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  1 / 1606 MEDLINE  
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[PMID]:27776337
[Au] Autor:Chlenski A; Dobratic M; Salwen HR; Applebaum M; Guerrero LJ; Miller R; DeWane G; Solomaha E; Marks JD; Cohn SL
[Ad] Endereço:Department of Pediatrics, University of Chicago, Chicago, IL, USA.
[Ti] Título:Secreted protein acidic and rich in cysteine (SPARC) induces lipotoxicity in neuroblastoma by regulating transport of albumin complexed with fatty acids.
[So] Source:Oncotarget;7(47):77696-77706, 2016 Nov 22.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:SPARC is a matrix protein that mediates interactions between cells and the microenvironment. In cancer, SPARC may either promote or inhibit tumor growth depending upon the tumor type. In neuroblastoma, SPARC is expressed in the stromal Schwannian cells and functions as a tumor suppressor. Here, we developed a novel in vivo model of stroma-rich neuroblastoma using non-tumorigenic SHEP cells with modulated levels of SPARC, mixed with tumorigenic KCNR cells. Tumors with stroma-derived SPARC displayed suppressed growth, inhibited angiogenesis and increased lipid accumulation. Based on the described chaperone function of SPARC, we hypothesized that SPARC binds albumin complexed with fatty acids and transports them to tumors. We show that SPARC binds albumin with Kd=18.9±2.3 uM, and enhances endothelial cell internalization and transendothelial transport of albumin in vitro. We also demonstrate that lipids induce toxicity in neuroblastoma cells and show that lipotoxicity is increased when cells are cultured in hypoxic conditions. Studies investigating the therapeutic potential of SPARC are warranted.
[Mh] Termos MeSH primário: Metabolismo dos Lipídeos/efeitos dos fármacos
Neuroblastoma/metabolismo
Osteonectina/genética
Osteonectina/metabolismo
Ácido Palmítico/farmacologia
Soroalbumina Bovina/metabolismo
[Mh] Termos MeSH secundário: Animais
Hipóxia Celular
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Feminino
Terapia Genética
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Camundongos
Modelos Biológicos
Neuroblastoma/genética
Neuroblastoma/terapia
Ácido Palmítico/química
Soroalbumina Bovina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Osteonectin); 0 (SPARC protein, human); 27432CM55Q (Serum Albumin, Bovine); 2V16EO95H1 (Palmitic Acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.12773


  2 / 1606 MEDLINE  
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[PMID]:29374693
[Au] Autor:Ernst BP; Mikstas C; Stöver T; Stauber R; Strieth S
[Ad] Endereço:Department of Otorhinolaryngology, University Hospital Frankfurt, Frankfurt, Germany benjamin.ernst@unimedizin-mainz.de.
[Ti] Título:Association of eIF4E and SPARC Expression with Lymphangiogenesis and Lymph Node Metastasis in Hypopharyngeal Cancer.
[So] Source:Anticancer Res;38(2):699-706, 2018 02.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Head and neck squamous cell carcinomas (HNSCC) are characterized by aggressiveness, early recurrence and lymph node metastasis. Therefore, there is an urgent need to identify new biomarkers and drug targets. MATERIALS AND METHODS: Neck dissection specimens from 11 patients diagnosed with hypopharyngeal cancer were analyzed for their lymphatic vessel density (LVD) by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunostaining, expression of eukaryotic initiation factor 4E (eIF4E) and levels of secreted protein acidic and rich in cysteine (SPARC) using immunoblot analysis. RESULTS: Compared to lymph node biopsies of healthy controIs, LVD was significantly increased in metastatic lymph nodes as well as in advanced primary tumors. Overexpression of eIF4E and SPARC was demonstrated in all hypopharyngeal cancer specimens. Notably, we observed that increased LVD significantly correlated with the expression of eIF4E as well as SPARC levels. CONCLUSION: eIF4E- and SPARC-associated signaling pathways may be associated with lymphangiogenesis and could be exploited to counteract the spread of hypopharyngeal cancer cells.
