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Pesquisa : D02.092.146.350 [Categoria DeCS]
Referências encontradas : 729 [refinar]
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[PMID]:28461660
[Au] Autor:Nichols J; Jones K
[Ti] Título:Derivation of Mouse Embryonic Stem (ES) Cell Lines Using Small-Molecule Inhibitors of Erk and Gsk3 Signaling (2i).
[So] Source:Cold Spring Harb Protoc;2017(5):pdb.prot094086, 2017 May 01.
[Is] ISSN:1559-6095
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The efficiency of embryonic stem (ES) cell derivation is very high if embryos are incubated, from the eight-cell stage, in the presence of the two inhibitors of signaling via the Erk and Gsk3 pathways (PD0325901 and CHIR99021, respectively, known as "2i"). The success rate may vary, depending on the quality of the embryos and the speed with which they are processed, but it is not unusual to obtain ES cell lines from all embryos allocated to the study, even from the least permissive strains. Furthermore, ES cells can be efficiently obtained from any complex genetic mouse model or for in vitro analysis and additional genetic manipulation in any background of choice.
[Mh] Termos MeSH primário: MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores
Quinase 3 da Glicogênio Sintase/antagonistas & inibidores
Células-Tronco Embrionárias Murinas/citologia
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Benzamidas/farmacologia
Processos de Crescimento Celular
Linhagem Celular
Meios de Cultura
Difenilamina/análogos & derivados
Difenilamina/farmacologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Camundongos
Piridinas/farmacologia
Pirimidinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamides); 0 (Chir 99021); 0 (Culture Media); 0 (PD 0325901); 0 (Pyridines); 0 (Pyrimidines); 9N3CBB0BIQ (Diphenylamine); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 2.7.11.26 (Glycogen Synthase Kinase 3)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1101/pdb.prot094086


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[PMID]:29179218
[Au] Autor:Wang L; Cui Y; Liu Q; Song Y; Hu Q; Tang M; Hescheler J; Xi J
[Ad] Endereço:Department of Physiology and Chinese-German Stem Cell Center, School of Basic Medicine, Huazhong University of Science and Technology, The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China.
[Ti] Título:Puerarin Enhances Ca2+ Reuptake and Ca2+ Content of Sarcoplasmic Reticulum in Murine Embryonic Stem Cell-Derived Cardiomyocytes via Upregulation of SERCA2a.
[So] Source:Cell Physiol Biochem;44(3):1199-1212, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: The embryonic stem cell-derived cardiomyocytes (ES-CMs) serve as potential sources for cardiac regenerative therapy. However, the immature sarcoplasmic reticulum (SR) function of ES-CMs prevents its application. In this report, we examined the effect of puerarin, an isoflavone compound, on SR function of murine ES-CMs. METHODS: Murine ES-CMs were harvested by embryoid body-based differentiation method. Confocal calcium imaging and whole-cell patch clamps were performed to assess the function of SR. The mRNA expression levels of SR-related genes were examined by quantitative PCR. The protein expression of sarcoplasmic reticulum calcium-ATPase 2a (SERCA2a) was evaluated by immunofluorescent and western blot. RESULTS: Long-term application of puerarin promotes basic properties of spontaneous calcium transient with increased amplitude, decay velocity, and decreased duration. Puerarin fails to alter ICa,L but increases the Ca2+ content of SR. Puerarin-treated ES-CMs have intact SR Ca2+ cycling with more SR Ca2+ reuptake. Long-term application of puerarin asynchronously upregulates the mRNA and protein expression of SERCA2a, as well as the transcripts of calsequestrin and triadin in developing ES-CMs. Application of puerarin during the stage of post-cardiac differentiation upregulates dose-dependently the transcripts of SERCA2a, phospholamban and tridin which can be reversed by the inhibitors of the PI3K/Akt and MAPK/ERK signaling pathways, but shows no effect on the protein expression of SERCA2a. CONCLUSION: This study demonstrates that long-term puerarin treatment enhances Ca2+ reuptake and Ca2+ content via upregulation of SERCA2a.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Isoflavonas/farmacologia
