Base de dados : MEDLINE
Pesquisa : D03.383.113 [Categoria DeCS]
Referências encontradas : 963 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 97 ir para página                         

  1 / 963 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27778062
[Au] Autor:Tutka P; Kondrat-Wróbel MW; Zaluska K; Zólkowska D; Florek-Luszczki M; Luszczki JJ
[Ad] Endereço:Department of Pharmacology, University of Rzeszów, Al. Rejtana 16c, 35-959, Rzeszów, Poland. tutka@umlub.pl.
[Ti] Título:Cytisine inhibits the protective activity of various classical and novel antiepileptic drugs against 6 Hz-induced psychomotor seizures in mice.
[So] Source:Psychopharmacology (Berl);234(2):281-291, 2017 Jan.
[Is] ISSN:1432-2072
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cytisine (CYT) is a partial agonist of brain α4ß2 nicotinic acetylcholine receptors widely used in Central/Eastern Europe for smoking cessation. OBJECTIVES: This study evaluated the effect of CYT on the ability of classical and novel antiepileptic drugs to prevent seizures evoked by the 6-Hz test, a model of psychomotor seizures in mice thought as a model of drug-resistant seizures. RESULTS: CYT administered intraperitoneally (i.p.) in a dose of 2 mg kg significantly inhibited the anticonvulsant activity of lacosamide, levetiracetam, and pregabalin, increasing their median effective doses 50 (ED ) values from 6.88 to 10.52 mg kg (P < 0.05) for lacosamide, from 22.08 to 38.26 mg kg (P < 0.05) for levetiracetam, and from 40.48 to 64.61 mg kg (P < 0.01) for pregabalin, respectively. There were no significant changes in total brain concentrations of lacosamide, levetiracetam, and pregabalin following CYT i.p. administration. CYT administered in a dose of 2 mg kg failed to change the protective action of clobazam, clonazepam, phenobarbital, tiagabine, and valproate in the 6-Hz test. Neither CYT (2 mg kg ) alone nor its combination with the anticonvulsant drugs (at their ED values from the 6-Hz test) affected motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; and grip strength and passive avoidance tests, respectively. CONCLUSION: CYT-evoked alterations in the protection provided by some antiepileptic drugs against seizures can be of serious concern for epileptic smokers, who might demonstrate therapeutic failure to lacosamide, levetiracetam, and pregabalin, resulting in possible breakthrough seizure attacks.
[Mh] Termos MeSH primário: Alcaloides/toxicidade
Anticonvulsivantes/uso terapêutico
Eletrochoque/efeitos adversos
Agonistas Nicotínicos/toxicidade
Convulsões/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/farmacologia
Azocinas/toxicidade
Relação Dose-Resposta a Droga
Masculino
Memória de Longo Prazo/efeitos dos fármacos
Memória de Longo Prazo/fisiologia
Camundongos
Fenobarbital/antagonistas & inibidores
Fenobarbital/farmacologia
Fenobarbital/uso terapêutico
Piracetam/análogos & derivados
Piracetam/antagonistas & inibidores
Piracetam/farmacologia
Piracetam/uso terapêutico
Quinolizinas/toxicidade
Convulsões/etiologia
Convulsões/psicologia
Ácido Valproico/antagonistas & inibidores
Ácido Valproico/farmacologia
Ácido Valproico/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Anticonvulsants); 0 (Azocines); 0 (Nicotinic Agonists); 0 (Quinolizines); 230447L0GL (etiracetam); 53S5U404NU (cytisine); 614OI1Z5WI (Valproic Acid); YQE403BP4D (Phenobarbital); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171205
[Lr] Data última revisão:
171205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1007/s00213-016-4461-0


  2 / 963 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29061790
[Au] Autor:Kamata E; Kawamoto T; Ueha T; Hara H; Fukase N; Minoda M; Morishita M; Takemori T; Fujiwara S; Nishida K; Kuroda R; Kurosaka M; Akisue T
[Ad] Endereço:Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
[Ti] Título:Synergistic Effects of a Smac Mimetic with Doxorubicin Against Human Osteosarcoma.
