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[PMID]:28764093
[Au] Autor:Li Y; Wang A; Bai Y; Wang S
[Ad] Endereço:College of Food Science and Nutritional Engineering, China Agricultural University, 17# Qinghua East Road, Haidian District, Beijing 100083, China. Electronic address: ying_li1992@163.com.
[Ti] Título:Acriflavine-immobilized eggshell membrane as a new solid-state biosensor for Sudan I-IV detection based on fluorescence resonance energy transfer.
[So] Source:Food Chem;237:966-973, 2017 Dec 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A novel solid-surface fluorescence biosensor for rapid detection of Sudan I-IV was proposed based on fluorescence resonance energy transfer (FRET). The biosensor was fabricated by immobilizing acriflavine (AY) on the eggshell membrane (ESM) with glutaraldehyde as cross-linking agent. FRET mechanism was demonstrated by using AY and Sudan dyes as donor and acceptor respectively, an efficient energy transfer in the present system was indicated by the sufficient spectral overlap integral (J) and proper Förster critical distance (R ). Under optimum conditions, the fluorescence of the AY-ESM could be efficiently quenched by Sudan I-IV and the corresponding linear range was 0.5-60µM with the detection limits (3σ/slope) of 0.16, 0.26, 0.21 and 0.17µM respectively. Compared to the detection of Sudan dyes in solution-state, the membrane biosensor exhibited advantages of low detection limits, high sensitivity and selectivity, as well as excellent stability. Recovery tests in spiked real samples also achieved satisfactory results.
[Mh] Termos MeSH primário: Compostos Azo/análise
Casca de Ovo
Naftóis/análise
[Mh] Termos MeSH secundário: Acriflavina
Animais
Técnicas Biossensoriais
Galinhas
Transferência Ressonante de Energia de Fluorescência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Azo Compounds); 0 (Naphthols); 1T3A50395T (Acriflavine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE


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[PMID]:28576876
[Au] Autor:Cheloni G; Tanturli M; Tusa I; Ho DeSouza N; Shan Y; Gozzini A; Mazurier F; Rovida E; Li S; Dello Sbarba P
[Ad] Endereço:Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio", Università degli Studi di Firenze, Florence, Italy.
[Ti] Título:Targeting chronic myeloid leukemia stem cells with the hypoxia-inducible factor inhibitor acriflavine.
[So] Source:Blood;130(5):655-665, 2017 Aug 03.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chronic myeloid leukemia (CML) is a hematopoietic stem cell (HSC)-driven neoplasia characterized by expression of the constitutively active tyrosine kinase BCR/Abl. CML therapy based on tyrosine kinase inhibitors (TKIs) is highly effective in inducing remission but not in targeting leukemia stem cells (LSCs), which sustain minimal residual disease and are responsible for CML relapse following discontinuation of treatment. The identification of molecules capable of targeting LSCs appears therefore of primary importance to aim at CML eradication. LSCs home in bone marrow areas at low oxygen tension, where HSCs are physiologically hosted. This study addresses the effects of pharmacological inhibition of hypoxia-inducible factor-1 (HIF-1), a critical regulator of LSC survival, on the maintenance of CML stem cell potential. We found that the HIF-1 inhibitor acriflavine (ACF) decreased survival and growth of CML cells. These effects were paralleled by decreased expression of c-Myc and stemness-related genes. Using different in vitro stem cell assays, we showed that ACF, but not TKIs, targets the stem cell potential of CML cells, including primary cells explanted from 12 CML patients. Moreover, in a murine CML model, ACF decreased leukemia development and reduced LSC maintenance. Importantly, ACF exhibited significantly less-severe effects on non-CML hematopoietic cells in vitro and in vivo. Thus, we propose ACF, a US Food and Drug Administration (FDA)-approved drug for nononcological use in humans, as a novel therapeutic approach to prevent CML relapse and, in combination with TKIs, enhance induction of remission.