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
Regulação para Cima/efeitos dos fármacos
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Androstadienos/farmacologia
Animais
Benzamidas/farmacologia
Proteínas de Ligação ao Cálcio/metabolismo
Calsequestrina/genética
Calsequestrina/metabolismo
Proteínas de Transporte/genética
Proteínas de Transporte/metabolismo
Diferenciação Celular/efeitos dos fármacos
Difenilamina/análogos & derivados
Difenilamina/farmacologia
Camundongos
Microscopia Confocal
Células-Tronco Embrionárias Murinas/citologia
Proteínas Musculares/genética
Proteínas Musculares/metabolismo
Miócitos Cardíacos/citologia
Miócitos Cardíacos/metabolismo
Técnicas de Patch-Clamp
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Retículo Sarcoplasmático/metabolismo
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/antagonistas & inibidores
ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética
Transdução de Sinais/efeitos dos fármacos
Tapsigargina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstadienes); 0 (Benzamides); 0 (Calcium-Binding Proteins); 0 (Calsequestrin); 0 (Carrier Proteins); 0 (Isoflavones); 0 (Muscle Proteins); 0 (PD 0325901); 0 (Vasodilator Agents); 0 (phospholamban); 0 (triadin); 67526-95-8 (Thapsigargin); 9N3CBB0BIQ (Diphenylamine); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases); SY7Q814VUP (Calcium); XVA4O219QW (wortmannin); Z9W8997416 (puerarin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1159/000485450


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[PMID]:28923853
[Au] Autor:Bruner JK; Ma HS; Li L; Qin ACR; Rudek MA; Jones RJ; Levis MJ; Pratz KW; Pratilas CA; Small D
[Ad] Endereço:Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
[Ti] Título:Adaptation to TKI Treatment Reactivates ERK Signaling in Tyrosine Kinase-Driven Leukemias and Other Malignancies.
[So] Source:Cancer Res;77(20):5554-5563, 2017 Oct 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:FMS-like tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia (AML). We hypothesized that FLT3/internal tandem duplication (ITD) leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here, we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared with either drug alone. ERK reactivation was also observed following inhibition of other tyrosine kinase-driven cancer cells, including EGFR-mutant lung cancer, HER2-amplified breast cancer, and BCR-ABL leukemia. These studies reveal an adaptive feedback mechanism in tyrosine kinase-driven cancers associated with reactivation of ERK signaling in response to targeted inhibition. .
[Mh] Termos MeSH primário: Leucemia Mieloide Aguda/tratamento farmacológico
Leucemia Mieloide Aguda/enzimologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Inibidores de Proteínas Quinases/farmacologia
[Mh] Termos MeSH secundário: Animais
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Benzamidas/administração & dosagem
Benzamidas/farmacologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Difenilamina/administração & dosagem
Difenilamina/análogos & derivados
Difenilamina/farmacologia
Feminino
Células HL-60
Seres Humanos
Células K562
Leucemia Mieloide Aguda/genética
Leucemia Mieloide Aguda/patologia
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Neoplasias/tratamento farmacológico
Neoplasias/enzimologia
Neoplasias/genética
Neoplasias/patologia
Niacinamida/administração & dosagem
Niacinamida/análogos & derivados
Niacinamida/farmacologia
Compostos de Fenilureia/administração & dosagem
Compostos de Fenilureia/farmacologia
Inibidores de Proteínas Quinases/administração & dosagem
Distribuição Aleatória
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamides); 0 (PD 0325901); 0 (Phenylurea Compounds); 0 (Protein Kinase Inhibitors); 25X51I8RD4 (Niacinamide); 9N3CBB0BIQ (Diphenylamine); 9ZOQ3TZI87 (sorafenib)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-16-2593


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[PMID]:28756218
[Au] Autor:Lu Z; Smyth SA; Peart TE; De Silva AO
[Ad] Endereço:Science & Technology Branch, Environment and Climate Change Canada, 867 Lakeshore Road, Burlington, Ontario, L7S 1A1, Canada. Electronic address: zhe.lu@canada.ca.
