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[PMID]:28471399
[Au] Autor:Wang CC; Wang YX; Yu NQ; Hu D; Wang XY; Chen XG; Liao YW; Yao J; Wang H; He L; Wu L
[Ad] Endereço:School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. w940984614@hotmail.com.
[Ti] Título:Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2.
[So] Source:Molecules;22(5), 2017 May 04.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic therapy (PDT) is a therapeutic approach used against malignant cells. To assess the synergistic effect of BGP extract on protoporphyrin IX (PpIX)-mediated photocytotoxicity, MTT assays were performed using A431 and HeLa cells. TUNEL assay and Annexin V-FITC/PI staining were performed to confirm the induction of apoptosis. Western blotting analysis was performed to examine the pro-apoptotic proteins, anti-apoptotic proteins and inflammation related proteins in A431 cells. Intracellular accumulation of PpIX was examined by flow cytometry. The synergistic effect of BGP extract in PpIX-PDT was also evaluated with a xenograft model. Our findings reveal that BGP extract increased PpIX-mediated photocytotoxicity in A431 and HeLa cells. PpIX-PDT with BGP extract treatment resulted in a decrease in Bcl-xL and an increase in NOXA, Bax and caspase-3 cleavage. The protein expression levels of p-IKKα/ß, NF-κB and COX-2 were upregulated by PpIX-PDT but significantly attenuated when in combination with BGP extract. BGP extract was also found to significantly enhance the intracellular accumulation of PpIX in A431 cells. BGP extract increased PpIX-mediated photocytotoxicity in a xenograft model as well. Our findings provide evidence for a synergistic effect of BGP extract in PpIX-PDT both in vitro and in vivo.
[Mh] Termos MeSH primário: Ciclo-Oxigenase 2/metabolismo
NF-kappa B/metabolismo
Fotoquimioterapia
Própole
Protoporfirinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Brasil
Linhagem Celular Tumoral
Cromatografia Líquida de Alta Pressão
Sinergismo Farmacológico
Citometria de Fluxo
Xenoenxertos
Seres Humanos
Camundongos Endogâmicos BALB C
Camundongos Nus
Protoporfirinas/farmacocinética
Espectrofotometria Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NF-kappa B); 0 (Protoporphyrins); 9009-62-5 (Propolis); C2K325S808 (protoporphyrin IX); EC 1.14.99.1 (Cyclooxygenase 2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


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[PMID]:28942278
[Au] Autor:Demirci Ö; Güven K; Asma D; Ögüt S; Ugurlu P
[Ad] Endereço:Science Faculty, Department of Biology, Dicle University, 21280, Turkey. Electronic address: ozdem22@gmail.com.
[Ti] Título:Effects of endosulfan, thiamethoxam, and indoxacarb in combination with atrazine on multi-biomarkers in Gammarus kischineffensis.
[So] Source:Ecotoxicol Environ Saf;147:749-758, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Studies addressing the toxicity of pesticides towards non-target organisms focus on the median lethal concentration and biochemical response of individual pesticides. However, when determining environmental risks, it is important to test the combined effects of pesticides, such as insecticides and herbicides, which are frequently used together in agricultural areas. Here we aimed to investigate the toxic effects of the combined use of the herbicide atrazine and the insecticides, endosulfan, indoxacarb, and thiamethoxam on Gammarus kischineffensis. To do this, we tested the activities of oxidative stress, detoxification, and neurotoxicity biomarkers. Compared to atrazine alone, we detected higher glutathione-S-transferase, catalase and superoxide dismutase activities (oxidative stress biomarkers) when atrazine was combined with either endosulfan or indoxacarb. However, higher IBR values were determined in organisms where pesticide mixtures were used according to individual use. Based on these results, mixtures of atrazine and other pesticides may cause synergistic effects and may be evidence of increased toxicity and oxidative stress.
