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Pesquisa : D12.776.157.530.450.074.500.500 [Categoria DeCS]
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[PMID]:26234359
[Au] Autor:Marin JJ; Al-Abdulla R; Lozano E; Briz O; Bujanda L; Banales JM; Macias RI
[Ti] Título:Mechanisms of Resistance to Chemotherapy in Gastric Cancer.
[So] Source:Anticancer Agents Med Chem;16(3):318-34, 2016.
[Is] ISSN:1875-5992
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Although surgical resection is the standard curative therapy for gastric cancer, these tumors are often diagnosed at an advanced stage, when surgery is not recommended. Alternative treatments such as radiotherapy and chemotherapy achieve only very modest results. There is therefore an urgent need to advance in this field of oncologic gastroenterology. The poor response of gastric cancer to chemotherapy is usually due to a combination of mechanisms of chemoresistance (MOC), which may include a reduction in drug uptake (MOC-1a), enhanced drug efflux (MOC-1b), a reduced proportion of active agents in tumor cells due to a reduction in pro-drug activation or an enhancement in drug inactivation (MOC-2), changes in the expression/function of the molecular targets of anticancer drugs (MOC-3), an enhanced ability of cancer cells to repair anticancer drug-induced DNA damage (MOC-4), and decreased expression/function of pro-apoptotic factors or up-regulation of anti-apoptotic genes (MOC-5). Two major goals of modern pharmacology aimed at overcoming this situation are the prediction of a lack of response to chemotherapy and the identification of the underlying mechanisms accounting for primary or acquired refractoriness to anticancer drugs. These are important issues if we are to select the best pharmacological regime for each patient and develop novel strategies to overcome chemoresistance. The present review reports updated information regarding the mechanisms of chemoresistance (from MOC-1 to MOC-5) in gastric cancer, the advances made in the prediction of the failure of chemotherapeutic treatment, and novel strategies based on gene therapy currently being developed to treat these tumors.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Citocromo P-450 CYP2A6/metabolismo
Resistência a Medicamentos Antineoplásicos
Transportadores de Ânions Orgânicos Dependentes de ATP/metabolismo
Proteínas de Transporte de Cátions Orgânicos/metabolismo
Neoplasias Gástricas/tratamento farmacológico
[Mh] Termos MeSH secundário: Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Carboxilesterase/genética
Carboxilesterase/metabolismo
Citocromo P-450 CYP2A6/genética
Reparo do DNA/efeitos dos fármacos
Terapia Genética
Seres Humanos
MicroRNAs/uso terapêutico
Terapia de Alvo Molecular
Estadiamento de Neoplasias
Transportadores de Ânions Orgânicos Dependentes de ATP/genética
Proteínas de Transporte de Cátions Orgânicos/genética
Neoplasias Gástricas/metabolismo
Neoplasias Gástricas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (MicroRNAs); 0 (Organic Anion Transporters, ATP-Dependent); 0 (Organic Cation Transport Proteins); EC 1.14.14.1 (Cytochrome P-450 CYP2A6); EC 3.1.1.1 (Carboxylesterase)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:170103
[Lr] Data última revisão:
170103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150804
[St] Status:MEDLINE


