Base de dados : MEDLINE
Pesquisa : D03.633.100.786 [Categoria DeCS]
Referências encontradas : 16615 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 1662 ir para página                         

  1 / 16615 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28456787
[Au] Autor:Hichert V; Scholl C; Steffens M; Paul T; Schumann C; Rüdiger S; Boeck S; Heinemann V; Kächele V; Seufferlein T; Stingl J
[Ad] Endereço:Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany.
[Ti] Título:Predictive blood plasma biomarkers for EGFR inhibitor-induced skin rash.
[So] Source:Oncotarget;8(21):35193-35204, 2017 May 23.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib, gefitinib, cetuximab and panitumumab. A common adverse effect is a typical papulopustular acneiform rash, whose occurrence and severity are positively correlated with overall survival in several cancer types. We studied molecules involved in epidermal growth factor receptor signaling which are quantifiable in plasma, with the aim of identifying biomarkers for the severity of rash. With a predictive value for the rash these biomarkers may also have a prognostic value for survival and disease outcome.The concentrations of amphiregulin, hepatocyte growth factor (HGF) and calcidiol were determined by specific enzyme-linked immunosorbent assays in plasma samples from 211 patients.We observed a significant inverse correlation between the plasma concentration of HGF and overall survival in patients with an inhibitor-induced rash (p-value = 0.0075; mean overall survival low HGF: 299 days, high HGF: 240 days) but not in patients without rash. The concentration of HGF was also significantly inversely correlated with severity of rash (p-value = 0.00124).High levels of HGF lead to increased signaling via its receptor MET, which can activate numerous pathways which are normally also activated by epidermal growth factor receptor. Increased HGF/MET signaling might compensate the inhibitory effect of epidermal growth factor receptor inhibitors in skin as well as tumor cells, leading to less severe skin rash and decreased efficacy of the anti-tumor therapy, rendering the plasma concentration of HGF a candidate for predictive biomarkers.
[Mh] Termos MeSH primário: Exantema/induzido quimicamente
Fator de Crescimento de Hepatócito/sangue
Neoplasias/sangue
Neoplasias/tratamento farmacológico
Inibidores de Proteínas Quinases/administração & dosagem
Proteínas Proto-Oncogênicas c-met/sangue
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Anfirregulina/sangue
Biomarcadores Tumorais/sangue
Calcifediol/sangue
Cetuximab/administração & dosagem
Cetuximab/efeitos adversos
Cloridrato de Erlotinib/administração & dosagem
Cloridrato de Erlotinib/efeitos adversos
Exantema/sangue
Feminino
Seres Humanos
Masculino
Meia-Idade
Neoplasias/genética
Neoplasias/metabolismo
Estudos Prospectivos
Inibidores de Proteínas Quinases/efeitos adversos
Quinazolinas/administração & dosagem
Quinazolinas/efeitos adversos
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Receptor do Fator de Crescimento Epidérmico/genética
Transdução de Sinais/efeitos dos fármacos
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AREG protein, human); 0 (Amphiregulin); 0 (Biomarkers, Tumor); 0 (HGF protein, human); 0 (Protein Kinase Inhibitors); 0 (Quinazolines); 67256-21-7 (Hepatocyte Growth Factor); DA87705X9K (Erlotinib Hydrochloride); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (MET protein, human); EC 2.7.10.1 (Proto-Oncogene Proteins c-met); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); P6YZ13C99Q (Calcifediol); PQX0D8J21J (Cetuximab); S65743JHBS (gefitinib)
[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:170501
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.17060


  2 / 16615 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
Texto completo
[PMID]:29211658
[Au] Autor:Marty FM; Ljungman P; Chemaly RF; Maertens J; Dadwal SS; Duarte RF; Haider S; Ullmann AJ; Katayama Y; Brown J; Mullane KM; Boeckh M; Blumberg EA; Einsele H; Snydman DR; Kanda Y; DiNubile MJ; Teal VL; Wan H; Murata Y; Kartsonis NA; Leavitt RY; Badshah C
[Ad] Endereço:From the Dana-Farber Cancer Institute and Brigham and Women's Hospital (F.M.M.) and Tufts Medical Center and Tufts University School of Medicine (D.R.S.), Boston; Karolinska University Hospital and Karolinska Institutet, Stockholm (P.L.); University of Texas M.D. Anderson Cancer Center, Houston (R.F
[Ti] Título:Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation.
