Weifen Xie

Second Military Medical University, Shanghai, Shanghai, Shanghai Shi, China

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Publications (12)33.93 Total impact

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    ABSTRACT: Cyclin G1 deficiency is associated with reduced incidence of carcinogen-induced hepatocellular carcinoma (HCC), but its function in HCC progression remains obscure. We report a critical role of cyclin G1 in HCC metastasis. Elevated expression of cyclin G1 was detected in HCCs (60.6%), and its expression levels were even higher in portal vein tumor thrombus. Clinicopathological analysis revealed a close correlation of cyclin G1 expression with distant metastasis and poor prognosis of HCC. Forced expression of cyclin G1 promoted epithelial-mesenchymal transition (EMT) and metastasis of HCC cells in vitro and in vivo. Cyclin G1 overexpression enhanced Akt activation through interaction with p85 (regulatory subunit of phosphoinositide 3-kinase [PI3K]), which led to subsequent phosphorylation of glycogen synthase kinase-3β (GSK-3β) and stabilization of Snail, a critical EMT mediator. These results suggest that elevated cyclin G1 facilitates HCC metastasis by promoting EMT via PI3K/Akt/GSK-3β/Snail-dependent pathway. Consistently, we have observed a significant correlation between cyclin G1 expression and p-Akt levels in a cohort of HCC patients, and found that combination of these two parameters is a more powerful predictor of poor prognosis. CONCLUSIONS: Cyclin G1 plays a pivotal role in HCC metastasis and may serve as a novel prognostic biomarker and therapeutic target.
    Hepatology 06/2012; 55(6):1787-98. DOI:10.1002/hep.25596 · 11.06 Impact Factor
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    ABSTRACT: Hypoxia-inducible factor (HIF) and cyclin D1 are both key mediators of cell growth and proliferation in normal and cancer cells. However, the interrelation between HIF and cyclin D1 remains unclear. In the present study, we observed the inverse correlation between cyclin D1 and HIF-1 in hypoxia condition. Overexpression of the dominant negative mutant of HIF-1alpha (DN-HIF) significantly enhanced cyclin D1 expression upon hypoxia or arsenite exposure, suggesting the negative regulation of cyclin D1 by HIF-1. Furthermore, we found that the impairment of HIF-1 increased cyclin D1 expression in A549 pulmonary cancer cells, which in turn promoted G1-S cell cycle transition and cell proliferation. Cyclin D1 expression was increased in s.c. xenograft of DN-HIF stably transfected A549 cells in nude mice compared with that of control cells. Chromatin immunoprecipitation assay revealed that HIF-1 was able to directly bind to the promoter region of cyclin D1, which indicates that the negative regulation of cyclin D1 by HIF-1 is through a direct mechanism. Inhibition of histone deacetylase (HDAC) by pretreatment of cells with trichostatin A or specific knockdown of HDAC7 by its shRNA antagonized the suppression of cyclin D1 by HIF-1, suggesting that HDAC7 is required for HIF-1-mediated cyclin D1 downregulation. Moreover, we found that 5-fluorouracil-triggered apoptosis of DN-HIF-transfected A549 cells was reduced by sicyclin D1 (cyclin D1-specific interference RNA) introduction, suggesting that clinical observation of HIF-1 overexpression-associated chemoresistance might be, at least partially, due to the negative regulation of cyclin D1.
    Cancer Research 02/2010; 70(5):2010-9. DOI:10.1158/0008-5472.CAN-08-4910 · 9.33 Impact Factor
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    ABSTRACT: Benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), the major metabolite of B[a]P, has been well recognized as one ubiquitous carcinogen, but the molecular mechanism involved in its carcinogenic effect remains obscure. In the present study, we found that bronchial epithelial cells (Beas-2B) and hepatocytes treated with B[a]PDE presented a significant increase of cyclin D1 expression. Moreover, Akt, p70(s6k), and MAPKs including JNK, Erks, and p38 were notably activated in B[a]PDE-treated Beas-2B cells, whereas NF-kappaB, NFAT, and Egr-1 were not. Our results demonstrated that JNK and Erks were required in B[a]PDE-induced cyclin D1 expression because the inhibition of JNK or Erks by a selective chemical inhibitor or dominant negative mutant robustly impaired the cyclin D1 induction by B[a]PDE. Furthermore, we found that overexpression of the dominant negative mutant of p85 (regulatory subunit of phosphatidylinositol 3-kinase) or Akt dramatically suppressed B[a]PDE-induced JNK and Erk activation as well as cyclin D1 expression, suggesting that cyclin D1 induction by B[a]PDE is via the phosphatidylinositol 3-kinase/Akt/MAPK-dependent pathway. In addition, we clarified that p70(s6k) is also involved in B[a]PDE-induced cyclin D1 expression because rampamycin pretreatment dramatically reduced cyclin D1 induction by B[a]PDE. More importantly, we demonstrated that up-regulated cyclin D1 by B[a]PDE plays a critical role in oncogenic transformation and tumorigenesis of Beas-2B cells. These results not only broaden our knowledge of the molecular mechanism of B[a]PDE carcinogenicity but also lead to the further study of chemoprevention of B[a]PDE-associated human cancers.
