Efeito dos Moduladores de MDR em Linhas Celulares de Adenocarcinoma Colo-Rectal

Resumo da comunicação apresentado ao XII Congresso Nacional de Medicina Nuclear, 12-14 Novembro 2009, Mealhad

Effects of Resistance Exercise on Endothelial Progenitor Cell Mobilization in Women

This study aimed to determine the effect of a single bout of resistance exercise at different intensities on the mobilization of circulating EPCs over 24 hours in women. In addition, the angiogenic factors stromal cell-derived factor 1 (SDF-1α), vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1-alpha (HIF-1α) and erythropoietin (EPO) were measured as potential mechanisms for exercise-induced EPCs mobilization. Thirty-eight women performed a resistance exercise session at an intensity of 60% (n = 13), 70% (n = 12) or 80% (n = 13) of one repetition maximum. Each session was comprised of three sets of 12 repetitions of four exercises: bench press, dumbbell curl, dumbbell squat, and standing dumbbell upright row. Blood was sampled at baseline and immediately, 6 hours, and 24 hours post-exercise. Circulating EPC and levels of VEGF, HIF-1α and EPO were significantly higher after exercise (P \u3c 0.05). The change in EPCs from baseline was greatest in the 80% group (P \u3c 0.05), reaching the highest at 6 hours post-exercise. The change in EPCs from baseline to 6 hours post-exercise was correlated with the change in VEGF (r = 0.492, P = 0.002) and HIF-1α (r = 0.388, P = 0.016). In general, a dose-response relationship was observed, with the highest exercise intensities promoting the highest increases in EPCs and angiogenic factors

Acção anti-cancerígena da Quercetina no Carcinoma Hepatocelular: o papel do GLUT-1

Hepatocellular Carcinoma (HCC) is one of the most fatal cancers, with rising incidence. Without specific treatment, the prognosis is very poor and diminished survival. The most effective therapy is liver transplantation and complete surgical resection, however, since only 15% of patients are candidates for such therapies, a wide range of patients are subjected to treatment with conventional therapies, and the rate success is greatly diminished. It is thought that the expression of glucose transporter 1 (GLUT-1) may be altered in HCC. A recent study showed that suppression of GLUT-1 expression, using siRNA (small interfering RNA) could significantly reduce tumorigenesis in HCC cell lines, suggesting that GLUT-1 may be a therapeutic target for this highly aggressive tumor. Thus, this project aims to evaluate the anticancer effect of quercetin, a possible inhibitor of GLUT-1, in a human HCC cell line HepG2, as well as check the effect of theis compound on 18F-FDG (a glucose radiolabelled analogue) uptake in this cell line. These results shown that quercetin have anti-proliferative effect on HCC cell line studied. This compound also have shown ability to decrease the 18F-FDG uptake. However, using flow cytometry it was found that HepG2 cells remain viable after treatment with quercetin, and this compound doesn’t inhibit the GLUT-1 protein expression. These results indicate that quercetin inhibits the GLUT-1 function, but doesn’t inhibit the expression of this transporter.Keywords: Quercetin, Hepatocellular Carcinoma, GLUT-1 O Carcinoma Hepatocelular (CHC) é um dos cancros mais letais, com uma crescente incidência em diversas regiões por todo o mundo. Sem tratamento específico, o prognóstico é muito pobre e a sobrevida diminuta. A terapia mais eficaz consiste no transplante hepático e na ressecção cirúrgica, no entanto, e uma vez que apenas 15% dos doentes são candidatos a tratamento cirúrgico, torna-se urgente a procura de novas opções terapêuticas para este tipo de tumor. Alguns estudos demonstraram que a expressão do transportador de glucose-1 (GLUT-1) pode estar alterada neste tipo de tumor. Um estudo recente demonstrou que a supressão da expressão de GLUT-1, recorrendo a siRNA (small interfering RNA) conseguiu reduzir significativamente a tumorigénese em culturas celulares de CHC, sugerindo que o GLUT-1 pode ser um alvo terapêutico para este tipo de tumor altamente agressivo. Assim, o objectivo deste trabalho experimental foi avaliar o efeito anti-cancerígeno da quercetina, um possível inibidor do GLUT-1, numa linha celular humana de CHC (HepG2, ATCC), assim como avaliar o seu efeito na captação de 18F-FDG, um análogo da glucose radiomarcado com Flúor-18. Com os resultados obtidos verificou-se que a quercetina possui a capacidade de inibir a proliferação da linha celular em estudo e, para além disso, parece ter influência na captação de 18F-FDG já que conseguiu diminuir a percentagem de captação do radiofármaco nesta linha celular. No entanto, através da técnica de citometria de fluxo verificou-se que as células permanecem viáveis, e que este composto não inibe a expressão proteica do GLUT-1. Estes resultados indicam que a quercetina inibe este transportador de glucose quanto à função, mas não quanto à expressão. Palavras-chave: Quercetina, Carcinoma Hepatocelular, GLUT-1

Beyond the limits of oxygen: effects of hypoxia in a hormone-independent prostate cancer cell line

Prostate cancer (PCa) has a high incidence worldwide. One of the major causes of PCa resistance is intratumoral hypoxia. In solid tumors, hypoxia is strongly associated with malignant progression and resistance to therapy, which is an indicator of poor prognosis. The antiproliferative effect and induced death caused by doxorubicin, epirubicin, cisplatin, and flutamide in a hormone-independent PCa cell line will be evaluated. The hypoxia effect on drug resistance to these drugs, as well as cell proliferation and migration, will be also analyzed. All drugs induced an antiproliferative effect and also cell death in the cell line under study. Hypoxia made the cells more resistant to all drugs. Moreover, our results reveal that long time cell exposure to hypoxia decreases cellular proliferation and migration. Hypoxia can influence cellular resistance, proliferation, and migration. This study shows that hypoxia may be a key factor in the regulation of PCa.info:eu-repo/semantics/publishedVersio