Base de dados : MEDLINE
Pesquisa : D08.811.913.696.620.500 [Categoria DeCS]
Referências encontradas : 30744 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 3075 ir para página                         

  1 / 30744 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29373584
[Au] Autor:Zhao X; Li R; Jin H; Jin H; Wang Y; Zhang W; Wang H; Chen W
[Ad] Endereço:Tianjin Institute of Health and Environmental Medicine, Tianjin, China.
[Ti] Título:Epigallocatechin-3-gallate confers protection against corticosterone-induced neuron injuries via restoring extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3 kinase/protein kinase B signaling pathways.
[So] Source:PLoS One;13(1):e0192083, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Extensive studies suggested epigallocatechin-3-gallate (EGCG) has significant neuroprotection against multiple central neural injuries, but the underlying mechanisms still remain poorly elucidated. Here we provide evidence to support the possible involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol-3 kinase/ protein kinase B (PI3K/AKT) pathways in EGCG-mediated protection against corticosterone-induced neuron injuries. As an essential stress hormone, corticosterone could induce obvious neurotoxicity in primary hippocampal neurons. Pre-treatment with EGCG ameliorated the corticosterone-induced neuronal injuries; however, it was blocked by pharmacological inhibitors for ERK1/2 (U0126) and PI3K/AKT (LY294002). Furthermore, the results confirmed that EGCG restored the corticosterone-induced decrease of ERK1/2 and PI3K/AKT phosphorylation, and attenuated the corticosterone-induced reduction of peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α) expression and ATP production. Taken together, these findings indicated that EGCG has significant neuroprotection against corticosterone-induced neuron injuries partly via restoring the ERK1/2 and PI3K/AKT signaling pathways as well as the PGC-1α-mediated ATP production.
[Mh] Termos MeSH primário: Catequina/análogos & derivados
Corticosterona/efeitos adversos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Neurônios/efeitos dos fármacos
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Proteínas Proto-Oncogênicas c-akt/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/biossíntese
Animais
Catequina/farmacologia
Células Cultivadas
Hipocampo/citologia
Hipocampo/efeitos dos fármacos
Fármacos Neuroprotetores/farmacologia
Fosforilação
Ratos
Ratos Wistar
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Neuroprotective Agents); 8L70Q75FXE (Adenosine Triphosphate); 8R1V1STN48 (Catechin); BQM438CTEL (epigallocatechin gallate); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0192083


  2 / 30744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29346447
[Au] Autor:Chang HJ; Shin HS; Kim TH; Yoo JY; Teasley HE; Zhao JJ; Ha UH; Jeong JW
[Ad] Endereço:Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI, United States of America.
[Ti] Título:Pik3ca is required for mouse uterine gland development and pregnancy.
[So] Source:PLoS One;13(1):e0191433, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The PI3K/AKT signaling pathway plays a critical role in the maintenance of equilibrium between cell survival and apoptosis. The Pik3ca gene is mutated in a range of human cancers. It has been found to be oncogenic, and mutations lead to constitutive activation of the PI3K/AKT pathway. The expression patterns of PIK3CA proteins in the uterus of mice during early pregnancy indicate that it may play a role in the regulation of glandular epithelial cells, which is required to support uterine receptivity. To further investigate the role of Pik3ca in uterine function, Pik3ca was conditionally ablated only in the PGR-positive cells (Pgrcre/+Pik3caf/f; Pik3cad/d). A defect of uterine gland development and decidualization led to subfertility observed in Pik3cad/d mice. Pik3cad/d mice showed significantly decreased uterine weight compared to Pik3caf/f mice. Interestingly, a significant decrease of gland numbers were detected in Pik3cad/d mice compared to control mice. In addition, we found a decrease of Foxa2 expression, which is a known uterine gland marker in Pik3cad/d mice. Furthermore, the excessive proliferation of endometrial epithelial cells was observed in Pik3cad/d mice. Our studies suggest that Pik3ca has a critical role in uterine gland development and female fertility.
