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[PMID]:29040285
[Au] Autor:Yang HJ; Bogomolnaya L; McClelland M; Andrews-Polymenis H
[Ad] Endereço:Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M University System Health Science Center, Bryan, TX, United States of America.
[Ti] Título:De novo pyrimidine synthesis is necessary for intestinal colonization of Salmonella Typhimurium in chicks.
[So] Source:PLoS One;12(10):e0183751, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:pyrE (STM3733) encodes orotate phosphoribosyltransferase (OPRTase; EC 2.4.2.10), the fifth enzyme of the de novo pyrimidine biosynthetic pathway. We identified a ΔpyrE mutant as under selection in screening of a Salmonella mutant library in 4-day old chicks. Here, we confirm that a ΔpyrE mutant colonizes 4-day old chicks poorly in competitive infection with isogenic wild type, and that the ability of this mutant to colonize chicks could be restored by providing a copy of pyrE in trans. We further show that our ΔpyrE mutant grows poorly in nutrient poor conditions in vitro, and that the ability of this mutant to grow is restored, both in vitro and in chicks, when precursors to the pyrimidine salvage pathway were provided. This finding suggests that the environment in the chick intestine during our infections lacks sufficient precursors of the pyrimidine salvage pathway to support Salmonella growth. Finally, we show that the colonization defect of a ΔpyrE mutant during infection occurs in to chicks, but not in CBA/J mice or ligated ileal loops in calves. Our data suggest that de novo pyrimidine synthesis is necessary for colonization of Salmonella Typhimurium in the chick, and that the salvage pathway is not used in this niche.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Galinhas/microbiologia
Orotato Fosforribosiltransferase/genética
Doenças das Aves Domésticas/microbiologia
Pirimidinas/biossíntese
Salmonelose Animal/microbiologia
Salmonella typhimurium/genética
Fatores de Virulência/genética
[Mh] Termos MeSH secundário: Animais
Proteínas de Bactérias/metabolismo
Bovinos
Contagem de Colônia Microbiana
Deleção de Genes
Expressão Gênica
Biblioteca Gênica
Teste de Complementação Genética
Especificidade de Hospedeiro
Camundongos
Camundongos Endogâmicos CBA
Orotato Fosforribosiltransferase/deficiência
Doenças das Aves Domésticas/metabolismo
Doenças das Aves Domésticas/patologia
Salmonelose Animal/metabolismo
Salmonelose Animal/patologia
Salmonella typhimurium/metabolismo
Salmonella typhimurium/patogenicidade
Fatores de Virulência/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Pyrimidines); 0 (Virulence Factors); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); K8CXK5Q32L (pyrimidine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171018
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183751


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[PMID]:28559281
[Au] Autor:McReynolds MR; Wang W; Holleran LM; Hanna-Rose W
[Ad] Endereço:From the Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802.
[Ti] Título:Uridine monophosphate synthetase enables eukaryotic NAD biosynthesis from quinolinic acid.
[So] Source:J Biol Chem;292(27):11147-11153, 2017 Jul 07.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:NAD biosynthesis is an attractive and promising therapeutic target for influencing health span and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD biosynthetic pathways. Here, we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, are reported to lack a NAD biosynthetic pathway. However, all the genes of the kynurenine pathway required for quinolinic acid (QA) production from tryptophan are present. Thus, we investigated the presence of NAD biosynthesis in this organism. By combining isotope-tracing and genetic experiments, we have demonstrated the presence of an intact biosynthesis pathway for NAD from tryptophan via QA, highlighting the functional conservation of this important biosynthetic activity. Supplementation with kynurenine pathway intermediates also boosted NAD levels and partially reversed NAD -dependent phenotypes caused by mutation of , which encodes a nicotinamidase required for NAD salvage biosynthesis, demonstrating contribution of synthesis to NAD homeostasis. By investigating candidate phosphoribosyltransferase genes in the genome, we determined that the conserved uridine monophosphate phosphoribosyltransferase (UMPS), which acts in pyrimidine biosynthesis, is required for NAD biosynthesis in place of the missing QPRTase. We suggest that similar underground metabolic activity of UMPS may function in other organisms. This mechanism for NAD biosynthesis creates novel possibilities for manipulating NAD biosynthetic pathways, which is key for the future of therapeutics.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans
Caenorhabditis elegans
Complexos Multienzimáticos
NAD
Orotato Fosforribosiltransferase
Orotidina-5´-Fosfato Descarboxilase
Ácido Quinolínico/metabolismo
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans/enzimologia
Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/metabolismo
Complexos Multienzimáticos/genética
Complexos Multienzimáticos/metabolismo
Mutação
NAD/biossíntese
NAD/genética
Orotato Fosforribosiltransferase/genética
Orotato Fosforribosiltransferase/metabolismo
Orotidina-5'-Fosfato Descarboxilase/genética
Orotidina-5'-Fosfato Descarboxilase/metabolismo
Triptofano/genética
Triptofano/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Multienzyme Complexes); 0U46U6E8UK (NAD); 74870-74-9 (uridine 5'-monophosphate synthase); 8DUH1N11BX (Tryptophan); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); EC 4.1.1.23 (Orotidine-5'-Phosphate Decarboxylase); F6F0HK1URN (Quinolinic Acid)
[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:170601
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.C117.795344


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[PMID]:28388410
[Au] Autor:Cantor JR; Abu-Remaileh M; Kanarek N; Freinkman E; Gao X; Louissaint A; Lewis CA; Sabatini DM
[Ad] Endereço:Department of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Inte
[Ti] Título:Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase.
[So] Source:Cell;169(2):258-272.e17, 2017 Apr 06.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A complex interplay of environmental factors impacts the metabolism of human cells, but neither traditional culture media nor mouse plasma mimic the metabolite composition of human plasma. Here, we developed a culture medium with polar metabolite concentrations comparable to those of human plasma (human plasma-like medium [HPLM]). Culture in HPLM, relative to that in traditional media, had widespread effects on cellular metabolism, including on the metabolome, redox state, and glucose utilization. Among the most prominent was an inhibition of de novo pyrimidine synthesis-an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates. We find that uric acid directly inhibits uridine monophosphate synthase (UMPS) and consequently reduces the sensitivity of cancer cells to the chemotherapeutic agent 5-fluorouracil. Thus, media that better recapitulates the composition of human plasma reveals unforeseen metabolic wiring and regulation, suggesting that HPLM should be of broad utility.
[Mh] Termos MeSH primário: Meios de Cultura/química
Complexos Multienzimáticos/antagonistas & inibidores
Orotato Fosforribosiltransferase/antagonistas & inibidores
Orotidina-5´-Fosfato Descarboxilase/antagonistas & inibidores
Ácido Úrico/metabolismo
[Mh] Termos MeSH secundário: Idoso
Animais
Técnicas de Cultura de Células
Linhagem Celular Tumoral
Fluoruracila/farmacologia
Glucose/metabolismo
Seres Humanos
Leucemia Mieloide Aguda/tratamento farmacológico
Leucemia Mieloide Aguda/patologia
Masculino
Camundongos
Meia-Idade
Complexos Multienzimáticos/química
Orotato Fosforribosiltransferase/química
Orotidina-5'-Fosfato Descarboxilase/química
Domínios Proteicos
Pirimidinas/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); 0 (Multienzyme Complexes); 0 (Pyrimidines); 268B43MJ25 (Uric Acid); 74870-74-9 (uridine 5'-monophosphate synthase); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); EC 4.1.1.23 (Orotidine-5'-Phosphate Decarboxylase); IY9XDZ35W2 (Glucose); K8CXK5Q32L (pyrimidine); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE


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[PMID]:28347333
[Au] Autor:Kim SY; Baek JY; Oh JH; Park SC; Sohn DK; Kim MJ; Chang HJ; Kong SY; Kim DY
[Ad] Endereço:Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Ilsan-ro 323, Goyang-si, Gyeonggi-do, 10408, Republic of Korea.
[Ti] Título:A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.
[So] Source:Radiat Oncol;12(1):62, 2017 Mar 27.
