科创中国

Objective: To study the expression, distribution and significance of the C2 gene in hepatocellular carcinoma (HCC) and gastric cancer tissue. Methods: The avidin-biotin-peroxidase complex (ABC) immunohistochemical method was used to detect the expression of C2 protein in 60 specimens of HCC and 58 specimens of gastric cancer tissue, and the western blot technique was used to detect the expression of C2 protein in 10 specimens of HCC and associated pericancerous tissue. Results: In 60 specimens of HCC and 42 specimens of associated pericancerous tissue, the rates of C2 protein detection were 27.3 and 83.3%, respectively; the latter being significantly greater than the former (P < 0.001). The expression of C2 protein was significantly correlated with the patient's age, HBsAg and α-fetoprotein (AFP; P < 0.05). The findings from western blotting were consistent with those from immunohistochemical methods. The rate of C2 protein detection was 20.4% in 49 specimens of HCC that were hepatitis-B virus encoded X antigen (HBxAg)-positive, but 63.6% in 11 HCC specimens that were HbxAg-negative. The rate of C2 protein detection was significantly lower in HbxAg-positive tissue than in HbxAg-negative tissue (P < 0.05). In 58 specimens of gastric cancer tissue and 44 specimens of associated pericancerous tissue, the rates of C2 protein detection were 41.4 and 77.3%, respectively. The rate was significantly higher in gastric cancer tissue than in associated pericancerous tissue (P < 0.05), and C2 protein detection was significantly correlated with pathological grading, tumor size and the depth of invasion (P < 0.05). Conclusions: Low expression of the C2 gene might be involved in the development of HCC and gastric cancer. The suppression of C2 by HBxAg may play an important role in the development of HCC. C2 may be a potential tumor suppression gene.

Qing Zhang;Jie Liu;Li Zhang;Qing Li;Xue Mei Zhang;Xin Wang;Tai Dong Qiao;代明 樊;Mark Feitelson

Chinese Journal of Digestive Diseases

2003

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.

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

Life Sciences

2011-4-25

Twist-1 protein (also called Twist) has been suggested to be involved in tumor epithelial-mesenchymal transition (EMT) related progression, however, the mechanism by which twist promotes lymph node metastasis is not fully understood. In the present study, we found that nuclear twist expression is clearly correlated with lymph node (LN) metastasis as determined by immunohistochemistry (IHC). A highly invasive EC109 cell subline, EC109-P, was established by repeated in vitro transwell isolations for the cell model. Immunofluorescence (IF) assay demonstrated that nuclear twist expression was markedly higher in the highly invasive EC109-P cell line when compared with EC109 and EC9706 cells. Based on our cell model, the function and mechanism by which twist regulates LN metastasis in ES CC was investigated. The results showed that the overexpression of Twist could significantly increase the invasion and VEGF-C expression of EC9706 cells, whereas the knockdown of twist expression results in the opposite effects. This finding was further strengthened by the results of the analysis of co-expression of twist and VEGF-C by IHC in ES CC clinical samples. In summary, our study indicates that nuclear twist plays an important role in ES CC lymphatic metastasis by increasing the expression of VEGF-C. The combination of twist and VEGF-C detection could be a reliable prediction of LN metastasis in ESCC.

Taiqian Gong;Zengfu Xue;Shanhong Tang;Xiushan Zheng;Guanghui Xu;Liucun Gao;Guohong Zhao;Liu Hong;Guangbo Tang;Hongwei Zhang;Ruwen Wang;Yaoguang Jiang;代明 樊

Cancer Biology and Therapy

2012-6

Xingshun Qi;Jia Jia;Ming Bai;代明 樊;Guohong Han

Annals of Gastroenterology

2014

The molecular adsorbent recirculating system (MARS) is a novel extracorporeal technique for liver support. We report the clinical results in a group of fourteen patients with drug-induced liver failure. Fourteen patients, aged 22-83 years, with acute or subacute liver failure [mean Child-Turcotte-Pugh (CTP) score 11 (range 8-15)] due to the intake of various drugs (diet pill overdose - 2; Chinese traditional medicine (CTM) - 4; antibiotic, paracetamol, tuberculostatic, or vasodilator abuse - 8) were treated with one to seven sessions of MARS. Beneficial effects such as the improvement of encephalopathy and prothrombin activity, as well as a reduction of bilirubin and ammonia were recorded during MARS treatments. Thirteen out of fourteen patients survived the hospitalization (93%), and two of the discharged patients died during the follow-up of 6-12 months. The overall survival rate was about 79%. MARS therapy can contribute to the improved treatment of drug-induced liver failure patients.

Xin Min Zhou;Ji Yan Miao;Yan Yang;Ling Zhao;Xin Wang;Li Xu;Jie Ding;Kai Chun Wu;代明 樊;Min Min Wang

Artificial Organs

2004-5

Liu Hong;Xiaohua Li;Haifeng Jin;Li Yan;Kaichun Wu;Jie Ding;Yunping Zhao;Wei Guo;代明 樊

Medical Hypotheses

2007

This paper aimed to systematically review the survival of Budd-Chiari syndrome and to identify the most robust prognostic predictors. Overall, 79 studies were included. According to the treatment modalities, the median 1-, 5-and 10-year survival rate was 93, 83 and 73% after interventional radiological treatment; 81, 75 and 72.5% after surgery other than liver transplantation; 82.5, 70.2 and 66.5% after liver transplantation and 68.1, 44.4% and unavailable after medical therapy alone. According to the publication years, the median 1-, 5-and 10-year survival rate was 68.6, 44.4% and unavailable before 1990; 75.1, 69.5 and 57% during the year 1991-1995; 77, 69.6 and 65.6% during the year 1996-2000; 86.5, 74 and 63.5% during the year 2001-2005 and 90, 82.5 and 72% after 2006. Bilirubin, creatinine and ascites were more frequently identified as significant prognostic factors in univariate analyses. But their statistical significance was less frequently achieved in multivariate analyses.

