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[PMID]:29238190
[Au] Autor:Salade L; Wauthoz N; Deleu M; Vermeersch M; De Vriese C; Amighi K; Goole J
[Ad] Endereço:Laboratoire de Pharmacie Galénique et de Biopharmacie, Université libre de Bruxelles (ULB), Brussels.
[Ti] Título:Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia.
[So] Source:Int J Nanomedicine;12:8531-8543, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:The aim of the present study was to develop a ghrelin-containing formulation based on liposomes coated with chitosan intended for nose-brain delivery for the treatment of cachexia. Among the three types of liposomes developed, anionic liposomes provided the best results in terms of encapsulation efficiency (56%) and enzymatic protection against trypsin (20.6% vs 0% for ghrelin alone) and carboxylesterase (81.6% vs 17.2% for ghrelin alone). Ghrelin presented both electrostatic and hydrophobic interactions with the anionic lipid bilayer, as demonstrated by isothermal titration calorimetry. Then, anionic liposomes were coated with -(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride. The coating involved a size increment from 146.9±2.7 to 194±6.1 nm, for uncoated and coated liposomes, respectively. The ζ-potential was similarly increased from -0.3±1.2 mV to 6±0.4 mV before and after coating, respectively. Chitosan provided mucoadhesion, with an increase in mucin adsorption of 22.9%. Enhancement of permeation through the Calu3 epithelial monolayer was also observed with 10.8% of ghrelin recovered in the basal compartment in comparison to 0% for ghrelin alone. Finally, aerosols generated from two nasal devices (VP3 and SP270) intended for aqueous dispersion were characterized with either coated or uncoated liposomes. Contrarily to the SP270 device, VP3 device showed minor changes between coated and uncoated liposome aerosols, as shown by their median volume diameters of 38.4±5.76 and 37.6±5.74 µm, respectively. Overall, the results obtained in this study show that the developed formulation delivered by the VP3 device can be considered as a potential candidate for nose-brain delivery of ghrelin.
[Mh] Termos MeSH primário: Caquexia/tratamento farmacológico
Sistemas de Liberação de Medicamentos/métodos
Grelina/administração & dosagem
Lipossomos/administração & dosagem
Lipossomos/química
[Mh] Termos MeSH secundário: Administração Intranasal/instrumentação
Adsorção
Aerossóis/química
Encéfalo/efeitos dos fármacos
Quitosana/análogos & derivados
Quitosana/química
Estabilidade de Medicamentos
Grelina/química
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Mucinas/metabolismo
Compostos de Amônio Quaternário/química
Eletricidade Estática
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aerosols); 0 (Ghrelin); 0 (Liposomes); 0 (Mucins); 0 (N-(2-hydroxypropyl)-3-trimethylammonium chitosan); 0 (Quaternary Ammonium Compounds); 9012-76-4 (Chitosan)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S147650


  2 / 11475 MEDLINE  
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[PMID]:29315346
[Au] Autor:Carvalho SB; Moreira AS; Gomes J; Carrondo MJT; Thornton DJ; Alves PM; Costa J; Peixoto C
[Ad] Endereço:iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.
[Ti] Título:A detection and quantification label-free tool to speed up downstream processing of model mucins.
[So] Source:PLoS One;13(1):e0190974, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mucins are high-molecular weight glycoproteins (0.25-20 MDa) containing one or more domains that are heavily O-glycosylated. Their implications as targets for cancer treatment have increased the interest in these glycoproteins, mainly in the fields of vaccines and antibodies. However, mucins present high heterogeneity, posing challenges that affect purification processes and quality control analysis. In that sense, it is necessary to develop and improve downstream processes and analytical methods to characterize these products. Here a tool based on biolayer interferometry analysis to improve mucin's detection and quantification in a fast, simple and label free-way is presented. Taking advantage of lectin recognition of mucins' carbohydrate structures, several lectins were evaluated and immobilized on streptavidin biosensors. Different assay conditions were optimized and the most suitable lectin, Aleuria aurantia lectin (AAL), was selected. Bovine Submaxillary Gland and human MUC5B mucins were used as proof of concept and were successfully detected and quantified at different stages of purification. High sensitivity levels were achieved with LOD and LOQ of 3.8 µg mL-1 and 11.7 µg mL-1 for BSM, and 0.2 µg mL-1 and 0.6 µg mL-1 for MUC5B. AAL binding specificity was also confirmed with fucose competition assays. Our method represents an advance on mucins detection and quantification since the existing methods present several disadvantages for process development. Hereafter, it can be applied to the optimization of new or already established downstream processes for mucins' purification.
