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  1 / 2513 MEDLINE  
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[PMID]:29442031
[Au] Autor:Peng Y; Xu B; Tang J; Wan Z; Sun H; Wang G; Zhu YS
[Ti] Título:Analysis of ABCG2 methylation in stool samples of Chinese healthy males by pyrosequencing.
[So] Source:Pharmazie;71(8):447-454, 2016 08 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:ABCG2, an efflux pump protein-BCRP coding gene, is involved in the acquisition of chemotherapeutic drug resistance. In recent years, the epigenetic regulation of ABCG2, such as DNA methylation, has become a research hotspot and been attracting widespread attention. Methylation Special PCR (MSP) has been the mainly used method for gene methylation detection for a long time. With the development of pyrosequencing (PSQ) instrument and the convenience, simpleness, and economical benefit it brings, it will become the mainstream method for gene methylation detection in the near future. This study aims to establish a pyrosequencing method for detecting the methylation sites on ABCG2 gene promoter up-stream region, the promoter region and the first exon region, and to detect the methylation level of each site in stool samples, respectively. Thus, it cannot only lay the methodological foundation for the study of BCRP-mediated multi-drug resistance mechanisms in tumor cells, but also can give knowledge of ABCG2 methylation distribution in the intestine of Chinese healthy males by detecting the ABCG2 methylation levels in stool samples as the exfoliated intestinal epithelial cells constantly shed into the stool.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética
Fezes/química
Proteínas de Neoplasias/genética
Análise de Sequência de Proteína/métodos
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Adulto
Grupo com Ancestrais do Continente Asiático
Ilhas de CpG/genética
Metilação de DNA
Epigênese Genética
Éxons
Voluntários Saudáveis
Seres Humanos
Masculino
Proteínas de Neoplasias/metabolismo
Regiões Promotoras Genéticas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCG2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Neoplasm Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6559


  2 / 2513 MEDLINE  
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[PMID]:28463231
[Au] Autor:Gaskill CF; Carrier EJ; Kropski JA; Bloodworth NC; Menon S; Foronjy RF; Taketo MM; Hong CC; Austin ED; West JD; Means AL; Loyd JE; Merryman WD; Hemnes AR; De Langhe S; Blackwell TS; Klemm DJ; Majka SM
[Ad] Endereço:Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine or Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee USA.
[Ti] Título:Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction.
[So] Source:J Clin Invest;127(6):2262-2276, 2017 Jun 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pulmonary vascular disease is characterized by remodeling and loss of microvessels and is typically attributed to pathological responses in vascular endothelium or abnormal smooth muscle cell phenotypes. We have challenged this understanding by defining an adult pulmonary mesenchymal progenitor cell (MPC) that regulates both microvascular function and angiogenesis. The current understanding of adult MPCs and their roles in homeostasis versus disease has been limited by a lack of genetic markers with which to lineage label multipotent mesenchyme and trace the differentiation of these MPCs into vascular lineages. Here, we have shown that lineage-labeled lung MPCs expressing the ATP-binding cassette protein ABCG2 (ABCG2+) are pericyte progenitors that participate in microvascular homeostasis as well as adaptive angiogenesis. Activation of Wnt/ß-catenin signaling, either autonomously or downstream of decreased BMP receptor signaling, enhanced ABCG2+ MPC proliferation but suppressed MPC differentiation into a functional pericyte lineage. Thus, enhanced Wnt/ß-catenin signaling in ABCG2+ MPCs drives a phenotype of persistent microvascular dysfunction, abnormal angiogenesis, and subsequent exacerbation of bleomycin-induced fibrosis. ABCG2+ MPCs may, therefore, account in part for the aberrant microvessel function and remodeling that are associated with chronic lung diseases.
