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[PMID]:28529319
[Au] Autor:Saharinen P; Eklund L; Alitalo K
[Ad] Endereço:Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, FI-00014 Helsinki, Finland.
[Ti] Título:Therapeutic targeting of the angiopoietin-TIE pathway.
[So] Source:Nat Rev Drug Discov;16(9):635-661, 2017 Sep.
[Is] ISSN:1474-1784
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The endothelial angiopoietin (ANG)-TIE growth factor receptor pathway regulates vascular permeability and pathological vascular remodelling during inflammation, tumour angiogenesis and metastasis. Drugs that target the ANG-TIE pathway are in clinical development for oncological and ophthalmological applications. The aim is to complement current vascular endothelial growth factor (VEGF)-based anti-angiogenic therapies in cancer, wet age-related macular degeneration and macular oedema. The unique function of the ANG-TIE pathway in vascular stabilization also renders this pathway an attractive target in sepsis, organ transplantation, atherosclerosis and vascular complications of diabetes. This Review covers key aspects of the function of the ANG-TIE pathway in vascular disease and describes the recent development of novel therapeutics that target this pathway.
[Mh] Termos MeSH primário: Angiopoietinas/antagonistas & inibidores
Terapia de Alvo Molecular/métodos
Receptores de TIE/antagonistas & inibidores
Doenças Vasculares/tratamento farmacológico
[Mh] Termos MeSH secundário: Inibidores da Angiogênese/farmacologia
Inibidores da Angiogênese/uso terapêutico
Animais
Seres Humanos
Modelos Biológicos
Transdução de Sinais/efeitos dos fármacos
Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Angiopoietins); 0 (Vascular Endothelial Growth Factor A); EC 2.7.10.1 (Receptors, TIE)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE
[do] DOI:10.1038/nrd.2016.278


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[PMID]:28049887
[Au] Autor:Kose E; Uno K; Hayashi H
[Ad] Endereço:Department of Pharmacotherapy, School of Pharmacy, Nihon University.
[Ti] Título:Evaluation of the Expression Profile of Extrapyramidal Symptoms Due to Antipsychotics by Data Mining of Japanese Adverse Drug Event Report (JADER) Database.
[So] Source:Yakugaku Zasshi;137(1):111-120, 2017.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Typical antipsychotics are easily expressed as adverse events such as extrapyramidal symptom (EPS). On the other hand, incidence of adverse events due to atypical antipsychotics is low. Therefore, currently, atypical antipsychotics are widely used to treat schizophrenia. However, it has been reported that there is no difference in the frequency of EPS in atypical and typical antipsychotics. This study aimed to evaluate the expression profile of EPS in atypical and typical antipsychotics treatment using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of EPS in the JADER database and calculated the reporting odds ratio (ROR) of antipsychotics potentially associated with EPS. We applied the Weibull shape parameter to time-to-event data in the JADER database. Consequently, there was little information to distinguish between the ROR of atypical and typical antipsychotics. A significant difference related to the time of onset of EPS in both antipsychotics was not recognized. However, when comparing each drug, Paliperidone, Perospirone, Blonanserin, and Aripiprazole were relatively developed as EPS in the early stage. On the other hand, Risperidone, Clozapine, Olanzapine, and Quetiapine were developed as EPS not only at an early stage but also after long-term use. In addition, this finding was suggested from the result of the cumulative incidence of EPS in each drug and of the time-to-onset analysis using Weibull distribution. These findings may contribute to future clinical practice because we revealed the expression profile of EPS in treatment with atypical and typical antipsychotics.
[Mh] Termos MeSH primário: Sistemas de Notificação de Reações Adversas a Medicamentos
Antipsicóticos/efeitos adversos
Doenças dos Gânglios da Base/induzido quimicamente
Doenças dos Gânglios da Base/epidemiologia
Mineração de Dados
Bases de Dados como Assunto
[Mh] Termos MeSH secundário: Seres Humanos
Incidência
Japão
Razão de Chances
Receptores de TIE
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); EC 2.7.10.1 (Receptors, TIE)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170105
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.16-00219


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[PMID]:27569719
[Au] Autor:Mishra SR; Parmar MS; Yadav VP; Reshma R; Bharati J; Bharti MK; Paul A; Chouhan VS; Taru Sharma G; Singh G; Sarkar M
[Ad] Endereço:Physiology & Climatology Division, Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
[Ti] Título:Expression and localization of angiopoietin family in corpus luteum during different stages of oestrous cycle and modulatory role of angiopoietins on steroidogenesis, angiogenesis and survivability of cultured buffalo luteal cells.