[Mh] Termos MeSH primário: Modelos Moleculares
Mucinas/metabolismo
[Mh] Termos MeSH secundário: Cromatografia em Gel
Eletroforese em Gel de Poliacrilamida
Glicosilação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Mucins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190974


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[PMID]:29309434
[Au] Autor:Ohneck EJ; Arivett BA; Fiester SE; Wood CR; Metz ML; Simeone GM; Actis LA
[Ad] Endereço:Department of Microbiology, Miami University, Oxford, OH, United States of America.
[Ti] Título:Mucin acts as a nutrient source and a signal for the differential expression of genes coding for cellular processes and virulence factors in Acinetobacter baumannii.
[So] Source:PLoS One;13(1):e0190599, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The capacity of Acinetobacter baumannii to persist and cause infections depends on its interaction with abiotic and biotic surfaces, including those found on medical devices and host mucosal surfaces. However, the extracellular stimuli affecting these interactions are poorly understood. Based on our previous observations, we hypothesized that mucin, a glycoprotein secreted by lung epithelial cells, particularly during respiratory infections, significantly alters A. baumannii's physiology and its interaction with the surrounding environment. Biofilm, virulence and growth assays showed that mucin enhances the interaction of A. baumannii ATCC 19606T with abiotic and biotic surfaces and its cytolytic activity against epithelial cells while serving as a nutrient source. The global effect of mucin on the physiology and virulence of this pathogen is supported by RNA-Seq data showing that its presence in a low nutrient medium results in the differential transcription of 427 predicted protein-coding genes. The reduced expression of ion acquisition genes and the increased transcription of genes coding for energy production together with the detection of mucin degradation indicate that this host glycoprotein is a nutrient source. The increased expression of genes coding for adherence and biofilm biogenesis on abiotic and biotic surfaces, the degradation of phenylacetic acid and the production of an active type VI secretion system further supports the role mucin plays in virulence. Taken together, our observations indicate that A. baumannii recognizes mucin as an environmental signal, which triggers a response cascade that allows this pathogen to acquire critical nutrients and promotes host-pathogen interactions that play a role in the pathogenesis of bacterial infections.
[Mh] Termos MeSH primário: Acinetobacter baumannii/patogenicidade
Genes Bacterianos
Mucinas/metabolismo
Virulência/genética
[Mh] Termos MeSH secundário: Células A549
Acinetobacter baumannii/genética
Acinetobacter baumannii/crescimento & desenvolvimento
Biofilmes
Interações Hospedeiro-Patógeno
Seres Humanos
Microscopia Eletrônica de Transmissão
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Análise de Sequência de RNA
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Mucins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190599


  4 / 11475 MEDLINE  
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[PMID]:29192828
[Au] Autor:Randell SH; Zeldin DC
[Ad] Endereço:1 Department of Cell Biology and Physiology.
[Ti] Título:A Slippery Cause of a Slimy Problem: Mucin Induction by an Esterified Lipid.
[So] Source:Am J Respir Cell Mol Biol;57(6):633-634, 2017 12.
[Is] ISSN:1535-4989
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Asma/metabolismo
Bronquite Crônica/metabolismo
Fibrose Cística/metabolismo
Células Caliciformes/metabolismo
Ácidos Hidroxieicosatetraenoicos/metabolismo
Fibrose Pulmonar Idiopática/metabolismo
Mucinas/biossíntese
[Mh] Termos MeSH secundário: Animais
Asma/patologia
Bronquite Crônica/patologia
Fibrose Cística/patologia
Células Caliciformes/patologia
Seres Humanos
Fibrose Pulmonar Idiopática/patologia
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 (Hydroxyeicosatetraenoic Acids); 0 (Mucins); 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1165/rcmb.2017-0275ED


  5 / 11475 MEDLINE  
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[PMID]:28458352
[Au] Autor:Matsuda T; Hiraoka S; Urashima H; Ogura A; Ishida T
[Ad] Endereço:Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University.
