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[PMID]:29441920
[Ti] Título:Pancreatic lipase and -amylase inhibitory activities of plants used in Traditional Chinese Medicine (TCM).
[So] Source:Pharmazie;71(7):420-424, 2016 Jul 07.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:To find new, plant based drugs for the treatment of obesity and/or diabetes mellitus type 2 through the inhibition of essential digestive enzymes, in vitro tests were carried out on selected plants or fungi with weight-reducing, blood glucose-reducing or related potential, used in Traditional Chinese Medicine (TCM). Aqueous and methanolic extracts of 32 Chinese herbal medicines were assayed for their in vitro inhibitory activity against pancreatic lipase (PL) and α-amylase (PA). PL activity was measured by using an enzymatic in vitro assay based on the hydrolysis kinetics of an oleate ester of 4-methylumbelliferone. For the determination of α-amylase activity an enzyme assay based on the hydrolytic cleavage of a modified starch derivative was used. Our findings have shown that the methanolic extract of Lycopus lucidus Turcz. var. hirtus Regel (Lamiaceae) was a very effective PL inhibitor (IC50: 88.3±4.1 µg/mL). A high anti-amylase activity showed the methanolic extract of Trichosanthes kirilowii Maxim. (Curcurbitaceae, IC50: 248.8±67.3 µg/mL). This work provides a priority list of interesting plants for further study with respect to the treatment of obesity and associated metabolic diseases.
[Mh] Termos MeSH primário: Lipase/antagonistas & inibidores
Pâncreas/enzimologia
Plantas/química
alfa-Amilases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Fungos/química
Hidrólise
Himecromona/química
Cinética
Lycopus/química
Medicina Tradicional Chinesa
Pâncreas/efeitos dos fármacos
Extratos Vegetais/farmacologia
Trichosanthes/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Extracts); 3T5NG4Q468 (Hymecromone); EC 3.1.1.3 (Lipase); EC 3.2.1.1 (alpha-Amylases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6569


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[PMID]:29244613
[Au] Autor:Susini V; Rossi VL; Sanesi A; Drazek L
[Ad] Endereço:a Department of Chemistry Ugo Schiff, University of Florence , Florence , Italy.
[Ti] Título:Kinetics study on recombinant alkaline phosphatase and correlation with the generated fluorescent signal.
[So] Source:J Immunoassay Immunochem;39(1):108-118, 2018.
[Is] ISSN:1532-4230
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Alkaline phosphatase (AP) (EC 3.1.3.1) is one of the most commonly used enzymes in immunoassays. In VIDAS® assays (bioMérieux, Marcy l'Etoile, France), AP catalyzes the hydrolysis of 4-methylumbelliferyl phosphate (4-MUP) in 4-methylumbelliferone (4-MU) producing a fluorescent signal. This work introduces an original method of characterization of the kinetic parameters K , V and K of AP embedded in VIDAS® assays. Assessment of such constants allows us to predict the fluorescent signal generated for given amounts of enzyme and its associated substrate; in the particular case of VIDAS®, it has been estimated that 0.06 nmol/L of AP produces 3144 Relative Fluorescent Values (RFV). ABBREVIATIONS: 4-MUP, 4-Methylumbelliferyl phosphate; 4-MU, 4-Methylumbelliferone; RFV, Relative Fluorescent Values; RFU, Relative Fluorescent Units; QDs, Quantum Dots; LoD, Limit of Detection.
[Mh] Termos MeSH primário: Fosfatase Alcalina/metabolismo
Fluorescência
[Mh] Termos MeSH secundário: Fosfatase Alcalina/química
Biocatálise
Ensaio de Imunoadsorção Enzimática
Hidrólise
Himecromona/análogos & derivados
Himecromona/química
Himecromona/metabolismo
Cinética
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Recombinant Proteins); 3368-04-5 (4-methylumbelliferyl phosphate); 3T5NG4Q468 (Hymecromone); EC 3.1.3.1 (Alkaline Phosphatase)
[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:171216
[St] Status:MEDLINE
[do] DOI:10.1080/15321819.2017.1408022


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[PMID]:29227082
[Au] Autor:Olkhovych NV
[Ti] Título:Chitotriosidase activity as additional biomarker in the diagnosis of lysosomal storage diseases.
