Base de dados : MEDLINE
Pesquisa : A11.251.860 [Categoria DeCS]
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  1 / 162071 MEDLINE  
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[PMID]:29211796
[Au] Autor:Saison-Ridinger M; DelGiorno KE; Zhang T; Kraus A; French R; Jaquish D; Tsui C; Erikson G; Spike BT; Shokhirev MN; Liddle C; Yu RT; Downes M; Evans RM; Saghatelian A; Lowy AM; Wahl GM
[Ad] Endereço:Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America.
[Ti] Título:Reprogramming pancreatic stellate cells via p53 activation: A putative target for pancreatic cancer therapy.
[So] Source:PLoS One;12(12):e0189051, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely dense fibrotic stroma, which contributes to tumor growth, metastasis, and drug resistance. During tumorigenesis, quiescent pancreatic stellate cells (PSCs) are activated and become major contributors to fibrosis, by increasing growth factor signaling and extracellular matrix deposition. The p53 tumor suppressor is known to restrict tumor initiation and progression through cell autonomous mechanisms including apoptosis, cell cycle arrest, and senescence. There is growing evidence that stromal p53 also exerts anti-tumor activity by paracrine mechanisms, though a role for stromal p53 in PDAC has not yet been described. Here, we demonstrate that activation of stromal p53 exerts anti-tumor effects in PDAC. We show that primary cancer-associated PSCs (caPSCs) isolated from human PDAC express wild-type p53, which can be activated by the Mdm2 antagonist Nutlin-3a. Our work reveals that p53 acts as a major regulator of PSC activation and as a modulator of PDAC fibrosis. In vitro, p53 activation by Nutlin-3a induces profound transcriptional changes, which reprogram activated PSCs to quiescence. Using immunofluorescence and lipidomics, we have also found that p53 activation induces lipid droplet accumulation in both normal and tumor-associated fibroblasts, revealing a previously undescribed role for p53 in lipid storage. In vivo, treatment of tumor-bearing mice with the clinical form of Nutlin-3a induces stromal p53 activation, reverses caPSCs activation, and decreases fibrosis. All together our work uncovers new functions for stromal p53 in PDAC.
[Mh] Termos MeSH primário: Carcinoma Ductal Pancreático/terapia
Reprogramação Celular
Genes p53
Neoplasias Pancreáticas/terapia
Células Estreladas do Pâncreas/metabolismo
[Mh] Termos MeSH secundário: Animais
Carcinoma Ductal Pancreático/metabolismo
Carcinoma Ductal Pancreático/patologia
Ésteres do Colesterol/metabolismo
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Neoplasias Pancreáticas/metabolismo
Neoplasias Pancreáticas/patologia
Transcrição Genética
Triglicerídeos/metabolismo
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholesterol Esters); 0 (Triglycerides)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189051


  2 / 162071 MEDLINE  
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[PMID]:29349655
[Au] Autor:Lo WJ; Lin CL; Chang YC; Bai LY; Lin CY; Liang JA; Li LY; Chao LM; Chiu CF; Chen CM; Yeh SP
[Ad] Endereço:Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
[Ti] Título:Total body irradiation tremendously impair the proliferation, differentiation and chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells.
[So] Source:Ann Hematol;97(4):697-707, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control. The irradiated and non-irradiated MSCs shared similar morphology, phenotype, and hematopoiesis-supporting function. However, irradiated MSCs showed much lower proliferative and differentiative potential. Irradiation also induced clonal cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo irradiation experiments, decreased proliferative and differentiative abilities and clonal cytogenetic abnormalities can also be found in MSCs isolated from transplant recipients who had received TBI-based conditioning previously. Thus, TBI used in HSCT drastically injury MSCs and may contribute to the development of some long-term complications associated with clonal cytogenetic abnormality and poor adipogenesis and osteogenesis after TBI.