[Mh] Termos MeSH primário: Anfípodes/efeitos dos fármacos
Monitoramento Ambiental/métodos
Herbicidas/toxicidade
Inseticidas/toxicidade
Poluentes do Solo/toxicidade
[Mh] Termos MeSH secundário: Anfípodes/enzimologia
Animais
Atrazina/toxicidade
Biomarcadores/análise
Relação Dose-Resposta a Droga
Sinergismo Farmacológico
Endossulfano/toxicidade
Dose Letal Mediana
Neonicotinoides/toxicidade
Nitrocompostos/toxicidade
Oxazinas/toxicidade
Estresse Oxidativo/efeitos dos fármacos
Tiazóis/toxicidade
Fatores de Tempo
Testes de Toxicidade Aguda
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Herbicides); 0 (Insecticides); 0 (Neonicotinoids); 0 (Nitro Compounds); 0 (Oxazines); 0 (Soil Pollutants); 0 (Thiazoles); 52H0D26MWR (indoxacarb); 747IC8B487 (thiamethoxam); OKA6A6ZD4K (Endosulfan); QJA9M5H4IM (Atrazine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170925
[St] Status:MEDLINE


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[PMID]:29184402
[Au] Autor:Wu X; Wang L; Qiu Y; Zhang B; Hu Z; Jin R
[Ad] Endereço:Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
[Ti] Título:Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia.
[So] Source:Int J Nanomedicine;12:8025-8034, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores
Nanopartículas/química
Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Compostos de Bifenilo/administração & dosagem
Compostos de Bifenilo/farmacologia
Liberação Controlada de Fármacos
Sinergismo Farmacológico
Feminino
Seres Humanos
Células Jurkat
Ácido Láctico/química
Camundongos
Nanopartículas/administração & dosagem
Nitrofenóis/administração & dosagem
Nitrofenóis/farmacologia
Piperazinas/administração & dosagem
Piperazinas/farmacologia
Ácido Poliglicólico/química
Sulfonamidas/administração & dosagem
Sulfonamidas/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-737); 0 (Biphenyl Compounds); 0 (Nitrophenols); 0 (Piperazines); 0 (Sulfonamides); 0 (polylactic acid-polyglycolic acid copolymer); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid); EC 2.7.11.1 (IRAK1 protein, human); EC 2.7.11.1 (IRAK4 protein, human); EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S146875


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[PMID]:28460451
[Au] Autor:Tsitsipatis D; Jayavelu AK; Müller JP; Bauer R; Schmidt-Arras D; Mahboobi S; Schnöder TM; Heidel F; Böhmer FD
[Ad] Endereço:Institute of Molecular Cell Biology, CMB, Jena University Hospital, Jena, Germany.
[Ti] Título:Synergistic killing of FLT3ITD-positive AML cells by combined inhibition of tyrosine-kinase activity and N-glycosylation.
[So] Source:Oncotarget;8(16):26613-26624, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fms-like tyrosine kinase 3 (FLT3) with internal tandem duplications (ITD) is a major oncoprotein in acute myeloid leukemia (AML), and confers an unfavorable prognosis. Interference with FLT3ITD signaling is therefore pursued as a promising therapeutic strategy. In this study we show that abrogation of FLT3ITD glycoprotein maturation using low doses of the N-glycosylation inhibitor tunicamycin has anti-proliferative and pro-apoptotic effects on FLT3ITD-expressing human and murine cell lines. This effect is mediated in part by arresting FLT3ITD in an underglycosylated state and thereby attenuating FLT3ITD-driven AKT and ERK signaling. In addition, tunicamycin caused pronounced endoplasmatic reticulum stress and apoptosis through activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activation of the gene encoding CCAAT-enhancer-binding protein homologous protein (CHOP). PERK inhibition with a small molecule attenuated CHOP induction and partially rescued cells from apoptosis. Combination of tunicamycin with potent FLT3ITD kinase inhibitors caused synergistic cell killing, which was highly selective for cell lines and primary AML cells expressing FLT3ITD. Although tunicamycin is currently not a clinically applicable drug, we propose that mild inhibition of N-glycosylation may have therapeutic potential in combination with FLT3 kinase inhibitors for FLT3ITD-positive AML.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Duplicação Gênica
Leucemia Mieloide Aguda/genética
Inibidores de Proteínas Quinases/farmacologia
Sequências de Repetição em Tandem
Tirosina Quinase 3 Semelhante a fms/genética
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Apoptose/genética
Linhagem Celular Tumoral
Sinergismo Farmacológico
Estresse do Retículo Endoplasmático
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Expressão Gênica
Glicosilação/efeitos dos fármacos
Seres Humanos
Leucemia Mieloide Aguda/tratamento farmacológico
Leucemia Mieloide Aguda/metabolismo
Leucemia Mieloide Aguda/patologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
Células Tumorais Cultivadas
Tunicamicina/farmacologia
Tirosina Quinase 3 Semelhante a fms/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 11089-65-9 (Tunicamycin); EC 2.7.10.1 (fms-Like Tyrosine Kinase 3); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15772


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[PMID]:28458336
[Au] Autor:Nakamura Y; Suzuki T; Kamimura M; Ikegami S; Uchiyama S; Kato H
[Ad] Endereço:Department of Orthopaedic Surgery, Shinshu University School of Medicine.