[So] Source:Reprod Domest Anim;51(6):855-869, 2016 Dec.
[Is] ISSN:1439-0531
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The objective of this study was to document the expression and localization of angiopoietin (ANGPT) family members comprising of angiopoietin (ANGPT1 and ANGPT2), and their receptors (Tie1 and Tie2) in buffalo corpus luteum (CL) obtained from different stages of the oestrous cycle, and the modulatory role of ANGPT1 and ANGPT2 alone or in combinations on progesterone (P ) secretion and mRNA expression of phosphotidylinositide-3kinase-protein kinase B (PI3K-AKT), phosphoinositide-dependent kinase (PDK), protein kinase B (AKT), Bcl2 associated death promoter (BAD), caspase 3 and von willebrand factor (vWF) in luteal cells obtained from midluteal phase (MLP) of oestrous cycle in buffalo. Real-time RT-PCR (qPCR), Western blot and immunohistochemistry were applied to investigate mRNA expression, protein expression and localization of examined factors whereas, the P secretion was assessed by RIA. The mRNA and protein expression of ANGPT1 and Tie2 was maximum (p < .05) in mid luteal phase (MLP) of oestrous cycle. The ANGPT2 mRNA and protein expression was maximum (p < .05) in early luteal phase, decreased in MLP and again increased in late luteal phase of oestrous cycle. ANGPT family members were localized in luteal cells and endothelial cells with a stage specific immunoreactivity. P secretion was highest (p < .05) with 100 ng/ml at 72 hr when luteal cells were treated with either protein alone. The mRNA expression of PDK, AKT and vWF was highest (p < .05) and BAD along with caspase 3 were lowest (p < .05) at 100 ng/ml at 72 hr of incubation period, when cultured luteal cells were treated with either protein alone or in combination. To conclude, our study explores the steroidogenic potential of angiopoietins to promote P secretion, luteal cell survival and angiogenesis through an autocrine and paracrine actions in buffalo CL.
[Mh] Termos MeSH primário: Angiopoietinas/metabolismo
Búfalos/fisiologia
Corpo Lúteo/metabolismo
Ciclo Estral/fisiologia
Neovascularização Fisiológica/fisiologia
Progesterona/metabolismo
[Mh] Termos MeSH secundário: Angiopoietinas/genética
Animais
Western Blotting
Caspase 3/genética
Caspase 3/metabolismo
Sobrevivência Celular/fisiologia
Células Cultivadas
Feminino
Regulação da Expressão Gênica/fisiologia
Células Lúteas/fisiologia
Fosfatidilinositóis/genética
Fosfatidilinositóis/metabolismo
Progesterona/genética
Transporte Proteico
Proteínas Proto-Oncogênicas c-akt/genética
Proteínas Proto-Oncogênicas c-akt/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Receptores de TIE/genética
Receptores de TIE/metabolismo
Proteína de Morte Celular Associada a bcl/genética
Proteína de Morte Celular Associada a bcl/metabolismo
Fator de von Willebrand/genética
Fator de von Willebrand/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiopoietins); 0 (Phosphatidylinositols); 0 (RNA, Messenger); 0 (bcl-Associated Death Protein); 0 (von Willebrand Factor); 4G7DS2Q64Y (Progesterone); EC 2.7.10.1 (Receptors, TIE); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170406
[Lr] Data última revisão:
170406
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160830
[St] Status:MEDLINE
[do] DOI:10.1111/rda.12739


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[PMID]:25959206
[Au] Autor:Xing Y; Su TT; Ruohola-Baker H
[Ad] Endereço:Department of Biochemistry, Institute for Stem Cell &Regenerative Medicine, University of Washington, Seattle Washington 98109, USA.
[Ti] Título:Tie-mediated signal from apoptotic cells protects stem cells in Drosophila melanogaster.
