Base de dados : MEDLINE
Pesquisa : A01.941.875 [Categoria DeCS]
Referências encontradas : 3989 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 399 ir para página                         

  1 / 3989 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29385186
[Au] Autor:Eladak S; Moison D; Guerquin MJ; Matilionyte G; Kilcoyne K; N'Tumba-Byn T; Messiaen S; Deceuninck Y; Pozzi-Gaudin S; Benachi A; Livera G; Antignac JP; Mitchell R; Rouiller-Fabre V; Habert R
[Ad] Endereço:Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Genetic Stability, Stem Cells and Radiation, Fontenay-aux-Roses, France.
[Ti] Título:Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis.
[So] Source:PLoS One;13(1):e0191934, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Using an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01 µM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models. METHODS: Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 µM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 µM BPA (~ 500 µg/kg/day) in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 µM and 0.038 µM respectively. Mice grafted with second trimester testes received 0.5 and 50 µg/kg/day BPA by oral gavage for 5 weeks. RESULTS: With first trimester human testes, using the hFeTA model, 10 µM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice. CONCLUSIONS: Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures.
[Mh] Termos MeSH primário: Compostos Benzidrílicos/toxicidade
Poluentes Ambientais/toxicidade
Células Intersticiais do Testículo/efeitos dos fármacos
Fenóis/toxicidade
Espermatozoides/efeitos dos fármacos
Testículo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Feminino
Xenoenxertos
Seres Humanos
Masculino
Camundongos
Camundongos Nus
Gravidez
Primeiro Trimestre da Gravidez
Segundo Trimestre da Gravidez
Radioimunoensaio
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Testículo/citologia
Testículo/embriologia
Testosterona/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzhydryl Compounds); 0 (Environmental Pollutants); 0 (Phenols); 3XMK78S47O (Testosterone); MLT3645I99 (bisphenol A)
[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:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191934


  2 / 3989 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28471399
[Au] Autor:Wang CC; Wang YX; Yu NQ; Hu D; Wang XY; Chen XG; Liao YW; Yao J; Wang H; He L; Wu L
[Ad] Endereço:School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. w940984614@hotmail.com.
[Ti] Título:Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2.
[So] Source:Molecules;22(5), 2017 May 04.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic therapy (PDT) is a therapeutic approach used against malignant cells. To assess the synergistic effect of BGP extract on protoporphyrin IX (PpIX)-mediated photocytotoxicity, MTT assays were performed using A431 and HeLa cells. TUNEL assay and Annexin V-FITC/PI staining were performed to confirm the induction of apoptosis. Western blotting analysis was performed to examine the pro-apoptotic proteins, anti-apoptotic proteins and inflammation related proteins in A431 cells. Intracellular accumulation of PpIX was examined by flow cytometry. The synergistic effect of BGP extract in PpIX-PDT was also evaluated with a xenograft model. Our findings reveal that BGP extract increased PpIX-mediated photocytotoxicity in A431 and HeLa cells. PpIX-PDT with BGP extract treatment resulted in a decrease in Bcl-xL and an increase in NOXA, Bax and caspase-3 cleavage. The protein expression levels of p-IKKα/ß, NF-κB and COX-2 were upregulated by PpIX-PDT but significantly attenuated when in combination with BGP extract. BGP extract was also found to significantly enhance the intracellular accumulation of PpIX in A431 cells. BGP extract increased PpIX-mediated photocytotoxicity in a xenograft model as well. Our findings provide evidence for a synergistic effect of BGP extract in PpIX-PDT both in vitro and in vivo.
[Mh] Termos MeSH primário: Ciclo-Oxigenase 2/metabolismo
NF-kappa B/metabolismo
Fotoquimioterapia
Própole
Protoporfirinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Brasil
Linhagem Celular Tumoral
Cromatografia Líquida de Alta Pressão
Sinergismo Farmacológico
Citometria de Fluxo
Xenoenxertos
Seres Humanos
Camundongos Endogâmicos BALB C
Camundongos Nus
Protoporfirinas/farmacocinética
Espectrofotometria Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NF-kappa B); 0 (Protoporphyrins); 9009-62-5 (Propolis); C2K325S808 (protoporphyrin IX); EC 1.14.99.1 (Cyclooxygenase 2)
[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:170505
[St] Status:MEDLINE


