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  1 / 41563 MEDLINE  
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[PMID]:28542191
[Au] Autor:Hahn G; Ponce-Alvarez A; Monier C; Benvenuti G; Kumar A; Chavane F; Deco G; Frégnac Y
[Ad] Endereço:Unité de Neuroscience, Information et Complexité (UNIC), CNRS, Gif-sur-Yvette, France.
[Ti] Título:Spontaneous cortical activity is transiently poised close to criticality.
[So] Source:PLoS Comput Biol;13(5):e1005543, 2017 May.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Brain activity displays a large repertoire of dynamics across the sleep-wake cycle and even during anesthesia. It was suggested that criticality could serve as a unifying principle underlying the diversity of dynamics. This view has been supported by the observation of spontaneous bursts of cortical activity with scale-invariant sizes and durations, known as neuronal avalanches, in recordings of mesoscopic cortical signals. However, the existence of neuronal avalanches in spiking activity has been equivocal with studies reporting both its presence and absence. Here, we show that signs of criticality in spiking activity can change between synchronized and desynchronized cortical states. We analyzed the spontaneous activity in the primary visual cortex of the anesthetized cat and the awake monkey, and found that neuronal avalanches and thermodynamic indicators of criticality strongly depend on collective synchrony among neurons, LFP fluctuations, and behavioral state. We found that synchronized states are associated to criticality, large dynamical repertoire and prolonged epochs of eye closure, while desynchronized states are associated to sub-criticality, reduced dynamical repertoire, and eyes open conditions. Our results show that criticality in cortical dynamics is not stationary, but fluctuates during anesthesia and between different vigilance states.
[Mh] Termos MeSH primário: Potenciais de Ação/fisiologia
Córtex Cerebral/fisiologia
Modelos Neurológicos
Vigília/fisiologia
[Mh] Termos MeSH secundário: Animais
Gatos
Biologia Computacional
Haplorrinos
Neurônios/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005543


  2 / 41563 MEDLINE  
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[PMID]:28268956
[Au] Autor:Hongbao Li; Fang Wang; Qiaosheng Zhang; Shaomin Zhang; Yiwen Wang; Xiaoxiang Zheng; Principe JC
[Ti] Título:Maximum correntropy based attention-gated reinforcement learning designed for brain machine interface.
[So] Source:Conf Proc IEEE Eng Med Biol Soc;2016:3056-3059, 2016 Aug.
[Is] ISSN:1557-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Reinforcement learning is an effective algorithm for brain machine interfaces (BMIs) which interprets the mapping between neural activities with plasticity and the kinematics. Exploring large state-action space is difficulty when the complicated BMIs needs to assign credits over both time and space. For BMIs attention gated reinforcement learning (AGREL) has been developed to classify multi-actions for spatial credit assignment task with better efficiency. However, the outliers existing in the neural signals still make interpret the neural-action mapping difficult. We propose an enhanced AGREL algorithm using correntropy as a criterion, which is more insensitive to noise. Then the algorithm is tested on the neural data where the monkey is trained to do the obstacle avoidance task. The new method converges faster during the training period, and improves from 44.63% to 68.79% on average in success rate compared with the original AGREL. The result indicates that the combination of correntropy criterion and AGREL can reduce the effect of the outliers with better performance when interpreting the mapping between neural signal and kinematics.
[Mh] Termos MeSH primário: Algoritmos
Atenção
Interfaces Cérebro-Computador
Dinâmica não Linear
Reforço (Psicologia)
[Mh] Termos MeSH secundário: Animais
Haplorrinos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170308
[St] Status:MEDLINE
[do] DOI:10.1109/EMBC.2016.7591374


