Base de dados : MEDLINE
Pesquisa : D03.633.400 [Categoria DeCS]
Referências encontradas : 2659 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 266 ir para página                         

  1 / 2659 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29324623
[Au] Autor:Hussar DA
[Ad] Endereço:Remington Professor of Pharmacy Philadelphia College of Pharmacy University of the Sciences Philadelphia, Pa.
[Ti] Título:New Drugs 2018, part 1.
[So] Source:Nursing;48(2):36-44, 2018 Feb.
[Is] ISSN:1538-8689
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Aprovação de Drogas
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/uso terapêutico
Anticorpos Neutralizantes/uso terapêutico
Antipirina/análogos & derivados
Antipirina/uso terapêutico
Benzamidas/uso terapêutico
Benzimidazóis/uso terapêutico
Carbamatos/uso terapêutico
Combinação de Medicamentos
Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico
Seres Humanos
Compostos Macrocíclicos/uso terapêutico
Naltrexona/análogos & derivados
Naltrexona/uso terapêutico
Peptídeos Natriuréticos/uso terapêutico
Piridinas/uso terapêutico
Quinoxalinas/uso terapêutico
Sofosbuvir/uso terapêutico
Sulfonamidas/uso terapêutico
Estados Unidos
United States Food and Drug Administration
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-493); 0 (Antibodies, Monoclonal); 0 (Antibodies, Neutralizing); 0 (Benzamides); 0 (Benzimidazoles); 0 (Carbamates); 0 (Drug Combinations); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (Macrocyclic Compounds); 0 (Natriuretic Peptides); 0 (Pyridines); 0 (Quinoxalines); 0 (Sulfonamides); 0 (bezlotoxumab); 0 (naldemedine); 0 (pibrentasvir); 0 (voxilaprevir); 5S6W795CQM (Naltrexone); 74RWP7W0J9 (betrixaban); 7IK8Z952OK (plecanatide); KCU0C7RS7Z (velpatasvir); S798V6YJRP (phenylmethylpyrazolone); T3CHA1B51H (Antipyrine); WJ6CA3ZU8B (Sofosbuvir)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:N
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1097/01.NURSE.0000529803.83288.e1


  2 / 2659 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29385160
[Au] Autor:Just S; Chenard BL; Ceci A; Strassmaier T; Chong JA; Blair NT; Gallaschun RJ; Del Camino D; Cantin S; D'Amours M; Eickmeier C; Fanger CM; Hecker C; Hessler DP; Hengerer B; Kroker KS; Malekiani S; Mihalek R; McLaughlin J; Rast G; Witek J; Sauer A; Pryce CR; Moran MM
[Ad] Endereço:Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
[Ti] Título:Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice.
[So] Source:PLoS One;13(1):e0191225, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Forty million adults in the US suffer from anxiety disorders, making these the most common forms of mental illness. Transient receptor potential channel canonical subfamily (TRPC) members 4 and 5 are non-selective cation channels highly expressed in regions of the cortex and amygdala, areas thought to be important in regulating anxiety. Previous work with null mice suggests that inhibition of TRPC4 and TRPC5 may have anxiolytic effects. HC-070 IN VITRO: To assess the potential of TRPC4/5 inhibitors as an avenue for treatment, we invented a highly potent, small molecule antagonist of TRPC4 and TRPC5 which we call HC-070. HC-070 inhibits recombinant TRPC4 and TRPC5 homomultimers in heterologous expression systems with nanomolar potency. It also inhibits TRPC1/5 and TRPC1/4 heteromultimers with similar potency and reduces responses evoked by cholecystokinin tetrapeptide (CCK-4) in the amygdala. The compound is >400-fold selective over a wide range of molecular targets including ion channels, receptors, and kinases. HC-070 IN VIVO: Upon oral dosing in mice, HC-070 achieves exposure levels in the brain and plasma deemed sufficient to test behavioral activity. Treatment with HC-070 attenuates the anxiogenic effect of CCK-4 in the elevated plus maze (EPM). The compound recapitulates the phenotype observed in both null TRPC4 and TRPC5 mice in a standard EPM. Anxiolytic and anti-depressant effects of HC-070 are also observed in pharmacological in vivo tests including marble burying, tail suspension and forced swim. Furthermore, HC-070 ameliorates the increased fear memory induced by chronic social stress. A careful evaluation of the pharmacokinetic-pharmacodynamic relationship reveals that substantial efficacy is observed at unbound brain levels similar to, or even lower than, the 50% inhibitory concentration (IC50) recorded in vitro, increasing confidence that the observed effects are indeed mediated by TRPC4 and/or TRPC5 inhibition. Together, this experimental data set introduces a novel, high quality, small molecule antagonist of TRPC4 and TRPC5 containing channels and supports the targeting of TRPC4 and TRPC5 channels as a new mechanism of action for the treatment of psychiatric symptoms.
