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| 1 | Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis显示文摘AIM:To determine the utility of connective tissue growth factor(CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus(HBV)-induced chronic liver diseases(CLD-B).METHODS:Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B(CHB) and 39 patients with HBVinduced active liver cirrhosis and 30 healthy individuals.Liver samples from 31 patients with CHB,8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1(TGF-β1) or CCN2 mRNA levels by in situ hybridization,and computer image analysis was performed to measure integrated optimal density(IOD) of CCN2 mRNA-positive cells in liver tissues.Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson's method.RESULTS:Serum CCN2 concentrations were,respectively,4.0-or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals(P < 0.01).There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues(r = 0.87,P < 0.01).The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B(r = 0.85,P < 0.01).Serum CCN2 was a reliable marker for the assessment of liver fibrosis,with areas under the receiver operating characteristic(ROC) curves(AUC) of 0.94 or 0.85 for,respectively,distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.CONCLUSION:Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis. | Rong-Li Piao David R Brigstock Jie Zhu Man-Li Zhang Run-Ping Gao | 2012 | World Journal of Gastroenterology2012，18，18： | 12 |
| 2 | Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function显示文摘AIM:To determine the effect of hammerhead ribozyme targeting connective tissue growth factor (CCN2)on human hepatic stellate cell(HSC)function. METHODS:CCN2 hammerhead ribozyme cDNA plus two self-cleaving sequences were inserted into pTriEx2 to produce pTriCCN2-Rz.Each vector was individually transfected into cultured LX-2 human HSCs,which were then stimulated by addition of transforming growth factor(TGF)-β1 to the culture medium.Semi- quantitative RT-PCR was used to determine mRNA levels for CCN2 or collagenⅠ,while protein levels of each molecule in cell lysates and conditioned medium were measured by ELISA.Cell-cycle progression of the transfected cells was assessed by flow cytometry. RESULTS:In pTriEx2-transfected LX-2 cells,TGF-β1 treatment caused an increase in the mRNA level for CCN2 or collagenⅠ,and an increase in produced and secreted CCN2 or extracellular collagenⅠprotein levels.pTriCCN2-Rz-transfected LX-2 cells showed decreased basal CCN2 or collagen mRNA levels,as well as produced and secreted CCN2 or collagenⅠprotein. Furthermore,the TGF-β1-induced increase in mRNA or protein for CCN2 or collagenⅠwas inhibited partially in pTriCCN2-Rz-transfected LX-2 cells.Inhibition of CCN2 using hammerhead ribozyme cDNA resulted in fewer of the cells transitioning into S phase.CONCLUSION:Endogenous CCN2 is a mediator of basal or TGF-β1-induced collagenⅠproduction in human HSCs and regulates entry of the cells into S phase. | Run-Ping Gao David R Brigstock | 2009 | World Journal of Gastroenterology2009，15，30： | 9 |
| 3 | Connective tissue growth factor is overexpressed in human hepatocellular carcinoma and promotes cell invasion and growth显示文摘AIM:To determine the expression characteristics of connective tissue growth factor(CTGF/CCN2) in human hepatocellular carcinoma(HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression and metastasis in vitro.METHODS:Liver samples from 36 patients(who underwent hepatic resection for the first HCC between 2006 and 2011) and 6 normal individuals were examined for transforming growth factor β1(TGF-β1) or CCN2 mRNA by in situ hybridization.Computer image analysis was performed to measure integrated optimal density of CCN2 mRNA-positive cells in carcinoma foci and the surrounding stroma.Fibroblast-specific protein-1(FSP-1) and E-cadherin were examined to evaluate the process of epithelial to mesenchymal transition,α-smooth muscle actin and FSP-1 were detected to identify hepatic stellate cells,and CD34 was measured to evaluate the extent of vascularization in liver tissues by immunohistochemical staining.CCN2 was assessed for its