[Mh] Termos MeSH primário: Acriflavina/farmacologia
Sistemas de Liberação de Medicamentos/métodos
Fator 1 Induzível por Hipóxia/antagonistas & inibidores
Leucemia Mielogênica Crônica BCR-ABL Positiva
Proteínas de Neoplasias/antagonistas & inibidores
Neoplasias Experimentais
Células-Tronco Neoplásicas/metabolismo
[Mh] Termos MeSH secundário: Animais
Sobrevivência Celular
Seres Humanos
Fator 1 Induzível por Hipóxia/metabolismo
Células K562
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
Camundongos
Células NIH 3T3
Proteínas de Neoplasias/metabolismo
Neoplasias Experimentais/tratamento farmacológico
Neoplasias Experimentais/metabolismo
Neoplasias Experimentais/patologia
Células-Tronco Neoplásicas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypoxia-Inducible Factor 1); 0 (Neoplasm Proteins); 1T3A50395T (Acriflavine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170810
[Lr] Data última revisão:
170810
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170604
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2016-10-745588


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[PMID]:27789234
[Au] Autor:Beiranvand ZS; Abbasi AR; Dehdashtian S; Karimi Z; Azadbakht A
[Ad] Endereço:Department of Chemistry, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran.
[Ti] Título:Aptamer-based electrochemical biosensor by using Au-Pt nanoparticles, carbon nanotubes and acriflavine platform.
[So] Source:Anal Biochem;518:35-45, 2017 Feb 01.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Herein, an ultrasensitive electrochemical aptasensor for quantitative detection of bisphenol A (BPA) was fabricated based on a novel signal amplification strategy. This aptasensor was developed by electrodeposition of gold-platinum nanoparticles (Au-PtNPs) on glassy carbon (GC) electrode modified with acid-oxidized carbon nanotubes (CNTs-COOH). In this protocol, acriflavine (ACF) was covalently immobilized at the surface of glassy carbon electrode modified with Au-PtNPs/CNTs-COOH nanocomposite. Attachment of BPA-aptamer at the surface of modified electrode was performed through the formation of phosphoramidate bonds between the amino group of ACF and phosphate group of the aptamer at 5'end. By interaction of BPA with the aptamer, the conformational of aptamer was changed which lead to retarding the interfacial electron transfer of ACF as a probe. Sensitive quantitative detection of BPA was carried out by monitoring the decrease of differential pulse voltammetric (DPV) responses of ACF peak current with increasing the BPA concentration. The resultant aptasensor exhibited good specificity, stability and reproducibility, indicating that the present strategy was promising for broad potential application.
[Mh] Termos MeSH primário: Acriflavina/química
Aptâmeros de Nucleotídeos/química
Compostos Benzidrílicos/análise
Técnicas Biossensoriais/métodos
Técnicas Eletroquímicas/métodos
Ouro/química
Nanopartículas Metálicas/química
Nanotubos de Carbono/química
Fenóis/análise
Platina/química
[Mh] Termos MeSH secundário: Eletrodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aptamers, Nucleotide); 0 (Benzhydryl Compounds); 0 (Nanotubes, Carbon); 0 (Phenols); 1T3A50395T (Acriflavine); 49DFR088MY (Platinum); 7440-57-5 (Gold); MLT3645I99 (bisphenol A)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


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[PMID]:27694309
[Au] Autor:Pépin G; Nejad C; Thomas BJ; Ferrand J; McArthur K; Bardin PG; Williams BR; Gantier MP
[Ad] Endereço:Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
[Ti] Título:Activation of cGAS-dependent antiviral responses by DNA intercalating agents.
[So] Source:Nucleic Acids Res;45(1):198-205, 2017 Jan 09.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells.
[Mh] Termos MeSH primário: Acriflavina/farmacologia
Antivirais/farmacologia
Fatores Imunológicos/farmacologia
Substâncias Intercalantes/farmacologia
Proteínas de Membrana/genética
Nucleotidiltransferases/genética
Proflavina/farmacologia
[Mh] Termos MeSH secundário: Animais
Brônquios/efeitos dos fármacos
Brônquios/imunologia
Brônquios/virologia
Linhagem Celular Transformada
Cercopithecus aethiops
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/imunologia
Células Epiteliais/virologia
Fibroblastos/efeitos dos fármacos
Fibroblastos/imunologia
Fibroblastos/virologia
Regulação da Expressão Gênica
Células HEK293
Interações Hospedeiro-Patógeno/efeitos dos fármacos
Interações Hospedeiro-Patógeno/imunologia
Seres Humanos
Proteínas de Membrana/agonistas
Proteínas de Membrana/imunologia
Camundongos
Nucleotídeos Cíclicos/imunologia
Nucleotídeos Cíclicos/metabolismo
Nucleotidiltransferases/imunologia
Cultura Primária de Células
Rhinovirus/efeitos dos fármacos
Rhinovirus/crescimento & desenvolvimento
Transdução de Sinais
Células Vero
Carga Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Immunologic Factors); 0 (Intercalating Agents); 0 (MPYS protein, human); 0 (Membrane Proteins); 0 (Nucleotides, Cyclic); 0 (cyclic guanosine monophosphate-adenosine monophosphate); 1T3A50395T (Acriflavine); CY3RNB3K4T (Proflavine); EC 2.7.7.- (MB21D1 protein, human); EC 2.7.7.- (Nucleotidyltransferases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161004
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkw878


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[PMID]:27693638
[Au] Autor:Cao J; Lin G; Gong Y; Pan P; Ma Y; Huang P; Ying M; Hou T; He Q; Yang B
[Ad] Endereço:Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
[Ti] Título:DNA-PKcs, a novel functional target of acriflavine, mediates acriflavine's p53-dependent synergistic anti-tumor efficiency with melphalan.