    Journal of Biological Chemistry 09/2009; 284(48):33311-9. DOI:10.1074/jbc.M109.046417 · 4.57 Impact Factor
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    ABSTRACT: Frequent exposure to nickel compounds has been considered as one of the potential causes of human lung cancer. However, the molecular mechanism of nickel-induced lung carcinogenesis remains obscure. In the current study, slight S-phase increase, significant G(2)/M cell cycle arrest, and proliferation blockage were observed in human bronchial epithelial cells (Beas-2B) upon nickel exposure. Moreover, the induction of cyclin D1 and cyclin E by nickel was shown for the first time in human pulmonary cells, which may be involved in nickel-triggered G(1)/S transition and cell transformation. In addition, we verified that hypoxia-inducible factor-1alpha, an important transcription factor of nickel response, was not required for the cyclin D1 or cyclin E induction. The role of p53 in nickel-induced G(2)/M arrest was excluded, respecting that its protein level, ser(15) phosphorylation, and transcriptional activity were not changed in nickel response. Further study revealed that cyclin A was not activated in nickel response, and cyclin B1, which not only promotes G(2)/M transition but also prevents M-phase exit of cells if not degraded in time, was up-regulated by nickel through a manner independent of hypoxia-inducible factor. More importantly, our results verified that overexpressed cyclin B1, veiling the effect of cyclin D1 or cyclin E, mediated nickel-caused M-phase blockage and cell growth inhibition, which may render pulmonary cells more sensitive to DNA damage and facilitates cancer initiation. These results will not only deepen our understanding of the molecular mechanism involved in nickel carcinogenecity, but also lead to the further study on chemoprevention of nickel-associated human cancer.
    Cancer Epidemiology Biomarkers & Prevention 07/2009; 18(6):1720-9. DOI:10.1158/1055-9965.EPI-09-0115 · 4.13 Impact Factor
  • Xin Jiang · Guifang Wang · Hongpei Cai · Weifen Xie ·
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    ABSTRACT: No abstract is available for this article.
    Liver international: official journal of the International Association for the Study of the Liver 04/2009; 29(4):566. DOI:10.1111/j.1478-3231.2008.01962.x · 4.85 Impact Factor
  • Bin Shi · Yiping Wang · Yuexiang Chen · Weizhong Chen · Weifen Xie ·
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    ABSTRACT: A 39-year-old man with chronic bleeding from Rendu-Osler-Weber disease in the small intestine was treated with argon plasma coagulation using a custom-made probe under double-balloon enteroscopy. A 10 month follow-up showed no evidence of bleeding.
    Case Reports 02/2009; 2009. DOI:10.1136/bcr.08.2008.0664
  • Bin Shi · Liang Zhu · Weifen Xie · Zhongbing Zhang · Guoqiang Wu ·
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    ABSTRACT: A model of intrahepatic portal hypertension was established in SD rats by injection of carbon tetrachloride (CCl4). By observing the opening angle of the portal vein, the zero-stress state of the portal veins was studied at different time during the pathogenesis of intrahepatic portal hypertension. After CCl4 injection, the opening angles of the portal veins were increased, in the tenth week, they were much greater than those in the corresponding controls (P<0.05). The results suggest that during the pathogenesis of portal hypertension, unequal remodeling exists in the portal veins to change its biomechanical properties, and the residual stress and strain of the portal veins in portal hypertensive rats are greater than those in normal controls.
    Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 09/2006; 23(4):753-5.