[Is] ISSN:1748-717X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m ) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome. METHODS: Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m /day and leucovorin 90 mg/m /day for 7 days a week during preoperative chemoradiation (50.4 Gy/28 fractions) in this phase II trial. Primary endpoint was pathologic complete response rate, and the secondary endpoint was to explore the association between clinical outcomes and genetic polymorphisms CYP2A6 (*4, *7, *9 and *10), UMPS G638C, and three ABCB1 genotypes (C1236T, C3435T, and G2677T). RESULTS: Ninety-one patients were given study treatment, and 90 underwent surgery. Pathologic complete response was noted in 10 patients (11.1%). There was no grade 4 or 5 toxicity; 20 (22.0%) experienced grade 3 toxicities, including diarrhea (10, 11.0%), abdominal pain (2, 2.2%), and anemia (2, 2.2%). Relapse-free survival and overall survival at 5 years were 88.6% and 94.2%, respectively. Patients with the UMPS 638 CC genotype experienced significantly more frequent grade 2 or 3 diarrhea (p for trend = 0.018). CONCLUSIONS: Preoperative chemoradiation with tegafur-uracil 400 mg/m /day with leucovorin was feasible, but did not meet the expected pathologic complete response rate. The UMPS 638 CC genotype might be a candidate biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer. TRIAL REGISTRATION: ISRCTN11812525 , registered on 25 July 2016. Retrospectively registered.
[Mh] Termos MeSH primário: Quimiorradioterapia Adjuvante/métodos
Terapia Neoadjuvante/métodos
Neoplasias Retais/tratamento farmacológico
Neoplasias Retais/genética
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/genética
Adulto
Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Quimiorradioterapia Adjuvante/efeitos adversos
Citocromo P-450 CYP2A6/genética
Feminino
Genótipo
Seres Humanos
Estimativa de Kaplan-Meier
Leucovorina/administração & dosagem
Leucovorina/efeitos adversos
Masculino
Meia-Idade
Complexos Multienzimáticos/genética
Terapia Neoadjuvante/efeitos adversos
Orotato Fosforribosiltransferase/genética
Orotidina-5'-Fosfato Descarboxilase/genética
Testes Farmacogenômicos
Polimorfismo de Nucleotídeo Único
Neoplasias Retais/radioterapia
Tegafur/administração & dosagem
Tegafur/efeitos adversos
Resultado do Tratamento
Uracila/administração & dosagem
Uracila/efeitos adversos
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCB1 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (Multienzyme Complexes); 1548R74NSZ (Tegafur); 56HH86ZVCT (Uracil); 74870-74-9 (uridine 5'-monophosphate synthase); EC 1.14.14.1 (CYP2A6 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP2A6); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); EC 4.1.1.23 (Orotidine-5'-Phosphate Decarboxylase); Q573I9DVLP (Leucovorin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.1186/s13014-017-0800-5


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[PMID]:28205048
[Au] Autor:Wortmann SB; Chen MA; Colombo R; Pontoglio A; Alhaddad B; Botto LD; Yuzyuk T; Coughlin CR; Descartes M; Grunewald S; Maranda B; Mills PB; Pitt J; Potente C; Rodenburg R; Kluijtmans LA; Sampath S; Pai EF; Wevers RA; Tiller GE; and additional individual contributors
[Ad] Endereço:Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), Mullner Hauptstrasse 48, 5020, Salzburg, Austria. s.wortmann-hagemann@salk.at.
[Ti] Título:Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences.
[So] Source:J Inherit Metab Dis;40(3):423-431, 2017 May.
[Is] ISSN:1573-2665
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue. METHODS AND RESULTS: We identified mild and isolated orotic aciduria in 11 unrelated individuals with diverse clinical signs and symptoms, the most common denominator being intellectual disability/developmental delay. Of note, none had blood count abnormalities, relevant hyperammonemia or altered plasma amino acid profile. All individuals were found to have heterozygous alterations in UMPS. Four of these variants were predicted to be null alleles with complete loss of function. The remaining variants were missense changes and predicted to be damaging to the normal encoded protein. Interestingly, family screening revealed heterozygous UMPS variants in combination with mild orotic aciduria in 19 clinically asymptomatic family members. CONCLUSIONS: We therefore conclude that heterozygous UMPS-mutations can lead to mild and isolated orotic aciduria without clinical consequence. Partial UMPS-deficiency should be included in the differential diagnosis of mild orotic aciduria. The discovery of heterozygotes manifesting clinical symptoms such as hypotonia and developmental delay are likely due to ascertainment bias.