[So] Source:Cancer Lett;383(1):115-124, 2016 12 01.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Acriflavine (ACF), a known antibacterial drug, has recently been recognized as a suitable candidate for cancer chemotherapy. However, the molecular target of ACF is not fully understood, which limits its application in cancer therapy. In this study, we established a structure-specific probe-based pull-down approach to comprehensively profile the potential target of ACF, and we identified DNA dependent protein kinase catalytic subunit (DNA-PKcs) as the direct target of ACF. Since DNA-PKcs facilitates the repair process following DNA double-strand breaks, we further developed a drug combination strategy that combined ACF with the bifunctional alkylating agent melphalan, which exerted a p53-dependent synergistic efficacy against human cancer cells both in vitro and in vivo. With these findings, our study demonstrated that structure-specific probe-based pull-down approaches can be used to identify new functional target of drug, and provided novel opportunities for the development of ACF-based antitumor chemotherapies.
[Mh] Termos MeSH primário: Acriflavina/farmacologia
Antineoplásicos Alquilantes/farmacologia
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Proteína Quinase Ativada por DNA/antagonistas & inibidores
Melfalan/farmacologia
Neoplasias/tratamento farmacológico
Proteínas Nucleares/antagonistas & inibidores
Inibidores de Proteínas Quinases/farmacologia
Proteína Supressora de Tumor p53/metabolismo
[Mh] Termos MeSH secundário: Acriflavina/metabolismo
Animais
Apoptose/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Ensaio Cometa
Quebras de DNA de Cadeia Dupla
Proteína Quinase Ativada por DNA/metabolismo
Relação Dose-Resposta a Droga
Sinergismo Farmacológico
Células HCT116
Células HeLa
Seres Humanos
Camundongos Nus
Simulação de Acoplamento Molecular
Neoplasias/enzimologia
Neoplasias/genética
Neoplasias/patologia
Proteínas Nucleares/metabolismo
Ligação Proteica
Inibidores de Proteínas Quinases/metabolismo
Transdução de Sinais/efeitos dos fármacos
Fatores de Tempo
Carga Tumoral/efeitos dos fármacos
Proteína Supressora de Tumor p53/genética
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents, Alkylating); 0 (Nuclear Proteins); 0 (Protein Kinase Inhibitors); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); 1T3A50395T (Acriflavine); EC 2.7.11.1 (DNA-Activated Protein Kinase); EC 2.7.11.1 (PRKDC protein, human); Q41OR9510P (Melphalan)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171029
[Lr] Data última revisão:
171029
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161004
[St] Status:MEDLINE


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[PMID]:27307282
[Au] Autor:Linxweiler M; Kadah BA; Bozzato A; Bozzato V; Hasenfus A; Kim YJ; Wagner M; Igressa A; Schick B; Charalampaki P
[Ad] Endereço:Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University Medical Center, Kirrbergerstr. 100, building 6, 66421, Homburg/Saar, Germany. maximilian.linxweiler@uks.eu.
[Ti] Título:Noninvasive histological imaging of head and neck squamous cell carcinomas using confocal laser endomicroscopy.
[So] Source:Eur Arch Otorhinolaryngol;273(12):4473-4483, 2016 Dec.
