioconjugated tumor necrosis factor-alpha (TNF-alpha) with divinyl ether and maleic anhydride copolymer (DIVEMA), which has intrinsic antitumor activity as a synthetic biological response modifier. The degree of modification could be controlled by the addition of 2,3-dimethylmaleic anhydride (DMMAn), which binds to amino groups of TNF-alpha by changing the pH. In addition, the specific activity of DIVEMA-TNF-alpha was hardly decreased in vitro. DIVEMA-TNF-alpha showed a marked antitumor effect compared to native TNF-alpha without any side effects such as sudden death, body-weight reduction, and decrease in platelet count on mice bearing solid tumors. These results suggest that DIVEMA is a useful polymeric modifier for-bioconjugation of TNF-alpha in order to increase its antitumor activity, and multifunctionally bioconjugated TNF-alpha may be a potentiated antitumor agent for therapeutic use.
[Mh] Termos MeSH primário: Antineoplásicos/química
Copolímero de Pirano/análogos & derivados
Fator de Necrose Tumoral alfa/química
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/uso terapêutico
Peso Corporal/efeitos dos fármacos
Cromatografia em Gel
Seres Humanos
Anidridos Maleicos/química
Camundongos
Modelos Químicos
Neoplasias Experimentais/tratamento farmacológico
Contagem de Plaquetas/efeitos dos fármacos
Copolímero de Pirano/uso terapêutico
Fator de Necrose Tumoral alfa/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Maleic Anhydrides); 0 (Tumor Necrosis Factor-alpha); 27100-68-1 (Pyran Copolymer); 6PP3N541QA (2,3-dimethylmaleic anhydride)
[Em] Mês de entrada:9711
[Cu] Atualização por classe:121115
[Lr] Data última revisão:
121115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:971105
[St] Status:MEDLINE


  10 / 153 MEDLINE  
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[PMID]:9089007
[Au] Autor:Black PL; McKinnon KM; Wooden SL; Ussery MA
[Ad] Endereço:Southern Research Institute-Frederick Research Center, MD, USA.
[Ti] Título:Antiviral activity of biological response modifiers in a murine model of AIDS. Requirement for augmentation of natural killer cell activity and synergy with oral AZT.
[So] Source:Int J Immunopharmacol;18(11):633-50, 1996 Nov.
[Is] ISSN:0192-0561
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We employed the Rauscher murine leukemia virus (RMuLV) as a murine retrovirus model of AIDS, to test biological response modifiers (BRM) and antiviral agents for potential therapeutic activity against the human immunodeficiency virus (HIV). We examined the relationship between the augmentation of natural killer (NK) cell activity and antiviral efficacy of a series of BRM, most of which are known inducers of interferon, in this model. Poly [I,C]-LC, MVE-2, and CL 246,738, but not Ampligen, soluble glucan, or 7-thia-8-oxoguanosine, consistently produced antiviral activity. In addition, the combination of suboptimal doses of oral 3'-azido-3'-deoxythymidine (AZT) (in drinking water) and poly [I,C]-LC produced a synergistic antiviral effect. With all the BRM tested, a consistent pattern emerged, namely that antiviral activity always correlated with the augmentation of splenic NK cell activity in infected animals. For instance, poly [I,C]-LC boosted NK activity much more in infected mice treated therapeutically (treatment initiated after infection) than prophylactically (treatment initiated before infection), and it had greater antiviral activity therapeutically than prophylactically. For the BRM tested, antiviral activity did not occur without augmentation of NK activity in infected mice. In contrast, augmentation of NK activity in uninfected mice bore no relationship to antiviral activity. Furthermore, elimination of NK cells by treating mice with anti-asialo GM1 abolished the antiviral activity of poly [I,C]-LC. Although splenic NK activity was ablated by anti-asialo GM1, serum interferon levels were not affected by this treatment. These results point to a causal connection between the augmentation of NK cell activity and the antiviral efficacy of these BRM in this murine AIDS model. NK cells thus appear to play a key role in resistance to this retrovirus, as has been suggested for HIV.
[Mh] Termos MeSH primário: Síndrome de Imunodeficiência Adquirida/imunologia
Fatores Imunológicos/farmacologia
Células Matadoras Naturais/fisiologia
Zidovudina/farmacologia
[Mh] Termos MeSH secundário: Síndrome de Imunodeficiência Adquirida/tratamento farmacológico
Acridinas/farmacologia
Acridinas/uso terapêutico
Animais
Anticorpos/farmacologia
Antivirais/farmacologia
Antivirais/uso terapêutico
Assialoglicoproteínas/imunologia
Modelos Animais de Doenças
Sinergismo Farmacológico
Feminino
Gangliosídeo G(M1)/imunologia
Glucanos/farmacologia
Glucanos/uso terapêutico
Guanosina/análogos & derivados
Guanosina/farmacologia
Guanosina/uso terapêutico
Fatores Imunológicos/uso terapêutico
Técnicas In Vitro
Células Matadoras Naturais/efeitos dos fármacos
Depleção Linfocítica
Camundongos
Camundongos Endogâmicos BALB C
Poli I-C/farmacologia
Poli I-C/uso terapêutico
Poli U/farmacologia
Poli U/uso terapêutico
Copolímero de Pirano/farmacologia
Copolímero de Pirano/uso terapêutico
Coelhos
Vírus Rauscher/imunologia
Organismos Livres de Patógenos Específicos
Ensaio de Placa Viral
Zidovudina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Acridines); 0 (Antibodies); 0 (Antiviral Agents); 0 (Asialoglycoproteins); 0 (Glucans); 0 (Immunologic Factors); 12133JR80S (Guanosine); 27100-68-1 (Pyran Copolymer); 27416-86-0 (Poly U); 37758-47-7 (G(M1) Ganglioside); 4B9XT59T7S (Zidovudine); 81541-26-6 (3,6-bis(2-piperidinoethoxy)acridine trihydrochloride); 85141ONN7O (isatoribine); 94325AJ25N (poly(I).poly(c12,U)); O84C90HH2L (Poly I-C)
[Em] Mês de entrada:9706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:961101
[St] Status:MEDLINE



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