Histology and histopathology Vol.22, nº 4 (2007)
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- PublicationOpen AccessNonsteroidal anti-inflammatory drugs and oxidative stress in cancer cells(Murcia : F. Hernández, 2007) Adachi, M.; Sakamoto, H.; Kawamura, R.; Wang, W.; Imai, K.; Shinomura, Y.Nonsteroidal antiinflammatory drugs (NSAIDs) induce apoptosis in a variety of cancer cells, including those of colon, prostate, breast and leukemia. In addition, the classical NSAIDs sulindac and aspirin are promising chemopreventive agents against colon cancer. NSAIDs inhibit cyclooxygenases (COX) preventing the formation of prostaglandins, prostacyclin and thromboxane. NSAIDs also exert other biological effects, including generation of reactive oxygen species (ROS) and inhibition of NF-kB-mediated signals. Despite many suggested mechanisms for their anticancer effects, it remains uncertain how they induce cell cycle arrest and apoptosis in cancer cells. Furthermore, there is little information on the selectivity of NSAIDs-mediated anticancer effects, although this is one of the most important issues in cancer therapy. Increased understanding of the biological basis for the anticancer activity of NSAIDs and their selectivity is essential for future therapeutic advances. In this paper, we propose that increased ROS generation is one of the key mechanisms for NSAIDs-mediated anticancer effects on various cancer cells.
- PublicationOpen AccessShort term regulation of hepatocyte glutathione content by hepatic sinusoidal cells in co-culture(Murcia : F. Hernández, 2007) Catalá-Rodríguez, M.; Pagani, R.; Portolés, M.T.antioxidant mechanisms may constitute the primary mechanisms of a number of pathologies. The liver plays a central role in this balance: parenchymal hepatic cells contain and export especially high levels of the antioxidant glutathione and activated Kupffer cells release inflammation mediators and reactive oxygen species. There is growing evidence of a paracrine regulation of hepatic function by means of a fluent intercellular communication which must still be fully elucidated, especially in basal conditions. In vivo models provide often too complex results but, in vitro, tissue interactions are left aside; therefore it is important to find new experimental models to address cell communication studies. Here we propose the complementary use of three models to study liver glutathione system regulation in basal conditions: pure parenchymal cells primary cultures, addition of sinusoidal cell conditioned media to parenchymal cells and co-culture of sinusoidal cells using porous membranes. We have also developed a high specifity immunofluorescent method for the complete characterization of sinusoidal cell populations by flow cytometry and confocal microscopy. Our results show that Kupffer cells possess higher levels of reactive oxygen species than sinusoidal endothelial cells even in basal conditions. We also report that the glutathione content of hepatic parenchymal cells in basal conditions and suggest the existence of a paracrine circuit in the management of liver oxidative stress.
- PublicationOpen AccessGel-forming mucins. Notions from in vitro studies(Murcia : F. Hernández, 2007) Perez-Vilar, J.; Mabolo, R.Mucus secretions form a protective barrier in the mucosa of the auditory, gastrointestinal, respiratory, and urogenital systems, and the conjunctiva in the eyes. A family of glycoproteins known as gel forming mucins is the major component of the mucus. Gel-forming mucins are among the largest and most complex proteins known. Their polypeptide chains comprise thousands of amino acid residues organized into different domains with diverse post-translational modifications, including O- and N-glycosylation, sulfation, proteolysis, and likely C-mannosylation. Moreover, these glycoproteins form disulfide-linked oligomers/multimers with molecular weights in the millions. Molecular polydispersity in terms of length, carbohydrate content and composition, is an invariable feature of purified mucins. This structural complexity makes it technically very difficult to study mucin biochemical and physical properties. It is not surprising, therefore, that our knowledge on mucin structure, biosynthesis and function still is incomplete. During the last decade, the use of recombinant mucins has allowed researchers to study the biochemical properties of protein domains, peptide motifs and amino acid residues common to all gel-forming mucins, and to propose specific roles for them. We review here the relative impact that these in vitro studies have had for our current understanding of two of the most important features of these macromolecules: formation of disulfide linked oligomers and mucin intragranular packaging.
- PublicationOpen AccessPrimary mammary osteogenic sarcoma(Murcia : F. Hernández, 2007) Khaldi, L.; Athanasiou, E.T.; Hadjitheofilou, C.Th.A 78 year-old female patient underwent a total mastectomy with axillary lymph node dissection for a primary breast osteosarcoma. Microscopically the tumor was identical to grade II skeletal osteosarcoma. Immunohistochemically no reactivity was detected, either for the epithelial markers EMA, AE1/AE3, CK8, 18, 19, or for HER-2/neu, estrogen and progesterone receptors, as well as fluorescent IN SITU hybridization for HER-2/neu. The diagnosis of this tumor fulfills certain clinicopathological criteria. Mammary osteosarcoma is usually developed in phyllodes tumors or carcinosarcomas of the breast as a result of metaplasia of the epithelial component. This rare tumor of the breast is occasionally associated with prior radiation therapy or well documented trauma. Mammary osteosarcoma is a biologically aggressive neoplasm with a 38% five-year survival rate. Surgical resection is the most effective therapy to date. Adjuvant treatment -chemotherapy or radiotherapy- has shown no clear benefit. An extensive review of the literature is also presented.
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