科创中国

Hepatitis B virus (HBV)-encoded X antigen (HBxAg) contributes to the development of hepatocellular carcinoma (HCC). A frequent characteristic of HCC is reduced or absent expression of the cell adhesion protein, E-cadherin, although it is not known whether HBxAg plays a role. To address this, the levels of E-cadherin were determined in HBxAg-positive and -negative HepG2 cells in culture, and in tumor and surrounding nontumor liver from a panel of HBV carriers. The results showed an inverse relationship between HBxAg and E-cadherin expression both in tissue culture and in vivo. In HBxAg-positive cells, E-cadherin was suppressed at both the mRNA and protein levels. This was associated with hypermethylation of the E-cadherin promoter. Depressed E-cadherin correlated with HBxAg trans-activation function, as did the migration of HepG2 cells in vitro. Decreased expression of E-cadherin was also associated with the accumulation of β-catenin in the cytoplasm and/ or nuclei in tissues and cell lines, which is characteristic of activated β-catenin. Additional work showed that HBxAg-activated β-catenin. Together, these results suggest that the HBxAg is associated with decreased expression of E-cadherin, accumulation of β-catenin in the cytoplasm and nucleus, and increased cell migration, which may contribute importantly to hepatocarcinogenesis. © 2006 Nature Publishing Group All rights reserved.

Liu J.;Lian Z.;Feitelson M. A.;Han S.;Wu K.;Ding J.;Fan D.;Waye M. M.Y.;Wang H.;Wu M. C.;Arbuthnot P.;Kew M.

Oncogene

2006

Cellular priori protein (PrP ^C ), a glycosylphosphatidylinositol-anchored membrane protein, was found in our lab to be widely expressed in gastric cancer cell lines. In order to evaluate its biological significance in human gastric cancer, we investigated its expression in a large series of gastric tissue samples (n = 124) by immunohistochemical staining with the monoclonal antibody 3F4. Compared with normal tissues, gastric adenocarcinoma showed increased PrP ^C expression, correlated with the histopathological differentiation (according to the WHO and Lauren classifications) and tumor progression (as documented by pTNM staging). To better understand the underlying mechanism, we introduced the PrP ^C and two pairs of RNAi into the poorly differentiated gastric cancer cell line AGS and found that PrP ^C suppressed ROS and slowed down apoptosis in transfected cells. Further study proved that the apoptosis-related protein Bcl-2 was upregulated whereas p53 and Bax were downregulated in the PrP ^C -transfected cells. A reverse effect was observed in PrP ^C siRNA-transfected cells. These results strongly suggested that PrP ^C might play a role as an effective antiapoptotic protein through Bcl-2-dependent apoptotic pathways in gastric cancer cells. Further study into the mechanism of these relationships might enrich the knowledge of PrP, better our understanding of the nature of gastric carcinoma, and further develop possible strategies to block or reverse the development of gastric carcinoma. Copyright © 2006 S. Karger AG.

Liang J.;Pan Y. L.;Ning X. X.;Sun L. J.;Lan M.;Hong L.;Du J. P.;Liu N.;Liu C. J.;Qiao T. D.;Fan D. M.

Tumor Biology

2006

Peroxisome proliferator-activated receptor gamma (PPARγ) ligands have been shown to inhibit angiogenesis. We showed that treatment with 15d-PGJ2, a PPARγ ligand, downregulate the expressions of angiopoietin-1 (Ang-1) in gastric cancer cells MKN45. The medium of MKN45 cells treated with 15d-PGJ2 significantly inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, Matrigel plug assay revealed that 15d-PGJ2 reduced in vivo angiogenesis induced by MKN45 cells. These modulations were restored by the addition of recombinant Ang-1. Our findings supported that 15d-PGJ2 suppressed angiogenesis of gastric cancer cells by downregulation of Ang-1. © 2005 Elsevier Ireland Ltd. All rights reserved.

Fu Yuan-Gen;Sung Joseph J.Y.;Bai Alfa H.C.;Chan Martin C.W.;Yu Jun;Leung Wai K.;Wu Kai-Chun;Fan Dai-Ming

Cancer Letters

2006

As a new gene, the monoclonal antibody against URG11 protein is not currently available. In this study, me monoclonal antibody (MAb) against URG11 was obtained with standard cell fusion technique and enzyme-linked immunosorbent assay (ELISA) screening. The peptide of URG11 used in making the MAb in this study was synthesized as described. One of the newly developed MAbs is named MAb 3D2, the isotype of which is IgG2a. Immunohistochemistry and Western blot showed that MAb 3D2 could recognize URG11 protein in both native and denatured forms. MAb 3D2 will be a useful tool for the functional research of URG11 in future studies. © Mary Ann Liebert, Inc.