[Mh] Termos MeSH primário: Fosfatidilinositol 3-Quinases/metabolismo
Útero/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Animais
Western Blotting
Proliferação Celular
Decídua/citologia
Decídua/crescimento & desenvolvimento
Implantação do Embrião
Feminino
Fertilidade
Camundongos
Camundongos Endogâmicos C57BL
Mutação
Fosfatidilinositol 3-Quinases/genética
Gravidez
Reação em Cadeia da Polimerase em Tempo Real
Útero/citologia
Útero/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.137 (Pik3ca protein, mouse)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180119
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191433


  3 / 30744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29320816
[Au] Autor:Ismail HAHA; Kang BH; Kim JS; Lee JH; Choi IW; Cha GH; Yuk JM; Lee YH
[Ad] Endereço:Department of Infection Biology, Chungnam National University School of Medicine, Daejeon 34134, Korea.
[Ti] Título:IL-12 and IL-23 Production in Toxoplasma gondii- or LPS-Treated Jurkat T Cells via PI3K and MAPK Signaling Pathways.
[So] Source:Korean J Parasitol;55(6):613-622, 2017 Dec.
[Is] ISSN:1738-0006
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:IL-12 and IL-23 are closely related in structure, and have been shown to play crucial roles in regulation of immune responses. However, little is known about the regulation of these cytokines in T cells. Here, we investigated the roles of PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was significantly increased in T cells after stimulation with T. gondii or LPS. T. gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2 in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells, but increased in LPS-stimulated cells. IL-12 and IL-23 production was significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS-stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively, IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T. gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells. And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23 production in Jurkat T cells through the regulation of the PI3K and MAPK pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23 production by T. gondii in Jurkat T cells is different from that of LPS.
[Mh] Termos MeSH primário: Interleucina-12/metabolismo
Interleucina-23/metabolismo
Lipopolissacarídeos/imunologia
Sistema de Sinalização das MAP Quinases/imunologia
Sistema de Sinalização das MAP Quinases/fisiologia
Fosfatidilinositol 3-Quinases/imunologia
Fosfatidilinositol 3-Quinases/fisiologia
Toxoplasma/imunologia
[Mh] Termos MeSH secundário: Células Cultivadas
Seres Humanos
Células Jurkat
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/fisiologia
Proteína Quinase 8 Ativada por Mitógeno/metabolismo
Proteína Quinase 8 Ativada por Mitógeno/fisiologia
Proteína Quinase 9 Ativada por Mitógeno/metabolismo
Proteína Quinase 9 Ativada por Mitógeno/fisiologia
Fosforilação
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-23); 0 (Lipopolysaccharides); 187348-17-0 (Interleukin-12); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.3347/kjp.2017.55.6.613


  4 / 30744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo SciELO Brasil
[PMID]:29267498
[Au] Autor:Ni XJ; Xu ZQ; Jin H; Zheng SL; Cai Y; Wang JJ
[Ad] Endereço:Transplantation Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
[Ti] Título:Ginsenoside Rg1 protects human renal tubular epithelial cells from lipopolysaccharide-induced apoptosis and inflammation damage.
