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[PMID]:29366480
[Au] Autor:Zhang N; Zhang Y; Zhao S; Sun Y
[Ad] Endereço:Department of Cardiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning 110001, PR China.
[Ti] Título:Septin4 as a novel binding partner of PARP1 contributes to oxidative stress induced human umbilical vein endothelial cells injure.
[So] Source:Biochem Biophys Res Commun;496(2):621-627, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Oxidative stress induced vascular endothelial cell injure is one of the key and initial event in the development of atherosclerosis. Septin4, as a member of GTP binding protein family, is widely expressed in the eukaryotic cells and considered to be an essential component of the cytoskeleton which is involved in many important physiological processes. However, whether Septin4 is involved in cardiovascular diseases, such as oxidative stress inducted endothelial cell injury still unclear. PARP1 as a DNA repair enzyme can be activated by identifying DNA damaged fragments, which consumes high levels of energy and leads to vascular endothelial cell apoptosis. Here, our results first found that Septin4 is involved in oxidative stress induced endothelial cell ROS production and apoptosis through knock-down and over-expression Septin4 approaches. Furthermore, to explore how Septin4 is involved in oxidative stress induced endothelial cells injure, we first identified that Septin4 is a novel PARP1 interacting protein and the interaction is enhanced under oxidative stress. In conclusions, our founding indicates that Septin4 is a novel essential factor involved in oxidative stress induced vascular endothelial cell injury by interacting with apoptosis-related protein PARP1.
[Mh] Termos MeSH primário: Células Endoteliais/metabolismo
Estresse Oxidativo
Poli(ADP-Ribose) Polimerase-1/metabolismo
Mapas de Interação de Proteínas
Septinas/metabolismo
[Mh] Termos MeSH secundário: Apoptose
Células Endoteliais/citologia
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Ligação Proteica
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Reactive Oxygen Species); EC 2.4.2.30 (PARP1 protein, human); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1); EC 3.6.1.- (SEPT4 protein, human); EC 3.6.1.- (Septins)
[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:180126
[St] Status:MEDLINE


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[PMID]:28470092
[Au] Autor:Song L; Peng X; Li Y; Xiao W; Jia J; Dong C; Gong Y; Zhou G; Han X
[Ad] Endereço:Department of Radiotherapy, the Chinese PLA 309th Hospital, Beijing, PR China.
[Ti] Título:The SEPT9 gene methylation assay is capable of detecting colorectal adenoma in opportunistic screening.
[So] Source:Epigenomics;9(5):599-610, 2017 May.
[Is] ISSN:1750-192X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: This study validated the detection of colorectal adenoma in opportunistic screening using the SEPT9 gene methylation assay. MATERIALS & METHODS: Plasma samples including 85 colorectal cancers, 364 adenomas, 216 hyperplastic polyps, 372 other gastrointestinal diseases and 324 normal subjects, were obtained and tested using the Epi proColon 2.0 CE assay. RESULTS & CONCLUSION: The SEPT9 assay detected 38.7% of all types of adenoma, including 27.8% of serrated adenoma, 28.7% of tubular adenoma, 53.7% of tubulovillous adenoma and 83.3% of villous adenoma. It also detected 27.5% of nonadvanced adenoma (NAA), 47.0% of advanced adenoma (AA) without high-grade dysplasia and 62.5% of AA with high-grade dysplasia. The average adenoma detection rate was 31.8% (95% CI: 28.3-35.4%) with the Boston Bowel Preparation Scale score at 7.6 ± 1.2 (mean ± SD). Our study provided strong evidence for the application of the SEPT9 assay in AA detection in opportunistic screening.
[Mh] Termos MeSH primário: Adenoma/genética
Biomarcadores Tumorais/genética
Neoplasias Colorretais/genética
Metilação de DNA
Septinas/genética
[Mh] Termos MeSH secundário: Adenoma/patologia
Idoso
Biomarcadores Tumorais/normas
Estudos de Casos e Controles
Neoplasias Colorretais/patologia
Seres Humanos
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Biomarkers, Tumor); EC 3.6.1.- (SEPT9 protein, human); EC 3.6.1.- (Septins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.2217/epi-2016-0146


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[PMID]:28817802
[Au] Autor:Boubakar L; Falk J; Ducuing H; Thoinet K; Reynaud F; Derrington E; Castellani V
[Ad] Endereço:NeuroMyoGene Institute UMR CNRS 5310 INSERM U 1217, University of Lyon, University of Lyon 1 Claude Bernard Lyon 1, 16 rue Raphael Dubois, 69000 Lyon, France.
