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[PMID]:28747142
[Au] Autor:Zhao Y; Stepto H; Schneider CK
[Ad] Endereço:1 Division of Advanced Therapies, National Institute for Biological Standards and Control (NIBSC) , Medicines and Health Products Regulatory Agency (MHRA), South Mimms, United Kingdom .
[Ti] Título:Development of the First World Health Organization Lentiviral Vector Standard: Toward the Production Control and Standardization of Lentivirus-Based Gene Therapy Products.
[So] Source:Hum Gene Ther Methods;28(4):205-214, 2017 08.
[Is] ISSN:1946-6544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gene therapy is a rapidly evolving field. So far, there have been >2,400 gene therapy products in clinical trials and four products on the market. A prerequisite for producing gene therapy products is ensuring their quality and safety. This requires appropriately controlled and standardized production and testing procedures that result in consistent safety and efficacy. Assuring the quality and safety of lentivirus-based gene therapy products in particular presents a great challenge because they are cell-based multigene products that include viral and therapeutic proteins as well as modified cells. In addition to the continuous refinement of a product, changes in production sites and manufacturing processes have become more and more common, posing challenges to developers regarding reproducibility and comparability of results. This paper discusses the concept of developing a first World Health Organization International Standard, suitable for the standardization of assays and enabling comparison of cross-trial and cross-manufacturing results for this important vector platform. The standard will be expected to optimize the development of gene therapy medicinal products, which is especially important, given the usually orphan nature of the diseases to be treated, naturally hampering reproducibility and comparability of results.
[Mh] Termos MeSH primário: Terapia Genética/normas
Vetores Genéticos/normas
Lentivirus/genética
Organização Mundial da Saúde
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Terapia Genética/métodos
Vetores Genéticos/genética
Células HEK293
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180310
[Lr] Data última revisão:
180310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1089/hgtb.2017.078


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[PMID]:29351307
[Au] Autor:Merentie M; Rissanen R; Lottonen-Raikaslehto L; Huusko J; Gurzeler E; Turunen MP; Holappa L; Mäkinen P; Ylä-Herttuala S
[Ad] Endereço:A. I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
[Ti] Título:Doxycycline modulates VEGF-A expression: Failure of doxycycline-inducible lentivirus shRNA vector to knockdown VEGF-A expression in transgenic mice.
[So] Source:PLoS One;13(1):e0190981, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vascular endothelial growth factor-A (VEGF-A) is the master regulator of angiogenesis, vascular permeability and growth. However, its role in mature blood vessels is still not well understood. To better understand the role of VEGF-A in the adult vasculature, we generated a VEGF-A knockdown mouse model carrying a doxycycline (dox)-regulatable short hairpin RNA (shRNA) transgene, which silences VEGF-A. The aim was to find the critical level of VEGF-A reduction for vascular well-being in vivo. In vitro, the dox-inducible lentiviral shRNA vector decreased VEGF-A expression efficiently and dose-dependently in mouse endothelial cells and cardiomyocytes. In the generated transgenic mice plasma VEGF-A levels decreased shortly after the dox treatment but returned back to normal after two weeks. VEGF-A expression decreased shortly after the dox treatment only in some tissues. Surprisingly, increasing the dox exposure time and dose led to elevated VEGF-A expression in some tissues of both wildtype and knockdown mice, suggesting that dox itself has an effect on VEGF-A expression. When the effect of dox on VEGF-A levels was further tested in naïve/non-transduced cells, the dox administration led to a decreased VEGF-A expression in endothelial cells but to an increased expression in cardiomyocytes. In conclusion, the VEGF-A knockdown was achieved in a dox-regulatable fashion with a VEGF-A shRNA vector in vitro, but not in the knockdown mouse model in vivo. Dox itself was found to regulate VEGF-A expression explaining the unexpected results in mice. The effect of dox on VEGF-A levels might at least partly explain its previously reported beneficial effects on myocardial and brain ischemia. Also, this effect on VEGF-A should be taken into account in all studies using dox-regulated vectors.
