Silvia Frede

Integrated survey on toxic effects of lindane on neotropical fish: Corydoras paleatus and Jenynsia multidentata.

We report the effect of lindane on fish experimentally exposed to lindane. Sublethal toxicity was assessed through (a) changes in histopathology; (b) the activity of GST in different organs; and (c) bioaccumulation in exposed fish. We present a survey on toxic effects of lindane at these three levels, proposing a sequence of dose-dependent effects. Physiological damage was reversible at lowest doses, but severe at the highest, including damage consistent with fibrosis in liver and karyolitic nucleus in brain of both studied species. Exposure of Jenynsia multidentata above 6 microg L(-1) caused activation a GST in liver and gills, followed by inhibition at 75 microg L(-1). Interestingly, the bioaccumulation rate was suddenly increased when GST was inhibited. Corydoras paleatus exposed to 6.0 microg L(-1) lindane did not present significant changes in GST activity; however, enzymatic inhibition was observed above 25 microg L(-1). The bioaccumulation rate in C. paleatus remained constant throughout the experiments. All in all, these results evidence that C. paleatus is more sensitive to lindane than J. multidentata.

Extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMPs) as regulators of tumor–host interaction in a spontaneous metastasis model in rats

EMMPRIN has a role in invasion and metastasis through the induction of MMPs and the consequent modulation of cell-substrate and cell–cell adhesion processes. The present study evaluates the expression of EMMPRIN protein and MMP-2/9 activity in tumor and parenchymal cells in a spontaneous metastasis model in rats. Moreover, we explore the regulation of EMMPRIN and MMP-9 by tumor-epithelial cell interactions in vitro. By zymography, we observed an increased proMMP-9 expression in both metastasized liver and spleen samples from tumor bearing rats. Immunohistochemical studies showed EMMPRIN-positive tumor cells in tumor biopsies as well as in spleen and liver samples from tumor bearing rats. Interestingly, a significant increase in EMMPRIN expression in hepatic cells was also detected. The regulation of EMMPRIN expression in tumor and liver cells in response to tumor–host interaction was investigated in vitro through a tumor cell line culture on extracellular matrix (ECM) molecules or in co-culture with normal rat liver cells (BRL3A cells). No significant changes in EMMPRIN expression were detected in tumor cells cultured on ECM molecules. On the other hand, EMMPRIN protein and MMP-9 mRNA expression were induced in BRL3A cells. The increase in EMMPRIN expression in BRL3A cells was inhibited by an anti-EMMPRIN antibody. These results reinforce the main role of EMMPRIN mediating tumor–host interactions that may evolve new opportunities for therapeutic interventions.

Decreased expression of intercellular adhesion molecule-1 (ICAM-1) and urokinase-type plasminogen activator receptor (uPAR) is associated with tumor cell spreading in vivo

The development of an effective antitumor immune response to control tumor growth is influenced by the tumor cell itself and/or by the tumor microenvironment. Tumor invasion and tumor cell spreading require a finely tuned regulation of the formation and loosening of adhesive contacts of tumor cells with the extracellular matrix (ECM). In our laboratory, a rat tumor cell line derived from a spontaneous rat sarcoma revealed, by flow cytometry, a high frequency of intercellular adhesion molecule-1 (ICAM-1, 70.1 ± 8.7%) and urokinase-type plaminogen activator receptor (uPAR, 51.2 ± 5.2%) positive cells, while a weak expression of MHC class II (IA, 2.2±0.2% and IE, 17.4±3.7%) and B7 (12.1±2.2%) antigens was detected. In our tumor experimental model, after implantation of tumor cells, visible tumor masses were present at days 5–7 with a relatively fast tumor growth until day 15 (progressive phase) followed by a suppression of the tumor growth (regressive phase). Here we present data that correlates a significant decrease in the frequency of ICAM-1 and uPAR expressing tumor cells with the appearance of tumor cells in sites distant from that of the primary tumor. In addition we describe the development of a cellular immune response which controls the tumor progression and is associated with an increase in the expression of major histocompatibility complex (MHC) class II IA antigen during tumor development. The histological examination at tumor progressive and regressive time points revealed the relevant presence of polymorphonuclear neutrophils (PMNs) evidencing colliquative necrosis in tumor growth areas. Taken together, these results support the idea that the balance between adhesive interactions, proteolytic activity and tumorigenicity may lead to a tumor invasive phenotype.

Vascular endothelium express CS-1 fibronectin in allergic contact dermatitis

Background: Allergic contact dermatitis (ACD) is a common human dermatosis in which not all the mechanisms involved in its pathogenesis have been elucidated.