  2 / 5 MEDLINE  
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PubMed Central Texto completo
Texto completo
[PMID]:23268600
[Au] Autor:Dahlin A; Geier E; Stocker SL; Cropp CD; Grigorenko E; Bloomer M; Siegenthaler J; Xu L; Basile AS; Tang-Liu DD; Giacomini KM
[Ad] Endereço:Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California 94158, United States.
[Ti] Título:Gene expression profiling of transporters in the solute carrier and ATP-binding cassette superfamilies in human eye substructures.
[So] Source:Mol Pharm;10(2):650-63, 2013 Feb 04.
[Is] ISSN:1543-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The barrier epithelia of the cornea and retina control drug and nutrient access to various compartments of the human eye. While ocular transporters are likely to play a critical role in homeostasis and drug delivery, little is known about their expression, localization and function. In this study, the mRNA expression levels of 445 transporters, metabolic enzymes, transcription factors and nuclear receptors were profiled in five regions of the human eye: cornea, iris, ciliary body, choroid and retina. Through RNA expression profiling and immunohistochemistry, several transporters were identified as putative targets for drug transport in ocular tissues. Our analysis identified SLC22A7 (OAT2), a carrier for the antiviral drug acyclovir, in the corneal epithelium, in addition to ABCG2 (BCRP), an important xenobiotic efflux pump, in retinal nerve fibers and the retinal pigment epithelium. Collectively, our results provide an understanding of the transporters that serve to maintain ocular homeostasis and which may be potential targets for drug delivery to deep compartments of the eye.
[Mh] Termos MeSH primário: Olho/metabolismo
Perfilação da Expressão Gênica/métodos
Transportadores de Ânions Orgânicos Dependentes de ATP/metabolismo
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP
Transportadores de Cassetes de Ligação de ATP/genética
Transportadores de Cassetes de Ligação de ATP/metabolismo
Aciclovir/metabolismo
Córnea/metabolismo
Seres Humanos
Imuno-Histoquímica
Técnicas In Vitro
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Transportadores de Ânions Orgânicos Dependentes de ATP/genética
Transportadores de Ânions Orgânicos Sódio-Independentes/genética
Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Retina/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (ABCG2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Neoplasm Proteins); 0 (Organic Anion Transporters, ATP-Dependent); 0 (Organic Anion Transporters, Sodium-Independent); 0 (SLC22A7 protein, human); X4HES1O11F (Acyclovir)
[Em] Mês de entrada:1308
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:121228
[St] Status:MEDLINE
[do] DOI:10.1021/mp300429e


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[PMID]:15367380
[Au] Autor:Itagaki S; Shimamoto S; Hirano T; Iseki K; Sugawara M; Nishimura S; Fujimoto M; Kobayashi M; Miyazaki K
[Ad] Endereço:Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, Japan.
[Ti] Título:Comparison of urinary excretion of phenolsulfonphthalein in an animal model for Wilson's disease (Long-Evans Cinnamon rats) with that in normal Wistar rats: involvement of primary active organic anion transporter.
[So] Source:J Pharm Pharm Sci;7(2):227-34, 2004 Jul 13.
[Is] ISSN:1482-1826
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The aim of this study was to determine the cause of the decline in phenolsulfonphthalein (PSP) excretion in Long-Evans Cinnamon (LEC) rats. METHODS: The uptake of PSP into rat renal basolateral membrane vesicles (BLMV) was studied. Cyclosporin A (CYA) was used to modulate an ATP-dependent primary active transporter. PSP was intravenously injected into rats with or without CYA. The transcellular transport of PSP was examined by using primary cultured renal proximal tubule cells (PTC). RESULTS: No significant difference was found between the uptake of PSP into renal BLMV of Wistar rats and that into renal BLMV of LEC rats. In the presence of CYA, the urinary excretion and the plasma concentrations of PSP in Wistar rats were decreased and increased, respectively. In primary cultured renal PTC from Wistar rats, the basal-to-apical transport of PSP was greater than that in the opposite direction and the basal-to-apical transport of PSP was substantially reduced by the addition of CYA. However, CYA did not affect the basal-to-apical transport of PSP in PTC from LEC rats. CONCLUSIONS: The results suggest that PSP is transported by primary active organic anion transporter and that the activity level of this transporter is reduced in LEC rats.
[Mh] Termos MeSH primário: Degeneração Hepatolenticular/metabolismo
Rim/metabolismo
Transportadores de Ânions Orgânicos Dependentes de ATP/fisiologia
Fenolsulfonaftaleína
Ratos Endogâmicos LEC/metabolismo
[Mh] Termos MeSH secundário: Animais
Ciclosporina/farmacologia
Modelos Animais de Doenças
Degeneração Hepatolenticular/urina
Técnicas In Vitro
Rim/efeitos dos fármacos
Cinética
Masculino
Transportadores de Ânions Orgânicos Dependentes de ATP/antagonistas & inibidores
Fenolsulfonaftaleína/metabolismo
Ratos
Ratos Wistar
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organic Anion Transporters, ATP-Dependent); 83HN0GTJ6D (Cyclosporine); I6G9Y0J1OJ (Phenolsulfonphthalein)
[Em] Mês de entrada:0412
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:040916
[St] Status:MEDLINE