  • Yuxiang Chen · Xingrong Zhang · Weifen Xie · Shi Li ·
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    ABSTRACT: To investigate the effect of lovastatin on proliferation and extracellular matrix secretion of hepatic stellate cells in vitro. Rat hepatic stellate cells were incubated with different concentration of lovastatin and geranyl geranypyrophosphate. Cell proliferation was assessed by MTT colorimetric assay. Cell cycle was analysed by flow cytometry. Type IV collagen and laminin were determined by ELISA, and c-jun and c-fos expression by immunocytochemistry and computer video text analysis system. Addition of 0.1 to 50 micromol/L lovastatin into culture medium had no toxicity to hepatic stellate cells, but could significantly inhibit hepatic stellate cell proliferation and provoke G0/G1 phase arrest in dose-dependent manner, and could also markedly inhibit the c-jun and c-fos expression and type IV collagen and laminin secretion, which could partly be antagonized by geranyl geranypyrophosphate. Lovastatin can significantly inhibit hepatic stellate cell proliferation and type IV collagen and laminin secretion, which might be partly related to its inhibitory effect on geranyl geranypyrophosphate formation.
    Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 11/2002; 10(5):370-3.
  • Dingkang Yao · Weifen Xie · Lei Wang ·
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    ABSTRACT: To improve the diagnosis and management of primary biliary cirrhosis (PBC). Clinical data of 22 cases of PBC were reviewed including the clinical manifestation, laboratory test, and the response to therapy. There were 20 female patients with an average of 50 years old in total of 22 PBC patients. The major symptoms were pruritus, fatigue, anorexia, and abdominal discomfort. The major signs included jaundice, hepatomegaly, splenmegaly, and ascites. Very high levels of serum alkaline phosphatase (ALP) and serum gamma glutamyl transpeptidase (GGT), hyperbilirubinemia and hypergammaglobulinemia were also detected in most of the patients. The aminotransferase level was only slightly elevated but the AST/ALT ratio was reversed. It took 8 months (ranging from 2 months to 5 years) to confirm the diagnosis after the clinical manifestation onset. Ursodeoxycholic acid could decrease the serum levels of ALP and bilirubin in 80% of the patients (12/15) and improve the symptom of pruritus and fatigue in 72.7% of the patients (11/15). PBC mainly affects middle-aged women and the main clinical manifestations are hepatosplenomegaly, jaundice, pruritus, and fatigue. Liver function test typically reveal a cholestatic pattern accompanied by hypergammagloblinemia and a positive antimitochondrial antibody (AMA) including M2 subtype (AMA-M2). Ursodeoxycholic acid could improve the abnormal liver function tests and clinical features in PBC patients
    Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 11/2002; 10(5):344-5.

  • Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 11/2002; 10(5):383.
  • Bin Shi · Liang Zhu · Weifen Xie · Zhongbing Zhang ·
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    ABSTRACT: The zero-stress state of the esophagus is the state in which the esophagus is stress-free. It is in close correlation with physiology and pathology of the esophagus. The purpose of the review is to describe briefly the basic theory of zero-stress state and its physiological and pathologic implications in the esophagus.
    Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 07/2002; 19(2):320-3.
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    ABSTRACT: OBJECTIVE: To investigate the effect of recombinant human tumor necrosis factor (rhTNF) on telomerase activity and promoter expression of catalytic protein subunit–human telomerase reverse transcriptase (hTERT) in hepatoma cell lines HepG2 cells and HepG1-6.METHODS: The tartrate-resistant acid phosphatase– enzyme-linked immunosorbent assay method (TRAP-ELISA) was used to determine telomerase activity in HepG2 and HepG1-6 cells that had been treated with different concentrations of rhTNF. The plasmid TERTluc(800), which contained 800 bp of the hTERT promoter, was transiently transfected into HepG2 cells by using Lipofect, and different concentrations of rhTNF were added into the culture media 2 h later. The activity of the hTERT promoter was tested 48 h after transfection.RESULTS: The telomerase activity of hepatoma cells was suppressed by rhTNF in a dose-dependent manner. Furthermore, the transient transfection of HepG2 cells with the TERTluc(800) plasmid revealed that hTERT promoter activity is not affected by 10 IU/mL rhTNF, whereas the expression of the hTERT promoter is inhibited by rhTNF at concentrations ranging from 10 to 1000 IU/mL; the extent of inhibition is linearly related to the rhTNF concentration. The activity of the hTERT promoter in cells treated with 1000 IU/mL of rhTNF decreased to 60.3% of that of the control. No extra suppressive effect was observed when a concentration of 10 000 IU/mL was used.CONCLUSIONS: These results suggest that the antitumor activity of rhTNF may be attributed to its inhibitory effect on hTERT promoter expression. Together with other studies, it may indicate that telomerase is not only involved in carcinogenesis, but is also one of the main targets of anticancer cytokines. Further analysis of the molecular mechanism underlying the regulation of telomerase by TNF and isolation of the related transcription factor may provide new means for cancer gene therapy.
    Chinese Journal of Digestive Diseases 12/2001; 2(4):198 - 201. DOI:10.1046/j.1443-9573.2001.00056.x