[So] Source:N Engl J Med;377(25):2433-2444, 2017 12 21.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cytomegalovirus (CMV) infection remains a common complication after allogeneic hematopoietic-cell transplantation. Letermovir is an antiviral drug that inhibits the CMV-terminase complex. METHODS: In this phase 3, double-blind trial, we randomly assigned CMV-seropositive transplant recipients, 18 years of age or older, in a 2:1 ratio to receive letermovir or placebo, administered orally or intravenously, through week 14 after transplantation; randomization was stratified according to trial site and CMV disease risk. Letermovir was administered at a dose of 480 mg per day (or 240 mg per day in patients taking cyclosporine). Patients in whom clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) developed discontinued the trial regimen and received anti-CMV treatment. The primary end point was the proportion of patients, among patients without detectable CMV DNA at randomization, who had clinically significant CMV infection through week 24 after transplantation. Patients who discontinued the trial or had missing end-point data at week 24 were imputed as having a primary end-point event. Patients were followed through week 48 after transplantation. RESULTS: From June 2014 to March 2016, a total of 565 patients underwent randomization and received letermovir or placebo beginning a median of 9 days after transplantation. Among 495 patients with undetectable CMV DNA at randomization, fewer patients in the letermovir group than in the placebo group had clinically significant CMV infection or were imputed as having a primary end-point event by week 24 after transplantation (122 of 325 patients [37.5%] vs. 103 of 170 [60.6%], P<0.001). The frequency and severity of adverse events were similar in the two groups overall. Vomiting was reported in 18.5% of the patients who received letermovir and in 13.5% of those who received placebo; edema in 14.5% and 9.4%, respectively; and atrial fibrillation or flutter in 4.6% and 1.0%, respectively. The rates of myelotoxic and nephrotoxic events were similar in the letermovir group and the placebo group. All-cause mortality at week 48 after transplantation was 20.9% among letermovir recipients and 25.5% among placebo recipients. CONCLUSIONS: Letermovir prophylaxis resulted in a significantly lower risk of clinically significant CMV infection than placebo. Adverse events with letermovir were mainly of low grade. (Funded by Merck; ClinicalTrials.gov number, NCT02137772 ; EudraCT number, 2013-003831-31 .).
[Mh] Termos MeSH primário: Acetatos/uso terapêutico
Antivirais/uso terapêutico
Infecções por Citomegalovirus/prevenção & controle
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Quinazolinas/uso terapêutico
[Mh] Termos MeSH secundário: Acetatos/efeitos adversos
Adolescente
Adulto
Idoso
Antivirais/efeitos adversos
Citomegalovirus/genética
Citomegalovirus/isolamento & purificação
Infecções por Citomegalovirus/epidemiologia
Infecções por Citomegalovirus/etiologia
DNA Viral/sangue
Método Duplo-Cego
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Quinazolinas/efeitos adversos
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AIC246); 0 (Acetates); 0 (Antiviral Agents); 0 (DNA, Viral); 0 (Quinazolines)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171207
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1706640


  3 / 16615 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29318300
[Au] Autor:Kolomoets O; Voskoboynik О; Antypenko O; Berest G; Nosulenko I; Palchikov V; Karpenko O; Kovalenko S
[Ti] Título:Design, Synthesis and Anti-inflammatory Activity of Derivatives 10-R-3-Aryl-6,7-dihydro-2H-[1,2,4] triazino[2,3-c]quinazolin-2-ones of Spiro-fused Cyclic Frameworks.
[So] Source:Acta Chim Slov;64(4):902-910, 2017 Dec.