  3 / 41563 MEDLINE  
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[PMID]:28076355
[Au] Autor:Insabato A; Pannunzi M; Deco G
[Ad] Endereço:Universitat Pompeu Fabra, Center for Brain and Cognition, Barcelona, Spain.
[Ti] Título:Multiple Choice Neurodynamical Model of the Uncertain Option Task.
[So] Source:PLoS Comput Biol;13(1):e1005250, 2017 Jan.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The uncertain option task has been recently adopted to investigate the neural systems underlying the decision confidence. Latterly single neurons activity has been recorded in lateral intraparietal cortex of monkeys performing an uncertain option task, where the subject is allowed to opt for a small but sure reward instead of making a risky perceptual decision. We propose a multiple choice model implemented in a discrete attractors network. This model is able to reproduce both behavioral and neurophysiological experimental data and therefore provides support to the numerous perspectives that interpret the uncertain option task as a sensory-motor association. The model explains the behavioral and neural data recorded in monkeys as the result of the multistable attractor landscape and produces several testable predictions. One of these predictions may help distinguish our model from a recently proposed continuous attractor model.
[Mh] Termos MeSH primário: Comportamento de Escolha/fisiologia
Modelos Neurológicos
Recompensa
Incerteza
[Mh] Termos MeSH secundário: Animais
Córtex Cerebral/fisiologia
Biologia Computacional
Haplorrinos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170111
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005250


  4 / 41563 MEDLINE  
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[PMID]:28124507
[Au] Autor:Cydylo MA; Davis AT; Kavanagh K
[Ad] Endereço:Wake Forest School of Medicine Department of Pathology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA.
[Ti] Título:Fatty liver promotes fibrosis in monkeys consuming high fructose.
[So] Source:Obesity (Silver Spring);25(2):290-293, 2017 Feb.
[Is] ISSN:1930-739X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Nonalcoholic fatty liver diseases (NAFLD) are related to development of liver fibrosis which currently has few therapeutic options. Rodent models of NAFLD inadequately model the fibrotic aspects of the disease and fail to demonstrate the spectrum of cardiometabolic diseases without genetic manipulation. This study aimed to document a monkey model of fatty liver and fibrosis, which naturally develop cardiometabolic disease pathophysiologies. METHODS: Twenty-seven cynomolgus monkeys (Macaca fascicularis) fed diets either low or high in simple carbohydrates, supplied as fructose [control and high-fructose diet (HRr)], on low-fat, cholesterol-free background were studied. The HFr was consumed for up to 7 years, and liver tissue was histologically evaluated for fat and fibrosis extent. RESULTS: The HFr diet increased steatosis, and its extent was related to duration of fructose exposure. Lipid droplet size also increased with HFr duration; however, compared with control, the lipid droplets were smaller on average. Fibrosis extent was significantly greater with fructose feeding and was predicted by fructose exposure, extent of fatty liver, and age. CONCLUSIONS: These data are the first to demonstrate that high-carbohydrate diets alone can generate both liver fat and fibrosis and thus allow further study of mechanisms and therapeutic options in the translational animal model.
[Mh] Termos MeSH primário: Frutose/administração & dosagem
Cirrose Hepática/etiologia
Cirrose Hepática/fisiopatologia
Fígado/patologia
Hepatopatia Gordurosa não Alcoólica/complicações
[Mh] Termos MeSH secundário: Animais
Dieta com Restrição de Gorduras
Modelos Animais de Doenças
Feminino
Haplorrinos
Macaca fascicularis
Masculino
Hepatopatia Gordurosa não Alcoólica/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
30237-26-4 (Fructose)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170622
[Lr] Data última revisão:
170622
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.1002/oby.21720