[Mh] Termos MeSH primário: Doxiciclina/farmacologia
Regulação da Expressão Gênica/efeitos dos fármacos
Técnicas de Silenciamento de Genes
Lentivirus/genética
RNA Interferente Pequeno/genética
Fator A de Crescimento do Endotélio Vascular/genética
[Mh] Termos MeSH secundário: Animais
Vetores Genéticos
Camundongos
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Small Interfering); 0 (Vascular Endothelial Growth Factor A); N12000U13O (Doxycycline)
[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:180120
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190981


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[PMID]:28456689
[Au] Autor:Mandic A; Strebinger D; Regali C; Phillips NE; Suter DM
[Ad] Endereço:The Institute of Bioengineering (IBI), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.
[Ti] Título:A novel method for quantitative measurements of gene expression in single living cells.
[So] Source:Methods;120:65-75, 2017 May 01.
[Is] ISSN:1095-9130
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gene expression is at the heart of virtually any biological process, and its deregulation is at the source of numerous pathological conditions. While impressive progress has been made in genome-wide measurements of mRNA and protein expression levels, it is still challenging to obtain highly quantitative measurements in single living cells. Here we describe a novel approach based on internal tagging of endogenous proteins with a reporter allowing luminescence and fluorescence time-lapse microscopy. Using luminescence microscopy, fluctuations of protein expression levels can be monitored in single living cells with high sensitivity and temporal resolution over extended time periods. The integrated protein decay reporter allows measuring protein degradation rates in the absence of protein synthesis inhibitors, and in combination with absolute protein levels allows determining absolute amounts of proteins synthesized over the cell cycle. Finally, the internal tag can be excised by inducible expression of Cre recombinase, which enables to estimate endogenous mRNA half-lives. Our method thus opens new avenues in quantitative analysis of gene expression in single living cells.
[Mh] Termos MeSH primário: Imagem Molecular/métodos
Proteínas/genética
Análise de Célula Única/métodos
Coloração e Rotulagem/métodos
Transcrição Genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Genes Reporter/genética
Vetores Genéticos/genética
Meia-Vida
Integrases/genética
Lentivirus/genética
Luminescência
Camundongos
Microscopia de Fluorescência/métodos
Imagem Molecular/instrumentação
Proteínas/química
Proteínas/metabolismo
Proteólise
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Análise de Célula Única/instrumentação
Coloração e Rotulagem/instrumentação
Imagem com Lapso de Tempo/instrumentação
Imagem com Lapso de Tempo/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteins); 0 (RNA, Messenger); EC 2.7.7.- (Cre recombinase); EC 2.7.7.- (Integrases)
[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:170501
[St] Status:MEDLINE


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[PMID]:29178837
[Au] Autor:Spinozzi G; Calabria A; Brasca S; Beretta S; Merelli I; Milanesi L; Montini E
[Ad] Endereço:San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS, San Raffaele Scientific Institute, Via Olgettina, 58, 20132, Milan, Italy.
[Ti] Título:VISPA2: a scalable pipeline for high-throughput identification and annotation of vector integration sites.
