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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptors TRAILR1/death receptor 4 (DR4) and TRAILR2/DR5 trigger cell death in many cancer cells but rarely exert cytotoxic activity on non-transformed cells. Against this background, a variety of recombinant TRAIL variants and anti-TRAIL death receptor antibodies have been developed and tested in preclinical and clinical studies. Despite promising results from mice tumor models, TRAIL death receptor targeting has failed so far in clinical studies to show satisfying anti-tumor efficacy. These disappointing results can largely be explained by two issues: First, tumor cells can acquire TRAIL resistance by several mechanisms defining a need for combination therapies with appropriate sensitizing drugs. Second, there is now growing preclinical evidence that soluble TRAIL variants but also bivalent anti-TRAIL death receptor antibodies typically require oligomerization or plasma membrane anchoring to achieve maximum activity. This review discusses the need for oligomerization and plasma membrane attachment for the activity of TRAIL death receptor agonists in view of what is known about the molecular mechanisms of how TRAIL death receptors trigger intracellular cell death signaling. In particular, it will be highlighted which consequences this has for the development of next generation TRAIL death receptor agonists and their potential clinical application.
Das Präsentieren ist eine Lernform, die die wesentlichen Ziele eines autonomen und handlungsorientierten Englischkurses erfüllt und die als Zentralqualifikation im universitären Bereich und außerakademischen Kontext gefordert wird. In dem vorliegenden Artikel wird auf die Vielfalt der Kompetenzen, die durch das Einüben von mündlichen Präsentationen erarbeitet werden, eingegangen. Präsentieren dient dabei nicht nur der sprachlichen Verbesserung und Routine in der Fremdsprache, sondern auch der allgemeinen Einübung der "Kunst der Präsentation" und der Vermittlung von Wissensinhalten. Die daraus entstehende Rolle der Lehrperson als Mediator im Unterrichtsgeschehen soll, ebenso wie ein Praxisbezug in Form von didaktischen Tipps und Lernerarrangements, nicht außen vor gelassen werden.
Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL) (1). Most patients initially respond well to standard therapy, but advanced MF is often treatment refractory. Thus, a combination of the available treatment options is an important strategy. Total skin electron beam radiation (TSEB) is effective in MF, with a complete remission rate of up to 90% in the early stages. However, in patients with more advanced stages, remission rates are considerably lower (2, 3). Denileukin diftitox (DD) (Ontak®) is a recombinant fusion protein of the receptor-binding domain of interleukin (IL)-2 and the enzymatic and translocation domains of diphtheria toxin (4). It targets the alpha-subunit of the IL-2-receptor (CD25). There are no reports on this combination therapy in MF.