[Ti] Título:Molecular Memory of Morphologies by Septins during Neuron Generation Allows Early Polarity Inheritance.
[So] Source:Neuron;95(4):834-851.e5, 2017 Aug 16.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transmission of polarity established early during cell lineage history is emerging as a key process guiding cell differentiation. Highly polarized neurons provide a fascinating model to study inheritance of polarity over cell generations and across morphological transitions. Neural crest cells (NCCs) migrate to the dorsal root ganglia to generate neurons directly or after cell divisions in situ. Using live imaging of vertebrate embryo slices, we found that bipolar NCC progenitors lose their polarity, retracting their processes to round for division, but generate neurons with bipolar morphology by emitting processes from the same locations as the progenitor. Monitoring the dynamics of Septins, which play key roles in yeast polarity, indicates that Septin 7 tags process sites for re-initiation of process growth following mitosis. Interfering with Septins blocks this mechanism. Thus, Septins store polarity features during mitotic rounding so that daughters can reconstitute the initial progenitor polarity.
[Mh] Termos MeSH primário: Polaridade Celular/genética
Forma Celular/genética
Regulação da Expressão Gênica no Desenvolvimento/genética
Neurogênese/genética
Neurônios/fisiologia
Septinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Ciclo Celular/genética
Diferenciação Celular/genética
Células Cultivadas
Córtex Cerebral/citologia
Embrião de Galinha
Eletroporação
Gânglios Espinais/citologia
Gânglios Espinais/embriologia
Neuritos/fisiologia
Neurônios/citologia
Técnicas de Cultura de Órgãos
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Septinas/genética
Medula Espinal/citologia
Medula Espinal/embriologia
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Leveduras/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Small Interfering); 0 (Transcription Factors); EC 3.6.1.- (Septins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE


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[PMID]:28791742
[Au] Autor:Mahmud MN; Oda M; Usui D; Inoshima Y; Ishiguro N; Kamatari YO
[Ad] Endereço:The United Graduate School of Veterinary Sciences, Gifu University, Gifu, 501-1193, Japan.
[Ti] Título:A multispecific monoclonal antibody G2 recognizes at least three completely different epitope sequences with high affinity.
[So] Source:Protein Sci;26(11):2162-2169, 2017 Nov.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A monoclonal antibody (mAb) G2 possesses an unusual characteristic of reacting with at least three proteins (ATP6V1C1, SEPT3, and C6H10orf76) other than its original antigen, chicken prion protein (ChPrP). The epitopes on ChPrP and ATP6V1C1 have been identified previously. In this study, we identified the epitope in the third protein, SEPT3. Interestingly, there was no amino acid sequence similarity among the epitopes on the three proteins. These epitopes had high binding affinities to G2 (K = ∼10 M for monovalent binding and K = ∼10 M for divalent binding), as determined using a SPR biosensor. This is the first report on a three-in-one mAb recognizing completely different epitope sequences with high affinity. Additionally, competitive ELISA indicated that the binding sites on G2, specific for the three different epitopes, overlapped, suggesting that the antigen-binding site may be flexible in the free form and capable of adapting to at least three different conformations to enable interactions with three different antigens.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/metabolismo
Epitopos/química
Proteínas Nucleares/química
Proteínas Priônicas/química
Septinas/química
ATPases Vacuolares Próton-Translocadoras/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Anticorpos Monoclonais/biossíntese
Anticorpos Monoclonais/química
Afinidade de Anticorpos
Especificidade de Anticorpos
Reações Antígeno-Anticorpo
Sítios de Ligação
Ligação Competitiva
Galinhas
Clonagem Molecular
Ensaio de Imunoadsorção Enzimática
Mapeamento de Epitopos
Epitopos/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Cinética
Proteínas Nucleares/genética
Proteínas Nucleares/imunologia
Proteínas Priônicas/genética
Proteínas Priônicas/imunologia
Ligação Proteica
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/imunologia
Septinas/genética
Septinas/imunologia
Ressonância de Plasmônio de Superfície
ATPases Vacuolares Próton-Translocadoras/genética
ATPases Vacuolares Próton-Translocadoras/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Epitopes); 0 (Nuclear Proteins); 0 (Prion Proteins); 0 (Recombinant Proteins); EC 3.6.1.- (Septins); EC 3.6.1.- (Vacuolar Proton-Translocating ATPases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1002/pro.3263


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[PMID]:28778437
[Au] Autor:Lindsey JW
[Ad] Endereço:Department of Neurology, University of Texas Health Science Center at Houston, United States. Electronic address: john.w.lindsey@uth.tmc.edu.
