@article{ZahoGhirlandoAlfonsoetal.2015,
  author    = {Zaho, Huaying and Ghirlando, Rodolfo and Alfonso, Carlos and Arisaka, Fumio and Attali, Ilan and Bain, David L. and Bakhtina, Marina M. and Becker, Donald F. and Bedwell, Gregory J. and Bekdemir, Ahmet and Besong, Tabot M. D. and Birck, Catherine and Brautigam, Chad A. and Brennerman, William and Byron, Olwyn and Bzowska, Agnieszka and Chaires, Jonathan B. and Chaton, Catherine T. and Coelfen, Helmbut and Connaghan, Keith D. and Crowley, Kimberly A. and Curth, Ute and Daviter, Tina and Dean, William L. and Diez, Ana I. and Ebel, Christine and Eckert, Debra M. and Eisele, Leslie E. and Eisenstein, Edward and England, Patrick and Escalante, Carlos and Fagan, Jeffrey A. and Fairman, Robert and Finn, Ron M. and Fischle, Wolfgang and Garcia de la Torre, Jose and Gor, Jayesh and Gustafsson, Henning and Hall, Damien and Harding, Stephen E. and Hernandez Cifre, Jose G. and Herr, Andrew B. and Howell, Elizabeth E. and Isaac, Richard S. and Jao, Shu-Chuan and Jose, Davis and Kim, Soon-Jong and Kokona, Bashkim and Kornblatt, Jack A. and Kosek, Dalibor and Krayukhina, Elena and Krzizike, Daniel and Kusznir, Eric A. and Kwon, Hyewon and Larson, Adam and Laue, Thomas M. and Le Roy, Aline and Leech, Andrew P. and Lilie, Hauke and Luger, Karolin and Luque-Ortega, Juan R. and Ma, Jia and May, Carrie A. and Maynard, Ernest L. and Modrak-Wojcik, Anna and Mok, Yee-Foong and M{\"u}cke, Norbert and Nagel-Steger, Luitgard and Narlikar, Geeta J. and Noda, Masanori and Nourse, Amanda and Obsil, Thomas and Park, Chad K and Park, Jin-Ku and Pawelek, Peter D. and Perdue, Erby E. and Perkins, Stephen J. and Perugini, Matthew A. and Peterson, Craig L. and Peverelli, Martin G. and Piszczek, Grzegorz and Prag, Gali and Prevelige, Peter E. and Raynal, Bertrand D. E. and Rezabkova, Lenka and Richter, Klaus and Ringel, Alison E. and Rosenberg, Rose and Rowe, Arthur J. and Rufer, Arne C. and Scott, David J. and Seravalli, Javier G. and Solovyova, Alexandra S. and Song, Renjie and Staunton, David and Stoddard, Caitlin and Stott, Katherine and Strauss, Holder M. and Streicher, Werner W. and Sumida, John P. and Swygert, Sarah G. and Szczepanowski, Roman H. and Tessmer, Ingrid and Toth, Ronald T. and Tripathy, Ashutosh and Uchiyama, Susumu and Uebel, Stephan F. W. and Unzai, Satoru and Gruber, Anna Vitlin and von Hippel, Peter H. and Wandrey, Christine and Wang, Szu-Huan and Weitzel, Steven E and Wielgus-Kutrowska, Beata and Wolberger, Cynthia and Wolff, Martin and Wright, Edward and Wu, Yu-Sung and Wubben, Jacinta M. and Schuck, Peter},
  title     = {A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0126420},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151903},
  pages     = {e0126420},
  year      = {2015},
  abstract  = {Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304\(\pm\)0.188) S (4.4\%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of \(\pm\)0.030 S (0.7\%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.},
  language  = {en}
}
@article{WernerLueckerathSchmidetal.2016,
  author    = {Werner, R. A. and L{\"u}ckerath, K. and Schmid, J. S. and Higuchi, T. and Kreissl, M. C. and Grelle, I. and Reiners, C. and Buck, A. K. and Lapa, C.},
  title     = {Thyroglobulin fluctuations in patients with iodine-refractory differentiated thyroid carcinoma on lenvatinib treatment - initial experience},
  series = {Scientific Reports},
  volume    = {6},
  journal   = {Scientific Reports},
  doi       = {10.1038/srep28081},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147407},
  pages     = {28081},
  year      = {2016},
