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Liu H.-Q.,Yancheng First Peoples Hospital | Song S.,Yancheng First Peoples Hospital | Wang J.-H.,Yancheng First Peoples Hospital | Zhang S.-L.,Yancheng Health Vocational and Technical College
Oncology Letters | Year: 2011

The present study aimed to investigate the expression of matrix metalloproteinase-3 (MMP-3) and the tissue inhibitor of metalloproteinase-3 (TIMP-3) in gastric cancer tissue, as well as to analyze the correlation between their expression and the occurrence of gastric cancer. Immunohistochemistry was used to determine the expression of MMP-3 and TIMP-3 in the gastric cancer tissue from 18 patients with early-stage gastric cancer (early-stage group) and 26 patients with advanced-stage gastric cancer (advanced-stage group). Transmission electron microscopy (TEM) was used to observe the lymphocytes and tumor cells in gastric cancer tissue. The results showed that the expression of TIMP-3 was significantly higher, whereas that of MMP-3 and MMP-3/TIMP-3 was lower in gastric cancer tissue of the early-stage group than in that of the advanced-stage group (P<0.05). The TEM images revealed increased lymphocytes and inconspicuous tumor cells penetrating the basement membrane in gastric cancer tissue of the early-stage group, and decreased lymphocytes and obvious tumor cells penetrating the basement membrane in the advanced-stage group. In conclusion, MMP-3 and TIMP-3 may be used as indices for the invasion and metastasis of gastric cancer and possess marked clinical significance in the prognostic judgment of gastric cancer. Source


Yao M.,Nantong University | Yao D.-F.,Nantong University | Bian Y.-Z.,Yancheng First Peoples Hospital | Zhang C.-G.,Nanjing Medical University | And 5 more authors.
Hepatobiliary and Pancreatic Diseases International | Year: 2011

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by a multi-cause, multi-stage and multi-focus process of tumor progression. Its prognosis is poor and early diagnosis is of utmost importance. This study was undertaken to investigate the dynamic expression of oncofetal antigen glypican-3 (GPC-3) and GPC-3 mRNA in hepatocarcinogenesis and to explore their early diagnostic value for HCC. METHODS: A hepatoma model was induced in male Sprague Dawley rats with 0.05% 2-fuorenylacetamide and confirmed by hematoxylin and eosin staining and gamma-glutamyltransferase (GGT) expression. Total RNA was purified and transcribed into cDNA by reverse transcription. Fragments of the GPC-3 gene were amplified by nested RT-PCR, and confirmed by sequencing GPC-3 was analyzed by immunohistochemistry, Western blotting or ELISA. RESULTS: Positive GPC-3 expression showed as brown granule-like staining localized in the cytoplasm. Histological examination of hepatocytes revealed three morphological stages of granule-like degeneration, atypical hyperplasia (precancerous), and cancer formation, with a progressive increase of liver total RNA and GGT expression. The incidence of liver GPC-3 mRNA and GPC-3, and serum GPC-3 was 100%, 100% and 77.8% in the HCC group, 100%, 100%, and 66.7% in the precancerous group, 83.3%, 83.3%, and 38.9% in the degeneration group, and no expression in the liver or blood of the control group, respectively. There was a positive correlation between liver GPC-3 mRNA and total RNA level (r=0.475, P<0.05) or liver GPC-3 (r=1.0, P<0.001) or serum GPC-3 (r= 0.994, P<0.001). CONCLUSION: Abnormal oncofetal antigen GPC-3 and GPC-3 mRNA expression in hepatocarcinogenesis may be promising molecular markers for early diagnosis of HCC. © 2011, Hepatobiliary Pancreat Dis Int. All rights reserved. Source


Liu H.-Q.,Peoples Hospital of Jiangsu Province | Zhang S.-L.,Yancheng Health Vocational and Technical College | Song S.,Yancheng First Peoples Hospital
Hepato-Gastroenterology | Year: 2012

