Base de dados : MEDLINE
Pesquisa : D12.776.624.664.700 [Categoria DeCS]
Referências encontradas : 55650 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 5565 ir para página                         

  1 / 55650 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28453858
[Au] Autor:McCormack SE; Li D; Kim YJ; Lee JY; Kim SH; Rapaport R; Levine MA
[Ad] Endereço:Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
[Ti] Título:Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.
[So] Source:J Clin Endocrinol Metab;102(7):2501-2507, 2017 Jul 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Pituitary stalk interruption syndrome (PSIS, ORPHA95496) is a congenital defect of the pituitary gland characterized by the triad of a very thin/interrupted pituitary stalk, an ectopic (or absent) posterior pituitary gland, and hypoplasia or aplasia of the anterior pituitary gland. Complex genetic patterns of inheritance of this disorder are increasingly recognized. Objective: The objective of this study was to identify a genetic cause of PSIS in an affected child. Methods: Whole exome sequencing (WES) was performed by using standard techniques, with prioritized genetic variants confirmed via Sanger sequencing. To investigate the effects of one candidate variant on mutant WDR11 function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. Results: We describe a child who presented in infancy with combined pituitary hormone deficiencies and whose brain imaging demonstrated a small anterior pituitary, ectopic posterior pituitary, and a thin, interrupted stalk. WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (c.253C>T;p.R85C) inherited from an unaffected mother, and a WDR11 (c.1306A>G;p.I436V) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind to its functional partner, EMX1, and to localize to the nucleus. Conclusions: WES in a child with PSIS and his unaffected family implicates a digenic mechanism of inheritance. In cases of hypopituitarism in which there is incomplete segregation of a monogenic genotype with the phenotype, the possibility that a second genetic locus is involved should be considered.
[Mh] Termos MeSH primário: Predisposição Genética para Doença
Hipopituitarismo/genética
Proteínas de Membrana/genética
Mutação
Hipófise/anormalidades
Proteínas Proto-Oncogênicas/genética
Receptores Acoplados a Proteínas-G/genética
Receptores de Peptídeos/genética
[Mh] Termos MeSH secundário: Exoma/genética
Genótipo
Heterozigoto
Seres Humanos
Hipopituitarismo/congênito
Hipopituitarismo/patologia
Recém-Nascido
Masculino
Linhagem
Síndrome
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Membrane Proteins); 0 (PROKR2 protein, human); 0 (Proto-Oncogene Proteins); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Peptide); 0 (WDR11 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2017-00332


  2 / 55650 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29295989
[Au] Autor:Gibori H; Eliyahu S; Krivitsky A; Ben-Shushan D; Epshtein Y; Tiram G; Blau R; Ofek P; Lee JS; Ruppin E; Landsman L; Barshack I; Golan T; Merquiol E; Blum G; Satchi-Fainaro R
[Ad] Endereço:Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
[Ti] Título:Amphiphilic nanocarrier-induced modulation of PLK1 and miR-34a leads to improved therapeutic response in pancreatic cancer.
[So] Source:Nat Commun;9(1):16, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The heterogeneity of pancreatic ductal adenocarcinoma (PDAC) suggests that successful treatment might rely on simultaneous targeting of multiple genes, which can be achieved by RNA interference-based therapeutic strategies. Here we show a potent combination of microRNA and siRNA delivered by an efficient nanocarrier to PDAC tumors. Using proteomic-microRNA profiles and survival data of PDAC patients from TCGA, we found a novel signature for prolonged survival. Accordingly, we used a microRNA-mimic to increase miR-34a together with siRNA to silence PLK1 oncogene. For in vivo dual-targeting of this combination, we developed a biodegradable amphiphilic polyglutamate amine polymeric nanocarrier (APA). APA-miRNA-siRNA polyplexes systemically administered to orthotopically inoculated PDAC-bearing mice showed no toxicity and accumulated at the tumor, resulting in an enhanced antitumor effect due to inhibition of MYC oncogene, a common target of both miR-34a and PLK1. Taken together, our findings warrant this unique combined polyplex's potential as a novel nanotherapeutic for PDAC.
[Mh] Termos MeSH primário: Carcinoma Ductal Pancreático/genética
Proteínas de Ciclo Celular/genética
Regulação Neoplásica da Expressão Gênica
MicroRNAs/genética
Neoplasias Pancreáticas/genética
Proteínas Serina-Treonina Quinases/genética
Proteínas Proto-Oncogênicas/genética
RNA Interferente Pequeno/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Animais
Carcinoma Ductal Pancreático/metabolismo
Carcinoma Ductal Pancreático/terapia
Proteínas de Ciclo Celular/metabolismo
Linhagem Celular Tumoral
Portadores de Fármacos/química
Feminino
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Estimativa de Kaplan-Meier
Masculino
Camundongos Endogâmicos C57BL
Camundongos SCID
Meia-Idade
Nanoestruturas/química
Neoplasias Pancreáticas/metabolismo
Neoplasias Pancreáticas/terapia
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas Proto-Oncogênicas/metabolismo
Proteínas Proto-Oncogênicas c-myc/genética
Proteínas Proto-Oncogênicas c-myc/metabolismo
Interferência de RNA
RNA Interferente Pequeno/química
Terapêutica com RNAi/métodos
Ensaios Antitumorais Modelo de Xenoenxerto/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Drug Carriers); 0 (MIRN34 microRNA, human); 0 (MicroRNAs); 0 (Proto-Oncogene Proteins); 0 (Proto-Oncogene Proteins c-myc); 0 (RNA, Small Interfering); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (polo-like kinase 1)
[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:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02283-9


