Base de dados : MEDLINE
Pesquisa : D08.811.277.656.300.480.525 [Categoria DeCS]
Referências encontradas : 8700 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 870 ir para página                         

  1 / 8700 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29304073
[Au] Autor:Saito J; Yokoyama U; Nicho N; Zheng YW; Ichikawa Y; Ito S; Umemura M; Fujita T; Ito S; Taniguchi H; Asou T; Masuda M; Ishikawa Y
[Ad] Endereço:Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan.
[Ti] Título:Tissue-type plasminogen activator contributes to remodeling of the rat ductus arteriosus.
[So] Source:PLoS One;13(1):e0190871, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: The ductus arteriosus (DA) closes after birth to adapt to the robust changes in hemodynamics, which require intimal thickening (IT) to occur. The smooth muscle cells of the DA have been reported to play important roles in IT formation. However, the roles of the endothelial cells (ECs) have not been fully investigated. We herein focused on tissue-type plasminogen activator (t-PA), which is a DA EC dominant gene, and investigated its contribution to IT formation in the DA. METHODS AND RESULTS: ECs from the DA and aorta were isolated from fetal rats using fluorescence-activated cell sorting. RT-PCR showed that the t-PA mRNA expression level was 2.7-fold higher in DA ECs than in aortic ECs from full-term rat fetuses (gestational day 21). A strong immunoreaction for t-PA was detected in pre-term and full-term rat DA ECs. t-PA-mediated plasminogen-plasmin conversion activates gelatinase matrix metalloproteinases (MMPs). Gelatin zymography revealed that plasminogen supplementation significantly promoted activation of the elastolytic enzyme MMP-2 in rat DA ECs. In situ zymography demonstrated that marked gelatinase activity was observed at the site of disruption in the internal elastic laminae (IEL) in full-term rat DA. In a three-dimensional vascular model, EC-mediated plasminogen-plasmin conversion augmented the IEL disruption. In vivo administration of plasminogen to pre-term rat fetuses (gestational day 19), in which IT is poorly formed, promoted IEL disruption accompanied by gelatinase activation and enhanced IT formation in the DA. Additionally, experiments using five human DA tissues demonstrated that the t-PA expression level was 3.7-fold higher in the IT area than in the tunica media. t-PA protein expression and gelatinase activity were also detected in the IT area of the human DAs. CONCLUSION: t-PA expressed in ECs may help to form IT of the DA via activation of MMP-2 and disruption of IEL.
[Mh] Termos MeSH primário: Canal Arterial/patologia
Ativador de Plasminogênio Tecidual/fisiologia
[Mh] Termos MeSH secundário: Animais
Canal Arterial/enzimologia
Células Endoteliais/metabolismo
Feminino
Gelatinases/metabolismo
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Metaloproteinases da Matriz/metabolismo
Plasminogênio/administração & dosagem
Gravidez
Interferência de RNA
Ratos
Ratos Wistar
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Ativador de Plasminogênio Tecidual/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
9001-91-6 (Plasminogen); EC 3.4.21.68 (Tissue Plasminogen Activator); EC 3.4.24.- (Gelatinases); EC 3.4.24.- (Matrix Metalloproteinases)
[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:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190871


  2 / 8700 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27779444
[Au] Autor:Salimi A; Roudkenar MH; Sadeghi L; Mohseni A; Seydi E; Pirahmadi N; Pourahmad J
[Ad] Endereço:a Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences , Tehran , Iran ; Department of Pharmacology and Toxicology , School of Pharmacy, Ardabil University of Medical Science , Ardabil , Iran ; Students Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Scie
[Ti] Título:Selective Anticancer Activity of Acacetin Against Chronic Lymphocytic Leukemia Using Both In Vivo and In Vitro Methods: Key Role of Oxidative Stress and Cancerous Mitochondria.
[So] Source:Nutr Cancer;68(8):1404-1416, 2016 Nov-Dec.
