Navegando por Palavras-chave "Platelets"

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    Avaliação do perfil de agregado plaquetário circulante e da expressão de OX40, CD40L e 4-1BB em pacientes idosos com câncer colorretal
    (Universidade Federal de São Paulo (UNIFESP), 2017-12-20) Lima, Petrus Moura de Andrade [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Torres, Leuridan Cavalcante [UNIFESP]; http://lattes.cnpq.br/4973562538598237; http://lattes.cnpq.br/7314943504526739; http://lattes.cnpq.br/5026314977391614; Universidade Federal de São Paulo (UNIFESP)
    A cada ano, mais de 1,2 milhões de pessoas são diagnosticadas com câncer colorretal (CCR) e cerca de 600.000 pessoas morrem por causa dessa doença. A incidência do câncer de cólon aumenta com a idade. O prognóstico dos pacientes com CCR tem melhorado nas últimas décadas, contudo, persiste uma sobrevida global menor nos idosos. O ambiente tumoral é composto por células do sistema imune, que refletem a tentativa desse sistema em promover uma resposta antitumoral. Complexas interações entre células e mediadores imunes no microambiente tecidual regulam o crescimento de tumores, progressão, metástase e angiogênese. O entendimento das alterações da imunidade na população idosa com CCR permitirá o surgimento de novos tratamentos com maiores taxas de resposta. O presente estudo teve por objetivo avaliar o perfil de agregado plaquetário circulante e da expressão de OX40, CD40L e 4-1BB em idosos com câncer colorretal. Foi realizado um estudo de corte transversal e translacional com grupo de comparação interna, envolvendo 41 idosos portadores de CCR e 75 idosos saudáveis. Foi realizada a análise dos valores percentuais de leucócitos, de agregado de plaquetas ativadas aos linfócitos, monócitos e neutrófilos no sangue periférico, e também a análise dos percentuais de expressão de OX40, p-selectina (CD62P) e CD40L em células T, B, neutrófilo e plaquetas por citometria de fluxo. Dosagem no plasma de s4-1BB e sCD40L por enzyme linked immunosorbentassay (ELISA). Testes de Mann-Whitney e Kruskal-Wallis foram usados para análise de medianas entre dois e três grupos, respectivamente. As variáveis de distribuição normal foram apresentadas em média e desvio padrão. Foi utilizado o teste t e ANOVA para a comparação das médias entre dois e três grupos, respectivamente. Foram considerados significantes valores de p<0.05. Toda a análise estatística foi realizada através do GraphPadPrism v6.0 Verificou-se níveis percentuais diminuídos de plaquetas/OX40+ nos pacientes com CCR (p<0,0001). Os níveis percentuais de linfócitos B/OX40+ estiveram aumentados nos pacientes metastáticos (p=0,01). Na análise do agregado de plaquetas em leucócitos no sangue periférico, verificou-se que os pacientes apresentaram níveis percentuais reduzidos de AGP-neutrófilos (p=0,004). Os pacientes apresentaram um elevado percentual de plaquetas expressando CD62P quando comparado aos controles (p=0,003). Observou-se nos pacientes valores percentuais reduzidos de expressão de CD40L em plaquetas (p<0,0001) e agregado de plaquetas a leucócitos. Os pacientes apresentaram níveis séricos reduzidos de sCD40L quando comparado aos controles (p=0,002). Os idosos com CCR possuem uma imunossupressão que favorece a progressão da doença. Esse conhecimento reveste-se de importância pela possibilidade do surgimento de novas terapias que possam ativar os mecanismos da resposta imune frente aos antígenos tumorais no CCR.
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    Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer
    (Biomed Central Ltd, 2016) Andrade, Sheila Siqueira [UNIFESP]; Gouvea, Iuri Estrada [UNIFESP]; Silva, Mariana Cristina C. [UNIFESP]; Castro, Eloisa Dognani [UNIFESP]; de Paula, Claudia A. A. [UNIFESP]; Okamoto, Debora [UNIFESP]; Oliveira, Lilian [UNIFESP]; Peres, Giovani Bravin [UNIFESP]; Ottaiano, Tatiana [UNIFESP]; Facina, Gil [UNIFESP]; Pinto Nazario, Afonso Celso [UNIFESP]; Campos, Antonio Hugo J. F. M.; Paredes-Gamero, Edgar Julian [UNIFESP]; Juliano, Maria [UNIFESP]; da Silva, Ismael D. C. G. [UNIFESP]; Oliva, Maria Luiza V. [UNIFESP]; Girao, Manoel J. B. C. [UNIFESP]
    Background: Breast cancer comprises clinically and molecularly distinct tumor subgroups that differ in cell histology and biology and show divergent clinical phenotypes that impede phase III trials, such as those utilizing cathepsin K inhibitors. Here we correlate the epithelial-mesenchymal-like transition breast cancer cells and cathepsin K secretion with activation and aggregation of platelets. Cathepsin K is up-regulated in cancer cells that proteolyze extracellular matrix and contributes to invasiveness. Although proteolytically activated receptors (PARs) are activated by proteases, the direct interaction of cysteine cathepsins with PARs is poorly understood. In human platelets, PAR-1 and -4 are highly expressed, but PAR-3 shows low expression and unclear functions. Methods: Platelet aggregation was monitored by measuring changes in turbidity. Platelets were immunoblotted with anti-phospho and total p38, Src-Tyr-416, FAK-Tyr-397, and TGF beta monoclonal antibody. Activation was measured in a flow cytometer and calcium mobilization in a confocal microscope. Mammary epithelial cells were prepared from the primary breast cancer samples of 15 women with Luminal-B subtype to produce primary cells. Results: We demonstrate that platelets are aggregated by cathepsin K in a dose-dependent manner, but not by other cysteine cathepsins. PARs-3 and -4 were confirmed as the cathepsin K target by immunodetection and specific antagonists using a fibroblast cell line derived from PARs deficient mice. Moreover, through co-culture experiments, we show that platelets activated by cathepsin K mediated the up-regulation of SHH, PTHrP, OPN, and TGF beta in epithelial-mesenchymal-like cells from patients with Luminal B breast cancer. Conclusions: Cathepsin K induces platelet dysfunction and affects signaling in breast cancer cells.