[Mh] Termos MeSH primário: Neoplasias Hipofaríngeas/metabolismo
Neoplasias Hipofaríngeas/patologia
Linfangiogênese/fisiologia
Proteínas de Transporte Nucleocitoplasmático/metabolismo
Osteonectina/metabolismo
[Mh] Termos MeSH secundário: Biomarcadores Tumorais/metabolismo
Carcinoma de Células Escamosas/metabolismo
Carcinoma de Células Escamosas/patologia
Feminino
Neoplasias de Cabeça e Pescoço/metabolismo
Neoplasias de Cabeça e Pescoço/patologia
Seres Humanos
Linfonodos/metabolismo
Linfonodos/patologia
Metástase Linfática/patologia
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (EIF4ENIF1 protein, human); 0 (Nucleocytoplasmic Transport Proteins); 0 (Osteonectin); 0 (SPARC protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180129
[St] Status:MEDLINE


  3 / 1606 MEDLINE  
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[PMID]:28463901
[Au] Autor:Matsuo K; Sato K; Suemoto K; Miyamoto-Mikami E; Fuku N; Higashida K; Tsuji K; Xu Y; Liu X; Iemitsu M; Hamaoka T; Tabata I
[Ad] Endereço:1Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu, Shiga, JAPAN; 2Faculty of Health and Sports Science, Juntendo University, Inzai, Chiba, JAPAN; and 3Department of Food Science and Nutrition, The University of Shiga Prefecture, Hikone, Shiga, JAPAN.
[Ti] Título:A Mechanism Underlying Preventive Effect of High-Intensity Training on Colon Cancer.
[So] Source:Med Sci Sports Exerc;49(9):1805-1816, 2017 Sep.
[Is] ISSN:1530-0315
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: We examined effects of high-intensity training on chemically induced aberrant crypt foci (ACF) in rat colon. We also investigated mechanisms that may underlie the results obtained, with a focus on secreted protein acidic and rich in cysteine (SPARC), which has been proposed as an exercise-related factor of colon cancer prevention. METHODS: After an administration of 1,2-dimethylhydrazine, F344 rats executed high-intensity intermittent swimming training (HIIST) (twelve 20-s swimming with a weight [16% body weight] with 10-s pauses between the bouts) 5 d·wk for 4 wk. The acute and chronic effects of the HIIST on SPARC were evaluated in rats. We evaluated the in vitro and in vivo effects of 5' AMP-activated protein kinase (AMPK) activator on SPARC in rat serum and epitrochlearis muscle. In human subjects, we determined serum SPARC after exhaustive bicycling consisting of six to seven bouts of exercise at 170% VË™O2max with 10-s rests between the bouts (high-intensity intermittent bicycling [HIIB]). The SPARC mRNA in human vastus lateralis was measured before and after the HIIB for 4 d·wk for 6 wk (HIIB-training [HIIBT]). RESULTS: The numbers of ACF were lower in the HIIST (47 ± 22) compared with the control (122 ± 47) rats (P < 0.05). SPARC in epitrochlearis and serum after HIIS of the trained rat was higher than that in the control resting rats. In vitro and vivo AMPK stimulation increased mRNA and SPARC protein in rat epitrochlearis, respectively. The human serum SPARC after the HIIB was elevated. SPARC mRNA in human muscle was elevated after the HIIBT. CONCLUSIONS: The results demonstrated that HIIST inhibits 1,2-dimethylhydrazine-induced colon ACF development. This effect may be explained by SPARC induction by the exercise intensity-related factor AMPK, potentially explaining the preventive effects of high-intensity intermittent exercise training against colon cancer.
[Mh] Termos MeSH primário: Neoplasias do Colo/prevenção & controle
Treinamento Intervalado de Alta Intensidade
Músculo Esquelético/metabolismo
Condicionamento Físico Animal/fisiologia
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Animais
Western Blotting
Colo/patologia
Transportador de Glucose Tipo 4/metabolismo
Seres Humanos
Masculino
Proteínas Mitocondriais/metabolismo
Modelos Animais
Osteonectina/metabolismo
Oxirredução
Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
Ratos Endogâmicos F344
Natação/fisiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glucose Transporter Type 4); 0 (Mitochondrial Proteins); 0 (Osteonectin); 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha); 0 (Ppargc1a protein, rat); 0 (SPARC protein, human); 0 (Slc2a4 protein, rat); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1249/MSS.0000000000001312


  4 / 1606 MEDLINE  
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[PMID]:28962925
[Au] Autor:Chen LZ; He CY; Su X; Peng JL; Chen DL; Ye Z; Yang DD; Wang ZX; Wang F; Shao JY; Xu RH
[Ad] Endereço:Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.