[Mh] Termos MeSH primário: Complexos Multienzimáticos/genética
Complexos Multienzimáticos/metabolismo
Orotato Fosforribosiltransferase/deficiência
Orotidina-5´-Fosfato Descarboxilase/deficiência
Erros Inatos do Metabolismo da Purina-Pirimidina/metabolismo
[Mh] Termos MeSH secundário: Anemia Megaloblástica/genética
Anemia Megaloblástica/metabolismo
Criança
Pré-Escolar
Feminino
Heterozigoto
Seres Humanos
Lactente
Deficiência Intelectual/genética
Deficiência Intelectual/metabolismo
Masculino
Mutação/genética
Orotato Fosforribosiltransferase/genética
Orotato Fosforribosiltransferase/metabolismo
Ácido Orótico/metabolismo
Orotidina-5'-Fosfato Descarboxilase/genética
Orotidina-5'-Fosfato Descarboxilase/metabolismo
Erros Inatos do Metabolismo da Purina-Pirimidina/genética
Pirimidinas/metabolismo
Distúrbios Congênitos do Ciclo da Ureia/genética
Distúrbios Congênitos do Ciclo da Ureia/metabolismo
Uridina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Multienzyme Complexes); 0 (Pyrimidines); 61H4T033E5 (Orotic Acid); 74870-74-9 (uridine 5'-monophosphate synthase); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); EC 4.1.1.23 (Orotidine-5'-Phosphate Decarboxylase); K8CXK5Q32L (pyrimidine); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1007/s10545-017-0015-9


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[PMID]:27928679
[Au] Autor:Han D; Xu Z
[Ad] Endereço:Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, 43403, USA.
[Ti] Título:Development of a pyrE-based selective system for Thermotoga sp. strain RQ7.
[So] Source:Extremophiles;21(2):297-306, 2017 Mar.
[Is] ISSN:1433-4909
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:To fully unlock the biotechnological potentials of Thermotoga species, this study aimed to expand the genetic toolbox of Thermotoga by developing a new selective system. The developed system was composed of two components: a recipient strain bearing a deletion in its orotate phosphoribosyltransferase gene pyrE and a shuttle vector expressing a heterologous pyrE as the selectable marker. A spontaneous uracil auxotroph, T. sp. strain RQ7-15, was isolated at 70 °C with 2 mg/ml 5-fluoroorotic acid. The mutant carried a 112 bp deletion in pyrE and was a suitable recipient strain. To avoid homologous recombination, the pyrE gene from another thermophilic bacterium Caldicellulosiruptor saccharolyticus was used as the selectable marker. The gene was cloned into two Thermotoga-E. coli shuttle vectors, controlled by different promoters: the promoter of Thermus S-layer protein (P ) in pDH25 and the promoter of the pyrimidine synthesis operon of T. sp. strain RQ7 (P ) in pDH28. After being introduced into the mutant strain RQ7-15 through natural transformation, both vectors allowed the host to thrive in a minimal medium. Single colonies of transformants were isolated and confirmed by polymerase chain reactions and restriction digestions. In summary, a pyrE-based selective system has been established in T. sp. strain RQ7.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Bacilos Gram-Negativos Anaeróbios Retos, Helicoidais e Curvos/genética
Óperon
Orotato Fosforribosiltransferase/genética
Regiões Promotoras Genéticas/genética
[Mh] Termos MeSH secundário: Marcadores Genéticos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Genetic Markers); EC 2.4.2.10 (Orotate Phosphoribosyltransferase)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM; S
[Da] Data de entrada para processamento:161209
[St] Status:MEDLINE
[do] DOI:10.1007/s00792-016-0902-2


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[PMID]:27913881
[Au] Autor:He MM; Zhang DS; Wang F; Wang ZX; Yuan SQ; Wang ZQ; Luo HY; Ren C; Qiu MZ; Jin Y; Wang DS; Chen DL; Zeng ZL; Li YH; He YY; Hao YT; Guo P; Wang FH; Zeng YX; Xu RH
[Ad] Endereço:State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China.
[Ti] Título:Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway.
[So] Source:Cancer Chemother Pharmacol;79(1):69-79, 2017 Jan.
