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ABSTRACT: Cadherin-17 (CDH17), as a structurally unique member of the cadherin superfamily, has been identified to predict a poor prognosis for gastric cancer (GC). Our previous study demonstrated the positive correlation between CDH17 and lymph node micrometastasis in GC. We sought to further identify the role of CDH17 in the tumorigenesis and lymphatic metastasis of GC. Hence, we inhibited the CDH17 expression in MKN-45 gastric cancer cells by using RNA interference. Consequently, the malignant potency of cancer cells was evaluated, and the change in NFκB signaling pathway was also probed. Tumor growth and lymphatic metastasis model were conducted in nude mice to confirm the hypothesis. Downregulation of CDH17 not only suppressed the proliferation, adherence and invasion potency of MKN-45 cells, but also induced cell cycle arrest. Meanwhile, the NFκB signaling pathway was inactivated as well, with the reductions of downstream proteins including VEGF-C and MMP-9. Moreover, silencing CDH17 inhibited tumor growth in vivo significantly, and there was no lymph node metastasis detected in the mice without CDH17 expression, as opposed to the positive nodes found in controls. CDH17 is a novel oncogene in gastric cancer cells, which is associated with lymphatic metastasis and proliferation strongly. The inactivation of NFκB signaling pathway might be involved in targeting CDH17 in GC. On the whole, CDH17 is proposed to serve as a biomarker and attractive therapeutic target in GC.
Cancer biology & therapy 01/2013; 14(3). · 2.64 Impact Factor
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ABSTRACT: Despite a relatively better prognosis, patients with node-negative gastric cancer still suffer from metastasis and recurrence. To investigae the prognostic factors and appropriate therapies for these pN0 tumors, we analyzed the predictors and evaluated the impact of chemotherapy and extensive lymphadenectomy on survival.
Clinicopathologic features of 153 patients with pN0 gastric cancer were studied retrospectively. The prognostic factors were analyzed stratifying by pT1 and pT2-3 stage. The 5-year survival rate (5-YSR) of patients in different groups of chemotherapy and lymph nodes retrieved were compared.
Multivariate analysis indicated pT, number of nodes retrieved, and chemotherapy as the independent predictors of advanced gastric cancer; anemia was the only independent predictor of early gastric cancer. Survival of patients with pT3 got improved significantly by intraoperative chemotherapy and retrieval of more than 25 nodes, but neither of them benefited patients with pT1-2. Moreover, in pT3 status, 5-YSR of patients with intraoperative chemotherapy was still poorer than those with postoperative chemotherapy and combined chemotherapy.
In pN0 gastric cancers, prognostic factors differed significantly between early stage and advanced stage. For patients with pT3, besides curative gastrectomy and postoperative chemotherapy, it might be beneficial to perform intraoperative chemotherapy and extensive lymphadenectomy.
Journal of Surgical Oncology 03/2012; 105(4):400-4. · 2.10 Impact Factor
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ABSTRACT: Compared with soybean oil, a fish oil-enriched emulsion can improve the clinical outcomes of patients requiring parenteral nutrition. However, the superiority of fish oil emulsion to medium-chain triacylglycerols/long-chain triacylglycerols for short-term administration has seldom been discussed.
Sixty-four adult patients with gastrointestinal diseases were randomly assigned to receive isocaloric and isonitrogenous total parenteral nutrition with an ω-3 fatty acid-enriched emulsion (Lipoplus; study group, n = 32) or medium-chain triacylglycerols/long-chain triacylglycerols (Lipofundin; control group, n = 32) for 5 d after surgery. Safety and efficacy parameters were assessed on postoperative days 1, 3, and 6.
Clinical outcomes including infectious complications and systemic inflammatory response syndrome were comparable between the two groups. Total bilirubin decreased over time in the study group versus an increase in the control group (P = 0.017). Activated partial thromboplastin time in the study group was prolonged significantly compared with the control group from days 1 to 3 (P = 0.002), although the prolongation stopped at the study termination. There were no differences in changes of C-reactive protein, interleukin (IL)-1, IL-8, IL-10, vascular endothelial growth factor (VEGF), and the distribution of the T-cell subpopulation between the two groups. However, fish oil consumption led to an increase in leukotriene B5/ leukotriene B4 and significant decreases in IL-6, tumor necrosis factor-α, and nuclear factor-κB. Furthermore, the overall changes in tumor necrosis factor-α and nuclear factor-κB were positively associated (R(2) = 0.295, P < 0.001).
Gastrointestinal surgery patients benefited from a fish oil-enriched emulsion rather than medium-chain triacylglycerols/long-chain triacylglycerols in the amelioration of liver function and immune status. The positive association of tumor necrosis factor-α and nuclear factor-κB might be involved in the potential anti-inflammation mechanism of fish oil.
Nutrition 11/2011; 28(6):623-9. · 3.03 Impact Factor
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ABSTRACT: Previous studies identified cadherin-17 (CDH17) as one of the most upregulated genes in node-positive gastric cancer. However, the prognostic significance of CDH17 in pN0 gastric cancer and its association with lymph node micrometastasis (LNMM) have not been investigated.
Clinicopathologic features of 191 patients with node-negative gastric cancer were studied retrospectively. All dissected lymph nodes were immunostained by cytokeratin to detect micrometastasis. CDH17 and lymphatic invasion (LVI) in primary carcinoma were evaluated by immunostaining of monoclonal CDH17 and D2-40 antibody. Correlation of CDH17 with clinicopathologic characteristics was subsequently assessed. Risk factors of LNMM were analyzed by univariate and multivariate logistic regression. Cox's proportional hazard model was applied to investigate independent prognostic factors of pN0 gastric cancer. Overall survival rates of patients with positive and negative CDH17 were compared, stratifying by pT stage, Lauren grade, and LNMM status.
CDH17 was observed in 126 patients (66.0%). Positive expression of CDH17 was significantly associated with the age, tumor size, pT, Lauren grade, LVI, and LNMM, and identified as one of the independent risk factors of LNMM. Negative predictors of pN0 gastric cancer included pT, Lauren grade, LNMM, and CDH17. Furthermore, in tumors of pT2-3, intestinal histotype, and negative-LNMM, the survival rate of patients with CDH17 was significantly lower than that of patients without CDH17.
CDH17 was positively associated with larger tumor size, deeper invasion, diffuse/mixed histotype, LVI, and LNMM, predicting a poor prognosis in pN0 gastric cancer. Additionally, CDH17 may also serve as a potential indicator of LNMM.
Annals of Surgical Oncology 10/2011; 19(5):1529-34. · 4.17 Impact Factor
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Chinese Medical Sciences Journal 09/2010; 25(3):189-92.
