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Claudins are involved in the formation of tight junctions in epithelial and endothelial cells. Claudins form a family of 24 members displaying organ- and tissue-specific patterns of expression. In the present study, we evaluated the specificity of the claudin-2 expression in various normal human tissues and gastrointestinal cancers by quantitative reverse transcriptase–polymerase chain reaction and immunohistochemistry. In 14 various normal tissues, claudin-2 mRNA was expressed in the kidney, liver, pancreas, stomach, and small intestine; the highest level of which was detected in the kidney. Colorectal cancers (CRCs) expressed claudin-2 mRNA at high levels. Immunohistochemical analysis of claudin-2 in 146 gastric cancers (GCs) and 99 CRCs demonstrated claudin-2 expression in 2.1% of GCs and 25.3% of CRCs, respectively. There was no obvious correlation between claudin-2 expression and clinicopathological parameters of CRCs. These results suggest that the expression of claudin-2 may involve organ specificity, and increased expression of claudin-2 may participate in colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]

Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis. [ABSTRACT FROM AUTHOR]

Cbl proteins play important roles in downregulation of growth factor receptors by acting as ubiquitin ligases and multi-adapter proteins. Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) has been shown to be controlled by Cbl. In the present study, we examined the expression of Cbl in gastric carcinomas and studied the correlation of Cbl expression with clinicopathological characteristics as well as EGFR expression. Cbl protein was expressed in 67% (82/122) of gastric carcinomas, and diffuse expression of Cbl was detected in 29% (35/122) of the cases. The incidence of cases with diffuse expression of Cbl was significantly higher in advanced cases (28/70, 40%) than in early cases (7/52, 14%) ( P=0.0010). Diffuse expression of Cbl was significantly associated with metastasis of tumor cells in lymph nodes ( P=0.0318). Diffuse expression of EGFR was significantly associated with depth of invasion ( P=0.0057), lymph-node metastasis ( P=0.0371) and tumor stages ( P=0.0278). As the grades of Cbl expression became stronger, the cases with diffuse EGFR expression increased, the positive correlation being significant ( P=0.049). All the cases with diffuse expression of Cbl and EGFR were found to show nodal metastasis and to be at an advanced stage. Moreover, the prognosis of the patients with synchronous diffuse expression of Cbl and EGFR was significantly poorer than that of the patients negative for Cbl and focal or negative for EGFR ( P=0.0086). The expression of Cbl protein was clearly induced in gastric carcinoma cell lines by transforming growth factor-a treatment. These results suggest that Cbl in connection with the EGFR system may be associated with stomach carcinogenesis, invasion and metastasis. Cbl may serve as a novel molecular marker for aggressive gastric carcinoma. [ABSTRACT FROM AUTHOR]

Patients with long-standing and extensive ulcerative colitis (UC) have an increased incidence of colorectal cancer (CRC). It has been reported that a DNA repair gene, O 6-methylguanine-DNA methyltransferase ( MGMT) is inactivated by promoter hypermethylation in sporadic CRCs. Hence, we investigated the promoter methylation status of MGMT by methylation specific polymerase chain reaction (PCR) in a total of 67 tissue samples (61 non-cancerous tissues and 6 cancer tissues) from 24 patients with UC. Promoter hypermethylation of MGMT was detected in one well-differentiated adenocarcinoma (16.7%) of 6 cancer samples and not detected in any of adenomas and dysplasias. In non-dysplastic tissues, promoter hypermethylation of MGMT was detected in 2 (3.7%, mucosa with mild inflammation) of 54 samples. The frequency of MGMT promoter hypermethylation in UC-associated CRCs found in this study (16.7%) is obviously lower than previously reported in sporadic CRCs (39.0?42.0%). We also confirmed that 42.9% (6/14) of sporadic CRCs showed the promoter methylation. These findings indicated that promoter hypermethylation of the MGMT gene is infrequent in patients with UC, and may not closely contribute to UC-associated colorectal tumorigenesis. A different genetic pathway for tumor progression may exist between sporadic CRC and UC-associated CRC. [ABSTRACT FROM AUTHOR]

Osteoprotegerin (OPG), identical with osteoclastogenesis inhibitory factor, is a member of a subgroup of the tumor necrosis factor (TNF)-receptor superfamily, which functions as a soluble decoy receptor. It has been reported that OPG expression is associated with bone metastasis of cancer of the breast and prostate. In the present study, we examined the expression of OPG in gastric carcinomas using immunohistochemistry and reverse-transcription polymerase chain reaction methods, and compared with clinicopathological parameters. The expression of OPG mRNA was confirmed in a gastric carcinoma cell line (MKN-7) and gastric carcinoma tissues. Immunohistochemically, strongly positive staining of OPG was found in 65% (67/103) of gastric carcinomas, whereas OPG protein was not detected in non-neoplastic mucosal epithelia. The expression of OPG protein in gastric carcinoma tissues correlates significantly with depth of tumor invasion, nodal metastases and advanced tumor stage. Furthermore, the prognosis of the cases with strong OPG expression was significantly worse than those with weak or no expression of OPG. These results suggest that OPG may participate in stomach carcinogenesis, invasion and metastasis, and may serve as a novel molecular marker for aggressive gastric cancer. [ABSTRACT FROM AUTHOR]