[Ti] Título:Alfacalcidol Increases the Therapeutic Efficacy of Ibandronate on Bone Mineral Density in Japanese Women with Primary Osteoporosis.
[So] Source:Tohoku J Exp Med;241(4):319-326, 2017 04.
[Is] ISSN:1349-3329
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Bisphosphonates (BPs) increase bone mineral density (BMD) through the inhibition of osteoclast activity. Among BPs, ibandronate (IBN) is a strong inhibitor of bone resorption. However, the effects of a vitamin D analogue, alfacalcidol (ALF), on IBN treatment for osteoporosis is unknown. Fifty-three treatment-naïve post-menopausal women with primary osteoporosis were recruited and divided into IBN-treatment group (IBN group) and IBN with ALF group (IBN/ALF group). IBN (1.0 mg) was intravenously injected once a month, with or without oral ALF (1.0 µg/day). Ultimately, 19 subjects in IBN group and 26 in IBN/ALF group were analyzed. Bone turnover markers were examined at 4, 6, 12, and 18 months, and BMD was measured at 6, 12, and 18 months. Compared with pre-treatment, bone turnover markers significantly decreased in both groups after 4 months. The levels of serum N-terminal propeptide of type-1 procollagen and tartrate-resistant acid phosphatase-5b, and urinary N-terminal telopeptide of type-I collagen were significantly lower in IBN/ALF group than those in IBN group at 12 months. Lumbar 1-4 (L)-BMD significantly increased from 6 months in IBN/ALF group and at 18 months in IBN group. L-BMD was significantly higher in IBN/ALF group (6.6% increase) than in IBN group (3.4%) at 18 months. Total hip (H)-BMD significantly increased from 6 months in IBN/ALF group and tended to improve in IBN group. H-BMD was significantly higher in IBN/ALF group (4.8%) than in IBN group (3.2%) at 18 months. In conclusion, treatment with ALF in combination with IBN improves BMD in post-menopausal women with osteoporosis.
[Mh] Termos MeSH primário: Conservadores da Densidade Óssea/uso terapêutico
Densidade Óssea/efeitos dos fármacos
Difosfonatos/uso terapêutico
Hidroxicolecalciferóis/uso terapêutico
Osteoporose/tratamento farmacológico
[Mh] Termos MeSH secundário: Absorciometria de Fóton
Administração Intravenosa
Administração Oral
Idoso
Grupo com Ancestrais do Continente Asiático
Sinergismo Farmacológico
Feminino
Quadril/diagnóstico por imagem
Seres Humanos
Hidroxicolecalciferóis/efeitos adversos
Pós-Menopausa
Fosfatase Ácida Resistente a Tartarato/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Density Conservation Agents); 0 (Diphosphonates); 0 (Hydroxycholecalciferols); EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase); UMD7G2653W (ibandronic acid); URQ2517572 (alfacalcidol)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1620/tjem.241.319


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[PMID]:29390394
[Au] Autor:Wang G; Chen W; Wu Y; Li Y; Leng Y; Liu A
[Ti] Título:Recombinant human thrombopoietin improves the efficacy of intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor in mobilizing peripheral blood stem cells in patients with multiple myeloma: A cohort study.