[So] Source:Ukr Biochem J;88(1):69-78, 2016 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:To date, several genetic variants that lead to a deficiency of chitotriosidase activity have been described. The duplication of 24 bp (dup24bp) in exon 10 of the CHIT1 gene, which causes a complete loss of enzymatic activity of the gene product, is the most common among the European population. The aim of the study was to evaluate the possibility of using chitotriosidase activity as an additional biomarker in diagnosis of lysosomal storage diseases (LSDs) in Ukraine, to determine this parameter in blood plasma of the patients with various lysosomal diseases and to assess the effect of the presence of dup24bp in the CHIT1 gene on this parameter. It has been shown that chitotriosidase activity in blood plasma is a convenient additional biochemical marker in the diagnosis of some LSDs, namely Gaucher disease, Niemann-Pick disease A, B, C and GM1-gangliosidosis. Reference ranges of the normal chitotriosidase activity were determined in blood plasma of Ukrainian population and found to be 8.0-53.1 nmol 4-methylumbelliferone/h·ml of plasma. The total allele frequency of the dup24bp in the CHIT1 gene in Ukrainian population was determined, which amounted to 0.26 (323/1244) that is higher than in European population. It was indicated that moleculargenetic screening of dup24bp in the CHIT1 gene is a necessary stage in a protocol for the laboratory diagnosis of Gaucher disease, Niemann-Pick disease A, B, C as well as GM1-gangliosidosis to avoid incorrect diagnosis.
[Mh] Termos MeSH primário: Gangliosidose GM1/genética
Doença de Gaucher/genética
Frequência do Gene
Hexosaminidases/genética
Doenças de Niemann-Pick/genética
[Mh] Termos MeSH secundário: Adulto
Alelos
Biomarcadores/metabolismo
Estudos de Casos e Controles
Éxons
Feminino
Gangliosidose GM1/classificação
Gangliosidose GM1/diagnóstico
Gangliosidose GM1/patologia
Doença de Gaucher/diagnóstico
Doença de Gaucher/patologia
Duplicação Gênica
Expressão Gênica
Testes Genéticos
Hexosaminidases/sangue
Hexosaminidases/deficiência
Seres Humanos
Himecromona/sangue
Masculino
Doenças de Niemann-Pick/classificação
Doenças de Niemann-Pick/diagnóstico
Doenças de Niemann-Pick/patologia
Ucrânia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 3T5NG4Q468 (Hymecromone); EC 3.2.1.- (Hexosaminidases); EC 3.2.1.- (chitotriosidase)
[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:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.069


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[PMID]:28972965
[Au] Autor:Morera DS; Hennig MS; Talukder A; Lokeshwar SD; Wang J; Garcia-Roig M; Ortiz N; Yates TJ; Lopez LE; Kallifatidis G; Kramer MW; Jordan AR; Merseburger AS; Manoharan M; Soloway MS; Terris MK; Lokeshwar VB
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, 1410 Laney Walker Boulevard, Room CN 1177A, Augusta, GA 30912-2100, USA.
[Ti] Título:Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.