[Is] ISSN:1532-7914
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The present study investigates the in vitro and in vivo effect of acacetin (4'-methoxy-5,7-dihydroxyflavone) on chronic lymphocytic leukemia (CLL) B-lymphocytes and mitochondria. CLL B-lymphocytes and healthy B-lymphocytes were obtained from CLL patients and healthy donors, respectively. Mitochondria were isolated from B-lymphocytes of both groups. Xenografts in severe combined immune deficient mice were used to examine the toxicity and anti CLL activity of acacetin. We evaluated and compared the mechanism of action of acacetin on CLL and healthy B-lymphocytes and their mitochondria. We have found that acacetin (10 µM) can selectively induce apoptosis on CLL B-lymphocyte (25% at 24 h) by directly targeting mitochondria, through increased reactive oxygen species (ROS) formation, MMP collapse, MPT, release of cytochrome c, caspase 3 activation, and finally apoptosis, while sparing normal healthy B-lymphocytes unaffected at similar concentrations. Besides, oral administration of acacetin showed a potent in vivo anticancer activity in CLL xenograft mouse models. Our in vivo findings indicate that acacetin accumulates and kills CLL B-lymphocyte in a rather selective way through targeting cancerous mitochondria and ROS formation, which ends in CLL therapy. Finally, we can recommend acacetin as a promising compound for further drug development assays for the CLL treatment.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Flavonas/farmacologia
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/patologia
[Mh] Termos MeSH secundário: Idoso
Animais
Antineoplásicos/farmacologia
Linfócitos B/efeitos dos fármacos
Linfócitos B/patologia
Citocromos c/metabolismo
Seres Humanos
Leucemia Linfocítica Crônica de Células B/patologia
Metaloproteinases da Matriz/metabolismo
Camundongos SCID
Meia-Idade
Estresse Oxidativo/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Flavones); 0 (Reactive Oxygen Species); 9007-43-6 (Cytochromes c); EC 3.4.24.- (Matrix Metalloproteinases); KWI7J0A2CC (acacetin)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE


  3 / 8700 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28455451
[Au] Autor:Okamura H; Emrich F; Trojan J; Chiu P; Dalal AR; Arakawa M; Sato T; Penov K; Koyano T; Pedroza A; Connolly AJ; Rabinovitch M; Alvira C; Fischbein MP
[Ad] Endereço:Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
[Ti] Título:Long-term miR-29b suppression reduces aneurysm formation in a Marfan mouse model.
[So] Source:Physiol Rep;5(8), 2017 Apr.
[Is] ISSN:2051-817X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aortic root aneurysm formation and subsequent dissection and/or rupture remain the leading cause of death in patients with Marfan syndrome. Our laboratory has reported that miR-29b participates in aortic root/ascending aorta extracellular matrix remodeling during early aneurysm formation in Marfan mice. Herein, we sought to determine whether miR-29b suppression can reduce aneurysm formation long-term. Marfan mice were treated with retro-orbital LNA-anti-miR-29b inhibitor or scrambled-control-miR before aneurysms develop either (1) a single dose prenatally (pregnant mice at 14.5 days post-coitum) ( = 8-10, each group) or (2) postnatally every other week, from 2 to 22 weeks of age, and sacrificed at 24 weeks ( = 8-10, each group). To determine if miR-29b blockade was beneficial even after aneurysms develop, a third group of animals were treated every other week, starting at 8 weeks of age, until sacrificed ( = 4-6, each group). miR-29b inhibition resulted in aneurysm reduction, increased elastogenesis, decreased matrix metalloproteinase activity and decreased elastin breakdown. Prenatal LNA-anti-miR-29b inhibitor treatment decreased aneurysm formation up to age 32 weeks, whereas postnatal treatment was effective up to 16 weeks. miR-29b blockade did not slow aortic growth once aneurysms already developed. Systemic miR-29b inhibition significantly reduces aneurysm development long-term in a Marfan mouse model. Drug administration during aortic wall embryologic development appears fundamental. miR-29b suppression could be a potential therapeutic target for reducing aneurysm formation in Marfan syndrome patients.