[So] Source:Nat Commun;6:7058, 2015 May 11.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Many types of normal and cancer stem cells are resistant to killing by genotoxins, but the mechanism for this resistance is poorly understood. Here we show that adult stem cells in Drosophila melanogaster germline and midgut are resistant to ionizing radiation (IR) or chemically induced apoptosis and dissect the mechanism for this protection. We find that upon IR the receptor tyrosine kinase Tie/Tie-2 is activated, leading to the upregulation of microRNA bantam that represses FOXO-mediated transcription of pro-apoptotic Smac/DIABLO orthologue, Hid in germline stem cells. Knockdown of the IR-induced putative Tie ligand, Pvf1, a functional homologue of human Angiopoietin, in differentiating daughter cells renders germline stem cells sensitive to IR, suggesting that the dying daughters send a survival signal to protect their stem cells for future repopulation of the tissue. If conserved in cancer stem cells, this mechanism may provide therapeutic options for the eradication of cancer.
[Mh] Termos MeSH primário: Apoptose/fisiologia
Drosophila melanogaster/metabolismo
Regulação Enzimológica da Expressão Gênica/fisiologia
Receptores de TIE/metabolismo
Células-Tronco/fisiologia
[Mh] Termos MeSH secundário: Animais
Deleção de Genes
Radiação Ionizante
Receptor TIE-2
Receptores de TIE/genética
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.7.10.1 (Receptor, TIE-2); EC 2.7.10.1 (Receptors, TIE)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150512
[St] Status:MEDLINE
[do] DOI:10.1038/ncomms8058


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[PMID]:25670042
[Au] Autor:Lai CW; Duh QY; Chen CW; Chuang FJ; Chang YJ; Lin MT; Wu MH
[Ad] Endereço:Department of Surgery, Buddhist Tzu Chi General Hospital, Taipei branch, Taipei, Taiwan.
[Ti] Título:VEGF-D and A Preoperative Serum Levels Predict Nodal and Distant Metastases in Differentiated Thyroid Cancer Patients.
[So] Source:World J Surg;39(7):1742-9, 2015 Jul.
[Is] ISSN:1432-2323
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Preoperative tumor aggressiveness biomarkers may help surgeons decide the extent of an operation. However, whether serum angiogenetic factors can be used to predict the prognosis of patients with differentiated thyroid cancer is still unclear. METHODS: Seventy-six DTC patients were prospectively recruited. Preoperative serum samples were collected and measured for Tie-2, Ang-1, Ang-2, VEGF-A, and VEGF-D levels. The potential correlations between their serum levels and clinicopathologic features as well as their prognoses were analyzed. RESULTS: Older age (>45 years old) and higher VEGF-A serum levels were independent predictors of extrathyroidal extension. The VEGF-D serum level was an independent factor for lymph node metastases and VEGF-A was an independent factor for distant metastases. None of these serum angiogenetic factors were significantly different between patients who were disease free and those with recurrences. The presence of lymph node metastases was the only independent factor for recurrence over the 2-year follow-up. CONCLUSION: Preoperative serum VEGF-A and VEGF-D levels were significantly elevated in DTC patients with distant and lymph node metastases. These findings, when combined with other clinicopathological factors, may help in surgical decisions.
[Mh] Termos MeSH primário: Adenocarcinoma Folicular/patologia
Biomarcadores Tumorais/sangue
Carcinoma Papilar/patologia
Metástase Linfática
Metástase Neoplásica
Neoplasias da Glândula Tireoide/patologia
Fator A de Crescimento do Endotélio Vascular/sangue
Fator D de Crescimento do Endotélio Vascular/sangue
[Mh] Termos MeSH secundário: Adenocarcinoma Folicular/sangue
Adenocarcinoma Folicular/cirurgia
Adolescente
Adulto
Fatores Etários
Idoso
Idoso de 80 Anos ou mais
Angiopoietinas/sangue
Carcinoma Papilar/sangue
Carcinoma Papilar/cirurgia
Criança
Feminino
Seres Humanos
Linfonodos/patologia
Masculino
Meia-Idade
Recidiva Local de Neoplasia/patologia
Prognóstico
Estudos Prospectivos
Receptores de TIE/sangue
Neoplasias da Glândula Tireoide/sangue
Neoplasias da Glândula Tireoide/cirurgia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Angiopoietins); 0 (Biomarkers, Tumor); 0 (VEGFA protein, human); 0 (VEGFD protein, human); 0 (Vascular Endothelial Growth Factor A); 0 (Vascular Endothelial Growth Factor D); EC 2.7.10.1 (Receptors, TIE)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150212
[St] Status:MEDLINE
[do] DOI:10.1007/s00268-015-3016-6


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[PMID]:25466648
[Au] Autor:Hilbert T; Klaschik S
[Ad] Endereço:Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany. Electronic address: thilbert@uni-bonn.de.