[So] Source:Braz J Med Biol Res;51(2):e6611, 2017 Dec 11.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Ginsenoside Rg1, one of the most notable active components of Panax ginseng, has been widely reported to exert anti-inflammatory actions. This study aimed to reveal whether ginsenoside Rg1 also exhibits beneficial roles against lipopolysaccharide (LPS)-induced apoptosis and inflammation in human renal tubular epithelial cells, and to evaluate the potential role of the component on tubulointerstitial nephritis treatment. HK-2 cells were treated with various doses of ginsenoside Rg1 (0, 50, 100, 150, and 200 µM) in the absence or presence of 5 µg/mL LPS. Thereafter, CCK-8 assay, flow cytometry, western blot, migration assay, reactive oxygen species (ROS) assay, and ELISA were carried out to respectively assess cell viability, apoptosis, migration, ROS activity, and the release of inflammatory cytokines. As a result, ginsenoside Rg1 protected HK-2 cells from LPS-induced injury, as cell viability was increased, cell apoptosis was decreased, and the release of MCP-1, IL-1ß, IL-6, and TNF-α was reduced. Ginsenoside Rg1 functioned to HK-2 cells in a dose-dependent manner, and the 150 µM dose exhibited the most protective functions. Ginsenoside Rg1 had no significant impact on cell migration and ROS activity, while it alleviated LPS-induced ROS release and migration impairment. Furthermore, the down-regulations of p-PI3K, p-AKT, and up-regulations of PTEN, p-IκBα, p-p65, Bcl-3 induced by LPS were recovered to some extent after ginsenoside Rg1 treatment. In conclusion, ginsenoside Rg1 protects HK-2 cells against LPS-induced inflammation and apoptosis via activation of the PI3K/AKT pathway and suppression of NF-κB pathway.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Apoptose/efeitos dos fármacos
Células Epiteliais/efeitos dos fármacos
Ginsenosídeos/farmacologia
Túbulos Renais/citologia
Lipopolissacarídeos
Nefrite/prevenção & controle
[Mh] Termos MeSH secundário: Análise de Variância
Western Blotting
Linhagem Celular
Ensaios de Migração Celular
Sobrevivência Celular/efeitos dos fármacos
Citocinas/análise
Citocinas/efeitos dos fármacos
Ensaio de Imunoadsorção Enzimática
Seres Humanos
Túbulos Renais/efeitos dos fármacos
Fosfatidilinositol 3-Quinases/análise
Fosfatidilinositol 3-Quinases/efeitos dos fármacos
Substâncias Protetoras/farmacologia
Proteínas Proto-Oncogênicas c-akt/análise
Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos
Espécies Reativas de Oxigênio/análise
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Cytokines); 0 (Ginsenosides); 0 (Lipopolysaccharides); 0 (Protective Agents); 0 (Reactive Oxygen Species); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); PJ788634QY (ginsenoside Rg1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


  5 / 30744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29442036
[Au] Autor:Pivodová V; Zahler S; Karas D; Valentová K; Ulrichova J
[Ti] Título: study of 2,3-dehydrosilybin and its galloyl esters as potential inhibitors of angiogenesis.
[So] Source:Pharmazie;71(8):478-483, 2016 08 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:2,3-Dehydrosilybin exhibits substantial anticancer and antiangiogenic effects, which can be potentially improved by semi-synthetic modification such as esterification with gallic acid. The aim of this study was to examine the potential antiangiogenic effect of 2,3-dehydrosilybin and its galloyl esters (3-O-galloyl-2,3-dehydrosilybin; 7-O-galloyl-2,3-dehydrosilybin; 20-O-galloyl-2,3-dehydrosilybin and 23-O-galloyl-2,3-dehydrosilybin) and to determine which molecular mechanism could be responsible for their activity. The effect on cell proliferation, tube formation, signal transduction pathways (PI3K/Akt and ERK) and the cell cycle was studied in human microvascular endothelial cells (HMEC). The results showed that all compounds decreased the growth of HMEC, but the strongest effect was observed for 20-O-galloyl-2,3-dehydrosilybin at 5 µmol/l. In addition, at 5 and 10 µmol/l, this was the only compound that significantly inhibited HMEC tube formation. Based on an assessment of Akt and ERK1/2 expression, we suggest that 20-O-galloyl-2,3-dehydrosilybin influences the angiogenic process through the Akt pathway.
[Mh] Termos MeSH primário: Inibidores da Angiogênese/farmacologia
Silimarina/farmacologia
[Mh] Termos MeSH secundário: Inibidores da Angiogênese/síntese química
Ciclo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células Endoteliais/efeitos dos fármacos
Ésteres/síntese química
Ésteres/farmacologia
Ácido Gálico/síntese química
Ácido Gálico/farmacologia
Seres Humanos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Microtúbulos/efeitos dos fármacos
Neovascularização Patológica/tratamento farmacológico
Proteína Oncogênica v-akt/efeitos dos fármacos
Fosfatidilinositol 3-Quinases/efeitos dos fármacos
Silimarina/síntese química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Esters); 0 (Silymarin); 4RKY41TBTF (silybin); 632XD903SP (Gallic Acid); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Oncogene Protein v-akt)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6579


  6 / 30744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29206995
[Au] Autor:Wyatt AW; Annala M; Aggarwal R; Beja K; Feng F; Youngren J; Foye A; Lloyd P; Nykter M; Beer TM; Alumkal JJ; Thomas GV; Reiter RE; Rettig MB; Evans CP; Gao AC; Chi KN; Small EJ; Gleave ME
[Ad] Endereço:Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Department of Medicine and Department of Radiation Oncology, UCSF Helen Diller Family Comprehensive
[Ti] Título:Concordance of Circulating Tumor DNA and Matched Metastatic Tissue Biopsy in Prostate Cancer.