[So] Source:Anticancer Res;37(11):6097-6106, 2017 11.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Second mitochondria-derived activator of caspase (Smac) is a proapoptogenic mitochondrial protein that antagonizes inhibitors of apoptosis proteins (IAPs), resulting in induction of apoptosis. In the present study we investigated the effects of a Smac mimetic in combination with doxorubicin against osteosarcoma. MATERIALS AND METHODS: In vitro effects of the combination of a Smac mimetic AT-406 and doxorubicin on cell proliferation and apoptosis in osteosarcoma cell lines were examined using cell proliferation assays, flow cytometry, and immunoblot analyses. For in vivo experiments, human osteosarcoma xenografts were treated with combination of the two substances, and tumor volume and apoptotic activity in treated tumors were assessed. RESULTS: In vitro studies revealed that combination of the two substances significantly inhibited osteosarcoma proliferation with decreased cIAP1 expression and induced apoptosis in osteosarcoma cells. Combination of the two substances significantly suppressed osteosarcoma growth in vivo. Moreover, decreased cIAP1 expression and increased apoptotic activity were observed in tumors treated by their combination of the substances. CONCLUSION: The Smac mimetic AT-406 showed an apoptotic effect and a synergistic antitumor effect with doxorubicin on osteosarcoma. The combination of AT-406 and doxorubicin may serve as a novel therapeutic strategy for osteosarcoma treatment.
[Mh] Termos MeSH primário: Azocinas/farmacologia
Compostos Benzidrílicos/farmacologia
Neoplasias Ósseas/tratamento farmacológico
Doxorrubicina/farmacologia
Sinergismo Farmacológico
Oligopeptídeos/farmacologia
Osteossarcoma/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antibióticos Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Neoplasias Ósseas/metabolismo
Neoplasias Ósseas/patologia
Proliferação Celular/efeitos dos fármacos
Quimioterapia Combinada
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Osteossarcoma/metabolismo
Osteossarcoma/patologia
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Azocines); 0 (Benzhydryl Compounds); 0 (N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide); 0 (Oligopeptides); 0 (SMAC peptide); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE


  3 / 963 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28825521
[Au] Autor:Furutani S; Okuhara D; Hashimoto A; Ihara M; Kai K; Hayashi H; Sattelle DB; Matsuda K
[Ad] Endereço:a Faculty of Agriculture, Department of Applied Biological Chemistry , Kindai University , Nara , Japan.
[Ti] Título:An L319F mutation in transmembrane region 3 (TM3) selectively reduces sensitivity to okaramine B of the Bombyx mori l-glutamate-gated chloride channel.
[So] Source:Biosci Biotechnol Biochem;81(10):1861-1867, 2017 Oct.
[Is] ISSN:1347-6947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Okaramines produced by Penicillium simplicissimum AK-40 activate l-glutamate-gated chloride channels (GluCls) and thus paralyze insects. However, the okaramine binding site on insect GluCls is poorly understood. Sequence alignment shows that the equivalent of residue Leucine319 of the okaramine B sensitive Bombyx mori (B. mori) GluCl is a phenylalanine in the okaramine B insensitive B. mori γ-aminobutyric acid-gated chloride channel of the same species. This residue is located in the third transmembrane (TM3) region, a location which in a nematode GluCl is close to the ivermectin binding site. The B. mori GluCl containing the L319F mutation retained its sensitivity to l-glutamate, but responses to ivermectin were reduced and those to okaramine B were completely blocked.