[Is] ISSN:1434-4726
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Confocal laser endomicroscopy (CLE) is an imaging technique that uses miniaturized fiberoptic probes to allow real-time histological imaging of human tissue. An application of CLE in otorhinolaryngology has hardly been investigated so far. In our study, we analyzed the applicability of CLE to visualize cancerous and healthy tissue of the head and neck region. Formalin-fixed tissue specimens from 135 head and neck squamous cell carcinoma (HNSCC) patients and 50 healthy controls were investigated using CLE with and without topical application of acriflavine. Four head and neck surgeons, four pathologists, and four laymen evaluated the CLE images of the HNSCC cases regarding the tumor localization and its border to healthy tissue. The tumor localization and the tumor border were correctly identified in 97 % by the pathologists, 85 % by the head and neck surgeons, and 70 % by the laymen. The main difference in evaluation results was seen in the correct identification of the tumor site (p < 0.05), while there was no significant difference in the identification of the tumor border. CLE is a valuable tool for real-time histological imaging of HNSCCs. It can help to visualize the tumor border and, thereby, facilitate a more precise tumor surgery.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/diagnóstico por imagem
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem
Microscopia Confocal/métodos
[Mh] Termos MeSH secundário: Acriflavina
Adulto
Idoso
Carcinoma de Células Escamosas/patologia
Feminino
Corantes Fluorescentes
Neoplasias de Cabeça e Pescoço/patologia
Seres Humanos
Masculino
Imagem Óptica
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorescent Dyes); 1T3A50395T (Acriflavine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160617
[St] Status:MEDLINE
[do] DOI:10.1007/s00405-016-4145-8


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[PMID]:26657503
[Au] Autor:Weijer R; Broekgaarden M; Krekorian M; Alles LK; van Wijk AC; Mackaaij C; Verheij J; van der Wal AC; van Gulik TM; Storm G; Heger M
[Ad] Endereço:Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
[Ti] Título:Inhibition of hypoxia inducible factor 1 and topoisomerase with acriflavine sensitizes perihilar cholangiocarcinomas to photodynamic therapy.
[So] Source:Oncotarget;7(3):3341-56, 2016 Jan 19.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of HIF-1-associated proteins in human perihilar cholangiocarcinomas, (2) investigate the role of HIF-1 in PDT-treated human perihilar cholangiocarcinoma cells, and (3) determine whether HIF-1 inhibition reduces survival signaling and enhances PDT efficacy. RESULTS: Increased expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was confirmed in human perihilar cholangiocarcinomas. PDT with liposome-delivered zinc phthalocyanine caused HIF-1α stabilization in SK-ChA-1 cells and increased transcription of HIF-1α downstream genes. Acriflavine was taken up by SK-ChA-1 cells and translocated to the nucleus under hypoxic conditions. Importantly, pretreatment of SK-ChA-1 cells with acriflavine enhanced PDT efficacy via inhibition of HIF-1 and topoisomerases I and II. METHODS: The expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was determined by immunohistochemistry in human perihilar cholangiocarcinomas. In addition, the response of human perihilar cholangiocarcinoma (SK-ChA-1) cells to PDT with liposome-delivered zinc phthalocyanine was investigated under both normoxic and hypoxic conditions. Acriflavine, a HIF-1α/HIF-1ß dimerization inhibitor and a potential dual topoisomerase I/II inhibitor, was evaluated for its adjuvant effect on PDT efficacy. CONCLUSIONS: HIF-1, which is activated in human hilar cholangiocarcinomas, contributes to tumor cell survival following PDT in vitro. Combining PDT with acriflavine pretreatment improves PDT efficacy in cultured cells and therefore warrants further preclinical validation for therapy-recalcitrant perihilar cholangiocarcinomas.
[Mh] Termos MeSH primário: Acriflavina/farmacologia
Neoplasias dos Ductos Biliares/terapia
DNA Topoisomerases Tipo I/química
Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores
Tumor de Klatskin/terapia
Fotoquimioterapia
Radiossensibilizantes/farmacologia
[Mh] Termos MeSH secundário: Anti-Infecciosos Locais/farmacologia
Apoptose
Neoplasias dos Ductos Biliares/metabolismo
Neoplasias dos Ductos Biliares/patologia
Western Blotting
Proliferação Celular
DNA Topoisomerases Tipo I/genética
DNA Topoisomerases Tipo I/metabolismo
Citometria de Fluxo
Seres Humanos
Hipóxia
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Tumor de Klatskin/metabolismo
Tumor de Klatskin/patologia
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Transdução de Sinais
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Infective Agents, Local); 0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (RNA, Messenger); 0 (Radiation-Sensitizing Agents); 1T3A50395T (Acriflavine); EC 5.99.1.2 (DNA Topoisomerases, Type I)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151215
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.6490


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[PMID]:26590290
[Au] Autor:Kovacevic J; Ziegler J; Walecka-Zacharska E; Reimer A; Kitts DD; Gilmour MW
[Ad] Endereço:Food, Nutrition and Health Program, Faculty of Land and Food Systems, University of British Columbia, Vancouver, BC, Canada jovana.kovacevic@ubc.ca.