  3 / 3989 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


  4 / 3989 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28467300
[Au] Autor:Ku AT; Shaver TM; Rao AS; Howard JM; Rodriguez CN; Miao Q; Garcia G; Le D; Yang D; Borowiak M; Cohen DN; Chitsazzadeh V; Diwan AH; Tsai KY; Nguyen H
[Ad] Endereço:Stem Cell and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.
[Ti] Título:TCF7L1 promotes skin tumorigenesis independently of ß-catenin through induction of LCN2.
[So] Source:Elife;6, 2017 05 03.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The transcription factor is an embryonic stem cell signature gene that is upregulated in multiple aggressive cancer types, but its role in skin tumorigenesis has not yet been defined. Here we document TCF7L1 upregulation in skin squamous cell carcinoma (SCC) and demonstrate that TCF7L1 overexpression increases tumor incidence, tumor multiplicity, and malignant progression in the chemically induced mouse model of skin SCC. Additionally, we show that downregulation of TCF7L1 and its paralogue TCF7L2 reduces tumor growth in a xenograft model of human skin SCC. Using separation-of-function mutants, we show that TCF7L1 promotes tumor growth, enhances cell migration, and overrides oncogenic RAS-induced senescence independently of its interaction with ß-catenin. Through transcriptome profiling and combined gain- and loss-of-function studies, we identified LCN2 as a major downstream effector of TCF7L1 that drives tumor growth. Our findings establish a tumor-promoting role for TCF7L1 in skin and elucidate the mechanisms underlying its tumorigenic capacity.
[Mh] Termos MeSH primário: Carcinogênese
Carcinoma de Células Escamosas/fisiopatologia
Lipocalina-2/metabolismo
Neoplasias Cutâneas/fisiopatologia
Proteína 1 Semelhante ao Fator 7 de Transcrição/metabolismo
beta Catenina/metabolismo
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Perfilação da Expressão Gênica
Xenoenxertos
Seres Humanos
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CTNNB1 protein, human); 0 (LCN2 protein, human); 0 (Lipocalin-2); 0 (TCF7L1 protein, human); 0 (Transcription Factor 7-Like 1 Protein); 0 (beta Catenin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


  5 / 3989 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460469
[Au] Autor:Lam CS; Ng L; Chow AK; Wan TM; Yau S; Cheng NS; Wong SK; Man JH; Lo OS; Foo DC; Poon JT; Pang RW; Law WL
[Ad] Endereço:Division of Colorectal Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
[Ti] Título:Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer.
[So] Source:Oncotarget;8(16):26858-26870, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Colorectal cancer is the third most common cancer in the world and liver is the most frequent site of distant metastasis with poor prognosis. The aim of this study is to investigate microRNAs leading to liver metastasis. We applied microarray analysis and quantitative PCR to identify and validate dysregulated miRNAs in liver metastases when compared to primary CRCs. Functional significance and the underlying molecular mechanism of selected miRNA was demonstrated by a series of in vitro and in vivo assays. Our microarray analysis and subsequent quantitative PCR validation revealed that miR-885-5p was strongly up-regulated in liver metastases and in CRC cell-lines derived from distant metastases. Overexpression of miR-885-5p significantly induced cell migration, cell invasion, formation of stress fibre in vitro and development of liver and lung metastases in vivo. MiR-885-5p induced metastatic potential of CRC by repressing cytoplasmic polyadenylation element binding protein 2 transcription through directly binding to two binding sites on its 3' untranslated region, and consequently led to up-regulation of TWIST1 and hence epithelial-mesenchymal transition. Our findings demonstrated the overexpression of miR-885-5p in liver metastasis and its roles in inducing CRC metastasis, potentiating development of miR-885-5p inhibitor to treat advanced CRC in the future.
[Mh] Termos MeSH primário: Neoplasias Colorretais/genética
Neoplasias Colorretais/patologia
Regulação Neoplásica da Expressão Gênica
MicroRNAs/genética
Interferência de RNA
Proteínas de Ligação a RNA/genética
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Animais
Linhagem Celular Tumoral
Movimento Celular/genética
Citoesqueleto/metabolismo
Modelos Animais de Doenças
Transição Epitelial-Mesenquimal/genética
Xenoenxertos
Seres Humanos
Neoplasias Hepáticas/secundário
Masculino
Camundongos
Metástase Neoplásica
Estadiamento de Neoplasias
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (CPEB2 protein, human); 0 (MIRN885 microRNA, human); 0 (MicroRNAs); 0 (RNA-Binding Proteins)
[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:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15844