  5 / 41563 MEDLINE  
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[PMID]:28430437
[Au] Autor:Yeung KS; Beno BR; Parcella K; Bender JA; Grant-Young KA; Nickel A; Gunaga P; Anjanappa P; Bora RO; Selvakumar K; Rigat K; Wang YK; Liu M; Lemm J; Mosure K; Sheriff S; Wan C; Witmer M; Kish K; Hanumegowda U; Zhuo X; Shu YZ; Parker D; Haskell R; Ng A; Gao Q; Colston E; Raybon J; Grasela DM; Santone K; Gao M; Meanwell NA; Sinz M; Soars MG; Knipe JO; Roberts SB; Kadow JF
[Ad] Endereço:Bristol-Myers Squibb Research and Development , P.O. Box 5100, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
[Ti] Título:Discovery of a Hepatitis C Virus NS5B Replicase Palm Site Allosteric Inhibitor (BMS-929075) Advanced to Phase 1 Clinical Studies.
[So] Source:J Med Chem;60(10):4369-4385, 2017 May 25.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The hepatitis C virus (HCV) NS5B replicase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection. Inspired by the overlay of bound structures of three structurally distinct NS5B palm site allosteric inhibitors, the high-throughput screening hit anthranilic acid 4, the known benzofuran analogue 5, and the benzothiadiazine derivative 6, an optimization process utilizing the simple benzofuran template 7 as a starting point for a fragment growing approach was pursued. A delicate balance of molecular properties achieved via disciplined lipophilicity changes was essential to achieve both high affinity binding and a stringent targeted absorption, distribution, metabolism, and excretion profile. These efforts led to the discovery of BMS-929075 (37), which maintained ligand efficiency relative to early leads, demonstrated efficacy in a triple combination regimen in HCV replicon cells, and exhibited consistently high oral bioavailability and pharmacokinetic parameters across preclinical animal species. The human PK properties from the Phase I clinical studies of 37 were better than anticipated and suggest promising potential for QD administration.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Antivirais/farmacocinética
Benzofuranos/farmacologia
Benzofuranos/farmacocinética
Hepacivirus/efeitos de drogas
Hepatite C/quimioterapia
Proteínas não Estruturais Virais/antagonistas & inibidores
[Mh] Termos MeSH secundário: Regulação Alostérica/efeitos de drogas
Sítio Alostérico/efeitos de drogas
Animais
Antivirais/química
Benzofuranos/química
Cães
Descoberta de Drogas
Haplorrinos
Hepatite C/virologia
Humanos
Masculino
Simulação de Acoplamento Molecular
Ratos
Ratos Sprague-Dawley
Proteínas não Estruturais Virais/química
Proteínas não Estruturais Virais/metabolismo
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Benzofurans); 0 (NS-5 protein, hepatitis C virus); 0 (Viral Nonstructural Proteins)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00328


  6 / 41563 MEDLINE  
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[PMID]:28092155
[Au] Autor:Huang Y; Zhang J; Yu Z; Zhang H; Wang Y; Lingel A; Qi W; Gu J; Zhao K; Shultz MD; Wang L; Fu X; Sun Y; Zhang Q; Jiang X; Zhang J; Zhang C; Li L; Zeng J; Feng L; Zhang C; Liu Y; Zhang M; Zhang L; Zhao M; Gao Z; Liu X; Fang D; Guo H; Mi Y; Gabriel T; Dillon MP; Atadja P; Oyang C
[Ad] Endereço:Novartis Institutes for BioMedical Research , 4218 Jinke Road, Shanghai 201203, China.
[Ti] Título:Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy.
[So] Source:J Med Chem;60(6):2215-2226, 2017 Mar 23.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3). Herein we disclose the discovery of a first-in-class potent, selective, and orally bioavailable EED inhibitor compound 43 (EED226). Guided by X-ray crystallography, compound 43 was discovered by fragmentation and regrowth of compound 7, a PRC2 HTS hit that directly binds EED. The ensuing scaffold hopping followed by multiparameter optimization led to the discovery of 43. Compound 43 induces robust and sustained tumor regression in EZH2 preclinical DLBCL model. For the first time we demonstrate that specific and direct inhibition of EED can be effective as an anticancer strategy.
[Mh] Termos MeSH primário: Antineoplásicos/química
Antineoplásicos/farmacologia
Complexo Repressor Polycomb 2/antagonistas & inibidores
Sulfonas/química
Sulfonas/farmacologia
Triazóis/química
Triazóis/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacocinética
Antineoplásicos/uso terapêutico
Proliferação de Células/efeitos de drogas
Cristalografia por Raios X
Cães
Feminino
Haplorrinos
Histonas/metabolismo
Humanos
Linfoma Difuso de Grandes Células B/quimioterapia
Linfoma Difuso de Grandes Células B/metabolismo
Lisina/metabolismo
Masculino
Metilação/efeitos de drogas
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Simulação de Acoplamento Molecular
Complexo Repressor Polycomb 2/química
Complexo Repressor Polycomb 2/metabolismo
Ratos
Sulfonas/farmacocinética
Sulfonas/uso terapêutico
Triazóis/farmacocinética
Triazóis/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (EED protein, human); 0 (EED226); 0 (Histones); 0 (Sulfones); 0 (Triazoles); EC 2.1.1.43 (Polycomb Repressive Complex 2); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170116
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.6b01576


