797 resultados para Rodent.
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Pós-graduação em Biologia Geral e Aplicada - IBB
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Pós-graduação em Patologia - FMB
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Objective: Local invasion of bone is a frequent complication of oral squamous cell carcinoma (OSCC). Development of these osteolytic lesions is mediated by osteoclasts. Receptor activation of NF-kappa B ligand (RANKL) signaling, counteracted by osteoprotegerin (OPG), regulates osteoclastogenesis. Previous studies in rodent models have demonstrated that inhibition of RANKL decreases tumor growth and lesions within bone. However, the contributory role of OSCC cells to this disease process has yet to be defined.Methods: RANKL expression was assessed in a panel of OSCC cell lines by qPCR, flow cytometry, and ELISA. Induction of osteoclastogenesis was assessed by co-culture with macrophages or with OSCC-derived conditioned medium. In an animal model of bone invasion, nude mice were injected intratibially with UMSCC-11B cells expressing a RANKL luciferase promoter to detect tumor-derived RANKL activity. Osteolytic lesions were analyzed by X-ray, micro-CT, and histological methods. RANKL expression was assessed in human OSCC tissues by immunohistochemistry.Results: We demonstrated that OSCCs express varied levels of all RANKL isoforms, both membrane-bound and soluble RANKL. Both co-culture and treatment with OSCC-conditioned media induced osteoclastogenesis. In mice, we demonstrated human RANKL promoter activity during bone invasion. Over the course of the experiment, animals suffered osteolytic lesions as RANKL-driven luciferase expression increased with time. After 8 weeks, human-derived RANKL was detected in areas of bone resorption by immunohistochemistry. Similar epithelial RANKL expression was detected in human OSCC tissues.Conclusion: These data demonstrate the ability of OSCCs to produce RANKL, directly altering the tumor microenvironment to increase osteoclastogenesis and mediate local bone invasion. (C) 2012 Elsevier Ltd. All rights reserved.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Background levels of exocyclic DNA adducts have been detected in rodent and human tissues. Several studies have focused on bifunctional electrophiles generated from lipid peroxidation as one of the endogenous sources of these lesions. We have previously shown that the reaction of 2'-deoxyguanosine (dGuo) with trans,trans-2,4-decadienal (DDE), a highly cytotoxic aldehyde generated as a product of lipid peroxidation in cell membranes, results in the formation of a number of different base derivatives. Three of these derivatives have been fully characterized as 1,N-2-etheno-2'-deoxyguanosine adducts. In the present work, four additional adducts, designated A3-A6, were isolated from in vitro reactions by reversed-phase HPLC and fully characterized on the basis of spectroscopic measurements. Adducts A3-A6 are four diastereoisomeric 1,N-2-hydroxyethano-2'-deoxyguanosine derivatives possessing a carbon side chain with a double bond and a hydroxyl group. The systematic name of these adducts is 6-hydroxy3-(2'-deoxy-beta-D-erythro-pentafuranosyl)-7-((E)-1-hydroxy-oct-2-enyl)-3,5,6,7-tetrahydro-imidazo- [1,2-a]purin-9-one. The proposed reaction mechanism yielding adducts A3-A6 involves DDE epoxidation at C2, followed by nucleophilic addition of the exocyclic amino group of dGuo to the C1 of the aldehyde and cyclization, via nucleophilic attack, on the C2 epoxy group by N-1. The formation of adducts A1-A6 has been investigated in acidic, neutral, and basic pH in the presence of H2O2 or tent-butyl hydroperoxide. Neutral conditions, in the presence of H2O2, have favored the formation of adducts A1 and A2, with minor amounts of A3-A6, which were prevalent under basic conditions. These data indicate that DDE can modify DNA bases through different oxidative pathways involving its two double bonds. It is important to structurally characterize DNA base derivatives induced by alpha,beta-unsaturated aldehydes so that the genotoxic risks associated with the lipid peroxidation process can be assessed.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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The lunulae, ossification of the meniscus, are found in several species of rodents. Some studies suggest that the lunulae may be anatomical features, because there are not any pathological findings in microscopy. The objective of this study was to investigate the presence of lunulae in capybara knees, the world's largest rodent, by simple tomographic scans and three-dimensional reconstruction. For this purpose, we used two adult capybaras, in which both knees were evaluated. The lunulae were visualized with three-dimensional images, and revealed a total of two cranially. With the presence of lunulae confirmed, the capybara may be included in the group of rodents that have this structural feature, which can also contribute to the distinction between pathological processes and normal anatomic structures on imaging tests.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Pós-graduação em Cirurgia Veterinária - FCAV
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Cancer is a multistep process that begins with the transformation of normal epithelial cells and continues with tumor growth, stromal invasion and metastasis. The remodeling of the peritumoral environment is decisive for the onset of tumor invasiveness. This event is dependent on epithelial–stromal interactions, degradation of extracellular matrix components and reorganization of fibrillar components. Our research group has studied in a new proposed rodent model the participation of cellular and molecular components in the prostate microenvironment that contributes to cancer progression. Our group adopted the gerbil Meriones unguiculatus as an alternative experimental model for prostate cancer study. This model has presented significant responses to hormonal treatments and to development of spontaneous and induced neoplasias. The data obtained indicate reorganization of type I collagen fibers and reticular fibers, synthesis of new components such as tenascin and proteoglycans, degradation of basement membrane components and elastic fibers and increased expression of metalloproteinases. Fibroblasts that border the region, apparently participate in the stromal reaction. The roles of each of these events, as well as some signaling molecules, participants of neoplastic progression and factors that promote genetic reprogramming during epithelial–stromal transition are also discussed.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Pós-graduação em Biologia Geral e Aplicada - IBB