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  1. AU="Prechtl, Stefan"
  2. AU="Kuanyshbek, Alibek"
  3. AU="Annukka Pasanen"
  4. AU="Yi, Ling Ka"
  5. AU="Kong, Hyejin"
  6. AU="Bilio, João"
  7. AU=Hill Stephen J
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  11. AU="Mizia-Stec, Katarzyna"
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  13. AU=Giroux Leprieur Etienne
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  17. AU="Butler, Eboneé N"
  18. AU="Moura-Alves, Márcio"
  19. AU="Marcet, Ismael"
  20. AU=Eichfelder Sebastian
  21. AU=Timins M E
  22. AU="Weber, Stephan"
  23. AU=Galuska David
  24. AU="Carrieri, Mariella"
  25. AU="Hafkamp, Frederique J"
  26. AU="Jessica M. Perkins"
  27. AU="Tariq, Syeda Sumayya"
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  1. Book: Handbuch Bilanzrecht

    Brösel, Gerrit / Fuchs, Ingo / Lamm, Martin / Lehnen, Alexander / Petersen, Karl / Prechtl, Stefan / Rogler, Silvia / Waschbusch, Gerd / Wastl, Ulrich / Zwirner, Christian

    Abschlussprüfung und Sonderfragen in der Rechnungslegung

    2018  

    Institution Bundesanzeiger Verlag GmbH
    Language German
    Size 900 Seiten, 24.4 cm x 16.5 cm
    Edition 2., aktualisierte und erweiterte Auflage
    Publisher Bundesanzeiger
    Publishing place Köln
    Document type Book
    ISBN 3846208736 ; 9783846208731
    Database ECONomics Information System

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  2. Article: Bilanzierung und Bewertung von discontinued operations nach IFRS 5

    Prechtl, Stefan / Schuster, Lars

    IRZ : Zeitschrift für internationale Rechnungslegung Vol. 5, No. 10 , p. 427-430

    2010  Volume 5, Issue 10, Page(s) 427–430

    Author's details Stefan Prechtl und Lars Schuster
    Keywords Betriebsvermögen ; Ausgründung ; Bilanzielle Bewertung ; IFRS
    Language German
    Publisher Beck
    Publishing place München
    Document type Article
    ZDB-ID 2235588-1
    ISSN 1862-5533
    Database ECONomics Information System

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  3. Article ; Online: A novel 3D high-content assay identifies compounds that prevent fibroblast invasion into tissue surrogates.

    Wenzel, Carsten / Otto, Saskia / Prechtl, Stefan / Parczyk, Karsten / Steigemann, Patrick

    Experimental cell research

    2015  Volume 339, Issue 1, Page(s) 35–43

    Abstract: Invasion processes underlie or accompany several pathological processes but only a limited number of high-throughput capable phenotypic models exist to test anti-invasive compounds in vitro. We here evaluated 3D co-cultures as a high-content phenotypic ... ...

    Abstract Invasion processes underlie or accompany several pathological processes but only a limited number of high-throughput capable phenotypic models exist to test anti-invasive compounds in vitro. We here evaluated 3D co-cultures as a high-content phenotypic screening system for fibrotic invasive processes. 3D multicellular spheroids were used as living tissue surrogates in co-culture with fluorescently labeled lung fibroblasts to monitor invasion processes by automated microscopy. This setup was used to screen a compound library containing 480 known bioactive substances. Identified hits prevented fibroblast invasion and could be subdivided into two hit classes. First, Prostaglandins were shown to prevent fibroblast invasion, most likely mediated by the prostaglandin EP2 receptor and generation of cAMP. Additionally, Rho-associated protein kinase (ROCK) inhibitors prevented fibroblast invasion, possibly by inactivation of myosin II. Importantly, both Prostaglandins and ROCK inhibitors are potential treatment options shown to be effective in in vitro and in vivo models of fibrotic diseases. This validates the presented novel phenotypic screening approach for the evaluation of potential inhibitors and the identification of novel compounds with activity in diseases that are associated with fibroblast invasion.
    MeSH term(s) Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Culture Techniques ; Female ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibroblasts/pathology ; High-Throughput Screening Assays ; Humans ; Image Processing, Computer-Assisted ; Immunoenzyme Techniques ; Prostaglandins/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Spheroids, Cellular/drug effects ; Spheroids, Cellular/metabolism ; Spheroids, Cellular/pathology ; Tumor Cells, Cultured ; rho-Associated Kinases/antagonists & inhibitors ; rho-Associated Kinases/metabolism
    Chemical Substances Prostaglandins ; Protein Kinase Inhibitors ; rho-Associated Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2015-11-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1493-x
    ISSN 1090-2422 ; 0014-4827
    ISSN (online) 1090-2422
    ISSN 0014-4827
    DOI 10.1016/j.yexcr.2015.10.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Book ; Thesis: Das "multidrug-resistance protein" (mrp) 1