Zou Xue;Li Xiaohua;Liu Jie;Fan Rui;Du Rui;Xie Huahong;Song Jiugang;Fan Daiming;Lian Zhaorui

Hybridoma

2006

Zinc ribbon domain containing 1 (ZNRD1) gene encoding a protein consisting of two zinc ribbon domains was recently cloned from the human HLA locus. So far, ZNRD1 has been found implicated in transcription regulation and might play potential roles in mediating several biological processes, including multidrug resistance, tumorigenesis and cell cycle. This article reviewed these recent findings and provided additional information to support the role of ZNRD1 gene as a novel candidate DNA damage repair related gene. Copyright © Experimental Oncology, 2006.

Hong L.;Han Y.;Chen Z.;Zhang X.;Xia L.;Han Z.;Lu Y.;Jin H.;Song J.;Qiao T.;Fan D.

Experimental Oncology

2006

Colorectal cancer is one of the most prevalent malignancies in the world. Chinese researchers and clinical doctors had been working hard in the last 12 years, exploring efficient and convenient methods for screening and early diagnosis. The 12 years research works indicated that SFOBT plus colonoscopy was the best detecting protocol for mass screening of colorectal cancer. Serial combined testing for tumor markers plus colonoscopy is the most commonly used strategy for early diagnosis. However, still no optimum method for early diagnosis was generally accepted by most researchers. Due to intrinsic defects of the techniques, several screening and diagnostic methods should be combined to bring each advantage into full play, in order to elevate the diagnostic level of colorectal cancer. © 2007 Springer-Verlag.

Li Shirong;Wang Jiheng;Lu Yuanyuan;Fan Daiming

Journal of Cancer Research and Clinical Oncology

2007

Gastric cancer is the second leading cause of cancer mortality worldwide. The major cause of treatment failure for gastric cancer is the development of multidrug resistance (MDR) to chemotherapy, which is currently one of the primary treatment options. Recently, research into the MDR of gastric cancer has revealed that, in addition to the classical ATP-binding cassette transporters, such as P-glycoprotein (P-gp) and MDR-associated protein (MRP)1, a number of other molecules might mediate the drug resistance of human gastric cancer. The absence of P-gp and MRP1 expression in some gastric cancer cases also indicates that there might be other mechanisms responsible for human gastric cancer MDR. These molecules belong to different functional families and might work together to confer MDR phenotypes. The new findings may provide new clues to the mechanisms of MDR and enable the selection of new candidates for targeting MDR in human gastric cancer. © 2007 Future Drugs Ltd.

Zhang Dexin;Fan Daiming

Expert Review of Anticancer Therapy

2007

OBJECTIVE: To investigate the effect of gene Af116609 on gastric cancer multi-drug resistance (MDR) by introducing it into gastric cancer multi-drug resistant (MDR) cell line SGC7901/VCR. METHODS: Gene Af116609 was cloned from SGC7901/VCR by RT-PCR and its differential expression between gastric cancer MDR cells and its parental cells was displayed by Northern blot. The gene was introduced to gastric cancer cells by transfection of recombinant eukaryotic expression vector by electroporation. MTT assay in vitro was applied to investigate its effect on multi-drug resistance phenotype of gastric cancer cells. RESULTS: The full length CDS of gene Af116609, as long as 327 bp, was cloned from gastric cancer MDR cell line SGC7901/VCR and its sequence was coincident with the hypothetical gene Af116609 in GenBank. It was overexpressed in MDR cells than its parental cells at mRNA level. In the MTT assay in vitro, the drug sensitive cells transfected with sense eukaryotic expression vector showed upregulated targeted gene, with increased resistance to vincristine, 5-fliorouracil and arabinoside, and decreased resistance to adriamycin, but no influence on resistance to methotrexate. However, the drug resistant cells transfected with anti-sense eukaryotic expression vector, showed down regulated targeted gene, with less resistance to all the five anticancer drugs to different degrees. CONCLUSION: Gene Af116609 is related to MDR phenotype of gastric cancer cells and may become a candidate molecular target to reverse the MDR of gastric cancer.

Jin Xiao-hang;Du Jing-ping;Yin Fang;Zhang Yu-mei;Hu Wen-hua;Cao Yun-xin;Shi Yong-quan;Zhao Yan-qiu;Qiao Tai-dong;Fan Dai-ming

Zhonghua Zhong Liu Za Zhi Chinese Journal of Oncology

2005

Fan Dai-ming

Zhonghua Yi Xue Za Zhi

2005

Background: Prevention and treatment of human cancer through immunotherapy has been difficult owing to lack of a specific target and poor immunity. It is of no surprise that cancer mucosa antigens (CMAs) may serve as attractive targets for cancer immunotherapy. Objective: To present and discuss the current state of the research on CMAs. Methods: We review the evidence that a number of CMAs have been used to augment immune responses against cancer and that some progress has been made. We envisage future developments toward identifying CMAs and their potential applications to cancer treatment. Results/conclusion: CMAs may reasonably be considered as novel targets for immunotherapy. More investigations should be performed to improve the success of immunotherapy in clinical trials. © 2008 Informa UK Ltd.

Hong Liu;Fan Daiming

Expert Opinion on Therapeutic Targets

2008