von Soyeon Bae ; Lea Heidrich ; Shaun R. Levick ; Martin M. Gossner ; Sebastian Seibold ; Wolfgang W. Weisser ; Paul Magdon ; Alla Serebryanyk ; Claus Bässler ; Deborah Schäfer ; Ernst-Detlef Schulze ; Inken Dörfler ; Jörg Müller ; Kirsten Jung ; Marco Heurich ; Markus Fischer ; Nicolas Roth ; Peter Schall ; Steffen Boch ; Stephan Wöllauer ; Swen C. Renner ; Jörg Müller
von Petros Christopoulos ; Martina Kirchner ; Farastuk Bozorgmehr ; Nikolaus Magios ; Daniel Kazdal ; Anna-Lena Volckmar ; Lena Marie Brückner ; Tilmann Bochtler ; Mark Kriegsmann ; Volker Endris ; Roland Penzel ; Katharina Kriegsmann ; Martin E. Eichhorn ; Felix Herth ; Claus Peter Heußel ; Rami El-Shafie ; Marc Schneider ; Thomas Muley ; Michael Meister ; Peter Schirmacher ; Helge Bischoff ; Frank Griesinger ; Albrecht Stenzinger ; Michael Thomas
Objective - Panel-based next-generation sequencing (NGS) is increasingly used for the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC) and could improve risk assessment in combination with clinical parameters. - Materials and methods - To this end, we retrospectively analyzed the outcome of 400 tyrosine kinase inhibitor (TKI)-treated EGFR+ NSCLC patients with validation of results in an independent cohort (n = 130). - Results - EGFR alterations other than exon 19 deletions (non-del19), TP53 co-mutations, and brain metastases at baseline showed independent associations of similar strengths with progression-free (PFS hazard ratios [HR] 2.1-2.3) and overall survival (OS HR 1.7-2.2), in combination defining patient subgroups with distinct outcome (EGFR+ NSCLC risk Score, "ENS", p < 0.001). Co-mutations beyond TP53 were rarely detected by our multigene panel (<5%) and not associated with clinical endpoints. Smoking did not affect outcome independently, but was associated with non-del19 EGFR mutations (p < 0.05) and comorbidities (p < 0.001). Laboratory parameters, like the blood lymphocyte-to-neutrophil ratio and serum LDH, correlated with the metastatic pattern (p < 0.01), but had no independent prognostic value. Reduced ECOG performance status (PS) was associated with comorbidities (p < 0.05) and shorter OS (p < 0.05), but preserved TKI efficacy. Non-adenocarcinoma histology was also associated with shorter OS (p < 0.05), but rare (2-3 %). The ECOG PS and non-adenocarcinoma histology could not be validated in our independent cohort, and did not increase the range of prognostication alongside the ENS. - Conclusions - EGFR variant, TP53 status and brain metastases predict TKI efficacy and survival in EGFR+ NSCLC irrespective of other currently available parameters ("ENS"). Together, they constitute a practical and reproducible approach for risk stratification of newly diagnosed metastatic EGFR+ NSCLC.
Lung cancer Amsterdam [u.a.] : Elsevier, 1985 148(2020), Seite 105-112 Online-Ressource
von Mark-Peter Ufen ; Claus-Henning Köhne ; M. Wischnewsky ; R. Wolters ; I. Novopashenny ; J. Fischer ; M. Constantinidou ; Kurt Possinger ; Anne C. Regierer
Trotz intensiver Forschung ist die Evolution und der Erhalt sexueller Reproduktion aufgrund scheinbar damit verbundener Kosten ein ungelöstes Rätsel bei dem vielfach empirische Daten fehlen um Erklärungsansätze zu überprüfen. Rotifera sind hierfür gute Versuchsobjekte, da sich unter diesen kleinen, schnell reproduzierenden aquatischen Metazoen obligat sexuelle, fakultativ sexuelle und auch obligat asexuelle Arten finden. Diese Arbeit untersucht dabei v.a. limitierende Faktoren für asexuelle Reproduktion, hauptsächlich an asexuellen bdelloiden aber auch an fakultativ sexuellen monogononten Rotifera. Es wurde untersucht ob und wie die Fähigkeit ausgetrocknet zu überdauern den asexuellen Bdelloiden hilft. Weiterhin wurde geschaut wie Monogononte und Bdelloide mit durch UVB-Strahlung potentiell erzeugten Mutationen umgehen, da Mutationen für asexuelle Arten eventuell problematisch sind. Zuletzt wurde getestet bei welchen Futter- und Temperaturbedingungen Monogononte sich bevorzugt sexuell anstatt asexuell vermehren. <dt.>
Despite much theoretical work, the evolution and maintenance of sexual reproduction in light of its apparent costs is not understood. Generally lacking are empirical data to test the proposed hypotheses. Rotifera, aquatic metazoans, are ideally suited to fill this gap as among these small, fast reproducing animals there are obligate sexual, facultative asexual and obligate asexual species. To this end the thesis focuses on the limits of asexual reproduction, primarily in the asexual bdelloid, but also in the facultative sexual monogonont rotifers. It is investigated how the ability to survive desiccation enables asexual bdelloids to survive despite missing sex. Furthermore, it was tested how monogononts versus bdelloids handle potential UVB-induced mutations, as mutations are thought to be difficult to handle for asexuals. At last it was monitored under different food- and temperature conditions when facultative sexual rotifers prefer to reproduce sexually instead of asexually. <engl.>
von Beate Schultheis ; G. Folprecht ; J. Kuhlmann ; R. Ehrenberg ; U. T. Hacker ; Claus-Henning Köhne ; M. Kornacker ; O. Cruzà Boix ; O. Lettieri ; J. Krauss ; R. Fischer ; S. Hamann ; D. Strumberg ; Klaus B. Mross