@article{WielandStrisselSchorleetal.2021,
  author    = {Wieland, Annalena and Strissel, Pamela L. and Schorle, Hannah and Bakirci, Ezgi and Janzen, Dieter and Beckmann, Matthias W. and Eckstein, Markus and Dalton, Paul D. and Strick, Reiner},
  title     = {Brain and breast cancer cells with PTEN loss of function reveal enhanced durotaxis and RHOB dependent amoeboid migration utilizing 3D scaffolds and aligned microfiber tracts},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {20},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13205144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248443},
  year      = {2021},
  abstract  = {Background: Glioblastoma multiforme (GBM) and metastatic triple-negative breast cancer (TNBC) with PTEN mutations often lead to brain dissemination with poor patient outcome, thus new therapeutic targets are needed. To understand signaling, controlling the dynamics and mechanics of brain tumor cell migration, we implemented GBM and TNBC cell lines and designed 3D aligned microfibers and scaffolds mimicking brain structures. Methods: 3D microfibers and scaffolds were printed using melt electrowriting. GBM and TNBC cell lines with opposing PTEN genotypes were analyzed with RHO-ROCK-PTEN inhibitors and PTEN rescue using live-cell imaging. RNA-sequencing and qPCR of tumor cells in 3D with microfibers were performed, while scanning electron microscopy and confocal microscopy addressed cell morphology. Results: In contrast to the PTEN wildtype, GBM and TNBC cells with PTEN loss of function yielded enhanced durotaxis, topotaxis, adhesion, amoeboid migration on 3D microfibers and significant high RHOB expression. Functional studies concerning RHOB-ROCK-PTEN signaling confirmed the essential role for the above cellular processes. Conclusions: This study demonstrates a significant role of the PTEN genotype and RHOB expression for durotaxis, adhesion and migration dependent on 3D. GBM and TNBC cells with PTEN loss of function have an affinity for stiff brain structures promoting metastasis. 3D microfibers represent an important tool to model brain metastasizing tumor cells, where RHO-inhibitors could play an essential role for improved therapy.},
  language  = {en}
}
@article{SchofferSchueleinArandetal.2016,
  author    = {Schoffer, Olaf and Sch{\"u}lein, Stefanie and Arand, Gerlinde and Arnholdt, Hans and Baaske, Dieter and Bargou, Ralf C. and Becker, Nikolaus and Beckmann, Matthias W. and Bodack, Yves and B{\"o}hme, Beatrix and Bozkurt, Tayfun and Breitsprecher, Regine and Buchali, Andre and Burger, Elke and Burger, Ulrike and Dommisch, Klaus and Elsner, Gudrun and Fernschild, Karin and Flintzer, Ulrike and Funke, Uwe and Gerken, Michael and G{\"o}bel, Hubert and Grobe, Norbert and Gumpp, Vera and Heinzerling, Lucie and Kempfer, Lana Raffaela and Kiani, Alexander and Klinkhammer-Schalke, Monika and Kl{\"o}cking, Sabine and Kreibich, Ute and Knabner, Katrin and Kuhn, Peter and Lutze, Stine and M{\"a}der, Uwe and Maisel, Tanja and Maschke, Jan and Middeke, Martin and Neubauer, Andreas and Niedostatek, Antje and Opazo-Saez, Anabelle and Peters, Christoph and Schell, Beatrice and Schenkirsch, Gerhard and Schmalenberg, Harald and Schmidt, Peter and Schneider, Constanze and Schubotz, Birgit and Seide, Anika and Strecker, Paul and Taubenheim, Sabine and Wackes, Matthias and Weiß, Steffen and Welke, Claudia and Werner, Carmen and Wittekind, Christian and Wulff, J{\"o}rg and Zettl, Heike and Klug, Stefanie J.},
  title     = {Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011},
  series = {BMC Cancer},
  volume    = {16},
  journal   = {BMC Cancer},
  number    = {936},
  doi       = {10.1186/s12885-016-2963-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164544},
  year      = {2016},
  abstract  = {Background Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. Methods Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. Results The number of annually documented cases increased by 53.2\% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95\% CI 0.97-0.97), sex (OR 1.18, 95\% CI 1.11-1.25), date of diagnosis (OR 1.05, 95\% CI 1.04-1.06), 'diagnosis during screening' (OR 3.24, 95\% CI 2.50-4.19) and place of residence (OR 1.23, 95\% CI 1.16-1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4\% (95\% CI 82.8-83.9\%). Conclusions No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008. "},
  language  = {en}
}
@article{WeigandBoosTasbihietal.2016,
  author    = {Weigand, Annika and Boos, Anja M. and Tasbihi, Kereshmeh and Beier, Justus P. and Dalton, Paul D. and Schrauder, Michael and Horch, Raymund E. and Beckmann, Matthias W. and Strissel, Pamela L. and Strick, Reiner},
