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  1 / 181 MEDLINE  
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[PMID]:29232390
[Au] Autor:Koenig A; Krug S; Mueller D; Barth PJ; Koenig U; Scharf M; Ellenrieder V; Michl P; Moll R; Homayunfar K; Kann PH; Stroebel P; Gress TM; Rinke A
[Ad] Endereço:Department of Gastroenterology and Endocrinology, Philipps-University of Marburg, Marburg, Germany.
[Ti] Título:Clinicopathological hallmarks and biomarkers of colorectal neuroendocrine neoplasms.
[So] Source:PLoS One;12(12):e0188876, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromogranin A (CgA) is a well-established marker for diagnosis and follow up of patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). Recently, it has been shown that plasma levels of CgA correlate with tumor load and predict survival of patients with NEN of the small bowel. It is assumed that this is as well valid for NEN of the colon and rectum, however, this is not supported by data. To evaluate this assumption, we analyzed 62 patients with NEN of the colon and rectum listed in the Marburg GEP-NEN registry for clinicopathological characteristics, expression and plasma levels of CgA. The present study demonstrates that immunohistochemical CgA and synaptophysin are good markers for histological diagnosis in patients with NEN of the colon and rectum. However, plasma CgA is a poor marker to follow-up these patients because only a minority exhibited increased levels which did not increase significantly during tumor progression. In contrast to NEN of the small bowel, there is no correlation of CgA plasma levels with tumor burden or survival. Patients with NEN of the colon and rectum displayed a relatively good prognosis resulting in a median survival of 8.5 years. However, a subset of patients affected by G3 neoplasms, exhibited a poorer prognosis with a median survival of 2.5 years. Taken together, CgA is a valuable marker for immunohistochemical diagnosis, but CgA plasma concentration is not suitable to mirror tumor burden or prognosis in patients with NEN of the colon and rectum.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Cromogranina B/sangue
Neoplasias Colorretais/patologia
Tumores Neuroendócrinos/patologia
[Mh] Termos MeSH secundário: Idoso
Neoplasias Colorretais/sangue
Progressão da Doença
Feminino
Seres Humanos
Masculino
Meia-Idade
Tumores Neuroendócrinos/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Chromogranin B)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188876


  2 / 181 MEDLINE  
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[PMID]:28338171
[Au] Autor:Chen L; Chen M; Chen J
[Ti] Título:[Advances of circulating biomarkers in gastroenteropancreatic neuroendocrine neoplasms].
[So] Source:Zhonghua Wei Chang Wai Ke Za Zhi;20(3):357-360, 2017 Mar 25.
[Is] ISSN:1671-0274
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:Gastroenteropancreatic neuroendocrine neoplam (GEP-NEN) is a rare group of tumors with its incidence rising significantly in recent decades. Because of the late presentation of the disease and limitations in conventional biomarkers, about 50% of GEP-NEN patients manifests advanced disease when diagnosed. Therefore, it is vital to identify circulating biomarkers which can not only be used for early diagnosis but also accurately evaluating the biological behavior of GEP-NEN. This review summarizes the advances of circulating biomarkers in diagnosing and evaluating efficacy of treatment in GEP-NEN. Well-known circulating biomarkers include chromogranin A (CgA), pancreastatin (PST), chromogranin B (CgB), neuron-specific enolase (NSE) and pancreatic peptide(PP). Novel biomarkers including circulating tumor cell(CTC), microRNA and NETest are promising biomarkers with potential clinical benefit, but further researches are needed before their clinical applications.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Cromogranina B/sangue
Cromogranina B/química
Neoplasias Gastrointestinais/sangue
Neoplasias Gastrointestinais/química
Neoplasias Gastrointestinais/diagnóstico
Neoplasias Gastrointestinais/genética
Tumores Neuroendócrinos/sangue
Tumores Neuroendócrinos/química
Tumores Neuroendócrinos/diagnóstico
Tumores Neuroendócrinos/genética
Neoplasias Pancreáticas/sangue
Neoplasias Pancreáticas/química
Neoplasias Pancreáticas/diagnóstico
Neoplasias Pancreáticas/genética
Polipeptídeo Pancreático/sangue
Fosfopiruvato Hidratase/sangue
[Mh] Termos MeSH secundário: Cromogranina A/sangue
Seres Humanos
MicroRNAs/sangue
Células Neoplásicas Circulantes
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CHGA protein, human); 0 (CHGB protein, human); 0 (Chromogranin A); 0 (Chromogranin B); 0 (MicroRNAs); 106477-83-2 (pancreastatin); 59763-91-6 (Pancreatic Polypeptide); EC 4.2.1.11 (Phosphopyruvate Hydratase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE


  3 / 181 MEDLINE  
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[PMID]:28334992
[Au] Autor:Miki M; Ito T; Hijioka M; Lee L; Yasunaga K; Ueda K; Fujiyama T; Tachibana Y; Kawabe K; Jensen RT; Ogawa Y
[Ad] Endereço:Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
[Ti] Título:Utility of chromogranin B compared with chromogranin A as a biomarker in Japanese patients with pancreatic neuroendocrine tumors.