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Bracht, Adelar
[PMID]:12421651
[Au] Autor:Fernandes TR; de Oliveira DS; Suzuki-Kemmelmeier F; Bracht A
[Ad] Endereço:Laboratory of Liver Metabolism, Department of Biochemistry, University of Maringá, 87020900 Maringá, Brazil.
[Ti] Título:Inhibition by extracellular ATP of organic anion transport in the perfused rat liver.
[So] Source:Eur J Pharmacol;454(2-3):225-34, 2002 Nov 15.
[Is] ISSN:0014-2999
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The action of extracellular ATP on organic anion transport in the bivascularly perfused rat liver was investigated, using bromosulfophthalein as a model substance. Transport was measured by means of the multiple-indicator dilution technique. The action of portal 100 microM ATP presented the following characteristics: (a) inhibition of bromosulfophthalein single pass extraction; the inhibition degree decreased with increasing bromosulfophthalein doses; (b) diminution of the influx rate coefficients; (c) 86.7% decrease of the maximal activity of the saturable component for bromosulfophthalein transport, but 100% increase of the non-saturable component; (d) diminution of the bromosulfophthalein flow-limited distribution space; (e) no significant alteration of the rate coefficients for metabolic sequestration. The action of ATP on organic anion transport in the intact liver occurred at much lower concentrations (10x) than those previously reported for isolated hepatocytes. This reinforces the suggestion that inhibition of organic anion transport could be a physiologically relevant effect of extracellular ATP.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/farmacologia
Espaço Extracelular/efeitos dos fármacos
Fígado/efeitos dos fármacos
Sulfobromoftaleína/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico/efeitos dos fármacos
Transporte Biológico/fisiologia
Relação Dose-Resposta a Droga
Espaço Extracelular/metabolismo
Fígado/metabolismo
Masculino
Transportadores de Ânions Orgânicos Dependentes de ATP/antagonistas & inibidores
Transportadores de Ânions Orgânicos Dependentes de ATP/metabolismo
Perfusão/métodos
Ratos
Ratos Wistar
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Organic Anion Transporters, ATP-Dependent); 0C2P5QKL36 (Sulfobromophthalein); 8L70Q75FXE (Adenosine Triphosphate)
[Em] Mês de entrada:0305
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:021108
[St] Status:MEDLINE


  5 / 5 MEDLINE  
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[PMID]:14650445
[Au] Autor:Poot M; Hudson FN; Grossmann A; Rabinovitch PS; Kavanagh TJ
[Ad] Endereço:Department of Human Genetics, University of Würzburg, 97074 Würzburg, Germany.
[Ti] Título:Probenicid inhibition of fluorescence extrusion after MCB-staining of rat-1 fibroblasts.
[So] Source:Cytometry;23(1):78-81, 1996 Jan 01.
[Is] ISSN:0196-4763
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The intracellular fluorescence level of cells stained continuously with monochlorobimane was monitored by flow cytometry in order to assess the initial rate of glutatione to monochlorobimane conjugation as a measure of glutathione S-transferase activity. In addition to a rapid initial increase and a plateau level, a decline in fluorescence intensity was found upon prolonged flow cytometric monitoring. Exposure to probenicid, an inhibitor of an ATP-dependent organic anion pump, prevented this decrease. Incubation with vanadate and verapamil was without effect. Thus, extrusion of fluorescentglutathione-conjugate perturbs the proportionality between initial glutathione level and monochlorobimane-dependent fluorescence intensity. Monitoring by flow cytometry the decrease in monochlorobimane-dependent fluorescence may be useful to detect multidrug resistant cells.
[Mh] Termos MeSH primário: Fibroblastos/metabolismo
Citometria de Fluxo/métodos
Glutationa Transferase/metabolismo
Histocitoquímica/métodos
Probenecid/farmacologia
[Mh] Termos MeSH secundário: Células 3T3
Animais
Fibroblastos/citologia
Fibroblastos/efeitos dos fármacos
Camundongos
Transportadores de Ânions Orgânicos Dependentes de ATP/antagonistas & inibidores
Transportadores de Ânions Orgânicos Dependentes de ATP/metabolismo
Pirazóis/metabolismo
Ratos
Uricosúricos/farmacologia
Vanadatos/farmacologia
Verapamil/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Organic Anion Transporters, ATP-Dependent); 0 (Pyrazoles); 0 (Uricosuric Agents); 3WHH0066W5 (Vanadates); 76421-73-3 (monochlorobimane); CJ0O37KU29 (Verapamil); EC 2.5.1.18 (Glutathione Transferase); PO572Z7917 (Probenecid)
[Em] Mês de entrada:0402
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:960101
[St] Status:MEDLINE



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