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Heme oxygenase-1 (HO-1) is known as a stress-inducible protein. The presesnt study is designed to investigate the relationship between HO-1 expression levels and clinical features of tongue cancer by using HO-1 responsiveness to stress as a clinical indicator. One hundred and twelve biopsy samples from tongue squamous cell

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Objective: Seprase is an integral membrane serine proteinase with gelatinase activity that may be involved in cancer invasion and metastasis. However, the pathophysiologic significance of its expression in gastric cancer tissue has not been fully elucidated. Methods: Seprase expression and distribution in gastric cancer specimens obtained from 133 patients were examined by immunohistochemistry and immunoblotting. Results: Immunohistochemistry showed that in intestinal-type cancer, which includes well and moderately differentiated adenocarcinoma, seprase immunoreactivity was mainly recognized in the moderately differentiated cells and not in the well differentiated cells. In the diffuse type, which includes poorly differentiated adenocarcinoma and signet ring cell carcinoma, seprase immunoreactivity was seen mainly in cells with poor cell-to-cell junctions. The reactive pattern in the cells was different between moderately differentiated adenocarcinoma and diffuse-type carcinoma. Besides the cytoplasm, the cell membrane also apparently reacted in the former, while only the cytoplasm reacted diffusely in the latter. Seprase immunoreactivity was also recognized in endothelial cells and stromal cells especially adjacent to tumor nests. The immunoreactivity of the stromal cells was more abundant in the intestinal type than in the diffuse type, and these stromal expressions of seprase in the intestinal type correlated with the liver (13/13 = 100% of cases with metastases) or lymph node metastases (33/34 = 97% of cases with metastases). Immunoblotting showed that the levels of seprase protein were higher in intestinal-type cancer than in diffuse-type cancer. Conclusion: These results suggested that there is a difference in seprase expression between intestinal- and diffuse-type gastric cancer; this difference may reflect distinct biological features of these types of cancer.

Increased evidence has shown that endothelin‐1 (ET‐1) derived from the arterial cells is involved in the development of atherosclerosis. ET‐1 and ET receptors are upregulated in both human and experimental animal atherosclerotic lesions. Plasma ET‐1 levels are significantly elevated in hypercholestolemic subjects and cholesterol‐fed animals. We hypothesized that plasma lipoproteins such as LDL and HDL retained in the arterial wall can affect ET‐1 production and secretion, thereby sustaining vascular functions. Using a two‐chamber culture system, we have demonstrated that endothelial cells (ECs) show a polar secretion of ET‐1; the majority of ET‐1 are secreted toward the basal side of the vessels. Furthermore, we found that LDL enhances whereas HDL inhibits the ET‐1 secretion from ECs in a polarized pattern. In order to demonstrate ET receptor distribution in the lesion, we recently studied both human and apoE‐KO mice. Our study showed that there is an increased expression of ETB receptors in foamy macrophages in the lesions. More importantly, medial smooth muscle cells (SMCs) beneath the foam cell lesions exhibited a higher intensity of ETB receptor immunoreactivity than those located in foam cell‐free areas. In such an area, ET‐1 immunoreactivity is also increased. These results suggest that accumulation of foamy macrophages may modulate the shift of ET receptor subtypes from ETA to ETB in SMCs and an enhanced ET system mediated by ETB receptors may play a pivotal role in the progression of atherosclerosis. This notion has been further supported by a recent finding that administration of ET receptor antagonists resulted in a significant reduction of atherosclerosis in apoE‐KO mice.