[Mh] Termos MeSH primário: Apoptose/efeitos da radiação
Células da Medula Óssea/efeitos da radiação
Aberrações Cromossômicas/efeitos da radiação
Células-Tronco Hematopoéticas/efeitos da radiação
Células Mesenquimais Estromais/efeitos da radiação
Lesões por Radiação/patologia
Irradiação Corporal Total/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Células-Tronco Adultas/efeitos da radiação
Células da Medula Óssea/citologia
Células da Medula Óssea/patologia
Diferenciação Celular/efeitos da radiação
Proliferação Celular/efeitos da radiação
Células Cultivadas
China
Transtornos Cromossômicos/etiologia
Transtornos Cromossômicos/patologia
Feminino
Transplante de Células-Tronco Hematopoéticas
Células-Tronco Hematopoéticas/citologia
Células-Tronco Hematopoéticas/patologia
Hospitais Universitários
Seres Humanos
Leucemia/patologia
Leucemia/terapia
Masculino
Células Mesenquimais Estromais/citologia
Células Mesenquimais Estromais/patologia
Necrose
Lesões por Radiação/etiologia
Condicionamento Pré-Transplante/efeitos adversos
Células Tumorais Cultivadas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[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:180120
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3231-y


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[PMID]:29270670
[Au] Autor:Lv C; Wang H; Tong Y; Yin H; Wang D; Yan Z; Liang Y; Wu D; Su Q
[Ad] Endereço:Department of General Surgery, Shengjing Hospital Affiliated to China Medical University, Shenyang City, Liaoning Province, 110004, People's Republic of China.
[Ti] Título:The function of BTG3 in colorectal cancer cells and its possible signaling pathway.
[So] Source:J Cancer Res Clin Oncol;144(2):295-308, 2018 Feb.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: B-cell translocation gene 3 (BTG3) has been identified as a candidate driver gene for various cancers, but its specific role in colorectal cancer (CRC) is poorly understood. We aimed to investigate the relationship between expression of BTG3 and clinicopathological features and prognosis, as well as to explore the effects and the role of a possible BTG3 molecular mechanism on aggressive colorectal cancer behavior. METHODS: BTG3 expression was assessed by immunohistochemistry (IHC) on specimens from 140 patients with CRC. The association of BTG3 expression with clinicopathological features was examined. To confirm the biological role of BTG3 in CRC, two CRC cell lines expressing BTG3 were used and BTG3 expression was knocked down by shRNA. CCK-8, cell cycle, apoptosis, migration, and invasion assays were performed. The influence of BTG3 knockdown was further investigated by genomic microarray to uncover the potential molecular mechanisms underlying BTG3-mediated CRC development and progression. RESULTS: BTG3 was downregulated in colorectal cancer tissues and positively correlated with pathological classification (p = 0.037), depth of invasion (p = 0.016), distant metastasis (p = 0.024), TNM stage (p = 0.007), and overall survival (OS) and disease-free survival (DFS). BTG3 knockdown promoted cell proliferation, migration, invasion, relieved G2 arrest, and inhibited apoptosis in HCT116 and LoVo cells. A genomic microarray analysis showed that numerous tumor-associated signaling pathways and oncogenes were altered by BTG3 knockdown. At the mRNA level, nine genes referred to the extracellular-regulated kinase/mitogen-activated protein kinase pathway were differentially expressed. Western blotting revealed that BTG3 knockdown upregulated PAK2, RPS6KA5, YWHAB, and signal transducer and activator of transcription (STAT)3 protein levels, but downregulated RAP1A, DUSP6, and STAT1 protein expression, which was consistent with the genomic microarray data. CONCLUSIONS: BTG3 expression might contribute to CRC carcinogenesis. BTG3 knockdown might strengthen the aggressive colorectal cancer behavior.
[Mh] Termos MeSH primário: Neoplasias Colorretais/metabolismo
Proteínas/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Movimento Celular/fisiologia
Proliferação Celular/fisiologia
Neoplasias Colorretais/genética
Neoplasias Colorretais/patologia
Regulação para Baixo
Feminino
Técnicas de Silenciamento de Genes
Células HCT116
Células HT29
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Inclusão em Parafina
Proteínas/genética
Transdução de Sinais
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BTG3 protein, human); 0 (Proteins)
[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:171223
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2561-9


  4 / 162071 MEDLINE  
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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


  5 / 162071 MEDLINE  
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[PMID]:28460441
[Au] Autor:Arora J; Sauer SJ; Tarpley M; Vermeulen P; Rypens C; Van Laere S; Williams KP; Devi GR; Dewhirst MW
[Ad] Endereço:Duke Cancer Institute, Duke University, Durham, NC, USA.
[Ti] Título:Inflammatory breast cancer tumor emboli express high levels of anti-apoptotic proteins: use of a quantitative high content and high-throughput 3D IBC spheroid assay to identify targeting strategies.
