@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{HenkenOosterhuisOehlschlaegeretal.2012,
  author    = {Henken, F. E. and Oosterhuis, K. and {\"O}hlschl{\"a}ger, Peter and Bosch, L. and Hooijberg, E. and Haanen, J. B. A. G. and Steenbergen, R. D. M.},
  title     = {Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7},
  series = {Vaccine},
  volume    = {30},
  journal   = {Vaccine},
  number    = {28},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0264-410X},
  doi       = {10.1016/j.vaccine.2012.04.013},
  pages     = {4259 -- 4266},
  year      = {2012},
  abstract  = {Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of 'gene-shuffled' (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.},
  language  = {en}
}
@article{ImmelGruetzkeSpaeteetal.2012,
  author    = {Immel, Timo and Gr{\"u}tzke, Martin and Sp{\"a}te, Anne-Katrin and Groth, Ulrich and {\"O}hlschl{\"a}ger, Peter and Huhn, Thomas},
  title     = {Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy},
  series = {Chemical Communications},
  volume    = {48},
  journal   = {Chemical Communications},
  number    = {46},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {1364-548X},
  doi       = {10.1039/C2CC31624B},
  pages     = {5790 -- 5792},
  year      = {2012},
  abstract  = {Chelate stabilization of a titanium(IV)-salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.},
  language  = {en}
}