[Ti] Título:Occurrence and fate of substituted diphenylamine antioxidants and benzotriazole UV stabilizers in various Canadian wastewater treatment processes.
[So] Source:Water Res;124:158-166, 2017 Nov 01.
[Is] ISSN:1879-2448
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Substituted diphenylamine antioxidants (SDPAs) and benzotriazole UV stabilizers (BZT-UVs) are additives used in industrial and consumer products to prevent degradation or color change of materials, but their environmental fate and disposition are not well characterized. In this study, SDPAs and BZT-UVs were analyzed in 68 liquid and 39 solid samples collected from 9 wastewater treatment plants (WWTPs) in Canada to investigate the occurrence and fate of these contaminants. The median concentrations of ΣSDPAs and ΣBZT-UVs was 483 and 76.2 ng L in influent, 28.4 and 4.84 ng L in effluent, and 2750 and 457 ng g in biosolids (dry weight), respectively. Dinonyl-diphenylamine (C9C9) was the predominant congener of SDPAs in all matrices (>40%). For target BZT-UVs, the major components were 2-(2H-benzotriazol-2-yl)-4,6-bis(1-methyl-1-phenylethyl)phenol (UV234) and 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV328). SDPAs and BZT-UVs were effectively removed (>90%) from the liquid stream in most WWTPs mainly through sludge sorption and separation, but biotransformation, UV treatment and filtration may also contribute to removal of some contaminants in advanced treatment plants. In contrast, the removal efficiency of target contaminants using chemically assisted primary treatment was low, likely due to the short hydraulic retention time of this site. Our results suggest that wastewater effluent is a vector of SDPAs and BZT-UVs to the aquatic environment. The results also highlight the high concentrations of SDPAs and BZT-UVs associated with the solid stream in WWTPs, which could affect the beneficial use of biosolids (e.g., compost or land applications).
[Mh] Termos MeSH primário: Antioxidantes/química
Difenilamina/química
Triazóis/química
Águas Residuais
Poluentes Químicos da Água/química
[Mh] Termos MeSH secundário: Canadá
Monitoramento Ambiental
Esgotos
Eliminação de Resíduos Líquidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Sewage); 0 (Triazoles); 0 (Waste Water); 0 (Water Pollutants, Chemical); 86110UXM5Y (benzotriazole); 9N3CBB0BIQ (Diphenylamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170731
[St] Status:MEDLINE


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[PMID]:28644741
[Au] Autor:Zheng X; Goodwin AF; Tian H; Jheon AH; Klein OD
[Ad] Endereço:1 Department of Stomatology, Peking University Third Hospital, Beijing, China.
[Ti] Título:Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor.
[So] Source:J Dent Res;96(12):1438-1444, 2017 Nov.
[Is] ISSN:1544-0591
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The role of Ras signaling during tooth development is poorly understood. Ras proteins-which are activated by many upstream pathways, including receptor tyrosine kinase cascades-signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor-which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells-provides a model for the study of ectodermal organ renewal and regeneration. Utilizing models of Ras dysregulation as well as inhibitors of the MAPK and PI3K pathways, we found that MAPK and PI3K regulate dental epithelial stem cell activity, transit-amplifying cell proliferation, and enamel formation in the mouse incisor.