[Mh] Termos MeSH primário: Células Mesenquimais Estromais/fisiologia
Microvasos/fisiopatologia
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Animais
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo
Diferenciação Celular
Linhagem da Célula
Células Cultivadas
Seres Humanos
Pulmão/irrigação sanguínea
Camundongos Transgênicos
Microvasos/patologia
Neovascularização Patológica/metabolismo
Pericitos/fisiologia
Estabilidade Proteica
Fibrose Pulmonar/metabolismo
Fibrose Pulmonar/patologia
Vasoconstrição
Via de Sinalização Wnt
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Abcg2 protein, mouse); EC 2.7.11.30 (Bmpr2 protein, mouse); EC 2.7.11.30 (Bone Morphogenetic Protein Receptors, Type II)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  3 / 2513 MEDLINE  
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Maia, Raquel Ciuvalschi
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[PMID]:27770655
[Au] Autor:da Cunha Vasconcelos F; Mauricio Scheiner MA; Moellman-Coelho A; Mencalha AL; Renault IZ; Rumjanek VM; Maia RC
[Ad] Endereço:Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenação de Pesquisa, Instituto Nacional de Câncer (INCA), RJ, Brazil.
[Ti] Título:Low ABCB1 and high OCT1 levels play a favorable role in the molecular response to imatinib in CML patients in the community clinical practice.
[So] Source:Leuk Res;51:3-10, 2016 12.
[Is] ISSN:1873-5835
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Despite the favorable clinical evolution of patients with chronic myeloid leukemia (CML), resistance or intolerance to imatinib is present in approximately 35% of patients. Sokal score is a widely used risk factor, however efflux and influx transporters are provisional risk factors implicated in imatinib resistance. This study analyzed Sokal score, ABCB1, ABCG2 and OCT1 mRNA transporter expression levels as well as P-glycoprotein expression and efflux transporters activity to seek a possible correlation between these factors and the molecular response at 12 months from imatinib start as well as 8-year overall survival (OS). Low plus intermediate Sokal score correlated to optimal imatinib responses, as well as OS at 8-years, thus confirming the established role of Sokal score as a prognostic factor in CML patients. Low ABCB1 and high OCT1 mRNA levels were associated with an optimal molecular response, while the inverse levels were associated with non-responders (warning and failure) patients. Our results suggest that ABCB1 and OCT1 mRNA expressions may present biological relevance to identify responder and non-responder patients to imatinib treatment.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Mesilato de Imatinib/uso terapêutico
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Transportador 1 de Cátions Orgânicos/genética
RNA Mensageiro/sangue
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/sangue
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/sangue
Adolescente
Adulto
Idoso
Resistência a Medicamentos Antineoplásicos
Feminino
Hospitais Comunitários
Seres Humanos
Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico
Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade
Masculino
Meia-Idade
Prognóstico
Indução de Remissão
Fatores de Risco
Taxa de Sobrevida
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCB1 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Antineoplastic Agents); 0 (Organic Cation Transporter 1); 0 (RNA, Messenger); 8A1O1M485B (Imatinib Mesylate)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


  4 / 2513 MEDLINE  
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[PMID]:29331377
[Au] Autor:Jeong WY; Yoo HY; Kim CW
[Ad] Endereço:Department of Biotechnology, BK21 Plus Program, College of Life Sciences and Biotechnology, Korea University, 1-5, Anam Dong, Seongbuk-Gu, Seoul 136-701, South Korea.
[Ti] Título:ß-cellulin promotes the proliferation of corneal epithelial stem cells through the phosphorylation of erk1/2.
[So] Source:Biochem Biophys Res Commun;496(2):359-366, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The proliferation of corneal epithelial stem cells (CESCs) is a very important process in the recovery of corneal wounds. Recent studies have shown that ß-cellulin (BC) is effective in the repair of other tissues. However, its mechanism of action in corneal wound healing is not yet clear. The purpose of this study was to investigate how BC accelerates wound healing of the cornea. Here, we confirmed that the proliferation of CESCs was induced at a specific concentration (0.2, 2 and 20 ng/mL) by treatment with BC. Markers associated with proliferation activity (ΔNp63, bmi-1, abcg2) were also upregulated. In vivo experiments showed that the corneal wound healing rate was increased in mice. We found that BC stimulates the phosphorylation of the erk1/2 signaling pathway, which is triggered during the recovery of mouse corneal wounds. However, the inhibition of erk1/2 phosphorylation delayed the recovery of mouse corneal wounds in an organ culture assay. According to these results, BC may be a potential treatment factor for corneal wound healing.