[So] Source:Oncotarget;8(16):25848-25863, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inflammatory breast cancer (IBC) is one of the most lethal breast cancer variants; with existing therapy, 5-yr survival rate is only 35%. Current barriers to successful treatment of IBC include frequent infiltration and the presence of tumor cell clusters, termed tumor emboli, within the breast parenchyma and lymphatics. Prior studies have identified the role of anti-apoptotic signaling, in particular hyperactivation of NFκB and its target genes, in IBC pathobiology and therapeutic resistance. The objectives of this study were to: (1) determine if IBC tumor emboli express anti-apoptotic proteins and (2) develop a high content, multiparametric assay to assess the morphology of the IBC 3D spheroids and to optimize a high throughput format to screen for compounds that can inhibit the formation of the IBC tumor clusters/embolic structures. Immunohistochemical analysis of IBC patient tumor samples with documented tumor emboli revealed high NFκB (p65) staining along with expression of XIAP, a potent anti-apoptotic protein known to interact with NFκB signaling in enhancing survival of malignant cells. Subsequently, the high content assay developed allowed for simultaneous imaging and morphometric analysis, including count and viability of spheroids derived from SUM149, rSUM149 and SUM190 cells and its application to evaluate XIAP and NFκB inhibitory agents. We demonstrate the efficacy of the off-patent drug disulfiram when chelated with copper, which we had previously reported to inhibit NFκB signaling, was highly effective in disrupting both IBC spheroids and emboli grown in vitro. Taken together, these results identify a high-throughput approach to target tumor spheroid formation for drug discovery. Finally, disulfiram is a safe and approved drug for management of alcohol abuse, warranting its evaluation for repurposing in IBC therapy.
[Mh] Termos MeSH primário: Proteínas Reguladoras de Apoptose/genética
Neoplasias Inflamatórias Mamárias/genética
Neoplasias Inflamatórias Mamárias/patologia
Células Neoplásicas Circulantes/metabolismo
[Mh] Termos MeSH secundário: Proteínas Reguladoras de Apoptose/metabolismo
Biomarcadores Tumorais
Técnicas de Cultura de Células
Sobrevivência Celular/genética
Cobre/farmacologia
Dissulfiram/farmacologia
Feminino
Expressão Gênica
Ensaios de Triagem em Larga Escala
Seres Humanos
Neoplasias Inflamatórias Mamárias/metabolismo
Mitocôndrias/metabolismo
NF-kappa B/genética
NF-kappa B/metabolismo
Esferoides Celulares
Células Tumorais Cultivadas
Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apoptosis Regulatory Proteins); 0 (Biomarkers, Tumor); 0 (NF-kappa B); 0 (X-Linked Inhibitor of Apoptosis Protein); 0 (XIAP protein, human); 789U1901C5 (Copper); TR3MLJ1UAI (Disulfiram)
[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.15667


  6 / 162071 MEDLINE  
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[PMID]:29353726
[Au] Autor:Czarnecka K; Chufarova N; Halczuk K; Maciejewska K; Girek M; Skibinski R; Jonczyk J; Bajda M; Kabzinski J; Majsterek I; Szymanski P
[Ad] Endereço:Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland. Electronic address: kamila.czarnecka@umed.lodz.pl.
[Ti] Título:Tetrahydroacridine derivatives with dichloronicotinic acid moiety as attractive, multipotent agents for Alzheimer's disease treatment.
[So] Source:Eur J Med Chem;145:760-769, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A novel series of 9-amino-1,2,3,4-tetrahydroacridine and 5,6-dichloronicotinic acid moiety were conjugated with different linkers. Afterwards new derivatives were evaluated as potential multifunctional acetylcholinesterase inhibitors (AChEIs), anti-Alzheimer's disease (AD) drug candidates. All the compounds were synthesized and tested for capacity for the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Specifically, the most promising derivative 3b (IC = 1.02 nM) had higher inhibitory potency compared to the reference drug, tacrine. Consequently, kinetic studies of 3b compound showed a mixed-type inhibition of both AChE and BuChE. Afterwards the best potent AChE inhibitor has been examined on amyloid ß (Aß) self-induced aggregation. Furthermore, 3b compound was tested in various concentrations and had moderate activity against Aß aggregation. Inhibition of Aß aggregation was 46.63% and 19.41% at 50 µM and 5  µM concentrations, respectively. Moreover, no cytotoxicity was observed for the mentioned concentrations. Therefore, 3b compound is a promising multipotent agent for the treatment of AD.