    Prechtl, Stefan

    ein funktionell wichtiger Aktivierungsmarker für T-Helferzellen der Maus

    1999  

    Author's details vorgelegt von Stefan Prechtl
    Language German
    Size III, 109 S, Ill., graph. Darst, 21 cm
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Bayreuth, 1999
    Database Former special subject collection: coastal and deep sea fishing

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  5. Book ; Thesis: Das "multidrug-resistance protein" (mrp) 1

    Prechtl, Stefan

    ein funktionell wichtiger Aktivierungsmarker für T-Helferzellen der Maus

    1999  

    Author's details vorgelegt von Stefan Prechtl
    Language German
    Size III, 109 S, Ill., graph. Darst, 21 cm
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Bayreuth, 1999
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  6. Article ; Online: Discovery of YAP1/TAZ pathway inhibitors through phenotypic screening with potent anti-tumor activity via blockade of Rho-GTPase signaling.

    Graham, Keith / Lienau, Philip / Bader, Benjamin / Prechtl, Stefan / Naujoks, Jan / Lesche, Ralf / Weiske, Joerg / Kuehnlenz, Julia / Brzezinka, Krzysztof / Potze, Lisette / Zanconato, Francesca / Nicke, Barbara / Montebaur, Anna / Bone, Wilhelm / Golfier, Sven / Kaulfuss, Stefan / Kopitz, Charlotte / Pilari, Sabine / Steuber, Holger /
    Hayat, Sikander / Kamburov, Atanas / Steffen, Andreas / Schlicker, Andreas / Buchgraber, Philipp / Braeuer, Nico / Font, Nuria Aiguabella / Heinrich, Tobias / Kuhnke, Lara / Nowak-Reppel, Katrin / Stresemann, Carlo / Steigemann, Patrick / Walter, Annette O / Blotta, Simona / Ocker, Matthias / Lakner, Ashley / von Nussbaum, Franz / Mumberg, Dominik / Eis, Knut / Piccolo, Stefano / Lange, Martin

    Cell chemical biology

    2024  

    Abstract: This study describes the identification and target deconvolution of small molecule inhibitors of oncogenic Yes-associated protein (YAP1)/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was ... ...

    Abstract This study describes the identification and target deconvolution of small molecule inhibitors of oncogenic Yes-associated protein (YAP1)/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was conducted using a cellular YAP1/TAZ reporter assay. Target deconvolution studies identified the geranylgeranyltransferase-I (GGTase-I) complex as the direct target of YAP1/TAZ pathway inhibitors. The small molecule inhibitors block the activation of Rho-GTPases, leading to subsequent inactivation of YAP1/TAZ and inhibition of cancer cell proliferation in vitro. Multi-parameter optimization resulted in BAY-593, an in vivo probe with favorable PK properties, which demonstrated anti-tumor activity and blockade of YAP1/TAZ signaling in vivo.
    Language English
    Publishing date 2024-03-19
    Publishing country United States
    Document type Journal Article
    ISSN 2451-9448
    ISSN (online) 2451-9448
    DOI 10.1016/j.chembiol.2024.02.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: High-content analysis in preclinical drug discovery.

    Denner, Philip / Schmalowsky, Janine / Prechtl, Stefan

    Combinatorial chemistry & high throughput screening

    2008  Volume 11, Issue 3, Page(s) 216–230

    Abstract: High-Content Analysis (HCA) has developed into an established tool and is used in a wide range of academic laboratories and pharmaceutical research groups. HCA is now routinely proving to be effective in providing functionally relevant results. It is ... ...

