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| 1 | Hepatocellular carcinoma: Therapy and prevention显示文摘Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, <5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets. | Hubert E Blum | 2005 | World Journal of Gastroenterology2005，11，47： | 27 |
| 2 | EGFR and HER2 expression in advanced biliary tract cancer显示文摘AIM:To analyze the pathogenetic role and potential clinical usefulness of the epidermal growth factor receptor(EGFR)and the human epidermal growth factor receptor 2(HER2)in patients with advanced biliary tract cancer(BTC). METHODS:EGFR and HER2 expression was studied in biopsy samples from 124 patients(51%women; median age 64.8 years),with advanced BTC diagnosed between 1997 and 2004.Five micrometers sections of paraffin embedded tissue were examined by standard, FDA approved immunohistochemistry.Tumors with scores of 2+or 3+for HER2 expression on immunochemistry were additionally tested for HER2 gene amplification by fluorescence in situ hybridisation(FISH).RESULTS:34/124 patients(27.4%)had gallbladder cancer,47(37.9%)had intrahepatic BTC and 43(34.7%)had extrahepatic or perihilar BTC.EGFR expression was examined in a subset of 56 samples. EGFR expression was absent in 22/56 tumors(39.3%). Of the remaining samples expression was scored as 1+in 12(21.5%),2+in 13(23.2%)and 3+in 9(16%), respectively.HER2 expression was as follows:score 0 73/124(58.8%),score 1+27/124(21.8%),score 2+ 21/124(17%)and score 3+4/124(3.2%).HER2 gene amplification was present in 6/124,resulting in an overall amplification rate of 5%. CONCLUSION:Our data suggest that routine testing and therapeutic targeting of HER2 does not seem to be useful in patients with BTC,while targeting EGFR may be promising. | Jan Harder Oliver Waiz Florian Otto Michael Geissler Manfred Olschewski Brigitte Weinhold Hubert E Blum Annette Schmitt-Graeff Oliver G Opitz | 2009 | World Journal of Gastroenterology2009，15，36： | 18 |
| 3 | Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia CD81显示文摘AIM: To further analyze the interaction of tupaia CD81 with hepatitis C virus (HCV) envelope protein E2. METHODS: A tupaia CD81 large extracellular loop (CD81 LEL), which binds to HCV E2 protein, was cloned and expressed as a GST-fusion protein, and interaction of HCV E2 protein with a tupaia CD81 LEL was evaluated by enzyme-linked immunosorbent assay (EIA). RESULTS: Although tupaia and human CD81 LEL differed in 6 amino acid changes, tupaia CD81 LEL was strongly recognized by anti-CD81 antibodies against human CD81 LEL conformation-dependent epitopes. Investigating LEL CD81-E2 interactions by EIA, we demonstrated that binding of tupaia CD81 LEL GST fusion protein to recombinant HCV E2 protein was markedly reduced compared to binding of human CD81 LEL GST fusion protein to recombinant HCV E2 protein. CONCLUSION: These data suggest that the structural differences in-between the tupaia and human CD81 may alter the interaction of the large extracellular loop with HCV envelope glycoprotein E2. These findings may be important for the understanding of the mechanisms of binding and entry of HCV to PTHs. | Zhan-Fei Tian Hong Shen Xi-Hua Fu Yi-Chun Chen Hubert E Blum Thomas F Baumert Xi-Ping Zhao | 2009 | World Journal of Gastroenterology2009，15，2： | 16 |
| 4 | Hepatitis C virus infection and apoptosis显示文摘Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades. | Richard Fischer Thomas Baumert Hubert E Blum | 2007 | World Journal of Gastroenterology2007，13，36： | 10 |