[Mh] Termos MeSH primário: Ansiolíticos/farmacologia
Antidepressivos/farmacologia
Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia
Canais de Cátion TRPC/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Ansiolíticos/química
Ansiolíticos/farmacocinética
Antidepressivos/química
Antidepressivos/farmacocinética
Ansiedade/tratamento farmacológico
Ansiedade/metabolismo
Ansiedade/psicologia
Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos
Complexo Nuclear Basolateral da Amígdala/metabolismo
Comportamento Animal/efeitos dos fármacos
Depressão/tratamento farmacológico
Depressão/metabolismo
Depressão/psicologia
Modelos Animais de Doenças
Medo/efeitos dos fármacos
Medo/fisiologia
Medo/psicologia
Compostos Heterocíclicos de 4 ou mais Anéis/química
Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética
Ensaios de Triagem em Larga Escala
Seres Humanos
Técnicas In Vitro
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Antidepressive Agents); 0 (HC-070); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (TRPC Cation Channels); 0 (TRPC4 ion channel); 0 (TRPC5 protein, human); 0 (Trpc5 protein, mouse)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191225


  3 / 2659 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28455854
[Au] Autor:Yan Q; Banwell MG; Coote ML; Lee R; Willis AC
[Ad] Endereço:Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT, 2601, Australia.
[Ti] Título:Establishing the True Structure of the Sorbicillinoid-Derived Isolate Rezishanone C by Total Synthesis.
[So] Source:Chem Asian J;12(13):1480-1484, 2017 Jul 04.
[Is] ISSN:1861-471X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The enantiomer, ent-4, of the true structure, 4, of the sorbicillinoid rezishanone C (sorbivinetone) has been synthesized from a homochiral cis-1,2-dihydrocatechol that is itself generated through the whole-cell biotransformation of toluene. These studies together with dispersion-corrected DFT calculations support the proposal that rezishanone C is an artefact of the isolation process and arises through a Diels-Alder reaction between ethyl vinyl ether and sorbicillinol (3).
[Mh] Termos MeSH primário: Cicloexanonas/química
Etil-Éteres/química
Compostos Heterocíclicos de 4 ou mais Anéis/síntese química
Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação
[Mh] Termos MeSH secundário: Reação de Cicloadição
Compostos Heterocíclicos de 4 ou mais Anéis/química
Estrutura Molecular
Teoria Quântica
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclohexanones); 0 (Ethyl Ethers); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (sorbicillinol); 6235C9592H (ethyl vinyl ether)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1002/asia.201700456


  4 / 2659 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29173760
[Au] Autor:Foy V; Schenk MW; Baker K; Gomes F; Lallo A; Frese KK; Forster M; Dive C; Blackhall F
[Ad] Endereço:Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, UK.
[Ti] Título:Targeting DNA damage in SCLC.
[So] Source:Lung Cancer;114:12-22, 2017 Dec.