  3 / 55650 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460439
[Au] Autor:Pant V; Larsson CA; Aryal N; Xiong S; You MJ; Quintas-Cardama A; Lozano G
[Ad] Endereço:Department of Genetics, M.D. Anderson Cancer Center, Houston, Texas, 77030, USA.
[Ti] Título:Tumorigenesis promotes Mdm4-S overexpression.
[So] Source:Oncotarget;8(16):25837-25847, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Disruption of the p53 tumor suppressor pathway is a primary cause of tumorigenesis. In addition to mutation of the p53 gene itself, overexpression of major negative regulators of p53, MDM2 and MDM4, also act as drivers for tumor development. Recent studies suggest that expression of splice variants of Mdm2 and Mdm4 may be similarly involved in tumor development. In particular, multiple studies show that expression of a splice variant of MDM4, MDM4-S correlates with tumor aggressiveness and can be used as a prognostic marker in different tumor types. However, in the absence of prospective studies, it is not clear whether expression of MDM4-S in itself is oncogenic or is simply an outcome of tumorigenesis. Here we have examined the role of Mdm4-S in tumor development in a transgenic mouse model. Our results suggest that splicing of Mdm4 does not promote tumor development and does not cooperate with other oncogenic insults to alter tumor latency or aggressiveness. We conclude that Mdm4-S overexpression is a consequence of splicing defects in tumor cells rather than a cause of tumor evolution.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica/genética
Expressão Gênica
Proteínas Nucleares/genética
Proteínas Proto-Oncogênicas/genética
[Mh] Termos MeSH secundário: Idoso
Animais
Biomarcadores
Linhagem Celular Tumoral
Aberrações Cromossômicas
Modelos Animais de Doenças
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
Masculino
Camundongos
Camundongos Transgênicos
Meia-Idade
Mutação
Polimorfismo de Nucleotídeo Único
Processamento de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (MDM4 protein, human); 0 (Nuclear Proteins); 0 (Proto-Oncogene Proteins)
[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.15552


  4 / 55650 MEDLINE  
              first record previous record next record last 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


  5 / 55650 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29373579
[Au] Autor:Schrade K; Tröger J; Eldahshan A; Zühlke K; Abdul Azeez KR; Elkins JM; Neuenschwander M; Oder A; Elkewedi M; Jaksch S; Andrae K; Li J; Fernandes J; Müller PM; Grunwald S; Marino SF; Vukicevic T; Eichhorst J; Wiesner B; Weber M; Kapiloff M; Rocks O; Daumke O; Wieland T; Knapp S; von Kries JP; Klussmann E
[Ad] Endereço:Max Delbrück Center for Molecular Medicine Berlin (MDC), Berlin, Germany.
[Ti] Título:An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells.
[So] Source:PLoS One;13(1):e0191423, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking.
[Mh] Termos MeSH primário: Proteínas de Ancoragem à Quinase A/metabolismo
Aquaporina 2/metabolismo
Membrana Celular/metabolismo
Túbulos Renais Coletores/citologia
Antígenos de Histocompatibilidade Menor/metabolismo
Proteínas Proto-Oncogênicas/metabolismo
Bibliotecas de Moléculas Pequenas/farmacologia
Proteína rhoA de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Membrana Celular/efeitos dos fármacos
Células HEK293
Seres Humanos
Ligação Proteica/efeitos dos fármacos
Transporte Proteico/efeitos dos fármacos
Bibliotecas de Moléculas Pequenas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (A Kinase Anchor Proteins); 0 (AKAP13 protein, human); 0 (Aquaporin 2); 0 (Minor Histocompatibility Antigens); 0 (Proto-Oncogene Proteins); 0 (Small Molecule Libraries); EC 3.6.5.2 (rhoA GTP-Binding Protein)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191423


