Mast cells (MC) may be one factor influencing the response of visceral afferent nerves to mechanical and chemical stimuli. The aim of this study was to evaluate the degree of infiltration and activity of colonic MC in irritable bowel syndrome (IBS). Biopsy specimens were obtained from the cecum and rectum of 14 diarrhea predominant IBS and 14 normal controls. Electron microscopy was used to determine the number of intact and degranulated colonic MC and to quantify these separately according to the distance between MC and enteric nerves. An increased number of MC in both cecum and rectum in the IBS group in comparison with the control group was demonstrated (p<0.05). Activated MC in close proximity to enteric nerves were significantly increased in both cecum and rectum of the IBS group compared to control group (p<0.005). In addition, activated MC were significantly increased in close proximity to the nerves compared to those in the remote area in both cecum and rectum of the IBS group (p<0.0001). MC were significantly increased and activated in both cecum and rectum of the IBS group compared to controls. MC may play a role in the gut sensory hypersensitivity of IBS.

BackgroundMatrix metalloproteinases (MMPs) have been implicated in the remodelling of extracellular matrix (ECM), including basement membrane. ECM remodelling is associated with pathological processes, including hepatic fibrosis, tumor invasion and metastasis. Tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were known to inhibit MMP-9 and MMP-2, respectively. In the present study, we examined the expression of TIMP-1 and TIMP-2 in surgical specimen pairs of hepatocellular carcinoma and nontumoral liver and the correlation between their expression and clinicopathological characteristics.MethodsThe localization of both transcripts and protein of TIMP-1 and TIMP-2 was studied by using in situ hybridization and immunohistochemistry.ResultsTIMP-1 and TIMP-2 mRNA transcripts were found in tumor cells, hepatocyte, sinusoidal cells, endothelial cells and stromal cells. Signal intensity of TIMP-1 was stronger than that of TIMP-2. The results of immunohistochemical stainings were concordant with those obtained by in situ hybridization. Expression of TIMP-1 and TIMP-2 was observed in tumorous tissue, in nontumorous tissue and in the portions of the tumors adjacent to the capsules. However, a clear difference in TIMP-1 and TIMP-2 mRNA expression was not observed among the three tissue types. The intensity of TIMP-2 expression was generally weaker than that of TIMP-1, and the intensity of TIMP-1 and TIMP-2 mRNA expression did not correlate with variable clinicopathological characteristics.ConclusionTIMPs was expressed in tumor cells and many cell types of the nontumoral liver. Further investigations for TIMPs’ unknown functional role are needed.

Background :Angiogenesis is of crucial importance for tumor growth and development of metastases. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and mutations of the p53 gene has been thought to upregulate VEGF. The purpose of our study was to evaluate the prognostic significance of these tumor biomarkers for angiogenesis relative to the information derived from established clinicopathological parameters in gastric cancer.Methods :In this study, we conducted an immunohistochemicai investigation of VEGF and p53 expression in 145 tissue samples obtained from gastric cancer patients undergoing curative surgical treatment. To evaluate angiogenesis, microvessel density (MVD) was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody.Results :High MVD was significantly associated with depth of tumor invasion and distant metastasis (p=0.004, 0.021, respectively). Moreover, overall survival for patients with high MVD were significantly lower than that of low MVD (p=0.048). Positive expression of VEGF correlated significantly with lymph node and distant metastasis (p=0.040, 0.048, respectively). However, no significant correlation was found between p53 expression and various clinicopathological parameters. VEGF positive tumors showed a higher MVD than VEGF negative tumors (p=0.028). The expression of p53 did not correlate with VEGF expression. Also, the relationship between the status of p53 expression and MVD had not statistically significant differences. In the multivariate analysis, status of VEGF, p53 expression and MVD were not an independent prognostic factor.Conclusion :VEGF seems to be an important, clinically relevant inducer of angiogenesis and angiogenesis assessed by the MVD may be a useful marker for predicting metastasis in gastric cancer. However, further studies are warranted to clarify the impact of p53 on the angiogenesis and the prognostic significance of angiogenesis in gastric cancer.

Abnormal expression of E-cadherin/catenin complex in cancer has been associated with poor differentiation and acquisition of invasiveness, suggesting a possible role of this protein as an invasion suppressor. In this study, we conducted an immunohistochemical investigation of all components of the E-cadherin/catenin complex in 65 gastric cancer patients. Abnormal expression of E-cadherin and, alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal type of gastric cancer, and correlated with poor differentiation. Abnormal expression of E-cadherin and beta-catenin correlated with poor survival. Abnormal expression of all four components of the complex was associated with poorly differentiated and diffuse-type carcinoma, and poor survival. In the multivariate analysis, abnormal expression of the E-cadherin/catenin complex was not an independent prognostic factor. These results suggest that the E-cadherin/catenin complex may be a useful marker of differentiation and prognosis in gastric cancer. Further studies are warranted to clarify the impact of the E-cadherin/catenin complex on prognostic factor of gastric cancer.

Increased production of matrix metalloproteinases (MMPs) has been associated with increases in invasive and metastatic potential in many types of human carcinoma. Tissue inhibitors of metalloproteinase (TIMP)-1 inhibits most interstitial collagenases and MMP-9. TIMP-2 binds specifically and noncovalently to the pro-form of MMP-2 and inhibits its enzyme activity. In this study, we examined TIMP-1 and TIMP-2 expressions in relation to clinicopathological variables in colorectal carcinoma with in situ hybridization and immunohistochemistry. TIMP-1 and TIMP-2 expressions were localized overwhelmingly to pericancer stromal cells, while malignant and normal mucosal cells were weak or negative. Strong stromal TIMP-1 immunoreactivity correlated with Dukes' stage (p=0.022), status of lymph node metastasis (p=0.044) and poor survival (p= 0.005). The degree of immunohistochemical staining of TIMP-2 did not correlate with all clinicopathological variables. The correlation between enhanced TIMP-1 expression and advanced stage and poor survival suggest a growth promoting activity of TIMP-1 in colorectal carcinoma.