[Is] ISSN:1872-8332
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:SCLC accounts for 15% of lung cancer worldwide. Characterised by early dissemination and rapid development of chemo-resistant disease, less than 5% of patients survive 5 years. Despite 3 decades of clinical trials there has been no change to the standard platinum and etoposide regimen for first line treatment developed in the 1970's. The exceptionally high number of genomic aberrations observed in SCLC combined with the characteristic rapid cellular proliferation results in accumulation of DNA damage and genomic instability. To flourish in this precarious genomic context, SCLC cells are reliant on functional DNA damage repair pathways and cell cycle checkpoints. Current cytotoxic drugs and radiotherapy treatments for SCLC have long been known to act by induction of DNA damage and the response of cancer cells to such damage determines treatment efficacy. Recent years have witnessed improved understanding of strategies to exploit DNA damage and repair mechanisms in order to increase treatment efficacy. This review will summarise the rationale to target DNA damage response in SCLC, the progress made in evaluating novel DDR inhibitors and highlight various ongoing challenges for their clinical development in this disease.
[Mh] Termos MeSH primário: Dano ao DNA/genética
Neoplasias Pulmonares/tratamento farmacológico
Rad51 Recombinase/antagonistas & inibidores
Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
[Mh] Termos MeSH secundário: Aurora Quinases/uso terapêutico
Azepinas/uso terapêutico
Benzimidazóis/uso terapêutico
Carbolinas/uso terapêutico
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Pontos de Checagem do Ciclo Celular/genética
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/genética
Citotoxinas/uso terapêutico
Dano ao DNA/efeitos dos fármacos
Reparo do DNA
Etoposídeo/uso terapêutico
Instabilidade Genômica/efeitos dos fármacos
Instabilidade Genômica/genética
Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico
Seres Humanos
Neoplasias Pulmonares/genética
Terapia de Alvo Molecular/métodos
Ftalazinas/uso terapêutico
Piperazinas/uso terapêutico
Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
Inibidores de Proteínas Quinases/uso terapêutico
Pirimidinas/uso terapêutico
Rad51 Recombinase/uso terapêutico
Carcinoma de Pequenas Células do Pulmão/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Azepines); 0 (Benzimidazoles); 0 (Carbolines); 0 (Cytotoxins); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (MLN 8237); 0 (PM 01183); 0 (Phthalazines); 0 (Piperazines); 0 (Poly(ADP-ribose) Polymerase Inhibitors); 0 (Protein Kinase Inhibitors); 0 (Pyrimidines); 01O4K0631N (veliparib); 6PLQ3CP4P3 (Etoposide); 9QHX048FRV (talazoparib); EC 2.7.11.1 (Aurora Kinases); EC 2.7.7.- (Rad51 Recombinase); WOH1JD9AR8 (olaparib)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  5 / 2659 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29247039
[Au] Autor:Joshi JJ; Coffey H; Corcoran E; Tsai J; Huang CL; Ichikawa K; Prajapati S; Hao MH; Bailey S; Wu J; Rimkunas V; Karr C; Subramanian V; Kumar P; MacKenzie C; Hurley R; Satoh T; Yu K; Park E; Rioux N; Kim A; Lai WG; Yu L; Zhu P; Buonamici S; Larsen N; Fekkes P; Wang J; Warmuth M; Reynolds DJ; Smith PG; Selvaraj A
[Ad] Endereço:H3 Biomedicine, Cambridge, Massachusetts.
[Ti] Título:H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma.
[So] Source:Cancer Res;77(24):6999-7013, 2017 Dec 15.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Activation of the fibroblast growth factor receptor FGFR4 by FGF19 drives hepatocellular carcinoma (HCC), a disease with few, if any, effective treatment options. While a number of pan-FGFR inhibitors are being clinically evaluated, their application to FGF19-driven HCC may be limited by dose-limiting toxicities mediated by FGFR1-3 receptors. To evade the potential limitations of pan-FGFR inhibitors, we generated H3B-6527, a highly selective covalent FGFR4 inhibitor, through structure-guided drug design. Studies in a panel of 40 HCC cell lines and 30 HCC PDX models showed that FGF19 expression is a predictive biomarker for H3B-6527 response. Moreover, coadministration of the CDK4/6 inhibitor palbociclib in combination with H3B-6527 could effectively trigger tumor regression in a xenograft model of HCC. Overall, our results offer preclinical proof of concept for H3B-6527 as a candidate therapeutic agent for HCC cases that exhibit increased expression of FGF19. .