[Ti] Título:The angiopoietin/TIE receptor system: Focusing its role for ischemia-reperfusion injury.
[So] Source:Cytokine Growth Factor Rev;26(3):281-91, 2015 Jun.
[Is] ISSN:1879-0305
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ischemia and reperfusion (I/R) are of fatal consequence for the affected organs, as they provoke a profound inflammatory reaction. This thoroughly destroys cells and tissues, inducing functional failure or even complete loss of organ function. Since I/R is primarily a vascular problem, the interaction between the endothelium and the surrounding environment is of great significance. The angiopoietins (ANG) and the TIE receptors are key players for the vascular homeostasis. This review summarizes biochemical and cellular mechanisms leading to I/R injury. After a brief introduction to the ANG/TIE system, a comprehensive overview of its role for the development of I/R syndrome is given. Finally, current therapeutic approaches to mitigate the consequences of I/R by modulating ANG/TIE signaling are reviewed in detail.
[Mh] Termos MeSH primário: Angiopoietinas/metabolismo
Receptores de TIE/metabolismo
Traumatismo por Reperfusão/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Traumatismo por Reperfusão/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Angiopoietins); 0 (Intercellular Signaling Peptides and Proteins); EC 2.7.10.1 (Receptors, TIE)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150525
[Lr] Data última revisão:
150525
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141204
[St] Status:MEDLINE


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[PMID]:25252074
[Au] Autor:Wong GL; Chan HL; Yu Z; Wong CK; Leung C; Ho PP; Chan CY; Chung VC; Chan ZC; Tse YK; Chim AM; Lau TK; Chan HY; Tse CH; Wong VW
[Ad] Endereço:Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.
[Ti] Título:Noninvasive assessments of liver fibrosis with transient elastography and Hui index predict survival in patients with chronic hepatitis B.
[So] Source:J Gastroenterol Hepatol;30(3):582-90, 2015 Mar.
[Is] ISSN:1440-1746
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND AIMS: The prognostic role of noninvasive assessments of liver fibrosis has been evolving. Our aim was to investigate the prognostic value of liver stiffness measurement (LSM) with transient elastography and serum-based Hui index to predict hepatic events and deaths in chronic hepatitis B (CHB) patients. METHODS: The main prospective cohort included 1555 consecutive CHB patients referred for transient elastography examination; a subgroup of 980 patients underwent follow-up assessments at least 3 years later formed the serial cohort. Cox proportional hazard model was performed to determine the relationship of LSM, Hui index and other clinical variables with hepatic events and deaths. RESULTS: During a mean follow-up of 69 ± 9 months, 119 patients (7.6%) developed hepatic events or deaths. Hepatic event-free survival was significantly decreased with increasing stages of LSM and Hui index. The 5-year cumulative probability of hepatic event-free survival of patients of Stage 1-7 of LSM were 99.3%, 98.8%, 95.7%, 90.9%, 89.6%, 74.6%, and 50.0%, respectively; that of Stage 1 to 3 of Hui index were 98.2%, 93.1%, and 77.5%, respectively. Independent predictors of hepatic event-free survival were age, baseline LSM, and follow-up Hui index. Serum ALT and body mass index affected the accuracy of prediction by LSM. Patients remained early stages of LSM or Hui index at follow-up visit had better survival compared to those remained at late stages. CONCLUSION: Baseline and change in noninvasive parameters of liver fibrosis, LSM and Hui index, are accurate to predict hepatic event-free survival in CHB patients.
[Mh] Termos MeSH primário: Técnicas de Imagem por Elasticidade/métodos
Hepatite B Crônica/complicações
Hepatite B Crônica/mortalidade
Cirrose Hepática/diagnóstico
Transaminases/sangue
[Mh] Termos MeSH secundário: Adulto
Fatores Etários
Idoso
Biomarcadores/sangue
Índice de Massa Corporal
Estudos de Coortes
Intervalo Livre de Doença
Feminino
Seguimentos
Seres Humanos
Cirrose Hepática/etiologia
Masculino
Meia-Idade
Valor Preditivo dos Testes
Prognóstico
Modelos de Riscos Proporcionais
Estudos Prospectivos
Receptores de TIE
Índice de Gravidade de Doença
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); EC 2.6.1.- (Transaminases); EC 2.7.10.1 (Receptors, TIE)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140925
[St] Status:MEDLINE
[do] DOI:10.1111/jgh.12779


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[PMID]:25203538
[Au] Autor:Weinl C; Wasylyk C; Garcia Garrido M; Sothilingam V; Beck SC; Riehle H; Stritt C; Roux MJ; Seeliger MW; Wasylyk B; Nordheim A
[Ad] Endereço:Department of Molecular Biology, Interfaculty Institute for Cell Biology, University of Tuebingen, Tuebingen, Germany.