[So] Source:Br J Cancer;117(10):1507-1517, 2017 Nov 07.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets. METHODS: Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models. RESULTS: In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial-mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with ß-catenin, Twist and Snail expression, but negatively with E-cadherin expression. CONCLUSIONS: This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Ácido Hialurônico/metabolismo
Neoplasias da Bexiga Urinária/metabolismo
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Transição Epitelial-Mesenquimal/efeitos dos fármacos
Seres Humanos
Himecromona/farmacologia
Estimativa de Kaplan-Meier
Camundongos
Camundongos Nus
Prognóstico
Neoplasias da Bexiga Urinária/mortalidade
Neoplasias da Bexiga Urinária/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 3T5NG4Q468 (Hymecromone); 9004-61-9 (Hyaluronic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171117
[Lr] Data última revisão:
171117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.318


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[PMID]:28710970
[Au] Autor:Grignon C; Dupuis A; Albouy-Llaty M; Condylis M; Barrier L; Carato P; Brunet B; Migeot V; Venisse N
[Ad] Endereço:University of Poitiers, School of Medicine and Pharmacy (Department of Analytical Chemistry, Pharmaceutics and Epidemiology), 6 rue de la Milétrie, 86034 Poitiers Cedex, France; University Hospital of Poitiers, Biology-Pharmacy-Public Health Department, 2 rue de la Milétrie, 86021 Poitiers Cedex, Fr
[Ti] Título:Validation of a probe for assessing deconjugation of glucuronide and sulfate phase II metabolites assayed through LC-MS/MS in biological matrices.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1061-1062:72-78, 2017 Sep 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:LC-MS/MS has been proposed in various areas such as Therapeutic Drug Monitoring (TDM), Human Biomonitoring (HBM), disease diagnosis, clinical toxicology and doping control to identify and quantify chemical parents and their metabolites in biological matrices. To determine the total content of a xenobiotic (unconjugated+conjugated forms), an enzymatic hydrolysis step is required. Most studies in the literature have not controlled the effectiveness of the deconjugation process because no method has been described for that purpose. Therefore the aim of this study was to develop and validate a deconjugation probe using a LC-MS/MS method. In order to estimate deconjugation using ß-glucuronidase and/or sulfatase, 4-methyl-umbelliferone (MU) and its conjugates were used as markers. Glucuronidase/sulfatase was added to plasma or urine spiked with 4-methylumbelliferyl-ß-d-glucuronide (MUG) and 4-methylumbelliferyl sulfate (MUS) and umbelliferone, which was used as the internal standard. After incubation at 37°C during 90min, MU appears as a result of the deconjugation of MUG and MUS. The concentrations of the 3 markers were determined using LC-MS/MS. Trueness and precision of the LC-MS/MS method were determined by quality control analysis at three different levels of concentration covering the whole range of calibration. In both matrices, the analytical method allows quantification of the different compounds, with good linearity, trueness and precision and negligible matrix effects. The method was applied with success to deconjugation assay using active glucuronidase/sulfatase in plasma and urine. The probe developed in this study allows to ensure that enzymatic preparation is working properly in the frame of a quality system.
[Mh] Termos MeSH primário: Cromatografia Líquida/métodos
Monitoramento de Medicamentos/métodos
Glucuronídeos/metabolismo
Sulfatos/metabolismo
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Glucuronídeos/análise
Seres Humanos
Himecromona/análogos & derivados
Limite de Detecção
Modelos Lineares
Reprodutibilidade dos Testes
Sulfatos/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glucuronides); 0 (Sulfates); 25892-63-1 (4-methylumbelliferyl sulfate); 3T5NG4Q468 (Hymecromone); 6160-80-1 (4-methylumbelliferyl glucuronide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170716
[St] Status:MEDLINE


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[PMID]:28282922
[Au] Autor:Kudo D; Suto A; Hakamada K
[Ad] Endereço:Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan. aikopapa@hirosaki-u.ac.jp.
[Ti] Título:The Development of a Novel Therapeutic Strategy to Target Hyaluronan in the Extracellular Matrix of Pancreatic Ductal Adenocarcinoma.
[So] Source:Int J Mol Sci;18(3), 2017 Mar 09.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases to affect humans, regardless of whether patients receive multimodal therapy (including surgery, radiotherapy, and chemotherapy). This resistance to intervention is currently considered to be caused by the desmoplastic change of the extracellular matrix (ECM) in PDAC tissues, which is characterized by the accumulation of cancer-associated fibroblasts, collagen, proteoglycan, and hyaluronan. Among these ECM components, hyaluronan has attracted interest because various studies have indicated that hyaluronan-rich PDAC is correlated with the progressive properties of cancer cells, both in experimental and clinical settings. Hence, the reduction of hyaluronan in cancer tissue may represent a novel therapeutic approach for PDAC. 4-methylumbelliferone (4-MU) is a derivative of coumarin that was reported to suppress the synthesis of hyaluronan in cultured human skin fibroblasts in 1995. As an additional study, our group firstly reported that 4-MU reduced the hyaluronan synthesis of mouse melanoma cells and exerted anti-cancer activity. Subsequently, we have showed that 4-MU inhibited liver metastasis in mice inoculated with human pancreatic cancer cells. Thereafter, 4-MU has been accepted as an effective agent for hyaluronan research and is expected to have clinical applications. This review provides an overview of the interaction between PDAC and hyaluronan, the properties of 4-MU as a suppressor of the synthesis of hyaluronan, and the perspectives of PDAC treatment targeting hyaluronan.
