@phdthesis{Lorenz2004,
  author    = {Lorenz, Judith},
  title     = {Immunhistochemische und zellbiologische Analyse humaner monoklonaler Antik{\"o}rper gegen kolorektale Karzinome},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-11532},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Drei verschiedene mit Hilfe der humanen Hybridomatechnologie aus einem Rektumkarzinompatienten isolierte humane monoklonale Antik{\"o}rper wurden immunhistochemisch und mit Hilfe zellbiologischer Tests untersucht. Die Ergebnisse der Immunperoxidasef{\"a}rbung geben erste Hinweise auf die Art und Verteilung der von den Antik{\"o}rpern erkannten Antigene. HH 98/81-33-154 und HH 99/71-81-149 f{\"a}rben nur wenige kolorektale Karzinome sowie einige Tumoren verschiedenen histologischen Ursprungs an und zeigen keine Reaktion mit normalen adulten oder fetalen Geweben. HH 101/99-14 reagiert dagegen außer mit zahlreichen Dickdarmkarzinomen auch mit einigen fetalen Geweben, was auf die Expression des spezifischen Antigens w{\"a}hrend der Fetalperiode schließen l{\"a}ßt. Neben den Kreuzreaktionen mit verschiedenen zentralnerv{\"o}sen Strukturen adulter Normalgewebe, die im Hinblick auf paraneoplastische neurologische Krankheitsbilder von Interesse sind, zeigt der Antik{\"o}rper weiterhin eine Affinit{\"a}t zu dr{\"u}sig differenzierten Tumoren. Im MTT-Assay auf Zellen der Kolonkarzinomzellinie CACO-2 bewirkte unverd{\"u}nnter Zellkultur{\"u}berstand der Antik{\"o}rper HH 98/81-33-154 und HH 101/99-14 eine starke Proliferationshemmung. Dieser Effekt konnte sowohl nach 24- als auch nach 48st{\"u}ndiger Inkubation, nicht jedoch mit verd{\"u}nntem {\"U}berstand nachgewiesen werden. Mit {\"U}berstand von HH 99/71-81-149 war hingegen nur eine schwache Hemmung mitochondrialer Dehydrogenasen zu verzeichnen. Zellen der Linien HT-29, COLO 206F sowie COLO 320 zeigten sich hingegen resistent gegen die antik{\"o}rpervermittelte Wachstumshemmung. Mit Hilfe des Cell Death Detection ELISAPLUS{\`O} konnte weiterhin belegt werden, daß HH 98/81-33-154 und HH 101/99-14 nicht nur das Wachstum von Tumorzellen hemmen, sondern {\"u}berdies auf der Zellinie CACO-2 Apoptose induzieren. In beiden funktionellen Tests {\"u}berstieg die gemessene Aktivit{\"a}t des niedriger konzentrierten HH 98/81-33-154 die von HH 101/99-14. Die relativ geringe Anzahl von Kreuzreaktionen mit gesundem Gewebe sowie die apoptoseinduzierende Aktivit{\"a}t von HH 98/81-33-154 und HH 101/99-14 unterstreichen die Eignung der Antik{\"o}rper als potentielle Immuntherapeutika f{\"u}r die adjuvante Behandlung des kolorektalen Karzinoms, einer weltweit zu den h{\"a}ufigsten Krebsarten z{\"a}hlenden Tumorerkrankung.},
  language  = {de}
}
@article{StephanTascilarYalcinMutluetal.2023,
  author    = {Stephan, Marlene and Tascilar, Koray and Yalcin-Mutlu, Melek and Hagen, Melanie and Haschka, Judith and Reiser, Michaela and Hartmann, Fabian and Kleyer, Arnd and Hueber, Axel J. and Manger, Bernhard and Figueiredo, Camille and Cobra, Jayme Fogagnolo and Tony, Hans-Peter and Finzel, Stephanie and Kleinert, Stefan and Wendler, J{\"o}rg and Schuch, Florian and Ronneberger, Monika and Feuchtenberger, Martin and Fleck, Martin and Manger, Karin and Ochs, Wolfgang and Schmitt-Haendle, Matthias and Lorenz, Hannes Martin and N{\"u}sslein, Hubert and Alten, Rieke and Henes, Joerg and Kr{\"u}ger, Klaus and Schett, Georg and Rech, J{\"u}rgen},
  title     = {Physical function of RA patients tapering treatment — a post hoc analysis of the randomized controlled RETRO trial},
  series = {Journal of Clinical Medicine},
  volume    = {12},
  journal   = {Journal of Clinical Medicine},
  number    = {11},
  issn      = {2077-0383},
  doi       = {10.3390/jcm12113723},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319349},