  title     = {Selective isolation and characterization of primary cells from normal breast and tumors reveal plasticity of adipose derived stem cells},
  series = {Breast Cancer Research},
  volume    = {18},
  journal   = {Breast Cancer Research},
  number    = {32},
  doi       = {10.1186/s13058-016-0688-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164759},
  year      = {2016},
  abstract  = {Background There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors. Methods A total of 17 cell lines were established and gene expression was analyzed for MEC and MES (n = 42) and ADSC (n = 48) and MUC1, pan-KRT, CD90 and GATA-3 by immunofluorescence. DNA fingerprinting to track cell line identity was performed between original primary tissues and isolates. Functional studies included ADSC differentiation, tumor MES and MEC invasion co-cultured with ADSC-conditioned media (CM) and MES adhesion and growth on 3D-printed scaffolds. Results Comparative analysis showed higher gene expression of EPCAM, CD49f, CDH1 and KRTs for normal MEC lines; MES lines e.g. Vimentin, CD10, ACTA2 and MMP9; and ADSC lines e.g. CD105, CD90, CDH2 and CDH11. Compared to the mean of all four normal breast cell lines, both breast tumor cell lines demonstrated significantly lower ADSC marker gene expression, but higher expression of mesenchymal and invasion gene markers like SNAI1 and MMP2. When compared with four normal ADSC differentiated lineages, both tumor ADSC showed impaired osteogenic and chondrogenic but enhanced adipogenic differentiation and endothelial-like structures, possibly due to high PDGFRB and CD34. Addressing a functional role for overproduction of adipocytes, we initiated 3D-invasion studies including different cell types from the same patient. CM from ADSC differentiating into adipocytes induced tumor MEC 3D-invasion via EMT and amoeboid phenotypes. Normal MES breast cells adhered and proliferated on 3D-printed scaffolds containing 20 fibers, but not on 2.5D-printed scaffolds with single fiber layers, important for tissue engineering. Conclusion Expression analyses confirmed successful simultaneous cell isolations of three different phenotypes from normal and tumor primary breast tissues. Our cell culture studies support that breast-tumor environment differentially regulates tumor ADSC plasticity as well as cell invasion and demonstrates applications for regenerative medicine.},
  language  = {en}
}
@article{LuekeHallerUtpateletal.2022,
  author    = {L{\"u}ke, Florian and Haller, Florian and Utpatel, Kirsten and Krebs, Markus and Meidenbauer, Norbert and Scheiter, Alexander and Spoerl, Silvia and Heudobler, Daniel and Sparrer, Daniela and Kaiser, Ulrich and Keil, Felix and Schubart, Christoph and T{\"o}gel, Lars and Einhell, Sabine and Dietmaier, Wolfgang and Huss, Ralf and Dintner, Sebastian and Sommer, Sebastian and Jordan, Frank and Goebeler, Maria-Elisabeth and Metz, Michaela and Haake, Diana and Scheytt, Mithun and Gerhard-Hartmann, Elena and Maurus, Katja and Br{\"a}ndlein, Stephanie and Rosenwald, Andreas and Hartmann, Arndt and M{\"a}rkl, Bruno and Einsele, Hermann and Mackensen, Andreas and Herr, Wolfgang and Kunzmann, Volker and Bargou, Ralf and Beckmann, Matthias W. and Pukrop, Tobias and Trepel, Martin and Evert, Matthias and Claus, Rainer and Kerscher, Alexander},
  title     = {Identification of disparities in personalized cancer care — a joint approach of the German WERA consortium},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {20},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14205040},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290311},
  year      = {2022},
  abstract  = {(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 W{\"u}rzburg, 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.},
  language  = {en}
}
@article{SchulmeyerFaschingHaeberleetal.2023,
  author    = {Schulmeyer, Carla E. and Fasching, Peter A. and H{\"a}berle, Lothar and Meyer, Julia and Schneider, Michael and Wachter, David and Ruebner, Matthias and P{\"o}schke, Patrik and Beckmann, Matthias W. and Hartmann, Arndt and Erber, Ramona and Gass, Paul},
  title     = {Expression of the immunohistochemical markers CK5, CD117, and EGFR in molecular subtypes of breast cancer correlated with prognosis},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {3},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13030372},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304987},
  year      = {2023},
  abstract  = {Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort-case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS.},
  language  = {en}
}