[Mh] Termos MeSH primário: Betacelulina/farmacologia
Células Epiteliais/efeitos dos fármacos
Epitélio Anterior/efeitos dos fármacos
Proteína Quinase 1 Ativada por Mitógeno/genética
Proteína Quinase 3 Ativada por Mitógeno/genética
Células-Tronco/efeitos dos fármacos
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Animais
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células Epiteliais/metabolismo
Células Epiteliais/patologia
Epitélio Anterior/lesões
Epitélio Anterior/metabolismo
Regulação da Expressão Gênica
Camundongos
Camundongos Endogâmicos BALB C
Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Técnicas de Cultura de Órgãos
Fosfoproteínas/genética
Fosfoproteínas/metabolismo
Fosforilação/efeitos dos fármacos
Complexo Repressor Polycomb 1/genética
Complexo Repressor Polycomb 1/metabolismo
Inibidores de Proteínas Quinases/farmacologia
Proteínas Proto-Oncogênicas/genética
Proteínas Proto-Oncogênicas/metabolismo
Células-Tronco/metabolismo
Células-Tronco/patologia
Transativadores/genética
Transativadores/metabolismo
Cicatrização/efeitos dos fármacos
Cicatrização/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Abcg2 protein, mouse); 0 (Betacellulin); 0 (Bmi1 protein, mouse); 0 (Btc protein, mouse); 0 (Phosphoproteins); 0 (Protein Kinase Inhibitors); 0 (Proto-Oncogene Proteins); 0 (Trans-Activators); 0 (Trp63 protein, mouse); EC 2.3.2.27 (Polycomb Repressive Complex 1); EC 2.7.11.24 (Mapk1 protein, mouse); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE


  5 / 2513 MEDLINE  
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[PMID]:29342177
[Au] Autor:Szabó E; Türk D; Telbisz Á; Kucsma N; Horváth T; Szakács G; Homolya L; Sarkadi B; Várady G
[Ad] Endereço:Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
[Ti] Título:A new fluorescent dye accumulation assay for parallel measurements of the ABCG2, ABCB1 and ABCC1 multidrug transporter functions.
[So] Source:PLoS One;13(1):e0190629, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ABC multidrug transporters are key players in cancer multidrug resistance and in general xenobiotic elimination, thus their functional assays provide important tools for research and diagnostic applications. In this study we have examined the potential interactions of three key human ABC multidrug transporters with PhenGreen diacetate (PGD), a cell permeable fluorescent metal ion indicator. The non-fluorescent, hydrophobic PGD rapidly enters the cells and, after cleavage by cellular esterases, in the absence of quenching metal ions, PhenGreen (PG) becomes highly fluorescent. We found that in cells expressing functional ABCG2, ABCB1, or ABCC1 transporters, cellular PG fluorescence is strongly reduced. This fluorescence signal in the presence of specific transporter inhibitors is increased to the fluorescence levels in the control cells. Thus the PG accumulation assay is a new, unique tool for the parallel determination of the function of the ABCG2, ABCB1, and ABCC1 multidrug transporters. Since PG has very low cellular toxicity, the PG accumulation assay also allows the selection, separation and culturing of selected cell populations expressing either of these transporters.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Corantes Fluorescentes/metabolismo
Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo
Proteínas de Neoplasias/metabolismo
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo
Linhagem Celular Tumoral
Citometria de Fluxo
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCB1 protein, human); 0 (ABCG2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Fluorescent Dyes); 0 (Multidrug Resistance-Associated Proteins); 0 (Neoplasm Proteins); Y49M64GZ4Q (multidrug resistance-associated protein 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190629


  6 / 2513 MEDLINE  
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Bento, Ricardo Ferreira
Texto completo SciELO Brasil
[PMID]:29236919
[Au] Autor:Massucci-Bissoli M; Lezirovitz K; Oiticica J; Bento RF
[Ad] Endereço:Departamento de Otorrinolaringologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR.