[Ti] Título:Antibodies to the Epstein-Barr virus proteins BFRF3 and BRRF2 cross-react with human proteins.
[So] Source:J Neuroimmunol;310:131-134, 2017 Sep 15.
[Is] ISSN:1872-8421
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:We hypothesize that the immune response to Epstein-Barr virus (EBV) drives the autoimmune damage in multiple sclerosis (MS). We investigated whether antibodies to two EBV proteins targeted by MS patients cross-react with self proteins. Using affinity columns, immunoprecipitation, and mass spectrometry, we found that antibodies to the EBV protein BFRF3 cross-react with the cytoplasmic protein septin-9, and antibodies to BRRF2 also bind mitochondrial proteins. Using Western blots and ELISA, we demonstrated that MS patients were more likely to have high levels of antibodies to one or another of these self antigens.
[Mh] Termos MeSH primário: Anticorpos Antivirais/sangue
Antígenos Virais/imunologia
Proteínas do Capsídeo/imunologia
Antígenos Nucleares do Vírus Epstein-Barr/imunologia
Esclerose Múltipla Recidivante-Remitente/imunologia
Septinas/imunologia
[Mh] Termos MeSH secundário: Adulto
Anticorpos Antivirais/imunologia
Estudos de Casos e Controles
Reações Cruzadas
Ensaio de Imunoadsorção Enzimática
Feminino
Seres Humanos
Imunoprecipitação
Masculino
Espectrometria de Massas
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (Capsid Proteins); 0 (Epstein-Barr Virus Nuclear Antigens); 0 (Epstein-Barr viral capsid antigen); EC 3.6.1.- (SEPT9 protein, human); EC 3.6.1.- (Septins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170806
[St] Status:MEDLINE


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[PMID]:28650995
[Au] Autor:Mazon-Moya MJ; Willis AR; Torraca V; Boucontet L; Shenoy AR; Colucci-Guyon E; Mostowy S
[Ad] Endereço:Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
[Ti] Título:Septins restrict inflammation and protect zebrafish larvae from Shigella infection.
[So] Source:PLoS Pathog;13(6):e1006467, 2017 Jun.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Shigella flexneri, a Gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. Infection by S. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. Recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. Septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial infection, yet septin function in vivo is poorly understood. Here, we use S. flexneri infection of zebrafish (Danio rerio) larvae to study in vivo the role of septins in inflammation and infection control. We found that depletion of Sept15 or Sept7b, zebrafish orthologs of human SEPT7, significantly increased host susceptibility to bacterial infection. Live-cell imaging of Sept15-depleted larvae revealed increasing bacterial burdens and a failure of neutrophils to control infection. Strikingly, Sept15-depleted larvae present significantly increased activity of Caspase-1 and more cell death upon S. flexneri infection. Dampening of the inflammatory response with anakinra, an antagonist of interleukin-1 receptor (IL-1R), counteracts Sept15 deficiency in vivo by protecting zebrafish from hyper-inflammation and S. flexneri infection. These findings highlight a new role for septins in host defence against bacterial infection, and suggest that septin dysfunction may be an underlying factor in cases of hyper-inflammation.