[Is] ISSN:1318-0207
[Cp] País de publicação:Slovenia
[La] Idioma:eng
[Ab] Resumo:Present work is devoted to the purposeful search of novel promising anti-inflammatory agents among the insufficiently known 3'-R-10'-R1-spiro[hetaryl-3(4),6'-[1,2,4]triazino[2,3-c]quinazolin]-2'(7'H)-ones. The virtual combinatorial library of previously unknown spiro-condensed derivatives of [1,2,4]triazino[2,3-c]quinazolines was formed and promising COX-2 inhibitors were identified by molecular docking method. Potential anti-inflammatory agents were synthesized by [5+1]-cyclocondensation of substituted 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones with heterocyclic ketones. The structures of synthsized compounds were verified by complex of physicochemical methods and spectral characteristics features were discussed. Obtained compounds were studied for anti-inflammatory activity using formalin induced paw edema model and highly active compounds were identified. Conducted SAR-analysis showed that combination of triazino[2,3-c] quinazoline moiety with spiro-condensed fragments is a reasonable approach for creating novel anti-inflammatory agents.
[Mh] Termos MeSH primário: Anti-Inflamatórios/síntese química
Desenho de Drogas
Quinazolinas/síntese química
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios/farmacologia
Espectroscopia de Ressonância Magnética
Simulação de Acoplamento Molecular
Quinazolinas/química
Quinazolinas/farmacologia
Ratos
Ratos Wistar
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Quinazolines)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE


  4 / 16615 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29335437
[Au] Autor:Zhang S; Zhang M; Jing Y; Yin X; Ma P; Zhang Z; Wang X; Di W; Zhuang G
[Ad] Endereço:State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
[Ti] Título:Deubiquitinase USP13 dictates MCL1 stability and sensitivity to BH3 mimetic inhibitors.
[So] Source:Nat Commun;9(1):215, 2018 01 15.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:MCL1 is a pivot member of the anti-apoptotic BCL-2 family proteins. While a distinctive feature of MCL1 resides in its efficient ubiquitination and destruction, the deubiquitinase USP9X has been implicated in the preservation of MCL1 expression by removing the polyubiquitin chains. Here we perform an unbiased siRNA screen and identify that the second deubiquitinase, USP13, regulates MCL1 stability in lung and ovarian cancer cells. Mechanistically, USP13 interacts with and stabilizes MCL1 via deubiquitination. As a result, USP13 depletion using CRISPR/Cas9 nuclease system inhibits tumor growth in xenografted nude mice. We further report that genetic or pharmacological inhibition of USP13 considerably reduces MCL1 protein abundance and significantly increases tumor cell sensitivity to BH3 mimetic inhibitors targeting BCL-2 and BCL-XL. Collectively, we nominate USP13 as a novel deubiquitinase which regulates MCL1 turnover in diverse solid tumors and propose that USP13 may be a potential therapeutic target for the treatment of various malignancies.
[Mh] Termos MeSH primário: Endopeptidases/metabolismo
Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo
Neoplasias/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Mh] Termos MeSH secundário: Compostos de Anilina/farmacologia
Animais
Benzilaminas/farmacologia
Sistemas CRISPR-Cas
Linhagem Celular Tumoral
Endopeptidases/genética
Células HEK293
Seres Humanos
Camundongos Endogâmicos BALB C
Camundongos Nus
Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores
Proteína de Sequência 1 de Leucemia de Células Mieloides/genética
Neoplasias/tratamento farmacológico
Neoplasias/genética
Ligação Proteica
Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Quinazolinas/farmacologia
Interferência de RNA
Sulfonamidas/farmacologia
Ubiquitinação/efeitos dos fármacos
Proteína bcl-X/antagonistas & inibidores
Proteína bcl-X/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aniline Compounds); 0 (Benzylamines); 0 (MCL1 protein, human); 0 (Myeloid Cell Leukemia Sequence 1 Protein); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Quinazolines); 0 (Sulfonamides); 0 (bcl-X Protein); 0 (spautin-1); EC 3.4.- (Endopeptidases); EC 3.4.- (USP13 protein, human); XKJ5VVK2WD (navitoclax)
[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:180117
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02693-9


  5 / 16615 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29331859
[Au] Autor:Albiol-Chiva J; Esteve-Romero J; Peris-Vicente J
[Ad] Endereço:Departament de Química Física i Analítica, Universitat Jaume I, 12071 Castelló, Spain.