  6 / 3989 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460465
[Au] Autor:McCormick A; Earp E; Elliot K; Cuthbert G; O'Donnell R; Wilson BT; Sutton R; Leeson C; Thomas HD; Blair H; Fordham S; Lunec J; Allan J; Edmondson RJ
[Ad] Endereço:Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
[Ti] Título:Functional characterisation of a novel ovarian cancer cell line, NUOC-1.
[So] Source:Oncotarget;8(16):26832-26844, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cell lines provide a powerful model to study cancer and here we describe a new spontaneously immortalised epithelial ovarian cancer cell line (NUOC-1) derived from the ascites collected at a time of primary debulking surgery for a mixed endometrioid / clear cell / High Grade Serous (HGS) histology. RESULTS: This spontaneously immortalised cell line was found to maintain morphology and epithelial markers throughout long-term culture. NUOC-1 cells grow as an adherent monolayer with a doubling time of 58 hours. The cells are TP53 wildtype, positive for PTEN, HER2 and HER3 expression but negative for oestrogen, progesterone and androgen receptor expression. NUOC-1 cells are competent in homologous recombination and non-homologous end joining, but base excision repair defective. Karyotype analysis demonstrated a complex tetraploid karyotype. SNP array analysis of parent and derived subpopulations (NUOC-1-A1 and NUOC-1-A2) cells demonstrated heterogeneous cell populations with numerous copy number alterations and a pro-amplification phenotype. The characteristics of this new cell line lends it to be an excellent model for investigation of a number of the identified targets. MATERIALS AND METHODS: The cell line has been characterised for growth, drug sensitivity, expression of common ovarian markers and mutations, clonogenic potential and ability to form xenografts in SCID mice. Copy number changes and clonal evolution were assessed by SNP arrays.
[Mh] Termos MeSH primário: Linhagem Celular Tumoral
Neoplasias Ovarianas/genética
Neoplasias Ovarianas/patologia
[Mh] Termos MeSH secundário: Animais
Bandeamento Cromossômico
Evolução Clonal/genética
Variações do Número de Cópias de DNA
Reparo do DNA
Modelos Animais de Doenças
Feminino
Amplificação de Genes
Genes myc
Xenoenxertos
Seres Humanos
Hibridização in Situ Fluorescente
Camundongos
Camundongos SCID
Meia-Idade
Mutação
Gradação de Tumores
Células-Tronco Neoplásicas/metabolismo
Proteína Supressora de Tumor p53/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tumor Suppressor Protein p53)
[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:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15821


  7 / 3989 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460460
[Au] Autor:Valdés-Mora F; Locke WJ; Bandrés E; Gallego-Ortega D; Cejas P; García-Cabezas MA; Colino-Sanguino Y; Feliú J; Del Pulgar TG; Lacal JC
[Ad] Endereço:Histone Variants Group, Epigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
[Ti] Título:Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.
[So] Source:Oncotarget;8(16):26755-26770, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied. We demonstrate that three CDC42-regulated genes offered a better prognostic value when combined with CDC42 compared to CDC42 alone. In particular, the concordant overexpression of CDC42 and silencing of the putative tumor suppressor gene CACNA2D2 dramatically improved the prognostic value. The CACNA2D2/CDC42 prognostic classifier was further validated in a third CRC cohort as well as in vitro and in vivo CRC models. Altogether, we show that CDC42 has an active oncogenic role in CRC via the transcriptional regulation of multiple cancer-related pathways and that CDC42-mediated silencing of CACNA2D2 is clinically relevant. Our results further support the use of CDC42 specific inhibitors for the treatment of the most aggressive types of CRC.
[Mh] Termos MeSH primário: Neoplasias Colorretais/genética
Neoplasias Colorretais/metabolismo
Regulação Neoplásica da Expressão Gênica
Transcriptoma
Proteína cdc42 de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Canais de Cálcio/genética
Linhagem Celular Tumoral
Movimento Celular
Proliferação Celular
Neoplasias Colorretais/diagnóstico
Neoplasias Colorretais/mortalidade
Modelos Animais de Doenças
Feminino
Perfilação da Expressão Gênica
Redes Reguladoras de Genes
Genes Supressores de Tumor
Xenoenxertos
Seres Humanos
Camundongos
Gradação de Tumores
Metástase Neoplásica
Estadiamento de Neoplasias
Prognóstico
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CACNA2D2 protein, human); 0 (Calcium Channels); EC 3.6.5.2 (cdc42 GTP-Binding Protein)
[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:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15815