[Mh] Termos MeSH primário: Aneurisma Aórtico/prevenção & controle
Terapia Genética/métodos
Síndrome de Marfan/terapia
MicroRNAs/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Aneurisma Aórtico/diagnóstico por imagem
Aneurisma Aórtico/etiologia
Aneurisma Aórtico/patologia
Modelos Animais de Doenças
Progressão da Doença
Ecocardiografia
Elastina/metabolismo
Matriz Extracelular/fisiologia
Feminino
Terapias Fetais/métodos
Masculino
Síndrome de Marfan/complicações
Síndrome de Marfan/genética
Metaloproteinases da Matriz/fisiologia
Camundongos Endogâmicos C57BL
Camundongos Mutantes
Terapia de Alvo Molecular/métodos
Cuidado Pré-Natal/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN29 microRNA, mouse); 0 (MicroRNAs); 9007-58-3 (Elastin); EC 3.4.24.- (Matrix Metalloproteinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  4 / 8700 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28471417
[Au] Autor:Neuhaus J; Schiffer E; Mannello F; Horn LC; Ganzer R; Stolzenburg JU
[Ad] Endereço:Department of Urology, Research Laboratory, University of Leipzig, Liebigstraße 19, 04103 Leipzig, Germany. jochen.neuhaus@medizin.uni-leipzig.de.
[Ti] Título:Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers-An Explorative Concept Study.
[So] Source:Int J Mol Sci;18(5), 2017 May 04.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Previously, we described prostate cancer (PCa) detection (83% sensitivity; 67% specificity) in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of larger seminal proteins, predominantly semenogelin 1 and 2, representing endpoints of the ejaculate liquefaction. Here we identified proteases putatively involved in PCa specific protein cleavage, and examined gene expression and tissue protein levels, jointly with cell localization in normal prostate (nP), benign prostate hyperplasia (BPH), seminal vesicles and PCa using qPCR, Western blotting and confocal laser scanning microscopy. We found differential gene expression of chymase (CMA1), matrix metalloproteinases (MMP3, MMP7), and upregulation of MMP14 and tissue inhibitors (TIMP1 and TIMP2) in BPH. In contrast tissue protein levels of MMP14 were downregulated in PCa. MMP3/TIMP1 and MMP7/TIMP1 ratios were decreased in BPH. In seminal vesicles, we found low-level expression of most proteases and, interestingly, we also detected TIMP1 and low levels of TIMP2. We conclude that MMP3 and MMP7 activity is different in PCa compared to BPH due to fine regulation by their inhibitor TIMP1. Our findings support the concept of seminal plasma biomarkers as non-invasive tool for PCa detection and risk stratification.
[Mh] Termos MeSH primário: Biomarcadores/metabolismo
Metaloproteinases da Matriz/metabolismo
Neoplasias da Próstata/metabolismo
Sêmen/enzimologia
[Mh] Termos MeSH secundário: Idoso
Estudos de Casos e Controles
Quimases/genética
Quimases/metabolismo
Seres Humanos
Masculino
Metaloproteinases da Matriz/genética
Meia-Idade
Estudo de Prova de Conceito
Neoplasias da Próstata/patologia
Inibidor Tecidual de Metaloproteinase-1/genética
Inibidor Tecidual de Metaloproteinase-1/metabolismo
Inibidor Tecidual de Metaloproteinase-2/genética
Inibidor Tecidual de Metaloproteinase-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (TIMP1 protein, human); 0 (TIMP2 protein, human); 0 (Tissue Inhibitor of Metalloproteinase-1); 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2); EC 3.4.21.39 (Chymases); EC 3.4.24.- (Matrix Metalloproteinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


  5 / 8700 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29309889
[Au] Autor:Barisic A; Devic Pavlic S; Ostojic S; Pereza N
[Ad] Endereço:Department of Biology and Medical Genetics, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. Electronic address: anita.barisic@uniri.hr.
[Ti] Título:Matrix metalloproteinase and tissue inhibitors of metalloproteinases gene polymorphisms in disorders that influence fertility and pregnancy complications: A systematic review and meta-analysis.
[So] Source:Gene;647:48-60, 2018 Mar 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) gene polymorphisms have been extensively evaluated as predisposing factors to human reproductive disorders. However, the evidence available is inconsistent. Therefore, we performed a systematic review and meta-analysis to provide the first comprehensive synopsis of case-control studies that investigated the association of MMP and TIMP gene polymorphisms with disorders that influence fertility and pregnancy complications. Literature search was performed using PubMed and Scopus databases. We included 42 case-control studies in the systematic review for the following disorders: adenomyosis, endometriosis, hypertensive disorders of pregnancy, preterm birth and recurrent spontaneous abortion. Although a large number of MMP and TIMP gene polymorphisms were tested, no exclusive and unambiguous risk factors were identified for any of the disorders. The majority of statistically significant associations were confirmed in just one study. Additionally, we performed two meta-analyses for MMP9 rs3918242 polymorphism in endometriosis/adenomyosis and preeclampsia but found no association with either disorder. Considering the modest associations and conflicting results between individual case-control studies, new data is needed for further research of this subject.