  6 / 55650 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28450733
[Au] Autor:An J; Rao A; Ko M
[Ad] Endereço:Department of Biological Sciences, Chonbuk National University, Jeonju, Korea.
[Ti] Título:TET family dioxygenases and DNA demethylation in stem cells and cancers.
[So] Source:Exp Mol Med;49(4):e323, 2017 04 28.
[Is] ISSN:2092-6413
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The methylation of cytosine and subsequent oxidation constitutes a fundamental epigenetic modification in mammalian genomes, and its abnormalities are intimately coupled to various pathogenic processes including cancer development. Enzymes of the Ten-eleven translocation (TET) family catalyze the stepwise oxidation of 5-methylcytosine in DNA to 5-hydroxymethylcytosine and further oxidation products. These oxidized 5-methylcytosine derivatives represent intermediates in the reversal of cytosine methylation, and also serve as stable epigenetic modifications that exert distinctive regulatory roles. It is becoming increasingly obvious that TET proteins and their catalytic products are key regulators of embryonic development, stem cell functions and lineage specification. Over the past several years, the function of TET proteins as a barrier between normal and malignant states has been extensively investigated. Dysregulation of TET protein expression or function is commonly observed in a wide range of cancers. Notably, TET loss-of-function is causally related to the onset and progression of hematologic malignancy in vivo. In this review, we focus on recent advances in the mechanistic understanding of DNA methylation-demethylation dynamics, and their potential regulatory functions in cellular differentiation and oncogenic transformation.
[Mh] Termos MeSH primário: Metilação de DNA
Oxigenases de Função Mista/metabolismo
Neoplasias/genética
Proteínas Proto-Oncogênicas/metabolismo
Células-Tronco/metabolismo
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular
Epigênese Genética
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Oxigenases de Função Mista/genética
Neoplasias/enzimologia
Neoplasias/metabolismo
Proteínas Proto-Oncogênicas/genética
Células-Tronco/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Proto-Oncogene Proteins); EC 1.- (Mixed Function Oxygenases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180224
[Lr] Data última revisão:
180224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1038/emm.2017.5


  7 / 55650 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29288948
[Au] Autor:Pan Z; Chen Y; Liu J; Jiang Q; Yang S; Guo L; He G
[Ad] Endereço:Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; State Key Laboratory of Biotherapy and Department of Breast Surgery, West China Hospital, Sichuan University and Collaborative Innov
[Ti] Título:Design, synthesis, and biological evaluation of polo-like kinase 1/eukaryotic elongation factor 2 kinase (PLK1/EEF2K) dual inhibitors for regulating breast cancer cells apoptosis and autophagy.
[So] Source:Eur J Med Chem;144:517-528, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Both PLK1 and EEF2K are serine/threonine kinases that play important roles in the proliferation and programmed cell death of various types of cancer. They are highly expressed in breast cancer tissues. Based on the multiple-complexes generated pharmacophore models of PLK1 and homology models of EEF2K, the integrated virtual screening is performed to discover novel PLK1/EEF2K dual inhibitors. The top ten hit compounds are selected and tested in vitro, and five of them display PLK1 and EEF2K inhibition in vitro. Based on the docking modes of the most potent hit compound, a series of derivatives are synthesized, characterized and biological assayed on the PLK1, EEF2K as well as breast cancer cell proliferation models. Compound 18i with satisfied inhibitory potency are shifted to molecular mechanism studies contained molecular dynamics simulations, cell cycles, apoptosis and autophagy assays. Our results suggested that these novel PLK1/EEF2K dual inhibitors can be used as lead compounds for further development breast cancer chemotherapy.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Neoplasias da Mama/tratamento farmacológico
Proteínas de Ciclo Celular/antagonistas & inibidores
Desenho de Drogas
Quinase do Fator 2 de Elongação/antagonistas & inibidores
Inibidores de Proteínas Quinases/farmacologia
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Proteínas Proto-Oncogênicas/antagonistas & inibidores
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Proteínas de Ciclo Celular/metabolismo
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Quinase do Fator 2 de Elongação/metabolismo
Feminino
Seres Humanos
Simulação de Acoplamento Molecular
Estrutura Molecular
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas Proto-Oncogênicas/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cell Cycle Proteins); 0 (Protein Kinase Inhibitors); 0 (Proto-Oncogene Proteins); EC 2.7.1.17 (EEF2K protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.1 (polo-like kinase 1); EC 2.7.11.20 (Elongation Factor 2 Kinase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE


  8 / 55650 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28448802
[Au] Autor:Sasi NK; Bhutkar A; Lanning NJ; MacKeigan JP; Weinreich M
[Ad] Endereço:Laboratory of Genome Integrity and Tumorigenesis, Van Andel Research Institute (VARI), Grand Rapids, MI 49503; Laboratory of Systems Biology, VARI; Graduate Program in Genetics, Michigan State University, East Lansing, MI 48824.
[Ti] Título:DDK Promotes Tumor Chemoresistance and Survival via Multiple Pathways.
[So] Source:Neoplasia;19(5):439-450, 2017 May.
[Is] ISSN:1476-5586
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:DBF4-dependent kinase (DDK) is a two-subunit kinase required for initiating DNA replication at individual origins and is composed of CDC7 kinase and its regulatory subunit DBF4. Both subunits are highly expressed in many diverse tumor cell lines and primary tumors, and this is correlated with poor prognosis. Inhibiting DDK causes apoptosis of tumor cells, but not normal cells, through a largely unknown mechanism. Firstly, to understand why DDK is often overexpressed in tumors, we identified gene expression signatures that correlate with DDK high- and DDK low-expressing lung adenocarcinomas. We found that increased DDK expression is highly correlated with inactivation of RB1-E2F and p53 tumor suppressor pathways. Both CDC7 and DBF4 promoters bind E2F, suggesting that increased E2F activity in RB1 mutant cancers promotes increased DDK expression. Surprisingly, increased DDK expression levels are also correlated with both increased chemoresistance and genome-wide mutation frequencies. Our data further suggest that high DDK levels directly promote elevated mutation frequencies. Secondly, we performed an RNAi screen to investigate how DDK inhibition causes apoptosis of tumor cells. We identified 23 kinases and phosphatases required for apoptosis when DDK is inhibited. These hits include checkpoint genes, G2/M cell cycle regulators, and known tumor suppressors leading to the hypothesis that inhibiting mitotic progression can protect against DDKi-induced apoptosis. Characterization of one novel hit, the LATS2 tumor suppressor, suggests that it promotes apoptosis independently of the upstream MST1/2 kinases in the Hippo signaling pathway.
[Mh] Termos MeSH primário: Adenocarcinoma/genética
Proteínas de Ciclo Celular/genética
Resistência a Medicamentos Antineoplásicos/genética
Neoplasias Pulmonares/genética
Proteínas Serina-Treonina Quinases/genética
[Mh] Termos MeSH secundário: Adenocarcinoma/tratamento farmacológico
Adenocarcinoma/patologia
Apoptose/efeitos dos fármacos
Proteínas de Ciclo Celular/antagonistas & inibidores
Proteínas de Ligação a DNA/genética
Fatores de Transcrição E2F/genética
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Fator de Crescimento de Hepatócito/genética
Seres Humanos
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Pulmonares/patologia
Fosforilação
Regiões Promotoras Genéticas
Proteínas Proto-Oncogênicas/genética
Proteínas de Ligação a Retinoblastoma/genética
Transdução de Sinais/efeitos dos fármacos
Proteína Supressora de Tumor p53/genética
Proteínas Supressoras de Tumor/genética
Ubiquitina-Proteína Ligases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (DBF4 protein, human); 0 (DNA-Binding Proteins); 0 (E2F Transcription Factors); 0 (Proto-Oncogene Proteins); 0 (RB1 protein, human); 0 (Retinoblastoma Binding Proteins); 0 (TP53 protein, human); 0 (Tumor Suppressor Protein p53); 0 (Tumor Suppressor Proteins); 0 (macrophage stimulating protein); 67256-21-7 (Hepatocyte Growth Factor); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.1.- (CDC7 protein, human); EC 2.7.1.11 (LATS2 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE


  9 / 55650 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29327347
[Au] Autor:Fujii S; Nakamura S; Oda A; Miki H; Tenshin H; Teramachi J; Hiasa M; Bat-Erdene A; Maeda Y; Oura M; Takahashi M; Iwasa M; Endo I; Yoshida S; Aihara KI; Kurahashi K; Harada T; Kagawa K; Nakao M; Sano S; Abe M
[Ad] Endereço:Department of Haematology, Endocrinology and Metabolism, Tokushima University Graduate School, Tokushima, Japan.
[Ti] Título:Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity.
[So] Source:Br J Haematol;180(2):246-258, 2018 01.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Proviral Integrations of Moloney virus 2 (PIM2) is overexpressed in multiple myeloma (MM) cells, and regarded as an important therapeutic target. Here, we aimed to validate the therapeutic efficacy of different types of PIM inhibitors against MM cells for their possible clinical application. Intriguingly, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a reduced PIM2 protein levels and impaired MM cell survival preferentially in acidic conditions, in contrast to other types of PIM inhibitors, including AZD1208, CX-6258 and PIM447. SMI-16a also suppressed the drug efflux function of breast cancer resistance protein, minimized the sizes of side populations and reduced in vitro colony-forming capacity and in vivo tumourigenic activity in MM cells, suggesting impairment of their clonogenic capacity. PIM2 is known to be subject to ubiquitination-independent proteasomal degradation. Consistent with this, the proteasome inhibitors bortezomib and carfilzomib increased PIM2 protein levels in MM cells without affecting its mRNA levels. However, SMI-16a mitigated the PIM2 protein increase and cooperatively enhanced anti-MM effects in combination with carfilzomib. Collectively, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a uniquely reduce PIM2 protein in MM cells, which may contribute to their profound efficacy in addition to their immediate kinase inhibition. Their combination with proteasome inhibitors is envisioned.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Mieloma Múltiplo/metabolismo
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Proteínas Proto-Oncogênicas/antagonistas & inibidores
Tiazolidinedionas/farmacologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Transformação Celular Neoplásica/efeitos dos fármacos
Modelos Animais de Doenças
Seres Humanos
Concentração de Íons de Hidrogênio
Camundongos
Mieloma Múltiplo/tratamento farmacológico
Mieloma Múltiplo/patologia
Inibidores de Proteassoma/farmacologia
Proteínas Serina-Treonina Quinases/metabolismo
Proteólise
Proteínas Proto-Oncogênicas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (PIM2 protein, human); 0 (Proteasome Inhibitors); 0 (Proto-Oncogene Proteins); 0 (Thiazolidinediones); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[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:180113
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15033


  10 / 55650 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28457890
[Au] Autor:Saunders A; Li D; Faiola F; Huang X; Fidalgo M; Guallar D; Ding J; Yang F; Xu Y; Zhou H; Wang J
[Ad] Endereço:The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine
[Ti] Título:Context-Dependent Functions of NANOG Phosphorylation in Pluripotency and Reprogramming.
[So] Source:Stem Cell Reports;8(5):1115-1123, 2017 May 09.
[Is] ISSN:2213-6711
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The core pluripotency transcription factor NANOG is critical for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Although NANOG is phosphorylated at multiple residues, the role of NANOG phosphorylation in ESC self-renewal is incompletely understood, and no information exists regarding its functions during reprogramming. Here we report our findings that NANOG phosphorylation is beneficial, although nonessential, for ESC self-renewal, and that loss of phosphorylation enhances NANOG activity in reprogramming. Mutation of serine 65 in NANOG to alanine (S65A) alone has the most significant impact on increasing NANOG reprogramming capacity. Mechanistically, we find that pluripotency regulators (ESRRB, OCT4, SALL4, DAX1, and TET1) are transcriptionally primed and preferentially associated with NANOG S65A at the protein level due to presumed structural alterations in the N-terminal domain of NANOG. These results demonstrate that a single phosphorylation site serves as a critical interface for controlling context-dependent NANOG functions in pluripotency and reprogramming.
[Mh] Termos MeSH primário: Reprogramação Celular
Células-Tronco Embrionárias/citologia
Células-Tronco Pluripotentes Induzidas/citologia
Mutação de Sentido Incorreto
Proteína Homeobox Nanog/metabolismo
Processamento de Proteína Pós-Traducional
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Células Cultivadas
Receptor Nuclear Órfão DAX-1/metabolismo
Proteínas de Ligação a DNA/metabolismo
Células-Tronco Embrionárias/metabolismo
Células-Tronco Pluripotentes Induzidas/metabolismo
Camundongos
Proteína Homeobox Nanog/química
Proteína Homeobox Nanog/genética
Fator 3 de Transcrição de Octâmero/metabolismo
Fosforilação
Domínios Proteicos
Proteínas Proto-Oncogênicas/metabolismo
Receptores Estrogênicos/metabolismo
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DAX-1 Orphan Nuclear Receptor); 0 (DNA-Binding Proteins); 0 (Esrrb protein, mouse); 0 (Nanog Homeobox Protein); 0 (Nanog protein, mouse); 0 (Nr0b1 protein, mouse); 0 (Octamer Transcription Factor-3); 0 (Pou5f1 protein, mouse); 0 (Proto-Oncogene Proteins); 0 (Receptors, Estrogen); 0 (Sall4 protein, mouse); 0 (TET1 protein, mouse); 0 (Transcription Factors)
[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:170502
[St] Status:MEDLINE



página 1 de 5565 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