[So] Source:J Natl Cancer Inst;109(12), 2017 Dec 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Real-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling. Methods: We performed targeted sequencing across 72 clinically relevant genes in 45 plasma cell-free DNA (cfDNA) samples collected at time of metastatic tissue biopsy. We compared ctDNA alterations with exome sequencing data generated from matched tissue and quantified the concordance of mutations and copy number alterations using the Fisher exact test and Pearson correlations. Results: Seventy-five point six percent of cfDNA samples had a ctDNA proportion greater than 2% of total cfDNA. In these patients, all somatic mutations identified in matched metastatic tissue biopsies were concurrently present in ctDNA. Furthermore, the hierarchy of variant allele fractions for shared mutations was remarkably similar between ctDNA and tissue. Copy number profiles between matched liquid and solid biopsy were highly correlated, and individual copy number calls in clinically actionable genes were 88.9% concordant. Detected alterations included AR amplifications in 22 (64.7%) samples, SPOP mutations in three (8.8%) samples, and inactivating alterations in tumor suppressors TP53 , PTEN , RB1 , APC , CDKN1B , BRCA2 , and PIK3R1 . In several patients, ctDNA sequencing revealed robust changes not present in paired solid biopsy, including clinically relevant alterations in the AR, WNT, and PI3K pathways. Conclusions: Our study shows that, in the majority of patients, a ctDNA assay is sufficient to identify all driver DNA alterations present in matched metastatic tissue and supports development of DNA biomarkers to guide mCRPC patient management based on ctDNA alone.
[Mh] Termos MeSH primário: DNA Tumoral Circulante/sangue
Neoplasias de Próstata Resistentes à Castração/genética
Neoplasias de Próstata Resistentes à Castração/patologia
[Mh] Termos MeSH secundário: Proteína da Polipose Adenomatosa do Colo/genética
Proteína BRCA2/genética
Biomarcadores Tumorais/sangue
Biomarcadores Tumorais/genética
Inibidor de Quinase Dependente de Ciclina p27/genética
Variações do Número de Cópias de DNA
Seres Humanos
Biópsia Líquida
Masculino
Mutação
Metástase Neoplásica
Proteínas Nucleares/genética
PTEN Fosfo-Hidrolase/genética
Fosfatidilinositol 3-Quinases/genética
Receptores Androgênicos/genética
Proteínas Repressoras/genética
Proteínas de Ligação a Retinoblastoma/genética
Proteína Supressora de Tumor p53/genética
Ubiquitina-Proteína Ligases/genética
Via de Sinalização Wnt/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (APC protein, human); 0 (Adenomatous Polyposis Coli Protein); 0 (BRCA2 Protein); 0 (BRCA2 protein, human); 0 (Biomarkers, Tumor); 0 (CDKN1B protein, human); 0 (Circulating Tumor DNA); 0 (Nuclear Proteins); 0 (RB1 protein, human); 0 (Receptors, Androgen); 0 (Repressor Proteins); 0 (Retinoblastoma Binding Proteins); 0 (SPOP protein, human); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.1.- (PIK3R1 protein, human); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 3.1.3.67 (PTEN Phosphohydrolase); EC 3.1.3.67 (PTEN protein, human)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx118


  7 / 30744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29028222
[Au] Autor:Choi HJ; Joo HS; Won HY; Min KW; Kim HY; Son T; Oh YH; Lee JY; Kong G
[Ad] Endereço:Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University,
[Ti] Título:Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.