[Mh] Termos MeSH primário: Azetidinas/farmacologia
Azocinas/farmacologia
Bombyx/efeitos dos fármacos
Bombyx/genética
Membrana Celular/metabolismo
Canais de Cloreto/química
Canais de Cloreto/metabolismo
Alcaloides de Indol/farmacologia
Mutação
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Bombyx/metabolismo
Canais de Cloreto/genética
Relação Dose-Resposta a Droga
Interações Medicamentosas
Ácido Glutâmico/farmacologia
Proteínas de Insetos/química
Proteínas de Insetos/genética
Proteínas de Insetos/metabolismo
Ivermectina/farmacologia
Modelos Moleculares
Conformação Proteica
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Azetidines); 0 (Azocines); 0 (Chloride Channels); 0 (Indole Alkaloids); 0 (Insect Proteins); 0 (glutamate-gated chloride channels); 0 (okaramine B); 3KX376GY7L (Glutamic Acid); 70288-86-7 (Ivermectin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE
[do] DOI:10.1080/09168451.2017.1359487


  4 / 963 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28618276
[Au] Autor:Chatterjee S; Deb U; Datta S; Walther C; Gupta DK
[Ad] Endereço:Defence Research Laboratory, DRDO, Post Bag No. 02, Tezpur, 784001, Assam, India.
[Ti] Título:Common explosives (TNT, RDX, HMX) and their fate in the environment: Emphasizing bioremediation.
[So] Source:Chemosphere;184:438-451, 2017 Oct.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Explosive materials are energetic substances, when released into the environment, contaminate by posing toxic hazards to environment and biota. Throughout the world, soils are contaminated by such contaminants either due to manufacturing operations, military activities, conflicts of different levels, open burning/open detonation (OB/OD), dumping of munitions etc. Among different forms of chemical explosives, 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro- 1,3,5,7-tetrazocine (HMX) are most common. These explosives are highly toxic as USEPA has recommended restrictions for lifetime contact through drinking water. Although, there are several utilitarian aspects in anthropogenic activities, however, effective remediation of explosives is very important. This review article emphasizes the details of appropriate practices to ameliorate the contamination. Critical evaluation has also been made to encompass the recent knowledge and advancement about bioremediation and phytoremediation of explosives (especially TNT, RDX and HMX) along with the molecular mechanisms of biodegradation.
[Mh] Termos MeSH primário: Biodegradação Ambiental
Substâncias Explosivas/química
[Mh] Termos MeSH secundário: Azocinas/química
Poluentes do Solo
Triazinas/química
Trinitrotolueno/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Azocines); 0 (Explosive Agents); 0 (Soil Pollutants); 0 (Triazines); 118-96-7 (Trinitrotoluene); LLW94W5BSJ (octogen); W91SSV5831 (cyclonite)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170616
[St] Status:MEDLINE


  5 / 963 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28582465
[Au] Autor:Qattan MY; Bakker EY; Rajendran R; Chen DW; Saha V; Liu J; Zeef L; Schwartz JM; Mutti L; Demonacos C; Krstic-Demonacos M
[Ad] Endereço:College of Applied Medical Sciences and Community Services (CAMS&CS), King Saud University, Riyadh, Saudi Arabia.
[Ti] Título:Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia.