[So] Source:BMC Bioinformatics;18(1):520, 2017 Nov 25.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Bioinformatics tools designed to identify lentiviral or retroviral vector insertion sites in the genome of host cells are used to address the safety and long-term efficacy of hematopoietic stem cell gene therapy applications and to study the clonal dynamics of hematopoietic reconstitution. The increasing number of gene therapy clinical trials combined with the increasing amount of Next Generation Sequencing data, aimed at identifying integration sites, require both highly accurate and efficient computational software able to correctly process "big data" in a reasonable computational time. RESULTS: Here we present VISPA2 (Vector Integration Site Parallel Analysis, version 2), the latest optimized computational pipeline for integration site identification and analysis with the following features: (1) the sequence analysis for the integration site processing is fully compliant with paired-end reads and includes a sequence quality filter before and after the alignment on the target genome; (2) an heuristic algorithm to reduce false positive integration sites at nucleotide level to reduce the impact of Polymerase Chain Reaction or trimming/alignment artifacts; (3) a classification and annotation module for integration sites; (4) a user friendly web interface as researcher front-end to perform integration site analyses without computational skills; (5) the time speedup of all steps through parallelization (Hadoop free). CONCLUSIONS: We tested VISPA2 performances using simulated and real datasets of lentiviral vector integration sites, previously obtained from patients enrolled in a hematopoietic stem cell gene therapy clinical trial and compared the results with other preexisting tools for integration site analysis. On the computational side, VISPA2 showed a > 6-fold speedup and improved precision and recall metrics (1 and 0.97 respectively) compared to previously developed computational pipelines. These performances indicate that VISPA2 is a fast, reliable and user-friendly tool for integration site analysis, which allows gene therapy integration data to be handled in a cost and time effective fashion. Moreover, the web access of VISPA2 ( http://openserver.itb.cnr.it/vispa/ ) ensures accessibility and ease of usage to researches of a complex analytical tool. We released the source code of VISPA2 in a public repository ( https://bitbucket.org/andreacalabria/vispa2 ).
[Mh] Termos MeSH primário: Interface Usuário-Computador
[Mh] Termos MeSH secundário: Algoritmos
Terapia Genética
Vetores Genéticos/genética
Vetores Genéticos/metabolismo
Transplante de Células-Tronco Hematopoéticas
Células-Tronco Hematopoéticas/citologia
Células-Tronco Hematopoéticas/metabolismo
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Lentivirus/genética
Lentivirus/fisiologia
Alinhamento de Sequência
Internalização do Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[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:171128
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1937-9


  5 / 6577 MEDLINE  
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[PMID]:29385199
[Au] Autor:Schaefer C; Mallela N; Seggewiß J; Lechtape B; Omran H; Dirksen U; Korsching E; Potratz J
[Ad] Endereço:Pediatric Hematology and Oncology, University Hospital Münster, Münster, Germany.
[Ti] Título:Target discovery screens using pooled shRNA libraries and next-generation sequencing: A model workflow and analytical algorithm.
[So] Source:PLoS One;13(1):e0191570, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the search for novel therapeutic targets, RNA interference screening has become a valuable tool. High-throughput technologies are now broadly accessible but their assay development from baseline remains resource-intensive and challenging. Focusing on this assay development process, we here describe a target discovery screen using pooled shRNA libraries and next-generation sequencing (NGS) deconvolution in a cell line model of Ewing sarcoma. In a strategy designed for comparative and synthetic lethal studies, we screened for targets specific to the A673 Ewing sarcoma cell line. Methods, results and pitfalls are described for the entire multi-step screening procedure, from lentiviral shRNA delivery to bioinformatics analysis, illustrating a complete model workflow. We demonstrate that successful studies are feasible from the first assay performance and independent of specialized screening units. Furthermore, we show that a resource-saving screen depth of 100-fold average shRNA representation can suffice to generate reproducible target hits despite heterogeneity in the derived datasets. Because statistical analysis methods are debatable for such datasets, we created ProFED, an analysis package designed to facilitate descriptive data analysis and hit calling using an aim-oriented profile filtering approach. In its versatile design, this open-source online tool provides fast and easy analysis of shRNA and other count-based datasets to complement other analytical algorithms.
[Mh] Termos MeSH primário: Descoberta de Drogas/métodos
Avaliação Pré-Clínica de Medicamentos/métodos
Biblioteca Gênica
RNA Interferente Pequeno/genética
[Mh] Termos MeSH secundário: Algoritmos
Linhagem Celular Tumoral
Biologia Computacional
Células HEK293
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Lentivirus/genética
Interferência de RNA
Sarcoma de Ewing/tratamento farmacológico
Sarcoma de Ewing/genética
Análise de Sequência de RNA
Fluxo de Trabalho
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Small Interfering)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191570


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[PMID]:29300759
[Au] Autor:Antoneli F; Passos FM; Lopes LR; Briones MRS
[Ad] Endereço:Laboratório de Genômica Evolutiva e Biocomplexidade, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo, UNIFESP, São Paulo, SP, Brazil.
