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[PMID]:28453600
[Au] Autor:Jinda W; Taylor TD; Suzuki Y; Thongnoppakhun W; Limwongse C; Lertrit P; Trinavarat A; Atchaneeyasakul LO
[Ad] Endereço:Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
[Ti] Título:Whole Exome Sequencing in Eight Thai Patients With Leber Congenital Amaurosis Reveals Mutations in the CTNNA1 and CYP4V2 Genes.
[So] Source:Invest Ophthalmol Vis Sci;58(4):2413-2420, 2017 04 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Our goal was to describe the clinical and molecular genetic findings in Thai patients with Leber congenital amaurosis (LCA). Methods: Whole exome sequencing (WES) was performed in eight unrelated patients. All genes responsible for inherited retinal diseases (IRDs) based on RetNet were selected for analysis. Potentially causative variants were filtered through a bioinformatics pipeline and validated using Sanger sequencing. Segregation analysis of the causative genes was performed in family members when available. Results: Eleven deleterious variants, six nonsense and five missense, were identified in seven genes: four LCA-associated genes (CEP290, IQCB1, NMNAT1, and RPGRIP1), one gene responsible for syndromic LCA (ALMS1), and two IRDs-related genes (CTNNA1 and CYP4V2). Clinical reassessment supported the diagnosis of syndromic LCA in those patients harboring potentially pathogenic variants in the ALMS1. Interestingly, two causative genes, CTNNA1 and CYP4V2, previously reported to cause butterfly-shaped pigment dystrophy (BSPD) and Bietti's crystalline dystrophy (BCD), respectively, were detected in two other patients. These two patients developed rapid and severe visual loss in contrast to BSPD and BCD patients in previous studies. The results of this study demonstrate that causative variants identified in the CTNNA1 and CYP4V2 genes are also associated with LCA. Conclusions: This is the first report describing the molecular genetics and clinical manifestations of Thai patients with LCA. The present study expands the spectrum of LCA-associated genes, which is a benefit for molecular diagnosis. The identification of mutations in the CTNNA1 and CYP4V2 genes requires further elucidation in larger cohorts with LCA.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Família 4 do Citocromo P450/genética
Predisposição Genética para Doença
Amaurose Congênita de Leber/genética
Mutação
alfa Catenina/genética
[Mh] Termos MeSH secundário: Criança
Pré-Escolar
Códon sem Sentido
Análise Mutacional de DNA
Exoma
Feminino
Seres Humanos
Lactente
Masculino
Mutação de Sentido Incorreto
Tailândia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CTNNA1 protein, human); 0 (Codon, Nonsense); 0 (alpha Catenin); EC 1.14.13.- (CYP4V2 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.16-21322


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[PMID]:28763560
[Au] Autor:Hirashima T; Miyata M; Ishihara K; Hasegawa T; Sugahara M; Ogino K; Yoshikawa M; Hata M; Kuroda Y; Muraoka Y; Ooto S; Yoshimura N
[Ad] Endereço:Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.
[Ti] Título:Choroidal Vasculature in Bietti Crystalline Dystrophy With CYP4V2 Mutations and in Retinitis Pigmentosa With EYS Mutations.
[So] Source:Invest Ophthalmol Vis Sci;58(10):3871-3878, 2017 Aug 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: We compare the choroidal vascular area between Bietti crystalline dystrophy (BCD) patients with CYP4V2 mutations, retinitis pigmentosa (RP) patients with EYS mutations, and normal controls, and investigate the correlation between choroidal vascular area and associated parameters. Methods: This prospective case-series study included consecutive nine eyes of nine BCD patients with CYP4V2 mutations (BCD group), 16 eyes of 16 RP patients with EYS mutations (EYS-RP group), and 16 eyes of 16 normal volunteers matched for age and axial length (control group). Using swept-source optical coherence tomography, we obtained en face images of the choroidal vasculature at the midpoint of the choriocapillaris layer-Sattler's layer (inner choroid) and Haller's layer (outer choroid). After binarization, we compared the inner and outer choroidal vascular areas among the three groups and identified associated factors. Results: The outer choroidal vascular area was 43.34 ± 5.76%, 53.73 ± 4.92%, and 52.80 ± 4.10% in the BCD, EYS-RP, and control groups, respectively. This value was significantly smaller in the BCD group than in the EYS-RP and control groups (P < 0.001 in both; no significant difference between the EYS-RP and control groups). In the BCD group, the outer choroidal vascular area was correlated strongly with the subfoveal inner choroidal thickness (P = 0.001, r = 0.91, respectively). The inner choroidal vasculature could not be identified in eight of nine eyes in the BCD group. Conclusions: The outer choroidal vascular narrowing might progress with the inner choroidal thinning in BCD, and the inner choroidal vasculature might be extinguished in advanced-stage BCD. Our findings may help to clarify the etiology of BCD.
