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Id: biblio-1022036
Autor: Guo, Haiyan; Wang, Qiang; Li, Yongjun; Yin, Xiuyuan; Zhang, Hao; Shi, Jianfei.
Título: Overexpression of CDC25C affects the cell cycle of ovarian granulosa cells from adult and young goats
Fonte: Electron. j. biotechnol;31:17-23, Jan. 2018. tab, ilus, graf.
Idioma: en.
Projeto: Key Natural Science Program of Jiangsu Higher Education Institutions; . Priority Academic Program Development of Jiangsu Higher Education Institutions.
Resumo: Background: CDC25 is a dual-specificity phosphatase that was first identified in the yeast Schizosaccharomyces pombe as a cell cycle-defective mutant. Although CDC25 is involved in the cell cycle of ovarian granulosa cells, the CDC25 signaling pathway has not been clarified fully. To explore the role of CDC25C in the cell cycle of goat ovarian granulosa cells, a CDC25C-overexpressing vector, pCMV-HA-CDC25C, was constructed and transfected into granulosa cells from adult and young white goats from Jiangsu Nantong. RT-PCR was used to measure CDC25C, CDK1, and WEE1 gene expression levels, and flow cytometry was used to distinguish ovarian granulosa cells in different phases of the cell cycle. Progesterone and estradiol levels in transfected ovarian granulosa cells were also measured. Results: In adult goat follicular granulosa cells transfected with pCMV-HA-CDC25C, CDC25C expression increased significantly, which greatly increased the relative gene expression levels of both CDK1 and WEE1. Additionally, progesterone and estradiol levels were increased in goat follicular granulosa cells overexpressing CDC25C. And the cell cycle results showed that transfection of pCMV-HA-CDC25C leads to a higher proportion of cells in S phase compared to the no vector-transfected groups. Conclusions: The results of this study indicated that the overexpression of CDC25C may increase the gene expression levels of both WEE1 and CDK1 in S phase and accelerate the transition of cells from G1 phase to S phase.
Descritores: Cabras
Ciclo Celular/fisiologia
Fosfatases cdc25/genética
Fosfatases cdc25/metabolismo
Células da Granulosa/enzimologia
-Progesterona/análise
Proteínas Tirosina Quinases/genética
Transfecção
Ciclo Celular/genética
Reação em Cadeia da Polimerase/métodos
Apoptose
Quinases Ciclina-Dependentes/genética
Estradiol/análise
Fertilização
Citometria de Fluxo
Fluorescência
Células da Granulosa/metabolismo
Limites: Animais
Feminino
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-951898
Autor: Ferreira, Paulo Michel Pinheiro; Pessoa, Cláudia.
Título: Molecular biology of human epidermal receptors, signaling pathways and targeted therapy against cancers: new evidences and old challenges
Fonte: Braz. J. Pharm. Sci. (Online);53(2):e16076, 2017. graf.
Idioma: en.
Projeto: Conselho Nacional de Desenvolvimento Científico e Tecnológico.
Resumo: ABSTRACT Human epidermal receptors (HER1/2/3/4) belong to the class of receptor-type tyrosine kinases. After binding a ligand, dimerization, it will ocurr activation of intracellular kinases after two-dimensional and cytoplasmic tail reciprocal transphosphorylation. This transphosphorylation recruits signaling pathways such as Ras/Raf/MEK/Erk1-2, PI3-K/AKT and JAK/STAT, which can affect the cell cycle, cytoskeleton reorganization, apoptosis, metastasis, differentiation, angiogenesis and transcription. HER deregulation is found in epithelial, mesenchymal and nervous neoplasms and is associated with poor prognosis and tumor severity. Since HER are promiscuous proteins when subjected to mutations, resultant modifications confer cellular metabolic superiority and activate complex, interconnected and overlapping networks of cytoplasmic signaling. Moreover, overexpression of HER1/2 is involved in tumor resistance to radiation and anti-hormone therapies. Indeed, HER2 expression is up to 100-fold higher in 25-30% of invasive breast cancers. These characteristics support the development of resistance to anti-HER1/2 chemotherapy such as monoclonal antibodies and tyrosine kinase inhibitors. Then, the challenges in research with HER-positive cancers include planning therapeutic strategies against known resistance mechanisms and identifying novel mechanisms as a way to overcome and control cell growth and malignant progression.
Descritores: Proteínas Tirosina Quinases
Biologia Molecular/classificação
Neoplasias
-Transdução de Sinais
Receptores Proteína Tirosina Quinases
Quimioterapia Combinada/estatística & dados numéricos
Responsável: BR40.1 - DBD - Divisão de Biblioteca e Documentacão do Conjunto das Químicas


