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Surveillance for hepatocellular carcinoma: In whom and how?

Therapeutic Advances in Gastroenterology 2011年第1期4卷 5-10页

作者： Serag, Hashem B. Davila, Jessica A. Houston Center for Quality of Care & Utilization Studies Sections of Health Services Research and Gastroenterology Michael E. DeBakey Veterans Affairs Medical Center Baylor College of Medicine Houston TX 2002 Holcombe Boulevard 77030 United States Houston Center for Quality of Care & Utilization Studies Section of Health Services Research Michael E. DeBakey Veterans Affairs Medical Center Baylor College of Medicine Houston TX United States

Hepatocellular carcinoma (HCC) accounts for 85-90% of all primary liver cancer. Each year, approximately half a million people worldwide are newly diagnosed with HCC. A similar number die of HCC, thus demonstrating the dismal prognosis of this cancer. The highest HCC incidence rates are reported from regions endemic for hepatitis B virus (HBV) infection, including Southeast Asia (e.g. North and South Korea, China, and Vietnam) and sub-Saharan Africa (e.g. Mozambique). Chronic HBV and hepatitis C virus (HCV) explain the majority of HCC cases.

关键词： Hepatocellular Cancer Hepatitis B virus Vietnam Africa south of the Sahara Southeast Asia human-centered computing Primary Malignant Neoplasm of Liver

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The Potential Interplay of Adipokines with Toll-Like Receptors in the Development of Hepatocellular Carcinoma

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GASTROENTEROLOGY RESEARCH AND PRACTICE 2011年第unknown期2011卷 1-10页

作者： Wang, Shen-Nien Wang, Sen-Te Lee, King Teh Kaohsiung Med Univ Dept Surg Coll Med Fac Med Kaohsiung Taiwan Kaohsiung Med Univ Grad Inst Med Coll Med Kaohsiung Taiwan Kaohsiung Med Univ Hosp Ctr Canc Kaohsiung 80756 Taiwan Taipei Med Univ Sch Med Dept Family Med Coll Med Taipei Taiwan Taipei Med Univ Hosp Dept Family Med Taipei Taiwan Kaohsiung Med Univ Hosp Div Hepatobiliary Surg Dept Surg Kaohsiung 80756 Taiwan

Toll-like receptors (TLRs) are not only crucial to the initiation of the immune system, but also play a key role in several human inflammatory diseases. Hepatocellular carcinoma (HCC) is among those human cancers, which arise from sites of chronic inflammation. Therefore, a number of studies have explored the potential contribution of TLRs to HCC occurrence, which is initiated by exposure to chronic hepatic inflammation of different etiologies (including ethanol, and chronic B and C viral infections). Recent epidemiological data have shown the association of obesity and HCC development. Given the fact that adipose tissues can produce a variety of inflammation-related adipokines, obesity has been characterized as a state of chronic inflammation. Adipokines are therefore considered as important mediators linking inflammation to several metabolic diseases, including cancers. More recently, many experts have also shown the bridging role of TLRs between inflammation and metabolism. Hopefully, to retrieve the potential interaction between TLRs and adipokines in carcinogenesis of HCC will shed a new light on the therapeutic alternative for HCC. In this paper, the authors first review the respective roles of TLRs and adipokines, discuss their mutual interaction in chronic inflammation, and finally anticipate further investigations of this interaction in HCC development.

关键词： Hepatocellular Cancer TLR Metabolic Diseases Adipose Tissue Adipokines Chronic inflammation Toll-Like Receptors human-centered computing Inflammation

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Characterization of Basigin Isoforms and the Inhibitory Function of Basigin-3 in human Hepatocellular Carcinoma Proliferation and Invasion

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MOLECULAR AND CELLULAR BIOLOGY 2011年第13期31卷 2591-2604页

作者： Liao, Cheng-Gong Kong, Ling-Min Song, Fei Xing, Jin-Liang Wang, Long-Xin Sun, Zhi-Jian Tang, Hao Yao, Hui Zhang, Yang Wang, Li Wang, Yu Yang, Xiang-Min Li, Yu Chen, Zhi-Nan Fourth Mil Med Univ Cell Engn Res Ctr Xian 710032 Peoples R China Fourth Mil Med Univ Dept Cell Biol State Key Lab Canc Biol Xian 710032 Peoples R China Fourth Mil Med Univ Dept Histol & Embryol Xian 710032 Peoples R China Fourth Mil Med Univ Dept Oncol State Key Lab Canc Biol Xijing Hosp Xian 710032 Peoples R China Urumqi Gen Hosp Lanzhou Mil Command PLA Dept Oncol Urumqi 830000 Peoples R China