[Mh] Termos MeSH primário: Amelogênese/fisiologia
Transdução de Sinais/fisiologia
Células-Tronco/fisiologia
Proteínas ras/metabolismo
[Mh] Termos MeSH secundário: Animais
Benzamidas/farmacologia
Proliferação Celular
Difenilamina/análogos & derivados
Difenilamina/farmacologia
Imunofluorescência
Incisivo
Indazóis/farmacologia
Camundongos
Proteínas Quinases Ativadas por Mitógeno/metabolismo
Modelos Animais
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação
Sulfonamidas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine); 0 (Benzamides); 0 (Indazoles); 0 (PD 0325901); 0 (Sulfonamides); 9N3CBB0BIQ (Diphenylamine); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.137 (Pik3cd protein, mouse); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 3.6.5.2 (ras Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE
[do] DOI:10.1177/0022034517717255


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[PMID]:28606806
[Au] Autor:Kwon OS; Hong SK; Kwon SJ; Go YH; Oh E; Cha HJ
[Ad] Endereço:College of Natural Sciences, Department of Life Sciences, Sogang University, Seoul, Republic of Korea.
[Ti] Título:BCL2 induced by LAMTOR3/MAPK is a druggable target of chemoradioresistance in mesenchymal lung cancer.
[So] Source:Cancer Lett;403:48-58, 2017 Sep 10.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Mesenchymal-type cancers after epithelial mesenchymal transition (EMT) were recently shown to acquire chemoresistance through expressing EMT specific transcription factors. However, druggable (or actionable) target(s) for chemoresistance in mesenchymal-type lung cancers remain unidentified. Here, we used a public clinical genomic database and mesenchymal lung cancer cells (MLCC) model derived from the A549 lung adenocarcinoma cell line to demonstrate that BCL2 expression, which is highly induced in mesenchymal-type lung cancers, as a predictor of poor prognosis in mesenchymal lung cancer patients and association with acquired chemoradioresistance. Thereby, combination treatment with BH3 mimetics, such as ABT-263 and ABT-737, clearly attenuated chemoresistance in MLCCs. BCL2 expression in MLCCs was induced by ERK1 activity through the upregulation of the MEK1/ERK1 scaffold protein MEK partner-1 (MP1). Interfering with the MEK1/MP1/ERK1 axis using a MEK1 inhibitor or MP1 depletion repressed BCL2 expression and sensitized MLCCs to chemoradiotherapy. Taken together, our results suggest that targeting druggable proteins in the MEK1/MP1/ERK1/BCL2 axis, such as MEK1 or BCL2, with currently available FDA approved drugs is a currently feasible approach to improve clinical outcomes of mesenchymal lung cancer patients.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Adenocarcinoma/terapia
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Quimiorradioterapia
Resistência a Medicamentos Antineoplásicos
Neoplasias Pulmonares/terapia
Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores
Fragmentos de Peptídeos/farmacologia
Inibidores de Proteínas Quinases/farmacologia
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Proteínas Proto-Oncogênicas/farmacologia
Tolerância a Radiação
[Mh] Termos MeSH secundário: Células A549
Adenocarcinoma/enzimologia
Adenocarcinoma/genética
Adenocarcinoma/patologia
Compostos de Anilina/farmacologia
Benzamidas/farmacologia
Compostos de Bifenilo/farmacologia
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Difenilamina/análogos & derivados
Difenilamina/farmacologia
Relação Dose-Resposta a Droga
Etoposídeo/farmacologia
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Neoplasias Pulmonares/enzimologia
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
MAP Quinase Quinase 1/antagonistas & inibidores
MAP Quinase Quinase 1/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/genética
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Proteínas Quinases Ativadas por Mitógeno/metabolismo
Mimetismo Molecular
Nitrofenóis/farmacologia
Piperazinas/farmacologia
Proteínas Proto-Oncogênicas c-bcl-2/genética
Interferência de RNA
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/efeitos da radiação
Sulfonamidas/farmacologia
Transfecção
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-737); 0 (Adaptor Proteins, Signal Transducing); 0 (Aniline Compounds); 0 (BCL2 protein, human); 0 (Bax protein (53-86)); 0 (Benzamides); 0 (Biphenyl Compounds); 0 (LAMTOR3 protein, human); 0 (Nitrophenols); 0 (PD 0325901); 0 (Peptide Fragments); 0 (Piperazines); 0 (Protein Kinase Inhibitors); 0 (Proto-Oncogene Proteins); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Sulfonamides); 6PLQ3CP4P3 (Etoposide); 9N3CBB0BIQ (Diphenylamine); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 2.7.12.2 (MAP Kinase Kinase 1); EC 2.7.12.2 (MAP2K1 protein, human); XKJ5VVK2WD (navitoclax)
[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:170614
[St] Status:MEDLINE


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[PMID]:28534510
[Au] Autor:Semenova G; Stepanova DS; Dubyk C; Handorf E; Deyev SM; Lazar AJ; Chernoff J
[Ad] Endereço:Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
[Ti] Título:Targeting group I p21-activated kinases to control malignant peripheral nerve sheath tumor growth and metastasis.