[Ti] Título:Development of a method to determine axitinib, lapatinib and afatinib in plasma by micellar liquid chromatography and validation by the European Medicines Agency guidelines.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1074-1075:61-69, 2018 Feb 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A method based on micellar liquid chromatography to quantify the tyrosine kinase inhibitors axitinib, lapatinib and afatinib in plasma is reported. The sample pretreatment was a simple 1/5-dilution in a pure micellar solution, filtration and direct injection, without requiring extraction or purification steps. The three drugs were resolved from the matrix in 17min, using an aqueous solution of 0.07M sodium dodecyl sulfate - 6.0% 1-pentanol, buffered at pH7 with 0.01M phosphate salt as mobile phase, running under isocratic mode at 1mL/min through a C18 column. The detection was performed by absorbance at 260nm. An accurate mathematical relationship was established between the retention factor of each drug and the surfactant/organic solvent concentration in the mobile phase, achieved with a limited number of experiments, in order to optimize these factors. A binding behavior of the analytes face to the micelles was found out. The method was successfully validated by the guidelines of the European Medicines Agency in terms of: selectivity, linearity (r >0.9995), calibration range (0.5 to 10mg/L), limit of detection (0.2mg/L), carry-over effect, accuracy (-8.1 to +6.9%), precision (<13.8%), dilution integrity, matrix effect, stability and robustness. The procedure was found reliable, practical, economic, accessible, short-time, easy-to-handle, inexpensive, environmental-friendly, safe, useful for the analysis of many samples per day. Finally, the method was applied to the analysis of incurred, using quality control samples in the same analytical run, with adequate results. Therefore, it can be implementable for routine analysis in clinical laboratories.
[Mh] Termos MeSH primário: Cromatografia Líquida/métodos
Imidazóis/sangue
Indazóis/sangue
Quinazolinas/sangue
[Mh] Termos MeSH secundário: Antineoplásicos/sangue
Antineoplásicos/uso terapêutico
Estabilidade de Medicamentos
Seres Humanos
Imidazóis/uso terapêutico
Indazóis/uso terapêutico
Limite de Detecção
Modelos Lineares
Micelas
Neoplasias/tratamento farmacológico
Quinazolinas/uso terapêutico
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Imidazoles); 0 (Indazoles); 0 (Micelles); 0 (Quinazolines); 0VUA21238F (lapatinib); 41UD74L59M (afatinib); C9LVQ0YUXG (axitinib)
[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:180115
[St] Status:MEDLINE


  6 / 16615 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460454
[Au] Autor:Shan X; Zhang Y; Chen H; Dong L; Wu B; Xu T; Hu J; Liu Z; Wang W; Wu L; Feng Z; Liang G
[Ad] Endereço:Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
[Ti] Título:Inhibition of epidermal growth factor receptor attenuates LPS-induced inflammation and acute lung injury in rats.
[So] Source:Oncotarget;8(16):26648-26661, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acute lung injury (ALI) and its severe form acute respiratory distress syndrome remain the leading cause of morbidity and mortality in intensive care units. Inhibition of epidermal growth factor receptor (EGFR) has been found to be able to reduce inflammatory response. However, it is still unclear whether EGFR inhibition can prevent ALI. This study aimed to validate the EGFR's role in ALI and investigated the effects of EGFR inhibition on lipopolysaccharides (LPS)-induced ALI in rats. In vitro, both pharmacological inhibitors (AG1478 and 451) and si-RNA silencing of EGFR significantly inhibited LPS-induced EGFR signaling activation and inflammatory response in human lung epithelial cells or macrophages. Mechanistically, LPS induced EGFR activation via TLR4 and c-Src signaling. In vivo, rat model with ALI induced by intratracheal instillation of LPS was treated by oral administration of AG1478 and 451. It was observed that AG1478 and 451 blocked the activation of EGFR signaling in lung tissue and reduced the LPS-induced infiltration of inflammatory cells, inflammatory gene expression, and lung injuries. This study demonstrates that TLR4/c-Src-dependent EGFR signaling plays an important role in LPS-induced ALI, and that EGFR may be a potential target in treating ALI.