Basigin, which has four isoforms, plays an important role in invasion of hepatocellular carcinoma (HCC). Detailed transcriptional regulation and functions of the basigin isoforms have not been reported except in the case of the predominant isoform basigin-2, which act as inducer of matrix metalloproteinases (MMPs). Here we determined that basigin-2, basigin-3, and basigin-4 were the most abundant transcript variants in human cell lines. GeneRacer PCR and luciferase reporter assays showed that basigin-3 and basigin-4 were initiated from an alternative promoter. Basigin-3 and basigin-4 were widely expressed in various normal human tissues at the mRNA level and were upregulated in HCC tissues compared to in normal tissues. Western blotting and confocal imaging showed that glycosylated basigin-3 and basigin-4 were expressed and localized to the plasma membrane. However, in cultured cell lines, only native basigin-3, and not basigin-4, was detected at protein level. Overexpression of basigin-3 inhibited HCC cell proliferation, MMP induction, and cell invasion in vitro and in vivo. Bimolecular fluorescence complementation assays and nuclear magnetic resonance (NMR) analysis indicated that basigin-3 interacted with basigin-2 to form hetero-oligomers. In conclusion, we systematically investigated the alternative splicing of basigin and found that basigin-3 could inhibit HCC proliferation and invasion, probably through interaction with basigin-2 as an endogenous inhibitor via hetero-oligomerization.

关键词： matrix metalloproteinase: MMP 141907-41-7 mRNA hetero-oligomer basigin-2: expression transcription regulation basigin-3: expression glycosylation basigin-4: expression cell proliferation cell invasion cell induction Cell Proliferation Matrix Metalloproteinases CD147 Antigens Glycosylation Protein Isoforms human-centered computing cell invasion Messenger RNA

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Mutation of Herpesvirus Saimiri ORF51 Glycoprotein Specifically Targets Infectivity to Hepatocellular Carcinoma Cell Lines

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JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY 2011年第unknown期2011卷 785158-785158页

作者： Turrell, Susan J. Whitehouse, Adrian Univ Leeds Inst Mol & Cellular Biol Fac Biol Sci Leeds LS2 9JT W Yorkshire England Univ Leeds Astbury Ctr Struct Mol Biol Leeds LS2 9JT W Yorkshire England

Herpesvirus saimiri (HVS) is a gamma herpesvirus with several properties that make it an amenable gene therapy vector;namely its large packaging capacity, its ability to persist as a nonintegrated episome, and its ability to infect numerous human cell types. We used RecA-mediated recombination to develop an HVS vector with a mutated virion protein. The heparan sulphate-binding region of HVS ORF51 was substituted for a peptide sequence which interacts with somatostatin receptors (SSTRs), overexpressed on hepatocellular carcinoma (HCC) cells. HVS mORF51 showed reduced infectivity in non-HCC human cell lines compared to wildtype virus. Strikingly, HVS mORF51 retained its ability to infect HCC cell lines efficiently. However, neutralisation assays suggest that HVS mORF51 has no enhanced binding to SSTRs. Therefore, mutation of the ORF51 glycoprotein has specifically targeted HVS to HCC cell lines by reducing the infectivity of other cell types;however, the mechanism for this targeting is unknown.

关键词： Saimiriine herpesvirus 2 Gene Transduction Agent peptide sequence Infectivity cell type Mutation Glycoproteins Herpesvirus 2, Saimiriine neutralization tests Hepatocellular Cancer Cell Line Pathogenicity human-centered computing

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Raman Based Hepatocellular Carcinoma Biomarker Detection

Raman Based Hepatocellular Carcinoma Biomarker Detection

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Annual International Conference of the IEEE Engineering in Medicine and Biology Society

作者： M. A. Santiago-Cordoba P. R. Romano A. MacKay M. C. Demirel Chemistry Department Pennsylvania State University Microbiology and Immunology Drexel Institute for Biotechnology and Virology Research and The Institute for Hepatitis and Virus Research Materials Research Institute and Department of Engineering Science Pennsylvania State University

ISBN: (纸本)9781424441211

Highly sensitive and selective biomarker detection is required for early detection of hepatocellular carcinoma (HCC). Disease progression has been shown to correlate with specific fucosylation of a validated HCC serum glycoprotein biomarker, alpha-fetoprotein (AFP) Carbohydrate binding proteins, such as lectins, can be used as diagnostic indicators for monitoring glycosylation changes during disease progression in hepatitis B virus (HBV) or hepatitis C virus (HCV) infected patients. We prepared surface-enhanced Raman spectroscopy (SERS) substrates, which provide controllable, well-organized nanoparticles on the surface, for the analysis of a fucose binding lectin AAL. The SERS based assay provides fast (<10 s), and reproducible (<5% variation) detection.