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    Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease
    (Japanese Circulation Soc, 2012-03-01) Franca, Carolina N. [UNIFESP]; Pinheiro, Luiz F. M. [UNIFESP]; Izar, Maria C. O. [UNIFESP]; Brunialti, Milena K. C. [UNIFESP]; Salomao, Reinaldo [UNIFESP]; Bianco, Henrique T. [UNIFESP]; Kasmas, Soraia H. [UNIFESP]; Barbosa, Simone P. [UNIFESP]; Nucci, Gilberto de; Fonseca, Francisco A. H. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Natl Inst Complex Fluids; Universidade Estadual de Campinas (UNICAMP)
    Background: Increased numbers of endothelial (EMP) and platelet (PMP) microparticles have been related to cardiovascular risk factors and coronary artery disease. Little is known about the early effects of statins and clopidogrel on these new biomarkers of vascular homeostasis. the aim of the present study was to evaluate pharmacokinetic interactions between atorvastatin and clopidogrel and their effects, alone or combined, on EMP, PMP, and endothelial progenitor cells (EPC).Methods and Results: A prospective open-label study enrolled subjects with stable coronary disease (n=26). Drugs were given daily for 3 weeks (atorvastatin 80 mg, visits 1-3; clopidogrel 75 mg, visits 2-4). Counts of EPC (CD34+/CD133+/KDR+), EMP (CD51+) and PMP (CD42+/CD31+), and pharmacokinetic parameters over 24 h were assessed at each visit. Atorvastatin plasma concentrations were increased by concomitant therapy with clopidogrel (maximum serum concentration [C-max], P=0.002; area under the clopidogrel or atorvastatin plasma concentration vs. time curve from 0 to the last detectable concentration [AUC(last)], P=0.03). After atorvastatin withdrawal there was an increase in clopidogrel plasma concentrations (C-max, P=0.009; AUC(last), P=0.039). PMP were inversely correlated with clopidogrel C. on visit 3 (rho=-0.57, P=0.006) and on visit 4 (rho=-0.54, P=0.01), and with clopidogrel AUC(last) on visit 3 (rho=-0.44, P=0.04), and on visit 4 (rho=-0.57, P=0.005). in addition, clopidogrel C-max was correlated with EPC (CD133+/KDR+) on visit 4 (rho=0.48, P=0.025). No correlations of atorvastatin and MP or EPC were found.Conclusions: the balance between platelet MP release and EPC mobilization seems influenced by clopidogrel plasma levels, suggesting a protective mechanism on coronary artery disease. (Circ J 2012; 76: 729-736)
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    Pharmacokinetic interactions between clopidogrel and rosuvastatin: Effects on vascular protection in subjects with coronary heart disease
    (Elsevier B.V., 2012-06-28) Pinheiro, Luiz Fernando Muniz [UNIFESP]; Franca, Carolina Nunes [UNIFESP]; Izar, Maria Cristina de Oliveira [UNIFESP]; Barbosa, Simone Pinto de Melo [UNIFESP]; Bianco, Henrique Tria [UNIFESP]; Kasmas, Soraia Hani [UNIFESP]; Mendes, Gustavo Duarte; Póvoa, Rui Manuel dos Santos [UNIFESP]; Fonseca, Francisco Antonio Helfenstein [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Galeno Lab
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    Reticulated platelets and thrombopoietin in schistosomiasis patients
    (Wiley-Blackwell, 2009-02-01) Koepke-Aguiar, L. A.; dE Leon, C. P.; Shigueoka, D. C.; Lourenco, D. M.; Kouyomdjian, M.; Borges, D. R.; Universidade Federal de São Paulo (UNIFESP)
    Schistosomiasis mansoni is a non-cirrhotic liver disease. in cirrhosis patients with portal hypertension, a decreased number of reticulated platelets associated with increased thrombopoietin serum levels were reported. We previously reported a 120/nl platelet cutoff level as a marker of clinically significant portal hypertension in schistosomiasis patients. To evaluate reticulated platelet counts and thrombopoietin serum levels (TPO) in schistosomiasis patients and correlate them with portal hypertension markers. Thirty-three schistosomiasis patients without co-morbidities were endoscopically classified as those with (n = 19) or without (n = 14) clinically significant portal hypertension. Flow cytometric determination of reticulated platelets was performed using CD41 antibody and thiazol orange. Ultrasonographic examinations were performed according to the Niamey protocol. TPO and hyaluronic acid serum levels were determined in duplicate using ELISA methods. the platelet number of 120/nl discriminates the two groups with 100% accuracy and 100% positive and negative predictive values, and correlates with spleen length and portal and splenic vein diameters. Differences in reticulated platelets and hyaluronic acid serum levels between both groups were significant (P = 0.025 and 0.012, respectively), but thrombopoietin serum levels were not (P = 0.769). Schistosomiasis patients with portal hypertension have increased reticulated platelets associated with normal TPO serum levels.