科创中国

Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein-coding proto-oncogenes and tumor-suppressor genes. Recent discoveries have shed new light on the involvement of a class of noncoding RNA known as microRNA (miRNA) in gastric cancer. A substantial number of miRNAs show differential expression in gastric cancer tissues. Genes coding for these miRNAs have been characterized as novel proto-oncogenes and tumor-suppressor genes based on findings that these miRNAs control malignant phenotypes of gastric cancer cells. In this connection, miRNA dysregulation promotes cell-cycle progression, confers resistance to apoptosis, and enhances invasiveness and metastasis. Moreover, certain polymorphisms in miRNA genes are associated with increased risks for atrophic gastritis and gastric cancer, whereas circulating levels of miRNAs may serve as biomarkers for early diagnosis. Several miRNAs have also been shown to correlate with gastric cancer progression, and thus may be used as prognostic markers. Elucidating the biological aspects of miRNA dysregulation may help us better understand the pathogenesis of gastric cancer and promote the development of miRNA-directed therapeutics against this deadly disease. © 2010 Macmillan Publishers Limited All rights reserved.

Wu W. K.K.;Lee C. W.;Cho C. H.;Yu J.;Sung J. J.Y.;Fan D.;Wu K.

Oncogene

2010

Background and Aim: Transjugular intrahepatic portosystemic shunt (TIPS) with polytetrafluoroethylene-(PTFE)-covered stent has been increasingly used for patients with complications of portal hypertension. It is still debated whether the new endoprostheses will improve some clinical outcomes (except for shunt patency) compared to the bare stents. The aims of our meta-analysis were to explore the patency and clinical outcomes of TIPS with PTFE-covered stent-grafts versus bare stents.Methods: Pertinent studies were retrieved through PubMed (1950-2010), MEDLINE (1950-2010), and reference lists of key articles. Outcome measures were primary patency, risk of encephalopathy and survival. Time-to-event data analysis was used to calculate the overall hazard ratios (HR).Results: Six studies were identified including a total of 1275 patients (346 TIPS with PTFE-covered stent-grafts and 929 TIPS with bare stents). Pooled shunt patency data from four eligible studies suggested a significant improvement of primary patency in patients who were treated with PTFE-covered stent-grafts (HR=0.28, 95% confidence interval [CI] 0.20-0.35). Pooled encephalopathy data from three eligible studies suggested a significant reduction of risk in the PTFE-covered group (HR=0.65, 95%CI 0.45-0.86). Pooled survival data from four eligible studies also suggested a significant decrease of mortality in the PTFE-covered group (HR=0.76, 95%CI 0.58-0.94). No statistical heterogeneity was observed between studies for either outcome.Conclusions: This meta-analysis shows that the use of PTFE-covered stent-grafts clearly improves shunt patency without increasing the risk of hepatic encephalopathy and with a trend towards better survival. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Yang Zhiping;Han Guohong;Wu Qiong;Yin Zhanxin;Qi Xingshun;Bai Ming;Wu Kaichun;Fan Daiming;Ye Xiaofei;Jin Zhichao

Journal of Gastroenterology and Hepatology Australia

2010

Han Guo-Hong;He Chuang-Ye;Qi Xing-Shun;Fan Dai-Ming

Journal of Gastroenterology and Hepatology Australia

2010

Zhao Yunping;Hong Liu;Fan Daiming;Wang Ruwen

Digestive Diseases and Sciences

2011

Our previous works revealed that human ribosomal protein S13 (RPS13) was up-regulated in multidrug-resistant gastric cancer cells and overexpression of RPS13 could protect gastric cancer cells from drug-induced apoptosis. The present study was designed to explore the role of RPS13 in tumorigenesis and development of gastric cancer. The expression of RPS13 in gastric cancer tissues and normal gastric mucosa was evaluated by immunohistochemical staining and Western blot analysis. It was found RPS13 was expressed at a higher level in gastric cancer tissues than that in normal gastric mucosa. RPS13 was then genetically overexpressed in gastric cancer cells or knocked down by RNA interference. It was demonstrated that up-regulation of RPS13 accelerated the growth, enhanced in vitro colony forming and soft agar cologenic ability and promoted in vivo tumour formation potential of gastric cancer cells. Meanwhile, down-regulation of RPS13 in gastric cancer cells resulted in complete opposite effects. Moreover, overexpression of RPS13 could promote G1 to S phase transition whereas knocking down of RPS13 led to G1 arrest of gastric cancer cells. It was further demonstrated that RPS13 down-regulated p27 ^kip1 expression and CDK2 kinase activity but did not change the expression of cyclin D, cyclin E, CDK2, CDK4 and p16 ^INK4A . Taken together, these data indicate that RPS13 could promote the growth and cell cycle progression of gastric cancer cells at least through inhibiting p27 ^kip1 expression. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Guo Xueyan;Shi Yongquan;Gou Yawen;Li Jipeng;Han Shuang;Zhang Yanqi;Ning Xiaoxuan;Sun Li;Chen Yu;Sun Shiren;Fan Daiming;Huo Jianhua

