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| 1 | Bifunctional chimeric SuperCD suicide gene -YCD: YUPRT fusion is highly effective in a rat hepatoma model显示文摘AIM: To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model.METHODS: To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine (5-FC), we generated a chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine deaminase (YCD) and the yeast uracil phosphoribosyltransferase (YUPRT) gene.RESULTS: In vitro stably transduced Morris rat hepatoma cells (MH) expressing the bifunctional SuperCD suicide gene (MH SuperCD) showed a clearly marked enhancement in cell killing when incubated with 5-FC as compared with MH ceils stably expressing YCD solely (MH YCD) or the cytosine deaminase gene of bacterial origin(MH BCD), respectively. In vivo, MH SuperCD tumors implanted both subcutaneously as well as orthotopically into the livers of syngeneic ACI rats demonstrated significant tumor regressions (P<0.01) under both high dose as well as low dose systemic 5-FC application,whereas MH tumors without transgene expression (MH naive) showed rapid progression. For the first time, an order of in vivo suicide gene effectiveness (SuperCD>>YCD > > BCD > > > negative control) was defi ned as a result of a directin vivo comparison of all three suicide genes.CONCLUSION: Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model,thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine. | Florian Graepler Marie-Luise Lemken Wolfgang A Wybranietz Ulrike Schmidt Irina Smirnow Christine D GroB Martin Spiegel Andrea Schenk Schenk Hansj(o|¨)rg Graf Ulrike A Lauer Reinhard Vonthein Michael Gregor Sorin Armeanu Michael Bitzer Ulrich M.Lauer | 2005 | World Journal of Gastroenterology2005，11，44： | 2 |
| 2 | A dual role fortumor-derived chemokine RANTES (CCL5) 显示文摘 | Adler E P Lemken C A Katchen N S Kurt R A | 2003 | Immunol Lett2003，90，23： | 1 |
| 3 | Focused Conference Group:P15- Endothelium in health and disease antihypertensive efficacy of dual ECE/NEP inhibition during the onset of spontaneous hypertension in rats显示文摘 | Nelissen J Heijnen BFJ Lemkens P | 2010 | Basic Clin Pharmacol Toxicol2010，107，： | 1 |
| 4 | Influence of pelvic floor muscle exercises on full spectrum therapy for nocturnal enuresis 显示文摘 | Van Kampen M Lemkens H Deschamps A | 2009 | J Urol2009，182，4： | 1 |
| 5 | Tonsillectomy as a day-case surgery: a safe procedure显示文摘 | Laureyns G Lemkens P Jorissen M | 2006 | B-ENT2006，2，3： | 1 |
| 6 | Septal suturing following nasal septoplasty, a valid alternative for nasal packing? 显示文摘 | Lemmens W Lemkens P | 2001 | Acta Otorhinolaryngol Belg2001，55，3： | 1 |
| 7 | Septal sururing following nasal septoplasty, a valid alternative for nasal packing显示文摘 | Lemmens W Lemkens P | 2001 | Acta Otorhinolaryngol Belg2001，55，3： | 1 |
| 8 | Septal suturing following nasal septoplasty, a valid ahemative for nasal packing?显示文摘 | Lemmens W Lemkens P | 2001 | Acta Otorhinolaryngol Belg2001，55，3： | 1 |
| 9 | Age-related hearing impairment (ARHI): environmental risk factors and genetic prospects显示文摘 | Erik Fransen Nele Lemkens Lut Van Laer Guy Van Camp | 2003 | Experimental Gerontology2003，，4： | 1 |
| 10 | Alice in Wonderland syn- drome and upper airway obstruction in infectious mononucleosis 显示文摘 | Piessens P Indesteege F Lemkens P | 2011 | B-ENT2011，7，1： | 1 |
| 11 | A dual role for tumor-derived chemokine RANTES (CCL5)显示文摘 | Evan P. Adler Charles A. Lemken Nicholas S. Katchen Robert A. Kurt | 2003 | Immunology Letters2003，，2： | 1 |
| 12 | Inhibition of metastasis by inhibition of tumor-derived CCL5显示文摘 | Stormes KA Lemken CA Lepre JV | | 0，，02： | 1 |
| 13 | ETA-receptor antagonists or allosteric modulators?显示文摘 | De Mey JG Compeer MG Lemkens P | 2011 | Trends Pharmacol Sci2011，32，6： | 1 |
| 14 | A dual role for tumor-derived chemokine RANTES (CCL5)显示文摘 | Adler EP Lemken CA Katchen NS | 2003 | Immunology Lett2003，90，23： | 1 |
| 15 | Fusion of HSV-1 VP22 to a bifunctional chimeric SuperCD suicide gene compensates for low suicide gene transduction efficiencies显示文摘 | Lemken ML Graepler F Wolf C | 2007 | Int J Oncol2007，30，5： | 1 |
| 16 | Effect of adenotonsillectomy on the use of respiratory medication 显示文摘 | Piessens P Hens G Lemkens N | 2012 | Int J Pediatr Otorhinolaryngol2012，76，6： | 1 |
| 17 | Evidence for intercellular trafficking of VP22 in living cells 显示文摘 | Lemken ML Wolf C Wybranietz WA | 2007 | Mol Ther2007，15，2： | 1 |
| 18 | Evidence for intercellular trafficking of VP22 in living cells显示文摘 | Lemken ML Wolf C Wybranietz WA | 2007 | Mol Ther2007，15，2： | 1 |
| 19 | Expression liver-directed genes by employing synthetic transcriptional control units显示文摘AIM: To generate and characterize the synthetic transcriptional control units for transcriptional targeting of the liver,thereby compensating for the lack of specificity of currently available gene therapeutic vector systems.METHODS: Synthetic transcriptional control unit constructs were generated and analyzed for transcriptional activities in different cell types by FACS quantification, semi-quantitative RT-PCR, and Western blotting. RESULTS: A new bifunctionally-enhanced green fluorescent protein (EGFP)/neor fusion gene cassette was generated,and could flexibly be used both for transcript quantification and for selection of stable cell clones. Then, numerous synthetic transcriptional control units consisting of a minimal promoter linked to 'naturally' derived composite enhancer elements from liver-specific expressed genes or binding sites of liver-specific transcription factors were inserted upstream of this reporter cassette. Following liposome-mediated transfection, EGFP reporter protein quantification by FACS analysis identified constructs encoding multimerized composite elements of the apolipoprotein B100 (ApoB) promoter or the ornithin transcarbamoylase (OTC) enhancer to exhibit maximum transcriptional activities in liver originating cell lines, but only background levels in non-liver originating cell lines. In contrast, constructs encoding only singular binding sites of liver-specific transcription factors, namely hepatocyte nuclear factor (HNF)1, HNF3, HNF4, HNF5, or CAAT/enhancer binding protein (C/EBP) only achieved background levels of EGFP expression. Finally, both semi-quantitative RT-PCR and Western blotting analysis of Hep3B cells demonstrated maximum transcriptional activities for a multimeric 4xApoB cassette construct, which fully complied with the data obtained by initial FACS analysis.CONCLUSION: Synthetic transcriptional control unit constructs not only exhibit a superb degree of structural compactness, but also provide new means for liver-directed expression of therapeutic genes. | Marie-Luise Lemken Wolfgang A.Wybranietz Ulrike Schmidt Florian Graepler Sorin Armeanu Michael Bitzer Ulrich M.Lauer | 2005 | World Journal of Gastroenterology2005，11，34： | 0 |
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