IL-37b gene transfer enhances the therapeutic efficacy of mesenchumal stromal cells in DSS-induced colitis mice.

AIM: To investigate whether the transfer of the IL-37b gene, a newly identified inhibitor of both innate and adaptive immunity, could improve the therapeutic efficacy of mesenchumal stromal cells (MSCs) in inflammatory bowel disease (IBD). METHODS: The expression of IL-37 in biopsied specimens of the patients with active ulcerative colitis (UC) was detected using RT-PCR and immunohistochemistry. Mice were treated with 3% dextran sulfate sodium (DSS) for 8 days to induce colitis. Before DSS treatment, the mice were injected with MSCs, MSC-eGFP or MSC-IL37b. Their body weight was measured each day, and the colons and spleens were harvested on d 10 for pathological and biochemical analyses. RESULTS: In biopsied specimens of the patients with active UC, the expression of IL-37 was dramatically elevated in inflamed mucosa, mainly in epithelial cells and infiltrating immune cells. Compared to MSC-eGFP or MSCs, MSC-IL37b administration significantly attenuated the body weight and colon length reduction, and decreased the histological score in DSS-induced colitis mice. Furthermore, MSC-IL37b administration increased the percentage of myeloid-derived suppressor cells (MDSCs) among total splenic mononuclear cells as well as the percentage of regulatory T cells (Tregs) among splenic CD4+ T cells in the mice. Moreover, MSC-IL37b administration increased the IL-2+ cells and decreased the IFN-γ+ cells among splenic CD4+ T cells. CONCLUSION: IL-37 is involved in the pathophysiology of UC. IL-37b gene transfer enhances the therapeutic efficacy of MSCs in DSS-induced colitis mice by inducing Tregs and MDSCs and regulating cytokine production.

[Clinicopathological analysis of biliary tract complications on post-liver transplantation patients].

OBJECTIVE: To analyze the pathohistological changes of the livers and the clinical features of patients with biliary tract complications after their orthotopic liver transplantations. METHODS: From Sept 1998 to June 2005 clinical and pathological data of 173 post-liver transplantation patients with biliary tract complications were analyzed. RESULTS: Biliary tract complications occurred within 3-2920 days after the transplantation operations. These complications occurred within 1-30 days, 31-90 days, 91-180 days, 180 days at rates of 49.71%, 17.92%, 4.62%, 27.74% respectively. The complications were of inflammatory nature in 171 cases, (72.25%), and of obstructive nature in 164 cases (27.74%). The main pathological changes were epithelium degeneration of interlobular bile ducts, inflammatory cell infiltration in portal areas, proliferation of interlobular bile ducts, fibrosis in portal areas, cholestasis in small bile ducts and hepatocytes. CONCLUSION: Many of the biliary tract complications of post-liver transplantation in our cases were of inflammatory nature and they often occurred within 30 days after the surgery. Obstructive nature complications often occurred in 90 days after the surgery and the prognosis of these cases was much poorer. The pathological changes of live tissues shown in liver biopsies are important for prognostic evaluation, differential diagnosis and categorization of biliary tract complications.

Expression and significance of Survivin mRNA in lung cancer tissue microarray detected by FISH.

OBJECTIVE: To investigate the expression of Survivin mRNA in lung cancer tissue microarray (TMA) by fluorescence in situ hybridization (FISH) method, and determine the role and significance of it in lung cancer genesis and progress. METHODS: The expression of Survivin mRNA was detected by FISH method and TMA technology. Fifty-four cases of lung cancer and 10 cases of normal lung tissue were examined. RESULTS: Survivin mRNA was expressed in 66.7% (36/54) of lung cancer; the positive ratio of lung cancer was significantly higher than that of normal lung tissue (0/10; chi2 = 15.238, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in poor differentiated cancer (20/24, 83.3%) than moderate and well differentiated cancer (16/30, 53.3%; chi2 = 5.40, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in group with lymph node metastasis (27/32, 84.4%) than without lymph node metastasis (9/22, 40.9%; chi2 = 11.084, P < 0.05). The positive ratio of Survivin mRNA was significantly higher in stage III-IV(12/13, 92.3%) than stage I - II (24/41, 58.5%; chi2 = 5.066, P < 0.05). CONCLUSION: Survivin mRNA highly expresses in lung cancer, which is related to the progress and malignant behavior. Survivin may play a promoting role in lung cancer genesis and progress and provide a basis for estimating prognosis and treatment.

[Expression of KAI1, MRP-1, and FAK proteins in lung cancer detected by high-density tissue microarray].

BACKGROUND & OBJECTIVE: The genesis, development, invasion, and metastasis of tumor are closely correlate with alterations of multi-genes. At present, the roles of Kang-ai-1 (KAI1), motility-related protein-1 (MRP-1), and focal adhesion kinase (FAK) in lung cancer have seldom been reported. This study was designed to investigate the roles of KAI1, MRP-1, and FAK in tumorigenesis and development of lung cancer, and their values in diagnosis and predicting the prognosis of lung cancer. METHODS: The expression of KAI1, MRP-1, and FAK proteins in a high-density tissue microarray containing 240 spots were detected by SP immunohistochemistry. RESULTS: The positive rates of KAI1 and MRP-1 were significantly lower in primary lung cancer than in normal lung tissue (25.9% vs. 100%, 42.6% vs. 100%, P<0.05). The positive rate of FAK was significantly higher in primary lung cancer than in normal lung tissue (44.4% vs. 10.0%, P<0.05). The expression of KAI1, FAK, and MRP-1 in primary lung cancer had no correlation with age and gender of the patients, and macroscopic and histological type of tumor, but had correlations with tumor differentiation, clinical stage, and lymph node metastasis. In addition, the expression of MRP-1 had correlation with histological type of tumor; the positive rate of MRP-1 was significantly lower in small cell lung cancer than in non-small cell lung cancer (0 vs. 50.0%, P<0.05). KAI1 expression was negatively correlated to FAK expression (rs=-0.458, P<0.05); MRP-1 expression was positively correlated with KAI1 expression (rs=0.535, P<0.05), and negatively correlated with FAK expression (rs=-0.438, P<0.05). CONCLUSIONS: The abnormal expression of KAI1, MRP-1, and FAK proteins are related to invasion and metastasis of lung cancer. Combined detection of the 3 proteins may be useful in predicting the development and prognosis of lung cancer.