[So] Source:J Natl Cancer Inst;110(4), 2018 Apr 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Methods: Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764). RBP2-mediated tamoxifen resistance was confirmed by invitro sulforhodamine B (SRB) colorimetric, colony-forming assays, and invivo xenograft models (n = 8 per group). RNA-seq analysis and receptor tyrosine kinase assay were performed to identify the tamoxifen resistance mechanism by RBP2. All statistical tests were two-sided. Results: RBP2 was associated with poor prognosis to tamoxifen therapy in ER-positive breast cancer (P = .04 in HYU cohort, P = .02 in KM plotter, P = .007 in METABRIC, log-rank test). Furthermore, RBP2 expression was elevated in patients with tamoxifen-resistant breast cancer (P = .04, chi-square test). Knockdown of RBP2 conferred tamoxifen sensitivity, whereas overexpression of RBP2 induced tamoxifen resistance invitro and invivo (MCF7 xenograft: tamoxifen-treated control, mean [SD] tumor volume = 70.8 [27.9] mm3, vs tamoxifen-treated RBP2, mean [SD] tumor volume = 387.9 [85.1] mm3, P < .001). Mechanistically, RBP2 cooperated with ER co-activators and corepressors and regulated several tamoxifen resistance-associated genes, including NRIP1, CCND1, and IGFBP4 and IGFBP5. Furthermore, epigenetic silencing of IGFBP4/5 by RBP2-ER-NRIP1-HDAC1 complex led to insulin-like growth factor-1 receptor (IGF1R) activation. RBP2 also increased IGF1R-ErbB crosstalk and subsequent PI3K-AKT activation via demethylase activity-independent ErbB protein stabilization. Combinational treatment with tamoxifen and PI3K inhibitor could overcome RBP2-mediated tamoxifen resistance (RBP2-overexpressing cells: % cell viability [SD], tamoxifen = 89.0 [3.8]%, vs tamoxifen with BKM120 = 41.3 [5.6]%, P < .001). Conclusions: RBP2 activates ER-IGF1R-ErbB signaling cascade in multiple ways to induce tamoxifen resistance, suggesting that RBP2 is a potential therapeutic target for ER-driven cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Carcinoma Ductal de Mama/metabolismo
Resistência a Medicamentos Antineoplásicos
Proteínas de Neoplasias/fisiologia
Receptores Estrogênicos/metabolismo
Proteína 2 de Ligação ao Retinoblastoma/fisiologia
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Análise de Variância
Animais
Antineoplásicos Hormonais/uso terapêutico
Neoplasias da Mama/química
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/patologia
Carcinoma Ductal de Mama/química
Carcinoma Ductal de Mama/tratamento farmacológico
Carcinoma Ductal de Mama/patologia
Proteínas de Transporte/metabolismo
Estudos de Coortes
Colorimetria
Intervalo Livre de Doença
Resistência a Medicamentos Antineoplásicos/genética
Feminino
Xenoenxertos
Seres Humanos
Estimativa de Kaplan-Meier
Células MCF-7
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Proteínas de Neoplasias/metabolismo
Células-Tronco Neoplásicas
Proteínas Nucleares/metabolismo
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfatidilinositol 3-Quinases/metabolismo
Receptor ErbB-2/metabolismo
Receptor IGF Tipo 1/metabolismo
Proteína 2 de Ligação ao Retinoblastoma/metabolismo
Tamoxifeno/uso terapêutico
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Antineoplastic Agents, Hormonal); 0 (Carrier Proteins); 0 (IGFBP5-interacting protein, human); 0 (Neoplasm Proteins); 0 (Nuclear Proteins); 0 (Receptors, Estrogen); 0 (nuclear receptor interacting protein 1); 094ZI81Y45 (Tamoxifen); EC 1.14.11.27 (Retinoblastoma-Binding Protein 2); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.10.1 (Receptor, ErbB-2); EC 2.7.10.1 (Receptor, IGF Type 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx207


  8 / 30744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28455143
[Au] Autor:Li H; Li B; Larose L
[Ad] Endereço:Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada; The Research Institute of McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
[Ti] Título:IRE1α links Nck1 deficiency to attenuated PTP1B expression in HepG2 cells.
