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[PMID]:29482389
[Au] Autor:Elzahabi HSA; Nossier ES; Khalifa NM; Alasfoury RA; El-Manawaty MA
[Ad] Endereço:a Department of Pharmaceutical Chemistry , Faculty of Pharmacy (Girls), Al-Azhar University , Cairo , Egypt.
[Ti] Título:Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold.
[So] Source:J Enzyme Inhib Med Chem;33(1):546-557, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC : 0.3, 6.6 and 7 µM) relative to the standard doxorubicin (IC : 0.6, 6.8 and 12.8 µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR ß, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100 µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Quinase 4 Dependente de Ciclina/antagonistas & inibidores
Inibidores de Proteínas Quinases/farmacologia
Piridinas/farmacologia
Pirimidinas/farmacologia
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Quinase 4 Dependente de Ciclina/metabolismo
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Piridinas/síntese química
Piridinas/química
Pirimidinas/síntese química
Pirimidinas/química
Receptor do Fator de Crescimento Epidérmico/metabolismo
Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 0 (Pyridines); 0 (Pyrimidines); 0 (pyrido(3,2-d)pyrimidine); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta); EC 2.7.11.22 (CDK4 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
[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:180228
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2018.1437729


  2 / 1806 MEDLINE  
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[PMID]:29325250
[Au] Autor:Fu Y; Guan WY; Wu HY; Wu HY; Fan ZW; Ye Q; Meng FQ
[Ad] Endereço:Department of Pathology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
[Ti] Título:[Myofibroma/myofibromatosis: a clinicopathologic analysis of 9 cases].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(1):45-50, 2018 Jan 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the clinical and histological features, diagnosis and differential diagnosis of myofibroma/myofibromatosis. The clinical data and pathology features of nine cases of myofibroma/myofibromatosis were collected from August 2011 to November 2016 in Affiliated Drum Tower Hospital, Nanjing University Medical School and Children's Hospital of Nanjing Medical University. Immunohistochemistry(IHC), PDGFRB molecular analysis and ETV6-NTRK3 gene fusion were performed and relevant literature reviewed. There were 7 males and 2 females, with age ranging from 3 days to 18 years (mean 5 years). The tumors were located in head and neck (eight cases) and trunk (one case). Clinically, the tumors presented as freely movable nodules. Microscopically, they appeared biphasic with alternating light- and dark-staining areas. The light-staining area consisted mainly of plump myoid spindle cells with eosinophilic cytoplasm arranged in nodules, short fascicles, or whorls.The dark-staining area was composed of round or polygonal cells with slightly hyperchromatic nuclei or small spindle cells arranged around a distinct hemangiopericytoma-like vascular pattern. IHC showed the tumor cells in the light-staining area were strongly positive for vimentin and SMA, while cells in dark-staining area were strongly positive for vimentin, and weakly for SMA. Tumor cells were negative for desmin, S-100 protein, h-Caldesmon, CD34 and STAT6. Analysis of PDGFRB mutations was performed in seven cases. Two cases showed 12 exon point mutation c. 1681 c>T(p.R561C), one case showed 14 exon point mutation c. 1998C>G (p.N666K). ETV6-NTRK3 gene fusion was not detected by fluorescence in situ hybridization in four patients under three years old. All cases were followed for 6 to 68 months, with two recurrences. Myofibroma/myofibromatosis is an uncommon benign myofibroblastic tumor of infancy and childhood. The tumor can appear biphasic, and may show PDGFRB point mutation which is of potential diagnostic value.
[Mh] Termos MeSH primário: Miofibroma
Miofibromatose
[Mh] Termos MeSH secundário: Adolescente
Antígenos CD34/análise
Proteínas de Ligação a Calmodulina/análise
Criança
Pré-Escolar
Desmina/análise
Diagnóstico Diferencial
Éxons
Feminino
Hemangiopericitoma/irrigação sanguínea
Seres Humanos
Imuno-Histoquímica
Hibridização in Situ Fluorescente
Masculino
Mutação
Miofibroma/diagnóstico
Miofibroma/genética
Miofibroma/patologia
Miofibromatose/diagnóstico
Miofibromatose/genética
Miofibromatose/patologia
Receptor beta de Fator de Crescimento Derivado de Plaquetas/análise
Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética
Proteínas S100/análise
Fator de Transcrição STAT6/análise
Vimentina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD34); 0 (Calmodulin-Binding Proteins); 0 (Desmin); 0 (S100 Proteins); 0 (STAT6 Transcription Factor); 0 (STAT6 protein, human); 0 (Vimentin); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.01.009


  3 / 1806 MEDLINE  
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[PMID]:29182023
[Au] Autor:Shi Q; Tao Z; Yang H; Fan Q; Wei D; Wan L; Lu X
[Ad] Endereço:a Key Lab of Transplant Engineering and Immunology , MOH, West China Hospital, Sichuan University , Chengdu , China.