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Carcinoma Hepatocelular/tratamento farmacológico
Transformação Celular Neoplásica/genética
Fatores de Crescimento de Fibroblastos/genética
Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico
Neoplasias Hepáticas/tratamento farmacológico
Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Carcinoma Hepatocelular/genética
Carcinoma Hepatocelular/patologia
Linhagem Celular Tumoral
Feminino
Seres Humanos
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/patologia
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (FGF19 protein, human); 0 (H3B-6527); 0 (Heterocyclic Compounds, 4 or More Rings); 62031-54-3 (Fibroblast Growth Factors); EC 2.7.10.1 (FGFR4 protein, human); EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 4)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-17-1865


  6 / 2659 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27773936
[Au] Autor:Liu Y; Qi Y; Bai ZH; Ni CX; Ren QH; Xu WH; Xu J; Hu HG; Qiu L; Li JZ; He ZG; Zhang JP
[Ad] Endereço:Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 310000, China.
[Ti] Título:A novel matrine derivate inhibits differentiated human hepatoma cells and hepatic cancer stem-like cells by suppressing PI3K/AKT signaling pathways.
[So] Source:Acta Pharmacol Sin;38(1):120-132, 2017 Jan.
[Is] ISSN:1745-7254
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, which has shown chemopreventive potential against various cancers. In this study, we evaluated the anticancer efficacy of a novel derivative of matrine, (6aS, 10S, 11aR, 11bR, 11cS)-10- methylamino-dodecahydro- 3a,7a-diazabenzo (de) (MASM), against human hepatocellular carcinoma (HCC) cells and their corresponding sphere cells in vitro and in vivo. Human HCC cell lines (Hep3B and Huh7) were treated with MASM. Cell proliferation was assessed using CCK8 and colony assays; cell apoptosis and cell cycle distributions were examined with flow cytometry. The expression of cell markers and signaling molecules was detected using Western blot and qRT-PCR analyses. A sphere culture technique was used to enrich cancer stem cells (CSC) in Hep3B and Huh7 cells. The in vivo antitumor efficacy of MASM was evaluated in Huh7 cell xenograft model in BALB/c nude mice, which were administered MASM (10 mg·kg ·d , ig) for 3 weeks. After the treatment was completed, tumor were excised and weighed. A portion of tumor tissue was enzymatically dissociated to obtain a single cell suspension for the spheroid formation assays. MASM (2, 10, 20 µmol/L) dose-dependently inhibited the proliferation of HCC cells, and induced apoptosis, which correlated with a reduction in Bcl-2 expression and an increase in PARP cleavage. MASM also induced cell cycle arrest in G /G phase, which was accompanied by increased p27 and decreased Cyclin D1 expression. Interestingly, MASM (2, 10, and 20 µmol/L) drastically reduced the EpCAM /CD133 cell numbers, suppressed the sphere formation, inhibited the expression of stem cell marker genes and promoted the expression of mature hepatocyte markers in the Hep3B and Huh7 spheroids. Additionally, MASM dose-dependently suppressed the PI3K/AKT/mTOR and AKT/GSK3ß/ß-catenin signaling pathways in Hep3B and Huh7 cells. In Huh7 xenograft bearing nude mice, MASM administration significantly inhibited Huh7 xenograft tumor growth and markedly reduced the number of surviving cancer stem-like cells in the tumors. MASM administration also reduced the expression of stem cell markers while increasing the expression of mature hepatocyte markers in the tumor tissues. The novel derivative of matrine, MASM, markedly suppresses HCC tumor growth through multiple mechanisms, and it may be a promising candidate drug for the treatment of hepatocellular carcinoma.