[Ti] Título:SPP1 rs4754 and its epistatic interactions with SPARC polymorphisms in gastric cancer susceptibility.
[So] Source:Gene;640:43-50, 2018 Jan 15.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The matricellular glycoprotein products of the SPP1 and SPARC genes play critical roles in many aggressive tumor phenotypes including gastric cancer. We sought to test whether the polymorphisms of these two genes, individually or jointly, influence gastric cancer susceptibility. Nine potentially functional, tagging single nucleotide polymorphisms (tagSNPs) of SPP1 and SPARC were selected and detected using the Kompetitive Allele Specific PCR method in 301 gastric cancer cases and 1441 healthy control subjects. We found that the genotype frequencies of SPP1 rs4754 in gastric cancer were significantly different from those in controls. The rs4754 TT genotype conferred an increased risk of gastric cancer, with unadjusted and adjusted ORs ranging from 1.75 to 1.95 (all P<0.05). The assessment of the effect modifications of sex and age on the genetic effects also confirmed the statistically significant association of the rs4754 TT genotype with increased gastric cancer risk. Epistatic interactions were found between SPP1 rs4754 and SPARC rs1054204, rs3210714 and rs3549 (all P values for interaction<0.05). During the assessment of the epistatic effects between pairs of interacting factors, increased gastric cancer risk was observed in the combined presence of the SPP1 rs4754 TT genotype and the common genotypes of interacting SPARC SNPs, with ORs ranging from 3.94 to 4.41. When the genetic influence of SPP1 rs4754 TT was excluded, the genetic effects of the SPARC rs1054204, rs3210714 and rs3549 common genotypes on gastric cancer susceptibility switched from being risky to beneficial. These data reveal an association between the SPP1 rs4754 polymorphism and altered risk of gastric cancer and highlight an important role of the epistatic effects of SPP rs4754 with SPARC polymorphisms in gastric carcinogenesis. Additional functional experiments and independent large-scale studies, especially in other ethnic populations, are needed to confirm our results.
[Mh] Termos MeSH primário: Epistasia Genética
Osteonectina/genética
Osteopontina/genética
Polimorfismo de Nucleotídeo Único
Neoplasias Gástricas/genética
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Feminino
Predisposição Genética para Doença
Seres Humanos
Masculino
Meia-Idade
Fatores de Risco
Neoplasias Gástricas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Osteonectin); 0 (SPARC protein, human); 0 (SPP1 protein, human); 106441-73-0 (Osteopontin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171001
[St] Status:MEDLINE


  5 / 1606 MEDLINE  
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[PMID]:29040309
[Au] Autor:Suarez-Bregua P; Saxena A; Bronner ME; Rotllant J
[Ad] Endereço:Aquatic Molecular Pathobiology Group, Institute of Marine Research (IIM-CSIC), Vigo, Spain.
[Ti] Título:Targeted Pth4-expressing cell ablation impairs skeletal mineralization in zebrafish.
[So] Source:PLoS One;12(10):e0186444, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Skeletal development and mineralization are essential processes driven by the coordinated action of neural signals, circulating molecules and local factors. Our previous studies revealed that the novel neuropeptide Pth4, synthesized by hypothalamic cells, was involved in bone metabolism via phosphate regulation in adult zebrafish. Here, we investigate the role of pth4 during skeletal development using single-cell resolution, two-photon laser ablation of Pth4:eGFP-expressing cells and confocal imaging in vivo. Using a stable transgenic Pth4:eGFP zebrafish line, we identify Pth4:eGFP-expressing cells as post-mitotic neurons. After targeted ablation of eGFP-expressing cells in the hypothalamus, the experimental larvae exhibited impaired mineralization of the craniofacial bones whereas cartilage development was normal. In addition to a decrease in pth4 transcript levels, we noted altered expression of phex and entpd5, genes associated with phosphate homeostasis and mineralization, as well as a delay in the expression of osteoblast differentiation markers such as sp7 and sparc. Taken together, these results suggest that Pth4-expressing hypothalamic neurons participate in the regulation of bone metabolism, possibly through regulating phosphate balance during zebrafish development.