[So] Source:PLoS One;12(6):e0178606, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glucocorticoids (GCs) and topoisomerase II inhibitors are used to treat acute lymphoblastic leukaemia (ALL) as they induce death in lymphoid cells through the glucocorticoid receptor (GR) and p53 respectively. Mechanisms underlying ALL cell death and the contribution of the bone marrow microenvironment to drug response/resistance remain unclear. The role of the microenvironment and the identification of chemoresistance determinants were studied by transcriptomic analysis in ALL cells treated with Dexamethasone (Dex), and Etoposide (Etop) grown in the presence or absence of bone marrow conditioned media (CM). The necroptotic (RIPK1) and the apoptotic (caspase-8/3) markers were downregulated by CM, whereas the inhibitory effects of chemotherapy on the autophagy marker Beclin-1 (BECN1) were reduced suggesting CM exerts cytoprotective effects. GCs upregulated the RIPK1 ubiquitinating factor BIRC3 (cIAP2), in GC-sensitive (CEM-C7-14) but not in resistant (CEM-C1-15) cells. In addition, CM selectively affected GR phosphorylation in a site and cell-specific manner. GR is recruited to RIPK1, BECN1 and BIRC3 promoters in the sensitive but not in the resistant cells with phosphorylated GR forms being generally less recruited in the presence of hormone. FACS analysis and caspase-8 assays demonstrated that CM promoted a pro-survival trend. High molecular weight proteins reacting with the RIPK1 antibody were modified upon incubation with the BIRC3 inhibitor AT406 in CEM-C7-14 cells suggesting that they represent ubiquitinated forms of RIPK1. Our data suggest that there is a correlation between microenvironment-induced ALL proliferation and altered response to chemotherapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Resistência a Medicamentos Antineoplásicos/genética
Regulação Neoplásica da Expressão Gênica
Glucocorticoides/farmacologia
Inibidores da Topoisomerase II/farmacologia
Microambiente Tumoral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Azocinas/farmacologia
Proteína 3 com Repetições IAP de Baculovírus
Beclina-1/genética
Beclina-1/metabolismo
Compostos Benzidrílicos/farmacologia
Células da Medula Óssea/patologia
Células da Medula Óssea/secreção
Caspase 3/genética
Caspase 3/metabolismo
Caspase 8/genética
Caspase 8/metabolismo
Linhagem Celular
Linhagem Celular Tumoral
Meios de Cultivo Condicionados/farmacologia
Dexametasona/farmacologia
Etoposídeo/farmacologia
Seres Humanos
Proteínas Inibidoras de Apoptose/antagonistas & inibidores
Proteínas Inibidoras de Apoptose/genética
Proteínas Inibidoras de Apoptose/metabolismo
Células K562
Necrose/induzido quimicamente
Necrose/genética
Necrose/metabolismo
Necrose/patologia
Fosforilação/efeitos dos fármacos
Proteína Serina-Treonina Quinases de Interação com Receptores/genética
Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
Receptores de Glucocorticoides/antagonistas & inibidores
Receptores de Glucocorticoides/genética
Receptores de Glucocorticoides/metabolismo
Transdução de Sinais
Transcriptoma
Microambiente Tumoral/genética
Ubiquitina-Proteína Ligases/antagonistas & inibidores
Ubiquitina-Proteína Ligases/genética
Ubiquitina-Proteína Ligases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Azocines); 0 (BECN1 protein, human); 0 (Beclin-1); 0 (Benzhydryl Compounds); 0 (Culture Media, Conditioned); 0 (Glucocorticoids); 0 (Inhibitor of Apoptosis Proteins); 0 (N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide); 0 (Receptors, Glucocorticoid); 0 (Topoisomerase II Inhibitors); 6PLQ3CP4P3 (Etoposide); 7S5I7G3JQL (Dexamethasone); EC 2.3.2.27 (BIRC3 protein, human); EC 2.3.2.27 (Baculoviral IAP Repeat-Containing 3 Protein); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.11.1 (RIPK1 protein, human); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases); EC 3.4.22.- (CASP3 protein, human); EC 3.4.22.- (CASP8 protein, human); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 8)
[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:170606
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178606


  6 / 963 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28442008
[Au] Autor:An C; Shi Y; He Y; Huang G; Liu Y; Yang S
[Ti] Título:Biotransformation of RDX and HMX by Anaerobic Granular Sludge with Enriched Sulfate and Nitrate.
[So] Source:Water Environ Res;89(5):472-479, 2017 May 01.