[Mh] Termos MeSH primário: Adenocarcinoma/metabolismo
Antineoplásicos/farmacologia
Matriz Extracelular/metabolismo
Ácido Hialurônico/metabolismo
Neoplasias Pancreáticas/metabolismo
[Mh] Termos MeSH secundário: Adenocarcinoma/tratamento farmacológico
Animais
Antineoplásicos/uso terapêutico
Matriz Extracelular/efeitos dos fármacos
Seres Humanos
Ácido Hialurônico/antagonistas & inibidores
Himecromona/farmacologia
Himecromona/uso terapêutico
Neoplasias Pancreáticas/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 3T5NG4Q468 (Hymecromone); 9004-61-9 (Hyaluronic Acid)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170312
[St] Status:MEDLINE


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[PMID]:28207787
[Au] Autor:Ouyang X; Panetta NJ; Talbott MD; Payumo AY; Halluin C; Longaker MT; Chen JK
[Ad] Endereço:Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, United States of America.
[Ti] Título:Hyaluronic acid synthesis is required for zebrafish tail fin regeneration.
[So] Source:PLoS One;12(2):e0171898, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Using genome-wide transcriptional profiling and whole-mount expression analyses of zebrafish larvae, we have identified hyaluronan synthase 3 (has3) as an upregulated gene during caudal fin regeneration. has3 expression is induced in the wound epithelium within hours after tail amputation, and its onset and maintenance requires fibroblast growth factor, phosphoinositide 3-kinase, and transforming growth factor-ß signaling. Inhibition of hyaluronic acid (HA) synthesis by the small molecule 4-methylumbelliferone (4-MU) impairs tail regeneration in zebrafish larvae by preventing injury-induced cell proliferation. In addition, 4-MU reduces the expression of genes associated with wound epithelium and blastema function. Treatment with glycogen synthase kinase 3 inhibitors rescues 4-MU-induced defects in cell proliferation and tail regeneration, while restoring a subset of wound epithelium and blastema markers. Our findings demonstrate a role for HA biosynthesis in zebrafish tail regeneration and delineate its epistatic relationships with other regenerative processes.
[Mh] Termos MeSH primário: Nadadeiras de Animais/fisiologia
Glucuronosiltransferase/fisiologia
Ácido Hialurônico/fisiologia
Regeneração/genética
Proteínas de Peixe-Zebra/fisiologia
Peixe-Zebra/fisiologia
[Mh] Termos MeSH secundário: Animais
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/genética
Epistasia Genética
Regulação da Expressão Gênica/efeitos dos fármacos
Glucuronosiltransferase/genética
Glucuronosiltransferase/metabolismo
Hialuronan Sintases
Ácido Hialurônico/biossíntese
Himecromona/farmacologia
Regeneração/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
Cicatrização/genética
Peixe-Zebra/metabolismo
Proteínas de Peixe-Zebra/genética
Proteínas de Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Zebrafish Proteins); 3T5NG4Q468 (Hymecromone); 9004-61-9 (Hyaluronic Acid); EC 2.4.1.17 (Glucuronosyltransferase); EC 2.4.1.212 (Hyaluronan Synthases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0171898


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[PMID]:28040269
[Au] Autor:Shinomiya K; Zaima K; Harada Y; Yasue M; Harikai N; Tokura K; Ito Y
[Ad] Endereço:School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan. Electronic address: shinomiya.kazufusa@nihon-u.ac.jp.
[Ti] Título:Comparison of the peak resolution and the stationary phase retention between the satellite and the planetary motions using the coil satellite centrifuge with counter-current chromatographic separation of 4-methylumbelliferyl sugar derivatives.