[Ti] Título:PDGFRß-specific affibody-directed delivery of a photosensitizer, IR700, is efficient for vascular-targeted photodynamic therapy of colorectal cancer.
[So] Source:Drug Deliv;24(1):1818-1830, 2017 Nov.
[Is] ISSN:1521-0464
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Vascular-targeted photodynamic therapy (PDT) is an important strategy for cancer therapy. Conventional vascular-targeted PDT has been achieved by passive photosensitizer (PS) delivery, which involves a high risk of adverse effects. Active PS delivery is urgently required for vascular-targeted PDT. Although endothelial cells and pericytes are major cellular components of tumor blood vessels, little attention has been paid to pericyte-targeted PDT for cancer therapy. PDGFRß is abundantly expressed in the pericytes of various tumors. In this experiment, a dimeric Z affibody with a 0.9 nM affinity for PDGFRß was produced. The Z affibody showed PDGFRß-dependent pericyte binding. Intravenously injected Z affibody was predominantly distributed on pericytes and thus accumulated in LS174T tumor grafts. The conjugate of the Z affibody and IR700 dye, i.e. Z , bound to PDGFRß pericytes but not to PDGFRß LS174T tumor cells. Accordingly, Z -mediated PDT in vitro induced the death of pericytes but not of LS174T tumor cells. In mice bearing LS174T tumor grafts, Z -mediated PDT damaged tumor blood vessels, thus inducing tumor destruction by intensifying tissue hypoxia. The average mass of tumor grafts administered with Z -mediated PDT was approximately 20-30% of that of the control, indicating that pericyte-targeted PDT is efficient for cancer therapy. In addition, Z -mediated PDT increased the tumor uptake of TNF-related apoptosis-inducing ligand (TRAIL) injected post-illumination. Consequently, combination therapy of Z -mediated PDT and TRAIL showed greater tumor suppression than Z -mediated PDT- or TRAIL-based monotherapy. These results demonstrated that active vascular-targeted PDT could be achieved by using Z affibody-directed delivery of PS.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/administração & dosagem
Neoplasias Colorretais/tratamento farmacológico
Fármacos Fotossensibilizantes/administração & dosagem
Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Linhagem Celular
Linhagem Celular Tumoral
Seres Humanos
Luz
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Pericitos/efeitos dos fármacos
Fotoquimioterapia/métodos
Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Photosensitizing Agents); 0 (TNF-Related Apoptosis-Inducing Ligand); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1080/10717544.2017.1407011


  4 / 1806 MEDLINE  
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[PMID]:28457731
[Au] Autor:Zhang XF; Dong M; Pan YH; Chen JN; Huang XQ; Jin Y; Shao CK
[Ad] Endereço:Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
[Ti] Título:Expression pattern of cancer-associated fibroblast and its clinical relevance in intrahepatic cholangiocarcinoma.
[So] Source:Hum Pathol;65:92-100, 2017 07.
[Is] ISSN:1532-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and lack of effective treatment, characterized by dense desmoplastic stroma rich in cancer-associated fibroblasts (CAFs), which have been indicated to facilitate tumor progression in several types of human cancer. However, the clinical relevance of CAFs in ICC has not been fully characterized. Here, we evaluated the histological phenotype of CAFs and immunohistochemical expressions of α-SMA, FSP-1, and PDGFRß in 71 ICC cases, and found that immature CAF phenotype was significantly associated with lymph node metastasis (P=.045), advanced TNM stage (P=.025) and poor 5-year overall survival (OS) (38.5% versus 78.6%, P=.015). In addition, α-SMA, FSP-1, and PDGFRß were positively expressed in stromal fibroblasts in 63.4% (45/71), 84.5% (60/71), and 78.9% (56/71) of patients, respectively. Positive expression of α-SMA was correlated with poor differentiation (P=.032); FSP-1 expression in stromal fibroblasts was linked with lymph node metastasis (P=.022) and immature phenotype (P=.048). What's more, positive expression of FSP-1 in cancer cells was observed in 22.5% (16/71) of cases and was correlated with worse 5-year OS (36.4% versus 76.7%, P=.014). Importantly, in multivariate analysis, histological CAF phenotype was an independent prognostic factor for OS in ICC. Our findings demonstrated histological categorization of CAFs was a useful predictor for prognosis, providing new evidence that CAFs play a crucial role in tumor progression and can serve as potential therapeutic targets in ICC.