[Mh] Termos MeSH primário: Lesão Pulmonar Aguda/etiologia
Lesão Pulmonar Aguda/metabolismo
Lipopolissacarídeos/efeitos adversos
Receptor do Fator de Crescimento Epidérmico/metabolismo
[Mh] Termos MeSH secundário: Lesão Pulmonar Aguda/tratamento farmacológico
Lesão Pulmonar Aguda/patologia
Animais
Linhagem Celular
Citocinas/genética
Citocinas/metabolismo
Mediadores da Inflamação/metabolismo
Macrófagos/imunologia
Macrófagos/metabolismo
Inibidores de Proteínas Quinases/farmacologia
Quinazolinas/farmacologia
Ratos
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Transdução de Sinais/efeitos dos fármacos
Receptor 4 Toll-Like/metabolismo
Tirfostinas/farmacologia
Quinases da Família src/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Inflammation Mediators); 0 (Lipopolysaccharides); 0 (Protein Kinase Inhibitors); 0 (Quinazolines); 0 (Toll-Like Receptor 4); 0 (Tyrphostins); 170449-18-0 (tyrphostin AG 1478); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.2 (CSK tyrosine-protein kinase); EC 2.7.10.2 (src-Family 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.15790


  7 / 16615 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29291441
[Au] Autor:Otvagin VF; Nyuchev AV; Kuzmina NS; Grishin ID; Gavryushin AE; Romanenko YV; Koifman OI; Belykh DV; Peskova NN; Shilyagina NY; Balalaeva IV; Fedorov AY
[Ad] Endereço:Lobachevsky State University of Nizhny Novgorod, Gagarina Av. 23, Nizhny Novgorod 603950, Russian Federation.
[Ti] Título:Synthesis and biological evaluation of new water-soluble photoactive chlorin conjugate for targeted delivery.
[So] Source:Eur J Med Chem;144:740-750, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A new water-soluble conjugate, consisting of a chlorin-based photosensitizing part, and a 4-arylaminoquinazoline moiety with high potential affinity to an epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), suitable for photodynamic therapy (PDT), was synthesized starting from methylpheophorbide-a in seven steps. An increased accumulation of this compound in A431 cells with high level of EGFR expression, in comparison with CHO and HeLa cells with low EGFR expression was observed. The prepared conjugate exhibits dark and photoinduced cytotoxicity at micromolar concentrations with IC /IC ratio of 11-18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.
[Mh] Termos MeSH primário: Sistemas de Liberação de Medicamentos
Fármacos Fotossensibilizantes/farmacologia
Porfirinas/farmacologia
Quinazolinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Células CHO
Linhagem Celular Tumoral
Cricetulus
Relação Dose-Resposta a Droga
Células HeLa
Seres Humanos
Camundongos
Camundongos Endogâmicos BALB C
Estrutura Molecular
Fotoquimioterapia
Fármacos Fotossensibilizantes/síntese química
Fármacos Fotossensibilizantes/química
Porfirinas/química
Quinazolinas/química
Solubilidade
Relação Estrutura-Atividade
Fator A de Crescimento do Endotélio Vascular/biossíntese
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Photosensitizing Agents); 0 (Porphyrins); 0 (Quinazolines); 0 (Vascular Endothelial Growth Factor A); 059QF0KO0R (Water); 2683-84-3 (chlorin)
[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:180102
[St] Status:MEDLINE


  8 / 16615 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:28450659
[Au] Autor:Amin Z; Jayalie VF; Rajabto W
[Ad] Endereço:Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia. zulkifliamin52@gmail.com.
[Ti] Título:Recent Management of Patients with Advanced Epidermal Growth Factor Receptor Mutation Non-small Cell Lung Cancer: Role of Afatinib and Lesson Learned for Developing Countries.
[So] Source:Acta Med Indones;49(1):79-88, 2017 Jan.