  7 / 41563 MEDLINE  
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[PMID]:28151659
[Au] Autor:Harris PA; Berger SB; Jeong JU; Nagilla R; Bandyopadhyay D; Campobasso N; Capriotti CA; Cox JA; Dare L; Dong X; Eidam PM; Finger JN; Hoffman SJ; Kang J; Kasparcova V; King BW; Lehr R; Lan Y; Leister LK; Lich JD; MacDonald TT; Miller NA; Ouellette MT; Pao CS; Rahman A; Reilly MA; Rendina AR; Rivera EJ; Schaeffer MC; Sehon CA; Singhaus RR; Sun HH; Swift BA; Totoritis RD; Vossenkämper A; Ward P; Wisnoski DD; Zhang D; Marquis RW; Gough PJ; Bertin J
[Ti] Título:Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases.
[So] Source:J Med Chem;60(4):1247-1261, 2017 Feb 23.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound 5 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochemical and ADMET properties of 5, combined with high potency, led to a predicted low oral dose in humans.
[Mh] Termos MeSH primário: Anti-Inflamatórios/química
Anti-Inflamatórios/farmacologia
Colite Ulcerativa/quimioterapia
Inflamação/quimioterapia
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/farmacologia
Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Benzazepinas/química
Benzazepinas/farmacologia
Colite Ulcerativa/imunologia
Citocinas/imunologia
Cães
Haplorrinos
Humanos
Inflamação/imunologia
Camundongos
Simulação de Acoplamento Molecular
Coelhos
Ratos
Proteína Serina-Treonina Quinases de Interação com Receptores/imunologia
Suínos
Porco Miniatura
Fator de Necrose Tumoral alfa/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Benzazepines); 0 (Cytokines); 0 (Protein Kinase Inhibitors); 0 (Tumor Necrosis Factor-alpha); EC 2.7.11.1 (RIPK1 protein, human); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170616
[Lr] Data última revisão:
170616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170202
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.6b01751


  8 / 41563 MEDLINE  
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[PMID]:28106992
[Au] Autor:Rombouts FJ; Andrés JI; Ariza M; Alonso JM; Austin N; Bottelbergs A; Chen L; Chupakhin V; Cleiren E; Fierens K; Fontana A; Langlois X; Leenaerts JE; Mariën J; Martínez Lamenca C; Salter R; Schmidt ME; Te Riele P; Wintmolders C; Trabanco AA; Zhang W; Macdonald G; Moechars D
[Ad] Endereço:Neuroscience Medicinal Chemistry, Janssen Research & Development, Janssen Pharmaceutica N. V. , Turnhoutseweg 30, B-2340 Beerse, Belgium.
[Ti] Título:Discovery of N-(Pyridin-4-yl)-1,5-naphthyridin-2-amines as Potential Tau Pathology PET Tracers for Alzheimer's Disease.
[So] Source:J Med Chem;60(4):1272-1291, 2017 Feb 23.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A mini-HTS on 4000 compounds selected using 2D fragment-based similarity and 3D pharmacophoric and shape similarity to known selective tau aggregate binders identified N-(6-methylpyridin-2-yl)quinolin-2-amine 10 as a novel potent binder to human AD aggregated tau with modest selectivity versus aggregated ß-amyloid (Aß). Initial medicinal chemistry efforts identified key elements for potency and selectivity, as well as suitable positions for radiofluorination, leading to a first generation of fluoroalkyl-substituted quinoline tau binding ligands with suboptimal physicochemical properties. Further optimization toward a more optimal pharmacokinetic profile led to the discovery of 1,5-naphthyridine 75, a potent and selective tau aggregate binder with potential as a tau PET tracer.
[Mh] Termos MeSH primário: Doença de Alzheimer/diagnóstico por imagem
Peptídeos beta-Amiloides/análise
Encéfalo/diagnóstico por imagem
Naftiridinas/química
Tomografia por Emissão de Pósitrons/métodos
Agregação Patológica de Proteínas/diagnóstico por imagem
Proteínas tau/análise
[Mh] Termos MeSH secundário: Aminação
Animais
Haplorrinos
Humanos
Camundongos
Naftiridinas/farmacocinética
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Naphthyridines); 0 (tau Proteins)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170616
[Lr] Data última revisão:
170616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170120
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.6b01173