[Mh] Termos MeSH primário: Neoplasias dos Ductos Biliares/química
Biomarcadores Tumorais/análise
Fibroblastos Associados a Câncer/química
Colangiocarcinoma/química
[Mh] Termos MeSH secundário: Actinas/análise
Neoplasias dos Ductos Biliares/mortalidade
Neoplasias dos Ductos Biliares/patologia
Proteínas de Ligação ao Cálcio/análise
Fibroblastos Associados a Câncer/patologia
Diferenciação Celular
Distribuição de Qui-Quadrado
Colangiocarcinoma/mortalidade
Colangiocarcinoma/secundário
Feminino
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Metástase Linfática
Masculino
Meia-Idade
Análise Multivariada
Estadiamento de Neoplasias
Fenótipo
Modelos de Riscos Proporcionais
Receptor beta de Fator de Crescimento Derivado de Plaquetas/análise
Fatores de Risco
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ACTA2 protein, human); 0 (Actins); 0 (Biomarkers, Tumor); 0 (Calcium-Binding Proteins); 0 (FSP1 protein, human); EC 2.7.10.1 (PDGFRB protein, human); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180117
[Lr] Data última revisão:
180117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  5 / 1806 MEDLINE  
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[PMID]:28924035
[Au] Autor:He C; Medley SC; Kim J; Sun C; Kwon HR; Sakashita H; Pincu Y; Yao L; Eppard D; Dai B; Berry WL; Griffin TM; Olson LE
[Ad] Endereço:Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
[Ti] Título:STAT1 modulates tissue wasting or overgrowth downstream from PDGFRß.
[So] Source:Genes Dev;31(16):1666-1678, 2017 Aug 15.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Platelet-derived growth factor (PDGF) acts through two conserved receptor tyrosine kinases: PDGFRα and PDGFRß. Gain-of-function mutations in human have been linked recently to genetic diseases characterized by connective tissue wasting (Penttinen syndrome) or overgrowth (Kosaki overgrowth syndrome), but it is unclear whether mutations alone are responsible. Mice with constitutive PDGFRß signaling caused by a kinase domain mutation (D849V) develop lethal autoinflammation. Here we used a genetic approach to investigate the mechanism of autoinflammation in mice and test the hypothesis that signal transducer and activator of transcription 1 (STAT1) mediates this phenotype. We show that mice with knockout ( ) are rescued from autoinflammation and have improved life span compared with mice. Furthermore, PDGFRß-STAT1 signaling suppresses PDGFRß itself. Thus, fibroblasts exhibit increased PDGFRß signaling, and mice develop progressive overgrowth, a distinct phenotype from the wasting seen in mice. Deletion of interferon receptors ( or ) does not rescue wasting in mice, indicating that interferons are not required for autoinflammation. These results provide functional evidence that elevated PDGFRß signaling causes tissue wasting or overgrowth reminiscent of human genetic syndromes and that the STAT1 pathway is a crucial modulator of this phenotypic spectrum.
[Mh] Termos MeSH primário: Transtornos do Crescimento/genética
Mutação
Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética
Fator de Transcrição STAT1/genética
[Mh] Termos MeSH secundário: Tecido Adiposo/patologia
Animais
Aorta/patologia
Atrofia
Osso e Ossos/anormalidades
Feminino
Fibroblastos/metabolismo
Fibrose
Transtornos do Crescimento/metabolismo
Transtornos do Crescimento/patologia
Hiperplasia
Inflamação/metabolismo
Interferons/fisiologia
Masculino
Camundongos
Camundongos Knockout
Músculo Liso Vascular/patologia
Células NIH 3T3
Fenótipo
Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo
Fator de Transcrição STAT1/metabolismo
Transdução de Sinais
Pele/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (STAT1 Transcription Factor); 0 (Stat1 protein, mouse); 9008-11-1 (Interferons); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171029
[Lr] Data última revisão:
171029
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1101/gad.300384.117


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[PMID]:28838832
[Au] Autor:Effendi N; Ogawa K; Mishiro K; Takarada T; Yamada D; Kitamura Y; Shiba K; Maeda T; Odani A
[Ad] Endereço:Kanazawa University, Graduate School of Pharmaceutical Sciences, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan; Universitas Muslim Indonesia, Faculty of Pharmacy, Urip Sumiharjo KM. 10, Makassar 90-231, Indonesia.