[Mh] Termos MeSH primário: Disenteria Bacilar/imunologia
Imunidade Inata/imunologia
Septinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Disenteria Bacilar/microbiologia
Interações Hospedeiro-Patógeno/imunologia
Seres Humanos
Inflamação/imunologia
Inflamação/microbiologia
Mucosa Intestinal/microbiologia
Larva/metabolismo
Neutrófilos/metabolismo
Neutrófilos/microbiologia
Shigella flexneri
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.6.1.- (Septins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006467


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[PMID]:28600072
[Au] Autor:Rex DK; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Levin TR; Lieberman D; Robertson DJ
[Ad] Endereço:Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: drex@iu.edu.
[Ti] Título:Colorectal Cancer Screening: Recommendations for Physicians and Patients From the U.S. Multi-Society Task Force on Colorectal Cancer.
[So] Source:Gastroenterology;153(1):307-323, 2017 Jul.
[Is] ISSN:1528-0012
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This document updates the colorectal cancer (CRC) screening recommendations of the U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gastroenterological Association, and The American Society for Gastrointestinal Endoscopy. CRC screening tests are ranked in 3 tiers based on performance features, costs, and practical considerations. The first-tier tests are colonoscopy every 10 years and annual fecal immunochemical test (FIT). Colonoscopy and FIT are recommended as the cornerstones of screening regardless of how screening is offered. Thus, in a sequential approach based on colonoscopy offered first, FIT should be offered to patients who decline colonoscopy. Colonoscopy and FIT are recommended as tests of choice when multiple options are presented as alternatives. A risk-stratified approach is also appropriate, with FIT screening in populations with an estimated low prevalence of advanced neoplasia and colonoscopy screening in high prevalence populations. The second-tier tests include CT colonography every 5 years, the FIT-fecal DNA test every 3 years, and flexible sigmoidoscopy every 5 to 10 years. These tests are appropriate screening tests, but each has disadvantages relative to the tier 1 tests. Because of limited evidence and current obstacles to use, capsule colonoscopy every 5 years is a third-tier test. We suggest that the Septin9 serum assay (Epigenomics, Seattle, Wash) not be used for screening. Screening should begin at age 50 years in average-risk persons, except in African Americans in whom limited evidence supports screening at 45 years. CRC incidence is rising in persons under age 50, and thorough diagnostic evaluation of young persons with suspected colorectal bleeding is recommended. Discontinuation of screening should be considered when persons up to date with screening, who have prior negative screening (particularly colonoscopy), reach age 75 or have <10 years of life expectancy. Persons without prior screening should be considered for screening up to age 85, depending on age and comorbidities. Persons with a family history of CRC or a documented advanced adenoma in a first-degree relative age <60 years or 2 first-degree relatives with these findings at any age are recommended to undergo screening by colonoscopy every 5 years, beginning 10 years before the age at diagnosis of the youngest affected relative or age 40, whichever is earlier. Persons with a single first-degree relative diagnosed at ≥60 years with CRC or an advanced adenoma can be offered average-risk screening options beginning at age 40 years.
[Mh] Termos MeSH primário: Adenoma/diagnóstico
Colonoscopia
Neoplasias Colorretais/diagnóstico
Detecção Precoce de Câncer/normas
Sangue Oculto
Vigilância da População
[Mh] Termos MeSH secundário: Adenoma/genética
Fatores Etários
Colonografia Tomográfica Computadorizada
Neoplasias Colorretais/genética
DNA/análise
Fezes/química
Seres Humanos
Fatores de Risco
Septinas/sangue
Sigmoidoscopia
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; PRACTICE GUIDELINE
[Nm] Nome de substância:
9007-49-2 (DNA); EC 3.6.1.- (SEPT9 protein, human); EC 3.6.1.- (Septins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170611
[St] Status:MEDLINE


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[PMID]:28530676
[Au] Autor:Lu H; Galeano MCR; Ott E; Kaeslin G; Kausalya PJ; Kramer C; Ortiz-Brüchle N; Hilger N; Metzis V; Hiersche M; Tay SY; Tunningley R; Vij S; Courtney AD; Whittle B; Wühl E; Vester U; Hartleben B; Neuber S; Frank V; Little MH; Epting D; Papathanasiou P; Perkins AC; Wright GD; Hunziker W; Gee HY; Otto EA; Zerres K; Hildebrandt F; Roy S; Wicking C; Bergmann C
[Ad] Endereço:Institute of Molecular and Cell Biology, Singapore.