    Abstract High-Content Analysis (HCA) has developed into an established tool and is used in a wide range of academic laboratories and pharmaceutical research groups. HCA is now routinely proving to be effective in providing functionally relevant results. It is essential to select the appropriate HCA application with regard to the targeted compound's cellular function. The cellular impact and compound specificity as revealed by HCA analysis facilitates reaching definitive conclusions at an early stage in the drug discovery process. This technology therefore has the potential to substantially improve the efficiency of pharmaceutical research. Recent advances in fluorescent probes have significantly boosted the success of HCA. Auto-fluorescent proteins which minimally hinder the functioning of the living cell have been playing a decisive role in cell biology research. For companies the severely restricted license conditions regarding auto-fluorescent proteins hamper their general use in pharmaceutical research. This has opened the field for other solutions such as self-labeling protein technology, which could potentially replace the well established methods that utilize auto-fluorescent proteins. In addition, direct labeling techniques have improved considerably and may supersede many of the approaches based on fusion proteins. Following sample preparation, treated cells are imaged and the resulting multiple fluorescent signals are subjected to contextual and statistical analysis. The extraordinary advantage of HCA is that it enables the large-scale and simultaneous quantification and correlation of multiple phenotypic responses and physiological reactions using sophisticated software solutions that permit assay-specific image analysis. Hence, HCA once more has demonstrated its outstanding potential to significantly support establishing effective pharmaceutical research processes in order to both advance research projects and cut costs.
    MeSH term(s) Animals ; Computational Biology ; Drug Evaluation, Preclinical/instrumentation ; Drug Evaluation, Preclinical/methods ; Humans ; Image Processing, Computer-Assisted/methods ; Laser Scanning Cytometry/instrumentation ; Laser Scanning Cytometry/methods ; Small Molecule Libraries
    Chemical Substances Small Molecule Libraries
    Language English
    Publishing date 2008-02-22
    Publishing country United Arab Emirates
    Document type Journal Article ; Review
    ZDB-ID 2064785-2
    ISSN 1875-5402 ; 1386-2073
    ISSN (online) 1875-5402
    ISSN 1386-2073
    DOI 10.2174/138620708783877780
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Quantification of histone H3 Lys27 trimethylation (H3K27me3) by high-throughput microscopy enables cellular large-scale screening for small-molecule EZH2 inhibitors.

    Luense, Svenja / Denner, Philip / Fernández-Montalván, Amaury / Hartung, Ingo / Husemann, Manfred / Stresemann, Carlo / Prechtl, Stefan

    Journal of biomolecular screening

    2015  Volume 20, Issue 2, Page(s) 190–201

    Abstract: EZH2 inhibition can decrease global histone H3 lysine 27 trimethylation (H3K27me3) and thereby reactivates silenced tumor suppressor genes. Inhibition of EZH2 is regarded as an option for therapeutic cancer intervention. To identify novel small-molecule ( ...

    Abstract EZH2 inhibition can decrease global histone H3 lysine 27 trimethylation (H3K27me3) and thereby reactivates silenced tumor suppressor genes. Inhibition of EZH2 is regarded as an option for therapeutic cancer intervention. To identify novel small-molecule (SMOL) inhibitors of EZH2 in drug discovery, trustworthy cellular assays amenable for phenotypic high-throughput screening (HTS) are crucial. We describe a reliable approach that quantifies changes in global levels of histone modification marks using high-content analysis (HCA). The approach was validated in different cell lines by using small interfering RNA and SMOL inhibitors. By automation and miniaturization from a 384-well to 1536-well plate, we demonstrated its utility in conducting phenotypic HTS campaigns and assessing structure-activity relationships (SAR). This assay enables screening of SMOL EZH2 inhibitors and can advance the mechanistic understanding of H3K27me3 suppression, which is crucial with regard to epigenetic therapy. We observed that a decrease in global H3K27me3, induced by EZH2 inhibition, comprises two distinct mechanisms: (1) inhibition of de novo DNA methylation and (II) inhibition of dynamic, replication-independent H3K27me3 turnover. This report describes an HCA assay for primary HTS to identify, profile, and optimize cellular active SMOL inhibitors targeting histone methyltransferases, which could benefit epigenetic drug discovery.
    MeSH term(s) Automation, Laboratory ; Cell Cycle/drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drug Discovery ; Enhancer of Zeste Homolog 2 Protein ; Gene Knockdown Techniques ; High-Throughput Screening Assays ; Histones/antagonists & inhibitors ; Histones/genetics ; Histones/metabolism ; Humans ; Inhibitory Concentration 50 ; Methylation/drug effects ; Microscopy ; Polycomb Repressive Complex 2/antagonists & inhibitors ; RNA Interference ; Small Molecule Libraries ; Structure-Activity Relationship
    Chemical Substances Histones ; Small Molecule Libraries ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
    Language English
    Publishing date 2015-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1433680-7
    ISSN 1552-454X ; 1087-0571
    ISSN (online) 1552-454X
    ISSN 1087-0571
    DOI 10.1177/1087057114559668
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Functional inhibition of acid sphingomyelinase by Fluphenazine triggers hypoxia-specific tumor cell death.

    Klutzny, Saskia / Lesche, Ralf / Keck, Matthias / Kaulfuss, Stefan / Schlicker, Andreas / Christian, Sven / Sperl, Carolyn / Neuhaus, Roland / Mowat, Jeffrey / Steckel, Michael / Riefke, Björn / Prechtl, Stefan / Parczyk, Karsten / Steigemann, Patrick

    Cell death & disease

    2017  Volume 8, Issue 3, Page(s) e2709

    Abstract: Owing to lagging or insufficient neo-angiogenesis, hypoxia is a feature of most solid tumors. Hypoxic tumor regions contribute to resistance against antiproliferative chemotherapeutics, radiotherapy and immunotherapy. Targeting cells in hypoxic tumor ... ...

