TY  - JOUR
A1  - Lüke, Florian
A1  - Haller, Florian
A1  - Utpatel, Kirsten
A1  - Krebs, Markus
A1  - Meidenbauer, Norbert
A1  - Scheiter, Alexander
A1  - Spoerl, Silvia
A1  - Heudobler, Daniel
A1  - Sparrer, Daniela
A1  - Kaiser, Ulrich
A1  - Keil, Felix
A1  - Schubart, Christoph
A1  - Tögel, Lars
A1  - Einhell, Sabine
A1  - Dietmaier, Wolfgang
A1  - Huss, Ralf
A1  - Dintner, Sebastian
A1  - Sommer, Sebastian
A1  - Jordan, Frank
A1  - Goebeler, Maria-Elisabeth
A1  - Metz, Michaela
A1  - Haake, Diana
A1  - Scheytt, Mithun
A1  - Gerhard-Hartmann, Elena
A1  - Maurus, Katja
A1  - Brändlein, Stephanie
A1  - Rosenwald, Andreas
A1  - Hartmann, Arndt
A1  - Märkl, Bruno
A1  - Einsele, Hermann
A1  - Mackensen, Andreas
A1  - Herr, Wolfgang
A1  - Kunzmann, Volker
A1  - Bargou, Ralf
A1  - Beckmann, Matthias W.
A1  - Pukrop, Tobias
A1  - Trepel, Martin
A1  - Evert, Matthias
A1  - Claus, Rainer
A1  - Kerscher, Alexander
T1  - Identification of disparities in personalized cancer care — a joint approach of the German WERA consortium
JF  - Cancers
N2  - (1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in Würzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy.
KW  - precision oncology
KW  - MTB
KW  - patient access
KW  - cancer care
KW  - outreach
KW  - real world data
KW  - outcomes research
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290311
SN  - 2072-6694
VL  - 14
IS  - 20
ER  - 
TY  - JOUR
A1  - Varagnolo, Linda
A1  - Lin, Quiong
A1  - Obier, Nadine
A1  - Plass, Christoph
A1  - Dietl, Johannes
A1  - Zenke, Martin
A1  - Claus, Rainer
A1  - Müller, Albrecht M.
T1  - PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells
JF  - Scientific Reports
N2  - Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different HK4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs.
KW  - ex vivo expansion
KW  - epigenomic landscapes
KW  - in vivo polycomb
KW  - transplantation states genes
KW  - EZH2 differentiation trichostatin
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148374
VL  - 5
IS  - 12319
ER  -