[Is] ISSN:1061-4303
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RDX and HMX are widely used energetic materials and they are recognized as environmental contaminants at numerous locations. The present study investigated the biotransformation of RDX and HMX by anaerobic granular sludge under sulfate- and nitrate-enriched conditions. The results showed that RDX and HMX could be transformed by anaerobic granular sludge when nitrate was present. However, the biotransformation of RDX and HMX was negatively influenced, especially with high nitrate concentrations. Sulfate-enriched conditions were more favorable for the removal of ammunition compounds by anaerobic granular sludge than nitrate-enriched conditions. The removal of RDX and HMX under both nitrate- and sulfate-enriched conditions was facilitated by the use of glucose as additional substrate. This knowledge may help identify factors required for rapid removal of RDX and HMX in high-rate bioreactors. These results can also be applied to devise an appropriate and practical biological treatment strategy for explosive contaminated wastewater.
[Mh] Termos MeSH primário: Azocinas/farmacocinética
Reatores Biológicos
Nitratos/metabolismo
Esgotos/microbiologia
Sulfatos/metabolismo
Triazinas/farmacocinética
Águas Residuais/análise
[Mh] Termos MeSH secundário: Anaerobiose
Biotransformação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Azocines); 0 (Nitrates); 0 (Sewage); 0 (Sulfates); 0 (Triazines); 0 (Waste Water); LLW94W5BSJ (octogen); W91SSV5831 (cyclonite)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE
[do] DOI:10.2175/106143017X14839994523622


  7 / 963 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27915971
[Au] Autor:Philchenkov A; Miura K
[Ad] Endereço:R. E. Kavetsky Institute of Experimental Pathology, Oncology & Radiobiology Kyiv, Ukraine.
[Ti] Título:The IAP Protein Family, SMAC Mimetics and Cancer Treatment.
[So] Source:Crit Rev Oncog;21(3-4):185-202, 2016.
[Is] ISSN:0893-9675
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Since the acquired resistance of cells to apoptosis is one of the major hallmarks of cancer, the endogenous inhibitors of apoptosis can be regarded as promising targets in the design of anticancer therapeutics. In addition to their antiapoptotic activity, inhibitor of apoptosis proteins (IAPs) are able to regulate numerous other cell functions, including proliferation, differentiation, and migration, as well as proinflammatory and immune responses. Study of the IAP family as target molecules in targeted therapies has recently focused on SMAC mimetics as synthetic IAP antagonists that have been under development as promising therapeutics. To overview the background of IAP proteins and to focus on the development of SMAC mimetics, the present review first looks at the mechanisms of IAP proteins' antiapoptotic activities and those for controlling those activities; then the SMAC mimetics, including birinapant, LCL161, and DEBIO1143/AT-406, and their clinical trials are introduced. To further clarify the processes to exert the efficacies of SMAC mimetics, it is necessary to determine therapeutic biomarkers that predict and assess them, which may include caspases and factors in the TNFα pathway.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Proteínas Inibidoras de Apoptose/efeitos dos fármacos
Neoplasias/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos/farmacologia
Azocinas/farmacologia
Azocinas/uso terapêutico
Compostos Benzidrílicos/farmacologia
Compostos Benzidrílicos/uso terapêutico
Proliferação Celular/efeitos dos fármacos
Dipeptídeos/farmacologia
Dipeptídeos/uso terapêutico
Seres Humanos
Indóis/farmacologia
Indóis/uso terapêutico
Neoplasias/tratamento farmacológico
Tiazóis/farmacologia
Tiazóis/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Azocines); 0 (Benzhydryl Compounds); 0 (Dipeptides); 0 (Indoles); 0 (Inhibitor of Apoptosis Proteins); 0 (LCL161); 0 (N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide); 0 (Thiazoles); 6O4Z07B57R (birinapant)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161206
[St] Status:MEDLINE


  8 / 963 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27562715
[Au] Autor:Zhao X; Sun B; Zhang J; Zhang R; Zhang Q
[Ad] Endereço:Department of Neurosurgery, CPLA Bethune International Peace Hospital, Shijiazhuang, Hebei, China. Electronic address: zhaoxiaoguang7972@126.com.