[Ti] Título:Evidence of progenitor cells in the adult human cochlea: sphere formation and identification of ABCG2.
[So] Source:Clinics (Sao Paulo);72(11):714-717, 2017 Nov.
[Is] ISSN:1980-5322
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The aim of this study was to search for evidence of stem or progenitor cells in the adult human cochlea by testing for sphere formation capacity and the presence of the stem cell marker ABCG2. METHODS: Cochleas removed from patients undergoing vestibular schwannoma resection (n=2) and from brain-dead organ donors (n=4) were dissociated for either flow cytometry analysis for the stem cell marker ABCG2 or a sphere formation assay that is widely used to test the sphere-forming capacity of cells from mouse inner ear tissue. RESULTS: Spheres were identified after 2-5 days in vitro, and the stem cell marker ABCG2 was detected using flow cytometric analysis after cochlear dissociation. CONCLUSIONS: Evidence suggests that there may be progenitor cells in the adult human cochlea, although further studies are required.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/análise
Cóclea/citologia
Proteínas de Neoplasias/análise
Células-Tronco/citologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Proliferação Celular
Feminino
Citometria de Fluxo
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCG2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Neoplasm Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE


  7 / 2513 MEDLINE  
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[PMID]:28455266
[Au] Autor:Patel A; Li TW; Anreddy N; Wang DS; Sodani K; Gadhia S; Kathawala R; Yang DH; Cheng C; Chen ZS
[Ad] Endereço:Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
[Ti] Título:Suppression of ABCG2 mediated MDR in vitro and in vivo by a novel inhibitor of ABCG2 drug transport.
[So] Source:Pharmacol Res;121:184-193, 2017 Jul.
[Is] ISSN:1096-1186
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cancer is a disease whose treatment is often limited due to the development of a phenomenon known as multidrug resistance (MDR). There is an immense demand for development of novel agents that can overcome the MDR in cancer. A group of transmembrane proteins called ATP-binding cassette transporters, present ubiquitously in the human body possesses a modular architecture, contributing immensely towards the development of MDR. An analysis of structural congeners among a group of compounds led to the discovery of CCTA-1523 that could selectively reverse ABCG2-mediated MDR in cancer cells in vitro and in vivo. CCTA-1523 (5µM) sensitized the ABCG2 overexpressing cancer cells and ABCG2 transfected cells to the substrate chemotherapeutic drugs. The reversal ability of CCTA-1523 was primarily due to the inhibition of the efflux function of ABCG2; also there was no change in the protein expression or the localization of the ABCG2 in the presence of CCTA-1523. The reversal effect of CCTA-1523 was reversible. Importantly, co-administration of CCTA-1523 restored the in vivo antitumor activity of doxorubicin in ABCG2 overexpressing tumor xenografts. Taken together, our findings indicate that CCTA-1523 is a potent, selective and reversible modulator of ABCG2 that may offer therapeutic promise for multidrug- resistant malignancies.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores
Acetanilidas/farmacologia
Antineoplásicos/farmacologia
Resistência a Múltiplos Medicamentos/efeitos dos fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Neoplasias/tratamento farmacológico
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Acetanilidas/uso terapêutico
Animais
Antineoplásicos/uso terapêutico
Transporte Biológico/efeitos dos fármacos
Linhagem Celular Tumoral
Doxorrubicina/farmacologia
Doxorrubicina/uso terapêutico
Seres Humanos
Masculino
Camundongos Nus
Neoplasias/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Acetanilides); 0 (Antineoplastic Agents); 0 (CCTA-1523); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  8 / 2513 MEDLINE  
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[PMID]:28921565
[Au] Autor:de Gooijer MC; Zhang P; Weijer R; Buil LCM; Beijnen JH; van Tellingen O
[Ad] Endereço:Division of Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066, CX, The Netherlands.
[Ti] Título:The impact of P-glycoprotein and breast cancer resistance protein on the brain pharmacokinetics and pharmacodynamics of a panel of MEK inhibitors.