  abstract  = {Tyrosine kinase inhibitors (TKI) have shown clinical effectiveness in iodine-refractory differentiated thyroid cancer (DTC). The corresponding role of serum thyroglobulin (Tg) in iodine-refractory DTC has not been investigated yet. 9 patients (3 female, 61 ± 8y) with progressive iodine-refractory DTC starting on lenvatinib were considered. Tumor restaging was performed every 2-3 months including contrast-enhanced computed tomography (CT, RECIST 1.1). Serum Tg was measured and compared to imaging findings. After treatment initiation, serum Tg levels dropped in all patients with a median reduction of 86.2\%. During long-term follow-up (median, 25.2 months), fluctuations in Tg could be observed in 8/9 subjects. According to RECIST, 6/9 subjects achieved a partial response or stable disease with the remaining 3/9 experiencing progressive disease (2/3 with Tg levels rising above baseline). All of the patients with disease progression presented with a preceding continuous rise in serum Tg, whereas tumor marker oscillations in the subjects with controlled disease were only intermittent. Initiation of lenvatinib in iodine-refractory DTC patients is associated with a significant reduction in serum Tg levels as a marker of treatment response. In the course of treatment, transient Tg oscillations are a frequent phenomenon that may not necessarily reflect morphologic tumor progression.},
  language  = {en}
}
@article{LapaReiterKircheretal.2016,
  author    = {Lapa, Constantin and Reiter, Theresa and Kircher, Malte and Schirbel, Andreas and Werner, Rudolf A. and Pelzer, Theo and Pizarro, Carmen and Skowasch, Dirk and Thomas, Lena and Schlesinger-Irsch, Ulrike and Thomas, Daniel and Bundschuh, Ralph A. and Bauer, Wolfgang R. and Gartner, Florian C.},
  title     = {Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {47},
  doi       = {10.18632/oncotarget.12799},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175423},
  pages     = {77807-77814},
  year      = {2016},
  abstract  = {Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR-PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25\% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up. In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1\% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively. Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.},
  language  = {en}
}
@article{DaenikenLutzJaeckhetal.1984,
  author    = {D{\"a}niken, A. von and Lutz, Werner K. and J{\"a}ckh, R. and Schlatter, C.},
  title     = {Investigation of the potential for binding of Di(2-ethylhexyl) phthalate (DEHP) and Di(2-ethylhexyl) adipate (DEHA) to liver DNA in vivo},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61004},
  year      = {1984},
  abstract  = {Investigation of the Potential for Binding of Di(2-ethylhexyl) Phthalate (DEHP) and Di(2- ethylhexyl) Adipate (DEHA) to Liver DNA in Vivo. VON D{\"A}NIKEN, A., LUTZ, W. K., J{\"A}CKH, R., AND ScHLATTER, C. (1984). Toxico/. App/. Pharmaco/. 73, 373-387. It was the aim oftbis investigation to determine whether covalent binding of di(2-ethylhexyl) phthalate (DEHP) to rat liver DNA and of di(2-ethylhexyl) adipate (DEHA) to mouse liver DNA could be a mechanism of action contributing to the observed induction of liver tumors after lifetime feeding of the respective rodent species with high doses of DEHP and DEHA. For this purpose, DEHP and DEHA radiolabeled in different parts of the molecule were administered orally to female rats and mice, respectively, with or witbout pretreatment for 4 weeks with 1\% unlabeled compound in the diet. Liver DNA was isolated after 16 hr and analyzed for radioactivity. The data were converted to a covalent binding index, CBI = (micromoles of substance bound per mole of DNA nucleotides)/(millimoles of substance applied per kilogram body weight), in order to allow a quantitative comparison also with other carcinogens and noncarcinogens. Administration of [\(^{14}\)H]carboxylate-labeled DEHP to rats resulted in no measurable DNA radioactivity. The Iimit of detection, CBI < 0.02 was about 100 times below the CBI of compounds where an observable tumor-inducing potential could be due to genotoxicity. With [\(^{14}\)C]- and [\(^{3}\)H]DEHP labeled in the alcohol moiety, radioactivity was clearly measurable in rat liver DNA. HPLC analysis of enzyme-degraded or acid-hydrolyzed DNA revealed that the natural nucleosides or purine bases were radiolabeled whereas no radioactivity was detectable in those fractions where tbe carcinogenmodified nucleoside or base adducts are expected. The