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Tonsil-derived mesenchymal stem cells (TMSCs) showed therapeutic effects on acute and chronic murine colitis models, owing to their immunomodulatory properties; therefore, we evaluated enhanced therapeutic effects of TMSCs on a murine colitis model using three-dimensional (3D) culture method. The expression of angiogenic factors, VEGF, and anti-inflammatory cytokines, IL-10, TSG-6, TGF-β, and IDO-1, was significantly higher in the 3D-TMSC-treated group than in the 2D-TMSC-treated group (P

Background The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has not been fully evaluated in inflammatory bowel disease. We evaluated the level of PD-1/PD-L1 in the mucosa of patients with ulcerative colitis and revealed the role of PD-1/PD-L1 in the immunomodulatory mechanism of tonsil-derived mesenchymal stem cells (T-MSCs). Methods We used chronic murine colitis model induced by dextran sodium sulphate (DSS). We measured the PD-1 and PD-L1 levels in inflamed colonic tissues before and after the treatment with T-MSC. We also measured the levels of PD-1 and PD-L1 in the colonic tissues from patients with ulcerative colitis and compared with those from normal controls. Results In chronic colitis model, the level of PD-L1 was decreased than normal controls (fold change) (1.0 vs. 0.46 ± 0.08, p = 0.05). However, the level of PD-1 was increased than normal controls (1.0 vs. 6.84 ± 8.16, p = 0.142). After treatment with T-MSC which showed significant improvement in body weight, disease activity index and colon length, the levels of PD-1 and PD-L1 were recovered; PD-L1 was significantly increased (1.04 ± 0.77 vs. 0.46 ± 0.08, p = 0.031) and the level of PD-1 was decreased (3.63 ± 1.94 vs. 6.84 ± 8.16, p = 0.537). When measuring the level of PD-1 and PD-L1 in both soluble medium and cell lysate of T-MSC, we found that the PD-1 and PD-L1 were expressed in both forms (182.63 pg/ml in soluble medium and 11.85 pg/protein (μg) in cell lysate after 7 days of differentiation period). In the analysis using human colonic tissues, a significantly increase in the levels of PD-1 and PD-L1 was observed in the colonic mucosa of patients with UC compared with normal controls (PD-1: 2.09 ± 3.95 vs. 7.93 ± 14.21, p = 0.034 and PD-L1: 2.24 ± 2.91 vs. 10.08 ± 18.13, p = 0.044). Conclusion The altered expression of PD-1 and PD-L1 in colonic mucosa may a possible mechanism of ulcerative colitis and T-MSC-derived PD-L1 could repress the colitis.

Background/Aims: RUNX3 (PEBP2αC/CBFA3/AML2) is a novel tumor suppressor gene in the human gastric carcinoma. The aims of this study were to determine the methylation of RUNX3 promoter and the association between RUNX3 methylation and the clinicopathological characteristics of patients with gastric carcinoma. Methods: Seventy-nine patients with gastric carcinoma were studied prospectively from April 2005 to May 2007. The methylations of RUNX3 promoter on the gastric carcinoma specimens and the corresponding nonneoplastic mucosa were evaluated by methylation-specific polymerase chain reaction. Results: Comparison of the results with the clinicopathological characteristics identified RUNX3 monoallelic methylation in 32.9% (26/79) of the gastric carcinoma patients and in 11.4% (9/79) of those with nonneoplastic mucosa (p=0.053). The monoallelic methylated gastric carcinoma specimens predominantly consisted of well- and moderately differentiated carcinomas (44.7%), with the unmethylated group constituting 22.0% of them (p=0.031). Among the 48 patients (60.8%) who underwent gastrectomy, there was no correlation between the two groups with regard to Lauren's classification (p=0.235), depth of invasion (p=0.990), nodal status (p=0.601), stage (p=0.900), lymphatic invasion (p=0.537), and vascular invasion (p=0.815). Conclusions: Methylation of the tumor suppressor gene RUNX3 might be one of the mechanisms involved in the pathogenesis of gastric carcinoma. (Gut and Liver 2008;2:119-125)