[So] Source:Jpn J Clin Oncol;47(6):520-528, 2017 Jun 01.
[Is] ISSN:1465-3621
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objective: Currently, serum chromogranin A is a well-established biomarker for pancreatic neuroendocrine tumors; however, other pancreatic diseases, oral use of a proton pump inhibitor and renal impairment can affect chromogranin A. Meanwhile, chromogranin B, belonging to the same granin family as chromogranin A, is not fully examined in these conditions. The present study aimed to evaluate the utility of chromogranin B as a pancreatic neuroendocrine tumor biomarker. Methods: Serum chromogranin B levels were determined by radioimmunoassay and serum chromogranin A levels by enzyme-linked immunosorbent assay in pancreatic neuroendocrine tumor (n = 91) and other pancreatic conditions, and in healthy people (n = 104), to assess the relationships with clinical features. Results: The diagnostic ability of chromogranin B was as good as chromogranin A. The area under the curve was 0.79 for chromogranin B (sensitivity/specificity: 72%/77%), and 0.78 for chromogranin A (sensitivity/specificity: 79%/64%). Chromogranin B was not affected by proton pump inhibitor use and age, which affected chromogranin A. The number of cases without liver metastases was larger in pancreatic neuroendocrine tumor patients with positive chromogranin B and negative chromogranin A. Though chromogranin A significantly elevated cases with proton pump inhibitor treatment and had positive correlation with age, chromogranin B did not have the tendencies. However, both chromogranin B and chromogranin A elevated in the case with renal impairment. In addition, the logistic regression analysis showed that chromogranin B was superior to chromogranin A in differentiation of pancreatic neuroendocrine tumor from other pancreatic diseases. Conclusions: Compared with chromogranin A, chromogranin B may be more useful during proton pump inhibitor treatment and can detect tumors without liver metastases. In addition, chromogranin B may be an excellent biomarker when differentiation of pancreatic neuroendocrine tumor from other pancreatic diseases is required.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Cromogranina A/sangue
Cromogranina B/sangue
Tumores Neuroendócrinos/sangue
Neoplasias Pancreáticas/sangue
[Mh] Termos MeSH secundário: Adulto
Fatores Etários
Idoso
Idoso de 80 Anos ou mais
Estudos de Casos e Controles
Ensaio de Imunoadsorção Enzimática
Feminino
Gastrinas/sangue
Seres Humanos
Modelos Logísticos
Masculino
Meia-Idade
Análise Multivariada
Tumores Neuroendócrinos/tratamento farmacológico
Neoplasias Pancreáticas/tratamento farmacológico
Inibidores da Bomba de Prótons/uso terapêutico
Curva ROC
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Chromogranin A); 0 (Chromogranin B); 0 (Gastrins); 0 (Proton Pump Inhibitors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1093/jjco/hyx032


  4 / 181 MEDLINE  
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[PMID]:28332369
[Au] Autor:Shin JG; Kim JH; Park CS; Kim BJ; Kim JW; Choi IG; Hwang J; Shin HD; Woo SI
[Ad] Endereço:Department of Life Science, Sogang University, Seoul, Korea.
[Ti] Título:Gender-Specific Associations between CHGB Genetic Variants and Schizophrenia in a Korean Population.
[So] Source:Yonsei Med J;58(3):619-625, 2017 May.