respective Iimits of detection were at 0.07 and 0.04 CBI units for the \(^{14}\)C and \(^{3}\)H Iabels, respectively. The experiments with [\(^{14}\)C]- and [\(^{3}\)H]DEHA, labeled in the alcobol moiety and administered to mice, revealed aminute radioactivity of <50 dpm/mg liver DNA, too little to allow a nucleoside analysis to determine that fraction of the radioactivity which bad been incorporated via biosynthesis. Expressed in the CBI units, values of 0.05 to 0.15 for \(^{14}\)C and 0.01 to 0.12 for \(^{3}\)H resulted. Determination of the level· of \(^{14}\)C02 expiration revealed a linear correlation with the speciftc activity of DNA. Experiments with 2-ethyl[ 1-\(^{14}\)C]hexanol perfonned with both rats and mice allowed the conclusion tbat most if not all DEHA radioactivity in mouse liver DNA was due to biosynthetic incorporation. A maximum possible true DNA binding by DEHA must be below CBI 0.01. Pretreatment of the animals witb unlabeled compound bad no effect on the DNA radioactivities in either species. The present negative data, in conjunction witb other negative short-term tests for mutagenicity, strongly indicate that covalent interaction with DNA is highly unlikely to be the mode of tumorigenic action of DEHP and DEHA in rodents.},
  subject      = {Toxikologie},
  language  = {en}
}
@article{HartmannReisslandMaieretal.2021,
  author    = {Hartmann, Oliver and Reissland, Michaela and Maier, Carina R. and Fischer, Thomas and Prieto-Garcia, Cristian and Baluapuri, Apoorva and Schwarz, Jessica and Schmitz, Werner and Garrido-Rodriguez, Martin and Pahor, Nikolett and Davies, Clare C. and Bassermann, Florian and Orian, Amir and Wolf, Elmar and Schulze, Almut and Calzado, Marco A. and Rosenfeldt, Mathias T. and Diefenbacher, Markus E.},
  title     = {Implementation of CRISPR/Cas9 Genome Editing to Generate Murine Lung Cancer Models That Depict the Mutational Landscape of Human Disease},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {9},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2021.641618},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230949},
  year      = {2021},
  abstract  = {Lung cancer is the most common cancer worldwide and the leading cause of cancer-related deaths in both men and women. Despite the development of novel therapeutic interventions, the 5-year survival rate for non-small cell lung cancer (NSCLC) patients remains low, demonstrating the necessity for novel treatments. One strategy to improve translational research is the development of surrogate models reflecting somatic mutations identified in lung cancer patients as these impact treatment responses. With the advent of CRISPR-mediated genome editing, gene deletion as well as site-directed integration of point mutations enabled us to model human malignancies in more detail than ever before. Here, we report that by using CRISPR/Cas9-mediated targeting of Trp53 and KRas, we recapitulated the classic murine NSCLC model Trp53fl/fl:lsl-KRasG12D/wt. Developing tumors were indistinguishable from Trp53fl/fl:lsl-KRasG12D/wt-derived tumors with regard to morphology, marker expression, and transcriptional profiles. We demonstrate the applicability of CRISPR for tumor modeling in vivo and ameliorating the need to use conventional genetically engineered mouse models. Furthermore, tumor onset was not only achieved in constitutive Cas9 expression but also in wild-type animals via infection of lung epithelial cells with two discrete AAVs encoding different parts of the CRISPR machinery. While conventional mouse models require extensive husbandry to integrate new genetic features allowing for gene targeting, basic molecular methods suffice to inflict the desired genetic alterations in vivo. Utilizing the CRISPR toolbox, in vivo cancer research and modeling is rapidly evolving and enables researchers to swiftly develop new, clinically relevant surrogate models for translational research.},
  language  = {en}
}
@article{BergfeldDasariWerneretal.2017,
  author    = {Bergfeld, Arne and Dasari, Prasad and Werner, Sandra and Hughes, Timothy R. and Song, Wen-Chao and Hortschansky, Peter and Brakhage, Axel A. and H{\"u}nig, Thomas and Zipfel, Peter F. and Beyersdorf, Niklas},