  8 / 3989 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460458
[Au] Autor:Fang Y; Wang J; Wang G; Zhou C; Wang P; Zhao S; Zhao S; Huang S; Su W; Jiang P; Chang A; Xiang R; Sun P
[Ad] Endereço:Department of Immunology, School of Medicine, Nankai University, Tianjin, China.
[Ti] Título:Inactivation of p38 MAPK contributes to stem cell-like properties of non-small cell lung cancer.
[So] Source:Oncotarget;8(16):26702-26717, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer stem cells (CSCs) are recognized as the major source for cancer initiation and recurrence. Yet, the mechanism by which the cancer stem cell properties are acquired and maintained in a cancer cell population is not well understood. In the current study, we observed that the level of active p38 MAPK is downregulated, while the level of the stemness marker SOX2 is upregulated in lung cancer tissues as compared to normal tissues. We further demonstrated that inactivation of p38 is a potential mechanism contributing to acquisition and maintenance of cancer stem cell properties in non-small cell lung cancer (NSCLC) cells. p38, in particular the p38γ and p38δ isoforms, suppresses the cancer stem cell properties and tumor initiating ability of NSCLC cells by promoting the ubiquitylation and degradation of stemness proteins such as SOX2, Oct4, Nanog, Klf4 and c-Myc, through MK2-mediated phosphorylation of Hsp27 that is an essential component of the proteasomal degradation machinery. In contrast, inactivation of p38 in lung cancer cells leads to upregulation of the stemness proteins, thus promoting the cancer stem cell properties of these cells. These findings have demonstrated a novel mechanism by which cancer stem cell properties are acquired and maintained in a cancer cell population, and have revealed a new function of the p38 pathway in suppressing cancer development. These studies have also identified a new pathway that can potentially serve as a target for cancer therapies aimed at eliminating CSCs.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/metabolismo
Neoplasias Pulmonares/metabolismo
Células-Tronco Neoplásicas/metabolismo
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Mh] Termos MeSH secundário: Animais
Biomarcadores
Carcinoma Pulmonar de Células não Pequenas/genética
Linhagem Celular Tumoral
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/metabolismo
Modelos Animais de Doenças
Ativação Enzimática
Regulação Neoplásica da Expressão Gênica
Xenoenxertos
Seres Humanos
Neoplasias Pulmonares/genética
Masculino
Camundongos
Fosforilação
Complexo de Endopeptidases do Proteassoma/metabolismo
Estabilidade Proteica
Proteólise
Fatores de Transcrição SOXB1/genética
Fatores de Transcrição SOXB1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (SOX2 protein, human); 0 (SOXB1 Transcription Factors); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[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:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15804


