Pazopanib for the Treatment of Patients with Advanced Renal Cell Carcinoma

Dramatic advances in the care of patients with advanced renal cell carcinoma have occurred over the last ten years, including insights into the molecular pathogenesis of this disease, that have now been translated into paradigm-changing therapeutic strategies. Elucidating the importance of signaling cascades related to angiogenesis is notable among these achievements. Pazopanib is a novel small molecule tyrosine kinase inhibitor that targets VEGFR-1, -2, and -3; PDGFR-α, PDGFR-β; and c-kit tyrosine kinases. This agent exhibits a distinct pharmacokinetic profile as well as toxicity profile compared to other agents in the class of VEGF signaling pathway inhibitors. This review will discuss the scientific rationale for the development of pazopanib, as well as preclinical and clinical trials that led to approval of pazopanib for patients with advanced renal cell carcinoma. The most recent information, including data from 2010 national meeting of the American Society of Clinical Oncology, and the design of ongoing Phase III trials, will be discussed. Finally, an algorithm utilizing Level I evidence for the treatment of patients with this disease will be proposed

Refoldable Foldamers:Global Conformational Switching by Deletion or Insertion of a Single Hydrogen Bond

Small changes in the structure of a foldamer may lead to gross changes in conformational preference. We show that the simple insertion or deletion of a single hydrogen bond by changes in pH or by photochemical deprotection is sufficient to refold a helical oligomer, interconverting M and P screw‐sense preference. As a consequence of the switch, information may be transmitted to a remote catalytic site, selectively directing the formation of either of two enantiomeric products by a reaction involving 1,22‐remote intermolecular asymmetric induction

Einsatz virtueller Transportsimulatoren zum umweltbewußten Gefahrensituationstraining

Die Auswertung der Statistiken des Statistischen Bundesamtes ergab, daß der größte Teil der Unfälle bei Gefahrguttransporten auf das Fehlverhalten der Fahrzeugführer zurückzuführen ist. Eine weitaus kleinere Zahl von Unfällen ist auf technische Mängel, Straßenverhältnisse oder Witterungseinflüsse zurückzuführen. Die Statistiken beweisen, dag 80 % aller Unfälle durch richtiges Verhalten der Fahrzeugführer vermieden werden könnte. Das richtige Verhalten muß aber trainiert werden, da gerade im Gefahrguttransport die Folgen eines Unfalls für den Fahrer, unbeteiligte Menschen und die Umwelt meist nicht absehbar sind