  title     = {Direct binding of the pH-regulated Protein 1 (Pra1) from Candida albicans inhibits cytokine secretion by mouse CD4\(^{+}\) T cells},
  series = {Frontiers in Microbiology},
  volume    = {8},
  journal   = {Frontiers in Microbiology},
  number    = {844},
  doi       = {10.3389/fmicb.2017.00844},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158274},
  year      = {2017},
  abstract  = {Opportunistic infections with the saprophytic yeast Candida albicans are a major cause of morbidity in immunocompromised patients. While the interaction of cells and molecules of innate immunity with C. albicans has been studied to great depth, comparatively little is known about the modulation of adaptive immunity by C. albicans. In particular, direct interaction of proteins secreted by C. albicans with CD4\(^{+}\) T cells has not been studied in detail. In a first screening approach, we identified the pH-regulated antigen 1 (Pra1) as a molecule capable of directly binding to mouse CD4\(^{+}\) T cells in vitro. Binding of Pra1 to the T cell surface was enhanced by extracellular Zn\(^{2+}\) ions which Pra1 is known to scavenge from the host in order to supply the fungus with Zn\(^{2+}\). In vitro stimulation assays using highly purified mouse CD4\(^{+}\) T cells showed that Pra1 increased proliferation of CD4\(^{+}\) T cells in the presence of plate-bound anti-CD3 monoclonal antibody. In contrast, secretion of effector cytokines such as IFNγ and TNF by CD4\(^{+}\) T cells upon anti-CD3/ anti-CD28 mAb as well as cognate antigen stimulation was reduced in the presence of Pra1. By secreting Pra1 C. albicans, thus, directly modulates and partially controls CD4\(^{+}\) T cell responses as shown in our in vitro assays.},
  language  = {en}
}
@article{WernerSchmidMueggeetal.2015,
  author    = {Werner, R.A. and Schmid, J.S. and Muegge, D.O. and L{\"u}ckerath, K. and Higuchi, T. and H{\"a}nscheid, H. and Grelle, I. and Reiners, C. and Herrmann, K. and Buck, A.K. and Lapa, C.},
  title     = {Prognostic value of serum tumor markers in medullary thyroid cancer patients undergoing vandetanib treatment},
  series = {Medicine},
  volume    = {94},
  journal   = {Medicine},
  number    = {45},
  doi       = {10.1097/MD.0000000000002016},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145154},
  pages     = {e2016},
  year      = {2015},
  abstract  = {Tyrosine kinase inhibitors (TKIs) such as vandetanib have shown clinical effectiveness in advanced medullary thyroid cancer (MTC). During TKI treatment, fluctuations in the tumor markers carcinoembryonic antigen (CEA) and calcitonin (CTN) are frequently observed. Their role for treatment monitoring and the decision-making process has not been fully elucidated yet. Twenty-one patients (male, 16, female, 5; mean age, 49±13 years) with progressive MTC receiving vandetanib (300mg orally per day) were considered. Tumor restaging was performed every 3 months including contrast-enhanced computed tomography (CT). Response was assessed according to recent criteria (Response Evaluation Criteria in Solid Tumors, RECIST 1.1). Additionally, CEA and CTN were measured at the day of CT imaging and alterations observed in tumor markers were compared to respective imaging findings (partial response, PR; stable disease, SD; progressive disease, PD). During long-term follow-up (510±350 days [range, 97-1140 days]), CTN and CEA levels initially dropped in 71.4\% and 61.9\% of the patients followed by fluctuations in serum marker levels. A rise in CTN ≥39.5\% between 2 subsequent measurements (defined by ROC analysis) had a sensitivity of 70.6\% and a specificity of 83.2\% in predicting PD with an accuracy of 82.0\% (area under the curve (AUC), 0.76). Oscillations in CEA levels were not predictive for PD. Whereas tumor marker fluctuations in MTC patients undergoing TKI treatment are a frequent phenomenon, a significant rise in CTN ≥40\% turns out to as an early indicator of tumor progression.},
  language  = {en}
}