[So] Source:Medicine (Baltimore);96(50):e9302, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The combination of intermediate-dose cyclophosphamide (ID-CTX) and granulocyte colony-stimulating factor (G-CSF) fails to mobilize peripheral blood stem cells (PBSCs) in approximately 20% of treated patients with multiple myeloma (MM).In this cohort study, patients with MM underwent PBSC mobilization with either an ID-CTX plus G-CSF plus recombinant human thrombopoietin (rhTPO) regimen (72 patients; TPO group), or an ID-CTX plus G-CSF regimen (70 patients; non-TPO group).In the TPO group, the median CD34+ harvest was 5.36 × 10 per kg of body weight (0.50-22.39 × 10 per kg of body weight), with a harvest success rate of 91.7% (66/72), and an excellence rate of 55.6% (40/72). In the non-TPO group, the median CD34+ harvest was 3.30 × 10 per kg of body weight (0.20-21.14 × 10 per kg of body weight), with a harvest success rate of 75.7% (53/70), and an excellence rate of 25.7% (18/70). The median count of the CD34+ cells collected, success rate of collection, and excellence rate of collection were significantly higher in the TPO group than in the non-TPO group (P=.0001, P=.01, and P = .0001, respectively). Time to granulocyte and platelet engraftment was faster among patients in the TPO group than that in those from the non-TPO group. No platelet engraftment delay (>21 days) was observed among patients in the TPO group, while 3 patients in the non-TPO group displayed delayed platelet engraftment.Adding rhTPO to the ID-CTX chemotherapy plus G-CSF regimen improved treatment efficacy in mobilizing PBSCs for autologous hematopoietic stem cell transplantation.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/uso terapêutico
Ciclofosfamida/uso terapêutico
Sinergismo Farmacológico
Fator Estimulador de Colônias de Granulócitos/uso terapêutico
Transplante de Células-Tronco Hematopoéticas
Mieloma Múltiplo/tratamento farmacológico
Células-Tronco de Sangue Periférico/efeitos dos fármacos
Trombopoetina/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Quimioterapia Combinada
Feminino
Seres Humanos
Masculino
Meia-Idade
Mieloma Múltiplo/patologia
Estadiamento de Neoplasias
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Alkylating); 143011-72-7 (Granulocyte Colony-Stimulating Factor); 8N3DW7272P (Cyclophosphamide); 9014-42-0 (Thrombopoietin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009302


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[PMID]:29338217
[Au] Autor:Naseeruddin R; Sumathi V; Prasad TNVKV; Sudhakar P; Chandrika V; Ravindra Reddy B
[Ad] Endereço:Department of Agronomy, Sri Venkateswara Agricultural College, ‡Nanotechnology Lab, Institute of Frontier Technology, Regional Agricultural Research Station (RARS), §Crop Physiology, Sri Venkateswara Agricultural College, and ∥Department of Statistics and Mathematics, Sri Venkateswara Agricultural
[Ti] Título:Unprecedented Synergistic Effects of Nanoscale Nutrients on Growth, Productivity of Sweet Sorghum [Sorghum bicolor (L.) Moench], and Nutrient Biofortification.
[So] Source:J Agric Food Chem;66(5):1075-1084, 2018 Feb 07.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Evidence-based synergistic effects of nanoscale materials (size of <100 nm in at least one dimension) were scantly documented in agriculture at field scale. Herein, we report for the first time on effects of nanoscale zinc oxide (n-ZnO), calcium oxide (n-CaO), and magnesium oxide (n-MgO) on growth and productivity of sweet sorghum [Sorghum bicolor (L.) Moench]. A modified sol-gel method was used to prepare nanoscale materials under study. Characterization was performed using transmission and scanning electron microscopies, X-ray diffraction, and dynamic light scattering. Average sizes (25, 53.7, and 53.5 nm) and ζ potentials (-10.9, -28.2, and -16.2 mV) of n-ZnO, n-CaO, and n-MgO were measured, respectively. The significant grain yield (17.8 and 14.2%), cane yield (7.2 and 8.0%), juice yield (10 and 12%), and higher sucrose yield (21.8 and 20.9%) were recorded with the application of nanoscale materials in the years 2014 and 2015, respectively. Nutrient uptake was significant with foliar application of nanoscale nutrients.