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Id: lil-654976
Autor: Petrola, Maria Juracy; Castro, Alana Joselina Montenegro de; Pitombeira, Maria Helena da Silva; Barbosa, Maritza Cavalcante; Quixadá, Acy Telles de Souza; Duarte, Fernando Barroso; Gonçalves, Romelia Pinheiro.
Título: Serum concentrations of nitrite and malondialdehyde as markers of oxidative stress in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors
Fonte: Rev. bras. hematol. hemoter;34(5):352-355, 2012. graf, tab.
Idioma: en.
Resumo: BACKGROUND: Chronic myeloid leukemia is a neoplasm characterized by clonal expansion of hematopoietic progenitor cells resulting from the (9:22)(q34,11) translocation. The tyrosine kinase abl fusion protein,the initial leukemogenic event in chronic myeloid leukemia, is constitutively activated thus inducing the production of reactive oxygen species. Of particular relevance is the fact that an increase in reactive oxygen species can facilitate genomic instability and may contribute to disease progression. OBJETIVE: To evaluate oxidative stress by determining the levels of malondialdehyde and nitrite in chronic myeloid leukemia patients under treatment with 1st and 2nd generation tyrosine kinase inhibitors monitored at a referral hospital in Fortaleza, Ceará. METHODS: A cross-sectional study was performed of 64 male and female adults. Patients were stratified according to treatment. The levels of malondialdehyde and nitrite were determined by spectrophotometry. Statistical differences between groups were observed using the Student t-test and Fisher's exact test. The results are expressed as mean ± standard error of mean. The significance level was set for a p-value < 0.05 in all analyses. RESULTS: The results show significantly higher mean concentrations of nitrite and malondialdehyde in chronic myeloid leukemia patients using second-generation tyrosine kinase inhibitors compared to patients on imatinib. Conclusion: It follows that chronic myeloid leukemia patients present higher oxidative activity and that the increases in oxidative damage markers can indicate resistance to 1st generation tyrosine kinase inhibitors.
Descritores: Proteínas Tirosina Quinases
Leucemia Mielogênica Crônica BCR-ABL Positiva
Estresse Oxidativo
Malondialdeído
Limites: Humanos
Masculino
Feminino
Adulto
Pessoa de Meia-Idade
Idoso
Idoso de 80 Anos ou mais
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: biblio-951946
Autor: Inturi, Srikanth; Avula, Prameela Rani.
Título: A sensitive bioanalytical method development and validation of cabozantinib in human plasma by LC-ESI-MS/MS
Fonte: Braz. J. Pharm. Sci. (Online);54(2):e17163, 2018. tab, graf.
Idioma: en.
Resumo: ABSTRACT A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of cabozantinib (CZ) in human plasma using cabozantinib-d4 (CZD4) as an internal standard (IS). Chromatographic separation was performed on Xbridge C18, 50 x 4.6 mm, 5 mm column with an isocratic mobile phase composed of 10mM Ammonium formate and Methanol in the ratio of (20:80 v/v), at a flow-rate of 0.7 mL/min. CZ and CZD4 were detected with proton adducts at m/z 502.2 ® 391.1 and 506.3 ® 391.2 in multiple reaction monitoring (MRM) positive mode respectively. Liquid-Liquid extraction method was used to extract the drug and IS. The method was validated over a linear concentration range of 5.0-5000.0 pg/mL with correlation coefficient (r2) ≥ 0.9994. This method demonstrated intra and inter-day precision within 1.95 to 2.37 and 2.93 to 9.3 % and Accuracy within 101.4 to 102.4 and 99.5 to 104.8 %. Cabozantinib was found to be stable throughout freeze-thawing cycles, bench top and postoperative stability studies
Descritores: Plasma
Farmacocinética
Estudo de Validação
-Proteínas Tirosina Quinases
Cromatografia Líquida/métodos
Espectrometria de Massas em Tandem/métodos
Responsável: BR1.1 - BIREME