stimulation of HepG2 cell migration and invasion using commercial kits while flow cytometry was used to determine CCN2 effects on HepG2 cell-cycle.RESULTS:In situ hybridization analysis showed that TGF-β1 mRNA was mainly detected in connective tissues and vasculature around carcinoma foci.In comparison to normal controls,CCN2 mRNA was enhanced 1.9-fold in carcinoma foci(12.36 ± 6.08 vs 6.42 ± 2.35) or 9.4-fold in the surrounding stroma(60.27 ± 28.71 vs 6.42 ± 2.35),with concomitant expression of CCN2 and TGF-β1 mRNA in those areas.Epithelial-mesenchymal transition phenotype related with CCN2 was detected in 12/36(33.3%) of HCC liver samples at the edges between carcinoma foci and vasculature.Incubation of HepG2 cells with CCN2(100 ng/mL) resulted in more of the cells transitioning into S phase(23.85 ± 2.35 vs 10.94 ± 0.23),and induced a significant migratory(4.0-fold) and invasive(5.7-fold) effect.TGF-β1-induced cell invasion was abrogated by a neutralizing CCN2 antibody showing that CCN2 is a downstream mediator of TGF-β1-induced hepatoma cell invasion.CONCLUSION:These data support a role for CCN2 in the growth and metastasis of HCC and highlight CCN2 as a potential novel therapeutic target. | Ming Xiu Ya-Hui Liu David R Brigstock Fang-Hui He Rui-Juan Zhang Run-Ping Gao | 2012 | World Journal of Gastroenterology2012，18，47： | 7 |
| 4 | An immortalized rat pancreatic stellate cell line RP-2 as a new cell model for evaluating pancreatic fibrosis,inflammation and immunity显示文摘BACKGROUND: Pancreatic stellate cells(PSCs) play a critical role in the pathogenesis of pancreatic fibrosis and have emerging functions as progenitor cells,immune cells or intermediaries in pancreatic exocrine secretion. Increasing evidence has shown that desmin as an exclusive cytoskeleton marker of PSC is only expressed in part of these cells. This study was to establish a desmin-positive PSC cell line and evaluate its actions on pancreatic fibrosis,inflammation and immunity.METHODS: The presence of cytoskeletal proteins,integrin α5β1 or TLR4,was determined by immunocytochemistry while the production of desmin,collagen I,MMP-1,MMP-2,TIMP-2,or CD14 was evaluated by Western blotting. The levels of desmin,collagen I,IL-1 and IL-6 m RNA were determined by real-time quantitative PCR. The secretion of cytokines was detected by ELISA. Cell function was assessed using adhesion,migration,or proliferation assays. RESULTS: A stable activated rat PSC cell line(designated as RP-2) was established by RSV promoter/enhancer-driven SV40 large T antigen expression. RP-2 cells retained typical PSC properties,exhibited a myofibroblast-like phenotype and persistently produced desmin. The cells produced collagen I protein,matrix metalloproteinases and inhibitors thereof. RP-2 cells demonstrated typical PSC functions,including proliferation,adherence,and migration,the latter two of which occurred in response to fibronectin and were mediated byintegrin α5β1. TLR4 and its response genes including proinflammatory cytokines(IL-1,IL-6,TNF-α) and chemotactic cytokines(MCP-1,MIP-1α,Rantes) were produced by RP-2 cells and activated by LPS. LPS-induced IL-1 or IL-6 m RNA expression in this cell line was fully blocked with My D88 inhibitor.CONCLUSION: RP-2 cells provide a novel tool for analyzing the properties and functions of PSCs in the pathogenesis of fibrosis,inflammation and immunity in the pancreas. | Rong-Li Piao Ming Xiu David R Brigstock Run-Ping Gao | 2015 | Hepatobiliary & Pancreatic Diseases International2015，14，6： | 6 |
| 5 | Focal autoimmune pancreatitis and chronic sclerosing sialadenitis mimicking pancreatic cancer and neck metastasis显示文摘Type 1 autoimmune pancreatitis(AIP)or chronic sclerosing sialadenitis(Küttner’s tumour)is an uncommon disorder that has recently been confirmed as an Ig G4-related disease.Here,we describe a rare case of a53-year-old male patient who primarily presented with pancreatic body mass,left neck mass and several lumps in his lower lip mimicking pancreatic cancer(PC)and neck metastasis.The patient underwent pancreatic body mass and labial gland lumps resection as well as an ultrasound-guided biopsy of the left neck mass.He was diagnosed with Ig G4-related focal type of AIP(f-AIP)and Küttner’s tumour by immunohistochemistry.The patient responded well to corticosteroid therapy andremains healthy with no signs of recurrence at one year follow-up.The differentiation of f-AIP from PC is very important to avoid unnecessary pancreatic resection. | Li Sun Qiang Zhou David R Brigstock Su Yan Ming Xiu Rong-Li Piao Yan-Hang Gao Run-Ping Gao | 2014 | World Journal of Gastroenterology2014，20，46： | 3 |
