Mucins are high-molecular-mass glycoproteins with high carbohydrate content and marked heterogeneity both in the apoprotein and in the oligosaccharide side chains. Mucin genes are expressed in a regulated manner, namely in the human stomach. The first aim of the present study was to characterise the expression of mucins and mucin-associated carbohydrate antigens in seven gastric carcinoma cell lines, and to compare their expression profiles with those of normal gastric tissues and human gastric carcinomas. Secondly, we aimed to see whether or not there is an association between the expression of mucins and mucin-associated carbohydrate antigens. Our results show that mucin expression in gastric carcinoma cell lines: (a) follows in part the mucin expression profile of normal gastric mucosa and gastric carcinomas with wide expression of MUC1 and MUC5AC; (b) parallels the aberrant pattern of mucin expression observed in human gastric carcinomas with occasional expression of MUC2, MUC3, MUC4 and MUC5B; (c) does not include, at least in our series, the expression of MUC6 mucin; and (d) follows in part the differentiation pattern of the carcinomas from which the cell lines originated, keeping S-Tn expression in cell lines derived from glandular carcinomas. Our results further demonstrate that there is no apparent relationship between the mucin core proteins and the simple mucin-type or Lewis carbohydrate antigens.
We have previously analyzed the expression of MUC1, underglycosylated MUC1, MUC2, MUC5AC, Tn, sialyl Tn, Lewis(a), sialyl Lewis(a), Lewis(x), and sialyl Lewis(x) in papillary thyroid carcinoma (PTC). The present study of 26 thoroughly scrutinized cases of PTC with "good" or "bad outcome" and a minimum of 10 yr of follow-up (or until death of the patients) was undertaken in an attempt to find if there is any relationship between the expression of the aforementioned antigens and the clinicopathologic and morphologic features of the cases and to evaluate the prognostic significance of the immunohistochemical pattern of PTC. We observed a significant or suggestive association between the expression of MUC1, underglycosylated MUC1, MUC2, Lewis(a), and Lewis(x) and the older age of the patients, and a suggestive association between Lewis(x) expression and lymph node metastasis and venous invasion. There was also a strong correlation between extrathyroid invasion, lymph node metastasis, intrathyroid dissemination, and venous invasion and patients outcome thus demonstrating, once more, the prominence of the classic clinicopathologic and morphologic features in the prognostic evaluation of PTC. The immunohistochemical study of mucins, simple mucin antigens, and histo-blood group antigens did not provide additional prognostic information, but for the significant association of Lewis(x) immunoreactivity to the group of "bad outcome."
We studied the immunohistochemical expression of mucins (MUC1, underglycosylated MUC1, MUC2, MUC5AC, and MUC6), simple mucin antigens (Tn, sialyl Tn, and T), and histo-blood group antigens (type 1-Lewis(a) and sialyl Lewis(a) type 2-Lewis(x) and sialyl Lewis(x)) in a series of 26 papillary thyroid carcinomas (PTC), 6 follicular carcinomas, and a control group of 32 cases of "normal" thyroid parenchyma adjacent to the tumors. PTC expressed more often, more intensively, and more extensively every antigen but MUC6, which was not observed in any case. The expression of MUC5AC was also extremely rare. MUC1 expression was related to the expression of underglycosylated MUC1, MUC2, Lewis(a), and sialyl Lewis(a). A trend toward an association between the expression of MUC1 and that of type 2 histo-blood group antigens was also observed. Whenever there was a dissociation between the expression of type 1 and type 2 Lewis antigens, MUC1 appeared closely related to type 1 and independent from type 2 histo-blood group antigens. We conclude that MUC1 plays a pivotal, though not exclusive, role in the glycosylation features of well differentiated thyroid carcinomas. Despite the prominent expression of mucins and carbohydrate antigens in PTC, no significant differences were observed between PTC and follicular carcinoma thus ruling out the possibility of using the aforementioned antigens as diagnostic markers per se.
Neospora caninum is an obligate intracellular protozoan responsible for abortion and stillbirths in cattle. We previously developed a mucosal vaccination approach using N. caninum membrane proteins and CpG adjuvant that conferred long-term protection against neosporosis in mice. Here, we have extended this approach by alternatively using the carbomer-based adjuvant Carbigen™ in the immunizing preparation. Immunized mice presented higher proportions and numbers of memory CD4+ and CD8+ T cells. Stimulation of spleen, lungs and liver leukocytes with parasite antigens induced a marked production of IFN-γ and IL-17A and, less markedly, IL-4. This balanced response was also evident in that both parasite-specific IgG1 and IgG2c were raised by immunization, together with specific intestinal IgA. Upon intraperitoneal infection with N. caninum, immunized mice presented lower parasitic burdens than sham-immunized controls. In the infected immunized mice, memory CD4+ T cells predominantly expressed T-bet and RORγt, and CD8+ T cells expressing T-bet were found increased. While spleen, lungs and liver leukocytes of both immunized and sham-immunized infected animals produced high amounts of IFN-γ, only the cells from immunized mice responded with high IL-17A production. Since in cattle both IFN-γ and IL-17A have been associated with protective mechanisms against N. caninum infection, the elicited cytokine profile obtained using CarbigenTM as adjuvant indicates that it could be worth exploring for bovine neosporosis vaccination.
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