关键词： Raman Lectins Biological Markers Disease Progression Hepatocellular Cancer alpha-Fetoproteins Early Diagnosis diagnostic indicator Hepatitis B virus surface enhanced Raman scattering human-centered computing Hepatitis C virus

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Systematic review of outcome of downstaging hepatocellular cancer before liver transplantation in patients outside the Milan criteria (Br J Surg 2011;98: 1201-1208)

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BRITISH JOURNAL OF SURGERY 2011年第9期98卷 1209-1209页

作者： Mirza, D. F. Univ Hosp Birmingham NHS Trust Queen Elizabeth Hosp Birmingham B15 2TH W Midlands England

The aim of this systematic review was to assess the evidence on tumour downstaging before liver transplantation in patients with hepatocellular carcinoma (HCC) initially staged beyond the Milan criteria.

关键词： Liver Cirrhosis Review, Systematic Patients partial hepatectomy Hepatocellular Cancer Cirrhosis bromine Patient Selection Nodule size human-centered computing Transplantation Liver Transplantation

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Claudin-1 Acts through c-Abl-Protein Kinase Cδ (PKCδ) Signaling and Has a Causal Role in the Acquisition of Invasive Capacity in human Liver Cells

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JOURNAL OF BIOLOGICAL CHEMISTRY 2010年第1期285卷 226-233页

作者： Yoon, Chang-Hwan Kim, Min-Jung Park, Myung-Jin Park, In-Chul Hwang, Sang-Gu An, Sungkwan Choi, Yung-Hyun Yoon, Gyesoon Lee, Su-Jae Hanyang Univ Dept Chem Res Inst Nat Sci Seoul 133791 South Korea Korea Inst Radiol & Med Sci Div Radiat Canc Biol Seoul 139706 South Korea Konkuk Univ Funct Genoproteome Res Ctr Seoul 143701 South Korea Dong Eui Univ Dept Biochem Coll Oriental Med Pusan 614052 South Korea Ajou Univ Sch Med Dept Biochem & Mol Biol Suwon 443721 South Korea

Claudins are identified as members of the tetraspanin family of proteins, which are integral to the structure and function of tight junction. Recent studies showed an increase in expression of claudins during tumorigenesis, which is associated with loss of cell-cell contact, dedifferentiation, and invasiveness. However, the molecular basis for the causal relationship between claudin expression and cancer progression is not fully understood yet. In this study, we show that claudin-1 plays a causal role in the acquisition of invasive capacity in human liver cells and that c-Abl-protein kinase C delta (PKC delta) signaling is critical for the malignant progression induced by claudin-1. Overexpression of claudin-1 clearly induced expression of matrix metalloproteinase-2 (MMP-2) and cell invasion and migration in normal liver cells as well as in non-invasive human hepatocellular carcinoma (HCC) cells. Conversely, small interfering RNA targeting of claudin-1 in invasive HCC cells completely inhibited cell invasion. Both c-Abl and PKC delta are found to be activated in normal liver cell line clones that stably overexpress claudin-1. Inhibition of either c-Abl or PKC delta alone clearly attenuated MMP-2 activation and impeded cell invasion and migration in both human HCC and normal liver cells expressing claudin-1. These results indicate that claudin-1 is both necessary and sufficient to induce invasive behavior in human liver cells and that activation of c-Abl-PKC delta signaling pathway is critically required for the claudin-1-induced acquisition of the malignant phenotype. The present observations raise the possibility of exploiting claudin-1 as a potential biomarker for the spread of liver cancer and might provide pivotal points for therapeutic intervention in HCC.

关键词： Hepatocytes liver cell line human-centered computing cell invasion Claudins

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A human-centered Semantic Service Platform for the Digital Ecosystems Environment

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WORLD WIDE WEB-INTERNET AND WEB INFORMATION SYSTEMS 2010年第1-2期13卷 75-103页

作者： Dong, Hai Hussain, Farookh Khadeer Chang, Elizabeth Curtin Univ Technol Digital Ecosyst & Business Intelligence Inst Bentley WA 6102 Australia

Digital Ecosystems (DEST) have emerged with the purpose of enhancing communications among small and medium enterprises (SMEs) within the worldwide Business Ecosystem. However, because of the diversity and heterogeneity of the services in the DEST environment, existing commercial products or research outputs cannot be directly applied to this field so as to fulfill the requirements of SMEs. human-centered computing has been applied to many areas, such as social classification, community-based ontology evolution, and more importantly, human-centered systems. In this paper, we propose a framework for a human-centered semantic service platform, in order to address the issue in the DEST environment. This framework incorporates the features of human-centered metadata publishing, maintenance and clustering, community-based ontology revolution and human-centered service retrieval, evaluation and ranking. To thoroughly validate the framework, we implement a prototype in the transport service domain, and conduct a series of evaluation experiments on the basis of this prototype.