[Mh] Termos MeSH primário: Vasos Sanguíneos/patologia
Corioide/irrigação sanguínea
Distrofias Hereditárias da Córnea
Família 4 do Citocromo P450/genética
Proteínas do Olho/genética
Mutação
Doenças Retinianas
Retinite Pigmentosa
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos de Casos e Controles
Corioide/patologia
Distrofias Hereditárias da Córnea/genética
Distrofias Hereditárias da Córnea/patologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
Doenças Retinianas/genética
Doenças Retinianas/patologia
Retinite Pigmentosa/genética
Retinite Pigmentosa/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (EYS protein, human); 0 (Eye Proteins); EC 1.14.13.- (CYP4V2 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21515


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[PMID]:28729181
[Au] Autor:Yi M; Shin JG; Lee SJ
[Ad] Endereço:Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Inje University, Busan, South Korea.
[Ti] Título:Expression of CYP4V2 in human THP1 macrophages and its transcriptional regulation by peroxisome proliferator-activated receptor gamma.
[So] Source:Toxicol Appl Pharmacol;330:100-106, 2017 Sep 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Because macrophages respond to a variety of pathological and pharmacological reagents, understanding the role of P450s in macrophages is important for therapeutic intervention. There has been a lack of research on CYP4 in macrophages, but fatty acid accumulation and lipid trafficking in macrophages have been suggested to be a main cause of atherosclerosis. All human CYP4 genes (n=12) were screened in THP1 macrophages by gene-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Only CYP4V2 exhibited strong expression of both mRNA and protein. Expression levels of both CYP4V2 mRNA and protein were significantly reduced after treatment with peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662. However, the expression levels of CYP4V2 were not changed by PPARα antagonist (GW6471) and liver X receptor alpha antagonist (22-S hydroxycholesterol). A metabolite of the CYP4V2 enzyme, 12-hydroxydodecanoic acid, was detected in THP1 macrophages, and this metabolite was significantly decreased after treatment with the PPARγ inhibitor GW9662 (>80% decreased, p<0.05). In summary, fatty acid metabolizing protein CYP4V2 was identified in human THP1 macrophages, and its expression was regulated by PPARγ. Further study is required to understand the role of CYP4V2 with regard to fat accumulation in the activated macrophage and atherosclerotic plaque development.
[Mh] Termos MeSH primário: Família 4 do Citocromo P450/genética
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos
Macrófagos/enzimologia
PPAR alfa/farmacologia
[Mh] Termos MeSH secundário: Anilidas/farmacologia
Linhagem Celular
Família 4 do Citocromo P450/biossíntese
Ácidos Graxos/metabolismo
Seres Humanos
Hidroxicolesteróis/farmacologia
Ácidos Láuricos/metabolismo
Receptores X do Fígado/antagonistas & inibidores
Macrófagos/efeitos dos fármacos
PPAR alfa/antagonistas & inibidores
PPAR alfa/genética
RNA Mensageiro/biossíntese
RNA Mensageiro/genética
RNA Interferente Pequeno/genética
Acetato de Tetradecanoilforbol/farmacologia
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-chloro-5-nitrobenzanilide); 0 (Anilides); 0 (Fatty Acids); 0 (Hydroxycholesterols); 0 (Lauric Acids); 0 (Liver X Receptors); 0 (PPAR alpha); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 1160N9NU9U (lauric acid); 17711-16-9 (22-hydroxycholesterol); 505-95-3 (12-hydroxydodecanoic acid); EC 1.14.13.- (CYP4V2 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4); NI40JAQ945 (Tetradecanoylphorbol Acetate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE


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[PMID]:28557975
[Au] Autor:Alnabulsi A; Swan R; Cash B; Alnabulsi A; Murray GI
[Ad] Endereço:Department of Pathology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25, 2ZD, UK.
[Ti] Título:The differential expression of omega-3 and omega-6 fatty acid metabolising enzymes in colorectal cancer and its prognostic significance.