[Is] ISSN:1976-2437
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Schizophrenia is a devastating mental disorder and is known to be affected by genetic factors. The chromogranin B (CHGB), a member of the chromogranin gene family, has been proposed as a candidate gene associated with the risk of schizophrenia. The secretory pathway for peptide hormones and neuropeptides in the brain is regulated by chromogranin proteins. The aim of this study was to investigate the potential associations between genetic variants of CHGB and schizophrenia susceptibility. MATERIALS AND METHODS: In the current study, 15 single nucleotide polymorphisms of CHGB were genotyped in 310 schizophrenia patients and 604 healthy controls. RESULTS: Statistical analysis revealed that two genetic variants (non-synonymous rs910122; rs2821 in 3'-untranslated region) were associated with schizophrenia [minimum p=0.002; odds ratio (OR)=0.72], even after correction for multiple testing (p(corr)=0.02). Since schizophrenia is known to be differentially expressed between sexes, additional analysis for sex was performed. As a result, these two genetic variants (rs910122 and rs2821) and a haplotype (ht3) showed significant associations with schizophrenia in male subjects (p(corr)=0.02; OR=0.64), whereas the significance disappeared in female subjects (p>0.05). CONCLUSION: Although this study has limitations including a small number of samples and lack of functional study, our results suggest that genetic variants of CHGB may have sex-specific effects on the risk of schizophrenia and provide useful preliminary information for further study.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Encéfalo/metabolismo
Cromogranina B/genética
Predisposição Genética para Doença/genética
Polimorfismo de Nucleotídeo Único/genética
Esquizofrenia/genética
[Mh] Termos MeSH secundário: Adulto
Encéfalo/fisiopatologia
Estudos de Casos e Controles
Feminino
Marcadores Genéticos/genética
Genótipo
Haplótipos
Seres Humanos
Masculino
Meia-Idade
República da Coreia/epidemiologia
Esquizofrenia/etnologia
Fatores Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromogranin B); 0 (Genetic Markers)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170510
[Lr] Data última revisão:
170510
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.3349/ymj.2017.58.3.619


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[PMID]:26760117
[Au] Autor:Ishii J; Yazawa T; Chiba T; Shishido-Hara Y; Arimasu Y; Sato H; Kamma H
[Ad] Endereço:Department of Pathology (J.I., T.C., Y.A., H.K.), Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan; Department of Diagnostic Pathology (T.Y.), Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical University,
[Ti] Título:PROX1 Promotes Secretory Granule Formation in Medullary Thyroid Cancer Cells.
[So] Source:Endocrinology;157(3):1289-98, 2016 Mar.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mechanisms of endocrine secretory granule (SG) formation in thyroid C cells and medullary thyroid cancer (MTC) cells have not been fully elucidated. Here we directly demonstrated that PROX1, a developmental homeobox gene, is transcriptionally involved in SG formation in MTC, which is derived from C cells. Analyses using gene expression databases on web sites revealed that, among thyroid cancer cells, MTC cells specifically and highly express PROX1 as well as several SG-forming molecule genes. Immunohistochemical analyses showed that in vivo MTC and C cells expressed PROX1, although follicular thyroid cancer and papillary thyroid cancer cells, normal follicular cells did not. Knockdown of PROX1 in an MTC cells reduced SGs detected by electron microscopy, and decreased expression of SG-related genes (chromogranin A, chromogranin B, secretogranin II, secretogranin III, synaptophysin, and carboxypeptidase E). Conversely, the introduction of a PROX1 transgene into a papillary thyroid cancer and anaplastic thyroid cancer cells induced the expression of SG-related genes. Reporter assays using the promoter sequence of chromogranin A showed that PROX1 activates the chromogranin A gene in addition to the known regulatory mechanisms, which are mediated via the cAMP response element binding protein and the repressor element 1-silencing transcription factor. Furthermore, chromatin immunoprecipitation-PCR assays demonstrated that PROX1 binds to the transcriptional regulatory element of the chromogranin A gene. In conclusion, PROX1 is an important regulator of endocrine SG formation in MTC cells.