[Ti] Título:A Kolmogorov-Smirnov test for the molecular clock based on Bayesian ensembles of phylogenies.
[So] Source:PLoS One;13(1):e0190826, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Divergence date estimates are central to understand evolutionary processes and depend, in the case of molecular phylogenies, on tests of molecular clocks. Here we propose two non-parametric tests of strict and relaxed molecular clocks built upon a framework that uses the empirical cumulative distribution (ECD) of branch lengths obtained from an ensemble of Bayesian trees and well known non-parametric (one-sample and two-sample) Kolmogorov-Smirnov (KS) goodness-of-fit test. In the strict clock case, the method consists in using the one-sample Kolmogorov-Smirnov (KS) test to directly test if the phylogeny is clock-like, in other words, if it follows a Poisson law. The ECD is computed from the discretized branch lengths and the parameter λ of the expected Poisson distribution is calculated as the average branch length over the ensemble of trees. To compensate for the auto-correlation in the ensemble of trees and pseudo-replication we take advantage of thinning and effective sample size, two features provided by Bayesian inference MCMC samplers. Finally, it is observed that tree topologies with very long or very short branches lead to Poisson mixtures and in this case we propose the use of the two-sample KS test with samples from two continuous branch length distributions, one obtained from an ensemble of clock-constrained trees and the other from an ensemble of unconstrained trees. Moreover, in this second form the test can also be applied to test for relaxed clock models. The use of a statistically equivalent ensemble of phylogenies to obtain the branch lengths ECD, instead of one consensus tree, yields considerable reduction of the effects of small sample size and provides a gain of power.
[Mh] Termos MeSH primário: Evolução Molecular
Modelos Genéticos
Filogenia
[Mh] Termos MeSH secundário: Animais
Ascomicetos/classificação
Ascomicetos/genética
Teorema de Bayes
Simulação por Computador
Ciclo-Oxigenase 1/genética
DNA/genética
Bases de Dados Genéticas
Produtos do Gene env/genética
Seres Humanos
Lentivirus/classificação
Lentivirus/genética
Distribuição de Poisson
Primatas/classificação
Primatas/genética
Proteínas/genética
Estatísticas não Paramétricas
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Gene Products, env); 0 (Proteins); 9007-49-2 (DNA); EC 1.14.99.1 (Cyclooxygenase 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180105
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190826


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[PMID]:28456379
[Au] Autor:Rivière I; Sadelain M
[Ad] Endereço:Center for Cell Engineering, Molecular Pharmacology and Immunology Programs, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
[Ti] Título:Chimeric Antigen Receptors: A Cell and Gene Therapy Perspective.
[So] Source:Mol Ther;25(5):1117-1124, 2017 May 03.
[Is] ISSN:1525-0024
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chimeric antigen receptors (CARs) are synthetic receptors that reprogram T lymphocytes to target chosen antigens. The targeting of CD19, a cell surface molecule expressed in the vast majority of leukemias and lymphomas, has been successfully translated in the clinic, earning CAR therapy a special distinction in the selection of "cancer immunotherapy" by Science as the breakthrough of the year in 2013. CD19 CAR therapy is predicated on advances in genetic engineering, T cell biology, tumor immunology, synthetic biology, target identification, cell manufacturing sciences, and regulatory compliance-the central tenets of CAR therapy. Here, we review two of these foundations: the genetic engineering approaches and cell types to engineer.