[Ti] Título:Preparation of an Ultrafine Rebamipide Ophthalmic Suspension with High Transparency.
[So] Source:Biol Pharm Bull;40(5):665-674, 2017.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:A 2% commercially available, milky-white, rebamipide micro-particle suspension is used to treat dry eyes, and it causes short-term blurring of the patient's vision. In the current study, to improve the transparency of a rebamipide suspension, we attempted to obtain a clear rebamipide suspension by transforming the rebamipide particles to an ultrafine state. In the initial few efforts, various rebamipide suspensions were prepared using a neutralizing crystallization method with additives, but the suspensions retained their opaque quality. However, as a consequence of several critical improvements in the neutralizing crystallization methods such as selection of additives for crystallization, process parameters during crystallization, the dispersion method, and dialysis, we obtained an ultrafine rebamipide suspension (2%) that was highly transparent (transmittance at 640 nm: 59%). The particle size and transparency demonstrated the fewest level of changes at 25°C after 3 years, compared to initial levels. During that period, no obvious particle sedimentation was observed. The administration of this ultrafine rebamipide suspension (2%) increased the conjunctival mucin, which was comparable to the commercially available micro-particle suspension (2%). The corneal and conjunctival concentration of rebamipide following ocular administration of the ultrafine suspension was slightly higher than that of the micro-particle suspension. The ultrafine rebamipide suspension (eye-drop formulation) with a highly transparent ophthalmic clearness should improve a patient's QOL by preventing even a shortened period of blurred vision.
[Mh] Termos MeSH primário: Alanina/análogos & derivados
Antiulcerosos/administração & dosagem
Antiulcerosos/química
Soluções Oftálmicas/química
Quinolonas/administração & dosagem
Quinolonas/química
[Mh] Termos MeSH secundário: Administração Oftálmica
Alanina/administração & dosagem
Alanina/química
Animais
Túnica Conjuntiva/efeitos dos fármacos
Túnica Conjuntiva/metabolismo
Córnea/efeitos dos fármacos
Córnea/metabolismo
Cristalização
Diálise
Masculino
Mucinas/metabolismo
Tamanho da Partícula
Coelhos
Suspensões
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Ulcer Agents); 0 (Mucins); 0 (Ophthalmic Solutions); 0 (Quinolones); 0 (Suspensions); LR583V32ZR (rebamipide); OF5P57N2ZX (Alanine)
[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:170502
[St] Status:MEDLINE
[do] DOI:10.1248/bpb.b16-00962


  6 / 11475 MEDLINE  
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[PMID]:29236729
[Au] Autor:Sveen LR; Grammes FT; Ytteborg E; Takle H; Jørgensen SM
[Ad] Endereço:Department of Biology, Section of Marine Developmental Biology, University of Bergen (UiB), Bergen, Norway.
[Ti] Título:Genome-wide analysis of Atlantic salmon (Salmo salar) mucin genes and their role as biomarkers.
[So] Source:PLoS One;12(12):e0189103, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to identify potential mucin genes in the Atlantic salmon genome and evaluate tissue-specific distribution and transcriptional regulation in response to aquaculture-relevant stress conditions in post-smolts. Seven secreted gel-forming mucin genes were identified based on several layers of evidence; annotation, transcription, phylogeny and domain structure. Two genes were annotated as muc2 and five genes as muc5. The muc2 genes were predominantly transcribed in the intestinal region while the different genes in the muc5 family were mainly transcribed in either skin, gill or pyloric caeca. In order to investigate transcriptional regulation of mucins during stress conditions, two controlled experiments were conducted. In the first experiment, handling stress induced mucin transcription in the gill, while transcription decreased in the skin and intestine. In the second experiment, long term intensive rearing conditions (fish biomass ~125 kg/m3) interrupted by additional confinement led to increased transcription of mucin genes in the skin at one, seven and fourteen days post-confinement.