[Mh] Termos MeSH primário: Calcificação Fisiológica/genética
Calcinose/genética
Hipotálamo/metabolismo
Neurônios/metabolismo
Osteoblastos/metabolismo
Proteína Relacionada ao Hormônio Paratireóideo/genética
Proteínas de Xenopus/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Densidade Óssea
Osso e Ossos/metabolismo
Osso e Ossos/patologia
Calcinose/patologia
Embrião não Mamífero
Regulação da Expressão Gênica no Desenvolvimento
Genes Reporter
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Hipotálamo/crescimento & desenvolvimento
Hipotálamo/lesões
Larva
Terapia a Laser
Neurônios/patologia
Osteoblastos/patologia
Osteogênese/genética
Osteonectina/genética
Osteonectina/metabolismo
Endopeptidase Neutra Reguladora de Fosfato PHEX/genética
Endopeptidase Neutra Reguladora de Fosfato PHEX/metabolismo
Proteína Relacionada ao Hormônio Paratireóideo/metabolismo
Fosfatos/metabolismo
Pirofosfatases/genética
Pirofosfatases/metabolismo
Transdução de Sinais
Fator de Transcrição Sp7
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Proteínas de Xenopus/metabolismo
Peixe-Zebra
Proteínas de Peixe-Zebra/genética
Proteínas de Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Osteonectin); 0 (Osterix protein, zebrafish); 0 (Parathyroid Hormone-Related Protein); 0 (Phosphates); 0 (Pth4 protein, zebrafish); 0 (Sp7 Transcription Factor); 0 (Transcription Factors); 0 (Xenopus Proteins); 0 (Zebrafish Proteins); 147336-22-9 (Green Fluorescent Proteins); EC 3.4.24.- (PHEX Phosphate Regulating Neutral Endopeptidase); EC 3.6.1.- (Entpd5 protein, zebrafish); EC 3.6.1.- (Pyrophosphatases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171018
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186444


  6 / 1606 MEDLINE  
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[PMID]:29025374
[Au] Autor:Park H; Lee Y; Lee H; Kim JW; Hwang JH; Kim J; Yoon YS; Han HS; Kim H
[Ad] Endereço:1 Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
[Ti] Título:The prognostic significance of cancer-associated fibroblasts in pancreatic ductal adenocarcinoma.
[So] Source:Tumour Biol;39(10):1010428317718403, 2017 Oct.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer-associated fibroblasts are abundant in the desmoplastic stroma of pancreatic ductal adenocarcinomas and are considered to play important roles in tumor progression. In this study, we investigated the expression status of secreted protein acidic and rich in cysteine, periostin, fibroblast-activated protein, and the newly developed proCOL11A1 antibody in the stroma of surgically resected pancreatic ductal adenocarcinomas and their prognostic implications. Tissue microarrays were constructed from 155 surgically resected pancreatic ductal adenocarcinomas and paired non-neoplastic pancreata and from another independent set of 48 normal/benign pancreata, and immunohistochemical stains were performed for proCOL11A1, fibroblast-activated protein, secreted protein acidic and rich in cysteine, and periostin. The immunohistochemical stain results were correlated with clinicopathological features and survival data. proCOL11A1, fibroblast-activated protein, secreted protein acidic and rich in cysteine, and periostin expression was significantly increased in the intratumoral stroma of pancreatic ductal adenocarcinomas compared to paired non-neoplastic pancreata (proCOL11A1: 145/155 (93.5%) vs 26/154 (16.9%); fibroblast-activated protein: 139/143 (97.2%) vs 82/132 (62.1%); secreted protein acidic and rich in cysteine: 113/150 (75.3%) vs 49/132 (37.1%); periostin: 135/151 (89.4%) vs 45/135 (33.3%); p < 0.001, all). While the four markers were expressed at lower levels in normal/benign pancreata, there were no significant differences in the expression frequencies among normal pancreas, acute pancreatitis, and chronic pancreatitis. Interestingly, on survival analysis, low intratumoral fibroblast-activated protein cancer-associated fibroblast counts (<100/high-power field) were associated with a significantly reduced overall survival compared to those with high fibroblast-activated protein cancer-associated fibroblast counts (p = 0.010; hazard ratio 5.2 (95% confidence interval 1.3-21.3)). Similar patterns were seen for proCOL11A and secreted protein acidic and rich in cysteine and overall and disease-free survival, although not statistically significant. In conclusion, we demonstrate that the presence of cancer-associated fibroblasts in the tumor stroma may not always be associated with a poor prognosis as suggested in many studies; on the contrary, it may even be associated with prolonged survival, supporting the recent experimental findings that tumor stroma may have a protective role rather than enhance aggressive behavior.