Background/Aims: Gastric cancer is associated with high morbidity and mortality, but reliable diagnostic and prognostic markers have not been established. Here we explored the clinical significance of two proteins, HER-2/neu and TOPIIα-associated with development and progression of various tumor types-in gastric cancer. We also analyzed the correlation between expression of these proteins and clinicopathological parameters of gastric tumors. Methodology: Tumor and adjacent normal tissue samples were collected from 62 patients with gastric cancer and subjected to immunohistochemistry with anti-HER-2/neu and -TOPIIá antibodies. Results: HER-2/neu (21.0%) and TOPIIá(80.6%) were expressed more commonly in gastric cancer than in normal gastric tissue (9.7% and 60.3%, respectively; p<0.05). However, there was no correlation between HER-2/neu and TOPIIá expression in gastric tumors. Further analysis showed a correlation between HER-2/neu expression and lymph node metastasis, distant metastases and tumor stage (p<0.05); TOPIIá was correlated with infiltration depth, distant metastases and tumor stage (p<0.05). Conclusions: HER-2/neu and TOPIIá are over expressed in gastric tumors and may promote disease progression. These proteins may therefore be useful as prognostic markers in evaluation of patients with gastric cancer. © H.G.E. Update Medical Publishing S.A. Source


Yu H.,Yancheng First Peoples Hospital | Yang W.,Nanjing Medical University
Biochemical and Biophysical Research Communications | Year: 2016

MiR-211 has strong inhibitive effects on melanoma cell growth, invasion and metastasis. However, how it is downregulated and whether other genes are involved its downstream regulation in melanoma are not clear. In this study, we firstly verified the expression of miR-211 in melanoma cell lines and observed that its downregulation is associated with increased DNMT1 expression. By performing qRT-PCR and MSP analysis, we confirmed that DNMT1 is negatively correlated with miR-211 expression and can modulate DNA methylation in the promoter region of miR-211. By performing bioinformatics analysis, we found that RAB22A is a possible target of miR-211, which has two broadly conversed binding sites with miR-211 in the 3'UTR. Following dual luciferase assay, qRT-PCR and western blot analysis confirmed the direct binding between miR-211 and RAB22A and the suppressive effect of miR-211 on RAB22A expression. Knockdown of RAB22A increased epithelial properties and impaired mesenchymal properties of the melanoma cells, suggesting that miR-211 modulates epithelial mesenchymal transition (EMT) of melanoma cells via downregulating RAB22A. In summary, the present study firstly demonstrated that DNMT1 mediated promoter methylation is a mechanism of miRNA suppression in melanoma and revealed a new tumor suppressor role of the miR-211 by targeting RAB22A in melanoma. The DNMT1/miR-211/RAB22A axis provides a novel insight into the pathogenesis of melanoma, particularly in the EMT process. © 2016 Elsevier Inc. Source


Dong M.,Nanjing Southeast University | Li J.,Nanjing Southeast University | Tang R.,Shanghai JiaoTong University | Zhu P.,Nanjing Southeast University | And 42 more authors.
Clinical Reviews in Allergy and Immunology | Year: 2015

Multiple genome-wide association studies of primary biliary cirrhosis (PBC) in both European and Japanese ancestries have shown significant associations of many genetic loci contributing to the susceptibility to PBC. Major differences in susceptibility loci between these two population groups were observed. In this study, we examined whether the most significant loci observed in either European and/or Japanese cohorts are associated with PBC in a Han Chinese population. In 1070 PBC patients and 1198 controls, we observed highly significant associations at CD80 (rs2293370, P = 2.67 × 10−8) and TNFSF15 (rs4979462, P = 3.86 × 10−8) and significant associations at 17q12-21 (rs9303277), PDGFB (rs715505), NF-κB1 (rs7665090), IL12RB2 (rs11209050), and STAT4 (rs7574865; all corrected P values <0.01). However, no association was observed for POU2AF1 (rs4938534), IL12A (rs485499 and rs2366408), IL7R (rs6897932), CXCR5 (rs715412), SOCS1 (rs725613), and TNFRSF1A (rs1800693). STAT4 (rs7574865) was strongly associated after additional control samples were analyzed. Our study is the first large-scale genetic analysis in a Han Chinese PBC cohort. These results do not only reflect that Han Chinese PBC patients share common genetic susceptibility genes with both their Japanese and European counterparts but also suggest a distinctly different genetic susceptibility profile. © 2015, Springer Science+Business Media New York. Source

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