[Mh] Termos MeSH primário: Biomarcadores/metabolismo
Genoma
Mucinas/genética
Salmão/genética
[Mh] Termos MeSH secundário: Animais
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Mucins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189103


  7 / 11475 MEDLINE  
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[PMID]:28468886
[Au] Autor:Sharma S; Carlsson B; Czakó R; Vene S; Haglund M; Ludvigsson J; Larson G; Hammarström L; Sosnovtsev SV; Atmar RL; Green KY; Estes MK; Svensson L
[Ad] Endereço:Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
[Ti] Título:Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades.
[So] Source:J Virol;91(14), 2017 Jul 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby to lead to immune evasion. To address this hypothesis, we measured the ability of human sera collected between 1979 and 2010 to block glycan binding of four pandemic GII.4 noroviruses isolated in the last 4 decades. In total, 268 sera were investigated for 50% blocking titer (BT ) values of virus-like particles (VLPs) against pig gastric mucin (PGM) using 4 VLPs that represent different GII.4 norovirus variants identified between 1987 and 2012. Pre- and postpandemic sera (sera collected before and after isolation of the reference NoV strain) efficiently prevented binding of VLP strains MD145 (1987), Grimsby (1995), and Houston (2002), but not the Sydney (2012) strain, to PGM. No statistically significant difference in virus-blocking titers was observed between pre- and postpandemic sera. Moreover, paired sera showed that blocking titers of ≥160 were maintained over a 6-year period against MD145, Grimsby, and Houston VLPs. Significantly higher serum blocking titers (geometric mean titer [GMT], 1,704) were found among IgA-deficient individuals than among healthy blood donors (GMT, 90.9) ( < 0.0001). The observation that prepandemic sera possess robust blocking capacity for viruses identified decades later suggests a common attachment factor, at least until 2002. Our results indicate that serum IgG possesses antibody-blocking capacity and that blocking titers can be maintained for at least 6 years against 3 decades of pandemic GII.4 NoV. Human noroviruses (NoVs) are the major cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) in saliva and gut recognize NoV and are the proposed ligands that facilitate infection. Polymorphisms in HBGA genes, and in particular a nonsense mutation in (G428A), result in resistance to global dominating GII.4 NoV. The emergence of new pandemic GII.4 strains occurs at intervals of several years and is proposed to be attributable to epochal evolution, including amino acid changes and immune evasion. However, it remains unclear whether exposure to a previous pandemic strain stimulates immunity to a pandemic strain identified decades later. We found that prepandemic sera possess robust virus-blocking capacity against viruses identified several decades later. We also show that serum lacking IgA antibodies is sufficient to block NoV VLP binding to HBGAs. This is essential, considering that 1 in every 600 Caucasian children is IgA deficient.
[Mh] Termos MeSH primário: Anticorpos Bloqueadores/sangue
Infecções por Caliciviridae/imunologia
Infecções por Caliciviridae/virologia
Mucinas/metabolismo
Norovirus/imunologia
Norovirus/fisiologia
Ligação Viral
[Mh] Termos MeSH secundário: Adulto
Idoso
Genótipo
Seres Humanos
Meia-Idade
Norovirus/classificação
Norovirus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Blocking); 0 (Mucins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


  8 / 11475 MEDLINE  
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[PMID]:29187936
[Au] Autor:Danquah KO; Adjei E; Quayson S; Adankwah E; Gyamfi D; Ossei PPS; Dzikunu G; Mensah P; Lepkor C
[Ad] Endereço:Department of Medical Laboratory Technology, Faculty of Allied Health Sciences, Kwame Nkrumah University of Science & Technology, Kumasi, Ghana.
[Ti] Título:Mucin expression patterns in histological grades of colonic cancers in Ghanaian population.
[So] Source:Pan Afr Med J;27:267, 2017.