[Mh] Termos MeSH primário: Adenocarcinoma/genética
Carcinoma Ductal Pancreático/genética
Moléculas de Adesão Celular/biossíntese
Colágeno Tipo XI/biossíntese
Gelatinases/biossíntese
Proteínas de Membrana/biossíntese
Osteonectina/biossíntese
Serina Endopeptidases/biossíntese
[Mh] Termos MeSH secundário: Adenocarcinoma/patologia
Adenocarcinoma/cirurgia
Adulto
Idoso
Biomarcadores Tumorais/biossíntese
Biomarcadores Tumorais/genética
Fibroblastos Associados a Câncer/metabolismo
Fibroblastos Associados a Câncer/patologia
Carcinoma Ductal Pancreático/patologia
Carcinoma Ductal Pancreático/cirurgia
Moléculas de Adesão Celular/genética
Colágeno Tipo XI/genética
Intervalo Livre de Doença
Feminino
Gelatinases/genética
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Masculino
Proteínas de Membrana/genética
Meia-Idade
Osteonectina/genética
Prognóstico
Serina Endopeptidases/genética
Análise Serial de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (COL11A1 protein, human); 0 (Cell Adhesion Molecules); 0 (Collagen Type XI); 0 (Membrane Proteins); 0 (Osteonectin); 0 (POSTN protein, human); 0 (SPARC protein, human); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.- (fibroblast activation protein alpha); EC 3.4.24.- (Gelatinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317718403


  7 / 1606 MEDLINE  
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[PMID]:28982537
[Au] Autor:Chioran A; Duncan S; Catalano A; Brown TJ; Ringuette MJ
[Ad] Endereço:Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada M5S 3G5.
[Ti] Título:Collagen IV trafficking: The inside-out and beyond story.
[So] Source:Dev Biol;431(2):124-133, 2017 11 15.
[Is] ISSN:1095-564X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Collagen IV networks endow basement membranes (BMs) with remarkable tensile strength and function as morphoregulatory substrata for diverse tissue-specific developmental events. A complex repertoire of intracellular and extracellular molecular interactions are required for collagen IV secretion and supramolecular assembly into BMs. These include intracellular chaperones such as Heat shock protein 47 (Hsp47) and the chaperone-binding trafficking protein Transport and Golgi organization protein 1 (Tango1). Mutations in these proteins lead to compromised collagen IV protomer stability and secretion, leading to defective BM assembly and function. In addition to intracellular chaperones, a role for extracellular chaperones orchestrating the transport, supramolecular assembly, and architecture of collagen IV in BM is emerging. We present evidence derived from evolutionarily distant model organisms that supports an extracellular collagen IV chaperone-like activity for the matricellular protein SPARC (Secreted Protein, Acidic, Rich in Cysteine). Loss of SPARC disrupts BM homeostasis and compromises tissue biomechanics and physiological function. Thus, the combined contributions of intracellular and extracellular collagen IV-associated chaperones and chaperone-like proteins are critical to ensure proper secretion and stereotypic assembly of collagen IV networks in BMs.