[Mh] Termos MeSH primário: Adenocarcinoma Folicular/genética
Adenoma/genética
Carcinoma Neuroendócrino/genética
Carcinoma/genética
Regulação Neoplásica da Expressão Gênica/genética
Proteínas de Homeodomínio/genética
Vesículas Secretórias/genética
Neoplasias da Glândula Tireoide/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Adenocarcinoma Folicular/metabolismo
Adenoma/metabolismo
Adulto
Idoso
Idoso de 80 Anos ou mais
Carboxipeptidase H/genética
Carcinoma/metabolismo
Carcinoma Neuroendócrino/metabolismo
Carcinoma Papilar
Imunoprecipitação da Cromatina
Cromogranina A/genética
Cromogranina B/genética
Cromograninas/genética
Feminino
Técnicas de Introdução de Genes
Técnicas de Silenciamento de Genes
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Secretogranina II/genética
Sinaptofisina/genética
Glândula Tireoide/metabolismo
Neoplasias da Glândula Tireoide/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromogranin A); 0 (Chromogranin B); 0 (Chromogranins); 0 (Homeodomain Proteins); 0 (SCG2 protein, human); 0 (SCG3 protein, human); 0 (SYP protein, human); 0 (Secretogranin II); 0 (Synaptophysin); 0 (Tumor Suppressor Proteins); 0 (prospero-related homeobox 1 protein); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160114
[St] Status:MEDLINE
[do] DOI:10.1210/en.2015-1973


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[PMID]:26608723
[Au] Autor:Monaghan PJ; Lamarca A; Valle JW; Hubner RA; Mansoor W; Trainer PJ; Darby D
[Ad] Endereço:The Christie Pathology Partnership, The Christie NHS Foundation Trust, Manchester, UK.
[Ti] Título:Routine measurement of plasma chromogranin B has limited clinical utility in the management of patients with neuroendocrine tumours.
[So] Source:Clin Endocrinol (Oxf);84(3):348-52, 2016 Mar.
[Is] ISSN:1365-2265
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Chromogranin A (CgA) and B (CgB) are markers for monitoring disease status in patients with gastroenteropancreatic neuroendocrine tumours (NETs). These are specialized diagnostic tests often necessitating referral of specimens to a supraregional assay service (SAS) laboratory for analysis. The aim of this audit was to assess whether measurement of either plasma CgA or CgB alone provides sufficient clinical information in comparison with the current practice of measuring both markers together. DESIGN: A retrospective analysis was undertaken for all chromogranin tests requested for patients with a known NET diagnosis. Results were categorized based on whether plasma concentrations were elevated for one or both CgA and CgB. RESULTS: A total of 325 sequential patients with a NET diagnosis had plasma chromogranin levels measured during the period of review. Baseline CgA was elevated in 60·9% of patients. Isolated elevations in CgA (with normal CgB) were found in 44·9% of patients, whilst combined elevations in both CgA and CgB were found in 16% of patients. Combined CgA and CgB concentrations within the normal range were observed for 38·5% of patients. Only two patients (0·6%) had an isolated elevation in CgB at baseline. Both patients had a diagnosis of pancreatic NET and were radiologically stable. Plasma CgA and CgB corresponded with disease stage (localized vs metastatic). CgB in addition to CgA did not provide any significant improvement in diagnostic performance for identification of metastatic disease compared to CgA alone. CONCLUSIONS: Based on this NET population and specific assay performance characteristics, CgA alone provides sufficient information for the management of NET patients; the routine estimation of CgB in all patients is not informative in clinical practice.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Cromogranina A/sangue
Cromogranina B/sangue
Tumores Neuroendócrinos/sangue
Tumores Neuroendócrinos/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Modelos Logísticos
Masculino
Meia-Idade
Tumores Neuroendócrinos/tratamento farmacológico
Curva ROC
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Chromogranin A); 0 (Chromogranin B)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151127
[St] Status:MEDLINE
[do] DOI:10.1111/cen.12985


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[PMID]:26314682
[Au] Autor:Martins-de-Souza D; Farias AS
[Ad] Endereço:UNICAMP's Neurobiology Center, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
[Ti] Título:Deciphering the biochemistry and identifying biomarkers to multiple sclerosis.
[So] Source:Proteomics;15(19):3281-2, 2015 Oct.
[Is] ISSN:1615-9861
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Multiple sclerosis is an idiopathic demyelinating disease of the CNS. Despite being extensively studied during the last decades, many molecular aspects of the disease are still to be elucidated. Moreover, biomarkers for treatment and early diagnosis are major issues to be tackled. In this edition of Kroksveen et al. (Proteomics 2015, 15, 3361-3369) present biomarker candidates for the early detection of multiple sclerosis. Despite the need for validation in larger sets of samples, this dataset contributes to resolve open questions associated to multiple sclerosis.