[Ti] Título:Tolerance of Listeria monocytogenes to Quaternary Ammonium Sanitizers Is Mediated by a Novel Efflux Pump Encoded by emrE.
[So] Source:Appl Environ Microbiol;82(3):939-53, 2015 Nov 20.
[Is] ISSN:1098-5336
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A novel genomic island (LGI1) was discovered in Listeria monocytogenes isolates responsible for the deadliest listeriosis outbreak in Canada, in 2008. To investigate the functional role of LGI1, the outbreak strain 08-5578 was exposed to food chain-relevant stresses, and the expression of 16 LGI1 genes was measured. LGI1 genes with putative efflux (L. monocytogenes emrE [emrELm]), regulatory (lmo1851), and adhesion (sel1) functions were deleted, and the mutants were exposed to acid (HCl), cold (4°C), salt (10 to 20% NaCl), and quaternary ammonium-based sanitizers (QACs). Deletion of lmo1851 had no effect on the L. monocytogenes stress response, and deletion of sel1 did not influence Caco-2 and HeLa cell adherence/invasion, whereas deletion of emrE resulted in increased susceptibility to QACs (P < 0.05) but had no effect on the MICs of gentamicin, chloramphenicol, ciprofloxacin, erythromycin, tetracycline, acriflavine, and triclosan. In the presence of the QAC benzalkonium chloride (BAC; 5 µg/ml), 14/16 LGI1 genes were induced, and lmo1861 (putative repressor gene) was constitutively expressed at 4 °C, 37 °C, and 52 °C and in the presence of UV exposure (0 to 30 min). Following 1 h of exposure to BAC (10 µg/ml), upregulation of emrE (49.6-fold), lmo1851 (2.3-fold), lmo1861 (82.4-fold), and sigB (4.1-fold) occurred. Reserpine visibly suppressed the growth of the ΔemrELm strain, indicating that QAC tolerance is due at least partially to efflux activity. These data suggest that a minimal function of LGI1 is to increase the tolerance of L. monocytogenes to QACs via emrELm. Since QACs are commonly used in the food industry, there is a concern that L. monocytogenes strains possessing emrE will have an increased ability to survive this stress and thus to persist in food processing environments.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Anti-Infecciosos Locais/farmacologia
Farmacorresistência Bacteriana/genética
Genes MDR
Listeria monocytogenes/efeitos dos fármacos
Listeria monocytogenes/genética
Compostos de Amônio Quaternário/farmacologia
[Mh] Termos MeSH secundário: Acriflavina/farmacologia
Proteínas de Bactérias/genética
Compostos de Benzalcônio/farmacologia
Células CACO-2
Canadá/epidemiologia
Manipulação de Alimentos/normas
Indústria de Processamento de Alimentos/normas
Ilhas Genômicas
Células HeLa
Seres Humanos
Listeria monocytogenes/fisiologia
Listeria monocytogenes/efeitos da radiação
Listeriose/epidemiologia
Listeriose/microbiologia
Listeriose/prevenção & controle
Testes de Sensibilidade Microbiana
Mutação
Triclosan/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Anti-Infective Agents, Local); 0 (Bacterial Proteins); 0 (Benzalkonium Compounds); 0 (Quaternary Ammonium Compounds); 1T3A50395T (Acriflavine); 4NM5039Y5X (Triclosan)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151122
[St] Status:MEDLINE
[do] DOI:10.1128/AEM.03741-15


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[PMID]:25970790
[Au] Autor:Cuyàs E; Martin-Castillo B; Corominas-Faja B; Massaguer A; Bosch-Barrera J; Menendez JA
[Ad] Endereço:a Metabolism & Cancer Group; Translational Research Laboratory; Catalan Institute of Oncology (ICO) ; Girona; Catalonia , Spain.
[Ti] Título:Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties.
[So] Source:Cell Cycle;14(22):3527-32, 2015.