[So] Source:Oncogene;36(38):5421-5431, 2017 Sep 21.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Malignant peripheral nerve sheath tumors (MPNSTs) are devastating sarcomas for which no effective medical therapies are available. Over 50% of MPSNTs are associated with mutations in NF1 tumor suppressor gene, resulting in activation of Ras and its effectors, including the Raf/Mek/Erk and PI3K/Akt/mTORC1 signaling cascades, and also the WNT/ß-catenin pathway. As Group I p21-activated kinases (Group I Paks, PAK1/2/3) have been shown to modulate Ras-driven oncogenesis, we asked if these enzymes might regulate signaling in MPNSTs. In this study we found a strong positive correlation between the activity of PAK1/2/3 and the stage of human MPNSTs. We determined that reducing Group I Pak activity diminished MPNST cell proliferation and motility, and that these effects were not accompanied by significant blockade of the Raf/Mek/Erk pathway, but rather by reductions in Akt and ß-catenin activity. Using the small molecule PAK1/2/3 inhibitor Frax1036 and the MEK1/2 inhibitor PD0325901, we showed that the combination of these two agents synergistically inhibited MPNST cell growth in vitro and dramatically decreased local and metastatic MPNST growth in animal models. Taken together, these data provide new insights into MPNST signaling deregulation and suggest that co-targeting of PAK1/2/3 and MEK1/2 may be effective in the treatment of patients with MPNSTs.
[Mh] Termos MeSH primário: Benzamidas/farmacologia
Difenilamina/análogos & derivados
Neoplasias da Bainha Neural/tratamento farmacológico
Inibidores de Proteínas Quinases/farmacologia
Quinases Ativadas por p21/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Difenilamina/farmacologia
Feminino
Seres Humanos
Camundongos
Camundongos SCID
Terapia de Alvo Molecular
Metástase Neoplásica
Neoplasias da Bainha Neural/enzimologia
Neoplasias da Bainha Neural/patologia
Distribuição Aleatória
Transdução de Sinais
Ensaios Antitumorais Modelo de Xenoenxerto
Quinases Ativadas por p21/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzamides); 0 (PD 0325901); 0 (Protein Kinase Inhibitors); 9N3CBB0BIQ (Diphenylamine); EC 2.7.11.1 (p21-Activated Kinases)
[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:170524
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.143


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[PMID]:28514527
[Au] Autor:Friton G; Thompson C; Karadzovska D; King S; King JN
[Ad] Endereço:Companion Animal Development, Elanco Animal Health Inc, Basel, Switzerland.
[Ti] Título:Efficacy and Safety of Injectable Robenacoxib for the Treatment of Pain Associated With Soft Tissue Surgery in Dogs.
[So] Source:J Vet Intern Med;31(3):832-841, 2017 May.