[Mh] Termos MeSH primário: Fertilidade/genética
Predisposição Genética para Doença/genética
Metaloproteinases da Matriz/genética
Polimorfismo de Nucleotídeo Único/genética
Complicações na Gravidez/genética
Inibidores Teciduais de Metaloproteinases/genética
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Feminino
Frequência do Gene/genética
Seres Humanos
Gravidez
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Tissue Inhibitor of Metalloproteinases); EC 3.4.24.- (Matrix Metalloproteinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  6 / 8700 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27770804
[Au] Autor:Natarajan K; Gottipati KR; Berhane K; Samten B; Pendurthi U; Boggaram V
[Ad] Endereço:Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX, 75708-3154, USA.
[Ti] Título:Proteases and oxidant stress control organic dust induction of inflammatory gene expression in lung epithelial cells.
[So] Source:Respir Res;17(1):137, 2016 10 22.
[Is] ISSN:1465-993X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Persistant inflammatory responses to infectious agents and other components in organic dust underlie lung injury and development of respiratory diseases. Organic dust components responsible for eliciting inflammation and the mechanisms by which they cause lung inflammation are not fully understood. We studied the mechanisms by which protease activities in poultry dust extracts and intracellular oxidant stress induce inflammatory gene expression in A549 and Beas2B lung epithelial cells. METHODS: The effects of dust extracts on inflammatory gene expression were analyzed by quantitative polymerase chain reaction (qPCR), enzyme linked immunosorbent (ELISA) and western blot assays. Oxidant stress was probed by dihydroethidium (DHE) labeling, and immunostaining for 4-hydroxynonenal (4-HNE). Effects on interleukin-8 (IL-8) promoter regulation were determined by transient transfection assay. RESULTS: Dust extracts contained trypsin and elastase activities, and activated protease activated receptor (PAR)-1 and -2. Serine protease inhibitors and PAR-1 or PAR-2 knockdown suppressed inflammatory gene induction. Dust extract induction of IL-8 gene expression was associated with increased DHE-fluorescence and 4-HNE staining, and antioxidants suppressed inflammatory gene induction. Protease inhibitors and antioxidants suppressed protein kinase C and NF-κB activation and induction of IL-8 promoter activity in cells exposed to dust extract. CONCLUSIONS: Our studies demonstrate that proteases and intracellular oxidants control organic dust induction of inflammatory gene expression in lung epithelial cells. Targeting proteases and oxidant stress may serve as novel approaches for the treatment of organic dust induced lung diseases. This is the first report on the involvement of oxidant stress in the induction of inflammatory gene expression by organic dust.
[Mh] Termos MeSH primário: Poeira
Células Epiteliais/efeitos dos fármacos
Mediadores da Inflamação/metabolismo
Pulmão/efeitos dos fármacos
Compostos Orgânicos/toxicidade
Estresse Oxidativo/efeitos dos fármacos
Peptídeo Hidrolases/metabolismo
Pneumonia/induzido quimicamente
[Mh] Termos MeSH secundário: Células A549
Animais
Anti-Inflamatórios/farmacologia
Antioxidantes/farmacologia
Células Epiteliais/enzimologia
Regulação da Expressão Gênica
Abrigo para Animais
Seres Humanos
Exposição por Inalação/efeitos adversos
Interleucina-8/genética
Interleucina-8/metabolismo
Pulmão/enzimologia
Metaloproteinases da Matriz/genética
Metaloproteinases da Matriz/metabolismo
Pneumonia/enzimologia
Pneumonia/genética
Pneumonia/prevenção & controle
Aves Domésticas
Receptor PAR-1/genética
Receptor PAR-1/metabolismo
Receptor PAR-2/genética
Receptor PAR-2/metabolismo
Inibidores de Serino Proteinase/farmacologia
Transdução de Sinais/efeitos dos fármacos
Fatores de Tempo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Antioxidants); 0 (Dust); 0 (IL8 protein, human); 0 (Inflammation Mediators); 0 (Interleukin-8); 0 (Organic Chemicals); 0 (Receptor, PAR-1); 0 (Receptor, PAR-2); 0 (Serine Proteinase Inhibitors); EC 3.4.- (Peptide Hydrolases); EC 3.4.24.- (Matrix Metalloproteinases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  7 / 8700 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29186705
[Au] Autor:Chelluboina B; Nalamolu KR; Mendez GG; Klopfenstein JD; Pinson DM; Wang DZ; Veeravalli KK
[Ad] Endereço:Departments of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA.