[Is] ISSN:1551-4005
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Antineoplásicos/farmacologia
Regulação Neoplásica da Expressão Gênica
Células-Tronco Neoplásicas/efeitos dos fármacos
Inibidores da Síntese de Proteínas/farmacologia
Ribossomos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Acriflavina/farmacologia
Ciclo Celular/efeitos dos fármacos
Ciclo Celular/genética
Linhagem Celular Tumoral
Proliferação Celular
Cicloeximida/farmacologia
Dactinomicina/farmacologia
Reposicionamento de Medicamentos
Emetina/farmacologia
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/metabolismo
Células Epiteliais/patologia
Feminino
Ensaios de Triagem em Larga Escala
Seres Humanos
Glândulas Mamárias Humanas
Análise em Microsséries
Células-Tronco Neoplásicas/metabolismo
Células-Tronco Neoplásicas/patologia
Fenótipo
Biossíntese de Proteínas
Puromicina/farmacologia
Ribossomos/genética
Ribossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antineoplastic Agents); 0 (Protein Synthesis Inhibitors); 1CC1JFE158 (Dactinomycin); 1T3A50395T (Acriflavine); 4A6ZS6Q2CL (Puromycin); 98600C0908 (Cycloheximide); X8D5EPO80M (Emetine)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:160428
[Lr] Data última revisão:
160428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150514
[St] Status:MEDLINE
[do] DOI:10.1080/15384101.2015.1044173


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[PMID]:25880748
[Au] Autor:Obstoy B; Salaun M; Veresezan L; Sesboüé R; Bohn P; Boland FX; Thiberville L
[Ad] Endereço:Quant.I.F Litis EA 4108, IRIB, Rouen University, Rouen, F-76000, France. berengere.obstoy@chu-rouen.fr.
[Ti] Título:Safety and performance analysis of acriflavine and methylene blue for in vivo imaging of precancerous lesions using fibered confocal fluorescence microscopy (FCFM): an experimental study.
[So] Source:BMC Pulm Med;15:30, 2015 Mar 31.
[Is] ISSN:1471-2466
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fibered confocal fluorescence microscopy (FCFM) allows in vivo investigation of pulmonary microstructures. However, the bronchial epithelium can only be imaged using exogenous fluorophores. The objective of this study is to compare methylene blue (MB) and acriflavine genotoxicity and to assess FCFM performance for in vivo imaging of precancerous lesions. METHODS: Genotoxicity was assessed using the comet assay on both cultured human lymphocytes and NCI-H460 cells, which had been exposed to MB or acriflavine before being illuminated at 660 or 488 nm, respectively. FCFM was performed on precancerous lesions in the hamster cheek pouch model, following topical application of the fluorophores. FCFM data were analyzed according to histology. RESULTS: No genotoxicity was found using 0.01% (w/v) MB after illumination at 660 nm for 2 and 15 min (5 mW). Acriflavine exposure (0.025%) led to DNA damages, increasing from 2 to 15 min of light exposure at 448 nm in both lymphocytes (83.4 to 88%, p = 0.021) and NCI H460 cell populations (79.9 to 84.6%, p = 0.045). In total, 11 invasive carcinoma, 24 reserve cell hyperplasia, and 17 dysplasia lesions were imaged using FCFM in vivo. With both fluorophores, the cellular density increased from hyperplasia to high-grade dysplasia (p < 0.05). With MB, the cellular diameter significantly decreased (48.9 to 13.9 µm) from hyperplasia to carcinoma (p < 0.05). In this model, a cut-off diameter of 30 µm enabled the diagnosis of high-grade lesions with a sensitivity of 94.7% and a specificity of 97%. CONCLUSION: Methylene blue can be used safely to image precancerous lesions in vivo. This study does not support the use of acriflavine in humans.
[Mh] Termos MeSH primário: Acriflavina
Carcinoma de Células Escamosas/patologia
Corantes Fluorescentes
Azul de Metileno
Microscopia Confocal/métodos
Microscopia de Fluorescência/métodos
Mucosa Bucal/patologia
Neoplasias Bucais/patologia
Imagem Óptica/métodos
Lesões Pré-Cancerosas/patologia
[Mh] Termos MeSH secundário: Acriflavina/farmacologia
Animais
Linhagem Celular Tumoral
Células Cultivadas
Ensaio Cometa
Células Epiteliais/efeitos dos fármacos
Corantes Fluorescentes/farmacologia
Seres Humanos
Microscopia Intravital
Pulmão/citologia
Linfócitos/efeitos dos fármacos
Mesocricetus
Azul de Metileno/farmacologia
Testes de Mutagenicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fluorescent Dyes); 1T3A50395T (Acriflavine); T42P99266K (Methylene Blue)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150417
[St] Status:MEDLINE
[do] DOI:10.1186/s12890-015-0020-4



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