[So] Source:Cell Signal;36:79-90, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PTP1B, a prototype of the non-receptor subfamily of the protein tyrosine phosphatase superfamily, plays a key role in regulating intracellular signaling from various receptor and non-receptor protein tyrosine kinases. Previously, we reported that silencing Nck1 in human hepatocellular carcinoma HepG2 cells enhances basal and growth factor-induced activation of the PI3K-Akt pathway through attenuating PTP1B expression. However, the underlying mechanism by which Nck1 depletion represses PTP1B expression remains unclear. In this study, we found that silencing Nck1 attenuates PTP1B expression in HepG2 cells through down-regulation of IRE1α. Indeed, we show that silencing Nck1 in HepG2 cells leads to decreased IRE1α expression and signaling. Accordingly, IRE1α depletion using siRNA in HepG2 cells enhances PI3K-dependent basal and growth factor-induced Akt activation, reproducing the effects of silencing Nck1 on activation of this pathway. In addition, depletion of IRE1α also leads to reduced PTP1B expression, which was rescued by ectopic expression of IRE1α in Nck1-depleted cells. Mechanistically, we found that silencing either Nck1 or IRE1α in HepG2 cells decreases PTP1B mRNA levels and stability. However, despite miR-122 levels, a miRNA targeting PTP1B 3' UTR and inducing PTP1B mRNA degradation in HepG2 cells, are increased in both Nck1- and IRE1α-depleted HepG2 cells, a miR-122 antagomir did not rescue PTP1B expression in these cells. Overall, this study highlights an important role for Nck1 in fine-tuning IRE1α expression and signaling that regulate PTP1B expression and subsequent activation of the PI3K-Akt pathway in HepG2 cells.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/deficiência
Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Endorribonucleases/metabolismo
Proteínas Oncogênicas/deficiência
Proteínas Oncogênicas/metabolismo
Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo
Proteínas Serina-Treonina Quinases/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/química
Animais
Ativação Enzimática/efeitos dos fármacos
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Inativação Gênica/efeitos dos fármacos
Células HeLa
Células Hep G2
Seres Humanos
Camundongos
MicroRNAs/metabolismo
Proteínas Oncogênicas/química
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação/efeitos dos fármacos
Ligação Proteica/efeitos dos fármacos
Domínios Proteicos
Proteína Tirosina Fosfatase não Receptora Tipo 1/genética
Proteínas Proto-Oncogênicas c-akt/metabolismo
Estabilidade de RNA/efeitos dos fármacos
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Transdução de Sinais/efeitos dos fármacos
Tapsigargina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (MIRN122 microRNA, human); 0 (MicroRNAs); 0 (Nck protein); 0 (Oncogene Proteins); 0 (RNA, Messenger); 67526-95-8 (Thapsigargin); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (ERN1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.1.- (Endoribonucleases); EC 3.1.3.48 (PTPN1 protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  9 / 30744 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29381400
[Au] Autor:Song ZY; Wang F; Cui SX; Qu XJ
[Ad] Endereço:a Department of Pharmacology, School of Basic Medical Sciences , Capital Medical University , Beijing , China.
[Ti] Título:Knockdown of CXCR4 Inhibits CXCL12-Induced Angiogenesis in HUVECs through Downregulation of the MAPK/ERK and PI3K/AKT and the Wnt/ß-Catenin Pathways.
[So] Source:Cancer Invest;36(1):10-18, 2018 Jan 02.
[Is] ISSN:1532-4192
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CXCL12 is an extracellular chemokine binding to cell surface receptor CXCR4. We found that activation of CXCL12/CXCR4 axis stimulated angiogenesis in endothelial cells. Knockdown of CXCR4 in endothelial cells prevented the branch points of angiogenesis. Endothelial cells exposed to CXCL12 presented high level of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and matrix metalloproteinase MMP-2, but not in CXCR4 knockdown cells. Further studies revealed that activation of CXCL12/CXCR4 axis in vascular endothelial cells stimulates the angiogenesis through upregulation of the MAPK/ERK and PI3K/AKT and Wnt/ß-catenin pathways. Conclusion, downregulation of CXCR4 could inhibit angiogenesis in cancer tissues.