[Mh] Termos MeSH primário: Cromogranina B/líquido cefalorraquidiano
Esclerose Múltipla/líquido cefalorraquidiano
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Masculino
[Pt] Tipo de publicação:COMMENT; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromogranin B)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151006
[Lr] Data última revisão:
151006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150829
[St] Status:MEDLINE
[do] DOI:10.1002/pmic.201500332


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[PMID]:26304852
[Au] Autor:Erickson LA; Vrana JA; Theis J; Rivera M; Lloyd RV; McPhail E; Zhang J
[Ad] Endereço:Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55901, USA. erickson.lori@mayo.edu.
[Ti] Título:Analysis of Amyloid in Medullary Thyroid Carcinoma by Mass Spectrometry-Based Proteomic Analysis.
[So] Source:Endocr Pathol;26(4):291-5, 2015 Dec.
[Is] ISSN:1559-0097
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Amyloid is a characteristic histologic feature in medullary thyroid carcinomas (MTC). We utilized a novel mass spectrometry-based proteomic analysis to determine if we could identify specific proteins associated with amyloid in MTC. We studied 9 MTC (1 multiple endocrine neoplasia type 2A, 1 familial MTC, and 7 sporadic). Laser microdissection was utilized to sample the amyloid which was then trypsin digested and evaluated by liquid chromatography electrospray tandem MS (LC-MS/MS) which identified the presence of amyloidogenic proteins in all cases of MTC. High levels of calcitonin were identified in all 9 cases of MTC. Secretogranin-1 was identified in 6 of 9 MTC. Calcitonin gene-related peptide was identified in 4 of 9 cases of MTC. LC-MS/MS proteomic analysis provides a rapid, highly specific, and sensitive method for identification of the specific type of amyloid in these endocrine tumors. This approach may allow classification of different forms of endocrine amyloid present in neuroendocrine tumors.
[Mh] Termos MeSH primário: Amiloide/análise
Calcitonina/análise
Carcinoma Neuroendócrino/química
Cromogranina B/análise
Proteômica/métodos
Espectrometria de Massas em Tandem/métodos
Neoplasias da Glândula Tireoide/química
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid); 0 (CHGB protein, human); 0 (Chromogranin B); 9007-12-9 (Calcitonin)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150826
[St] Status:MEDLINE
[do] DOI:10.1007/s12022-015-9390-7


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[PMID]:26208914
[Au] Autor:Delépine C; Nectoux J; Letourneur F; Baud V; Chelly J; Billuart P; Bienvenu T
[Ad] Endereço:Inserm, U1016, Faculté de Médecine, Laboratoire de Génétique et de Physiopathologie des Maladies Mentales, Institut Cochin, 24 Rue du Faubourg Saint Jacques, 75014, Paris, France.
[Ti] Título:Astrocyte Transcriptome from the Mecp2(308)-Truncated Mouse Model of Rett Syndrome.
[So] Source:Neuromolecular Med;17(4):353-63, 2015 Dec.
[Is] ISSN:1559-1174
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mutations in the gene encoding the transcriptional modulator methyl-CpG binding protein 2 (MeCP2) are responsible for the neurodevelopmental disorder Rett syndrome which is one of the most frequent sources of intellectual disability in women. Recent studies showed that loss of Mecp2 in astrocytes contributes to Rett-like symptoms and restoration of Mecp2 can rescue some of these defects. The goal of this work is to compare gene expression profiles of wild-type and mutant astrocytes from Mecp2(308/y) mice (B6.129S-MeCP2/J) by using Affymetrix mouse 2.0 microarrays. Results were confirmed by quantitative real-time RT-PCR and by Western blot analysis. Gene set enrichment analysis utilizing Ingenuity Pathways was employed to identify pathways disrupted by Mecp2 deficiency. A total of 2152 genes were statistically differentially expressed between wild-type and mutated samples, including 1784 coding transcripts. However, only 257 showed fold changes >1.2. We confirmed our data by replicative studies in independent primary cultures of cortical astrocytes from Mecp2-deficient mice. Interestingly, two genes known to encode secreted proteins, chromogranin B and lipocalin-2, showed significant dysregulation. These proteins secreted from Mecp2-deficient glia may exert negative non-cell autonomous effects on neuronal properties, including dendritic morphology. Moreover, transcriptional profiling revealed altered Nr2f2 expression which may explain down- and upregulation of several target genes in astrocytes such as Ccl2, Lcn2 and Chgb. Unraveling Nr2f2 involvement in Mecp2-deficient astrocytes could pave the way for a better understanding of Rett syndrome pathophysiology and offers new therapeutic perspectives.