[Ti] Título:Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease.
[So] Source:Nat Genet;49(7):1025-1034, 2017 Jul.
[Is] ISSN:1546-1718
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in DZIP1L, which encodes DAZ interacting protein 1-like, in patients with ARPKD. We further validated these findings through loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and to the distal ends of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone. In agreement with a defect in the diffusion barrier, we found that the ciliary-membrane translocation of the PKD proteins polycystin-1 and polycystin-2 is compromised in DZIP1L-mutant cells. Together, these data provide what is, to our knowledge, the first conclusive evidence that ARPKD is not a homogeneous disorder and further establish DZIP1L as a second gene involved in ARPKD pathogenesis.
[Mh] Termos MeSH primário: Rim Policístico Autossômico Recessivo/genética
[Mh] Termos MeSH secundário: Anormalidades Múltiplas/embriologia
Anormalidades Múltiplas/genética
Proteínas Adaptadoras de Transdução de Sinal/deficiência
Proteínas Adaptadoras de Transdução de Sinal/genética
Proteínas Adaptadoras de Transdução de Sinal/fisiologia
Animais
Centríolos/metabolismo
Cromossomos Humanos Par 3/genética
Cílios/metabolismo
Consanguinidade
Modelos Animais de Doenças
Embrião não Mamífero/anormalidades
Feminino
Técnicas de Silenciamento de Genes
Ligação Genética
Seres Humanos
Masculino
Proteínas de Membrana/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Linhagem
Rim Policístico Autossômico Recessivo/embriologia
Transporte Proteico
Septinas/metabolismo
Canais de Cátion TRPP/metabolismo
Peixe-Zebra/embriologia
Peixe-Zebra/genética
Proteínas de Peixe-Zebra/deficiência
Proteínas de Peixe-Zebra/genética
Proteínas de Peixe-Zebra/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (DZIP1L protein, human); 0 (DZIP1L protein, mouse); 0 (DZIP1L protein, zebrafish); 0 (Membrane Proteins); 0 (TRPP Cation Channels); 0 (Zebrafish Proteins); 0 (polycystic kidney disease 1 protein); 0 (polycystic kidney disease 2 protein); EC 3.6.1.- (Septins); EC 3.6.1.- (septin 2 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE
[do] DOI:10.1038/ng.3871


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[PMID]:28515105
[Au] Autor:Schröck A; Leisse A; de Vos L; Gevensleben H; Dröge F; Franzen A; Wachendörfer M; Schröck F; Ellinger J; Teschke M; Wilhelm-Buchstab T; Landsberg J; Holdenrieder S; Hartmann G; Field JK; Bootz F; Kristiansen G; Dietrich D
[Ad] Endereço:Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany.
[Ti] Título:Free-Circulating Methylated DNA in Blood for Diagnosis, Staging, Prognosis, and Monitoring of Head and Neck Squamous Cell Carcinoma Patients: An Observational Prospective Cohort Study.
[So] Source:Clin Chem;63(7):1288-1296, 2017 Jul.