  year      = {2023},
  abstract  = {Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50\% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline.},
  language  = {en}
}
@article{RechHueberFinzeletal.2016,
  author    = {Rech, Juergen and Hueber, Axel J. and Finzel, Stephanie and Englbrecht, Matthias and Haschka, Judith and Manger, Bernhard and Kleyer, Arnd and Reiser, Michaela and Cobra, Jayme Fogagnolo and Figueiredo, Camille and Tony, Hans-Peter and Kleinert, Stefan and Wendler, Joerg and Schuch, Florian and Ronneberger, Monika and Feuchtenberger, Martin and Fleck, Martin and Manger, Karin and Ochs, Wolfgang and Schmitt-Haendle, Matthias and Lorenz, Hanns-Martin and Nuesslein, Hubert and Alten, Rieke and Henes, Joerg and Krueger, Klaus and Schett, Georg},
  title     = {Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment},
  series = {Annals of the Rheumatic Diseases},
  volume    = {75},
  journal   = {Annals of the Rheumatic Diseases},
  number    = {9},
  doi       = {10.1136/annrheumdis-2015-207900},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187519},
  pages     = {1637-1644},
  year      = {2016},
  abstract  = {Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. Methods MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. Results Moderate-to-high MBDA scores were found in 33\% of patients with RA overall. Twice as many patients who relapsed (58\%) had moderate/high MBDA compared with patients who remained in remission (21\%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13\%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3\%) and MBDA-ACPA+ (31.8\%) and high in patients who were MBDA+/ACPA+ (76.4\%). Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80\% of the patients. Trial registration number EudraCT 2009-015740-42.},
  language  = {en}
}
@article{StrittNurdenFavieretal.2016,
  author    = {Stritt, Simon and Nurden, Paquita and Favier, Remi and Favier, Marie and Ferioli, Silvia and Gotru, Sanjeev K. and van Eeuwijk, Judith M.M. and Schulze, Harald and Nurden, Alan T. and Lambert, Michele P. and Turro, Ernest and Burger-Stritt, Stephanie and Matsushita, Masayuki and Mittermeier, Lorenz and Ballerini, Paola and Zierler, Susanna and Laffan, Michael A. and Chubanov, Vladimir and Gudermann, Thomas and Nieswandt, Bernhard and Braun, Attila},
  title     = {Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg\(^{2+}\) homeostasis and cytoskeletal architecture},
  series = {Nature Communications},
  volume    = {7},
  journal   = {Nature Communications},
  doi       = {10.1038/ncomms11097},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173843},
  year      = {2016},
  abstract  = {Mg\(^{2+}\) plays a vital role in platelet function, but despite implications for life-threatening conditions such as stroke or myocardial infarction, the mechanisms controlling [Mg\(^{2+}\)]i in megakaryocytes (MKs) and platelets are largely unknown. Transient receptor potential melastatin-like 7 channel (TRPM7) is a ubiquitous, constitutively active cation channel with a cytosolic α-kinase domain that is critical for embryonic development and cell survival. Here we report that impaired channel function of TRPM7 in MKs causes macrothrombocytopenia in mice (Trpm7\(^{fl/fl-Pf4Cre}\)) and likely in several members of a human pedigree that, in addition, suffer from atrial fibrillation. The defect in platelet biogenesis is mainly caused by cytoskeletal alterations resulting in impaired proplatelet formation by Trpm7\(^{fl/fl-Pf4Cre}\) MKs, which is rescued by Mg\(^{2+}\) supplementation or chemical inhibition of non-muscle myosin IIA heavy chain activity. Collectively, our findings reveal that TRPM7 dysfunction may cause macrothrombocytopenia in humans and mice.},
  language  = {en}
}