[Mh] Termos MeSH primário: Colágeno Tipo IV/metabolismo
[Mh] Termos MeSH secundário: Animais
Membrana Basal/metabolismo
Evolução Molecular
Seres Humanos
Osteonectina/metabolismo
Dobramento de Proteína
Transporte Proteico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Collagen Type IV); 0 (Osteonectin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE


  8 / 1606 MEDLINE  
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[PMID]:28818666
[Au] Autor:Chen Y; Zhang Y; Tan Y; Liu Z
[Ad] Endereço:Department of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, No.57 Changping Road, Shantou, Guangdong 515041, China; Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China.
[Ti] Título:Clinical significance of SPARC in esophageal squamous cell carcinoma.
[So] Source:Biochem Biophys Res Commun;492(2):184-191, 2017 Oct 14.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is matricellular protein that modulates interactions between cells and the extracellular matrix. The role of SPARC in carcinogenesis is controversialin that SPARC can be a tumor suppressor, but overexpression of SPARC is associated with poorer prognosis. METHODS: We collected 145 esophageal squamous cell carcinoma and adjacent normal tissues in Shantou, a high incidence region for esophageal cancer. The mRNA and protein expression levels of SPARC in cancer tissue and in adjacent normal mucosa were measured by qRT-PCR, western blot and immunohistochemistry (IHC). RESULTS: The mRNA and protein levels of SPARCwere5.78-fold higher in cancer tissues compared with the case-matched normal epithelium. High expression levels of SPARC in ESCC parenchyma, as detected by IHC, were related to lymph node metastasis and poor prognosis (p = 0.049 and p = 0.04). CONCLUSION: High expression of SPARC in the parenchyma may be a potential predictor of prognosis, suggesting SPARC could serve as a therapeutic target in ESCC.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/diagnóstico
Carcinoma de Células Escamosas/patologia
Neoplasias Esofágicas/diagnóstico
Neoplasias Esofágicas/patologia
Esôfago/patologia
Osteonectina/análise
Osteonectina/genética
Regulação para Cima
[Mh] Termos MeSH secundário: Adulto
Idoso
Carcinoma de Células Escamosas/genética
Neoplasias Esofágicas/genética
Esôfago/metabolismo
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Metástase Linfática/diagnóstico
Metástase Linfática/genética
Metástase Linfática/patologia
Masculino
Meia-Idade
Prognóstico
RNA Mensageiro/análise
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Osteonectin); 0 (RNA, Messenger); 0 (SPARC protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE


  9 / 1606 MEDLINE  
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[PMID]:28692738
[Au] Autor:Chong RS; Lee YS; Chu SWL; Toh LZ; Wong TTL
[Ad] Endereço:Singapore National Eye Centre, Singapore 2Singapore Eye Research Institute, Singapore 3Duke NUS Graduate Medical School, Singapore.
[Ti] Título:Inhibition of Monocyte Chemoattractant Protein 1 Prevents Conjunctival Fibrosis in an Experimental Model of Glaucoma Filtration Surgery.
[So] Source:Invest Ophthalmol Vis Sci;58(9):3432-3439, 2017 Jul 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: To evaluate the effect of treatment with monocyte chemoattractant protein-1 receptor inhibitor (MCP-Ri) to maintain bleb survival and prevent fibrosis in an experimental model of glaucoma filtration surgery (GFS). Methods: GFS was performed on one eye of C57/Bl6 mice (n = 36) that was treated with MCP-Ri, mitomycin-C (MMC), or vehicle at the time of surgery. Real-time polymerase chain reaction was used to evaluate conjunctival expression of monocyte chemoattractant protein-1 (MCP-1), TGFB1, TGFB2, collagen 1a1 (Col1a1), sparc (Sparc), and fibronectin at 2 and 7 days following surgery. Anterior segment slit-lamp examination, optical coherence tomography, and confocal microscopy were performed in vivo at day 14. Eyes were processed for immunohistochemical staining of F4/80, a monocyte-macrophage marker, at day 2. In vitro experiments were also performed to compare the effect of MMC, MCP-Ri, and vehicle on the viability of mouse Tenon's fibroblasts. Results: Treatment with MCP-Ri results in a greater reduction in the percentage of F4/80-positive cells in conjunctival blebs and lesser MCP-1 gene expression following experimental GFS than MMC or control. Both MMC and MCP-Ri reduced Col1a1 and Sparc expression, but not fibronectin. TGFB1 decreased with MCP-Ri but not MMC; MMC but not MCP-Ri reduced TGFB2. MMC and MCP-Ri treatment resulted in the preservation of bleb height at day 14, as compared to control. MCP-Ri was less toxic to mouse Tenon's fibroblasts in comparison with MMC. Conclusions: Targeting MCP-1 results in prolonged bleb survival following experimental GFS with less cellular toxicity as compared to MMC. MCP inhibition could provide a safer alternative to conventional antifibrotic adjunctive treatments in GFS.