[Is] ISSN:1530-8561
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Circulating cell-free DNA methylation testing in blood has recently received regulatory approval for screening of colorectal cancer. Its application in other clinical settings, including staging, prognosis, prediction, and recurrence monitoring is highly promising, and of particular interest in head and neck squamous cell carcinomas (HNSCCs) that represent a heterogeneous group of cancers with unsatisfactory treatment guidelines. METHODS: Short stature homeobox 2 ( ) and septin 9 ( ) DNA methylation in plasma from 649 prospectively enrolled patients (training study: 284 HNSCC/122 control patients; testing study: 141 HNSCC/102 control patients) was quantified before treatment and longitudinally during surveillance. RESULTS: In the training study, 59% of HNSCC patients were methylation-positive at 96% specificity. Methylation levels correlated with tumor and nodal category ( < 0.001). Initially increased methylation levels were associated with a higher risk of death [ : hazard ratio (HR) = 5.27, = 0.001; : HR = 2.32, = 0.024]. Disease recurrence/metastases were detected in 47% of patients up to 377 days earlier compared to current clinical practice. The onset of second cancers was detected up to 343 days earlier. In the testing study, sensitivity (52%), specificity (95%), prediction of overall survival ( : HR = 2.78, = 0.022; : HR = 2.50, = 0.026), and correlation with tumor and nodal category ( <0.001) were successfully validated. CONCLUSIONS: Methylation testing in plasma is a powerful diagnostic tool for molecular disease staging, risk stratification, and disease monitoring. Patients with initially high biomarker levels might benefit from intensified treatment and posttherapeutic surveillance. The early detection of a recurrent/metastatic disease or a second malignancy could lead to an earlier consecutive treatment, thereby improving patients' outcomes.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Carcinoma de Células Escamosas/diagnóstico
Metilação de DNA
Neoplasias de Cabeça e Pescoço/diagnóstico
[Mh] Termos MeSH secundário: Carcinoma de Células Escamosas/sangue
Estudos de Coortes
Neoplasias de Cabeça e Pescoço/sangue
Proteínas de Homeodomínio/sangue
Proteínas de Homeodomínio/genética
Seres Humanos
Estadiamento de Neoplasias
Valor Preditivo dos Testes
Prognóstico
Septinas/sangue
Septinas/genética
Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Homeodomain Proteins); 0 (SHOX2 protein, human); EC 3.6.1.- (SEPT9 protein, human); EC 3.6.1.- (Septins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1373/clinchem.2016.270207


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[PMID]:28476887
[Au] Autor:Pinto APA; Pereira HM; Zeraik AE; Ciol H; Ferreira FM; Brandão-Neto J; DeMarco R; Navarro MVAS; Risi C; Galkin VE; Garratt RC; Araujo APU
[Ad] Endereço:From the Instituto de Física de São Carlos, Universidade de São Paulo, CEP: 13563-120, São Carlos, SP, Brazil.
[Ti] Título:Filaments and fingers: Novel structural aspects of the single septin from .
[So] Source:J Biol Chem;292(26):10899-10911, 2017 Jun 30.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Septins are filament-forming GTP-binding proteins involved in many essential cellular events related to cytoskeletal dynamics and maintenance. Septins can self-assemble into heterocomplexes, which polymerize into highly organized, cell membrane-interacting filaments. The number of septin genes varies among organisms, and although their structure and function have been thoroughly studied in opisthokonts (including animals and fungi), no structural studies have been reported for other organisms. This makes the single septin from (CrSEPT) a particularly attractive model for investigating whether functional homopolymeric septin filaments also exist. CrSEPT was detected at the base of the flagella in , suggesting that CrSEPT is involved in the formation of a membrane-diffusion barrier. Using transmission electron microscopy, we observed that recombinant CrSEPT forms long filaments with dimensions comparable with those of the canonical structure described for opisthokonts. The GTP-binding domain of CrSEPT purified as a nucleotide-free monomer that hydrolyzes GTP and readily binds its analog guanosine 5'-3- -(thio)triphosphate. We also found that upon nucleotide binding, CrSEPT formed dimers that were stabilized by an interface involving the ligand (G-interface). Across this interface, one monomer supplied a catalytic arginine to the opposing subunit, greatly accelerating the rate of GTP hydrolysis. This is the first report of an arginine finger observed in a septin and suggests that CrSEPT may act as its own GTP-activating protein. The finger is conserved in all algal septin sequences, suggesting a possible correlation between the ability to form homopolymeric filaments and the accelerated rate of hydrolysis that it provides.
[Mh] Termos MeSH primário: Chlamydomonas reinhardtii/química
Complexos Multiproteicos/química
Proteínas de Plantas/química
Multimerização Proteica
Septinas/química
[Mh] Termos MeSH secundário: Chlamydomonas reinhardtii/enzimologia
Chlamydomonas reinhardtii/genética
Complexos Multiproteicos/genética
Complexos Multiproteicos/metabolismo
Complexos Multiproteicos/ultraestrutura
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Septinas/genética
Septinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Multiprotein Complexes); 0 (Plant Proteins); EC 3.6.1.- (Septins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170507
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.762229



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