@article{LeursMezoOehlschlaegeretal.2012, author = {Leurs, Ulrike and Mezo, Gabor and {\"O}hlschl{\"a}ger, Peter and Orban, Erika and Marquard, Andrea and Manea, Marilena}, title = {Design, synthesis, in vitro stability and cytostatic effect of multifunctional anticancer drug-bioconjugates containing GnRH-III as a targeting moiety}, series = {Peptide Science}, volume = {98}, journal = {Peptide Science}, number = {1}, publisher = {Wiley}, address = {New York, NY}, issn = {1097-0282}, doi = {10.1002/bip.21640}, pages = {1 -- 10}, year = {2012}, abstract = {Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.}, language = {en} } @article{LempiaeinenCouttetBolognanietal.2012, author = {Lempi{\"a}inen, Harri and Couttet, Philippe and Bolognani, Federico and M{\"u}ller, Arne and Dubost, Val{\´e}rie and Luisier, Rapha{\"e}lle and Rio-Espinola, Alberto del and Vitry, Veronique and Unterberger, Elif B. and Thomson, John P. and Treindl, Fridolin and Metzger, Ute and Wrzodek, Clemens and Hahne, Florian and Zollinger, Tulipan and Brasa, Sarah and Kalteis, Magdalena and Marcellin, Magali and Giudicelli, Fanny and Braeuning, Albert and Morawiec, Laurent and Zamurovic, Natasa and L{\"a}ngle, Ulrich and Scheer, Nico and Sch{\"u}beler, Dirk and Goodman, Jay and Chibout, Salah-Dine and Marlowe, Jennifer and Theil, Dietlinde and Heard, David J. and Grenet, Olivier and Zell, Andreas and Templin, Markus F. and Meehan, Richard R. and Wolf, Roland C. and Elcombe, Clifford R. and Schwarz, Michael and Moulin, Pierre and Terranova, R{\´e}mi and Moggs, Jonathan G.}, title = {Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion}, series = {Toxicological Sciences}, volume = {131}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1094-2025}, doi = {10.1093/toxsci/kfs303}, pages = {375 -- 386}, year = {2012}, abstract = {The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.}, language = {en} } @article{LawsonScheerPhametal.2001, author = {Lawson, Nathan D. and Scheer, Nico and Pham, Van N. and Kim, Ceol-Hee and Chitnis, Ajay B. and Campos-Ortega, Jos{\´e} A. and Weinstein, Brant M.}, title = {Notch signaling is required for arterial-venous differentiation during embryonic vascular development}, series = {Development}, volume = {128}, journal = {Development}, number = {19}, issn = {1477-9129}, pages = {3675 -- 3683}, year = {2001}, language = {en} } @misc{LauthWolfBurkhart1998, author = {Lauth, Jakob and Wolf, Gerhard and Burkhart, Bernd}, title = {Preparation of alkoxylation products in the presence of mixed hydroxides modified with additives : United States Patent ; patent number 5,741,947 ; date of patent: Apr. 21, 1998 / assignee: BASF Aktiengesellschaft. Inventors: Gerhard Wolf ; Bernd Burkhart ; Guenter Lauth ...}, publisher = {[United States Trademark and Patent Office]}, address = {[Alexandria, VA]}, pages = {8 S.}, year = {1998}, language = {en} } @misc{LauthTruebenbachHagemeyer1999, author = {Lauth, Jakob and Tr{\"u}benbach, Peter and Hagemeyer, Alfred}, title = {Monomodal and polymodal catalyst supports and catalysts having narrow pore size distributions and their production : United States Patent ; patent number 5,935,898 ; date of patent: Aug. 10, 1999 / assignee: BASF Aktiengesellschaft. Inventors: Peter Trubenbach ; Alfred Hagemeyer ; Gunter Lauth ...}, publisher = {[United States Patent and Trademark Office]}, address = {[Alexandria, VA]}, pages = {27 S. : graph. Darst.}, year = {1999}, language = {en} } @article{LauthSolomunHirschwaldetal.1989, author = {Lauth, Jakob and Solomun, T. and Hirschwald, W. and Christmann, K.}, title = {The interaction of carbon monoxide with a ruthenium(1010) surface}, series = {Surface Science. 210 (1989), H. 1-2}, journal = {Surface Science. 210 (1989), H. 1-2}, isbn = {0039-6028}, pages = {201 -- 224}, year = {1989}, language = {en} } @article{LauthSolomunHirschwaldetal.1989, author = {Lauth, Jakob and Solomun, T. and Hirschwald, W. and Christmann, K.}, title = {The interaction of carbon monoxide with a ruthenium(1010) surface}, series = {Surface Science Letters. 210 (1989), H. 1-2}, journal = {Surface Science Letters. 210 (1989), H. 1-2}, isbn = {0167-2584}, pages = {A74 -- A75}, year = {1989}, language = {en} } @misc{LauthMuellerHoelderich1994, author = {Lauth, Jakob and M{\"u}ller, Ulrich and Hoelderich, Wolfgang}, title = {Colored crystalline aluminophosphates and/or silicoaluminophosphates of the AEL or VFI type : United States Patent ; patent number 5,360,474 ; date of patent: Nov. 1, 1994 / assignee: BASF Aktiengesellschaft}, publisher = {[United States Trademark and Patent Office]}, address = {[Alexandria, VA]}, pages = {12 S. : Ill.}, year = {1994}, language = {en} } @misc{LauthMuellerHoelderich1994, author = {Lauth, Jakob and M{\"u}ller, Ulrich and Hoelderich, Wolfgang}, title = {Preparation of aluminophosphates and silicoaluminophosphates having the AEL structure using 1,2-bis-( 4-pyridyl)-ethane : United States Patent ; patent number 5,324,493 ; date of patent: Jun. 28, 1994 / assignee: BASF Aktiengesellschaft. Inventors: Ulrich Mueller ; Wolfgang Hoelderich ; Guenter Lauth}, publisher = {[United States Trademark and Patent Office]}, address = {[Alexandria, VA]}, pages = {6 S. : Ill.}, year = {1994}, language = {en} } @book{LauthHoelderichWagenblast1993, author = {Lauth, Jakob and Hoelderich, Wolfgang and Wagenblast, Gerhard}, title = {Molecular sieves containing azo dyes ; Internationale [Pantent]anmeldung WO93/17965 ; Ver{\"o}ffentlichungsdatum: 16.09.1993 / Anmelder: BASF AG}, publisher = {Weltorganisation f{\"u}r geistiges Eigentum, Internat. B{\"u}ro}, address = {[Genf]}, pages = {45 S.}, year = {1993}, language = {en} }