Journal of Cellular and Molecular Medicine

2011

Colon carcinogenesis represents a stepwise progression from benign polyps to invasive adenocarcinomas and distant metastasis. It is believed that these pathologic changes are contributed by aberrant activation or inactivation of protein-coding proto-onco genes and tumor suppressor genes. However, recent discoveries in microRNA (miRNA) research have reshaped our understanding of the role of non-protein-coding genes in carcinogenesis. In this regard, a remarkable number of miRNAs exhibit differential expression in colon cancer tissues. These miRNAs alter cell proliferation, apoptosis and metastasis through their interactions with intracellular signaling networks. From a clinical perspective, polymorphisms within miRNA-binding sites are associated with the risk for colon cancer, whereas miRNAs isolated from feces or blood may serve as biomarkers for early diagnosis. Altered expression of miRNA or polymorphisms in miRNA-related genes have also been shown to correlate with patient survival or treatment outcome. With further insights into miRNA dysregulation in colon cancer and the advancement of RNA delivery technology, it is anticipated that novel miRNA-based therapeutics will emerge. © The Author 2010. Published by Oxford University Press. All rights reserved.

Wu William K.K.;Lee Chung W.;Cho Chi H.;Yu Jun;Sung Joseph J.Y.;Law Priscilla T.Y.;Fan Daiming;Wu Kaichun

Carcinogenesis

2011

Aim: Nuclear factor-kappa B inhibitor alpha (IκBα) polymorphisms were found to be associated with inflammatory diseases. However, the association between IκBα polymorphisms with gastric cancer is still unknown. We aim to investigate the association between IκBα polymorphisms and gastric cancer risk in a large population-based case-control study among southern Chinese. Main methods: A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 1010 gastric cancer patients and 1500 healthy controls were enrolled in this study. IκBα polymorphisms were identified by sequencing of IκBα gene ranging from the 2 kb promoter region to the 3.5 kb genomic region. Polymorphisms in IκBα were analyzed by TaqMan SNP genotyping assay. Key findings: rs17103265 deletion homozygote (-/-) had significantly increased gastric cancer risk (OR = 2.11, 95% CI = 1.17-3.83, P = 0.01), compared with rs17103265 T homozygote (TT). rs17103265 (-/-) genotype was significantly associated with increased risk of intestinal-type gastric cancer with (OR = 2.21, 95% CI = 1.19-4.08, P = 0.01), but not with the diffuse or mix type of gastric cancer. rs17103265 (-/-) was associated with poorly differentiated gastric cancer (OR = 2.05, 95% CI = 1.07-3.94, P = 0.03), but not with moderately or well differentiated gastric cancer. A significant decrease in luciferase activity was observed in rs17103265 deletion allele as compared with the vector containing the rs17103265 T allele (P < 0.0001). rs17103265 polymorphism was not associated with the prognosis of gastric cancer patients. Significance: IκBα rs17103265 deletion homozygote is a novel genetic risk factor for gastric carcinogenesis, especially for the development of certain subtypes of gastric cancer in southern Chinese population. © 2011 Elsevier Inc.