  9 / 3989 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460457
[Au] Autor:Trivedi T; Zheng Y; Fournier PGJ; Murthy S; John S; Schillo S; Dunstan CR; Mohammad KS; Zhou H; Seibel MJ; Guise TA
[Ad] Endereço:Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia.
[Ti] Título:The vitamin D receptor is involved in the regulation of human breast cancer cell growth via a ligand-independent function in cytoplasm.
[So] Source:Oncotarget;8(16):26687-26701, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vitamin D has pleiotropic effects on multiple tissues, including malignant tumors. Vitamin D inhibits breast cancer growth through activation of the vitamin D receptor (VDR) and via classical nuclear signaling pathways. Here, we demonstrate that the VDR can also function in the absence of its ligand to control behaviour of human breast cancer cells both outside and within the bone microenvironment. Stable shRNA expression was used to knock down VDR expression in MCF-7 cells, generating two VDR knockdown clonal lines. In ligand-free culture, knockdown of VDR in MCF-7 cells significantly reduced proliferation and increased apoptosis, suggesting that the VDR plays a ligand-independent role in cancer cell growth. Implantation of these VDR knockdown cells into the mammary fat pad of nude mice resulted in reduced tumor growth in vivo compared with controls. In the intra-tibial xenograft model, VDR knockdown greatly reduced the ability of the cells to form tumors in the bone microenvironment. The in vitro growth of VDR knockdown cells was rescued by the expression of a mutant form of VDR which is unable to translocate to the nucleus and hence accumulates in the cytoplasm. Thus, our data indicate that in the absence of ligand, the VDR promotes breast cancer growth both in vitro and in vivo and that cytoplasmic accumulation of VDR is sufficient to produce this effect in vitro. This new mechanism of VDR action in breast cancer cells contrasts the known anti-proliferative nuclear actions of the VDR-vitamin D ligand complex.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Receptores de Calcitriol/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose/genética
Neoplasias Ósseas/genética
Neoplasias Ósseas/metabolismo
Neoplasias Ósseas/patologia
Neoplasias da Mama/genética
Linhagem Celular Tumoral
Proliferação Celular
Citoplasma/metabolismo
Modelos Animais de Doenças
Feminino
Expressão Gênica
Técnicas de Silenciamento de Genes
Xenoenxertos
Seres Humanos
Ligantes
Camundongos
Mutação
Osteosclerose/genética
Osteosclerose/metabolismo
Transporte Proteico
Receptores de Calcitriol/genética
Vitamina D/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Receptors, Calcitriol); 0 (VDR protein, human); 1406-16-2 (Vitamin D)
[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:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15803


  10 / 3989 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460453
[Au] Autor:Yu T; Wu Y; Hu Q; Zhang J; Nie E; Wu W; Wang X; Wang Y; Liu N
[Ad] Endereço:Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
[Ti] Título:CBX7 is a glioma prognostic marker and induces G1/S arrest via the silencing of CCNE1.
[So] Source:Oncotarget;8(16):26637-26647, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromobox homolog 7 (CBX7) cooperates with other polycomb group (PcG) proteins to maintain target genes in a silenced state. However, the precise role of CBX7 in tumor progression is still controversial. We found that the expression of CBX7 in four public databases was significantly lower in high grade glioma (HGG). The reduced expression of CBX7 correlated with poor outcome in HGG patients. Both KEGG and GO analyses indicated that genes that were negatively correlated to CBX7 were strongly associated with the cell cycle pathway. We observed that decreased CBX7 protein levels enhanced glioma cells proliferation, migration and invasion. Then, we verified that CBX7 overexpression arrested cells in the G0/G1 phase. Moreover, we demonstrated that the underlying mechanism involved in CBX7 induced repression of CCNE1 promoter requiring the recruitment of histone deacetylase 2 (HADC2). Finally, in vivo bioluminescence imaging and survival times of nude mice revealed that CBX7 behaved as a tumor suppressor in gliomas. In summary, our results validate the assumption that CBX7 is a tumor suppressor of gliomas. Moreover, CBX7 is a potential and novel prognostic biomarker in glioma patients. We also clarified that CBX7 silences CCNE1 via the combination of CCNE1 promoter and the recruitment of HDAC2.
[Mh] Termos MeSH primário: Ciclina E/genética
Pontos de Checagem da Fase G1 do Ciclo Celular/genética
Inativação Gênica
Glioma/genética
Glioma/mortalidade
Proteínas Oncogênicas/genética
Complexo Repressor Polycomb 1/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Modelos Animais de Doenças
Feminino
Regulação Neoplásica da Expressão Gênica
Glioma/patologia
Xenoenxertos
Histona Desacetilase 2/metabolismo
Seres Humanos
Masculino
Camundongos
Gradação de Tumores
Complexo Repressor Polycomb 1/metabolismo
Prognóstico
Regiões Promotoras Genéticas
Ligação Proteica
RNA Interferente Pequeno/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CBX7 protein, human); 0 (CCNE1 protein, human); 0 (Cyclin E); 0 (Oncogene Proteins); 0 (RNA, Small Interfering); EC 2.3.2.27 (Polycomb Repressive Complex 1); EC 3.5.1.98 (Histone Deacetylase 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:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15789



página 1 de 399 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