[Is] ISSN:1939-1676
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used routinely to control pain and inflammation after surgery in dogs. Robenacoxib is a cyclooxygenase-2 selective NSAID. HYPOTHESIS/OBJECTIVE: Assess the clinical efficacy and safety of an injectable formulation of robenacoxib in dogs undergoing surgery. ANIMALS: Three hundred and seventeen client-owned dogs (N = 159 robenacoxib or N = 158 placebo). METHODS: In this prospective, multicenter, randomized, masked, placebo-controlled, parallel-group study, dogs received a SC injection of either robenacoxib, at a target dose of 2.0 mg/kg, or placebo once prior to surgery and for 2 additional days postoperatively. Pain assessments were performed using the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF). The primary efficacy variable was treatment success/failure, with failure defined as the need for rescue therapy to control pain or withdrawal of the dog from the study due to an adverse event. RESULTS: Significantly (P = .006) more dogs administered robenacoxib were considered treatment successes (108 of 151, 73.7%) compared to dogs given placebo (85 of 152, 58.1%). Total pain scores (P < .01), pain at the surgery sites (response to touch, P < .01), and posture/activity (P < .05) were significantly improved at 3, 5, and 8 hours postextubation in dogs receiving robenacoxib versus placebo. CONCLUSIONS AND CLINICAL IMPORTANCE: Robenacoxib administered by SC injection prior to surgery and for 2 additional days postoperatively was effective and well tolerated in the control of postoperative pain and inflammation associated with soft tissue surgery in dogs.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/uso terapêutico
Difenilamina/análogos & derivados
Cães/cirurgia
Manejo da Dor/veterinária
Fenilacetatos/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/administração & dosagem
Anti-Inflamatórios não Esteroides/efeitos adversos
Difenilamina/administração & dosagem
Difenilamina/efeitos adversos
Difenilamina/uso terapêutico
Feminino
Injeções Subcutâneas/veterinária
Masculino
Manejo da Dor/métodos
Medição da Dor/veterinária
Dor Pós-Operatória/prevenção & controle
Dor Pós-Operatória/veterinária
Fenilacetatos/administração & dosagem
Fenilacetatos/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Phenylacetates); 9N3CBB0BIQ (Diphenylamine); Z588009C7C (robenacoxib)
[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:170518
[St] Status:MEDLINE
[do] DOI:10.1111/jvim.14698


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[PMID]:28411470
[Au] Autor:Ashikhmin A; Makhneva Z; Bolshakov M; Moskalenko A
[Ad] Endereço:Institute of Basic Biological Problems, Russian Academy of Sciences, Pushchino 142290, Russia. Electronic address: AshikhminAA@gmail.com.
[Ti] Título:Incorporation of spheroidene and spheroidenone into light-harvesting complexes from purple sulfur bacteria.
[So] Source:J Photochem Photobiol B;170:99-107, 2017 May.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Spheroidene and spheroidenone from the non-sulfur bacterium Rhodobacter (Rba.) sphaeroides were incorporated into diphenylamine (DPA) LH1-RC and LH2 complexes from sulfur bacteria Allochromatium (Alc.) minutissimum and Ectothiorhodospira (Ect.) haloalkaliphila in which carotenoid (Car) biosynthesis was inhibited by ~95%. A series of biochemical characteristics of the modified LH2 complexes was studied (electrophoretic mobility, absorption and CD spectra, Car composition, Car-to-BChl energy transfer and thermal stability). It was found that the electrophoretic mobility of the complexes with incorporated Cars did not change compared to that of the control and DPA-complexes, indicating the absence of any significant change in the structure of LH complexes upon DPA-treatment and subsequent incorporation of Cars. The analysis of fluorescence excitation spectra of the spheroidene-incorporated LH2 complex (LH2:sph) and the spheroidenone-incorporated LH2 complex (LH2:sph-ne) showed that spheroidene and spheroidenone exhibited relatively low efficiencies of energy transfer to BChl, when incorporated into the LH2 DPA-complexes from Alc. minutissimum and Ect. haloalkaliphila, although, they showed high efficiencies, being in their natural state in the LH2 complexes from Rba. sphaeroides. A significant increase in thermostability observed for the LH2:sph and LH2:sph-ne complexes with respect to the LH2 DPA-complexes indicated that the two incorporated Cars stabilized the structure of the LH2 complexes.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Carotenoides/química
Chromatiaceae/metabolismo
Complexos de Proteínas Captadores de Luz/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/química
Carotenoides/biossíntese
Carotenoides/farmacologia
Cromatografia Líquida de Alta Pressão
Dicroísmo Circular
Difenilamina/química
Transferência de Energia/efeitos dos fármacos
Complexos de Proteínas Captadores de Luz/análise
Complexos de Proteínas Captadores de Luz/química
Estabilidade Proteica
Espectrometria de Fluorescência
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Light-Harvesting Protein Complexes); 13836-61-8 (spheroidene); 13836-70-9 (spheroidenone); 36-88-4 (Carotenoids); 9N3CBB0BIQ (Diphenylamine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170416
[St] Status:MEDLINE


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[PMID]:28283079
[Au] Autor:Yoshitake R; Saeki K; Watanabe M; Nakaoka N; Ong SM; Hanafusa M; Choisunirachon N; Fujita N; Nishimura R; Nakagawa T
[Ad] Endereço:Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
[Ti] Título:Molecular investigation of the direct anti-tumour effects of nonsteroidal anti-inflammatory drugs in a panel of canine cancer cell lines.