[Ti] Título:Mesenchymal Stem Cell Treatment Prevents Post-Stroke Dysregulation of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases.
[So] Source:Cell Physiol Biochem;44(4):1360-1369, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Stem cell treatment is one of the potential treatment options for ischemic stroke. We recently demonstrated a protective effect of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in a rat model of ischemic stroke. The treatment attenuated apoptosis and prevented DNA damage. A collection of published studies, including several from our laboratory, indicated the induction and detrimental role for several matrix metalloproteinases (MMPs) in post-stroke brain injury. We hypothesized that the HUCB-MSCs treatment after focal cerebral ischemia prevents the dysregulation of MMPs and induces the expression of endogenous tissue inhibitors of metalloproteinases (TIMPs) to neutralize the elevated activity of MMPs. METHODS: To test our hypothesis, we administered HUCB-MSCs (0.25 million cells/animal and 1 million cells/animal) intravenously via tail vein to male Sprague-Dawley rats that were subjected to a transient (two-hour) right middle cerebral artery occlusion (MCAO) and one-day reperfusion. Ischemic brain tissues obtained from various groups of rats seven days after reperfusion were subjected to real-time PCR, immunoblot, and immunofluorescence analysis. RESULTS: HUCB-MSCs treatment prevented the induction of MMPs, which were upregulated in ischemia-induced rats that received no treatment. HUCB-MSCs treatment also prevented the induction of TIMPs expression. The extent of prevention of MMPs and TIMPs induction by HUCB-MSCs treatment is similar at both the doses tested. CONCLUSION: Prevention of stroke-induced MMPs upregulation after HUCB-MSCs treatment is not mediated through TIMPs upregulation.
[Mh] Termos MeSH primário: Metaloproteinases da Matriz/metabolismo
Transplante de Células-Tronco Mesenquimais
Acidente Vascular Cerebral/terapia
Inibidores Teciduais de Metaloproteinases/metabolismo
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Sangue Fetal/citologia
Masculino
Metaloproteinases da Matriz/genética
Células Mesenquimais Estromais/citologia
Células Mesenquimais Estromais/metabolismo
Microscopia de Fluorescência
Artéria Cerebral Média/lesões
Ratos
Ratos Sprague-Dawley
Inibidores Teciduais de Metaloproteinases/genética
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tissue Inhibitor of Metalloproteinases); EC 3.4.24.- (Matrix Metalloproteinases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1159/000485533


  8 / 8700 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28464560
[Au] Autor:Wilkinson DJ; Habgood A; Lamb HK; Thompson P; Hawkins AR; Désilets A; Leduc R; Steinmetzer T; Hammami M; Lee MS; Craik CS; Watson S; Lin H; Milner JM; Rowan AD
[Ad] Endereço:Newcastle University, Newcastle upon Tyne, UK.
[Ti] Título:Matriptase Induction of Metalloproteinase-Dependent Aggrecanolysis In Vitro and In Vivo: Promotion of Osteoarthritic Cartilage Damage by Multiple Mechanisms.
[So] Source:Arthritis Rheumatol;69(8):1601-1611, 2017 08.
