FABIO LUIZ NAVARRO MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
3 resultados
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- Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase(2012) FERREIRA, Adilson Kleber; MENEGUELO, Renato; MARQUES, Fabio Luiz Navarro; RADIN, Adriano; FILHO, Otaviano Mendonca R.; CLARO NETO, Salvador; CHIERICE, Gilberto Orivaldo; MARIA, Durvanei AugustoPhosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes, especially phosphatidylcholine. We recently reported that synthetic Pho-s has potent effects on a wide variety of tumor cells. To determine if Pho-s has a potential antitumor activity, in this study we evaluated the activity of Pho-s against the B16-F10 melanoma both in vitro and in mice bearing a dorsal tumor. The treatment of B16F10 cells with Pho-s resulted in a dose-dependent inhibition of cell proliferation. At low concentrations, this activity appears to be involved in the arrest of the cell cycle at G2/M, while at high concentrations Pho-s induces apoptosis. In accordance with these results, the loss of mitochondrial potential and increased caspase-3 activity suggest that Phos has dual antitumor effects; i.e. it induces apoptosis at high concentrations and modulates the cell cycle at lower concentrations. In vivo, we evaluated the effect of Pho-s in mice bearing B16-F10 melanoma. The results show that Pho-s reduces the tumoral volume increasing survival rate. Furthermore, the tumor doubling time and tumor delays were substantially reduced when compared with untreated mice. Histological analyses reveal that Pho-s induces changes in cell morphology, typical characteristics of apoptosis, in addition the large areas of necrosis correlating with a reduction of tumor size. The results presented here support the hypothesis that Pho-s has antitumor effects by the induction of apoptosis as well as the inhibition of cell proliferation by arrest at G2/M. Thus, Pho-s can be regarded as a promising agent for the treatment of melanoma.
- Comparison of Clamping Modalities in a Rabbit Model of Normothermic Renal Ischemia(2011) FORMIGA, Cipriano C.; MITRE, Anuar I.; CASTILHO, Lisias N.; BUCHPIGUEL, Carlos Alberto; MARQUES, Fabio L. N.; RADIN, Adriano; SROUGI, MiguelPurpose: The objective of this study was to investigate the patterns of renal function recovery with different renal vessel clamping modalities during a prolonged warm ischemia (WI) condition in an experimental two-kidney rabbit model. Materials and Methods: Twenty-eight rabbits were randomly clustered into four groups and underwent laparotomy with different types of renal pedicle clamping. Group 1 (n = 4) was sham-operated. Group 2 (n = 8) underwent 80 minutes of WI with artery only clamping. Group 3 (n = 8) underwent arteriovenous clamping for 80 minutes, and group 4 (n = 8) received an arteriovenous clamping for 80 minutes with 10-second declamping periods every 20 minutes. Serum levels of creatinine (SCr) were recorded preoperatively and on postoperative days (PODs) 1, 3, and 7. Renal function was evaluated by (99m)technetium-mercaptoacetyltriglycine scintigraphy. Afterward, the animals were euthanized, and the kidneys were harvested and evaluated microscopically. Results: Renal function completely recuperated on POD 7 in the groups that underwent artery only and ateriovenous intermittent clamping, and both of these methods were superior to ateriovenous clamping (P < 0.001). SCr showed a similar variation in all the clamping groups and did not demonstrate statistical differences among the groups. Histopathologic changes were similar among the ischemic groups. Conclusion: The less deleterious clamping modalities in this experimental model were the artery only and intermittent en bloc clamping methods.
conferenceObject Preparation of new [[Tc-99m](MeOBzEN)(H2O)(CO)(3)](+) complexes and in vitro evaluation as potential tumor diagnostic radiopharmaceutical(2013) RADIN, Adriano; MARQUES, Fabio Luiz Navarro; NAGAI, Maria Aparecida; BUCHPIGUEL, Carlos AlbertoObjectives: In the present study we sought to prepare and evaluate the uptake of [[99m Tc](MeOBzEN)(H2O)(CO)3] + in breast cancer cells, MDA-MB-231, in suspension or in monolayer and to compare the results with [[99m Tc](MIBI)6] +, and a well-established radiopharmaceutical for breast cancer detection. Methods: The ligand L1: N-(4-methoxybenzil)ethylenediamine and L2: N,N ́-(di-4-methoxybenzil)ethylenediamine was synthesized by reaction between ethylenediamine and 4-methoxybenzaldehyde, followed by NaBH4 reduction. [[99m Tc](L1)(H2O)(CO)3] + and [[99m Tc](L2)(H2O)(CO)3] + (figure 1) were obtained by CO/NaBH4 standard reaction procedure, and quality controls (LogP, electrophoresis, HPLC) were performed. MDA-MB-23 was growth in RPMI-1640 culture media with 10% fetal bovine serum and part was allowed in suspension and other part was adhered in 12-well plates. Technetium radiopharmaceuticals were added to cells in suspension or monolayer and incubated at 37°C. At 10, 30 and 60 minutes, culture medium and cells were separated by centrifugation and activity was measured in a well counter. Figure 1. Structure of [[99m Tc](MeOBzEN)(H2O)(CO)3] + complex and uptake behavior in MDA-MB-231 cell culture (sus = suspension; mon = monolayer) Results: Ligands were obtained in 68% yield and technetium complex with overall yield high of 90% and were stable at least for four hours, LogP values were 0.266 ± 0.075 and 0.718 ± 0.018, for complex L1 and L2, against 1.330 ± 0.127 for MIBI. Complexes charge was inconclusive, once it depends of electrolitic system. Uptakes of both new complexes were high as compared to [[99m Tc](MIBI)6] +, and the value depends if cells are in suspension or adhered, as show in figure 1. Conclusions: The new [[99mTc](MeOBzEN)(H2O)(CO)3]+ were obtained in high yields and uptake in MDA-MD-231 culture cell is higher than [[99m Tc](MIBI)6]+, suggesting a potential use as radiopharmaceutical. However, it's not clear difference between uptake in suspension and adhered cell and further investigation are been undertaken, including animal imaging.