[Mh] Termos MeSH primário: Alcaloides/química
Alcaloides/farmacologia
Carcinoma Hepatocelular/patologia
Proliferação Celular/efeitos dos fármacos
Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia
Neoplasias Hepáticas/patologia
Células-Tronco Neoplásicas/efeitos dos fármacos
Quinolizinas/química
Quinolizinas/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Contagem de Células
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Diferenciação Celular
Linhagem Celular Tumoral
Ciclina D1/biossíntese
Relação Dose-Resposta a Droga
Molécula de Adesão da Célula Epitelial/metabolismo
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Camundongos
Camundongos Nus
Células-Tronco Neoplásicas/enzimologia
Células-Tronco Neoplásicas/metabolismo
Fosfatidilinositol 3-Quinases
Antígeno Nuclear de Célula em Proliferação/biossíntese
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (10-methylaminododecahydro-3a,7a-diazabenzo(de)anthracene-8-thione); 0 (Alkaloids); 0 (Antineoplastic Agents); 0 (EPCAM protein, human); 0 (Epithelial Cell Adhesion Molecule); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (Proliferating Cell Nuclear Antigen); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Quinolizines); 0 (p27 antigen); 136601-57-5 (Cyclin D1); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); N390W430AC (matrine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1038/aps.2016.104


  7 / 2659 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28956664
[Au] Autor:Han Y; Mesplède T; Wainberg MA
[Ad] Endereço:a McGill University AIDS Centre, Lady Davis Institute for Medical Research , Jewish General Hospital , Montreal , QC , Canada.
[Ti] Título:Investigational HIV integrase inhibitors in phase I and phase II clinical trials.
[So] Source:Expert Opin Investig Drugs;26(11):1207-1213, 2017 Nov.
[Is] ISSN:1744-7658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: To date, three HIV integrase strand transfer inhibitors (INSTIs), i.e. raltegravir, elvitegravir and dolutegravir, have been approved for clinical use. Recent research has focused on new integrase inhibitors including those targeting non-catalytic sites of HIV integrase. Areas covered: This paper reviews two investigational INSTIs in phase I and II clinical trials, bictegravir (BIC) and cabotegravir (CAB), as well as an investigational noncatalytic integrase inhibitor (NCINI) termed BI 224436. Expert opinion: Data from phase I and II clinical trials demonstrate that CAB has good efficacy and is well-tolerated. CAB is promising because it can be formulated both orally and as a long-acting (LA) injectable for treatment and prevention of HIV infection. Since LA-CAB formulation offers the possibility of favourable dosing, it may help individuals who struggle with adherence issues. BIC also represents a promising safe, effective and well-tolerated drug that can be administered as a single once-daily regimen in coformulation with emtricitabine and tenofovir alafenamide (FTC/TAF). Ongoing phase III trials should clarify optimal doses and reveal the potential clinical advantages of these new drugs and formulations over other current regimens. Exploration of novel HIV integrase inhibitors acting through mechanisms different from those of INSTIs is still needed.
[Mh] Termos MeSH primário: Drogas em Investigação/administração & dosagem
Infecções por HIV/tratamento farmacológico
Inibidores de Integrase de HIV/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Ensaios Clínicos Fase I como Assunto
Ensaios Clínicos Fase II como Assunto
Drogas em Investigação/efeitos adversos
Drogas em Investigação/farmacologia
Infecções por HIV/enzimologia
Inibidores de Integrase de HIV/efeitos adversos
Inibidores de Integrase de HIV/farmacologia
Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem
Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos
Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia
Seres Humanos
Adesão à Medicação
Piridonas/administração & dosagem
Piridonas/efeitos adversos
Piridonas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Drugs, Investigational); 0 (GSK1265744); 0 (HIV Integrase Inhibitors); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (Pyridones); 0 (bictegravir)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170929
[St] Status:MEDLINE
[do] DOI:10.1080/13543784.2017.1378643


  8 / 2659 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28937996
[Au] Autor:Zainabadi K; Liu CJ; Caldwell ALM; Guarente L
[Ad] Endereço:Glenn Center for the Science of Aging, Department of Biology, Koch Institute, MIT, Cambridge, Massachusetts, United States of America.