[Mh] Termos MeSH primário: Astrócitos/metabolismo
Proteína 2 de Ligação a Metil-CpG/deficiência
Proteínas do Tecido Nervoso/genética
Síndrome de Rett/genética
Transcriptoma
[Mh] Termos MeSH secundário: Proteínas da Fase Aguda/secreção
Animais
Fator II de Transcrição COUP/biossíntese
Fator II de Transcrição COUP/genética
Células Cultivadas
Córtex Cerebral/patologia
Cromogranina B/secreção
Modelos Animais de Doenças
Feminino
Perfilação da Expressão Gênica
Estudo de Associação Genômica Ampla
Lipocalina-2
Lipocalinas/secreção
Masculino
Proteína 2 de Ligação a Metil-CpG/genética
Camundongos
Camundongos Endogâmicos
NF-kappa B/metabolismo
Proteínas do Tecido Nervoso/biossíntese
Análise de Sequência com Séries de Oligonucleotídeos
Proteínas Oncogênicas/secreção
Interferência de RNA
Reação em Cadeia da Polimerase em Tempo Real
Reprodutibilidade dos Testes
Síndrome de Rett/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acute-Phase Proteins); 0 (COUP Transcription Factor II); 0 (Chromogranin B); 0 (Lipocalin-2); 0 (Lipocalins); 0 (Mecp2 protein, mouse); 0 (Methyl-CpG-Binding Protein 2); 0 (NF-kappa B); 0 (Nerve Tissue Proteins); 0 (Nr2f2 protein, mouse); 0 (Oncogene Proteins); 0 (chromogranin B, mouse); 126469-30-5 (Lcn2 protein, mouse)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150726
[St] Status:MEDLINE
[do] DOI:10.1007/s12017-015-8363-9


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[PMID]:26152395
[Au] Autor:Kroksveen AC; Jaffe JD; Aasebø E; Barsnes H; Bjørlykke Y; Franciotta D; Keshishian H; Myhr KM; Opsahl JA; van Pesch V; Teunissen CE; Torkildsen Ø; Ulvik RJ; Vethe H; Carr SA; Berven FS
[Ad] Endereço:The KG Jebsen Centre for MS-research, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
[Ti] Título:Quantitative proteomics suggests decrease in the secretogranin-1 cerebrospinal fluid levels during the disease course of multiple sclerosis.
[So] Source:Proteomics;15(19):3361-9, 2015 Oct.
[Is] ISSN:1615-9861
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS with unknown cause. Proteins with different abundance in the cerebrospinal fluid (CSF) from relapsing-remitting MS (RRMS) patients and neurological controls could give novel insight to the MS pathogenesis and be used to improve diagnosis, predict prognosis and disease course, and guide in therapy decisions. We combined iTRAQ labeling and Orbitrap mass spectrometry to discover proteins with different CSF abundance between six RRMS patients and 18 neurological disease controls. From 777 quantified proteins seven were selected as biomarker candidates, namely chitinase-3-like protein 1, secretogranin-1 (Sg1), cerebellin-1, neuroserpin, cell surface glycoprotein MUC18, testican-2 and glutamate receptor 4. An independent sample set of 13 early-MS patients, 13 RRMS patients and 13 neurological controls was used in a multiple reaction monitoring verification study. We found the intracellular calcium binding protein Sg1 to be increased in early-MS patients compared to RRMS and neurological controls. Sg1 should be included in further studies to elucidate its role in the early phases of MS pathogenesis and its potential as a biomarker for this disease.
[Mh] Termos MeSH primário: Cromogranina B/líquido cefalorraquidiano
Esclerose Múltipla/líquido cefalorraquidiano
[Mh] Termos MeSH secundário: Adulto
Biomarcadores
Cromogranina B/genética
Progressão da Doença
Regulação para Baixo
Feminino
Seres Humanos
Masculino
Espectrometria de Massas
Meia-Idade
Esclerose Múltipla/diagnóstico
Esclerose Múltipla/metabolismo
Esclerose Múltipla/patologia
Proteômica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (CHGB protein, human); 0 (Chromogranin B)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151006
[Lr] Data última revisão:
151006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150709
[St] Status:MEDLINE
[do] DOI:10.1002/pmic.201400142



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