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Qinghai Z.,Zhumadian Center Hospital | Yanying W.,Zhumadian Center Hospital | Yunfang C.,Zhumadian Center Hospital | Xukui Z.,PLA Jinan General Hospital | Xiaoqiao Z.,PLA Jinan General Hospital
Gene | Year: 2014

We selected six tagged single-nucleotide polymorphisms (SNPs) in the IL-17A and IL-17F genes, and evaluated the relationship between the six common SNPs and H. pylori infection, tobacco smoking and subsites of gastric cancer in gastric cancer patients. Genotyping of IL-17A (rs2275913, rs3748067 and rs3819025) and IL-17A (rs763780, rs9382084, and rs12203582) was performed in a 384-well plate format on the MassARRAY® platform. An unconditional multiple logistical regression model was performed to determine the association between IL-17A and IL-17F genetic variations and gastric cancer risk. Unconditional logistic regression analysis showed that subjects carrying the rs2275913AA and rs3748067 TT genotypes were 1.70 and 3.45 times more likely to develop gastric cancer. Furthermore, rs2275913 and rs3748067 genetic variants significantly interacted with H. pylori infection on the risk of gastric cancer. The interaction between rs3748067 and rs9382084 genetic variants and tobacco smoking trend was significant. In addition, rs2275913, rs3748067 and rs9382084 genetic variants were only associated with non-cardia gastric cancer. The findings suggest that the rs2275913, rs3748067 and rs9382084 polymorphisms increase the risk of gastric cancer, and they interact with H. pylori infection, tobacco smoking and subsites of gastric cancer. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer. © 2013 Elsevier B.V. Source


Zhang X.,PLA Jinan General Hospital | Zheng L.,PLA Jinan General Hospital | Sun Y.,PLA Jinan General Hospital | Wang T.,Shandong University | Wang B.,PLA Jinan General Hospital
Oncology Reports | Year: 2015

Irradiation has been reported to increase radioresistance and epithelial-mesenchymal transition (EMT) in gastric cancer (GC) cells. The Notch pathway is critically implicated in cancer EMT and radioresistance. In the present study, we investigated the use of a Notch-1 inhibiting compound as a novel therapeutic candidate to regulate radiation-induced EMT in GC cells. According to previous screening, tangeretin, a polymethoxylated flavonoid from citrus fruits was selected as a Notch-1 inhibitor. Tangeretin enhanced the radiosensitivity of GC cells as demonstrated by MTT and colony formation assays. Tangeretin also attenuated radiation-induced EMT, invasion and migration in GC cells, accompanied by a decrease in Notch-1, Jagged1/2, Hey-1 and Hes-1 expressions. Tangeretin triggered the upregulation of miR-410, a tumor-suppressive microRNA. Furthermore, re-expression of miR-410 prevented radiation-induced EMT and cell invasion. An in vivo tumor xenograft model confirmed the antimetastasis effect of tangeretin as we observed in vitro. In nude mice, tumor size was considerably diminished by radiation plus tangeretin co-treatment. Tangeretin almost completely inhibited lung metastasis induced by irradiation. Tangeretin may be a novel antimetastatic agent for radiotherapy. © 2014, Spandidos Publications. All rights reserved. Source


Zhang X.,PLA Jinan General Hospital | Zheng L.,PLA Jinan General Hospital | Sun Y.,PLA Jinan General Hospital
Tumor Biology | Year: 2014

We aimed to explore the association between interleukin-17 (IL-17) polymorphisms, Helicobacter pylori infection, and subsites in gastric cancer risk in a Chinese population. We genotyped three promoter polymorphisms (rs2275913G>A, rs3748067C>T, and rs763780T>C) of IL-17 in a case-control study of 260 gastric cancer patients and 512 healthy controls. An unconditional multiple logistical regression model was used to calculate the effects of IL-17 gene polymorphisms on gastric cancer risk. The rs2275913 AA (adjusted OR=1.69, 95% CI=1.15-2.49) and rs3748067 TT (adjusted OR=1.73, 95% CI=1.03-2.94) genotypes were associated with an increased risk of gastric cancer. We observed a significant interaction among rs2275913G>A, rs3748067C>T, and H. pylori infection on the risk of gastric cancer (p for interaction of 0.036 and 0.048, respectively). H. pylori infection subjects carrying the rs2275913 AA (adjusted OR=2.48, 95% CI=1.49-4.12) and rs3748067 TT (adjusted OR=2.54, 95% CI=1.34-5.12) genotypes had a greatly increased risk of gastric cancer compared to negative H. pylori participants. Similarly, subjects carrying the rs2275913 AA (adjusted OR=2.09, 95% CI=1.25-3.45) and rs3748067 TT (adjusted OR=2.29, 95% CI=1.20-4.20) genotypes had a moderately increased risk of noncardia gastric cancer. A significant interaction was observed between the rs2275913G>A and rs3748067C>T genotype and subsites of gastric cancer (p for interaction of 0.044 and 0.008, respectively). The rs2275913G>A and rs763780T>C polymorphisms increase gastric cancer risk, and interact with H. pylori infection and subsites. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer. © International Society of Oncology and BioMarkers (ISOBM) 2013. Source

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