[Is] ISSN:1937-8688
[Cp] País de publicação:Uganda
[La] Idioma:eng
[Ab] Resumo:Introduction: Myriad roles of mucins in normal tissues have been well documented, including lubrication of the epithelial surfaces; protection from physical damage; facilitation in cell-cell signaling and suppression of inflammatory activity. Pathological expression of mucins has been noted in cancer development and progression. This study sought to identify and quantify the types of mucins produced during various histological grades of colon cancer and to assess the diagnostic significance. Methods: Formalin fixed, paraffin-embedded tissue blocks, comprising three (3) normal colon and twenty-two (22) colon cancer tissues, were retrieved from the archives of the histopathology department of the Komfo Anokye Teaching Hospital. They were stained with Haematoxylin and eosin (H&E) for diagnosis and grading of tumours. Tissues were pre-digested with diastase and stained with Alcian blue (pH 2.5)/Periodic Acid Schiff to characterize the mucin variants present. Results: Our findings indicated that normal colonic tissues expressed exceptionally high amount of acid mucin and low amount of neutral mucin. However, there was a general decrease in mucin expression in colon cancers compared to normal colon tissues. Additional findings suggested that as cancer progresses from low grade to high grade of adenocarcinoma of the colon, there was generally a considerable decrease in the acid mucin production and an increase in the neutral mucin expression. In contrast, a sizeable subpopulation of high-grade adenocarcinomas of colon showed a rather opposite mucin expression pattern- increase in acid mucin and a decrease in neutral mucin. Conclusion: As colonic cancer progresses, there are corresponding changes in the mucin types and content such that there are decrease in acid mucin and increase in neutral mucin expressions.
[Mh] Termos MeSH primário: Adenocarcinoma/patologia
Neoplasias do Colo/patologia
Mucinas/genética
[Mh] Termos MeSH secundário: Adenocarcinoma/diagnóstico
Adenocarcinoma/genética
Neoplasias do Colo/diagnóstico
Neoplasias do Colo/genética
Progressão da Doença
Regulação Neoplásica da Expressão Gênica
Gana
Hospitais de Ensino
Seres Humanos
Concentração de Íons de Hidrogênio
Gradação de Tumores
Coloração e Rotulagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mucins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.11604/pamj.2017.27.267.9793


  9 / 11475 MEDLINE  
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[PMID]:29187496
[Au] Autor:Shibata H; Ohike N; Norose T; Isobe T; Suzuki R; Imai H; Shiokawa A; Aoki T; Murakami M; Mizukami H; Tanaka JI; Takimoto M
[Ad] Endereço:Department of Pathology, Showa University Hospital, Tokyo, Japan hshibata@med.showa-u.ac.jp.
[Ti] Título:Mucinous Cystic Neoplasms Lined by Abundant Mucinous Epithelium Frequently Involve KRAS Mutations and Malignant Progression.
[So] Source:Anticancer Res;37(12):7063-7068, 2017 12.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Pancreatic and hepatic mucinous cyst neoplasms (MCNs) have a malignant potential, but indolent MCNs are not uncommon. MATERIALS AND METHODS: The pathological and genetic characteristics of resected MCNs (n=15) categorized by the amount of mucin of the lining epithelium were investigated. RESULTS: MCNs were divided into two groups: (i) a rich (r)-MCN group (n=6), in which more than half of the epithelium was lined by abundant mucinous epithelium; and (ii) a poor (p)-MCN group (n=9), which consisted of the remaining cases. Three patients in the r-MCN group showed invasive carcinoma or high-grade dysplasia, whereas all patients in the p-MCN group showed low-grade dysplasia. Mutations of Kirsten rat sarcoma viral oncogene homolog (KRAS) were more frequent in the r-MCN group (83%) (p-MCN; 11%, p<0.05). CONCLUSION: Mucinous MCNs more frequently have KRAS mutations and higher risk of malignant progression.