    Abstract Owing to lagging or insufficient neo-angiogenesis, hypoxia is a feature of most solid tumors. Hypoxic tumor regions contribute to resistance against antiproliferative chemotherapeutics, radiotherapy and immunotherapy. Targeting cells in hypoxic tumor areas is therefore an important strategy for cancer treatment. Most approaches for targeting hypoxic cells focus on the inhibition of hypoxia adaption pathways but only a limited number of compounds with the potential to specifically target hypoxic tumor regions have been identified. By using tumor spheroids in hypoxic conditions as screening system, we identified a set of compounds, including the phenothiazine antipsychotic Fluphenazine, as hits with novel mode of action. Fluphenazine functionally inhibits acid sphingomyelinase and causes cellular sphingomyelin accumulation, which induces cancer cell death specifically in hypoxic tumor spheroids. Moreover, we found that functional inhibition of acid sphingomyelinase leads to overactivation of hypoxia stress-response pathways and that hypoxia-specific cell death is mediated by the stress-responsive transcription factor ATF4. Taken together, the here presented data suggest a novel, yet unexplored mechanism in which induction of sphingolipid stress leads to the overactivation of hypoxia stress-response pathways and thereby promotes their pro-apoptotic tumor-suppressor functions to specifically kill cells in hypoxic tumor areas.
    Language English
    Publishing date 2017-03-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/cddis.2017.130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Functional and Structural Characterization of Bub3·BubR1 Interactions Required for Spindle Assembly Checkpoint Signaling in Human Cells.

    Prinz, Florian / Puetter, Vera / Holton, Simon J / Andres, Dorothee / Stegmann, Christian M / Kwiatkowski, Dennis / Prechtl, Stefan / Petersen, Kirstin / Beckmann, Georg / Kreft, Bertolt / Mumberg, Dominik / Fernández-Montalván, Amaury

    The Journal of biological chemistry

    2016  Volume 291, Issue 21, Page(s) 11252–11267

    Abstract: The spindle assembly checkpoint (SAC) is an essential safeguarding mechanism devised to ensure equal chromosome distribution in daughter cells upon mitosis. The proteins Bub3 and BubR1 are key components of the mitotic checkpoint complex, an essential ... ...

    Abstract The spindle assembly checkpoint (SAC) is an essential safeguarding mechanism devised to ensure equal chromosome distribution in daughter cells upon mitosis. The proteins Bub3 and BubR1 are key components of the mitotic checkpoint complex, an essential part of the molecular machinery on which the SAC relies. In the present work we have performed a detailed functional and biochemical characterization of the interaction between human Bub3 and BubR1 in cells and in vitro Our results demonstrate that genetic knockdown of Bub3 abrogates the SAC, promotes apoptosis, and inhibits the proliferation of human cancer cells. We also show that the integrity of the human mitotic checkpoint complex depends on the specific recognition between BubR1 and Bub3, for which the BubR1 Gle2 binding sequence motif is essential. This 1:1 binding event is high affinity, enthalpy-driven and with slow dissociation kinetics. The affinity, kinetics, and thermodynamic parameters of the interaction are differentially modulated by small regions in the N and C termini of the Gle2 binding domain sequence, suggesting the existence of "hotspots" for this protein-protein interaction. Furthermore, we show that specific disruption of endogenous BubR1·Bub3 complexes in human cancer cells phenocopies the effects observed in gene targeting experiments. Our work enhances the current understanding of key members of the SAC and paves the road for the pursuit of novel targeted cancer therapies based on SAC inhibition.
    MeSH term(s) Apoptosis ; Cell Cycle Proteins/chemistry ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Gene Knockdown Techniques ; HeLa Cells ; Humans ; Kinetics ; M Phase Cell Cycle Checkpoints/genetics ; M Phase Cell Cycle Checkpoints/physiology ; MCF-7 Cells ; Models, Molecular ; Poly-ADP-Ribose Binding Proteins ; Protein Interaction Domains and Motifs ; Protein-Serine-Threonine Kinases/chemistry ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Spindle Apparatus/genetics ; Spindle Apparatus/metabolism ; Thermodynamics
    Chemical Substances BUB3 protein, human ; Cell Cycle Proteins ; Poly-ADP-Ribose Binding Proteins ; RNA, Messenger ; BUB1 protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2016-03-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M115.702142
    Database MEDical Literature Analysis and Retrieval System OnLINE

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