| 5 | Pseudomonas exotoxin antisense RNA selectively kills hepatitis B virus infected cells显示文摘AIM: To present an approach for selectively killing retrovirus-infected cells that combines the toxicity of Pseudomonas exotoxin (PE) and the presence of reverse transcriptase (RT) in infected cells. METHODS: PE antisense toxin RNA has palindromic stem loops at its 5' and 3' ends enabling self-primed generation of cDNA in the presence of RT. The RT activity expressed in retrovirus-infected cells converts 'antisense-toxin-RNA' into a lethal toxin gene exclusively in these cells. RESULTS: Using cotransfection studies with PE-expressing RNAs and β-gal expressing reporter plasmids, we show that, in HepG2 and HepG2.2.15 hepatoma cells as well as in duck hepatitis B virus (DHBV) infected cells, HBV or DHBV-polymerase reverse transcribe a lethal cDNA copy of an antisense toxin RNA, which is composed of sequences complementary to a PE gene and eukaryotic transcription and translation signals. CONCLUSION: This finding may have important implications as a novel therapeutic strategy aimed at the elimination of HBV infection. | Peter Hafkemeyer Ulrich Brinkmann Elizabeth Brinkmann Ira Pastan Hubert E Blum Thomas F Baumert | 2008 | World Journal of Gastroenterology2008，14，18： | 2 |
| 6 | From Opttimization and Variational Inequalities to Equilibrium Problems显示文摘 | Blum E and Oettli W | 1994 | Mathematics Student1994，63，： | 1 |
| 7 | Periodontal care may improve systemic inflammation显示文摘 | Blum A Front E Peleg A | 2007 | Clin Invest Ned2007，30，3： | 1 |
| 8 | Relevance and safety of telomerase for human tissue engineering, 显示文摘 | Klinger R Y Blum J L Hearn B Lebow B Niklason L E | 2006 | PNAS2006，103，8： | 1 |
| 9 | Spatial diversity in radars - models and detection performance 显示文摘 | FISHLER E HAIMOVICH A BLUM R | 2006 | IEEE Trans on Signal Processing2006，54，3： | 1 |
| 10 | Hepatitis C vires-induced epatocarcinogenesis显示文摘 | Bartosch B Thimme R Blum H E | 2009 | J Hepatol2009，51，4： | 1 |
| 11 | Determining chemical toxicity toaquatic species:The use of QSARs and surrogate organisms显示文摘 | Blum D J W Speece R E | 1990 | Environmental Science and Technology1990，24，3： | 1 |
| 12 | Spatial di-versity in radar-models and detection performance显示文摘 | Fisher E Haimovich A Blum R S | 2006 | IEEE Transactions on Signal Processing2006，54，3： | 1 |
| 13 | Spatial Diversity in Radars-Models and Detection Performance显示文摘 | FISHLER E HAIMOVICH A BLUM R S | 2006 | IEEE Transactions on Signal Processing2006，54，3： | 1 |
| 14 | Erythropoietin and G-CSF receptors in human tumor cells:expression and aspects regarding functionality显示文摘 | Westphal G Niederberger E Blum C | 2002 | Tumori2002，88，2： | 1 |
| 15 | CI-h oxidation and emissions of CI-h and N20 from Lolium perenne swards under elevated atmospheric CO2显示文摘 | Baggs E M Blum H | 2004 | Soil Biol Bioch2004，，36： | 1 |
| 16 | Renal slit diaphragm-the open zipper and the failing heart显示文摘 | Blum S Nakhoul F Khankin E | 2007 | Isr Med Assoc J2007，9，2： | 1 |
| 17 | Isolation and characterization of parvalbumins from the skeletal mus- cle of higher vertebrates 显示文摘 | Lehky P Blum H E Stein E A | 1974 | The Journal of Biological Chemistry1974，249，13： | 1 |
| 18 | Isotope geochemistry of mercury in source rocks, mineral deposits and spring deposits of the california coast ranges, USA显示文摘 | Smith C N Kesler S E Blum J D | 2008 | Earth and Planetary Science Letters2008，269，34： | 1 |
| 19 | From Optimization and Variational Inequalities to Equilibrium Problems显示文摘 | BLUM E OETTLI W | 1994 | Math Student1994，63，： | 1 |
| 20 | Spatial Diversity in Radar-Models and Detection Per- formance 显示文摘 | FISHER E HAIMOVICH A BLUM R S | 2006 | IEEE Trans on Signal Process2006，54，3： | 1 |
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