[Is] ISSN:0125-9326
[Cp] País de publicação:Indonesia
[La] Idioma:eng
[Ab] Resumo:Lung cancer is a devastating disease with a high incidence, mortality and morbidity rate, especially in developing countries. Conventional treatment with cytotoxic chemotherapy has some limitations attributed to chemoresistance and toxicity. Recent advances have shown that first generation Tyrosine Kinase Inhibitor (TKI), Gefitinib and Erlotinib, and the newest available second generation Tyrosine Kinase Inhibitor (TKI), Afatinib, have the potential to be an option in the management of patients with epidermal growth factor receptor/ EGFR mutation positive advanced/ metastatic non-small cell lung cancer. Afatinib works by binding to EGFR irreversibly, thus inactivating the tyrosine kinase receptor. Some studies demostrated that Afatinib first-line may result in longer progression free survival (PFS) and better disease control, and as an alternative for patients who intolerance to Gefitinib or Erlotinib. In Indonesia, the era of National Health Insurance has been implemented and National Health Insurance has covered treatment for cancer, including first generation TKIs, Gefitinib dan erlotinib, for patients with EGFR mutation positive advanced/ metastatic non-small cell lung cancer at Cipto Mangunkusumo National Hospital. Afatinib, as one of the newest available second generation TKI, may be given free of charge too as an alternative if the National Health Insurance will be covered in the future. Further research is needed to know the efficacy and adverse effects that may occur in patients from developing countries.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Inibidores de Proteínas Quinases/uso terapêutico
Quinazolinas/uso terapêutico
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica
Países em Desenvolvimento
Intervalo Livre de Doença
Cloridrato de Erlotinib/uso terapêutico
Seres Humanos
Indonésia
Ensaios Clínicos Controlados Aleatórios como Assunto
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Receptor do Fator de Crescimento Epidérmico/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 0 (Quinazolines); 41UD74L59M (afatinib); DA87705X9K (Erlotinib Hydrochloride); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); S65743JHBS (gefitinib)
[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:170429
[St] Status:MEDLINE


  9 / 16615 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
Texto completo
[PMID]:29336009
[Au] Autor:Sim EH; Yang IA; Wood-Baker R; Bowman RV; Fong KM
[Ad] Endereço:GenesisCare Radiation Oncology, 1 Medical Place, Urraween, Queensland, Australia, 4655.
[Ti] Título:Gefitinib for advanced non-small cell lung cancer.
[So] Source:Cochrane Database Syst Rev;1:CD006847, 2018 01 16.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The role of gefitinib for the treatment of advanced non-small cell lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the available evidence from all randomised trials. OBJECTIVES: To determine the effectiveness and safety of gefitinib as first-line, second-line or maintenance treatment for advanced NSCLC. SEARCH METHODS: We performed searches in CENTRAL, MEDLINE and Embase from inception to 17 February 2017. We handsearched relevant conference proceedings, clinical trial registries and references lists of retrieved articles. SELECTION CRITERIA: We included trials assessing gefitinib, alone or in combination with other treatment, compared to placebo or other treatments in the first- or successive-line treatment of patients with NSCLC, excluding compassionate use. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodology. Two authors independently assessed the search results to select those with sound methodological quality. We carried out all analyses on an intention-to-treat basis. We recorded the following outcome data: overall survival, progression-free survival, toxicity, tumour response and quality of life. We also collected data for the following subgroups: Asian ethnicity and positive epidermal growth factor receptor (EGFR) mutation. MAIN RESULTS: We included 35 eligible randomised controlled trials (RCTs), which examined 12,089 patients.General populationGefitinib did not statistically improve overall survival when compared with placebo or chemotherapy in either first- or second-line settings. Second-line gefitinib prolonged time to treatment failure (TTF) (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90, P < 0.0001) when compared with placebo. Maintenance gefitinib improved progression-free survival (HR 0.70, 95% CI 0.53 to 0.91, P = 0.007) after first-line therapy.Studies in patients of Asian ethnicity or that conducted subgroup analysesSecond-line gefitinib