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Background and Aim: Hepatoid gland neoplasms (HGNs) constitute one of the most common cutaneous tumors that arise from perianal glands in dogs and are clinically characterized by rapid growth. Cyclooxygenase-2 (COX-2), the inducible form of the enzyme, is associated with several hallmarks of tumorigenesis. Its expression has been confirmed in several human and animal neoplastic tissues, but there are no reports in hepatoid gland tissues. Therefore, this study aimed to investigate COX-2 immunoexpression in canine HGNs, compare the expression among groups of normal hepatoid glands, hepatoid gland adenomas (HGAs), hepatoid gland epitheliomas (HGEs), and hepatoid gland carcinomas (HGCs), and assess the association of the COX-2 expression with clinicopathological features. Materials and Methods: Sixty-one formalin-fixed paraffin-embedded canine hepatoid gland tissues (20 samples of HGAs, 16 of HGEs, 15 of HGCs, and 10 of normal hepatoid glands) were analyzed for COX-2 expression using immunohistochemistry with scoring for percentage positivity and intensity. Multiple comparisons of COX-2 expression among normal and neoplastic hepatoid glands and the associations between COX-2 expression and clinicopathological features were analyzed. Results: Cyclooxygenase-2 expression was not detected in 60% of normal hepatoid glands and 25% of HGAs. Seventy-five percent of HGAs had a weak expression, while 43.7% and 56.3% of HGEs showed weak and moderate expression, respectively. The expression of HGCs ranged from weak (13.3%) to moderate (33.3%) and strong (53.3%). The immunoreactivity score of COX-2 labeling was significantly different among the normal and neoplastic hepatoid glands (p < 0.0001). The highest score was observed in the HGCs. Only in HGCs, the strong COX-2 expression was significantly associated with some clinicopathological features, including tissue invasion (p = 0.007) and necrosis (p = 0.029). Conclusion: These results suggest that COX-2 may play a role in the modulation of neoplastic cell growth. These preliminary data lead to further investigation on the potential of COX-2 expression as a prognostic indicator and COX-2 inhibitors for canine HGCs treatment.
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BACKGROUND: To date, human peripheral blood mononuclear cells (PBMCs) have been used mainly in immune stimulation assays and the interpretation of data can be influenced by the previous immunological history of donors and cross reactivity with other infectious agents. Resolving these limitations requires an alternative in vitro model to uncover the primary response profiles. METHODS: A novel in vitro model of mononuclear cells (MNCs) generated from haematopoietic stem cells (HSCs) was developed and these cells were then co-cultured with various antigens from Plasmodium falciparum and Plasmodium vivax to investigate the response of naïve immune cells to malaria antigens by flow cytometry. RESULTS: In vitro stimulation of naïve lymphocytes showed that CD4+ and CD8+ T lymphocytes were significantly reduced (P < 0.01) by exposure to lysates of infected erythrocytes or intact erythrocytes infected with P. falciparum. The depletion was associated with the expression of CD95 (Fas receptor) on the surface of T lymphocytes. Maturation of T lymphocytes was affected differently, showing elevated CD3+CD4+CD8+ and CD3+CD4-CD8- T lymphocytes after stimulation with cell lysates of P. falciparum and P. vivax, respectively. In addition, antigen presenting monocytes and dendritic cells derived from haematopoietic stem cells showed impaired HLA-DR expression as a consequence of exposure to different species of malaria parasites. CONCLUSION: These results suggest that naïve mononuclear cells differentiated in vitro from HSCs could provide a valid model for the assessment of immunity. P. falciparum and P. vivax malaria parasites could modulate various populations of immune cells starting from newly differentiated mononuclear cells.