[Mh] Termos MeSH primário: Antígenos CD19/genética
Terapia Baseada em Transplante de Células e Tecidos/métodos
Leucemia/terapia
Linfoma/terapia
Proteínas Mutantes Quiméricas/genética
Receptores de Antígenos de Linfócitos T/genética
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Antígenos CD19/imunologia
Engenharia Celular/métodos
Expressão Gênica
Vetores Genéticos/química
Vetores Genéticos/imunologia
Seres Humanos
Imunoterapia/métodos
Lentivirus/genética
Lentivirus/imunologia
Leucemia/genética
Leucemia/imunologia
Leucemia/patologia
Linfoma/genética
Linfoma/imunologia
Linfoma/patologia
Proteínas Mutantes Quiméricas/imunologia
Engenharia de Proteínas/métodos
Receptores de Antígenos de Linfócitos T/imunologia
Retroviridae/genética
Retroviridae/imunologia
Linfócitos T/classificação
Linfócitos T/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, CD19); 0 (CD19 molecule, human); 0 (Mutant Chimeric Proteins); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:29433476
[Au] Autor:Wen L; Wen YC; Ke GJ; Sun SQ; Dong K; Wang L; Liao RF
[Ad] Endereço:Department of Ophthalmology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, 230022, China.
[Ti] Título:TRPV4 regulates migration and tube formation of human retinal capillary endothelial cells.
[So] Source:BMC Ophthalmol;18(1):38, 2018 Feb 12.
[Is] ISSN:1471-2415
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ca entry plays an important role in modulating endothelial cell migration and tube formation. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a Ca -permeable channel that is widely expressed in endothelial cells. It has been reported that TRPV4 is expressed in HRCECs and regulates Ca entry. However, the function of TRPV4 in human retinal capillary endothelial cells (HRCECs) remains unknown. METHODS: In this study we used western blot and immunostaining assay to verify TRPV4 expression in HRCECs. And then we pretreated HRCECs with HC067047 and transfected with specific shRNA of TRPV4. The functional presence of TrpV4 was determined by using fluorescence, migration and tube formation assay in TrpV4 knockdown cells or control cells. RESULTS: Using western blot and immunostaining, we confirmed TRPV4 expression in HRCECs. Moreover, inhibition of TRPV4 using the specific inhibitor HC067047 and the knockdown of TRPV4 with shRNA significantly suppressed tube formation and migration by HRCECs. CONCLUSIONS: TRPV4 is essential for HRCEC migration and tube formation, and maybe a potential therapeutic target for retinal vascular diseases.
[Mh] Termos MeSH primário: Movimento Celular/fisiologia
Células Endoteliais/citologia
Células Endoteliais/metabolismo
Vasos Retinianos/fisiologia
Canais de Cátion TRPV/fisiologia
[Mh] Termos MeSH secundário: Western Blotting
Cálcio/metabolismo
Agonistas dos Canais de Cálcio/farmacologia
Bloqueadores dos Canais de Cálcio/farmacologia
Contagem de Células
Células Endoteliais/efeitos dos fármacos
Técnica Indireta de Fluorescência para Anticorpo
Células HEK293
Seres Humanos
Lentivirus/genética
RNA Interferente Pequeno/genética
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channel Agonists); 0 (Calcium Channel Blockers); 0 (RNA, Small Interfering); 0 (TRPV Cation Channels); 0 (TRPV4 protein, human); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180218
[Lr] Data última revisão:
180218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180214
[St] Status:MEDLINE
[do] DOI:10.1186/s12886-018-0697-2


  9 / 6577 MEDLINE  
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[PMID]:29300772
[Au] Autor:Yang F; Yu N; Wang H; Zhang C; Zhang Z; Li Y; Li D; Yan L; Liu H; Xu Z
[Ad] Endereço:Department of Urology, Qilu Hospital of Shandong University, Jinan, P.R. China.
[Ti] Título:Downregulated expression of hepatoma-derived growth factor inhibits migration and invasion of prostate cancer cells by suppressing epithelial-mesenchymal transition and MMP2, MMP9.