[Ti] Título:Short-chain C6 ceramide sensitizes AT406-induced anti-pancreatic cancer cell activity.
[So] Source:Biochem Biophys Res Commun;479(2):166-172, 2016 Oct 14.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our previous study has shown that AT406, a first-in-class small molecular antagonist of IAPs (inhibitor of apoptosis proteins), inhibits pancreatic cancer cell proliferation in vitro and in vivo. The aim of this research is to increase AT406's sensitivity by adding short-chain C6 ceramide. We show that co-treatment of C6 ceramide dramatically potentiated AT406-induced caspase/apoptosis activation and cytotoxicity in established (Panc-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells. Reversely, caspase inhibitors largely attenuated C6 ceramide plus AT406-induced above cancer cell death. Molecularly, C6 ceramide downregulated Bcl-2 to increase AT406's sensitivity in pancreatic cancer cells. Intriguingly, C6 ceramide-mediated AT406 sensitization was nullified with Bcl-2 shRNA knockdown or pretreatment of the Bcl-2 inhibitor ABT-737. In vivo, liposomal C6 ceramide plus AT406 co-administration dramatically inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) mice. The combined anti-tumor activity was significantly more potent than either single treatment. Expressions of IAPs (cIAP1/XIAP) and Bcl-2 were downregulated in Panc-1 xenografts with the co-administration. Together, we demonstrate that C6 ceramide sensitizes AT406-mediated anti-pancreatic cancer cell activity possibly via downregulating Bcl-2.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Azocinas/farmacologia
Compostos Benzidrílicos/farmacologia
Ceramidas/farmacologia
Neoplasias Pancreáticas/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Compostos de Bifenilo/farmacologia
Western Blotting
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Sinergismo Farmacológico
Seres Humanos
Imuno-Histoquímica
Proteínas Inibidoras de Apoptose/metabolismo
Masculino
Camundongos SCID
Nitrofenóis/farmacologia
Neoplasias Pancreáticas/genética
Neoplasias Pancreáticas/metabolismo
Piperazinas/farmacologia
Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores
Proteínas Proto-Oncogênicas c-bcl-2/genética
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Interferência de RNA
Sulfonamidas/farmacologia
Fatores de Tempo
Carga Tumoral/efeitos dos fármacos
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-737); 0 (Azocines); 0 (Benzhydryl Compounds); 0 (Biphenyl Compounds); 0 (Ceramides); 0 (Inhibitor of Apoptosis Proteins); 0 (N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide); 0 (Nitrophenols); 0 (Piperazines); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Sulfonamides)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171008
[Lr] Data última revisão:
171008
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160827
[St] Status:MEDLINE


  9 / 963 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:27520705
[Au] Autor:Perimenis P; Galaris A; Voulgari A; Prassa M; Pintzas A
[Ad] Endereço:Laboratory of Signal Mediated Gene Expression, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
[Ti] Título:IAP antagonists Birinapant and AT-406 efficiently synergise with either TRAIL, BRAF, or BCL-2 inhibitors to sensitise BRAFV600E colorectal tumour cells to apoptosis.
[So] Source:BMC Cancer;16:624, 2016 08 12.