[Ti] Título:Synthesis and evaluation of radioiodinated 1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine derivatives for platelet-derived growth factor receptor ß (PDGFRß) imaging.
[So] Source:Bioorg Med Chem;25(20):5576-5585, 2017 Oct 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Platelet-derived growth factor receptor ß (PDGFRß) is a transmembrane tyrosine kinase receptor and it is upregulated in various malignant tumors. Radiolabeled PDGFRß inhibitors can be a convenient tool for the imaging of tumors overexpressing PDGFRß. In this study, [ I]-1-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl}piperidin-4-amine ([ I]IIQP) and [ I]-N-3-iodobenzoyl-1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}-piperidin-4-amine ([ I]IB-IQP) were designed and synthesized, and their potential as PDGFRß imaging agents was evaluated. In cellular uptake experiments, [ I]IIQP and [ I]IB-IQP showed higher uptake by PDGFRß-positive cells than by PDGFRß-negative cells, and the uptake in PDGFRß-positive cells was inhibited by co-culture with PDGFRß ligands. The biodistribution of both radiotracers in normal mice exhibited hepatobiliary excretion as the main route. In mice inoculated with BxPC3-luc (PDGFRß-positive), the tumor uptake of radioactivity at 1h after the injection of [ I]IIQP was significantly higher than that after the injection of [ I]IB-IQP. These results indicated that [ I]IIQP can be a suitable PDGFRß imaging agent. However, further modification of its structure will be required to obtain a more appropriate PDGFRß-targeted imaging agent with a higher signal/noise ratio.
[Mh] Termos MeSH primário: Neoplasias Mamárias Experimentais/diagnóstico
Imagem Molecular
Sondas Moleculares/química
Receptor beta de Fator de Crescimento Derivado de Plaquetas/análise
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Feminino
Seres Humanos
Radioisótopos do Iodo
Células MCF-7
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Sondas Moleculares/síntese química
Sondas Moleculares/farmacocinética
Estrutura Molecular
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Iodine Radioisotopes); 0 (Molecular Probes); EC 2.7.10.1 (PDGFRB protein, human); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE


  7 / 1806 MEDLINE  
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[PMID]:28826084
[Au] Autor:Qin M; Tian Y; Sun X; Yu S; Xia J; Gong P; Zhang H; Zhao Y
[Ad] Endereço:Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenyang 110016, PR China.
[Ti] Título:Novel methyl indolinone-6-carboxylates containing an indole moiety as angiokinase inhibitors.
[So] Source:Eur J Med Chem;139:492-502, 2017 Oct 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A novel series of methyl indolinone-6-carboxylates bearing an indole moiety were identified as potent angiokinase inhibitors. The most active compound, A8, potently targeted the kinase activities of vascular endothelial growth factor receptors 2 and 3, and platelet-derived growth factor receptors α and ß, with IC values in the nanomolar range. In addition, A8 effectively suppressed the proliferation of human umbilical vein endothelial cells, and HT-29 and MCF-7 cancer cells, by inducing apoptosis. Compound A8 is thus a promising candidate for further investigation.
[Mh] Termos MeSH primário: Ácidos Carboxílicos/farmacologia
Indóis/farmacologia
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Ácidos Carboxílicos/síntese química
Ácidos Carboxílicos/química
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
Seres Humanos
Indóis/síntese química
Indóis/química
Estrutura Molecular
Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores
Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo
Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores
Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo
Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores
Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo
Relação Estrutura-Atividade
Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
Receptor 3 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carboxylic Acids); 0 (Indoles); 0 (indolinone-6-carboxylate); EC 2.7.10.1 (FGFR1 protein, human); EC 2.7.10.1 (FLT4 protein, human); EC 2.7.10.1 (KDR protein, human); EC 2.7.10.1 (PDGFRB protein, human); EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE


  8 / 1806 MEDLINE  
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[PMID]:28737764
[Au] Autor:Gong J; Han J; He J; Liu J; Han P; Wang Y; Li M; Li D; Ding X; Du Z; Liao J; Tian D
[Ad] Endereço:Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
[Ti] Título:Paired related homeobox protein 1 regulates PDGF-induced chemotaxis of hepatic stellate cells in liver fibrosis.