  9 / 41563 MEDLINE  
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[PMID]:28106991
[Au] Autor:Perreault S; Chandrasekhar J; Cui ZH; Evarts J; Hao J; Kaplan JA; Kashishian A; Keegan KS; Kenney T; Koditek D; Lad L; Lepist EI; McGrath ME; Patel L; Phillips B; Therrien J; Treiberg J; Yahiaoui A; Phillips G
[Ad] Endereço:Gilead Sciences, Inc. , 199 E. Blaine Street, Seattle, Washington 98102, United States.
[Ti] Título:Discovery of a Phosphoinositide 3-Kinase (PI3K) ß/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kß Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856.
[So] Source:J Med Chem;60(4):1555-1567, 2017 Feb 23.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phosphoinositide 3-kinase (PI3K) ß signaling is required to sustain cancer cell growth in which the tumor suppressor phosphatase and tensin homolog (PTEN) has been deactivated. This manuscript describes the discovery, optimization, and in vivo evaluation of a novel series of PI3Kß/δ inhibitors in which PI3Kß potency was built in a PI3Kδ-selective template. This work led to the discovery of a highly selective PI3Kß/δ inhibitor displaying excellent pharmacokinetic profile and efficacy in a human PTEN-deficient LNCaP prostate carcinoma xenograft tumor model.
[Mh] Termos MeSH primário: Classe Ia de Fosfatidilinositol 3-Quinase/antagonistas & inibidores
PTEN Fosfo-Hidrolase/genética
Neoplasias da Próstata/quimioterapia
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo
Cães
Haplorrinos
Humanos
Masculino
Camundongos
Modelos Moleculares
Próstata/efeitos de drogas
Próstata/metabolismo
Próstata/patologia
Neoplasias da Próstata/genética
Neoplasias da Próstata/metabolismo
Inibidores de Proteínas Quinases/farmacocinética
Inibidores de Proteínas Quinases/farmacologia
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); EC 2.7.1.137 (Class Ia Phosphatidylinositol 3-Kinase); EC 3.1.3.67 (PTEN Phosphohydrolase); EC 3.1.3.67 (PTEN protein, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170616
[Lr] Data última revisão:
170616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170120
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.6b01821


  10 / 41563 MEDLINE  
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[PMID]:28187870
[Au] Autor:Tan BH; Guo CY; Xiong TQ; Chen LM; Li YC
[Ad] Endereço:Laboratory Teaching Center of Basic Medicine, Norman Bethune Health Science Center of Jilin University, Changchun, Jilin Province, 130021, PR China.
[Ti] Título:The unique organization of filamentous actin in the medullary canal of the medulla oblongata.
[So] Source:Tissue Cell;49(2 Pt B):336-344, 2017 Apr.
[Is] ISSN:1532-3072
[Cp] País de publicação:Scotland
[La] Idioma:eng
[Ab] Resumo:In the central canal, F-actin is predominantly localized in the apical region, forming a ring-like structure around the circumference of the lumen. However, an exception is found in the medulla oblongata, where the apical F-actin becomes interrupted in the ventral aspect of the canal. To clarify the precise localization of F-actin, the fluorescence signals for F-actin were converted to the peroxidase/DAB reaction products in this study by a phalloidin-based ultrastructural technique, which demonstrated that F-actin is located mainly in the microvilli and terminal webs in the ependymocytes. It is because the ventrally oriented ependymocytes do not possess well-developed microvilli or terminal web that led to a discontinuous labeling of F-actin in the medullary canal. Since spinal motions can change the shape and size of the central canal, we next examined the cytoskeletons in the medullary canal in both rats and monkeys, because these two kinds of animals show different kinematics at the atlanto-occipital articulation. Our results first demonstrated that the apical F-actin in the medullary canal is differently organized in the animals with different head-neck kinemics, which suggests that the mechanic stretching of spinal motions is capable of inducing F-actin reorganization and the subsequent cell-shape changes in the central canal.
[Mh] Termos MeSH primário: Citoesqueleto de Actina/ultraestrutura
Actinas/metabolismo
Bulbo/ultraestrutura
Canal Vertebral/ultraestrutura
[Mh] Termos MeSH secundário: Citoesqueleto de Actina/metabolismo
Actinas/isolamento & purificação
Animais
Fenômenos Biomecânicos
Haplorrinos
Bulbo/metabolismo
Ratos
Canal Vertebral/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE



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