[So] Source:J Chromatogr A;1481:64-72, 2017 Jan 20.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Coil satellite centrifuge (CSC) produces the complex satellite motion consisting of the triplicate rotation of the coiled column around three axes including the sun axis (the angular velocity, ω ), the planet axis (ω ) and the satellite axis (the central axis of the column) (ω ) according to the following formula: ω =ω +ω . Improved peak resolution in the separation of 4-methylumbelliferyl sugar derivatives was achieved using the conventional multilayer coiled columns with ethyl acetate/1-butanol/water (3: 2: 5, v/v) for the lower mobile phase at the combination of the rotation speeds (ω , ω , ω )=(300, 150, 150rpm), and (1:4:5, v/v) for the upper mobile phase at (300:100:200rpm). The effect of the satellite motion on the peak resolution and the stationary phase retention was evaluated by each CSC separation with the different rotation speeds of ω and ω under the constant revolution speed at ω =300rpm. With the lower mobile phase, almost constant peak resolution and stationary phase retention were yielded regardless of the change of ω and ω , while with the upper mobile phase these two values were sensitively varied according to the different combination of ω and ω . For example, when ω =147 or 200rpm is used, no stationary phase was retained in the coiled column while ω =150rpm could retain enough volume of stationary phase for separation. On the other hand, the combined rotation speeds at (ω , ω , ω )=(300, 300, 0rpm) or (300, 0, 300rpm) produced insufficient peak resolution regardless of the choice of the mobile phase apparently due to the lack of rotation speed except at (300, 0, 300rpm) with the upper mobile phase. At lower rotation speed of ω =300rpm, better peak resolution and stationary phase retention were obtained by the satellite motion (ω ) than by the planetary motion (ω ), or ω >ω . The effect of the hydrophobicity of the two-phase solvent systems on the stationary phase retention was further examined using the n-hexane/ethyl acetate/1-butanol/methanol/water system at different volume ratios. In the satellite motion at (ω , ω , ω )=(300, 150, 150rpm), almost constant stationary phase retention was obtained with the lower mobile phase regardless of the hydrophobicity of the solvent system whereas the stationary phase retention varied according to the volume ratio of the two-phase solvent system for the upper mobile phase. However, stable stationary phase retention was observed with either phase used as the mobile phase. In order to analyze the acceleration acting on the coiled column, an acceleration sensor was set on the column holder by displacing the multilayer column. The combination of the rotation speeds at (300, 100, 200rpm) showed double loops in the acceleration track, whereas (300, 150, 150rpm) showed a single loop, and all other combinations showed, complex tracks. The overall results indicate that the satellite motion is seriously affected by the combination of rotation speeds and the hydrophobicity of the two-phase solvent system when the upper phase was used as the mobile phase for separation.
[Mh] Termos MeSH primário: Carboidratos/isolamento & purificação
Centrifugação/instrumentação
Centrifugação/métodos
Distribuição Contracorrente/métodos
Himecromona/isolamento & purificação
[Mh] Termos MeSH secundário: 1-Butanol/química
Aceleração
Acetatos/química
Carboidratos/química
Hexanos/química
Interações Hidrofóbicas e Hidrofílicas
Himecromona/química
Metanol/química
Rotação
Solventes/química
Gravidade Específica
Água/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetates); 0 (Carbohydrates); 0 (Hexanes); 0 (Solvents); 059QF0KO0R (Water); 2DDG612ED8 (n-hexane); 3T5NG4Q468 (Hymecromone); 8PJ61P6TS3 (1-Butanol); Y4S76JWI15 (Methanol)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170102
[St] Status:MEDLINE


  9 / 1075 MEDLINE  
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[PMID]:27706810
[Au] Autor:Ikuta K; Ota T; Zhuo L; Urakawa H; Kozawa E; Hamada S; Kimata K; Ishiguro N; Nishida Y
[Ad] Endereço:Department of Orthopaedic Surgery, Nagoya University Graduate School and School of Medicine 65, Nagoya, 466-8550, Japan.
[Ti] Título:Antitumor effects of 4-methylumbelliferone, a hyaluronan synthesis inhibitor, on malignant peripheral nerve sheath tumor.
[So] Source:Int J Cancer;140(2):469-479, 2017 Jan 15.
