3 results
Search Results
Now showing 1 - 3 of 3
- ItemOxaliplatin-DNA adduct formation in white blood cells of cancer patients(London : Nature Publishing Group, 2008) Pieck, A.C.; Drescher, A.; Wiesmann, K.G.; Messerschmidt, J.; Weber, G.; Strumberg, D.; Hilger, R.A.; Scheulen, M.E.; Jaehde, U.In this study, we investigated the kinetics of oxaliplatin-DNA adduct formation in white blood cells of cancer patients in relation to efficacy as well as oxaliplatin-associated neurotoxicity. Thirty-seven patients with various solid tumours received 130 mg m−2 oxaliplatin as a 2-h infusion. Oxaliplatin-DNA adduct levels were measured in the first cycle using adsorptive stripping voltammetry. Platinum concentrations were measured in ultrafiltrate and plasma using a validated flameless atomic absorption spectrometry method. DNA adduct levels showed a characteristic time course, but were not correlated to platinum pharmacokinetics and varied considerably among individuals. In patients showing tumour response, adduct levels after 24 and 48 h were significantly higher than in nonresponders. Oxaliplatin-induced neurotoxicity was more pronounced but was not significantly different in patients with high adduct levels. The potential of oxaliplatin-DNA adduct measurements as pharmacodynamic end point should be further investigated in future trials.
- ItemRecent developments in peptide-based nucleic acid delivery(Basel : MDPI, 2008) Veldhoen, Sandra; Laufer, Sandra D.; Restle, TobiasDespite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cellpenetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisenseoligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls.
- ItemQuantitative Analyse zur Beschreibung dynamischer Prozesse in lebenden Systemen, Teilprojekt C: Dynamik der phospho-spezifischen Interaktion der Ena/VASP-Proteine in den cAMP/cGMP-abhängigen Signalwegen : Schlussbericht ; Laufzeit des Vorhabens: 01.12.2008 - 31.12.2009(Hannover : Technische Informationsbibliothek (TIB), 2009) Rudolf-Virchow-Zentrum; Leibniz-Institut für Analytische Wissenschaften[no abstract available]