[So] Source:PLoS One;13(1):e0190725, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatoma-derived growth factor (HDGF) is commonly over-expressed and plays critical roles in the development and progression in a variety of cancers. It has previously been shown that HDGF is overregulated in prostate cancer cells compared to normal prostate cells, which is correlated with cellular migration and invasion of prostate cancer. Here, the molecular mechanisms of HDGF in prostate cancer is investigated. It is shown that HDGF knockdown reduces prostate cancer cellular migration and invasion in both androgen-sensitive LNCaP cells and androgen-insensitive DU145 and PC3 cells. Furthermore, Western blot analysis reveals that HDGF knockdown inhibits epithelial-mesenchymal transition (EMT) of prostate cancer cells by upregulation of protein E-cadherin and downregulation of proteins N-cadherin, Vimentin, Snail and Slug. In addition, mechanistic studies reveal that proteins MMP2 and MMP9 are down-regulated. In conclusion, our data suggested that HDGF knockdown inhibits cellular migration and invasion in vitro of prostate cancer via modulating epithelial-mesenchymal transition (EMT) signaling pathway, as well as MMP2 and MMP9 signaling pathway. These results supported that HDGF is a relevant protein in the progression of prostate cancer and may serve as a potentially therapeutic target for prostate cancer as well as its downstream targets.
[Mh] Termos MeSH primário: Movimento Celular/fisiologia
Transição Epitelial-Mesenquimal/fisiologia
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Metaloproteinases da Matriz Secretadas/metabolismo
Invasividade Neoplásica/fisiopatologia
Neoplasias da Próstata/metabolismo
[Mh] Termos MeSH secundário: Antígenos CD/metabolismo
Western Blotting
Caderinas/metabolismo
Linhagem Celular Tumoral
Regulação para Baixo
Técnicas de Silenciamento de Genes
Vetores Genéticos
Seres Humanos
Peptídeos e Proteínas de Sinalização Intercelular/genética
Lentivirus/genética
Masculino
RNA Mensageiro/metabolismo
RNA Interferente Pequeno
Reação em Cadeia da Polimerase em Tempo Real
Vimentina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CDH1 protein, human); 0 (CDH2 protein, human); 0 (Cadherins); 0 (Intercellular Signaling Peptides and Proteins); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 0 (Vimentin); 0 (hepatoma-derived growth factor); EC 3.4.24.- (Matrix Metalloproteinases, Secreted)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180105
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190725


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[PMID]:29281682
[Au] Autor:Brown K; Legros S; Ortega FA; Dai Y; Doss MX; Christini DJ; Robinson RB; Foley AC
[Ad] Endereço:Greenberg Division of Cardiology, Weill Medical College of Cornell University, New York, New York, United States of America.
[Ti] Título:Overexpression of Map3k7 activates sinoatrial node-like differentiation in mouse ES-derived cardiomyocytes.
[So] Source:PLoS One;12(12):e0189818, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In vivo, cardiomyocytes comprise a heterogeneous population of contractile cells defined by unique electrophysiologies, molecular markers and morphologies. The mechanisms directing myocardial cells to specific sub-lineages remain poorly understood. Here we report that overexpression of TGFß-Activated Kinase (TAK1/Map3k7) in mouse embryonic stem (ES) cells faithfully directs myocardial differentiation of embryoid body (EB)-derived cardiac cells toward the sinoatrial node (SAN) lineage. Most cardiac cells in Map3k7-overexpressing EBs adopt markers, cellular morphologies, and electrophysiological behaviors characteristic of the SAN. These data, in addition to the fact that Map3k7 is upregulated in the sinus venous-the source of cells for the SAN-suggest that Map3k7 may be an endogenous regulator of the SAN fate.
[Mh] Termos MeSH primário: Diferenciação Celular/genética
MAP Quinase Quinase Quinases/genética
Miócitos Cardíacos/citologia
Nó Sinoatrial/citologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Vetores Genéticos
Lentivirus/genética
Camundongos
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:
EC 2.7.11.25 (MAP Kinase Kinase Kinases); EC 2.7.11.25 (MAP kinase kinase kinase 7)
[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:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189818



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