[Ti] Título:Elk3 deficiency causes transient impairment in post-natal retinal vascular development and formation of tortuous arteries in adult murine retinae.
[So] Source:PLoS One;9(9):e107048, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Serum Response Factor (SRF) fulfills essential roles in post-natal retinal angiogenesis and adult neovascularization. These functions have been attributed to the recruitment by SRF of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs) Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown. We generated a new Elk3 knockout mouse line and showed that Elk3 had specific, non-redundant functions in the retinal vasculature. In Elk3(-/-) mice, post-natal retinal angiogenesis was transiently delayed until P8, after which it proceeded normally. Interestingly, tortuous arteries developed in Elk3(-/-) mice from the age of four weeks, and persisted into late adulthood. Tortuous vessels have been observed in human pathologies, e.g. in ROP and FEVR. These human disorders were linked to altered activities of vascular endothelial growth factor (VEGF) in the affected eyes. However, in Elk3(-/-) mice, we did not observe any changes in VEGF or several other potential confounding factors, including mural cell coverage and blood pressure. Instead, concurrent with the post-natal transient delay of radial outgrowth and the formation of adult tortuous arteries, Elk3-dependent effects on the expression of Angiopoietin/Tie-signalling components were observed. Moreover, in vitro microvessel sprouting and microtube formation from P10 and adult aortic ring explants were reduced. Collectively, these results indicate that Elk3 has distinct roles in maintaining retinal artery integrity. The Elk3 knockout mouse is presented as a new animal model to study retinal artery tortuousity in mice and human patients.
[Mh] Termos MeSH primário: Artérias/anormalidades
Instabilidade Articular/patologia
Neovascularização Patológica/patologia
Proteínas Proto-Oncogênicas c-ets/deficiência
Proteínas Proto-Oncogênicas c-ets/genética
Retina/patologia
Neovascularização Retiniana/patologia
Vasos Retinianos/patologia
Dermatopatias Genéticas/patologia
Malformações Vasculares/patologia
[Mh] Termos MeSH secundário: Angiopoietinas/genética
Angiopoietinas/metabolismo
Animais
Artérias/metabolismo
Artérias/patologia
Modelos Animais de Doenças
Feminino
Instabilidade Articular/genética
Instabilidade Articular/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Neovascularização Patológica/genética
Neovascularização Patológica/metabolismo
Receptores de TIE/genética
Receptores de TIE/metabolismo
Retina/metabolismo
Neovascularização Retiniana/genética
Neovascularização Retiniana/metabolismo
Vasos Retinianos/metabolismo
Fator de Resposta Sérica/genética
Fator de Resposta Sérica/metabolismo
Transdução de Sinais/fisiologia
Dermatopatias Genéticas/genética
Dermatopatias Genéticas/metabolismo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Fatores de Crescimento do Endotélio Vascular/genética
Fatores de Crescimento do Endotélio Vascular/metabolismo
Malformações Vasculares/genética
Malformações Vasculares/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Angiopoietins); 0 (Elk3 protein, mouse); 0 (Proto-Oncogene Proteins c-ets); 0 (Serum Response Factor); 0 (Transcription Factors); 0 (Vascular Endothelial Growth Factors); EC 2.7.10.1 (Receptors, TIE)
[Em] Mês de entrada:1505
[Cu] Atualização por classe:150804
[Lr] Data última revisão:
150804
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140910
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0107048


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[PMID]:24658178
[Au] Autor:Zhao J; Chen L; Shu B; Tang J; Zhang L; Xie J; Qi S; Xu Y
[Ad] Endereço:Department of Burns, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
[Ti] Título:Granulocyte/macrophage colony-stimulating factor influences angiogenesis by regulating the coordinated expression of VEGF and the Ang/Tie system.