[Is] ISSN:1432-0843
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach. PATIENTS AND METHODS: A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics. RESULTS: The ORR and DCR were 41.0 and 76.9%. The median PFS, TTF, and OS were 4.13, 3.70, and 11.40 months. Grade 3-4 AEs occurred in only 13 patients, and grade 4 AEs occurred in only 1 of them. High OPRT/TS and peritoneal metastasis (vs. liver metastasis) independently predicted responding. High OPRT/DPD independently predicted grade 3-4 AEs. High AUC of 5-FU and metastatic/recurrent sites ≤2 (vs. >3) independently predicted prolonged PFS. Low baseline plasmic DPD independently predicted prolonged OS. CONCLUSIONS: Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC. CLINICALTRIALS. GOV IDENTIFIER: NCT02090153.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Ácido Oxônico/metabolismo
Neoplasias Gástricas/tratamento farmacológico
Tegafur/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Citocromo P-450 CYP2A6/genética
Intervalo Livre de Doença
Combinação de Medicamentos
Feminino
Fluoruracila/farmacocinética
Seres Humanos
Leucovorina/administração & dosagem
Leucovorina/efeitos adversos
Masculino
Meia-Idade
Orotato Fosforribosiltransferase/sangue
Ácido Oxônico/administração & dosagem
Ácido Oxônico/efeitos adversos
Testes Farmacogenômicos
Neoplasias Gástricas/genética
Neoplasias Gástricas/mortalidade
Tegafur/administração & dosagem
Tegafur/efeitos adversos
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Combinations); 150863-82-4 (S 1 (combination)); 1548R74NSZ (Tegafur); 5VT6420TIG (Oxonic Acid); EC 1.14.14.1 (CYP2A6 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP2A6); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170602
[Lr] Data última revisão:
170602
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161204
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1007/s00280-016-3209-1


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[PMID]:27798895
[Au] Autor:Koda K; Miyauchi H; Kosugi C; Kaiho T; Takiguchi N; Kobayashi S; Maruyama T; Matsubara H; (Boso Clinical Oncology Group)
[Ad] Endereço:Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan k-koda@med.teikyo-u.ac.jp.
[Ti] Título:Tumor 5-FU-related mRNA Expression and Efficacy of Oral Fluoropyrimidines in Adjuvant Chemotherapy of Colorectal Cancer.
[So] Source:Anticancer Res;36(10):5325-5331, 2016 10.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: It has not been elucidated whether the clinical efficacy of oral fluoropyrimidines for adjuvant chemotherapy of colorectal cancer varies with tumor biological characteristics. PATIENTS AND METHODS: A multicenter randomized trial was performed comparing oral tegafur/gimeracil/oteracil (S-1) and uracil-tegafur/ leucovorin (UFT/LV) as adjuvant therapy for stage III colorectal cancer. Postoperative survival was compared based on the 5-FU-related mRNA levels in cancer tissues. RESULTS: Among patients with tumor expressing dihydropyrimidine dehydrogenase (DPD) mRNA within the 66.7th percentile (lower 2/3) of all cases, overall survival (OS) was significantly better in the S-1 than in the UFT/LV group. In the S-1 group, patients with low DPD-expressing tumors had significantly better OS than those with highly expressing tumors. Patients with low thymidine synthase (TS)-expressing tumors had significantly better OS than those with highly expressing tumors. CONCLUSION: The efficacy of oral fluoropyrimidines as adjuvant chemotherapy for colorectal cancer may be influenced by the level of 5-FU-related mRNA in cancer tissues.
[Mh] Termos MeSH primário: Antimetabólitos Antineoplásicos/uso terapêutico
Carcinoma
Quimioterapia Adjuvante
Neoplasias Colorretais
Fluoruracila/uso terapêutico
Leucovorina/uso terapêutico
Ácido Oxônico/uso terapêutico
Tegafur/uso terapêutico
[Mh] Termos MeSH secundário: Administração Oral
Adulto
Idoso
Antimetabólitos Antineoplásicos/efeitos adversos
Carcinoma/tratamento farmacológico
Carcinoma/enzimologia
Carcinoma/genética
Quimioterapia Adjuvante/efeitos adversos
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/enzimologia
Neoplasias Colorretais/genética
Di-Hidrouracila Desidrogenase (NADP)/genética
Combinação de Medicamentos
Feminino
Fluoruracila/efeitos adversos
Seres Humanos
Leucovorina/efeitos adversos
Masculino
Meia-Idade
Orotato Fosforribosiltransferase/genética
Ácido Oxônico/efeitos adversos
RNA Mensageiro/metabolismo
Tegafur/efeitos adversos
Tetra-Hidrofolato Desidrogenase/genética
Timidina Fosforilase/genética
Timidilato Sintase/genética
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (Drug Combinations); 0 (RNA, Messenger); 150863-82-4 (S 1 (combination)); 1548R74NSZ (Tegafur); 5VT6420TIG (Oxonic Acid); EC 1.3.1.2 (Dihydrouracil Dehydrogenase (NADP)); EC 1.5.1.3 (Tetrahydrofolate Dehydrogenase); EC 2.1.1.45 (Thymidylate Synthase); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); EC 2.4.2.4 (Thymidine Phosphorylase); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170127
[Lr] Data última revisão:
170127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE


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Fotocópia
[PMID]:27574833
[Au] Autor:Nyhan WL; Gangoiti JA
[Ad] Endereço:Biochemical Genetics Laboratory, Department of Pediatrics, University of California San Diego, La Jolla, California, United States.