[Mh] Termos MeSH primário: Acetilcolinesterase/metabolismo
Acridinas/farmacologia
Doença de Alzheimer/tratamento farmacológico
Butirilcolinesterase/metabolismo
Inibidores da Colinesterase/farmacologia
Ácidos Nicotínicos/farmacologia
[Mh] Termos MeSH secundário: Acridinas/química
Doença de Alzheimer/metabolismo
Peptídeos beta-Amiloides/antagonistas & inibidores
Peptídeos beta-Amiloides/metabolismo
Animais
Inibidores da Colinesterase/síntese química
Inibidores da Colinesterase/química
Relação Dose-Resposta a Droga
Electrophorus
Cavalos
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Ácidos Nicotínicos/química
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5,6-dichloronicotinic acid); 0 (Acridines); 0 (Amyloid beta-Peptides); 0 (Cholinesterase Inhibitors); 0 (Nicotinic Acids); EC 3.1.1.7 (Acetylcholinesterase); EC 3.1.1.8 (Butyrylcholinesterase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180123
[St] Status:MEDLINE


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[PMID]:29353724
[Au] Autor:Jin K; Yin H; De Clercq E; Pannecouque C; Meng G; Chen F
[Ad] Endereço:Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai 200433, People's Republic of China.
[Ti] Título:Discovery of biphenyl-substituted diarylpyrimidines as non-nucleoside reverse transcriptase inhibitors with high potency against wild-type and mutant HIV-1.
[So] Source:Eur J Med Chem;145:726-734, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A novel series of diarylpyrimidine (DAPY) derivatives bearing the biphenyl motif with multiple substituted groups was synthesized as human immunodeficiency virus (HIV)-1 non-nucleoside reverse transcriptase inhibitors. All of the target compounds were evaluated for their in vitro activity against HIV in MT-4 cells. Most of the compounds exhibited excellent activity with low nanomolar EC values against wild-type, single and double mutant HIV-1 strains. Compound 4b displayed an EC value of 1 nM against HIV-1 IIIB, 1.3 nM against L100I, 0.84 nM against K103 N, 1.5 nM against Y181C, 11 nM against Y188L, 2 nM against E138K, 10 nM against K103 N + Y181C, and almost 110 nM against F227L + V106. The improvement in the selectivity and potency of the target molecules against the wild-type and mutant HIV-1 strains validated our hypothesis. The biphenyl ring in the DAPY derivatives could strengthen the π-π stacking effect between the target molecule and the non-nucleoside inhibitor-binding pocket in the reverse transcriptase by extending the conjugating systems. This research represented a significant step toward the discovery of novel therapeutic DAPYs for treating acquired immunodeficiency syndrome in patients infected with HIV-1.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/farmacologia
Compostos de Bifenilo/farmacologia
Transcriptase Reversa do HIV/antagonistas & inibidores
HIV-1/efeitos dos fármacos
Pirimidinas/farmacologia
Inibidores da Transcriptase Reversa/farmacologia
[Mh] Termos MeSH secundário: Fármacos Anti-HIV/síntese química
Fármacos Anti-HIV/química
Compostos de Bifenilo/química
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Descoberta de Drogas
Transcriptase Reversa do HIV/metabolismo
HIV-1/genética
Seres Humanos
Testes de Sensibilidade Microbiana
Simulação de Acoplamento Molecular
Estrutura Molecular
Mutação
Pirimidinas/síntese química
Pirimidinas/química
Inibidores da Transcriptase Reversa/síntese química
Inibidores da Transcriptase Reversa/química
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Biphenyl Compounds); 0 (Pyrimidines); 0 (Reverse Transcriptase Inhibitors); 2L9GJK6MGN (diphenyl); EC 2.7.7.49 (HIV Reverse Transcriptase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180123
[St] Status:MEDLINE


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[PMID]:29339255
[Au] Autor:Sun G; Wang J; Guo X; Lei M; Zhang Y; Wang X; Shen X; Hu L
[Ad] Endereço:Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Stake Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 2100
[Ti] Título:Design, synthesis and biological evaluation of LX2343 derivatives as neuroprotective agents for the treatment of Alzheimer's disease.
[So] Source:Eur J Med Chem;145:622-633, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A series of LX2343 derivatives were designed, synthesized and evaluated as neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the compounds displayed potent neuroprotective activities. Especially for compound A6, exhibited a remarkable EC value of 0.22 µM. Further investigation demonstrated that compound A6 can significantly reduce Aß production and increase Aß clearance, and alleviate Tau hyperphosphorylation. Most importantly, compound A6 could ameliorate learning and memory impairments in APP/PS1 transgenic mice. The present study evidently showed that compound A6 is a potent neuroprotective agent and might serve as a promising lead candidate for the treatment of Alzheimer's disease.
[Mh] Termos MeSH primário: Acetamidas/farmacologia
Doença de Alzheimer/tratamento farmacológico
Desenho de Drogas
Fármacos Neuroprotetores/farmacologia
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Acetamidas/síntese química
Acetamidas/química
Peptídeos beta-Amiloides/antagonistas & inibidores
Peptídeos beta-Amiloides/metabolismo
Animais
Relação Dose-Resposta a Droga
Células HEK293
Seres Humanos
Aprendizagem em Labirinto/efeitos dos fármacos
Transtornos da Memória/tratamento farmacológico
Camundongos
Camundongos Transgênicos
Estrutura Molecular
Fármacos Neuroprotetores/síntese química
Fármacos Neuroprotetores/química
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetamides); 0 (Amyloid beta-Peptides); 0 (LX2343); 0 (Neuroprotective Agents); 0 (Sulfonamides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  9 / 162071 MEDLINE  
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[PMID]:29339250
[Au] Autor:Wei Q; Ning JY; Dai X; Gao YD; Su L; Zhao BX; Miao JY
[Ad] Endereço:Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, PR China.
[Ti] Título:Discovery of novel HSP90 inhibitors that induced apoptosis and impaired autophagic flux in A549 lung cancer cells.
[So] Source:Eur J Med Chem;145:551-558, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Heat shock protein 90 (HSP90) inhibition has aroused increasing enthusiasm in antitumor strategies in recent years. According to our previous studies, we synthesized a series of coumarin pyrazoline compounds HCP1-HCP6 that might be HSP90 inhibitors. Interactions between HCP1-HCP6 and HSP90 were examined and antitumor activities of them were investigated in A549 lung cancer cells. Results showed that all the six derivatives could interact with HSP90, in which HCP1 exhibited the best binding ability and inhibited the activity of HSP90. Meanwhile, HCP1-HCP6 reduced the cell viability of A549 cells and HCP1 possessed the lowest IC value. Above all HCP1 exerted better HSP90 inhibitory and anticancer effects than our initially identified HSP90 inhibitor DPB. As to the underlying mechanism, HCP1-HCP6 not only induced apoptosis as DPB but also blocked autophagic flux in A549 cells. Therefore, we discovered a novel HSP90 inhibitor HCP1 that had better biological activity and provided us a useful tool to explore the underlying mechanism of lung cancer therapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Cumarínicos/farmacologia
Descoberta de Drogas
Proteínas de Choque Térmico HSP90/antagonistas & inibidores
Pirazóis/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Proliferação Celular/efeitos dos fármacos
Cumarínicos/síntese química
Cumarínicos/química
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Pirazóis/síntese química
Pirazóis/química
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Coumarins); 0 (HSP90 Heat-Shock Proteins); 0 (Pyrazoles); A4VZ22K1WT (coumarin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  10 / 162071 MEDLINE  
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[PMID]:29335212
[Au] Autor:Gupta N; Qayum A; Raina A; Shankar R; Gairola S; Singh S; Sangwan PL
[Ad] Endereço:Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India.
[Ti] Título:Synthesis and biological evaluation of novel bavachinin analogs as anticancer agents.
[So] Source:Eur J Med Chem;145:511-523, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A library of 28 analogs of bavachinin including aliphatic and aromatic ethers, epoxide, chalcone, oxime, semicarbazide, oxime ether and triazole derivatives have been synthesized and evaluated for cytotoxicity against four different human cancer cell lines. Bio-evaluation studies exhibited better cytotoxic profile for many analogs compare to bavachinin. Best results were observed for a 1,2,3-triazole analog (17i) with IC values 7.72, 16.08, 7.13 and 11.67 µM against lung (A549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell lines respectively. This analog showed three and four fold improvement in cytotoxicity against HCT-116 and A549 cell lines than parent molecule (1). Structure activity relationship (SAR) study for all synthesized analogs was carried out. Further, mechanistic study of the lead molecule (17i) revealed that it inhibits colony formation and in vitro migration of human colon cancer cells (HCT-116). Also, it induced the morphological changes and mediated the apoptotic cell death of HCT-116 cells with perturbance in mitochondrial membrane potential (MMP) and PARP cleavage.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Flavonoides/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Flavonoides/síntese química
Flavonoides/química
Seres Humanos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Estrutura Molecular
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Flavonoids); 19879-30-2 (bavachinin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE



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