[So] Source:Lab Invest;97(9):1020-1032, 2017 Sep.
[Is] ISSN:1530-0307
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Activation of the platelet-derived growth factor (PDGF)/PDGF beta receptor (PDGFßR) axis has a critical role in liver fibrosis. However, the mechanisms that regulate the PDGF signaling are yet to be elucidated. The present study demonstrates that paired related homeobox protein 1 (Prrx1) is involved in PDGF-dependent hepatic stellate cell (HSCs) migration via modulation of the expression of metalloproteinases MMP2 and MMP9. PDGF elevated the level of Prrx1 through the activation of ERK/Sp1 and PI3K/Akt/Ets1 pathways. In vivo, an adenoviral-mediated Prrx1 shRNA administration attenuated liver fibrosis in thioacetamide-induced fibrotic models. These studies reveal a role of Prrx1 as a modulator of PDGF-dependent signaling in HSCs, and inhibiting its expression may offer a therapeutic approach for hepatic fibrosis.
[Mh] Termos MeSH primário: Quimiotaxia/fisiologia
Células Estreladas do Fígado/metabolismo
Proteínas de Homeodomínio/metabolismo
Cirrose Hepática/metabolismo
Fator de Crescimento Derivado de Plaquetas/metabolismo
Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Proteínas de Homeodomínio/genética
Seres Humanos
Fígado/patologia
Masculino
Camundongos Endogâmicos C57BL
Ratos
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Homeodomain Proteins); 0 (Platelet-Derived Growth Factor); 0 (Prx1 protein, rat); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170725
[St] Status:MEDLINE
[do] DOI:10.1038/labinvest.2017.65


  9 / 1806 MEDLINE  
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[PMID]:28725989
[Au] Autor:Jawhar M; Naumann N; Schwaab J; Baurmann H; Casper J; Dang TA; Dietze L; Döhner K; Hänel A; Lathan B; Link H; Lotfi S; Maywald O; Mielke S; Müller L; Platzbecker U; Prümmer O; Thomssen H; Töpelt K; Panse J; Vieler T; Hofmann WK; Haferlach T; Haferlach C; Fabarius A; Hochhaus A; Cross NCP; Reiter A; Metzgeroth G
[Ad] Endereço:Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
[Ti] Título:Imatinib in myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB in chronic or blast phase.
[So] Source:Ann Hematol;96(9):1463-1470, 2017 Sep.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20-80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×10 /L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0-13)​. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3-34) and 19 months (range 7-110), respectively. In patients with blast phase (myeloid, n = 2; lymphoid, n = 3), treatment included combinations of imatinib (n = 5), intensive chemotherapy (n = 3), and/or allogeneic stem cell transplantation (n = 3). All 3 transplanted patients (complex karyotype, n = 2) experienced early relapse. Initially, patients were treated with imatinib 400 mg/day (n = 15) or 100 mg/day (n = 7), the dose was reduced from 400 mg/day to 100 mg/day during follow-up in 9 patients. After a median treatment of 71 months (range 1-135), the 5-year survival rate was 83%; 4/22 (18%) patients died (chronic phase; n = 2; blast phase, n = 2) due to progression (n = 3) or comorbidity while in remission (n = 1). Of note, 3/4 patients had a complex karyotype. In summary, the most important characteristics of myeloid/lymphoid neoplasms with rearrangement of PDGFRB include (a) male predominance, (b) frequent lack of hypereosinophilia,
[Mh] Termos MeSH primário: Crise Blástica
Eosinofilia
Rearranjo Gênico
Neoplasias Hematológicas
Mesilato de Imatinib/administração & dosagem
Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética
[Mh] Termos MeSH secundário: Cariótipo Anormal
Adulto
Idoso
Idoso de 80 Anos ou mais
Crise Blástica/tratamento farmacológico
Crise Blástica/genética
Crise Blástica/mortalidade
Crise Blástica/patologia
Intervalo Livre de Doença
Eosinofilia/tratamento farmacológico
Eosinofilia/genética
Eosinofilia/mortalidade
Eosinofilia/patologia
Feminino
Seguimentos
Neoplasias Hematológicas/tratamento farmacológico
Neoplasias Hematológicas/genética
Neoplasias Hematológicas/mortalidade
Neoplasias Hematológicas/patologia
Seres Humanos
Masculino
Meia-Idade
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Fatores de Risco
Fatores Sexuais
Taxa de Sobrevida
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
8A1O1M485B (Imatinib Mesylate); EC 2.7.10.1 (PDGFRB protein, human); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3067-x


  10 / 1806 MEDLINE  
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[PMID]:28711648
[Au] Autor:Hiraki-Hotokebuchi Y; Yamada Y; Kohashi K; Yamamoto H; Endo M; Setsu N; Yuki K; Ito T; Iwamoto Y; Furue M; Oda Y
[Ad] Endereço:Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
[Ti] Título:Alteration of PDGFRß-Akt-mTOR pathway signaling in fibrosarcomatous transformation of dermatofibrosarcoma protuberans.