[So] Source:Br J Cancer;116(12):1612-1620, 2017 Jun 06.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Colorectal cancer is a common malignancy and one of the leading causes of cancer-related deaths. The metabolism of omega fatty acids has been implicated in tumour growth and metastasis. METHODS: This study has characterised the expression of omega fatty acid metabolising enzymes CYP4A11, CYP4F11, CYP4V2 and CYP4Z1 using monoclonal antibodies we have developed. Immunohistochemistry was performed on a tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosa. RESULTS: The differential expression of CYP4A11 and CYP4F11 showed a strong association with survival in both the whole patient cohort (hazard ratio (HR)=1.203, 95% CI=1.092-1.324, χ =14.968, P=0.001) and in mismatch repair-proficient tumours (HR=1.276, 95% CI=1.095-1.488, χ =9.988, P=0.007). Multivariate analysis revealed that the differential expression of CYP4A11 and CYP4F11 was independently prognostic in both the whole patient cohort (P=0.019) and in mismatch repair proficient tumours (P=0.046). CONCLUSIONS: A significant and independent association has been identified between overall survival and the differential expression of CYP4A11 and CYP4F11 in the whole patient cohort and in mismatch repair-proficient tumours.
[Mh] Termos MeSH primário: Neoplasias Colorretais/química
Neoplasias Colorretais/enzimologia
Citocromo P-450 CYP4A/análise
Família 4 do Citocromo P450/análise
[Mh] Termos MeSH secundário: Idoso
Colo/química
Neoplasias Colorretais/patologia
Reparo de Erro de Pareamento de DNA
Ácidos Graxos Ômega-3/metabolismo
Ácidos Graxos Ômega-6/metabolismo
Feminino
Seres Humanos
Mucosa Intestinal/química
Metástase Linfática
Masculino
Prognóstico
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids, Omega-3); 0 (Fatty Acids, Omega-6); EC 1.14.13.- (CYP4V2 protein, human); EC 1.14.13.194 (CYP4F11 protein, human); EC 1.14.14.1 (CYP4Z1 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4); EC 1.14.15.3 (CYP4A11 protein, human); EC 1.14.15.3 (Cytochrome P-450 CYP4A)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.135


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[PMID]:28376131
[Au] Autor:Au NT; Reyes M; Boyer BB; Hopkins SE; Black J; O'Brien D; Fohner AE; Yracheta J; Thornton T; Austin MA; Burke W; Thummel KE; Rettie AE
[Ad] Endereço:Department of Medicinal Chemistry, University of Washington, Seattle, Washington, United States of America.
[Ti] Título:Dietary and genetic influences on hemostasis in a Yup'ik Alaska Native population.
[So] Source:PLoS One;12(4):e0173616, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fish and marine animals are important components of the subsistence diet of Alaska Native people, resulting in a high ω3 PUFA intake. The historical record for circumpolar populations highlights a tendency for facile bleeding, possibly related to ω3 PUFA effects on platelet activation and/or vitamin K-dependent clotting factors. To evaluate these two scenarios in Yup'ik people of southwestern Alaska, we examined the association between dietary ω3 PUFA intake and activities of clotting factor II, V, fibrinogen, PT, INR, PTT, and sP-selectin in 733 study participants, using the nitrogen isotope ratio of red blood cells as a biomarker of ω3 PUFA consumption. sP-selectin alone correlated strongly and inversely with ω3 PUFA consumption. Approximately 36% of study participants exhibited PIVKA-II values above the threshold of 2 ng/ml, indicative of low vitamin K status. To assess genetic influences on vitamin K status, study participants were genotyped for common vitamin K cycle polymorphisms in VKORC1, GGCX and CYP4F2. Only CYP4F2*3 associated significantly with vitamin K status, for both acute (plasma vitamin K) and long-term (PIVKA-II) measures. These findings suggest: (i) a primary association of ω3 PUFAs on platelet activation, as opposed to vitamin K-dependent clotting factor activity, (ii) that reduced CYP4F2 enzyme activity associates with vitamin K status. We conclude that high ω3 PUFA intake promotes an anti-platelet effect and speculate that the high frequency of the CYP4F2*3 allele in Yup'ik people (~45%) evolved in response to a need to conserve body stores of vitamin K due to environmental limitations on its availability.