[So] Source:Int J Cancer;142(2):381-391, 2018 Jan 15.
[Is] ISSN:1097-0215
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitogen/extracellular signal-regulated kinase (MEK) inhibitors have been tested in clinical trials for treatment of intracranial neoplasms, including glioblastoma (GBM), but efficacy of these drugs has not yet been demonstrated. The blood-brain barrier (BBB) is a major impediment to adequate delivery of drugs into the brain and may thereby also limit the successful implementation of MEK inhibitors against intracranial malignancies. The BBB is equipped with a range of ATP-dependent efflux transport proteins, of which P-gp (ABCB1) and BCRP (ABCG2) are the two most dominant for drug efflux from the brain. We investigated their impact on the pharmacokinetics and target engagement of a panel of clinically applied MEK inhibitors, in order to select the most promising candidate for brain cancers in the context of clinical pharmacokinetics and inhibitor characteristics. To this end, we used in vitro drug transport assays and conducted pharmacokinetic and pharmacodynamic studies in wildtype and ABC-transporter knockout mice. PD0325901 displayed more promising characteristics than trametinib (GSK1120212), binimetinib (MEK162), selumetinib (AZD6244), and pimasertib (AS703026): PD0325901 was the weakest substrate of P-gp and BCRP in vitro, its brain penetration was only marginally higher in Abcb1a/b;Abcg2 mice, and efficient target inhibition in the brain could be achieved at clinically relevant plasma levels. Notably, target inhibition could also be demonstrated for selumetinib, but only at plasma levels far above levels in patients receiving the maximum tolerated dose. In summary, our study recommends further development of PD0325901 for the treatment of intracranial neoplasms.
[Mh] Termos MeSH primário: Subfamília B de Transportador de Cassetes de Ligação de ATP/fisiologia
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/fisiologia
Encéfalo/efeitos dos fármacos
MAP Quinase Quinase 1/antagonistas & inibidores
Inibidores de Proteínas Quinases/farmacologia
Inibidores de Proteínas Quinases/farmacocinética
[Mh] Termos MeSH secundário: Animais
Barreira Hematoencefálica/efeitos dos fármacos
Barreira Hematoencefálica/metabolismo
Encéfalo/metabolismo
Camundongos
Camundongos Knockout
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Abcg2 protein, mouse); 0 (Protein Kinase Inhibitors); 0 (multidrug resistance protein 3); EC 2.7.12.2 (MAP Kinase Kinase 1); EC 3.6.3.44 (Abcb1b protein, mouse)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171214
[Lr] Data última revisão:
171214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE
[do] DOI:10.1002/ijc.31052


  9 / 2513 MEDLINE  
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[PMID]:28968913
[Au] Autor:Stiburkova B; Pavelcova K; Zavada J; Petru L; Simek P; Cepek P; Pavlikova M; Matsuo H; Merriman TR; Pavelka K
[Ad] Endereço:Institute of Rheumatology.
[Ti] Título:Functional non-synonymous variants of ABCG2 and gout risk.
[So] Source:Rheumatology (Oxford);56(11):1982-1992, 2017 Nov 01.
