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| 1 | Osteopontin increases hepatocellular carcinoma cell growth in a CD44 dependant manner显示文摘AIM:To investigate the role of osteopontin(OPN) and its splice variants in the proliferation of hepatocellular carcinoma(HCC).METHODS:The expression of OPN variants in HCC cell lines as well as HCC tissue samples and nontumour tissue was studied using polymerase chain reaction.OPN variant cDNAs were cloned into a mammalian expression vector allowing both transient expression and the production of stable OPN expressing cell lines.OPN expression was studied in these cells using Western blotting,immunofluoresnce and enzyme linked immunosorbent assay.A CD44 blocking antibody and siRNA targeting of CD44 were used to examine the role of this receptor in the OPN stimulated cell growth observed in culture.Huh-7 cells stably expressing either OPN-A,-B or-C were injected subcutaneously into the flanks of nude mice to observe in vivo tumour growth.Expression of OPN mRNA and protein in these tumours was examined using reverse transcriptionpolymerase chain reaction and immunohistochemistry.RESULTS:OPN is expressed in HCC in 3 forms,the full length OPN-A and 2 splice variants OPN-B and-C.OPN variant expression was noted in HCC tissue as well as cognate surrounding cirrhotic liver tissue.Expression of these OPN variants in the HCC derived cell line Huh-7 resulted in secretion of OPN into the culture medium.Transfer of OPN conditioned media to na ve Huh-7 and HepG2 cells resulted in significant cell growth suggesting that all OPN variants can modulate cell proliferation in a paracrine manner.Furthermore the OPN mediated increase in cellular proliferation was dependent on CD44 as only CD44 positive cell lines responded to OPN conditioned media while siRNA knockdown of CD44 blocked the proliferative effect.OPN expression also increased the proliferation of Huh-7 cells in a subcutaneous nude mouse tumour model,with Huh-7 cells expressing OPN-A showing the greatest proliferative effect.CONCLUSION:This study demonstrates that OPN plays a significant role in the proliferation of HCC through interaction with the cell surface receptor CD44.Modulation of this interaction could represent a novel strategy for the control of HCC. | Renee J Phillips Karla J Helbig Kylie H Van der Hoek Devanshi Seth Michael R Beard | 2012 | World Journal of Gastroenterology2012，18，26： | 12 |
| 2 | Impact of alcohol on hepatitis C virus replication and interferon signaling显示文摘Hepatitis C virus (HCV) is one of the main etiological factors responsible for liver disease worldwide. It has been estimated that there are over 170 million people infected with HCV worldwide. Of these infected individuals, approximately 75% will go on to develop a life long necroinflammatory liver disease, which over decades, can result in serious complications, such as cirrhosis and hepatocellular carcinoma. Currently there is no effective vaccine and whilst antiviral therapies have been improved, they are still only effective in approximately 50% of individuals. HCV infection stands as a major cause of global morbidity and suffering, and places a signifi cant burden on health systems. The second highest cause of liver disease in the western world is alcoholic liver disease. Frequently, HCV infected individuals consume alcohol, and the combined effect of HCV and alcohol consumption is deleterious for both liver disease and response to treatment. This review discusses the impact of alcohol metabolism on HCV replication and the negative impact on interferon (IFN)-α treatment, with a particular focus on how alcohol and HCV act synergistically to increase oxidative stress, ultimately leading to exacerbated liver disease and a reduction in the effi cacy of IFN-α treatment. A better understanding of the complicated mechanisms at play in hepatocytes infected with HCV and metabo- lizing alcohol will hopefully provide better treatment options for chronic hepatitis C individuals that consume alcohol. | Erin M McCartney Michael R Beard | 2010 | World Journal of Gastroenterology2010，16，11： | 5 |
| 3 | Synchronized multiple spacecraft rotations显示文摘 | Lawton J R Beard R W | 2002 | Automatic2002，38，8： | 1 |
| 4 | Coordinated Target Assignment and Intercept for Unmanned Air Vehicles 显示文摘 | Beard R W McLain T W | 2002 | IEEE Transaction on Robotics and Automation2002，18，6： | 1 |
| 5 | Mammalian X chromosome inactivation 显示文摘 | Jaenisch R Beard C Lee J | 1998 | Novartis Found Symp1998，214，： | 1 |
| 6 | High-level expression and purification of untagged and histidine-tagged HIV-1 reverse transcriptase显示文摘 | Hou E W Prasad R Beard W A | 2004 | Protein Exp Purif2004，34，1： | 1 |
| 7 | Identification of gene-selective modulators of the bile acid receptor FXR显示文摘 | Dussault I Beard R Lin M | 2003 | J Biol Chem2003，278，9： | 1 |
| 8 | 1 Physical ac-tivity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus显示文摘 | Russo-NeustadtA A Beard R C HuangYM eta | 2000 | Neuro science2000，101，2： | 1 |
| 9 | Consensus seeking in multiagent systems under dynamically changing interaction topologies显示文摘 | Ren W Beard R W | 2005 | IEEE Trans on Automatic Control2005，50，5： | 1 |
| 10 | Subsidy free pricing of interruptible service contracts 显示文摘 | BEARD T R SWEENEY H GROPPER D M | 1995 | Energy Economics1995，17，1： | 1 |
| 11 | Consensus seeking in multiagent systems under dynamically changing interaction topologies显示文摘 | REN W BEARD R W | 2005 | IEEE Transactions on Automatic Control2005，50，5： | 1 |
| 12 | Consensus seeking in multiagent systems under dynamically changing interaction topologies显示文摘 | REN W BEARD R | 2005 | IEEE Transactions on Automatic Control2005，50，5： | 1 |
| 13 | Decentralized scheme for spacecraft formation flying via the virtual structure approach显示文摘 | Ren W Beard R W | 2004 | Journal of Guidance Control and Dynamics2004，27，1： | 1 |
| 14 | Information consensus in mul- tivehicle cooperative control: Collective group behavior through lo- cal interaction 显示文摘 | WRen R W Beard E M Atkins | 2007 | IEEE Control Systems Magazine2007，27，2： | 1 |
| 15 | On silica activity and serpentinization显示文摘 | Frost B R Beard J S | 2007 | Journal of Petrology2007，48，7： | 1 |
| 16 | Screen for novel cry genes by hybridization显示文摘 | Beard C E Ranasinghe C A Khurst R J | 2001 | Lett Appl Microbiol2001，33，： | 1 |
| 17 | Information consensus in multivehicle cooperative control 显示文摘 | REN W BEARD R W ATKINS E M | 2007 | IEEE Control Systems Maga- zine2007，27，2： | 1 |
| 18 | Consensus seeking in multiagent systems under dynanically changing interaction topologies显示文摘 | REN W BEARD R W | 2005 | IEEE Trans on Automatic Control2005，50，5： | 1 |
| 19 | Iron isotope fractionation by Fe(Ⅱ) oxidizing photoautotrophic bacteria 显示文摘 | Croal L R Johnson C M Beard B L | 2004 | Geochimica et Cosmochimica Acta2004，68，： | 1 |
| 20 | Identification of gene-selective modulators of the bile acid receptor FXR显示文摘 | Dussault I Beard R Lin M | 2003 | J Biol Chem2003，278，9： | 1 |
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