[Ti] Título:SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis.
[So] Source:PLoS One;12(9):e0185236, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Overexpression or pharmacological activation of SIRT1 has been shown to extend the lifespan of mice and protect against aging-related diseases. Here we show that pharmacological activation of SIRT1 protects in two models of osteoporosis. Ovariectomized female mice and aged male mice, models for post-menopausal and aging-related osteoporosis, respectively, show significant improvements in bone mass upon treatment with SIRT1 agonist, SRT1720. Further, we find that calorie restriction (CR) results in a two-fold upregulation of sirt1 mRNA expression in bone tissue that is associated with increased bone mass in CR mice. Reciprocally, SIRT1 whole-body knockout (KO) mice, as well as osteoblast and osteoclast specific KOs, show a low bone mass phenotype; though double knockout mice (containing SIRT1 deleted in both osteoblasts and osteoclasts) do not show a more severe phenotype. Altogether, these findings provide strong evidence that SIRT1 is a positive regulator of bone mass and a promising target for the development of novel therapeutics for osteoporosis.
[Mh] Termos MeSH primário: Conservadores da Densidade Óssea/farmacologia
Densidade Óssea/efeitos dos fármacos
Osso e Ossos/efeitos dos fármacos
Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia
Osteoporose/tratamento farmacológico
Sirtuína 1/metabolismo
[Mh] Termos MeSH secundário: Envelhecimento/efeitos dos fármacos
Envelhecimento/metabolismo
Animais
Densidade Óssea/fisiologia
Osso e Ossos/diagnóstico por imagem
Osso e Ossos/metabolismo
Restrição Calórica
Modelos Animais de Doenças
Feminino
Masculino
Camundongos da Linhagem 129
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Osteoblastos/efeitos dos fármacos
Osteoblastos/metabolismo
Osteoclastos/efeitos dos fármacos
Osteoclastos/metabolismo
Osteoporose/diagnóstico por imagem
Osteoporose/metabolismo
Ovariectomia
Fenótipo
RNA Mensageiro/metabolismo
Sirtuína 1/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Density Conservation Agents); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (RNA, Messenger); 0 (SRT1720); EC 3.5.1.- (Sirt1 protein, mouse); EC 3.5.1.- (Sirtuin 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185236


  9 / 2659 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28935273
[Au] Autor:Rustin G; Vergote I; Micha JP; Duska LR; Reed N; Bendell J; Spitz D; Dark G; Hoch U; Tagliaferri M; Hannah AL; Garcia AA
[Ad] Endereço:Mount Vernon Hospital, Middlesex, United Kingdom.
[Ti] Título:A multicenter, open-label, expanded phase 2 study to evaluate the safety and efficacy of etirinotecan pegol, a polymer conjugate of irinotecan, in women with recurrent platinum-resistant or refractory ovarian cancer.
[So] Source:Gynecol Oncol;147(2):276-282, 2017 Nov.
[Is] ISSN:1095-6859
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Etirinotecan pegol (EP) is a novel polyethylene glycol conjugated form of irinotecan with documented activity in platinum-resistant ovarian cancer (PROC). We report the results of the expanded portion of a phase II study of EP in patients with PROC who received prior pegylated liposomal doxorubicin (PLD) or who were unable to receive it. METHODS: This multicenter, open-label, phase II study evaluated EP q21d for PROC. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.0. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Patient populations evaluated included a modified intent-to-treat (mITT) group consisting of all patients who received at least one dose and with measurable disease and a primary efficacy (pEFF) group (subset of the mITT population who received prior PLD). RESULTS: One hundred thirty-nine patients were enrolled. Of the 132 patients in the mITT group, 20 achieved an ORR (15.2%; 95% CI 9.5-22.4); median PFS and OS were 4.4 months and 10.2 months, respectively. In the pEFF group (n=104), 15 patients (14.4%; 95% CI 8.3-22.7) achieved an ORR; median PFS and OS were 4.4 months and 10.9 months, respectively. The most common grade 3/4 toxicities were diarrhea (20%), abdominal pain (17%), vomiting (14%), dehydration (13%), and nausea (13%). Severe diarrhea was reduced to 15% with strict adherence to screening and management guidelines. CONCLUSIONS: This study confirms the activity and safety of single-agent EP in patients with PROC, including patients who received prior PLD. Further evaluation earlier in the disease course and in combination is warranted.