[Mh] Termos MeSH primário: Quimiocina CXCL12/genética
Regulação para Baixo/genética
Regulação Neoplásica da Expressão Gênica/genética
Neovascularização Patológica/genética
Receptores CXCR4/genética
Transdução de Sinais/genética
[Mh] Termos MeSH secundário: Linhagem Celular
Células Endoteliais/metabolismo
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Sistema de Sinalização das MAP Quinases/genética
Metaloproteinase 2 da Matriz/genética
Proteínas Quinases Ativadas por Mitógeno/genética
Fosfatidilinositol 3-Quinases/genética
Proteínas Proto-Oncogênicas c-akt/genética
Receptor do Fator de Crescimento Epidérmico/genética
Regulação para Cima/genética
Fator A de Crescimento do Endotélio Vascular/genética
Via de Sinalização Wnt/genética
beta Catenina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CXCL12 protein, human); 0 (CXCR4 protein, human); 0 (Chemokine CXCL12); 0 (Receptors, CXCR4); 0 (Vascular Endothelial Growth Factor A); 0 (beta Catenin); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); EC 3.4.24.24 (Matrix Metalloproteinase 2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1080/07357907.2017.1422512


  10 / 30744 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29441929
[Au] Autor:Wang J; Li L; Wu K; Ge W; Zhang Z; Gong L; Yuan D
[Ti] Título:Knockdown of long noncoding RNA urothelial cancer-associated 1 enhances cisplatin chemosensitivity in tongue squamous cell carcinoma cells.
[So] Source:Pharmazie;71(10):598-602, 2016 Oct 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Cisplatin-based chemotherapy has been found to improve the prognosis of patients with tongue squamous cell carcinoma (TSCC), the most common oral cancer with a poor prognosis. Chemoresistance to cisplatin appears to be an important clinical problem for cisplatin-based TSCC chemotherapy. Long noncoding RNAs (lncRNAs) play important roles in regulating tumor cells' sensitivity to chemotherapeutic agents. A recent study has shown that the expression of lncRNA UCA1 is significantly enhanced in TSCCs, suggesting that UCA1 may play a role in TSCC progression. In the present study, we explored the effects and the underlying mechanisms of UCA1 on cisplatin chemosensitivity/chemoresistance and apoptosis in TSCC cells. Transient transfection of siRNA was used to knock down UCA1 in human TSCC cell lines CAL 27 and SCC-9, where UCA1 was highly overexpressed compared to normal human tongue tissues. Knockdown of UCA1 markedly increased cisplatin-induced caspase 3 activity and apoptosis in CAL 27 and SCC-9 cells. On the other hand, it decreased cisplatin-induced phosphatidylinositol 3-kinase (PI3K) activity and activation phosphorylation of Akt. UCA1 knockdown resulted in one magnitude decrease in the half maximal inhibitory concentration (IC50) of cisplatin in CAL 27 and SCC-9 cells, from 8.9 mM and 20.7 mM down to 0.6 mM and 1.7 mM, respectively. In conclusion, this study has shown that UCA1 knockdown markedly increased cisplatin-induced apoptosis and chemosensitivity in TSCC cells, likely through inhibiting cisplatin-activated PI3K/Akt signaling. It provides new insights into the functional role of UCA1 in cancer cells and suggests that UCA1 knockdown could be a new strategy to increase cisplatin chemosensitivity and thereby improve the therapeutic outcomes of cisplatin-based chemotherapy for TSCC.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Carcinoma de Células Escamosas/tratamento farmacológico
Cisplatino/farmacologia
RNA Longo não Codificante/genética
Neoplasias da Língua/tratamento farmacológico
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Caspase 3/biossíntese
Caspase 3/genética
Linhagem Celular Tumoral
Resistência a Medicamentos Antineoplásicos/genética
Técnicas de Silenciamento de Genes
Seres Humanos
Proteína Oncogênica v-akt/biossíntese
Proteína Oncogênica v-akt/genética
Fosfatidilinositol 3-Quinases
RNA Interferente Pequeno/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (RNA, Long Noncoding); 0 (RNA, Small Interfering); 0 (UCA1 RNA, human); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Oncogene Protein v-akt); EC 3.4.22.- (CASP3 protein, human); EC 3.4.22.- (Caspase 3); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6625



página 1 de 3075 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