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Id: biblio-889392
Autor: Suneetha, Achanta; Donepudi, Sharmila.
Título: HPLC method development and validation for the estimation of Axitinib in rabbit plasma
Fonte: Braz. J. Pharm. Sci. (Online);53(3):e00012, 2017. tab, graf.
Idioma: en.
Resumo: ABSTRACT A rapid, sensitive, and accurate high performance liquid chromatography for the determination of Axitinib (AN) in rabbit plasma is developed using crizotinibe as an internal standard (IS). Axitinib is a tyrosine kinase inhibitor, used in the treatment of advanced kidney cancer, which works by slowing or stopping the growth of cancer cells. The chromatographic separation was performed on a Waters 2695, Kromosil (150 mm × 4.6 mm, 5 µm) column using a mobile phase containing buffer (pH 4.6) and acetonitrile in the ratio of 65:35 v/v with a flow rate of1 mL/min. The analyte and internal standard were extracted using liquid-liquid extraction with acetonitrile. The elution was detected by photo diode array detector at 320 nm.The total chromatographic runtime is 10.0 min with a retention time for Axitinib and IS of 5.685, and 3.606 min, respectively. The method was validated over a dynamic linear range of 0.002-0.2µg/mL for Axitinib with a correlation coefficient of r2 0.999.
Descritores: Cromatografia Líquida de Alta Pressão/métodos
Estudo de Validação
-Proteínas Tirosina Quinases/antagonistas & inibidores
Neoplasias Renais/tratamento farmacológico
Limites: Coelhos
Responsável: BR40.1 - DBD - Divisão de Biblioteca e Documentacão do Conjunto das Químicas


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Id: biblio-978408
Autor: Macía Pérez, Ivis; Fernández Delgado, Norma D; Hernández Padrón, Carlos; Quintero Sierra, Yamilé.
Título: Aplasia medular por inhibidores de la tirosina cinasa en pacientes con leucemia mieloide crónica / Bone marrow aplasia following tyrosin kinase inhibitors in patients with chronic myeloid leukemia
Fonte: Rev. cuba. hematol. inmunol. hemoter;34(1):102-104, ene.-mar. 2018.
Idioma: es.
Descritores: Proteínas Tirosina Quinases/uso terapêutico
Aplasia Pura de Série Vermelha/terapia
-Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia
Aplasia Pura de Série Vermelha/complicações
Limites: Humanos
Masculino
Feminino
Tipo de Publ: Carta
Responsável: CU1.1 - Biblioteca Médica Nacional