[Mh] Termos MeSH primário: Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico
Recidiva Local de Neoplasia/tratamento farmacológico
Neoplasias Epiteliais e Glandulares/tratamento farmacológico
Neoplasias Ovarianas/tratamento farmacológico
Polietilenoglicóis/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/efeitos adversos
Antineoplásicos/uso terapêutico
Resistência a Medicamentos Antineoplásicos
Feminino
Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos
Seres Humanos
Meia-Idade
Compostos Organoplatínicos/farmacologia
Polietilenoglicóis/efeitos adversos
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (Organoplatinum Compounds); 30IQX730WE (Polyethylene Glycols); LJ16641SFT (etirinotecan pegol)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE


  10 / 2659 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28910661
[Au] Autor:Wang LL; Zhao DS; Shi W; Li ZQ; Wu ZT; Li P; Li HJ
[Ad] Endereço:State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
[Ti] Título:Describing the holistic toxicokinetics of hepatotoxic Chinese herbal medicines by a novel integrated strategy: Dioscorea bulbifera rhizome as a case study.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1064:40-48, 2017 Oct 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:It is vital to monitor the holistic toxicokinetics of toxic Chinese herbal medicines (CHMs) for safety. Although an integrated strategy based on the area under the curve (AUC) has been proposed to characterize the pharmacokinetic/toxicokinetic properties of CHMs, improvement is still needed. This study attempted to use 50% inhibitory concentration (IC ) as weighting coefficient to investigate holistic toxicokinetics of the major diosbulbins i.e. diosbulbin A (DA), diosbulbin B (DB), and diosbulbin C (DC) after oral administration of Dioscorea bulbifera rhizome (DBR) extract. Firstly, the cytotoxicities of the three diosbulbins on human hepatic L02 cells were evaluated and the IC values were calculated. Then, integrated toxicokinetics of multiple diosbulbins based on AUC and IC were determined. Finally, correlations between integrated plasma concentrations and hepatic injury biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bile acid (TBA) were analyzed. As a result, integrated plasma concentrations were correlated well with TBA and the correlation between TBA and IC -weighting integrated plasma concentrations was better than that of AUC-weighting integrated plasma concentrations. In conclusion, the newly developed IC -weighting method is expected to generate more reasonable integrated toxicokinetic parameters, which will help to guide the safe usage of DBR in clinical settings.
[Mh] Termos MeSH primário: Dioscorea/química
Medicamentos de Ervas Chinesas
Compostos Heterocíclicos de 4 ou mais Anéis/sangue
Toxicocinética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Cromatografia Líquida
Medicamentos de Ervas Chinesas/administração & dosagem
Medicamentos de Ervas Chinesas/farmacocinética
Medicamentos de Ervas Chinesas/toxicidade
Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética
Compostos Heterocíclicos de 4 ou mais Anéis/toxicidade
Seres Humanos
Concentração Inibidora 50
Modelos Lineares
Fígado/efeitos dos fármacos
Fígado/patologia
Masculino
Espectrometria de Massas
Ratos
Ratos Sprague-Dawley
Reprodutibilidade dos Testes
Rizoma/química
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drugs, Chinese Herbal); 0 (Heterocyclic Compounds, 4 or More Rings); 20086-06-0 (diosbulbin B)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE



página 1 de 266 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde