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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.
Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7
(2011)
Suburethral slings as well as different meshes are widely used treating stress urinary incontinence and prolaps in women. With the development of MiniSlings and special meshes using less alloplastic material anchorage systems become more important to keep devices in place and to put some tension especially on the MiniSlings. To date, there are many different systems of MiniSlings of different companies on the market which differ in the structure of the used meshes and anchors. A new objective measurement method to compare different properties of MiniSling systems (mesh and anchor) is presented in this article. Ballistic gelatine acts as soft tissue surrogate. Significant differences in parameters like pull-out strength of anchors or shrinkage of meshes under loading conditions have been determined. The form and size of the anchors as well as the structural stability of the meshes are decisive for a proper integration. The tested anchorings sytems showed markedly different mechanical function at their respective load bearing capacity. As the stable fixation of the device in tissue is a prerequisite for a permanet reinforcement, the proposed test system permits further optimisation of anchor and mesh devices to improve the success of the surgical treatment
Thin films of poly(ethyleneterephthalate) [PET]were exposed to radiation dose ranging from 10 to 30 kGy by using gamma rays in the range 12.8-177.8 MGy using swift light ions of hydrogen. There was no effect of the radiation dose on the optical behaviour of PET as a result of exposure to radiation dose up to 30 kGy brought about by gamma rays but a significant decrease in the optical band gap values was observed when PET was exposed to swift light ions of hydrogen. The data obtained are discussed in terms of optical studies carried out on PET using swift heavy ions.
Testing of a 10 kW diffusive micro-mix combustor for hydrogen-fuelled micro-scale gas turbines
(2007)
One-chip integrated dual amperometric/field-effect sensor for the detection of dissolved hydrogen
(2011)
Media Delivery Based on Service Aware Transport Overlay Networks / Kampmann, Markus ; Hartung, Frank
(2007)
Planwirtschaft
(2004)
Roboterfußball - Wissenschaft, die auch Spass macht / Ferrein, Alexander ; Lakemeyer, Gerhard
(2006)
Logic-based robot control in highly dynamic domains / Ferrein, Alexander ; Lakemeyer, Gerhard
(2008)
Embedding fuzzy controllers in golog / Ferrein, Alexander ; Schiffer, Stefan ; Lakemeyer, Gerhard
(2009)