[So] Source:Vet J;221:38-47, 2017 Mar.
[Is] ISSN:1532-2971
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested as effective adjunctive anti-tumour agents in human and veterinary medicine. However, the molecular mechanisms associated with their anti-tumour effects and correlations with the expression of cyclooxygenase (COX) and related molecules in tumours remain controversial. The objective of this study was to compare the expression profiles of COX and related molecules with NSAID sensitivity and to explore the molecular mechanisms of anti-tumour effects. The expression profiles of COXs, prostaglandins (PGs), PGD synthases, and PGE synthases were obtained, and their correlations with in vitro sensitivity to the NSAIDs piroxicam, carprofen, and robenacoxib were examined, using 26 canine cancer cell lines. Subsequently, microarray analysis was performed using one melanoma cell line to gain insight into mechanisms by which NSAIDs could exert cytotoxic effects. No strong correlation was observed between the cellular expression of COX and related molecules and sensitivity to NSAID treatment. Additionally, NSAIDs inhibited cell growth only at considerably higher concentrations than those required for functional COX inhibition. Microarray data demonstrated that five genes (SLC16A6, PER2, SLC9A8, HTR2B, and BRAF) were significantly upregulated and that four genes (LOC488305, H2AFJ, LOC476445, and ANKRD43) were significantly downregulated by NSAID exposure to the melanoma cell line. These results suggest that the direct in vitro anti-tumour effects of NSAIDs might be mediated by COX/PG-independent pathways. Novel candidate genes that could potentially be involved in the anti-tumour effects of NSAIDs were identified. Further validation and elucidation of their associated mechanisms will contribute to patient selection in clinical settings and the development of effective combination therapies.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/uso terapêutico
Antineoplásicos/uso terapêutico
Doenças do Cão/tratamento farmacológico
Neoplasias/veterinária
[Mh] Termos MeSH secundário: Animais
Carbazóis/uso terapêutico
Linhagem Celular Tumoral
Inibidores de Ciclo-Oxigenase/uso terapêutico
Dinoprostona/metabolismo
Difenilamina/análogos & derivados
Difenilamina/uso terapêutico
Cães
Relação Dose-Resposta a Droga
Perfilação da Expressão Gênica/veterinária
Neoplasias/tratamento farmacológico
Fenilacetatos/uso terapêutico
Piroxicam/uso terapêutico
Prostaglandina D2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antineoplastic Agents); 0 (Carbazoles); 0 (Cyclooxygenase Inhibitors); 0 (Phenylacetates); 13T4O6VMAM (Piroxicam); 9N3CBB0BIQ (Diphenylamine); FFL0D546HO (carprofen); K7Q1JQR04M (Dinoprostone); RXY07S6CZ2 (Prostaglandin D2); Z588009C7C (robenacoxib)
[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:170312
[St] Status:MEDLINE



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