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Id: biblio-898930
Autor: Vieira-Mion, Ana Lucia; Pereira, Noemi Farah; Funke, Vaneuza Araujo Moreira; Pasquini, Ricardo.
Título: Molecular response to imatinib mesylate of Brazilian patients with chronic myeloid leukemia
Fonte: Rev. bras. hematol. hemoter;39(3):210-215, July-Sept. 2017. tab, graf.
Idioma: en.
Resumo: Abstract Background Imatinib mesylate has revolutionized the treatment of chronic myeloid leukemia leading to significant reductions of BCR-ABL1 transcript levels in peripheral blood. Objective To evaluate the response to imatinib mesylate treatment (400 mg/day) in Brazilian patients in the chronic phase of chronic myeloid leukemia monitored by quantitative real time polymerase chain reaction. Methods Between October 2002 and October 2010, 3169 peripheral blood samples were collected from 1403 patients from 3 to 5 months, 6 to 11 months, 12 to 17 months, 18 to 23 months and ≥24 months after beginning imatinib treatment. Eighty-two patients had samples available and analyzed for all time intervals. BCR-ABL1 quantification was performed by quantitative real time polymerase chain reaction using the ABL1 gene as the control. Results of the BCR-ABL1 ratio as a percentage were reported by the international scale (IS) using the laboratory conversion factor (0.51). Results In the first interval, 80.8% of patients achieved the optimal response (BCR-ABL1 IS ≤ 10%). In the second period, 69.1% achieved optimal response (BCR-ABL1 IS ≤ 1%) and, between 12 and 17 months, 47.3% achieved major molecular response (BCR-ABL1 IS ≤ 0.1%). Conclusions The results of this retrospective study show that the response to imatinib treatment (400 mg/day) of Brazilian patients in the chronic phase of chronic myeloid leukemia is within the expected profile when compared to patients reported in international prospective randomized studies.
Descritores: Brasil
Leucemia Mielogênica Crônica BCR-ABL Positiva
Mesilato de Imatinib
-Proteínas Tirosina Quinases
Proteínas de Fusão bcr-abl
Reação em Cadeia da Polimerase em Tempo Real
Limites: Humanos
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: biblio-898946
Autor: Kumar, Rajiv; Kapoor, Rajan.
Título: Primary imatinib failure rescued by dasatinib and maintained by reintroduction of imatinib
Fonte: Rev. bras. hematol. hemoter;39(4):360-363, Oct.-Dec. 2017. graf.
Idioma: en.
Descritores: Proteínas Tirosina Quinases
Leucemia Mielogênica Crônica BCR-ABL Positiva
Mesilato de Imatinib
Limites: Humanos
Masculino
Idoso
Tipo de Publ: Relatos de Casos
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: biblio-859362
Autor: Custodio, Marcelo Graziano; Andreghetto, Flavia Maziero; Pires, Tatiana Lanças Camargo; Horacio, Marcelo Pereira; Tunala, Roberto Gaspar.
Título: Gefitinibe na Primeira Linha de Tratamento para o Câncer de Pulmão de não Pequenas Células / Gefitinib as Non-Small Cell Lung Cancer First Line Treatment
Fonte: Pulmäo RJ;25(2):29-34, 2016.
Idioma: pt.
Resumo: Introdução: os inibidores de tirosina quinase (TKIs - tyrosine kinase inhibitor) são o tratamento de primeira linha no câncer de pulmão de não pequenas células (CPNPC) localmente avançado ou metastático com mutação do EGFR (receptor do fator de crescimento epidérmico - epidermal growth factor receptor). Esta revisão compara o tratamento do CPNPC com o gefitinibe, um TKI de primeira geração, versus o tratamento quimioterápico. Método: foi realizada revisão de literatura com palavras-chave relevantes e análise descritiva dos resultados. Resultados: os pacientes com CPNPC e mutação do EGFR apresentaram melhora da sobrevida livre de progressão (SLP), taxa de resposta objetiva (TRO) e taxa de controle da doença (TCR) em relação à quimioterapia citotóxica. A taxa de eventos adversos graves, eventos adversos que levaram à descontinuação do tratamento e os que levaram à redução de dose foram menores com o gefitinibe. O gefitinibe também foi relacionado à melhora da qualidade devida. Conclusão: o uso do gefitinibe em primeira linha no tratamento do CPNPC com mutação EGFR demonstrou superioridade de eficácia, segurança e qualidade de vida, quando comparado ao tratamento quimioterápico.

Introduction: tyrosine kinase inhibitors (TKIs) are the first line treatment for EGFR (epidermal growth factor receptor) mutated non-small cells lung cancer (NSCLC) locally advanced or metastatic. The aim of this review is to compare the treatment of NSCLC with the first-generation EGFR-TKI gefitinib versus chemotherapy . Methods: a review of the literature was performed using relevant keywords and descriptive analysis of the results. Results: patients with NSCLC and EGFR mutation showed improved progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) compared cytotoxic chemotherapy. The rate of serious adverse events, adverse events leading to discontinuation of treatment and that led to dose reduction were lower with gefitinib. Quality of life improvement was also related to the treatment with gefitinib. Conclusion: the use of gefitinib as first-line treatment of EGFR mutated NSCLC showed improved efficacy, safety and quality of life when compared to chemotherapy.
Descritores: Proteínas Tirosina Quinases
Receptores ErbB
Carcinoma Pulmonar de Células não Pequenas/terapia
Limites: Humanos
Masculino
Feminino
Responsável: BR674.1 - IDT - Biblioteca do Instituto de Doenças do Tórax


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Id: biblio-940952
Autor: Fabrro, Doriano(edt); McCormich, Frank.
Título: Protein Tyrosine Kinases: from inhibitors to useful drugs.
Fonte: Totowa; Humana Press; 2006. 290 p.
Idioma: en.
Descritores: Proteínas Tirosina Quinases
Proteínas Tirosina Quinases/análise
Proteínas Tirosina Quinases/uso terapêutico
Limites: Masculino
Feminino
Humanos
Responsável: BR1719.1 - Biblioteca do CPqRR
BR1719.1; 616.99, F113p, 2006. 000313



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