[So] Source:PLoS One;9(3):e92691, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Granulocyte/macrophage colony-stimulating factor (GM-CSF) can accelerate wound healing by promoting angiogenesis. The biological effects of GM-CSF in angiogenesis and the corresponding underlying molecular mechanisms, including in the early stages of primitive endothelial tubule formation and the later stages of new vessel maturation, have only been partially clarified. This study aimed to investigate the effects of GM-CSF on angiogenesis and its regulatory mechanisms. Employing a self-controlled model (Sprague-Dawley rats with deep partial-thickness burn wounds), we determined that GM-CSF can increase VEGF expression and decrease the expression ratio of Ang-1/Ang-2 and the phosphorylation of Tie-2 in the early stages of the wound healing process, which promotes the degradation of the basement membrane and the proliferation of endothelial cells. At later stages of wound healing, GM-CSF can increase the expression ratio of Ang-1/Ang-2 and the phosphorylation of Tie-2 and maintain a high VEGF expression level. Consequently, pericyte coverages were higher, and the basement membrane became more integrated in new blood vessels, which enhanced the barrier function of blood vessels. In summary, we report here that increased angiogenesis is associated with GM-CSF treatment, and we indicate that VEGF and the Ang/Tie system may act as angiogenic mediators of the healing effect of GM-CSF on burn wounds.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/efeitos dos fármacos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia
Neovascularização Fisiológica/efeitos dos fármacos
Neovascularização Fisiológica/genética
Receptores de TIE/genética
Ribonuclease Pancreático/genética
Fator A de Crescimento do Endotélio Vascular/genética
[Mh] Termos MeSH secundário: Animais
Queimaduras/genética
Queimaduras/metabolismo
Proliferação Celular/efeitos dos fármacos
Células Endoteliais/metabolismo
Metaloproteinase 2 da Matriz/genética
Metaloproteinase 2 da Matriz/metabolismo
Metaloproteinase 9 da Matriz/genética
Metaloproteinase 9 da Matriz/metabolismo
Pericitos/efeitos dos fármacos
Pericitos/metabolismo
Fosforilação
Ratos
Receptores de TIE/metabolismo
Ribonuclease Pancreático/metabolismo
Cicatrização/efeitos dos fármacos
Cicatrização/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Vascular Endothelial Growth Factor A); 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor); EC 2.7.10.1 (Receptors, TIE); EC 3.1.27.- (angiogenin); EC 3.1.27.5 (Ribonuclease, Pancreatic); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[Em] Mês de entrada:1411
[Cu] Atualização por classe:150514
[Lr] Data última revisão:
150514
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140325
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0092691


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[PMID]:24003209
[Au] Autor:Jeltsch M; Leppänen VM; Saharinen P; Alitalo K
[Ad] Endereço:Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, FIN-00014 Helsinki, Finland.
[Ti] Título:Receptor tyrosine kinase-mediated angiogenesis.
[So] Source:Cold Spring Harb Perspect Biol;5(9), 2013 Sep 01.
[Is] ISSN:1943-0264
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The endothelial cell is the essential cell type forming the inner layer of the vasculature. Two families of receptor tyrosine kinases (RTKs) are almost completely endothelial cell specific: the vascular endothelial growth factor (VEGF) receptors (VEGFR1-3) and the Tie receptors (Tie1 and Tie2). Both are key players governing the generation of blood and lymphatic vessels during embryonic development. Because the growth of new blood and lymphatic vessels (or the lack thereof) is a central element in many diseases, the VEGF and the Tie receptors provide attractive therapeutic targets in various diseases. Indeed, several drugs directed to these RTK signaling pathways are already on the market, whereas many are in clinical trials. Here we review the VEGFR and Tie families, their involvement in developmental and pathological angiogenesis, and the different possibilities for targeting them to either block or enhance angiogenesis and lymphangiogenesis.
[Mh] Termos MeSH primário: Desenvolvimento Embrionário/fisiologia
Células Endoteliais/enzimologia
Modelos Biológicos
Neovascularização Patológica/fisiopatologia
Neovascularização Fisiológica/fisiologia
Receptores de TIE/metabolismo
Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo
[Mh] Termos MeSH secundário: Inibidores da Angiogênese/metabolismo
Ligantes
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Ligands); EC 2.7.10.1 (Receptors, TIE); EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
[Em] Mês de entrada:1403
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130905
[St] Status:MEDLINE



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