| 6 | Rare case of Helicobacter pylori-positive multiorgan Ig G4-related disease and gastric cancer显示文摘A 61-year-old male from Northeast China presented with a 2-mo history of abdominal distension,pruritus and jaundice.Laboratory testing revealed an elevated serum Ig G4 level.A computed tomography scan showed a typical feature of autoimmune pancreatitis(AIP) and cholecystocholangitis.Early gastric cancer was incidentally discovered when endoscopic untrasound-guided fine needle aspiration(EUSFNA) of the pancreas was carried out.The patient underwent radical subtotal gastrectomy for gastric cancer combined with cholecystectomy.Helicobacter pylori(H.pylori) and Ig G4-positive plasmacytes were detected in gastric cancer tissue,pancreatic EUSFNA sample and resected gallbladder specimen by immunohistochemistry.The patient was diagnosed with H.pylori-positive Ig G4-related AIP and sclerosing cholecystocholangitis as well as H.pylori-positive gastric cancer.He responded well to steroid therapy and remains healthy with no signs of recurrence at one year follow-up.We speculate that H.pylori might act as a trigger via direct or indirect action in the initiation of onset of gastric cancer and multiorgan Ig G4-related disease. | Min Li Qiang Zhou Kun Yang David R Brigstock Lu Zhang Ming Xiu Li Sun Run-Ping Gao | 2015 | World Journal of Gastroenterology2015，21，11： | 2 |
| 7 | The connective tissue growth factor/cysteine- rich 61/nephroblastoma overexpressed (CCN) family显示文摘 | Brigstock D R | 1999 | Endocr Rev1999，20，2： | 2 |
| 8 | Low density lipoprotein receptor--related protein (LRP) is a heparin--dependent adhesionreceptor for connective tissue growth factor (CTGF) in ratactivated hepatic stellate ceils 显示文摘 | Gao R Brigstock DR | 2003 | Hepatol Res2003，27，： | 1 |
| 9 | Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells显示文摘 | Williams EJ Gaca MD Brigstock DR | 2000 | J Hepatol2000，32，5： | 1 |
| 10 | Connective tissue growth factor (CT-GF/CCN2) in hepatic fibrosis显示文摘 | Rchfal AW Brigstock DR | 2003 | Hepatol Res2003，26，1： | 1 |
| 11 | Connective tissue growth factor: what's in a name? 显示文摘 | Moussad E E Brigstock D R | 2000 | Mol Genet Metab2000，71，12： | 1 |
| 12 | Low density lipoprotein receptorrelated protein (LRP) is a heparin depened ent adhesion receptor for connective tissue growth factor(CTGF) in rat activated hepatic stellate cell显示文摘 | Gao R Brigstock DR | 2003 | Hepatol Res2003，27，3： | 1 |
| 13 | Propos al for a unified CCN nomenclature 显示文摘 | Brigstock DR Goldschmeding R Katsube KI | 2003 | Mol Pathol2003，56，： | 1 |
| 14 | Regulation of pancreatic function by connective tissue growth factor (CTGF, CCN2) 显示文摘 | CHARRIER A BRIGSTOCK DR | 2013 | Cytokine Growth Factor Rev2013，24，1： | 1 |
| 15 | Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells显示文摘 | Williams FJ Gaca MD Brigstock DR | 2000 | J Hepatol2000，32，： | 1 |
| 16 | Connective tissue growth factor ( CCN2 ) in rat pancreatic stellate cell function : integrin alpha 5 beta 1 as a novel CCN2 receptor 显示文摘 | Gao R Brigstock DR | 2005 | Gastroenterology2005，129，3： | 1 |
| 17 | Ac-SDKP reverses cardiac fibrosis in mrs with renovasculax hypertension显示文摘 | PENG H CARRETERO O A BRIGSTOCK D R | 2003 | Hypertension2003，42，6： | 1 |
| 18 | Connective tissue growth factor:what' s in a name?显示文摘 | Moussad EE Brigstock DR | 2000 | Mol Genet Metab2000，7，1： | 1 |
| 19 | Connective Tissue Growth Factor: What's in a Name? 显示文摘 | Moussad EE Brigstock DR | 2000 | Mol Genet Metab2000，71，12： | 1 |
| 20 | Regulation of hepatic stellate cells by connective tissue growth factor 显示文摘 | Huang G Brigstock DR | 2012 | Front Biosci2012，17，2： | 1 |
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