TY  - JOUR
A1  - Ben Khaled, Najib
A1  - Hammer, Katharina
A1  - Ye, Liangtao
A1  - Alnatsha, Ahmed
A1  - Widholz, Sebastian A.
A1  - Piseddu, Ignazio
A1  - Sirtl, Simon
A1  - Schneider, Julia
A1  - Munker, Stefan
A1  - Mahajan, Ujjwal Mukund
A1  - Montero, Juan José
A1  - Griger, Joscha
A1  - Mayerle, Julia
A1  - Reiter, Florian P.
A1  - De Toni, Enrico N.
T1  - TRAIL receptor targeting agents potentiate PARP inhibitor efficacy in pancreatic cancer independently of BRCA2 mutation status
JF  - Cancers
N2  - Chemotherapy, the standard treatment for pancreatic ductal adenocarcinoma (PDAC), has only a modest effect on the outcome of patients with late-stage disease. Investigations of the genetic features of PDAC have demonstrated a frequent occurrence of mutations in genes involved in homologous recombination (HR), especially in the breast cancer susceptibility gene 2 (BRCA2). Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, is approved as a maintenance treatment for patients with advanced PDAC with germline BRCA1/2 mutations following a platinum-containing first-line regimen. Limitations to the use of PARP inhibitors are represented by the relatively small proportion of patients with mutations in BRCA1/2 genes and the modest capability of these substances of inducing objective response. We have previously shown that pancreatic cancer with BRCA2 mutations exhibits a remarkably enhanced sensitivity towards tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) receptor-stimulating agents. We thus aimed to investigate the effect of combined treatment with PARP inhibitors and TRAIL receptor-stimulating agents in pancreatic cancer and its dependency on the BRCA2 gene status. The respective effects of TRAIL-targeting agents and the PARP inhibitor olaparib or of their combination were assessed in pancreatic cancer cell lines and patient-derived organoids. In addition, BRCA2-knockout and -complementation models were investigated. The effects of these agents on apoptosis, DNA damage, cell cycle, and receptor surface expression were assessed by immunofluorescence, Western blot, and flow cytometry. PARP inhibition and TRAIL synergized to cause cell death in pancreatic cancer cell lines and PDAC organoids. This effect proved independent of BRCA2 gene status in three independent models. Olaparib and TRAIL in combination caused a detectable increase in DNA damage and a concentration-dependent cell cycle arrest in the G2/M and S cell cycle phases. Olaparib also significantly increased the proportion of membrane-bound death receptor 5. Our results provide a preclinical rationale for the combination of PARP inhibitors and TRAIL receptor agonists for the treatment of pancreatic cancer and suggest that the use of PARP inhibitors could be extended to patients without BRCA2 mutations if used in combination with TRAIL agonists.
KW  - apoptosis
KW  - DNA damage
KW  - pancreatic neoplasms
KW  - poly(ADP-ribose) polymerase inhibitors
KW  - TNF-related apoptosis-inducing ligand
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290884
SN  - 2072-6694
VL  - 14
IS  - 21
ER  - 
TY  - JOUR
A1  - Hammer, Julia
T1  - My presentation ... Presenting in English
N2  - 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.
N2  - Presentations are a type of learning which achieve the goals of the autonomous and activity-oriented English class. Moreover, presentations are a central aspect of what is demanded at the university level as well as in other non-academic contexts. The following article deals with the multitude of competencies which can be used to practice making oral presentations in EFL classroom situations. Oral presentations do not only improve speaking and routines in the foreign language, but they also offer practice in the "art of presentations" as well as they impart knowledge to the listener. Thereby, the article understands the role of the teacher as a mediator within the classroom while simultaneously incorporating pedagogical tips and strategies which can be applied to the EFL classroom.
KW  - Präsentation
KW  - Fremdsprachenlernen
KW  - Fremdsprachenunterricht
KW  - Lernautonomie
KW  - Lernstrategien
KW  - Präsentationstechniken
KW  - Aufgabenorientierung
KW  - Learner autonomy
KW  - learning strategies
KW  - presentation techniques
KW  - task-based teaching
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-49819
N1  - Aus urheberrechtlichen Gründen wurde der Zugriff auf den Volltext zu diesem Dokument gesperrt.
ER  -