[Mh] Termos MeSH primário: Biofortificação/métodos
Compostos de Cálcio/administração & dosagem
Óxido de Magnésio/administração & dosagem
Nanopartículas/administração & dosagem
Óxidos/administração & dosagem
Sorghum/crescimento & desenvolvimento
Óxido de Zinco/administração & dosagem
[Mh] Termos MeSH secundário: Agricultura/métodos
Compostos de Cálcio/metabolismo
Sinergismo Farmacológico
Óxido de Magnésio/metabolismo
Microscopia Eletrônica de Varredura
Óxidos/metabolismo
Tamanho da Partícula
Sorghum/efeitos dos fármacos
Óxido de Zinco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Compounds); 0 (Oxides); 3A3U0GI71G (Magnesium Oxide); C7X2M0VVNH (lime); SOI2LOH54Z (Zinc Oxide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b04467


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[PMID]:28454547
[Au] Autor:Pignochino Y; Capozzi F; D'Ambrosio L; Dell'Aglio C; Basiricò M; Canta M; Lorenzato A; Vignolo Lutati F; Aliberti S; Palesandro E; Boccone P; Galizia D; Miano S; Chiabotto G; Napione L; Gammaitoni L; Sangiolo D; Benassi MS; Pasini B; Chiorino G; Aglietta M; Grignani G
[Ad] Endereço:Sarcoma Unit, Medical Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Torino, Italy. ymera.pignochino@ircc.it.
[Ti] Título:PARP1 expression drives the synergistic antitumor activity of trabectedin and PARP1 inhibitors in sarcoma preclinical models.
[So] Source:Mol Cancer;16(1):86, 2017 04 28.
[Is] ISSN:1476-4598
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Enhancing the antitumor activity of the DNA-damaging drugs is an attractive strategy to improve current treatment options. Trabectedin is an isoquinoline alkylating agent with a peculiar mechanism of action. It binds to minor groove of DNA inducing single- and double-strand-breaks. These kinds of damage lead to the activation of PARP1, a first-line enzyme in DNA-damage response pathways. We hypothesized that PARP1 targeting could perpetuate trabectedin-induced DNA damage in tumor cells leading finally to cell death. METHODS: We investigated trabectedin and PARP1 inhibitor synergism in several tumor histotypes both in vitro and in vivo (subcutaneous and orthotopic tumor xenografts in mice). We searched for key determinants of drug synergism by comparative genomic hybridization (aCGH) and gene expression profiling (GEP) and validated their functional role. RESULTS: Trabectedin activated PARP1 enzyme and the combination with PARP1 inhibitors potentiated DNA damage, cell cycle arrest at G2/M checkpoint and apoptosis, if compared to single agents. Olaparib was the most active PARP1 inhibitor to combine with trabectedin and we confirmed the antitumor and antimetastatic activity of trabectedin/olaparib combination in mice models. However, we observed different degree of trabectedin/olaparib synergism among different cell lines. Namely, in DMR leiomyosarcoma models the combination was significantly more active than single agents, while in SJSA-1 osteosarcoma models no further advantage was obtained if compared to trabectedin alone. aCGH and GEP revealed that key components of DNA-repair pathways were involved in trabectedin/olaparib synergism. In particular, PARP1 expression dictated the degree of the synergism. Indeed, trabectedin/olaparib synergism was increased after PARP1 overexpression and reduced after PARP1 silencing. CONCLUSIONS: PARP1 inhibition potentiated trabectedin activity in a PARP1-dependent manner and PARP1 expression in tumor cells might be a useful predictive biomarker that deserves clinical evaluation.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Dioxóis/administração & dosagem
Poli(ADP-Ribose) Polimerase-1/genética
Sarcoma/tratamento farmacológico
Tetra-Hidroisoquinolinas/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Hibridização Genômica Comparativa
Dano ao DNA/efeitos dos fármacos
Sinergismo Farmacológico
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Camundongos
Ftalazinas/administração & dosagem
Piperazinas/administração & dosagem
Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores
Sarcoma/genética
Sarcoma/patologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Dioxoles); 0 (Phthalazines); 0 (Piperazines); 0 (Tetrahydroisoquinolines); EC 2.4.2.30 (PARP1 protein, human); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1); ID0YZQ2TCP (trabectedin); WOH1JD9AR8 (olaparib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1186/s12943-017-0652-5


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[PMID]:29206032
[Au] Autor:Rajendran K; Anwar A; Khan NA; Siddiqui R
[Ad] Endereço:Department of Biological Sciences, School of Science and Technology, Sunway University , Bandar Sunway 47500, Malaysia.
[Ti] Título:Brain-Eating Amoebae: Silver Nanoparticle Conjugation Enhanced Efficacy of Anti-Amoebic Drugs against Naegleria fowleri.
[So] Source:ACS Chem Neurosci;8(12):2626-2630, 2017 12 20.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against primary amoebic meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV-visible spectrophotometry. Atomic force microscopy determined their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiamoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying existing drugs to enhance their antiamoebic effects is a useful avenue that holds promise in improving the treatment of brain-eating amoebae infection due to N. fowleri.