prolonged overall survival over placebo (HR 0.66, 95% CI 0.48 to 0.91, P = 0.01). In the first-line setting, progression-free survival was improved with gefitinib over chemotherapy alone (HR 0.65, 95% CI 0.43 to 0.98, P = 0.04, moderate quality of evidence). Gefitinib given in combination with a chemotherapy regimen improved progression-free survival versus either gefitinib alone or chemotherapy alone (HR 0.69, 95% CI 0.49 to 0.96, P = 0.03; HR 0.69, 95% CI 0.62 to 0.77, P < 0.00001, respectively). In the second-line setting, progression-free survival was superior in patients given gefitinib over placebo or chemotherapy (HR 0.69, 95% CI 0.52 to 0.91, P = 0.009; HR 0.71, 95% CI 0.57 to 0.88, P = 0.002; moderate quality of evidence, respectively). Combining gefitinib with chemotherapy in the second-line setting was superior to gefitinib alone (HR 0.65, 95% CI 0.43 to 0.97, P = 0.04). As maintenance therapy, gefitinib improved progression-free survival when compared with placebo (HR 0.42, 95% CI 0.33 to 0.54, P < 0.00001).Patients with EGFR mutation-positive tumoursStudies in patients with EGFR mutation-positive tumours showed an improvement in progression-free survival in favour of gefitinib over first-line and second-line chemotherapy (HR 0.47, 95% CI 0.36 to 0.61, P < 0.00001; HR 0.24, 95% CI 0.12 to 0.47, P < 0.0001, respectively). Gefitinib as maintenance therapy following chemotherapy improved overall and progression-free survival (HR 0.39, 95% CI 0.15 to 0.98, P = 0.05; HR 0.17, 95% CI 0.07 to 0.41, P < 0.0001, respectively) in one phase III study when compared to placebo.Toxicities from gefitinib included skin rash, diarrhoea and liver transaminase derangements. Toxicities from chemotherapy included anaemia, neutropenia and neurotoxicity.In terms of quality of life, gefitinib improved Functional Assessment of Cancer Therapy-Lung (FACT-L) (standardised mean difference (SMD) 10.50, 95% CI 9.55 to 11.45, P < 0.000001), lung cancer subscale (SMD 3.63, 95% CI 3.08 to 4.19, P < 0.00001) and Trial Outcome Index (SMD 9.87, 95% CI 1.26 to 18.48, P < 0.00001) scores when compared with chemotherapy. AUTHORS' CONCLUSIONS: This systematic review shows that gefitinib, when compared with standard first- or second-line chemotherapy or maintenance therapy, probably has a beneficial effect on progression-free survival and quality of life in selected patient populations, particularly those with tumours bearing sensitising EGFR mutations.Patients with EGFR mutations lived longer when given maintenance gefitinib than those given placebo.One study conducted subgroup analysis and showed that gefitinib improved overall survival over placebo in the second-line setting in patients of Asian ethnicity. All other studies did not detect any benefit on overall survival. The data analysed in this review were very heterogenous. We were limited in the amount of data that could be pooled, largely due to variations in study design. The risk of bias in most studies was moderate, with some studies not adequately addressing potential selection, attrition and reporting bias. This heterogeneity may have an impact on the applicability of the resultsCombining gefitinib with chemotherapy appears to be superior in improving progression-free survival to either gefitinib or chemotherapy alone, however further data and phase III studies in these settings are required.Gefitinib has a favourable toxicity profile when compared with current chemotherapy regimens. Although there is no improvement in overall survival, gefitinib compares favourably with cytotoxic chemotherapy in patients with EGFR mutations with a prolongation of progression-free survival and a lesser side effect profile.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Quinazolinas/uso terapêutico
[Mh] Termos MeSH secundário: Antineoplásicos/efeitos adversos
Carcinoma Pulmonar de Células não Pequenas/etnologia
Carcinoma Pulmonar de Células não Pequenas/genética
Intervalo Livre de Doença
Genes erbB-1
Seres Humanos
Neoplasias Pulmonares/etnologia
Neoplasias Pulmonares/genética
Mutação
Qualidade de Vida
Quinazolinas/efeitos adversos
Ensaios Clínicos Controlados Aleatórios como Assunto
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Quinazolines); S65743JHBS (gefitinib)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD006847.pub2


  10 / 16615 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28464908
[Au] Autor:Chia SK; Ellard SL; Mates M; Welch S; Mihalcioiu C; Miller WH; Gelmon K; Lohrisch C; Kumar V; Taylor S; Hagerman L; Goodwin R; Wang T; Sakashita S; Tsao MS; Eisenhauer E; Bradbury P
[Ad] Endereço:Medical Oncology, British Columbia Cancer Agency (BCCA), Vancouver, BC, Canada. schia@bccancer.bc.ca.