[Mh] Termos MeSH primário: Nativos do Alasca/genética
Dieta
Hemostasia/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Alaska
Animais
Biomarcadores/sangue
Coagulação Sanguínea/genética
Fatores de Coagulação Sanguínea/genética
Fatores de Coagulação Sanguínea/metabolismo
Carbono-Carbono Ligases/genética
Estudos Transversais
Família 4 do Citocromo P450/genética
Ácidos Graxos Ômega-3/administração & dosagem
Feminino
Genótipo
Seres Humanos
Inuítes/genética
Masculino
Meia-Idade
Selectina-P/sangue
Ativação Plaquetária/genética
Polimorfismo de Nucleotídeo Único
Precursores de Proteínas/sangue
Protrombina
Vitamina K/sangue
Vitamina K Epóxido Redutases/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Blood Coagulation Factors); 0 (Fatty Acids, Omega-3); 0 (P-Selectin); 0 (Protein Precursors); 12001-79-5 (Vitamin K); 53230-14-1 (acarboxyprothrombin); 9001-26-7 (Prothrombin); EC 1.14.13.30 (CYP4F2 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4); EC 1.17.4.4 (VKORC1 protein, human); EC 1.17.4.4 (Vitamin K Epoxide Reductases); EC 6.4.- (Carbon-Carbon Ligases); EC 6.4.- (glutamyl carboxylase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173616


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[PMID]:28353616
[Au] Autor:Jiang J; Liu K; Zou J; Ma H; Yang H; Zhang X; Jiao Y
[Ad] Endereço:aDivision of Vascular Surgery, Department of General Surgery bDepartment of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
[Ti] Título:Associations between polymorphisms in coagulation-related genes and venous thromboembolism: A meta-analysis with trial sequential analysis.
[So] Source:Medicine (Baltimore);96(13):e6537, 2017 Mar.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Recently, several studies showed that the polymorphisms in the coagulation-related genes might be associated with venous thromboembolism (VTE); however, the results were still controversial. We performed a meta-analysis with trial sequential analysis to investigate the associations between the endothelial cell-activated protein C receptor (EPCR) rs9574, F11 rs2289252, F11 rs2036914, FGG rs2066865, FGG rs1049636, CYP4V2 rs13146272, SERPINC1 rs2227589, and GP6 rs1613662 polymorphisms with the risk of VTE. METHODS: We searched both the common English-language databases and the Chinese literature databases. Two authors selected studies according to inclusion and exclusion criteria. Crude odds ratios with 95% confidence intervals (CI) were calculated to estimate the strength of this association. Between-study heterogeneity was assessed with the chi-square-based Q test and the I statistic. RESULTS: Overall, a total of 20 studies were included. The meta-analysis revealed that the F11 rs2289252, F11 rs2036914, FGG rs2066865, and CYP4V2 rs13146272 polymorphisms were closely related to the development of VTE in the white race under the best genetic models after multiple testing adjustments. The EPCR rs9574, FGG rs1049636, SERPINC1 rs2227589, and GP6 rs1613662 polymorphisms might be potential candidates in the pathogenesis of VTE, but trial sequential analyses and sensitivity analyses indicated that the evidences were limited. Larger scale studies were demanded to avoid false-positive outcomes. CONCLUSIONS: Finally, our study demonstrated the important role of rs2289252, rs2036914, rs2066865, and rs13146272 polymorphisms in the development of VTE in the white race. Rs9574, rs1049636, rs2227589 and rs1613662 polymorphisms might be risk factors of VTE. However, more studies involving diverse races are needed to probe the ethnic difference and the underlying mechanisms of significant associations.
[Mh] Termos MeSH primário: Família 4 do Citocromo P450/genética
Fator XI/genética
Fibrinogênio/genética
Tromboembolia Venosa/genética
[Mh] Termos MeSH secundário: Antígenos CD/genética
Antitrombina III/genética
Receptor de Proteína C Endotelial
Seres Humanos
Glicoproteínas da Membrana de Plaquetas/genética
Receptores de Superfície Celular/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Endothelial Protein C Receptor); 0 (PROCR protein, human); 0 (Platelet Membrane Glycoproteins); 0 (Receptors, Cell Surface); 0 (SERPINC1 protein, human); 0 (platelet membrane glycoprotein VI); 9000-94-6 (Antithrombin III); 9001-32-5 (Fibrinogen); 9013-55-2 (Factor XI); EC 1.14.13.- (CYP4V2 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170330
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000006537


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[PMID]:28347661
[Au] Autor:Yi M; Cho SA; Min J; Kim DH; Shin JG; Lee SJ
[Ad] Endereço:Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Inje University, Bokji-ro 75, Busanjin-gu, Busan 47392, South Korea.
[Ti] Título:Functional characterization of a common CYP4F11 genetic variant and identification of functionally defective CYP4F11 variants in erythromycin metabolism and 20-HETE synthesis.
