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Schuhmacher, Bianca ; Rengstl, Benjamin ; Döring, Claudia ; Bein, Julia ; Newrzela, Sebastian ; Brunnberg, Uta ; Kvasnicka, Hans Michael ; Vornanen, Martine ; Küppers, Ralf ; Hansmann, Martin-Leo ; Hartmann, Sylvia
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma, but can transform into diffuse large B cell lymphoma (DLBCL), showing a more aggressive clinical behavior. Little is known about these cases on the molecular level. Therefore, the aim of the present study was to characterize DLBCL transformed from NLPHL (LP-DLBCL) by gene expression profiling (GEP). GEP revealed an inflammatory signature pinpointing to a specific host response. In a coculture model resembling this host response, DEV tumor cells showed an impaired growth behavior. Mechanisms involved in the reduced tumor cell proliferation included a downregulation of MYC and its target genes. Lack of MYC expression was also confirmed in 12/16 LP-DLBCL by immunohistochemistry. Furthermore, CD274/PD-L1 was upregulated in DEV tumor cells after coculture with T cells or monocytes and its expression was validated in 12/19 cases of LP-DLBCL. Thereby, our data provide new insights into the pathogenesis of LP-DLBCL and an explanation for the relatively low tumor cell content. Moreover, the findings suggest that treatment of these patients with immune checkpoint inhibitors may enhance an already ongoing host response in these patients.
Prieto García, Cristian ; Hartmann, Oliver ; Reissland, Michaela ; Braun, Fabian ; Fischer, Thomas ; Walz, Susanne ; Schülein‐Völk, Christina ; Eilers, Ursula ; Ade, Carsten P. ; Calzado, Marco A. ; Orian, Amir ; Maric, Hans-Michael ; Münch, Christian ; Rosenfeldt, Mathias Tillmann ; Eilers, Martin ; Diefenbacher, Markus Elmar
The transcription factor ∆Np63 is a master regulator of epithelial cell identity and essential for the survival of squamous cell carcinoma (SCC) of lung, head and neck, oesophagus, cervix and skin. Here, we report that the deubiquitylase USP28 stabilizes ∆Np63 and maintains elevated ∆NP63 levels in SCC by counteracting its proteasome‐mediated degradation. Impaired USP28 activity, either genetically or pharmacologically, abrogates the transcriptional identity and suppresses growth and survival of human SCC cells. CRISPR/Cas9‐engineered in vivo mouse models establish that endogenous USP28 is strictly required for both induction and maintenance of lung SCC. Our data strongly suggest that targeting ∆Np63 abundance via inhibition of USP28 is a promising strategy for the treatment of SCC tumours.
Es wird gezeigt, daß man die langwelligen Absorptionsspektren der magnetisch normalen oktaedrischen Komplexionen mit den Übergangsmetallionen Ti3+, V3+, Cr3+, Mn3+ und Fe3+ verstehen kann, wenn man annimmt, daß die schwachen langwelligen Banden durch Übergänge zwischen den Aufspaltungsprodukten der jeweiligen Grundterme entstehen, wobei die Auf-spaltungen durch das elektrostatische Feld der Liganden zustande kommen.
Die Lichtabsorptionseigenschaften einer Reihe von Lösungen der Komplexionen des dreiwertigen Vanadins vom Typus [V A6]3+, wo A H2O, CH3OH, C2H5OH sowie iso-C4H9OH ist, wurden gemessen. Ferner wurden die Absorptionsspektren von kristallisiertem Ammonium-sowie Caesiumvanadin(III)-alaun aufgenommen.
Intensitätsverhältnisse und spektrale Lage der in allen Spektren auftretenden langwelligen Banden stehen in guter Übereinstimmung mit den Aussagen der Theorie für den Fall eines Zentralions mit zwei d-Elektronen bei Oh-Symmetrie des Komplexfeldes.
Die FOURIER-Nullkomponente der Bindungsmatrix Gij G(0) in 1 Beziehung (5.16) wurde durch Summation spezieller Diagramme in der sogen. „Kettenapproximation“ und der „Wassermelonenapproximation“ näherungsweise berechnet. Auf der Basis von (5.16) in 1 wurde in der Kettenapproximation und der Wassermelonenapproximation die magnetische Suszeptibilität und die Magnetisierung des dreidimensionalen ISING-Modells bestimmt. In der Kettenapproximation wurden ferner die freie Energie, die innere Energie und die Atomwärme des dreidimensionalen ISING-Ferromagneten sowie die Druck-Dichte-Isothermen des dreidimensionalen Gittergases ausgerechnet.
Die „Selbstenergien“ Gn in 1 wurden durch näherungsweise Auswertung einer größeren Klasse von Selbstenergiediagrammen approximativ berechnet. Das Gleichungssystem (3.3) in 1 für die renormierten Semiinvarianten wurde umgeformt und durch zusätzliche Näherungsannahmen vereinfacht. Durch Näherungsansätze für die Semiinvarianten M2, M3,... konnten einfache Gleichungen für die Magnetisierung M1 hergeleitet werden. Diese Gleichungen wurden numerisch gelöst. Auf der Grundlage der Beziehungen (3.5) und (4.8) in 1 wurden ferner die innere Energie, die freie Energie und die Atomwärme des zweidimensionalen Ising-Ferromagneten sowie die Druck-Dichte-Isothermen des zweidimensionalen Gittergases numerisch ausgerechnet.