[Mh] Termos MeSH primário: Amebicidas/administração & dosagem
Nanopartículas Metálicas/administração & dosagem
Naegleria fowleri/efeitos dos fármacos
Naegleria fowleri/fisiologia
Nanoconjugados/administração & dosagem
Nanoconjugados/química
Prata/administração & dosagem
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Combinação de Medicamentos
Sinergismo Farmacológico
Fluconazol/administração & dosagem
Nanopartículas Metálicas/química
Nanopartículas Metálicas/ultraestrutura
Naegleria fowleri/citologia
Nanocápsulas/administração & dosagem
Nanocápsulas/química
Nanocápsulas/ultraestrutura
Nanoconjugados/ultraestrutura
Nistatina/administração & dosagem
Tamanho da Partícula
Prata/química
Taxa de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amebicides); 0 (Drug Combinations); 0 (Nanocapsules); 0 (Nanoconjugates); 1400-61-9 (Nystatin); 3M4G523W1G (Silver); 8VZV102JFY (Fluconazole)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.7b00430


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[PMID]:29384621
[Au] Autor:Jasim R; Schneider EK; Han M; Azad MAK; Hussein M; Nowell C; Baker MA; Wang J; Li J; Velkov T
[Ti] Título:A Fresh Shine onCystic Fibrosis Inhalation Therapy: Antimicrobial Synergy of Polymyxin B in Combination with Silver Nanoparticles.
[So] Source:J Biomed Nanotechnol;13(4):447-57, 2017 Apr.
[Is] ISSN:1550-7033
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This in vitro study aimed to investigate the synergistic antibacterial activity of polymyxin B in combination with 2 nm silver nanoparticles (NPs) against Gram-negative pathogens commonly isolated from the cystic fibrosis (CF) lung. The in vitro synergistic activity of polymyxin B with silver NPs was assessed using the checkerboard assay against polymyxinsusceptible and polymyxin-resistant Pseudomonas aeruginosa isolates from the lungs of CF patients. The combination was also examined against the Gram-negative species Haemophilus influenzae, Burkholderia cepacia, Burkholderia pseudomallei, Stenotrophomonas maltophilia, Klebsiella pneumoniae and Acinetobacter baumannii that are less common in the CF lung. The killing kinetics of the polymyxin B-silver NPs combinations was assessed against P. aeruginosa by static time-kill assays over 24 h. Polymyxin B and silver NPs alone were not active against polymyxin-resistant (MIC ≥4 mg/L) P. aeruginosa. Whereas, the combination of a clinically-relevant concentration of polymyxin B (2 mg/L) with silver NPs (4 mg/L) successfully inhibited the growth of polymyxin-resistant P. aeruginosa isolates from CF patients as demonstrated by ≥2 log10 decrease in bacterial count (CFU/mL) after 24 h. Treatment of P. aeruginosa cells with the combination induced cytosolic GFP release and an increase of cellular reactive oxygen species. In the nitrocefin assay, the combination displayed a membrane permeabilizing activity superior to each of the drugs alone. The combination of polymyxin B and silver NPs displays excellent synergistic activity against highly polymyxin-resistant P. aeruginosa and is potentially of considerable clinical utility for the treatment of problematic CF lung infections.
[Mh] Termos MeSH primário: Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos
Fibrose Cística/tratamento farmacológico
Fibrose Cística/microbiologia
Nanopartículas Metálicas/administração & dosagem
Pneumonia Bacteriana/diagnóstico por imagem
Polimixina B/administração & dosagem
Prata/administração & dosagem
[Mh] Termos MeSH secundário: Administração por Inalação
Anti-Infecciosos/administração & dosagem
Anti-Infecciosos/química
Sobrevivência Celular/efeitos dos fármacos
Fibrose Cística/patologia
Difusão
Relação Dose-Resposta a Droga
Combinação de Medicamentos
Sinergismo Farmacológico
Seres Humanos
Nanopartículas Metálicas/química
Pneumonia Bacteriana/microbiologia
Polimixina B/química
Terapia Respiratória/métodos
Prata/química
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Drug Combinations); 1404-26-8 (Polymyxin B); 3M4G523W1G (Silver)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE



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