[Ti] Título:A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor inhibitor, in human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer.
[So] Source:Breast Cancer Res;19(1):54, 2017 May 02.
[Is] ISSN:1465-542X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The mechanisms of resistance to anti-human epidermal growth factor receptor 2 (HER 2) therapies are unclear but may include the tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor (VEGF) and AXL pathways. Foretinib is an inhibitor of c-Met, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AXL, Fms-like tyrosine kinase 3 (FLT3), angiopoiten receptor (TIE-2), RET and RON kinases. This phase Ib study sought to establish the associated toxicities, pharmacokinetics (PK) and recommended phase II doses (RP2D) of foretinib and lapatinib in a cohort of HER-2-positive patients with metastatic breast cancer (MBC). METHODS: Women with HER-2 positive MBC, Performance status (PS 0-2), and no limit on number of prior chemotherapies or lines of anti-HER-2 therapies were enrolled. A 3 + 3 dose escalation design was utilized. Four dose levels were intended with starting doses of foretinib 30 mg and lapatinib 750 mg orally once a day (OD) on a 4-weekly cycle. Assessment of c-MET status from the primary archival tissue was performed. RESULTS: We enrolled 19 patients, all evaluable for toxicity assessment and for response evaluation. Median age was 60 years (34-86 years), 95% were PS 0-1, 53% were estrogen receptor-positive and 95% had at least one prior anti-HER-2-based regimen. The fourth dose level was reached (foretinib 45 mg/lapatinib 1250 mg) with dose-limiting toxicities of grade-3 diarrhea and fatigue. There was only one grade-4 non-hematological toxicity across all dose levels. There were no PK interactions between the agents. A median of two cycles was delivered across the dose levels (range 1-20) with associated progression-free survival of 3.2 months (95% CI 1.61-4.34 months). By immunohistochemical assessment with a specified cutoff, none of the 17 samples tested were classified as positive for c-Met. CONCLUSIONS: The RP2D of the combined foretinib and lapatinib is 45 mg and 1000 mg PO OD, respectively. Limited activity was seen with this combination in a predominantly unselected cohort of HER-2-positive patients with MBC.
[Mh] Termos MeSH primário: Anilidas/administração & dosagem
Neoplasias da Mama/tratamento farmacológico
Inibidores de Proteínas Quinases/administração & dosagem
Quinazolinas/administração & dosagem
Quinolinas/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica
Neoplasias da Mama/genética
Neoplasias da Mama/patologia
Intervalo Livre de Doença
Feminino
Seres Humanos
Meia-Idade
Metástase Neoplásica
Proteínas Proto-Oncogênicas/antagonistas & inibidores
Proteínas Proto-Oncogênicas/genética
Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores
Proteínas Proto-Oncogênicas c-met/genética
Receptores Proteína Tirosina Quinases/antagonistas & inibidores
Receptores Proteína Tirosina Quinases/genética
Receptor ErbB-2/genética
Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anilides); 0 (GSK 1363089); 0 (Protein Kinase Inhibitors); 0 (Proto-Oncogene Proteins); 0 (Quinazolines); 0 (Quinolines); 0VUA21238F (lapatinib); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (MET protein, human); EC 2.7.10.1 (Proto-Oncogene Proteins c-met); EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases); EC 2.7.10.1 (Receptor, ErbB-2); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1); EC 2.7.10.1 (axl receptor tyrosine kinase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1186/s13058-017-0836-3



página 1 de 1662 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