Histology and histopathology Vol.22, nº12 (2007)
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- PublicationOpen AccessOxidative damage in age-related macular degeneration(Murcia: F. Hernández, 2007) Shen, J.K.; Dong, A.; Hackett, S.F.; Bell, W.R.; Green, W.R.; Campochiaro, P.A.Epidemiologic studies have suggested that elderly patients who consumed diets rich in antioxidants throughout their lives are less likely to be afflicted with age-related macular degeneration (AMD). This led to the Age-Related Eye Disease Study, which showed that supplements containing antioxidant vitamins and zinc reduce the risk of progression to severe stages of AMD. Despite these data that indirectly implicate oxidative damage in the pathogenesis of AMD, there has not been any direct demonstration of increased oxidative damage in the retinas of patients with AMD. In this study, we used biomarkers of oxidative damage in postmortem eyes from patients with AMD and comparably aged patients without AMD to directly assess for oxidative damage. Sections from 4 eyes with no pathologic features of AMD showed no immunofluorescent staining for markers of oxidative damage, while sections from 8 of 12 eyes with advanced geographic atrophy showed evidence of widespread oxidative damage in both posterior and anterior retina. Only 2 of 8 eyes with choroidal neovascularization and 2 of 16 eyes with diffuse drusen and no other signs of AMD showed evidence of oxidative damage. These data suggest that widespread oxidative damage occurs in the retina of some patients with AMD and is more likely to be seen in patients with advanced geographic atrophy. This does not rule out oxidative damage as a pathogenic mechanism in patients with CNV, but suggests that a subpopulation of patients with geographic atrophy may have a major deficiency in the oxidative defense system that puts the majority of cells in the retina at risk for oxidative damage.
- PublicationOpen AccessStandardization of an orthotopic mouse brain tumor model following transplantation of CT-2A astrocytoma cells(Murcia: F. Hernández, 2007) Martínez Murillo, R.; Martínez, A.Animal models of glial-derived neoplasms are needed to study the biological mechanisms of glioma tumorigenesis and those that sustain the disease state. With the aim to develop and characterize a suitable in vivo experimental mouse model for infiltrating astrocytoma, with predictable and reproducible growth patterns that recapitulate human astrocytoma, this study was undertaken to analyze the long-term course of a syngeneic orthotopically implanted CT-2A mouse astrocytoma in C57BL/6J mice. Intracranial injection of CT-2A cells into caudate-putamen resulted in development of an aggressive tumor showing typical features of human glioblastoma multiforme, sharing close histological, immunohistochemical, proliferative, and metabolic profiles. To simulate metastatic disease to the brain, CT-2A cells were injected through the internal carotid artery. Tumors identical to those obtained by intracranial injection were obtained. Finally, CT-2A cells were re-isolated from experimental brain tumors and transcranially re-injected into the caudate-putamen of healthy mice. These cells generated new tumors that were indistinguishable from the initial ones, suggesting in vivo self-renewal of tumor cells. Small-animal models are essential for testing novel biological therapies directed against relevant molecular targets. In a preliminary study, experimental CT-2A tumors were chronically treated with the small molecule 77427, a gastrin-releasing peptide (GRP) blocker compound that inhibits angiogenesis. Treated animals developed significantly smaller tumors than controls, suggesting an antitumor action for 77427 in glioblastomas. We conclude that the orthotopic CT-2A tumor model, as described herein, is appropriate to explore the mechanisms of glioma development and for preclinical trials of promising drugs.
- PublicationOpen AccessPrimary hepatic malignant fibrous histiocytoma: A case report and review of the literature(Murcia: F. Hernández, 2007) Ye, M-F.; Zheng, S.; Xu, J.H.; Chen, L-R.Primary malignant fibrous histiocytoma (MFH) of the liver remains extremely rare with only several cases having been reported in literature. We report a case of hepatic MFH in a 53-year-old man who presented with upper abdominal pain, and weight loss for one month. Ultrasound and computed tomography (CT) scan showed a large mass with fine tumor vessels over the left lobe of the liver. Histopathological findings indicated a mesenchymal tumor consisting of spindle cells in storiform pattern intermingled with histiocytelike cells and giant cells. Immunohistochemically, most tumor cells expressed vimentin, alpha-1 antichymotrypsin, alpha-1 antitrypsin and CD68. Morphological and immunohistochemical findings support that the tumor should be classified as a primary malignant fibrous histiocytoma. The literatures is briefly reviewed.
- PublicationOpen AccessNFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases(Murcia: F. Hernández, 2007) Sun, X-F.; Zhang, H.Nuclear factor-kB (NF-kB) is responsible for the expression by regulating many genes for immune response, cell adhesion, differentiation, proliferation, angiogenesis and apoptosis. The function of NF-kB is inhibited by binding to NF-kB inhibitor (IkB), and imbalance of NF-kB and IkB has been associated with development of many diseases, including tumours. In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn’s disease (CD), rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, giant cell arthritis, type 1 diabetes, multiple sclerosis, celiac disease, and Parkinson’s disease, as well as susceptibility of several cancers, such as oral squamous cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma, breast cancer and myeloma.
- PublicationOpen AccessActin cytoskeletal organization in human osteoblasts grown on different dental titanium implant surfaces(Murcia: F. Hernández, 2007) Salido, M.; Vilches, J.I.; Gutiérrez, J.L.; Vilches, J.The understanding of the cellular basis of osteoblastic cell-biomaterial interaction is crucial to the analysis of the mechanism of osseointegration. Cell adhesion is a complex process that is dependent on the cell types and on the surface microtopography and chemistry of the substrate. We have studied the role of microtopography in modulating cell adhesion, in vitro, using a human osteoblastic cell line for the assessment of actin cytoskeletal organization. Through application of CLSM combining reflection and fluorescence, 2D or 3D images of cytoskeleton were obtained. On smooth surfaces, Ti CP machined, predominantly planar bone cells with an axial ratio of 1.1 were randomly oriented, with stress fibers running in all directions, and thin filopodia. On TiCP Osseotite® surfaces the osteoblastic cells conformed to the irregular terrain of the sustrate with focal adhesion sites only established on the relative topographical peaks separated for a longer distance than in the machined surface, and defined wide lamellopodia and long filopodia, with enhanced expression of stress fibers, forming large clear focal contacts with the rough surface. The cytoskeletal organization of cells cultured on rough titanium supports an active role for the biomaterial surface in the events that govern osteoblastic cell adhesion. The results enforce the role of the rough sustrate surface in affecting osteoblastic cell adhesion and provide valuable information for the design of material surfaces that are required for the development of an appropriate osteogenic surface for osteoblastic anchorage, compared to machined surface, in dental implants.
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