Wang Shiyan;Zhang Mingdong;Sung Joseph J.Y.;Yu Jun;Zeng Zhirong;Hu Pinjin;Tian Linwei;Wu Kaichun;Fan Daiming;Chu Jianhong

Life Sciences

2011

Aliment Pharmacol Ther 2011; 33: 1087-1103 Summary Background It is important to evaluate whether screening for JAK2V617F mutation should be routinely performed in patients with Budd-Chiari syndrome (BCS) and portal venous system thrombosis (PVST). However, the prevalence of JAK2V617F mutation in such patients is substantially varied, and its association with development of myeloproliferative disorders (MPD) is deficiently identified. Aims To estimate the prevalence of JAK2V617F mutation and to explore the significance of screening for JAK2V617F mutation in these patients. Methods All observational studies regarding the prevalence of JAK2V617F mutation in patients with BCS and PVST were identified via PubMed and MEDLINE databases. Primary items were the proportions of JAK2V617F mutation and MPD. Results Twenty-three studies fulfilled the inclusion criteria. Regardless of underlying aetiological factors, the pooled prevalence of JAK2V617F mutation was 37% and 24% in patients with BCS and PVST respectively. After pre-existing MPD was excluded, the pooled prevalence was decreased to 26% and 19%. Heterogeneity among studies was significant for the prevalence of JAK2V617F mutation. Compared with healthy subjects and patients with thrombosis in other sites, the prevalence of JAKV617F mutation was significantly higher in patients with BCS and PVST. The prevalence of MPD was significantly higher in patients with JAK2V617F mutation than those without. Conclusions JAK2V617F mutation is frequently found in patients with BCS and PVST, but there is a huge variation of prevalence among the included studies. Additionally, it is more specific to thrombosis in splanchnic areas and strongly associated with the development of MPD in these patients. Further studies are needed to evaluate whether the screening test should be widely performed in Asian countries and cirrhotic patients. © 2011 Blackwell Publishing Ltd.

Qi X.;Yang Z.;Bai M.;Shi X.;Han G.;Fan D.

Alimentary Pharmacology and Therapeutics

2011

Background: MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. A previous report has shown that let-7 family members can act as tumor suppressors in many cancers. Through miRNA array, we found that let-7f was downregulated in the highly metastatic potential gastric cancer cell lines GC9811-P and SGC7901-M, when compared with their parental cell lines, GC9811 and SGC7901-NM; however, the mechanism was not clear. In this study, we investigate whether let-7f acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. Methodology/Principal: Real-time PCR showed decreased levels of let-7f expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7f-mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7f could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7f. Luciferase reporter assays demonstrated that let-7f directly binds to the 3′UTR of MYH9, which codes for myosin IIA, and real-time PCR and Western blotting further indicated that let-7f downregulated the expression of myosin IIA at the mRNA and protein levels. Conclusions/Significance: Our study demonstrated that overexpression of let-7f in gastric cancer could inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene MYH9. These data suggest that let-7f may be a novel therapeutic candidate for gastric cancer, given its ability to reduce cell invasion and metastasis. © 2011 Liang et al.

Liang Shuli;He Lijie;Zhao Xiaodi;Miao Yu;Gu Yong;Guo Changcun;Xue Zengfu;Dou Weijia;Hu Fengrong;Wu Kaichun;Nie Yongzhan;Fan Daiming

Plos One

2011

Background and Aim: Hepatic encephalopathy (HE) is a very common complication in patients after transjugular intrahepatic portosystemic shunt (TIPS). The purpose of this study is to determine the most robust predictors of post-TIPS HE by performing a systematic review of studies that identified the risk factors for patients with post-TIPS HE. Methods: A PUBMED search was performed using the predefined rule. Studies were selected for analysis based on certain inclusion and exclusion criteria. Data were extracted from each study on the basis of predefined items. Meta-analyses were executed to verify the relevant risk factors. Results: Thirty studies were included in this systematic review. In the 30 studies, the numbers of variables evaluated by univariate and multivariate analyses were 60 and 32, respectively. The numbers of variables found to be significant in univariate and multivariate analyses were 18 and 14, respectively. According to the accumulated number of studies that identified these variables as significant, the three most vigorous predictors of post-TIPS HE were age, prior HE and Child-Pugh class/score in both univariate analysis and multivariate analysis. Our meta-analysis showed that patients with HE before TIPS or higher Child-Pugh class/score had increased risk of post-TIPS HE. Conclusions: Increased age, prior HE and higher Child-Pugh class/score were the most robust predictors for post-TIPS HE. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Bai Ming;Qi Xingshun;Yin Zhanxin;Yuan Shanshan;Han Guohong;Nie Yongzhan;Yang Zhiping;Wu Kaichun;Fan Daiming

Journal of Gastroenterology and Hepatology Australia

2011