Xingshun Qi;Weirong Ren;Yongji Wang;Xiaozhong Guo;代明 樊

Expert Review of Gastroenterology and Hepatology

2015-7-1

Objective To construct in vitro transcription vectors of genes of c- erbB-2 specific ribozyme and its substrate and to probe its in vitro cleavage action. Methods According to the computer design, a specific restriction site EcoR V was added to the 3' end of the ribozyme gene (RZ1). Then, the RZ1 gene and its substrate gene were cloned into the in vivo transcription vector pGEM3Zf(-) separately. The recombinants containing RZ1 gene were first screened by agrose gel electrophoresis through EcoR V digestion and was identified by automatic sequencing. The products of in vitro transcription were labeled with ³²P. In vitro cleavage reaction was performed at 37°C for 1h under the presence of Mg⁺⁺. The cleavage product was analyzed by polyacrilamide gel electrophoresis. After autoradiography, the cleavage rate was counted by image analysis. Results The recombinants containing the RZ1 gene were successfully selected by the EcoR V digestion and were designated as pGM3Z-RZ1. The automatic sequence analysis proved that the synthesized RZ1 gene was correct. The target gene was also cloned into the pGEM3Zf(-) under SP6 promoter. After in vitro transcription, the cleavage reaction was shown to have cut off 79.3% target RNA in 1h. Conclusion The c-erbB-2 oncogene- specific ribozyme has a high activity in vitro. It lays a foundation for the study of the therapeutic use of ribozyme in gene therapy of cancer.

B. Feng;Z. Xueyong;代明 樊

Chinese Journal of Oncology

1999

Objective: This prospective non-randomized controlled trial aimed to compare the efficacy of sorafenib in combination with transarterial chemoembolization (TACE) vsTACE alone for the treatment of patients with unresectable intermediate or advanced hepatocellular carcinoma. Methods: A total of 304 patients were enrolled, in which 82 received concurrent sorafenib (400mg orally twice daily, initiated within 14 days after TACE), and these patients were matched with 164 patients who received TACE alone at a 1:2 ratio using propensity score matching to minimize selection bias. The response to treatment, time-to-progression (TTP), overall survival (OS) as well as adverse events were compared between the two groups. Results: During a median follow-up period of 21.4 weeks (range 0.5-103 weeks), the addition of sorafenib prolonged TTP (6.3 vs 4.3 months; hazard ratio [HR] 0.60, 95% CI 0.422-0.853, P=0.004) and median survival (7.5 vs 5.1 months; HR 0.61, 95% CI 0.423-0.884, P=0.009) compared with TACE alone. Significant prognostic factors for OS by multivariate analysis included the use of sorafenib, Barcelona Clinic Liver Cancer stage, metastasis/vascular invasion and Child-Pugh score. Conclusions: The combined use of sorafenib and TACE was generally well tolerated and significantly improved OS and TTP compared with TACE alone in patients with intermediate or advanced HCC. Further studies are warranted to confirm the safety and efficacy of this combination therapy.

Wei Bai;Yong Ji Wang;Yan Zhao;Xing Shun Qi;Zhan Xin Yin;Chuang Ye He;Rui Jun Li;Kai Chun Wu;Jie Lai Xia;代明 樊;Guo Hong Han

Journal of Digestive Diseases

2013-4

Identifying an effective therapeutic target is pivotal in the treatment of gastric cancer. In this study, we investigated the expression of p75 neurotrophin receptor (p75NTR) in gastric cancer and the impact of its alteration on tumor growth. p75NTR expression was absent or significantly decreased in 212 cases of gastric cancers compared with the normal gastric mucosa (P < .05). Moreover, p75NTR expression was also lost or significantly decreased in various human gastric cancer cell lines. p75NTR inhibited in vitro growth activities and caused dramatic attenuation of tumor growth in animal models by induction of cell cycle arrest. Upregulation of p75NTR led to downregulation of cyclin A, cyclin D1, cyclin E, cyclin-dependent kinase 2, p-Rb, and PCNA, but to upregulation of Rb and p27 expressions. Conversely, downregulating p75NTR with specific siRNA yielded inverse results. The rescue of tumor cells from cell cycle progression by a death domain-deleted dominant-negative antagonist of p75NTR (Δp75NTR) showed that the death domain transduced antiproliferative activity in a ligand-independent manner and further demonstrated the inhibitive effect of p75NTR on growth in gastric cancer. Therefore, we provided evidence that p75NTR was a potential tumor suppressor and may be used as a therapeutic target for gastric cancer.

Haifeng Jin;Yanglin Pan;Lina Zhao;Huihong Zhai;Xiaohua Li;Li Sun;Lijie He;Yu Chen;Liu Hong;Yulei Du;代明 樊

Neoplasia

2007-6