[Is] ISSN:2326-5205
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To assess the ability of matriptase, a type II transmembrane serine proteinase, to promote aggrecan loss from the cartilage of patients with osteoarthritis (OA) and to determine whether its inhibition can prevent aggrecan loss and cartilage damage in experimental OA. METHODS: Aggrecan release from human OA cartilage explants and human stem cell-derived cartilage discs was evaluated, and cartilage-conditioned media were used for Western blotting. Gene expression was analyzed by real-time polymerase chain reaction. Murine OA was induced by surgical destabilization of the medial meniscus, and matriptase inhibitors were administered via osmotic minipump or intraarticular injection. Cartilage damage was scored histologically and aggrecan cleavage was visualized immunohistochemically using specific neoepitope antibodies. RESULTS: The addition of soluble recombinant matriptase promoted a time-dependent release of aggrecan (and collagen) from OA cartilage, which was sensitive to metalloproteinase inhibition and protease-activated receptor 2 antagonism. Although engineered human (normal) cartilage discs failed to release aggrecan following matriptase addition, both matrix metalloproteinase- and aggrecanase-mediated cleavages of aggrecan were detected in human OA cartilage. Additionally, while matriptase did not directly degrade aggrecan, it promoted the accumulation of low-density lipoprotein receptor-related protein 1 (LRP-1) in conditioned media of the OA cartilage explants. Matriptase inhibition via neutralizing antibody or small molecule inhibitor significantly reduced cartilage damage scores in murine OA, which was associated with reduced generation of metalloproteinase-mediated aggrecan cleavage. CONCLUSION: Matriptase potently induces the release of metalloproteinase-generated aggrecan fragments as well as soluble LRP-1 from OA cartilage. Therapeutic targeting of matriptase proteolytic activity reduces metalloproteinase activity, further suggesting that this serine proteinase may have potential as a disease-modifying therapy in OA.
[Mh] Termos MeSH primário: Agrecanas/efeitos dos fármacos
Cartilagem Articular/efeitos dos fármacos
Osteoartrite do Joelho/metabolismo
Serina Endopeptidases/farmacologia
[Mh] Termos MeSH secundário: Proteína ADAMTS4/efeitos dos fármacos
Proteína ADAMTS4/metabolismo
Proteína ADAMTS5/efeitos dos fármacos
Proteína ADAMTS5/metabolismo
Idoso
Idoso de 80 Anos ou mais
Agrecanas/metabolismo
Animais
Anticorpos Neutralizantes/farmacologia
Western Blotting
Cartilagem Articular/metabolismo
Cartilagem Articular/patologia
Endopeptidases/efeitos dos fármacos
Endopeptidases/metabolismo
Feminino
Perfilação da Expressão Gênica
Seres Humanos
Imuno-Histoquímica
Técnicas In Vitro
Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/efeitos dos fármacos
Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo
Masculino
Metaloproteinases da Matriz/efeitos dos fármacos
Metaloproteinases da Matriz/metabolismo
Proteínas de Membrana/antagonistas & inibidores
Proteínas de Membrana/metabolismo
Meniscos Tibiais/cirurgia
Camundongos
Meia-Idade
Osteoartrite do Joelho/patologia
Reação em Cadeia da Polimerase em Tempo Real
Proteínas Recombinantes/farmacologia
Serina Endopeptidases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aggrecans); 0 (Antibodies, Neutralizing); 0 (Low Density Lipoprotein Receptor-Related Protein-1); 0 (Membrane Proteins); 0 (Recombinant Proteins); EC 3.4.- (Endopeptidases); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.109 (ST14 protein, human); EC 3.4.21.109 (St14 protein, mouse); EC 3.4.24.- (ADAMTS5 Protein); EC 3.4.24.- (Matrix Metalloproteinases); EC 3.4.24.82 (ADAMTS4 Protein); EC 3.4.99.- (aggrecanase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180119
[Lr] Data última revisão:
180119
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/art.40133


  9 / 8700 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29277763
[Au] Autor:Kambayashi Y; Fujimura T; Furudate S; Lyu C; Hidaka T; Kakizaki A; Sato Y; Tanita K; Aiba S
[Ad] Endereço:Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
[Ti] Título:The Expression of Matrix Metalloproteinases in Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-expressing Cancer of Apocrine Origin.