[Is] ISSN:1462-0332
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: Common dysfunctional variants of ATP binding cassette subfamily G member 2 (Junior blood group) (ABCG2), a high-capacity urate transporter gene, that result in decreased urate excretion are major causes of hyperuricemia and gout. In the present study, our objective was to determine the frequency and effect on gout of common and rare non-synonymous and other functional allelic variants in the ABCG2 gene. Methods: The main cohort recruited from the Czech Republic consisted of 145 gout patients; 115 normouricaemic controls were used for comparison. We amplified, directly sequenced and analysed 15 ABCG2 exons. The associations between genetic variants and clinical phenotype were analysed using the t-test, Fisher's exact test and a logistic and linear regression approach. Data from a New Zealand Polynesian sample set and the UK Biobank were included for the p.V12M analysis. Results: In the ABCG2 gene, 18 intronic (one dysfunctional splicing) and 11 exonic variants were detected: 9 were non-synonymous (2 common, 7 rare including 1 novel), namely p.V12M, p.Q141K, p.R147W, p.T153M, p.F373C, p.T434M, p.S476P, p.D620N and p.K360del. The p.Q141K (rs2231142) variant had a significantly higher minor allele frequency (0.23) in the gout patients compared with the European-origin population (0.09) and was significantly more common among gout patients than among normouricaemic controls (odds ratio = 3.26, P < 0.0001). Patients with non-synonymous allelic variants had an earlier onset of gout (42 vs 48 years, P = 0.0143) and a greater likelihood of a familial history of gout (41% vs 27%, odds ratio = 1.96, P = 0.053). In a meta-analysis p.V12M exerted a protective effect from gout (P < 0.0001). Conclusion: Genetic variants of ABCG2, common and rare, increased the risk of gout. Non-synonymous allelic variants of ABCG2 had a significant effect on earlier onset of gout and the presence of a familial gout history. ABCG2 should thus be considered a common and significant risk factor for gout.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética
Gota/genética
Hiperuricemia/genética
Proteínas de Neoplasias/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Alelos
República Tcheca
Grupo com Ancestrais do Continente Europeu/genética
Feminino
Predisposição Genética para Doença
Variação Genética
Seres Humanos
Modelos Lineares
Modelos Logísticos
Masculino
Meia-Idade
Nova Zelândia
Grupo com Ancestrais Oceânicos/genética
Reino Unido
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCG2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Neoplasm Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE
[do] DOI:10.1093/rheumatology/kex295


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[PMID]:28916341
[Au] Autor:Gujarati NA; Zeng L; Gupta P; Chen ZS; Korlipara VL
[Ad] Endereço:Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, United States.
[Ti] Título:Design, synthesis and biological evaluation of benzamide and phenyltetrazole derivatives with amide and urea linkers as BCRP inhibitors.
[So] Source:Bioorg Med Chem Lett;27(20):4698-4704, 2017 10 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Breast cancer resistant protein (BCRP/ABCG2), a 72kDa plasma membrane transporter protein is a member of ABC transporter superfamily. Increased expression of BCRP causes increased efflux and therefore, reduced intracellular accumulation of many unrelated chemotherapeutic agents leading to multidrug resistance (MDR). A series of 31 benzamide and phenyltetrazole derivatives with amide and urea linkers has been synthesized to serve as potential BCRP inhibitors in order to overcome BCRP-mediated MDR. The target derivatives were tested for their cytotoxicity and reversal effects in human non-small cell lung cancer cell line H460 and mitoxantrone resistant cell line H460/MX20 using the MTT assay. In the benzamide series, compounds 6 and 7 exhibited a fold resistance of 1.51 and 1.62, respectively at 10µM concentration which is similar to that of FTC, a known BCRP inhibitor. Compounds 27 and 31 were the most potent analogues in the phenyltetrazole series with amide linker with a fold resistance of 1.39 and 1.32, respectively at 10µM concentration. For the phenyltetrazole series with urea linker, 38 exhibited a fold resistance of 1.51 which is similar than that of FTC and is the most potent compound in this series. The target compounds did not exhibit reversal effect in P-gp overexpressing resistant cell line SW620/Ad300 suggesting that they are selective BCRP inhibitors.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores
Benzamidas/química
Benzamidas/farmacologia
Desenho de Drogas
Proteínas de Neoplasias/antagonistas & inibidores
Tetrazóis/química
Tetrazóis/farmacologia
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Amidas/química
Antineoplásicos/síntese química
Antineoplásicos/química
Antineoplásicos/farmacologia
Benzamidas/síntese química
Linhagem Celular Tumoral
Resistência a Múltiplos Medicamentos/efeitos dos fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Proteínas de Neoplasias/metabolismo
Relação Estrutura-Atividade
Tetrazóis/síntese química
Ureia/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCG2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Amides); 0 (Antineoplastic Agents); 0 (Benzamides); 0 (Neoplasm Proteins); 0 (Tetrazoles); 6X80438640 (benzamide); 8W8T17847W (Urea)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170917
[St] Status:MEDLINE



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