[So] Source:Arch Biochem Biophys;620:43-51, 2017 Apr 15.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CYP4F11, together with CYP4F2, plays an important role in the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid. We identified 21 variants by whole exome sequencing, including 4 non-synonymous variants in Korean subjects. The proteins of the wild-type CYP4F11 and the four coding variants (C276R, D315N, D374Y, and D446N) were expressed in Escherichia coli DH5α cells and purified to give cytochrome P450-specific carbon monoxide difference spectra. Wild-type CYP4F2 was also expressed and purified to compare its activity with the CYP4F11 wild-type. Wild-type CYP4F11 exhibited the highest maximal clearance for erythromycin N-demethylase activity followed by the variants D374Y, D446N, C276R, and D315N. In particular, the CYP4F11 D315N protein showed about 50% decrease in intrinsic clearance compared to the wild type. The ability of wild-type CYP4F11 and the variants to synthesize 20-HETE from arachidonic acid was similar; the CYP4F11 D315N variant, however, showed only 68% of wild-type activity. Furthermore, the ability of CYP4F2 to synthesize 20-HETE was 1.7-fold greater than that of CYP4F11. Overall, our results suggest that the metabolism of CYP4F11 substrates may be reduced in individuals carrying the CYP4F11 D315N genetic variant and individuals carrying the common D446N CYP4F11 variant likely exhibit comparable 20-HETE synthesis as individuals expressing wild-type CYP4F11.
[Mh] Termos MeSH primário: Ácido Araquidônico
Família 4 do Citocromo P450
Exoma
Ácidos Hidroxieicosatetraenoicos
Mutação de Sentido Incorreto
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Ácido Araquidônico/química
Ácido Araquidônico/metabolismo
Família 4 do Citocromo P450/química
Família 4 do Citocromo P450/genética
Família 4 do Citocromo P450/metabolismo
Eritromicina/química
Feminino
Seres Humanos
Ácidos Hidroxieicosatetraenoicos/biossíntese
Ácidos Hidroxieicosatetraenoicos/química
Masculino
Proteínas Recombinantes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydroxyeicosatetraenoic Acids); 0 (Recombinant Proteins); 27YG812J1I (Arachidonic Acid); 63937KV33D (Erythromycin); 79551-86-3 (20-hydroxy-5,8,11,14-eicosatetraenoic acid); EC 1.14.13.194 (CYP4F11 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE


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[PMID]:28236635
[Au] Autor:Li C; Zheng L; Xin Y; Tan Z; Zhang Y; Meng X; Wang Z; Xi T
[Ad] Endereço:School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
[Ti] Título:The competing endogenous RNA network of CYP4Z1 and pseudogene CYP4Z2P exerts an anti-apoptotic function in breast cancer.
[So] Source:FEBS Lett;591(7):991-1000, 2017 Apr.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The competing endogenous RNA network (ceRNET) is involved in tumorigenesis and has become a hot spot of research. The ceRNET between CYP4Z1 and the pseudogene CYP4Z2P promotes angiogenesis and mediates tamoxifen resistance in breast cancer. Nevertheless, the effects of this ceRNET on cell apoptosis and related mechanisms remain unclear. In the present study, we found that downregulation of CYP4Z1 or the CYP4Z2P 3'-UTR promotes cell apoptosis, mirroring the functions of human telomerase reverse transcriptase (hTERT). Furthermore, the ceRNET between CYP4Z1 and pseudogene CYP4Z2P modulates hTERT expression by operating as a sub-ceRNET for hTERT. Our data demonstrate that the ceRNET between CYP4Z1 and pseudogene CYP4Z2P acts as a sub-ceRNET for hTERT and, thus, inhibits breast cancer apoptosis.
[Mh] Termos MeSH primário: Apoptose/genética
Família 4 do Citocromo P450/genética
Pseudogenes/genética
RNA Neoplásico/genética
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas/genética
Sequência de Bases
Western Blotting
Neoplasias da Mama/genética
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Linhagem Celular Tumoral
Família 4 do Citocromo P450/metabolismo
Regulação para Baixo
Feminino
Regulação Neoplásica da Expressão Gênica
Células HEK293
Seres Humanos
Células MCF-7
MicroRNAs/genética
RNA Neoplásico/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Homologia de Sequência de Aminoácidos
Telomerase/genética
Telomerase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (MIRN125 microRNA, human); 0 (MicroRNAs); 0 (RNA, Neoplasm); EC 1.14.14.1 (CYP4Z1 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4); EC 2.7.7.49 (TERT protein, human); EC 2.7.7.49 (Telomerase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12608


  9 / 363 MEDLINE  
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[PMID]:28198005
[Au] Autor:Johnson JA; Caudle KE; Gong L; Whirl-Carrillo M; Stein CM; Scott SA; Lee MT; Gage BF; Kimmel SE; Perera MA; Anderson JL; Pirmohamed M; Klein TE; Limdi NA; Cavallari LH; Wadelius M
[Ad] Endereço:Department of Pharmacotherapy and Translational Research, College of Pharmacy, and Center for Pharmacogenomics, University of Florida, Gainesville, Florida, USA.