[Mh] Termos MeSH primário: Antifibrinolíticos/farmacologia
Quimiocina CCL2/antagonistas & inibidores
Túnica Conjuntiva/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
Fibroblastos/efeitos dos fármacos
Fibrose/prevenção & controle
Implantes para Drenagem de Glaucoma
Glaucoma/tratamento farmacológico
Receptores CCR2/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Sobrevivência Celular/efeitos dos fármacos
Quimiocina CCL2/metabolismo
Colágeno/metabolismo
Modelos Animais de Doenças
Fibronectinas/metabolismo
Cirurgia Filtrante
Glaucoma/cirurgia
Camundongos
Camundongos Endogâmicos C57BL
Mitomicina/farmacocinética
Osteonectina/metabolismo
Fator de Crescimento Transformador beta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifibrinolytic Agents); 0 (Chemokine CCL2); 0 (Enzyme Inhibitors); 0 (Fibronectins); 0 (Osteonectin); 0 (Receptors, CCR2); 0 (SPARC protein, mouse); 0 (Transforming Growth Factor beta); 50SG953SK6 (Mitomycin); 9007-34-5 (Collagen)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21480


  10 / 1606 MEDLINE  
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[PMID]:28605029
[Au] Autor:Melstrom LG; Salazar MD; Diamond DJ
[Ad] Endereço:Department of Surgery and Experimental Therapeutics, City of Hope National Medical Center, Duarte, California.
[Ti] Título:The pancreatic cancer microenvironment: A true double agent.
[So] Source:J Surg Oncol;116(1):7-15, 2017 Jul.
[Is] ISSN:1096-9098
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The tumor microenvironment in pancreatic cancer is a complex balance of pro- and anti-tumor components. The dense desmoplasia consists of immune cells, extracellular matrix, growth factors, cytokines, and cancer associated fibroblasts (CAF) or pancreatic stellate cells (PSC). There are a multitude of targets including hyaluronan, angiogenesis, focal adhesion kinase (FAK), connective tissue growth factor (CTGF), CD40, chemokine (C-X-C motif) receptor 4 (CXCR-4), immunotherapy, and Vitamin D. The developing clinical therapeutics will be reviewed.
[Mh] Termos MeSH primário: Neoplasias Pancreáticas/patologia
Microambiente Tumoral
[Mh] Termos MeSH secundário: Adenocarcinoma/tratamento farmacológico
Adenocarcinoma/patologia
Inibidores da Angiogênese/farmacologia
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia
Linfócitos T CD4-Positivos/patologia
Linfócitos T CD8-Positivos/patologia
Fibroblastos Associados a Câncer/patologia
Carcinogênese
Transformação Celular Neoplásica
Ensaios Clínicos como Assunto
Fator de Crescimento do Tecido Conjuntivo/antagonistas & inibidores
Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores
Proteínas Hedgehog/antagonistas & inibidores
Seres Humanos
Ácido Hialurônico/metabolismo
Imunoterapia
Macrófagos/patologia
Células Mieloides/patologia
Neutrófilos/patologia
Osteonectina/antagonistas & inibidores
Neoplasias Pancreáticas/tratamento farmacológico
Células Estreladas do Pâncreas/patologia
Vitamina D/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Angiotensin II Type 1 Receptor Blockers); 0 (Hedgehog Proteins); 0 (Osteonectin); 0 (SPARC protein, human); 139568-91-5 (Connective Tissue Growth Factor); 1406-16-2 (Vitamin D); 9004-61-9 (Hyaluronic Acid); EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1002/jso.24643



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