[So] Source:Hum Pathol;67:60-68, 2017 Sep.
[Is] ISSN:1532-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dermatofibrosarcoma protuberans (DFSP) is a cutaneous mesenchymal tumor of intermediate malignancy and fibroblastic/myofibroblastic differentiation. Fibrosarcomatous (FS) component is a high-grade component of DFSP. The detailed oncogenic difference between DFSP and FS components is not clear. We thus investigated the Akt-mTOR pathway in both components. We used 65 tumor samples obtained from 65 patients. The phosphorylation of Akt-mTOR pathway proteins (Akt, mTOR, 4EBP1, and S6RP) and PDGFRα/ß was assessed by immunohistochemical staining, the results of which were confirmed by Western blotting. The immunohistochemical results were as follows: in ordinary DFSP components, p-PDGFRα-positive tumors were 41.9% (18/43 cases), p-PDGFRß 55.8% (24/43 cases), p-Akt 51.2% (22/43 cases), p-mTOR 39.5% (17/43 cases), p-4EBP1 46.5% (20/43 cases), and p-S6RP 41.8% (18/43 cases); in DFSP components of FS-DFSP, 52.6% (10/19 cases), 47.4% (9/19 cases), 52.6% (10/19 cases), 36.8% (7/19 cases), 52.6% (10/19 cases), and 52.6% (10/19 cases); and in FS components, 45.5% (10/22 cases), 36.4% (8/22 cases), 72.7% (16/22 cases), 54.5% (12/22 cases), 72.7% (16/22 cases), and 68.2% (15/22 cases), respectively. There were significant positive correlations of the phosphorylation of most of the Akt-mTOR pathway proteins (p-Akt, p-mTOR, p-4EBP1, and p-S6RP) with each other (P < .05). Phospho-PDGFRß was well correlated with the phosphorylation of Akt-mTOR pathway proteins in DFSP components of ordinary and FS-DFSPs, but these correlations were weaker in FS components. This study suggested the association of activation of Akt-mTOR pathway proteins and PDGFR with the progression of DFSP to FS. The Akt-mTOR pathway is thus a potential therapeutic target in imatinib-resistant DFSP/FS.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica/química
Dermatofibrossarcoma/enzimologia
Proteínas Proto-Oncogênicas c-akt/análise
Receptor beta de Fator de Crescimento Derivado de Plaquetas/análise
Neoplasias Cutâneas/enzimologia
Serina-Treonina Quinases TOR/análise
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/análise
Adolescente
Adulto
Idoso
Biópsia
Western Blotting
Transformação Celular Neoplásica/metabolismo
Criança
Pré-Escolar
Dermatofibrossarcoma/patologia
Progressão da Doença
Feminino
Seres Humanos
Imuno-Histoquímica
Lactente
Masculino
Meia-Idade
Fosfoproteínas/análise
Fosforilação
Receptor alfa de Fator de Crescimento Derivado de Plaquetas/análise
Proteínas Quinases S6 Ribossômicas/análise
Transdução de Sinais
Neoplasias Cutâneas/patologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (EIF4EBP1 protein, human); 0 (Phosphoproteins); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.10.1 (PDGFRB protein, human); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170717
[St] Status:MEDLINE



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