[Is] ISSN:1097-0215
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hyaluronan (HA) has been shown to play important roles in the growth, invasion and metastasis of malignant tumors. Our previous study showing that high HA expression in malignant peripheral nerve sheath tumors (MPNST) is predictive of poor patient prognosis, prompted us to speculate that inhibition of HA synthesis in MPNST might suppress the tumorigenicity. The aim of our study was to investigate the antitumor effects of 4-methylumbelliferone (MU), an HA synthesis inhibitor, on human MPNST cells and tissues. The effects of MU on HA accumulation and tumorigenicity in MPNST cells were analyzed in the presence or absence of MU in an in vitro as well as in vivo xenograft model using human MPNST cell lines, sNF96.2 (primary recurrent) and sNF02.2 (metastatic). MU significantly inhibited cell proliferation, migration and invasion in both MPNST cell lines. HA binding protein (HABP) staining, particle exclusion assay and quantification of HA revealed that MU significantly decreased HA accumulation in the cytoplasms and pericellular matrices in both MPNST cell lines. The expression levels of HA synthase2 (HAS2) and HA synthase3 (HAS3) mRNA were downregulated after treatment with MU. MU induced apoptosis of sNF96.2 cells, but not sNF02.2 cells. MU administration significantly inhibited the tumor growth of sNF96.2 cells in the mouse xenograft model. To the best of our knowledge, our study demonstrates for the first time the antitumor effects of MU on human MPNST mediated by inhibition of HA synthesis. Our results suggest that MU may be a promising agent with novel antitumor mechanisms for MPNST.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Ácido Hialurônico/metabolismo
Himecromona/farmacologia
Neoplasias da Bainha Neural/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Feminino
Seres Humanos
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Invasividade Neoplásica/patologia
Neoplasias da Bainha Neural/metabolismo
RNA Mensageiro/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (RNA, Messenger); 3T5NG4Q468 (Hymecromone); 9004-61-9 (Hyaluronic Acid)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170501
[Lr] Data última revisão:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161006
[St] Status:MEDLINE
[do] DOI:10.1002/ijc.30460


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[PMID]:27671299
[Au] Autor:Huang RZ; Hua SX; Wang CY; Pan YM; Qin JM; Ding ZY; Zhang Y; Wang HS
[Ad] Endereço:State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, China.
[Ti] Título:4-Methylumbelliferones Analogues as Anticancer Agents: Synthesis and in Cell Pharmacological Studies.
[So] Source:Anticancer Agents Med Chem;17(4):576-589, 2017.
[Is] ISSN:1875-5992
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cancer is one of the most serious clinical problems worldwide, and considerable efforts have been devoted to discovering therapeutic agents with novel modes of action. Natural and synthetic coumarin derivatives have attracted intense research interest due to their diverse structural features and remarkable array of biological properties. OBJECTIVE: In the present study, we synthesized a series of 4-MU derivatives containing urea-piperazine and thioureapiperazine moieties and evaluated their antitumor activities to find efficacy antitumor drugs. METHOD: Cell proliferation, apoptosis, cell cycle, the generation of reactive oxygen species and calcium were measured using MTT assay and flow cytometry, respectively. The expression of apoptosis- and proliferation-related proteins was determined by western blotting. The effect of 4l on apoptosis-related mRNA expression in NCI-H460 cells was detected by RT-PCR. RESULTS: Most of the target compounds exhibited potential anticancer activities against tested cancer cells but had low cytotoxicity to normal cells. Compound 4l inhibited the growth and proliferation of NCI-H460 cells and resulted in apoptosis. Successive studies conducted with 4l in NCI-H460 cells demonstrated that this compound induced the intracellular reactive oxygen species generation and calcium overload, suppressed nuclear factor-κB (NF-κB) activity and regulated anti- and pro-apoptotic proteins. In addition, compound 4l effectively arrested NCI-H460 cells in G2 phase and altered the cell cycle regulatory proteins especially cyclin B1. CONCLUSION: Compound 4l exerts significant anticancer effects on NCI-H460 cells in vitro through targeting of mitochondria-dependent apoptotic pathway. These results indicate that the strategy for rational design of 4-MU derivatives may identify potential anticancer agents.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Himecromona/análogos & derivados
Himecromona/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Cálcio/metabolismo
Ciclo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Himecromona/síntese química
Himecromona/química
Estrutura Molecular
Espécies Reativas de Oxigênio/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Reactive Oxygen Species); 3T5NG4Q468 (Hymecromone); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160928
[St] Status:MEDLINE
[do] DOI:10.2174/1871520616666160926113109



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