[Ti] Título:Hereditary Orotic Aciduria and the Excretion of Orotidine.
[So] Source:Neuropediatrics;47(6):408-409, 2016 Dec.
[Is] ISSN:1439-1899
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Orotic aciduria and deficiency of uridine monophosphate synthetase have been observed in a patient, studied over 10 years, who had no megaloblastic anemia. Excretion of orotic acid and orotidine were 8.24 and 0.52 mmol/mol of creatinine. The ratio of 15.85 differed appreciably from that of 6 patients reported with no megaloblastic anemia. The analysis of orotidine by gas chromotography mass spectrometry was conducted. Patients with orotic aciduria with and without megaloblastic anemia cannot be distinguished by ratio of orotic acid to orotidine.
[Mh] Termos MeSH primário: Orotato Fosforribosiltransferase/deficiência
Ácido Orótico/urina
Orotidina-5´-Fosfato Descarboxilase/deficiência
Erros Inatos do Metabolismo da Purina-Pirimidina/urina
Uridina/análogos & derivados
[Mh] Termos MeSH secundário: Criança
Feminino
Seres Humanos
Orotato Fosforribosiltransferase/efeitos dos fármacos
Orotato Fosforribosiltransferase/urina
Orotidina-5'-Fosfato Descarboxilase/efeitos dos fármacos
Orotidina-5'-Fosfato Descarboxilase/urina
Uridina/uso terapêutico
Uridina/urina
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
61H4T033E5 (Orotic Acid); B350MC02GZ (orotidine); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); EC 4.1.1.23 (Orotidine-5'-Phosphate Decarboxylase); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160831
[St] Status:MEDLINE


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Fotocópia
[PMID]:27027693
[Ti] Título:In brief: Uridine triacetate (Xuriden) for hereditary orotic aciduria.
[So] Source:Med Lett Drugs Ther;58(1491):e49, 2016 Mar 28.
[Is] ISSN:1523-2859
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Acetatos/uso terapêutico
Orotato Fosforribosiltransferase/deficiência
Ácido Orótico/urina
Orotidina-5´-Fosfato Descarboxilase/deficiência
Erros Inatos do Metabolismo da Purina-Pirimidina/tratamento farmacológico
Uridina/uso terapêutico
[Mh] Termos MeSH secundário: Acetatos/administração & dosagem
Acetatos/efeitos adversos
Acetatos/economia
Administração Oral
Biomarcadores/urina
Custos de Medicamentos
Seres Humanos
Erros Inatos do Metabolismo da Purina-Pirimidina/diagnóstico
Erros Inatos do Metabolismo da Purina-Pirimidina/enzimologia
Erros Inatos do Metabolismo da Purina-Pirimidina/genética
Erros Inatos do Metabolismo da Purina-Pirimidina/urina
Resultado do Tratamento
Uridina/administração & dosagem
Uridina/efeitos adversos
Uridina/análogos & derivados
Uridina/economia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetates); 0 (Biomarkers); 2WP61F175M (uridine triacetate); 61H4T033E5 (Orotic Acid); EC 2.4.2.10 (Orotate Phosphoribosyltransferase); EC 4.1.1.23 (Orotidine-5'-Phosphate Decarboxylase); WHI7HQ7H85 (Uridine)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160331
[St] Status:MEDLINE



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