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.
- Analgesic Effect of Crotalphine in a New Model of Rat Bone Cancer Pain(2012) CURY, Yara; GUTIERREZ, Vanessa P.; BRIGATTE, Patricia; ZAMBELLI, Vanessa O.; PICOLO, Gisele; CARVALHO, Juliana S. de; MARQUES, FabioBackground: Crotalphine (CRP), a peptide first identified and isolated from the South American rattlesnake Crotalus durissus terrificus venom, induces analgesic effect mediated by opioid receptors. The aim of this work is to characterize the analgesic effect of crotalphine in a new model of bone cancer pain induced by inoculation of Walker 256 tumor cells into the rat femoral cavity. Methods: Bone tumor implantation and metastasis were determined by histopathological analysis. Bone metabolic alterations were determined by scintigraphy, using 99mTc-MDP. Femoral images were obtained before and 7, 14 and 21 days after tumor cell injection. Bone cancer pain was characterized by the presence of hyperalgesia (rat paw pressure test) and allodynia (von Frey filaments). Results and Discussion: Photomicrographs analyzed 21 days after injection of tumor cells, demonstrated the presence of tumor cells in the femur of the animals. Incorporation of 99mTc-MDP was significant 7, 14 and 21 days, suggesting the development of tumor on the femoral cavity. Histopathological analysis demonstrated the presence of tumor cells in the lung and spleen, but not in the liver and kidneys of the rats. The results indicate that cells inoculated into femoral bone marrow can spread to some organs, including lymphoid organs. Hyperalgesia and allodynia were detected on days 1, 3, 7, 14 and 21 after cell inoculation. Interestingly, the paw withdrawal threshold in the von Frey test was reduced not only in the ipsilateral hind paw but also in the contralateral one, demonstrating the existence of bilateral allodynia (mirror-image pain). To evaluate the involvement of prostanoids in these nociceptive phenomena, Indomethacin, a cyclooxygenase inhibitor, was administered 3,7,14 and 21 days after tumor cell injection. Indomethacin only partially inhibited hyperalgesia and allodynia induced by bone cancer, indicating the involvement of prostanoids in bone cancer pain. The contribution of prostanoids is more significant within the first 3 days after cell injection. CRP (8μg/kg) administered on day 21, blocked hyperalgesia, allodynia and mirror image pain. The analgesic effect was detected up to 2 days after peptide administration and was blocked by κ-opioid receptor antagonist and partially inhibited by δ-opioid antagonists, indicating the involvement of opioid receptors. Morphine only partially inhibited allodynia and hyperalgesia. Conclusions: Results indicate that injection of tumor cells causes bone cancer and pain. CRP induces a potent and long-lasting antinociception in this model, with higher efficacy as compared to standard analgesic drugs.
bookPart Radiofarmácia(2012) FERREIRA, Roberta Morgado; MARQUES, Fabio Luiz Navarro