In liver injuries, the quiescent hepatic stellate cells (HSCs) promptly change to activated HSCs, which are easily identified by the intense immunoreactivity for a-smooth muscle actin. However, reproducible markers for quiescent HSCs in formalin-fixed, paraffin-embedded liver tissue sections have not yet been reported. We immunohistochemically examined the expression of vinculin, one major protein of dense plaques, on cultured LI90 cells and on HSCs in normal and diseased human and rat livers. In cultured LI90 cells, vinculin appeared as small linear patches. Although vinculin was consistently negative in the routine liver tissue sections, an antigen retrieval technique using microwave oven heating yielded excellent effects. Using this technique, the formalin-fixed, paraffin-embedded human and rat normal liver tissue sections showed the vinculin immunoreactivity along the sinusoidal wall. Immunoelectron microscopic observation of hepatic parenchyma demonstrated that the vinculin was exclusively expressed in quiescent HSCs. In fetal rat livers, vinculin-positive quiescent HSCs gradually increased in number with gestation. In diseased livers the activated HSCs showed more intense immunoreaction for vinculin. These results indicate that, using microwave pretreatment, vinculin is expressed in quiescent and activated HSCs in routinely processed liver tissue sections. It could allow us to evaluate the development and distribution of quiescent HSCs and to examine the relationship between quiescent and activated HSCs. [ABSTRACT FROM AUTHOR]

abstract thrombospondin-1 (tsp-1) has been shown to play a role in angiogenesis in a variety of cancers, but some studies indicated a difference in the mechanism of tsp-1 on neovascularization according to organ or histological type. wild-type p53 protein has been shown to induce tsp-1 expression. we examined the expression of tsp-1 protein in 80 gastric carcinomas using immunohistochemistry and studied the relationship with microvessel counts, p53 expression and clinicopathological factors. we also performed reverse-transcriptase polymerase chain reaction analysis for the tsp-1 mrna expression in gastric carcinoma cell lines and gastric cancer tissue after laser capture microdissection. strong expression of tsp-1 protein was detected in 30 (38%) of the 80 cases. positive staining for tsp-1 was seen in the cytoplasm of the cancer cells. tsp-1 mrna expression was confirmed in a majority of gastric carcinoma cell lines and carcinoma tissues. microvessel counts were significantly higher in tumors with strong tsp-1 protein expression than in those without expression or weak expression of tsp-1 (p=0.011). no significant correlation was found between tsp-1 expression and p53 staining and clinicopathological factors. our results support an idea that increased tsp-1 expression may be associated with an angiogenic phenotype in gastric carcinoma and suggest that tsp-1 may play diverse roles in each organ. [ABSTRACT FROM AUTHOR]

Abstract. Integrin-linked kinase (ILK), a serine/threonine protein kinase, implicates in cellular control of cell-matrix interactions and cell proliferation that is associated with a highly invasive phenotype of certain tumors. To study whether ILK is involved in the development and progression of gastric carcinoma, we examined the expression of ILK in gastric carcinoma cell lines, primary gastric carcinomas and corresponding non-neoplastic mucosa using reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry and analyzed the relationship with clinicopathological parameters. The expression of ILK mRNA was detected in 4 of 5 gastric carcinoma cell lines and 22 of 35 (63%) microdissected tumor samples of primary gastric carcinoma using RT-PCR. The incidence of cases with ILK mRNA expression was significantly higher in scirrhous and intermediate type (82%) than in medullary type (44%) (P=0.0204). Significant association was detected between ILK mRNA expression and presence of nodal metastasis (P=0.0388). Immunohistochemically, strong expression of ILK protein (over 50% of tumor cells were positive) was detected in 69% (84/122) of primary gastric carcinomas, whereas no ILK expression was found in non-neoplastic gastric epithelia. Strong expression of ILK protein was significantly associated with scirrhous and intermediate type (P=0.0217), deep invasion of tumor cells in gastric wall (P=0.0006), and presence of nodal metastasis (P=0.0176). These results strongly suggest that ILK may participate not only in stomach carcinogenesis especially of scirrhous and intermediate types but also in invasion and metastasis of gastric carcinoma. ILK might be a novel molecular marker for aggressive gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract. We examined regeneration and fibrosis in the necrotic areas of hepatic stellate cells (HSCs). Acute hepatic injury was induced in rats by administration of an intraperitoneal injection of high-dose dimethylnitrosamine (50 mg/kg body weight). Liver samples were obtained from rats 6, 12, 24, 36 h and 2, 3, 5, 7, 10, and 14 days after the injection. They were examined by light and electron microscopy and by immunohistochemical methods. Hemorrhagic necrosis became most prominent 36 h after treatment and extended into zones 3 and 2. In the submassive necrotic areas the sinusoidal structure was destroyed. No HSCs positive for α-smooth muscle actin or desmin were present. On day 5, when necrotic tissues were almost removed by infiltrating macrophages, HSCs strongly positive for α-smooth muscle actin and desmin appeared along the surface of the preserved parenchyma and migrated into the necrotic areas along the residual reticulin fibers. By day 14 most of the necrotic areas were almost completely replaced by the regeneration of hepatocytes and central to central (C-C) bridging fibrosis. Our results indicate that following submassive complete necrosis, HSCs in the preserved liver parenchyma have roles in the formation of sinusoidal wall for remodeling in necrotic areas via their activation, proliferation, and migration into the necrotic areas. [ABSTRACT FROM AUTHOR]