The calcium-sensing receptor (CaSR) is known to have differential expression in various carcinomas and normal tissues. It has been shown to be involved in carcinogenesis or tumor suppression. However, its role in gastric cancer remains unknown. This study was performed to determine the CaSR expression level in gastric cancer and non-tumor gastric tissues and to examine the related clinicopathological factors.Thirty-one pairs of gastric cancer tissues and matched non-tumor gastric tissues were obtained from surgical tissues after gastrectomy. Using real-time polymerase chain reaction, we measured CaSR mRNA expression. We evaluated the association between CaSR mRNA expression and clinicopathological variables based on the downregulation or upregulation of CaSR mRNA expression in gastric cancer tissues compared to those of matched non-tumor gastric tissues. By immunohistochemistry, we confirmed CaSR expression levels in gastric cancer tissues.Downregulation of CaSR mRNA was observed in 77.4% of gastric cancer tissues compared to their matched normal tissues. Downregulated CaSR was associated with a tendency for deeper invasion into the proper muscle (p = 0.028) and more advanced stage (II-IV; p = 0.012).We conclude that downregulation of CaSR may contribute to the prevention or suppression of tumor outgrowth.

Objectives Rifaximin, a poorly absorbed antibiotics, has gut-specific therapeutic effects. Although frequently prescribed to manipulate intestinal luminal bacterial population in various diseases, the possible induction of antibacterial cross-resistance to a target pathogen is a major concern in long-term rifaximin administration. We aimed to evaluate whether rifampin-resistant staphylococci could evolve after rifaximin treatment in cirrhotic patients. Method A total of 25 cirrhotic patients who were administered rifaximin for the prevention of hepatic encephalopathy were enrolled. Swabs from both hands and the perianal skin were acquired on day 0 (before rifaximin treatment), period 1 (1–7 weeks after treatment), and period 2 (8–16 weeks after treatment) the staphylococcal strain identification and rifampin-resistance testing. Results A total of 198 staphylococcal isolates from 15 species were identified. Staphylococcus epidermidis was isolated most frequently, and Staphylococcus haemolyticus was the most common resistant species both from hands and perianal skin. Eleven patients (44.0%) developed rifampin-resistant staphylococcal isolates in period 1. Among these patients, only six (54.5%) were found to have rifampin-resistant isolates in period 2, with no significant infectious events. Rifampin-resistant staphylococcal isolates were more frequently found in perianal skin than from the hands. No patients acquired a newly resistant strain in period 2. Conclusions About one-half of cirrhotic patients in this study developed rifampin-resistant staphylococcal isolates after rifaximin treatment. Although the resistant strains were no longer detected in about half of the patients in the short-term, the long-term influence of this drug treatment should be determined.

Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1)-MMP, TIMP-1, and TIMP-2 in biopsy tissues of gastric cancer, and the correlation between their expression and clinicopathological parameters. Biopsy specimens from 66 patients with gastric carcinoma were available for this study. To determine the expression of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out on tumor and normal tissues, respectively, sampled during diagnostic gastroscopic examination. Immunohistochemical staining of representative samples using monoclonal antibody directed against MT1-MMP was done, and the clinicopathological variables were reviewed retrospectively. The expression level of MMPs and TIMPs was evaluated using the tumor : normal (T/N) ratios of MMPs and TIMPs. The T/N ratio of MT1-MMP mRNA showed a significant correlation with lymph node metastasis and tumor stage (P < 0.05). The other RT-PCR data of MMP-2, MMP-9, TIMP-1, and TIMP-2 did not show any significant correlation with clinicopathological parameters. Immunohistochemistry for MT1-MMP showed a positive immunoreaction in gastric adenocarcinoma and negative staining in normal mucosa. The correlation between the increased expression of MT1-MMP and clinicopathological variables reflects a role in predicting the aggressive behavior of gastric cancer. Because an RT-PCR assay can be performed on biopsy specimens obtained before surgery, an evaluation of MT1-MMP expression in biopsy specimens by RT-PCR may provide useful preoperative information on tumor aggressiveness.