[Ti] Título:Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update.
[So] Source:Clin Pharmacol Ther;102(3):397-404, 2017 Sep.
[Is] ISSN:1532-6535
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry.
[Mh] Termos MeSH primário: Anticoagulantes/administração & dosagem
Citocromo P-450 CYP2C9/genética
Família 4 do Citocromo P450/genética
Vitamina K Epóxido Redutases/genética
Varfarina/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Criança
Relação Dose-Resposta a Droga
Genótipo
Seres Humanos
Farmacogenética
Guias de Prática Clínica como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticoagulants); 5Q7ZVV76EI (Warfarin); EC 1.14.13.- (CYP2C9 protein, human); EC 1.14.13.- (Cytochrome P-450 CYP2C9); EC 1.14.13.30 (CYP4F2 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4); EC 1.17.4.4 (VKORC1 protein, human); EC 1.17.4.4 (Vitamin K Epoxide Reductases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170216
[St] Status:MEDLINE
[do] DOI:10.1002/cpt.668


  10 / 363 MEDLINE  
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[PMID]:28150878
[Au] Autor:Yin J; Liu H; Liu Z; Owzar K; Han Y; Su L; Wei Y; Hung RJ; Brhane Y; McLaughlin J; Brennan P; Bickeboeller H; Rosenberger A; Houlston RS; Caporaso N; Landi MT; Heinrich J; Risch A; Christiani DC; Amos CI; Wei Q
[Ad] Endereço:Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Suzhou, China.
[Ti] Título:Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus.
[So] Source:Mol Carcinog;56(6):1663-1672, 2017 Jun.
[Is] ISSN:1098-2744
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The fatty acids (FAs) metabolism is suggested to play a pivotal role in the development of lung cancer, and we explored that by conducting a pathway-based analysis. We performed a meta-analysis of published datasets of six genome wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium, which included 12 160 cases with lung cancer and 16 838 cancer-free controls. A total of 30 722 single-nucleotide polymorphisms (SNPs) from 317 genes relevant to FA metabolic pathways were identified. An additional dataset from the Harvard Lung Cancer Study with 984 cases and 970 healthy controls was also added to the final meta-analysis. In the initial meta-analysis, 26 of 28 SNPs that passed false discovery rate multiple tests were mapped to the CYP4F3 gene. Among the 26 top ranked hits was a proxy SNP, CYP4F3 rs4646904 (P = 8.65 × 10 , FDR = 0.018), which is suggested to change splicing pattern/efficiency and to be associated with gene expression levels. However, after adding data of rs4646904 from the Harvard GWAS, the significance in the combined analysis was reduced to P = 3.52 × 10 [odds ratio (OR) = 1.07, 95% confidence interval (95%CI) = 1.03-1.12]. Interestingly, the small Harvard dataset also pointed to the same direction of the association in subgroups of smokers (OR = 1.07) and contributed to a combined OR of 1.13 (95% CI = 1.06-1.20, P = 6.70 × 10 ). The results suggest that a potentially functional SNP in CYP4F3 (rs4646904) may contribute to the etiology of lung cancer, especially in smokers. Additional mechanistic studies are warranted to unravel the potential biological significance of the finding.
[Mh] Termos MeSH primário: Família 4 do Citocromo P450/genética
Neoplasias Pulmonares/genética
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Família 4 do Citocromo P450/metabolismo
Ácidos Graxos/genética
Ácidos Graxos/metabolismo
Loci Gênicos
Predisposição Genética para Doença
Estudo de Associação Genômica Ampla
Genótipo
Seres Humanos
Neoplasias Pulmonares/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Fatty Acids); EC 1.14.13.30 (CYP4F3 protein, human); EC 1.14.14.1 (Cytochrome P450 Family 4)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170203
[St] Status:MEDLINE
[do] DOI:10.1002/mc.22622



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