[Is] ISSN:1471-2407
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: High expression levels of Inhibitors of Apoptosis Proteins (IAPs) have been correlated with poor cancer prognosis and block the cell death pathway by interfering with caspase activation. SMAC-mimetics are small-molecule inhibitors of IAPs that mimic the endogenous SMAC and promote the induction of cell death by neutralizing IAPs. METHODS: In this study, anti-tumour activity of new SMAC-mimetics Birinapant and AT-406 is evaluated against colorectal adenocarcinoma cells and IAP cross-talk with either oncogenic BRAF or BCL-2, or with the TRAIL are further exploited towards rational combined protocols. RESULTS: It is shown that pre-treatment of SMAC-mimetics followed by their combined treatment with BRAF inhibitors can decrease cell viability, migration and can very efficiently sensitize colorectal tumour cells to apoptosis. Moreover, co-treatment of TRAIL with SMAC-mimetics can efficiently sensitize resistant tumour cells to apoptosis synergistically, as shown by median effect analysis. Finally, Birinapant and AT-406 can synergise with BCL-2 inhibitor ABT-199 to reduce viability of adenocarcinoma cells with high BCL-2 expression. CONCLUSIONS: Proposed synergistic rational anticancer combined protocols of IAP antagonists Birinapant and AT-406 in 2D and 3D cultures can be later further exploited in vivo, from precision tumour biology to precision medical oncology.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Azocinas/farmacologia
Compostos Benzidrílicos/farmacologia
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia
Neoplasias Colorretais/genética
Dipeptídeos/farmacologia
Indóis/farmacologia
Proteínas Proto-Oncogênicas B-raf/genética
Sulfonamidas/farmacologia
Ligante Indutor de Apoptose Relacionado a TNF/farmacologia
[Mh] Termos MeSH secundário: Células CACO-2
Técnicas de Cultura de Células
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Neoplasias Colorretais/tratamento farmacológico
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Sinergismo Farmacológico
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Células HCT116
Células HT29
Seres Humanos
Mutação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Azocines); 0 (Benzhydryl Compounds); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (Dipeptides); 0 (Indoles); 0 (N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide); 0 (PLX 4720); 0 (Sulfonamides); 0 (TNF-Related Apoptosis-Inducing Ligand); 6O4Z07B57R (birinapant); EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); N54AIC43PW (venetoclax)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160814
[St] Status:MEDLINE
[do] DOI:10.1186/s12885-016-2606-5


  10 / 963 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
[PMID]:27400521
[Au] Autor:Wu YH; Han ZB; Ma JZ; He Y; Liu LY; Xin SG; Yu Z
[Ti] Título:[Intermolecular Interactions between Cytisine and Bovine Serum Albumin A Synchronous Fluorescence Spectroscopic Analysis and Molecular Docking Research].
[So] Source:Guang Pu Xue Yu Guang Pu Fen Xi;36(3):765-9, 2016 Mar.
[Is] ISSN:1000-0593
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:Cytisine (Cy) is one of the alkaloids that exist naturally in the plant genera Laburnum of the family Fabaceae. With strong bioactivities, Cy is commercialized for smoking cessation for years. In this work, the study of intermolecular interactions between Cy and bovine serum albumin (BSA) was performed by applying fluorescence spectroscopic methods under simulated physiological conditions. The mechanism of fluorescence quenching of BSA by Cy was also studied. Parameters such as bathing temperature, time and solution pH were investigated to optimize the fluorescence quenching. The binding type, binding ratio and binding constant between BSA and Cy were calculated by using the Stem-Volmer equation. Experimental results indicated that Cy can quench the fluorescent emission of BSA statically by forming a 1 : 1 type non-covalent complex and the binding constant is 5.6 x 10(3) L x mol(-1). Synchronous fluorescence spectral research shows Cy may affect the fluorescence emission of Trp residues of BSA. Furthermore, molecular docking is utilized to model the complex and probe the plausible quenching mechanism. It can be noted that the hydrogen bindings and hydrophobic interactions between Cy and BSA change the micro-environment of Trp213, which leads to the fluorescence quenching of BSA.
[Mh] Termos MeSH primário: Alcaloides/química
Simulação de Acoplamento Molecular
Soroalbumina Bovina/química
Espectrometria de Fluorescência
[Mh] Termos MeSH secundário: Azocinas/química
Interações Hidrofóbicas e Hidrofílicas
Quinolizinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Azocines); 0 (Quinolizines); 27432CM55Q (Serum Albumin, Bovine); 53S5U404NU (cytisine)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160713
[St] Status:MEDLINE



página 1 de 97 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