[Mh] Termos MeSH primário: Epitélio/metabolismo
Neoplasias Hepáticas/genética
Mutação
Neoplasias Císticas, Mucinosas e Serosas/genética
Neoplasias Pancreáticas/genética
Proteínas Proto-Oncogênicas p21(ras)/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Progressão da Doença
Epitélio/patologia
Feminino
Seres Humanos
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Masculino
Meia-Idade
Mucinas/metabolismo
Neoplasias Císticas, Mucinosas e Serosas/metabolismo
Neoplasias Císticas, Mucinosas e Serosas/patologia
Neoplasias Pancreáticas/metabolismo
Neoplasias Pancreáticas/patologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (KRAS protein, human); 0 (Mucins); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171211
[Lr] Data última revisão:
171211
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE


  10 / 11475 MEDLINE  
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[PMID]:28745318
[Au] Autor:Ye J; Wei X; Shang Y; Pan Q; Yang M; Tian Y; He Y; Peng Z; Chen L; Chen W; Wang R
[Ad] Endereço:Department of Gastroenterology, Institute of Gastroenterology of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China.
[Ti] Título:Core 3 mucin-type O-glycan restoration in colorectal cancer cells promotes MUC1/p53/miR-200c-dependent epithelial identity.
[So] Source:Oncogene;36(46):6391-6407, 2017 Nov 16.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The attachment of cell-surface carbohydrates to proteins mediated by the amino acids serine or threonine (O-glycan) is involved in tumor metastasis; the roles of O-glycans vary depending on their structure, but the detailed mechanisms by which O-glycans trigger signaling to control tumor metastasis are largely unknown. In this study, we found that the reduced expression of core 3 synthase correlated with metastasis to lymph nodes and distant organs, resulting in poor prognosis for colorectal cancer (CRC) patients. Mechanically, we revealed that mucin-type core 3 O-glycan was synthesized at the membrane-tethered MUC1 N terminus because of core 3 synthase expression in colon cancer cells. This further inhibited the translocation of MUC1-C to the nucleus, initiated p53 gene transcription that was dependent on the inhibition of MUC1-C nucleus translocation, activated p53-mediated miR-200c expression and resulted in mesenchymal-epithelial transition (MET). Inhibition of MUC1 via small interfering RNA (siRNA) in re-expressed core 3 synthase colon cancer cells further inhibited MUC1-C nucleus translocation, increased p53 and miR-200c expression, and enhanced MET. However, inhibition of p53 via siRNA or miR-200c via miR-200c inhibitor in re-expressed core 3 synthase colon cancer cells promoted the epithelial-mesenchymal transition (EMT) in a reversible manner. Core 3 synthase mRNA levels and the p53 mRNA levels or miR-200c levels in the colon cancerous samples were positively correlated. Our findings suggest a novel mechanism linking mucin-type core 3 O-glycan to the EMT-MET plasticity of CRC cells via MUC1/p53/miR-200c-dependent signaling cascade and shed light on therapeutic strategies to treat this malignancy.
[Mh] Termos MeSH primário: Neoplasias Colorretais/genética
Transição Epitelial-Mesenquimal/genética
MicroRNAs/genética
Mucina-1/genética
Polissacarídeos/metabolismo
Proteína Supressora de Tumor p53/genética
[Mh] Termos MeSH secundário: Western Blotting
Células CACO-2
Linhagem Celular Tumoral
Núcleo Celular/metabolismo
Neoplasias Colorretais/metabolismo
Neoplasias Colorretais/patologia
Regulação Neoplásica da Expressão Gênica
Células HCT116
Células HT29
Seres Humanos
MicroRNAs/metabolismo
Mucina-1/metabolismo
Mucinas/metabolismo
N-Acetilglucosaminiltransferases/genética
N-Acetilglucosaminiltransferases/metabolismo
Transporte Proteico
Interferência de RNA
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN200 microRNA, human); 0 (MUC1 protein, human); 0 (MicroRNAs); 0 (Mucin-1); 0 (Mucins); 0 (Polysaccharides); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); EC 2.4.1.- (N-Acetylglucosaminyltransferases); EC 2.4.1.- (UDP-GlcNAc GalNAc-peptide beta1,3-N-acetylglucosaminyltransferase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171201
[Lr] Data última revisão:
171201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.241



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