关键词： digital ecosystems (abbreviated as DEST) human-centered computing human-centered systems ontology revolution QoS evaluation service platform

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human-Agent Collaboration for Time-Stressed Multicontext Decision Making

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IEEE TRANSACTIONS ON SYSTEMS MAN AND CYBERNETICS PART A-SYSTEMS AND humanS 2010年第2期40卷 306-320页

作者： Fan, Xiaocong McNeese, Michael Sun, Bingjun Hanratty, Timothy Allender, Laurel Yen, John Penn State Univ University Pk PA 16802 USA Telenav Inc Sunnyvale CA 94086 USA USA Res Lab Aberdeen Proving Ground MD 21005 USA

Multicontext team decision making under time stress is an extremely challenging issue faced by various real-world application domains. In this paper, we employ an experience-based cognitive agent architecture (called R-CAST) to address the informational challenges associated with military command and control (C-2) decision-making teams, the performance of which can be significantly affected by dynamic context switching and tasking complexities. Using context switching frequency and task complexity as two factors, we conducted an experiment to evaluate whether the use of R-CAST agents as teammates and decision aids can benefit C-2 decision-making teams. Members from a U. S. Army Reserve Officer Training Corps organization were randomly recruited as human participants. They were grouped into ten human-human teams, each composed of two participants, and ten human-agent teams, each composed of one participant and two R-CAST agents, as teammates and decision aids. The statistical inference of experimental results indicates that R-CAST agents can significantly improve the performance of C-2 teams in multi-context decision making under varying time-stressed situations.

关键词： Cognitive agents context switching human-centered computing naturalistic decision making

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Association of Meat and Fat Intake With Liver Disease and Hepatocellular Carcinoma in the NIH-AARP Cohort

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JOURNAL OF THE NATIONAL CANCER INSTITUTE 2010年第17期102卷 1354-1365页

作者： Freedman, Neal D. Cross, Amanda J. McGlynn, Katherine A. Abnet, Christian C. Park, Yikyung Hollenbeck, Albert R. Schatzkin, Arthur Everhart, James E. Sinha, Rashmi NCI Div Canc Epidemiol & Genet NIH Dept Hlth & Human ServNutr Epidemiol Branch Rockville MD 20852 USA AARP Washington DC USA NIDDKD Div Digest Dis & Nutr NIH Dept Hlth & Human Serv Bethesda MD 20892 USA

Background Several plausible mechanisms, including fat, iron, heterocyclic amines, and N-nitroso compounds, link meat intake with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Few studies have investigated these associations. Methods We prospectively examined the relationship between meat and associated exposures with CLD mortality (n = 551;not including HCC) and HCC incidence (n = 338) in 495 006 men and women of the National Institutes of Health-AARP Diet and Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the fifth (Q5) vs the first (Q1) quintile were estimated from multivariable adjusted Cox proportional hazards regression models. All tests of statistical significance were two-sided. Results We found inverse associations between white meat and risk of CLD (HR = 0.52, 95% CI = 0.39 to 0.70, 7.5 vs 18.2 cases per 100 000 person-years) and HCC (HR = 0.52, 95% CI = 0.36 to 0.77, 5.8 vs 14.3 cases per 100 000 person-years). Red meat was associated with higher risk of CLD (HR = 2.59, 95% CI = 1.86 to 3.61, 22.3 vs 6.2 cases per 100 000 person-years) and HCC (HR = 1.74, 95% CI = 1.16 to 2.61, 14.9 vs 5.7 cases per 100 000 person-years). Among fat types, results were strongest for saturated fat (for CLD, HR = 3.50, 95% CI = 2.48 to 4.96, 23.0 vs 6.5 cases per 100 000 person-years;for HCC, HR = 1.87, 95% CI = 1.23 to 2.85, 14.5 vs 6.3 cases per 100 000 person-years). After mutual adjustment, risk estimates persisted for saturated fat, red meat, and white meat. Heme iron, processed meat, nitrate, and nitrite were positively associated with CLD but not with HCC. Individual heterocyclic amines, 2-amino-3,4,8-trimethylimidazo[4,5,-f] quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b] pyridine (PhIP), were not associated with either outcome. Conclusion Our results suggest that red meat and saturated fat may be associated with increased CLD and HCC risk, whereas

关键词： Hepatocellular Cancer saturated fats Meat Liver Diseases Red Meat human-centered computing Dietary Fats Heart Rate

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