[So] Source:Anticancer Res;38(1):113-120, 2018 01.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive tumor entity. Since there is no conventional therapy for advanced PCAC, exploratory treatments are sometimes used. As we previously reported, receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL)/RANK signaling on M2 macrophages promotes the production of chemokines and proinflammatory cytokines to maintain the immunosuppressive tumor environment of extramammary Paget's disease (EMPD). Since EMPD is a skin adenocarcinoma of apocrine gland origin that expresses high levels of RANKL and matrix metalloproteinase (MMP) 7, and EMPD is associated with the presence of RANK M2 macrophages, we hypothesized that tumor-associated macrophages (TAMs) in adenocarcinomas such as PCAC might also express RANKL and MMP7. MATERIALS AND METHODS: We employed immunohistochemical staining of RANKL and MMP7 in the lesional skin from five patients with PCAC, and microarray analysis of MMPs using human monocyte-derived macrophages. RESULTS: According to DNA microarray analysis, the expression of MMP1 and MMP25 was augmented. The DNA microarray results were verified by using real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining of MMP1 and MMP25 as well as chemokine (C-C motif) ligand (CCL) 5 in the lesional skin from five patients with PCAC showed a substantial number of MMP1-bearing cells and MMP25-bearing cells, as well as CCL5-producing cells, that were distributed in the lesional skin. CONCLUSION: Our study suggests that the RANKL/RANK pathway contributes to the development and maintenance of the immunosuppressive tumor microenvironment and denosumab may be a promising adjuvant therapy targeting TAMs in cancer of apocrine origin.
[Mh] Termos MeSH primário: Adenocarcinoma/metabolismo
Macrófagos/metabolismo
Metaloproteinases da Matriz/metabolismo
Ligante RANK/metabolismo
Neoplasias Cutâneas/metabolismo
[Mh] Termos MeSH secundário: Glândulas Apócrinas
Quimiocina CCL5/genética
Quimiocina CCL5/metabolismo
Seres Humanos
Metaloproteinases da Matriz/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCL5 protein, human); 0 (Chemokine CCL5); 0 (RANK Ligand); 0 (TNFSF11 protein, human); EC 3.4.24.- (Matrix Metalloproteinases)
[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:171227
[St] Status:MEDLINE


  10 / 8700 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
[PMID]:29061824
[Au] Autor:Chou PY; Lee MM; Lin SY; Sheu MJ
[Ad] Endereço:Department of Nursing, Hung Kuang University, Taichung, Taiwan, R.O.C.
[Ti] Título:Pipoxolan Exhibits Antitumor Activity Toward Oral Squamous Cell Carcinoma Through Reactive Oxygen Species-mediated Apoptosis.
[So] Source:Anticancer Res;37(11):6391-6400, 2017 11.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Pipoxolan is frequently prescribed as a smooth muscle relaxant. Pipoxolan has also been shown to have anticancer activity. Our study investigated whether pipoxolan induced apoptosis in oral squamous cell carcinoma (OSCC). Cell cytotoxicity was evaluated by the MTT assay. Cell apoptosis and cell-cycle distribution were measured by annexin V/propidium iodide (PI) double staining and flow cytometry, respectively. Apoptotic-related proteins were assessed by western blotting. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Following exposure of TW206 OSCC cells to pipoxolan, a time-dependently decrease in MMP and an increase in ROS were observed. However, these effects were significantly abrogated by the free radical scavenger N-acetyl-L-cysteine. Since high levels of ROS were produced early in the treatment, intracellular ROS seemed to play a key role in pipoxolan-induced apoptosis. In HSC-3 OSCC cells, our results demonstrated that pipoxolan treatment caused a time-dependent increase of protein expression of active caspase-3 and -9, cytosolic cytochrome c, cleavage of poly (ADP-ribose) polymerase, and B-cell lymphoma 2 (BCL2)-like protein 4 (BAX). However, expression of BCL2 itself was reduced. Clearly, such an increase in BAX/BCL2 ratio would be associated with apoptosis. In addition, pipoxolan markedly suppressed the protein expression of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and phosphorylation of protein kinase B (AKT). These data suggest that pipoxolan acts against HSC-3 in vitro via intrinsic apoptotic signaling pathways, and inhibition of PI3K/AKT signaling.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Carcinoma de Células Escamosas/metabolismo
Dioxolanos/farmacologia
Neoplasias Bucais/metabolismo
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Apoptose
Proteínas Reguladoras de Apoptose/metabolismo
Carcinoma de Células Escamosas/tratamento farmacológico
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Ensaios de Seleção de Medicamentos Antitumorais
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Metaloproteinases da Matriz/metabolismo
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Neoplasias Bucais/tratamento farmacológico
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Apoptosis Regulatory Proteins); 0 (Dioxolanes); 0 (Reactive Oxygen Species); 493GZJ5T6I (pipoxolan); EC 3.4.24.- (Matrix Metalloproteinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE



página 1 de 870 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde