{ "types" : { "Bookmark" : { "pluralLabel" : "Bookmarks" }, "Publication" : { "pluralLabel" : "Publications" }, "GoldStandardPublication" : { "pluralLabel" : "GoldStandardPublications" }, "GoldStandardBookmark" : { "pluralLabel" : "GoldStandardBookmarks" }, "Tag" : { "pluralLabel" : "Tags" }, "User" : { "pluralLabel" : "Users" }, "Group" : { "pluralLabel" : "Groups" }, "Sphere" : { "pluralLabel" : "Spheres" } }, "properties" : { "count" : { "valueType" : "number" }, "date" : { "valueType" : "date" }, "changeDate" : { "valueType" : "date" }, "url" : { "valueType" : "url" }, "id" : { "valueType" : "url" }, "tags" : { "valueType" : "item" }, "user" : { "valueType" : "item" } }, "items" : [ { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/23c8b11ffd4fb40227fe762877205c8df/pumaizi", "tags" : [ "izi","2014","pfizenmaier","kontermann" ], "intraHash" : "3c8b11ffd4fb40227fe762877205c8df", "interHash" : "7b787e72c6fbfdbe20e9d5da2b89a01a", "label" : "Immuno-LipoTRAIL: Targeted delivery of TRAIL-functionalized liposomal nanoparticles", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Bioconjugate Chemistry", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/24766622", "author": [ "Oliver Seifert","Nadine Pollak","Anja Nusser","Frank Steiniger","Ronny Rüger","Klaus Pfizenmaier","Roland E. Kontermann" ], "authors": [ {"first" : "Oliver", "last" : "Seifert"}, {"first" : "Nadine", "last" : "Pollak"}, {"first" : "Anja", "last" : "Nusser"}, {"first" : "Frank", "last" : "Steiniger"}, {"first" : "Ronny", "last" : "Rüger"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "25","number": "5","pages": "879--887","abstract": "The TNF-related apoptosis-inducing ligand (TRAIL) is a powerful inducer of apoptosis in tumor cells; however, clinical studies with recombinant soluble TRAIL were rather disappointing. Here, we developed TRAIL-functionalized liposomes (LipoTRAIL, LT) to mimic membrane-displayed TRAIL for efficient activation of death receptors DR4 and DR5 and enhanced induction of apoptosis, which were combined with an anti-EGFR single-chain Fv fragment (scFv) for targeted delivery to EGFR-positive tumor cells. These immuno-LipoTRAILs (ILTs) bound specifically to EGFR-expressing cells (Colo205) and exhibited increased cytotoxicity compared with that of nontargeted LTs. Compared to that of the soluble TRAIL, the plasma half-life of the functionalized liposomes was strongly extended, and increased antitumor activity of LT and ILT was demonstrated in a xenograft tumor model. Thus, we established a multifunctional liposomal TRAIL formulation (ILT) with improved pharmacokinetic and pharmacodynamic behavior, characterized by targeted delivery and increased induction of apoptosis due to multivalent TRAIL presentation.", "pmid" : "24766622", "issn" : "15204812", "doi" : "10.1021/bc400517j", "bibtexKey": "Seifert2014a" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2b0d96f2155578a8bd39321d5f76833c7/pumaizi", "tags" : [ "izi","2014","kontermann" ], "intraHash" : "b0d96f2155578a8bd39321d5f76833c7", "interHash" : "b60886559d06c01430c6953275983388", "label" : "Expression and Purification of Recombinant Antibody Formats and Antibody Fusion Proteins", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "incollection", "booktitle": "Methods in molecular biology (Clifton, N.J.)", "year": "2014", "url": "https://doi.org/10.1007/978-1-62703-992-5_18", "author": [ "Martin Siegemund","Fabian Richter","Oliver Seifert","Felix Unverdorben","Roland E. Kontermann" ], "authors": [ {"first" : "Martin", "last" : "Siegemund"}, {"first" : "Fabian", "last" : "Richter"}, {"first" : "Oliver", "last" : "Seifert"}, {"first" : "Felix", "last" : "Unverdorben"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "1131","pages": "273--295","abstract": "In the laboratory-scale production of antibody fragments or antibody fusion proteins, it is often difficult to keep track on the most suitable affinity tags for protein purification from either prokaryotic or eukaryotic host systems. Here, we describe how such recombinant proteins derived from Escherichia coli lysates as well as HEK293 cell culture supernatants are purified by IMAC and by different affinity chromatography methods based on fusions to FLAG-tag, Strep-tag, and Fc domains.", "pmid" : "24515473", "issn" : "1940-6029", "doi" : "10.1007/978-1-62703-992-5_18", "bibtexKey": "Siegemund2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/20997ad4e90286b3cd068be2caa2ca139/pumaizi", "tags" : [ "izi","2014","kontermann" ], "intraHash" : "0997ad4e90286b3cd068be2caa2ca139", "interHash" : "f6901d67bf488a5f783b0554b3968060", "label" : "Generation of \u201CLYmph Node Derived Antibody Libraries\u201D (LYNDAL) for selecting fully human antibody fragments with therapeutic potential", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "mAbs","publisher":"Taylor & Francis", "year": "2014", "url": "https://doi.org/10.4161/mabs.27236", "author": [ "Philipp Diebolder","Armin Keller","Stephanie Haase","Anne Schlegelmilch","Jonathan D Kiefer","Tamana Karimi","Tobias Weber","Gerhard Moldenhauer","Roland Kehm","Anna M Eis-Hübinger","Dirk Jäger","Philippe A Federspil","Christel Herold-Mende","Gerhard Dyckhoff","Roland E Kontermann","Michaela AE Arndt","Jürgen Krauss" ], "authors": [ {"first" : "Philipp", "last" : "Diebolder"}, {"first" : "Armin", "last" : "Keller"}, {"first" : "Stephanie", "last" : "Haase"}, {"first" : "Anne", "last" : "Schlegelmilch"}, {"first" : "Jonathan D", "last" : "Kiefer"}, {"first" : "Tamana", "last" : "Karimi"}, {"first" : "Tobias", "last" : "Weber"}, {"first" : "Gerhard", "last" : "Moldenhauer"}, {"first" : "Roland", "last" : "Kehm"}, {"first" : "Anna M", "last" : "Eis-Hübinger"}, {"first" : "Dirk", "last" : "Jäger"}, {"first" : "Philippe A", "last" : "Federspil"}, {"first" : "Christel", "last" : "Herold-Mende"}, {"first" : "Gerhard", "last" : "Dyckhoff"}, {"first" : "Roland E", "last" : "Kontermann"}, {"first" : "Michaela AE", "last" : "Arndt"}, {"first" : "Jürgen", "last" : "Krauss"} ], "volume": "6","number": "1","pages": "130-142","note": "PMID: 24256717","abstract": "The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected \u201CLYmph Node Derived Antibody Libraries\u201D (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro, the most potent antibody neutralized 50\\% HSV-2 at 4.5 nM as a dimeric (scFv)2. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential.", "eprint" : "https://doi.org/10.4161/mabs.27236", "doi" : "10.4161/mabs.27236", "bibtexKey": "doi:10.4161/mabs.27236" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2e62b85241f48a5801e653c60ae1457c9/pumaizi", "tags" : [ "boettinger","izi","2014" ], "intraHash" : "e62b85241f48a5801e653c60ae1457c9", "interHash" : "9b697ef34663c00b5d5088284da0c037", "label" : "Purification of PEGylated Proteins, with the example of PEGylated lysozyme and PEGylated scFv", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Methods in Molecular Biology", "year": "2014", "url": "https://doi.org/10.1007/978-1-62703-977-2_37", "author": [ "Anna Moosmann","Egbert Müller","Heiner Böttinger" ], "authors": [ {"first" : "Anna", "last" : "Moosmann"}, {"first" : "Egbert", "last" : "Müller"}, {"first" : "Heiner", "last" : "Böttinger"} ], "volume": "1129","pages": "527--538","abstract": "PEGylation is a common and highly accepted possibility for half-life prolongation of proteins by increasing the hydrodynamic size. The chromatographic purification of PEGylated protein, using PEG (poly-ethylene glycol) of different PEG chain lengths, with the example of lysozyme and a scFv, is described in detail here, and helpful suggestions for the purification of other PEGylated proteins are listed. The relevant characterization methods for PEGylated proteins, important for the successful purification, are also described. The purification starts with a CEX (cation exchange) chromatography leading to about 95 \\% purity for polishing HIC (hydrophobic interaction chromatography) is described.", "isbn" : "978-1-62703-976-5", "issn" : "10643745", "doi" : "10.1007/978-1-62703-977-2_37", "bibtexKey": "moosmann2014purification" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/229e9eb25e9d65ac615b0e8fe76186276/pumaizi", "tags" : [ "izi","2014","kontermann" ], "intraHash" : "29e9eb25e9d65ac615b0e8fe76186276", "interHash" : "f09d28f80ac3fe6e356648fd9f6fcb24", "label" : "Tumor-antigen-binding bispecific antibodies for cancer treatment", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Seminars in Oncology", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/25440609", "author": [ "Ulrich H. Weidle","Roland E. Kontermann","Ulrich Brinkmann" ], "authors": [ {"first" : "Ulrich H.", "last" : "Weidle"}, {"first" : "Roland E.", "last" : "Kontermann"}, {"first" : "Ulrich", "last" : "Brinkmann"} ], "volume": "41","number": "5","pages": "653--660","abstract": "Bi- and multispecific antibody derivatives (bsAbs) can be considered as the next generation of targeted biologics for cancer therapy. The general concept of bsAbs is a physical connection of recombinant antibody-derived entities with at least two binding specificities. This generates bsAbs that bind at least two antigens or epitopes, thus altering their binding functionalities and specificities in comparison to \"normal\" antibodies. Most bsAbs are produced as recombinant proteins, either as large IgG-like proteins that contain Fc regions, or as smaller entities with multiple antigen-binding regions but without Fc. Application of bsAbs in experimental cancer therapy currently includes molecules that bind different cell surface proteins to achieve more complete blockage of proliferative or angiogenesis-associated pathways. This approach of blocking more than one pathway component, or to simultaneously hit complementing pathways, also may limit potential escape mechanisms of cancer cells. BsAbs also are applied in the clinic as vehicles to deliver immune effector cells and/or cytokines to tumors.", "isbn" : "1532-8708 (Electronic)$\\backslash$r0093-7754 (Linking)", "pmid" : "25440609", "issn" : "15328708", "doi" : "10.1053/j.seminoncol.2014.08.004", "bibtexKey": "Weidle2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2bb6fa01b58a12738199a0e8572d4b238/pumaizi", "tags" : [ "izi","2014","pfizenmaier","kontermann" ], "intraHash" : "bb6fa01b58a12738199a0e8572d4b238", "interHash" : "382d4c9f13ebbd2b4a9d2051211ea0c0", "label" : "Astrocyte-specific activation of TNFR2 promotes oligodendrocyte maturation by secretion of leukemia inhibitory factor", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Glia", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/24310780", "author": [ "Roman Fischer","Harald Wajant","Roland Kontermann","Klaus Pfizenmaier","Olaf Maier" ], "authors": [ {"first" : "Roman", "last" : "Fischer"}, {"first" : "Harald", "last" : "Wajant"}, {"first" : "Roland", "last" : "Kontermann"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Olaf", "last" : "Maier"} ], "volume": "62","number": "2","pages": "272--283","abstract": "Tumor necrosis factor (TNF) and its receptors TNFR1 and TNFR2 have pleiotropic effects in neurodegenerative disorders. For example, while TNFR1 mediates neurodegenerative effects in multiple sclerosis, TNFR2 is protective and contributes to remyelination. The exact mode of TNFR2 action, however, is poorly understood. Here, we show that TNFR2-mediated activation of the PI3K-PKB/Akt pathway in primary astrocytes increased the expression of neuroprotective genes, including that encoding the neurotrophic cytokine leukemia inhibitory factor (LIF). To investigate whether intercellular signaling between TNFR2-stimulated astrocytes and oligodendrocytes plays a role in oligodendrocyte maturation, we established an astrocyte-oligodendrocyte coculture model, composed of primary astrocytes from huTNFR2-transgenic (tgE1335) mice and oligodendrocyte progenitor cells (OPCs) from wild-type mice, capable of differentiating into mature myelinating oligodendrocytes. In this model, selective stimulation of human TNFR2 on astrocytes, promoted differentiation of cocultured OPCs to myelin basic protein-positive mature oligodendrocytes. Addition of LIF neutralizing antibodies inhibited oligodendrocyte differentiation, indicating a crucial role of TNFR2-induced astrocyte derived LIF for oligodendrocyte maturation.", "pmid" : "24310780", "issn" : "08941491", "doi" : "10.1002/glia.22605", "bibtexKey": "Fischer2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/28a941ec402e96cb93320a0f838f1e3c0/pumaizi", "tags" : [ "izi","2014","kontermann" ], "intraHash" : "8a941ec402e96cb93320a0f838f1e3c0", "interHash" : "83b1ebe0855fc368b6eee054dfa55226", "label" : "Process development of periplasmatically produced single chain fragment variable against epidermal growth factor receptor in Escherichia coli", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biotechnology","publisher":"Elsevier BV", "year": "2014", "url": "https://doi.org/10.1016%2Fj.jbiotec.2014.10.003", "author": [ "Robert Lindner","Anna Moosmann","Alexander Dietrich","Heiner Böttinger","Roland Kontermann","Martin Siemann-Herzberg" ], "authors": [ {"first" : "Robert", "last" : "Lindner"}, {"first" : "Anna", "last" : "Moosmann"}, {"first" : "Alexander", "last" : "Dietrich"}, {"first" : "Heiner", "last" : "Böttinger"}, {"first" : "Roland", "last" : "Kontermann"}, {"first" : "Martin", "last" : "Siemann-Herzberg"} ], "volume": "192","pages": "136--145", "doi" : "10.1016/j.jbiotec.2014.10.003", "bibtexKey": "Lindner_2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/22de28f709d84c534a6f6d9107fd61fc4/pumaizi", "tags" : [ "olayioye","izi","2014" ], "intraHash" : "2de28f709d84c534a6f6d9107fd61fc4", "interHash" : "1b33d6e19ae974b567be3fe1b7a368f7", "label" : "Functional cross-talk between ras and rho pathways: A ras-specific gtpase-activating protein (p120RasGAP) competitively inhibits the rhogap activity of deleted in liver cancer (DLC) tumor suppressor by masking the catalytic arginine finger", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biological Chemistry", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/24443565", "author": [ "Mamta Jaiswal","Radovan Dvorsky","Ehsan Amin","Sarah L. Risse","Eyad K. Fansa","Si Cai Zhang","Mohamed S. Taha","Aziz R. Gauhar","Saeideh Nakhaei-Rad","Claus Kordes","Katja T. Koessmeier","Ion C. Cirstea","Monilola A. Olayioye","Dieter Häussinger","Mohammad R. Ahmadian" ], "authors": [ {"first" : "Mamta", "last" : "Jaiswal"}, {"first" : "Radovan", "last" : "Dvorsky"}, {"first" : "Ehsan", "last" : "Amin"}, {"first" : "Sarah L.", "last" : "Risse"}, {"first" : "Eyad K.", "last" : "Fansa"}, {"first" : "Si Cai", "last" : "Zhang"}, {"first" : "Mohamed S.", "last" : "Taha"}, {"first" : "Aziz R.", "last" : "Gauhar"}, {"first" : "Saeideh", "last" : "Nakhaei-Rad"}, {"first" : "Claus", "last" : "Kordes"}, {"first" : "Katja T.", "last" : "Koessmeier"}, {"first" : "Ion C.", "last" : "Cirstea"}, {"first" : "Monilola A.", "last" : "Olayioye"}, {"first" : "Dieter", "last" : "Häussinger"}, {"first" : "Mohammad R.", "last" : "Ahmadian"} ], "volume": "289","number": "10","pages": "6839--6849","abstract": "The three deleted in liver cancer genes (DLC1-3) encode Rho-specific GTPase-activating proteins (RhoGAPs). Their expression is frequently silenced in a variety of cancers. The RhoGAP activity, which is required for full DLC-dependent tumor suppressor activity, can be inhibited by the Src homology 3 (SH3) domain of a Ras-specific GAP (p120RasGAP). Here, we comprehensively investigated the molecular mechanism underlying cross-talk between two distinct regulators of small GTP-binding proteins using structural and biochemical methods. We demonstrate that only the SH3 domain of p120 selectively inhibits the RhoGAP activity of all three DLC isoforms as compared with a large set of other representative SH3 or RhoGAP proteins. Structural and mutational analyses provide new insights into a putative interaction mode of the p120 SH3 domain with the DLC1 RhoGAP domain that is atypical and does not follow the classical PXXP-directed interaction. Hence, p120 associates with the DLC1 RhoGAP domain by targeting the catalytic arginine finger and thus by competitively and very potently inhibiting RhoGAP activity. The novel findings of this study shed light on the molecular mechanisms underlying the DLC inhibitory effects of p120 and suggest a functional cross-talk between Ras and Rho proteins at the level of regulatory proteins.", "isbn" : "1083-351X (Electronic)$\\backslash$r0021-9258 (Linking)", "pmid" : "24443565", "issn" : "1083351X", "doi" : "10.1074/jbc.M113.527655", "bibtexKey": "Jaiswal2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2f6aa2fc89ac1b794f67e0986811176df/pumaizi", "tags" : [ "olayioye","izi","2014" ], "intraHash" : "f6aa2fc89ac1b794f67e0986811176df", "interHash" : "7387874d3aa3648fd190fabb6d0e2b55", "label" : "A WXW Motif Is Required for the Anticancer Activity of the TAT-RasGAP317\u2013326 Peptide", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biological Chemistry", "year": "2014", "url": "http://www.jbc.org/lookup/doi/10.1074/jbc.M114.576272", "author": [ "David Barras","Nadja Chevalier","Vincent Zoete","Rosemary Dempsey","Karine Lapouge","Monilola A. Olayioye","Olivier Michielin","Christian Widmann" ], "authors": [ {"first" : "David", "last" : "Barras"}, {"first" : "Nadja", "last" : "Chevalier"}, {"first" : "Vincent", "last" : "Zoete"}, {"first" : "Rosemary", "last" : "Dempsey"}, {"first" : "Karine", "last" : "Lapouge"}, {"first" : "Monilola A.", "last" : "Olayioye"}, {"first" : "Olivier", "last" : "Michielin"}, {"first" : "Christian", "last" : "Widmann"} ], "volume": "289","number": "34","pages": "23701--23711","abstract": "TAT-RasGAP317-326, a cell-permeable 10-amino acid-long peptide derived from the N2 fragment of p120 Ras GTPase-activating protein (RasGAP), sensitizes tumor cells to apoptosis induced by various anticancer therapies. This RasGAP-derived peptide, by targeting the deleted in liver cancer-1 (DLC1) tumor suppressor, also hampers cell migration and invasion by promoting cell adherence and by inhibiting cell movement. Here, we systematically investigated the role of each amino acid within the RasGAP317-326 sequence for the anticancer activities of TAT-RasGAP317-326. We report here that the first three amino acids of this sequence, tryptophan, methionine, and tryptophan (WMW), are necessary and sufficient to sensitize cancer cells to cisplatin-induced apoptosis and to reduce cell migration. The WMW motif was found to be critical for the binding of fragment N2 to DLC1. These results define the interaction mode between the active anticancer sequence of RasGAP and DLC1. This knowledge will facilitate the design of small molecules bearing the tumor-sensitizing and antimetastatic activities of TAT-RasGAP317-326.", "pmid" : "25008324", "issn" : "0021-9258", "doi" : "10.1074/jbc.M114.576272", "bibtexKey": "Barras2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/24c29ff2df698ac2ee6e5ac658b16a8fb/pumaizi", "tags" : [ "olayioye","izi","2014","pfizenmaier","kontermann" ], "intraHash" : "4c29ff2df698ac2ee6e5ac658b16a8fb", "interHash" : "3f89113ac48f88a51fecf5b60ce09091", "label" : "EGFR-targeted TRAIL and a Smac mimetic synergize to overcome apoptosis resistance in KRAS mutant colorectal cancer cells", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "PLoS ONE", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/25198428", "author": [ "Yvonne Möller","Martin Siegemund","Sven Beyes","Ricarda Herr","Daniele Lecis","Domenico Delia","Roland Kontermann","Tilman Brummer","Klaus Pfizenmaier","Monilola A. Olayioye" ], "authors": [ {"first" : "Yvonne", "last" : "Möller"}, {"first" : "Martin", "last" : "Siegemund"}, {"first" : "Sven", "last" : "Beyes"}, {"first" : "Ricarda", "last" : "Herr"}, {"first" : "Daniele", "last" : "Lecis"}, {"first" : "Domenico", "last" : "Delia"}, {"first" : "Roland", "last" : "Kontermann"}, {"first" : "Tilman", "last" : "Brummer"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Monilola A.", "last" : "Olayioye"} ], "editor": [ "John Souglakos" ], "editors": [ {"first" : "John", "last" : "Souglakos"} ], "volume": "9","number": "9","pages": "e107165","abstract": "TRAIL is a death receptor ligand that induces cell death preferentially in tumor cells. Recombinant soluble TRAIL, however, performs poorly as an anti-cancer therapeutic because oligomerization is required for potent biological activity. We previously generated a diabody format of tumor-targeted TRAIL termed Db$\\alpha$EGFR-scTRAIL, comprising single-stranded TRAIL molecules (scTRAIL) and the variable domains of a humanized variant of the EGFR blocking antibody Cetuximab. Here we define the bioactivity of Db$\\alpha$EGFR-scTRAIL with regard to both EGFR inhibition and TRAIL receptor activation in 3D cultures of Caco-2 colorectal cancer cells, which express wild-type K-Ras. Compared with conventional 2D cultures, Caco-2 cells displayed strongly enhanced sensitivity toward Db$\\alpha$EGFR-scTRAIL in these 3D cultures. We show that the antibody moiety of Db$\\alpha$EGFR-scTRAIL not only efficiently competed with ligand-induced EGFR function, but also determined the apoptotic response by specifically directing Db$\\alpha$EGFR-scTRAIL to EGFR-positive cells. To address how aberrantly activated K-Ras, which leads to Cetuximab resistance, affects Db$\\alpha$EGFR-scTRAIL sensitivity, we generated stable Caco-2tet cells inducibly expressing oncogenic K-RasG12V. In the presence of doxycycline, these cells showed increased resistance to Db$\\alpha$EGFR-scTRAIL, associated with the elevated expression of the anti-apoptotic proteins cIAP2, Bcl-xL and FlipS. Co-treatment of cells with the Smac mimetic SM83 restored the Db$\\alpha$EGFR-scTRAIL-induced apoptotic response. Importantly, this synergy between Db$\\alpha$EGFR-scTRAIL and SM83 also translated to 3D cultures of oncogenic K-Ras expressing HCT-116 and LoVo colorectal cancer cells. Our findings thus support the notion that Db$\\alpha$EGFR-scTRAIL therapy in combination with apoptosis-sensitizing agents may be promising for the treatment of EGFR-positive colorectal cancers, independently of their KRAS status.", "isbn" : "1932-6203 (Electronic)$\\backslash$r1932-6203 (Linking)", "pmid" : "25198428", "issn" : "19326203", "doi" : "10.1371/journal.pone.0107165", "bibtexKey": "Moller2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2683a862d7271775dd7814063af4fe257/pumaizi", "tags" : [ "izi","2014","pfizenmaier","kontermann" ], "intraHash" : "683a862d7271775dd7814063af4fe257", "interHash" : "6d2c5ec3ad660aa209080532179d5bd9", "label" : "Tetravalent Antibody-scTRAIL Fusion Proteins with Improved Properties", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Molecular Cancer Therapeutics", "year": "2014", "url": "http://mct.aacrjournals.org/cgi/doi/10.1158/1535-7163.MCT-13-0396", "author": [ "O. Seifert","A. Plappert","S. Fellermeier","M. Siegemund","K. Pfizenmaier","R. E. Kontermann" ], "authors": [ {"first" : "O.", "last" : "Seifert"}, {"first" : "A.", "last" : "Plappert"}, {"first" : "S.", "last" : "Fellermeier"}, {"first" : "M.", "last" : "Siegemund"}, {"first" : "K.", "last" : "Pfizenmaier"}, {"first" : "R. E.", "last" : "Kontermann"} ], "volume": "13","number": "1","pages": "101--111","abstract": "We applied the immunoglobulin E (IgE) heavy-chain domain 2 (EHD2) as the covalently linked homodimerization module to generate antibody-scTRAIL fusion proteins. By fusing a humanized single-chain fragment variable (scFv) directed against EGFR to the N-terminus of the EHD2 and a single-chain derivative of TRAIL (scTRAIL) to the C-terminus of the EHD2, we produced a dimeric, tetravalent fusion protein. The fusion protein retained its binding activity for EGFR and TRAIL receptors. In vitro, the targeted antibody-scTRAIL fusion protein exhibited an approximately 8- to 18-fold increased cytotoxic activity compared with the untargeted EHD2-scTRAIL fusion protein. This resulted in increased antitumor activity in a subcutaneous Colo205 xenograft tumor murine model. In summary, the scFv-EHD2-scTRAIL fusion protein combines target cell selectivity with an increased TRAIL activity leading to improved antitumor activities.", "isbn" : "4971168567", "pmid" : "24092811", "issn" : "1535-7163", "doi" : "10.1158/1535-7163.MCT-13-0396", "bibtexKey": "Seifert2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2575595b91074ef282c6390302545ab11/pumaizi", "tags" : [ "izi","2014","kontermann" ], "intraHash" : "575595b91074ef282c6390302545ab11", "interHash" : "5be653c0663a1d59183d691e1d3c1fd6", "label" : "In vivo near-infrared fluorescence imaging of FAP-expressing tumors with activatable FAP-targeted, single-chain Fv-immunoliposomes", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Controlled Release", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/24810115", "author": [ "Ronny Rüger","Felista L. Tansi","Markus Rabenhold","Frank Steiniger","Roland E. Kontermann","Alfred Fahr","Ingrid Hilger" ], "authors": [ {"first" : "Ronny", "last" : "Rüger"}, {"first" : "Felista L.", "last" : "Tansi"}, {"first" : "Markus", "last" : "Rabenhold"}, {"first" : "Frank", "last" : "Steiniger"}, {"first" : "Roland E.", "last" : "Kontermann"}, {"first" : "Alfred", "last" : "Fahr"}, {"first" : "Ingrid", "last" : "Hilger"} ], "volume": "186","pages": "1--10","abstract": "Molecular and cellular changes that precede the invasive growth of solid tumors include the release of proteolytic enzymes and peptides in the tumor stroma, the recruitment of phagocytic and lymphoid infiltrates and alteration of the extracellular matrix. The reactive tumor stroma consists of a large number of myofibroblasts, characterized by high expression of fibroblast activation protein alpha (FAP). FAP, a type-II transmembrane sialoglycoprotein is an attractive target in diagnosis and therapy of several pathologic disorders especially cancer. In the underlying work, a fluorescence-activatable liposome (fluorescence-quenched during circulation and fluorescence activation upon cellular uptake), bearing specific single-chain Fv fragments directed against FAP (scFv\u2032FAP) was developed, and its potential for use in fluorescence diagnostic imaging of FAP-expressing tumor cells was evaluated by whole body fluorescence imaging. The liposomes termed anti-FAP-IL were prepared via post-insertion of ligand-phospholipid-conjugates into preformed DY-676-COOH-containing liposomes. The anti-FAP-IL revealed a homogeneous size distribution and showed specific interaction and binding with FAP-expressing cells in vitro. The high level of fluorescence quenching of the near-infrared fluorescent dye sequestered in the aqueous interior of the liposomes enables fluorescence imaging exclusively upon uptake and degradation by cells, which results in fluorescence activation. Only FAP-expressing cells were able to take up and activate fluorescence of anti-FAP-IL in vitro. Furthermore, anti-FAP-IL accumulated selectively in FAP-expressing xenograft models in vivo, as demonstrated by blocking experiments using free scFv\u2032FAP. The local tumor fluorescence intensities were in agreement with the intrinsic degree of FAP-expression in different xenograft models. Thus, anti-FAP-IL can serve as a suitable in vivo diagnostic tool for pathological disorders accompanied by high FAP-expression. © 2014 Elsevier B.V. All rights reserved.", "pmid" : "24810115", "issn" : "18734995", "doi" : "10.1016/j.jconrel.2014.04.050", "bibtexKey": "Ruger2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2610be9f2a99c444d8e87723bfc9c8c2b/pumaizi", "tags" : [ "izi","2014","mueller","kontermann" ], "intraHash" : "610be9f2a99c444d8e87723bfc9c8c2b", "interHash" : "69aef0d5f4b721d9e4420fb21018c1c8", "label" : "Combining Antibody-Directed Presentation of IL-15 and 4-1BBL in a Trifunctional Fusion Protein for Cancer Immunotherapy", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Molecular Cancer Therapeutics", "year": "2014", "url": "http://mct.aacrjournals.org/cgi/doi/10.1158/1535-7163.MCT-13-0282", "author": [ "V. Kermer","N. Hornig","M. Harder","A. Bondarieva","R. E. Kontermann","D. Muller" ], "authors": [ {"first" : "V.", "last" : "Kermer"}, {"first" : "N.", "last" : "Hornig"}, {"first" : "M.", "last" : "Harder"}, {"first" : "A.", "last" : "Bondarieva"}, {"first" : "R. E.", "last" : "Kontermann"}, {"first" : "D.", "last" : "Muller"} ], "volume": "13","number": "1","pages": "112--121","abstract": "Influencing the cytokine receptor network that modulates the immune response holds great potential for cancer immunotherapy. Although encouraging results have been obtained by focusing on individual members of the common gamma-chain (gammac) receptor family and TNF receptor superfamily so far, combination strategies might be required to further improve the effectiveness of the antitumor response. Here, we propose the combination of interleukin (IL)-15 and 4-1BBL in a single, tumor-directed molecule. Therefore, a trifunctional antibody fusion protein was generated, composed of a tumor-specific recombinant antibody, IL-15 linked to a fragment of the IL-15Ralpha chain (RD) and the extracellular domain of 4-1BBL. In soluble and targeted forms, the trifunctional antibody fusion protein RD\\_IL-15\\_scFv\\_4-1BBL was shown to stimulate activated T-cell proliferation and induce T-cell cytotoxicity to a similar degree as the bifunctional scFv\\_RD\\_IL-15 fusion protein. On the other hand, in targeted form, the trifunctional fusion protein was much more effective in inducing T-cell proliferation and IFN-gamma release of unstimulated peripheral blood mononuclear cells (PBMC). Here, the additional signal enhancement could be attributed to the costimulatory activity of 4-1BBL, indicating a clear benefit for the simultaneous presentation of IL-15 and 4-1BBL in one molecule. Furthermore, the trifunctional antibody fusion protein was more effective than the corresponding bifunctional fusion proteins in reducing metastases in a tumor mouse model in vivo. Hence, the targeted combination of IL-15 and 4-BBL in the form of a trifunctional antibody-fusion protein is a promising new approach for cancer immunotherapy.", "isbn" : "1538-8514 (Electronic)$\\backslash$r1535-7163 (Linking)", "pmid" : "24198185", "eprint" : "1512.00567", "issn" : "1535-7163", "archiveprefix" : "arXiv", "arxivid" : "1512.00567", "doi" : "10.1158/1535-7163.MCT-13-0282", "bibtexKey": "Kermer2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2ca2046bbe8d767621a6484b3bb73419f/pumaizi", "tags" : [ "olayioye","izi","2014","hausser" ], "intraHash" : "ca2046bbe8d767621a6484b3bb73419f", "interHash" : "f3ce052c468a60b3e8c837adab255116", "label" : "Elevated protein kinase D3 (PKD3) expression supports proliferation of Triple-negative breast cancer cells and contributes to mTORC1-S6K1 pathway activation", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biological Chemistry", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/24337579", "author": [ "Bettina Huck","Stephan Duss","Angelika Hausser","Monilola A. Olayioye" ], "authors": [ {"first" : "Bettina", "last" : "Huck"}, {"first" : "Stephan", "last" : "Duss"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Monilola A.", "last" : "Olayioye"} ], "volume": "289","number": "6","pages": "3138--3147","abstract": "Here, we show that the expression of the Golgi-localized serine-threonine kinase protein kinase D3 (PKD3) is elevated in triple-negative breast cancer (TNBC). Using an antibody array, we identified PKD3 to trigger the activation of S6 kinase 1 (S6K1), a main downstream target of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Accordingly, PKD3 knockdown in TNBC cells led to reduced S6K1 phosphorylation, which was associated with impaired activation of mTORC1 at endolysosomal membranes, the accumulation of the mannose 6-phosphate receptor in and the recruitment of the autophagy marker light chain 3 to enlarged acidic vesicles. We further show that PKD3 depletion strongly inhibited cell spreading and proliferation of TNBC cells, identifying this kinase as a potential novel molecular therapeutic target in TNBC. Together, our data suggest that PKD3 in TNBC cells provides a molecular connection between the Golgi and endolysosomal compartments to enhance proliferative mTORC1-S6K1 signaling.", "isbn" : "4971168569301", "pmid" : "24337579", "issn" : "00219258", "doi" : "10.1074/jbc.M113.502633", "bibtexKey": "Huck2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/27598db8e3df70742cabfebd7e3288716/pumaizi", "tags" : [ "izi","2014","scheuric" ], "intraHash" : "7598db8e3df70742cabfebd7e3288716", "interHash" : "73cfef0b6deb77acfd9964d9100b8312", "label" : "Dominant negative effects of tumor necrosis factor (tnf)-related apoptosis-inducing ligand (TRAIL) receptor 4 on TRAIL receptor 1 signaling by Formation of heteromeric complexes", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biological Chemistry", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/24764293", "author": [ "Simon Neumann","Jan Hasenauer","Nadine Pollak","Peter Scheurich" ], "authors": [ {"first" : "Simon", "last" : "Neumann"}, {"first" : "Jan", "last" : "Hasenauer"}, {"first" : "Nadine", "last" : "Pollak"}, {"first" : "Peter", "last" : "Scheurich"} ], "volume": "289","number": "23","pages": "16576--16587","abstract": "The cytokine TNF-related apoptosis-inducing ligand (TRAIL) and its cell membrane receptors constitute an elaborate signaling system fulfilling important functions in immune regulation and tumor surveillance. Activation of the death receptors TRAILR1 and TRAILR2 can lead to apoptosis, whereas TRAILR3 and TRAILR4 are generally referred to as decoy receptors, which have been shown to inhibit TRAIL-induced apoptosis. The underlying molecular mechanisms, however, remain unclear. Alike other members of the TNF receptor superfamily, TRAIL receptors contain a pre-ligand binding assembly domain (PLAD) mediating receptor oligomerization. Still, the stoichiometry of TRAIL receptor oligomers as well as the issue of whether the PLAD mediates only homotypic or also heterotypic interactions remained inconclusive until now. Performing acceptor-photobleaching FRET studies with receptors 1, 2, and 4, we demonstrate interactions in all possible combinations. Formation of dimers was shown by chemical cross-linking experiments for interactions of TRAILR2 and heterophilic interactions between the two death receptors or between either of the death receptors and TRAILR4. Implications of the demonstrated receptor-receptor interactions on signaling were investigated in suitable cellular models. Both apoptosis induction and activation of the transcription factor NF$\\kappa$B were significantly reduced in the presence of TRAILR4. Our experimental data combined with mathematical modeling show that the inhibitory capacity of TRAILR4 is attributable to signaling-independent mechanisms, strongly suggesting a reduction of signaling competent death receptors through formation heteromeric receptor complexes. In summary, we propose a model of TRAIL receptor interference driven by PLAD-mediated formation of receptor heterodimers on the cell membrane.", "isbn" : "4971168567", "pmid" : "24764293", "issn" : "1083351X", "doi" : "10.1074/jbc.M114.559468", "bibtexKey": "Neumann2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2d452c3ab4a077d0bd7af6eac6a1b1dc5/pumaizi", "tags" : [ "izi","2014","kontermann" ], "intraHash" : "d452c3ab4a077d0bd7af6eac6a1b1dc5", "interHash" : "115dbd220474fa9e30af447c7ab8d0c7", "label" : "Characterization of the biological anti-staphylococcal functionality of hUK-66 IgG1, ahumanized monoclonal antibody as substantial component for an immunotherapeutic approach", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Human Vaccines and Immunotherapeutics", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/24495867", "author": [ "Babett Oesterreich","Birgit Lorenz","Tim Schmitter","Roland Kontermann","Michael Zenn","Bastian Zimmermann","Markus Haake","Udo Lorenz","Knut Ohlsen" ], "authors": [ {"first" : "Babett", "last" : "Oesterreich"}, {"first" : "Birgit", "last" : "Lorenz"}, {"first" : "Tim", "last" : "Schmitter"}, {"first" : "Roland", "last" : "Kontermann"}, {"first" : "Michael", "last" : "Zenn"}, {"first" : "Bastian", "last" : "Zimmermann"}, {"first" : "Markus", "last" : "Haake"}, {"first" : "Udo", "last" : "Lorenz"}, {"first" : "Knut", "last" : "Ohlsen"} ], "volume": "10","number": "4","pages": "926--937","abstract": "Multi-antigen immunotherapy approaches against Staphylococcus aureus are expected to have the best chance of clinical success when used in combinatorial therapy, potentially incorporating opsonic killing of bacteria and toxin neutralization. We recently reported the development of a murine monoclonal antibody specific for the immunodominant staphylococcal antigen A (IsaA), which showed highly efficient staphylococcal killing in experimental infection models of S. aureus. If IsaA-specific antibodies are to be used as a component of combination therapy in humans, the binding specificity and biological activity of the humanized variant must be preserved. Here, we describe the functional characterization of a humanized monoclonal IgG1 variant designated, hUK-66. The humanized antibody showed comparable binding kinetics to those of its murine parent, and recognized the target antigen IsaA on the surface of clinically relevant S. aureus lineages. Furthermore, hUK-66 enhances the killing of S. aureus in whole blood (a physiological environment) samples from healthy subjects and patients prone to staphylococcal infections such as diabetes and dialysis patients, and patients with generalized artery occlusive disease indicating no interference with already present natural antibodies. Taken together, these data indicate that hUK-66 mediates bacterial killing even in high risk patients and thus, could play a role for immunotherapy strategies to combat severe S. aureus infections.", "pmid" : "24495867", "issn" : "2164554X", "doi" : "10.4161/hv.27692", "bibtexKey": "Oesterreich2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/24dadb218ba507b13fa2768eb19eb96b3/pumaizi", "tags" : [ "olayioye","izi","2014" ], "intraHash" : "4dadb218ba507b13fa2768eb19eb96b3", "interHash" : "ee1b20ea6c1fdada2238625f3b22012f", "label" : "MiR149 functions as a tumor suppressor by controlling breast epithelial cell migration and invasion", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Cancer Research", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/25035394", "author": [ "Annabell Bischoff","Bettina Huck","Bettina Keller","Michaela Strotbek","Simone Schmid","Melanie Boerries","Hauke Busch","Dafne Müller","Monilola A. Olayioye" ], "authors": [ {"first" : "Annabell", "last" : "Bischoff"}, {"first" : "Bettina", "last" : "Huck"}, {"first" : "Bettina", "last" : "Keller"}, {"first" : "Michaela", "last" : "Strotbek"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Melanie", "last" : "Boerries"}, {"first" : "Hauke", "last" : "Busch"}, {"first" : "Dafne", "last" : "Müller"}, {"first" : "Monilola A.", "last" : "Olayioye"} ], "volume": "74","number": "18","pages": "5256--5265","abstract": "Deregulated molecular signaling pathways are responsible for the altered adhesive, migratory, and invasive properties of cancer cells. The different breast cancer subtypes are characterized by the expression of distinct miRNAs, short non-coding RNAs that posttranscriptionally modulate the expression of entire gene networks. Profiling studies have revealed downregulation of miR149 in basal breast cancer. Here, we show that miR149 expression severely impairs cell spreading, migration, and invasion of basal-like breast cancer cells. We identify signaling molecules, including the small GTPases Rap1a and Rap1b, downstream of integrin receptors as miR149 targets, providing an explanation for the defective Src and Rac activation during cell adhesion and spreading upon miR149 expression. Suppression of cell spreading by miR149 could be rescued, at least in part, by expression of constitutively active Rac. Finally, we demonstrate that increased miR149 levels block lung colonization in vivo. On the basis of our findings, we propose that miR149 downregulation in basal breast cancer facilitates the metastatic dissemination of tumor cells by supporting aberrant Rac activation. Cancer Res; 74(18); 5256\u201365. ©2014 AACR.", "isbn" : "4971168569301", "pmid" : "25035394", "issn" : "15387445", "doi" : "10.1158/0008-5472.CAN-13-3319", "bibtexKey": "Bischoff2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/23baea7951ec6e343193980b32ebaf4ba/pumaizi", "tags" : [ "izi","2014","pfizenmaier" ], "intraHash" : "3baea7951ec6e343193980b32ebaf4ba", "interHash" : "5f99ba81584c65f54f521ab56f0bdbfd", "label" : "Antibody-mediated inhibition of TNFR1 attenuates disease in a mouse model of multiple sclerosis", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "PLoS ONE", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/24587232", "author": [ "Sarah K. Williams","Olaf Maier","Roman Fischer","Richard Fairless","Sonja Hochmeister","Aleksandar Stojic","Lara Pick","Doreen Haar","Sylvia Musiol","Maria K. Storch","Klaus Pfizenmaier","Ricarda Diem" ], "authors": [ {"first" : "Sarah K.", "last" : "Williams"}, {"first" : "Olaf", "last" : "Maier"}, {"first" : "Roman", "last" : "Fischer"}, {"first" : "Richard", "last" : "Fairless"}, {"first" : "Sonja", "last" : "Hochmeister"}, {"first" : "Aleksandar", "last" : "Stojic"}, {"first" : "Lara", "last" : "Pick"}, {"first" : "Doreen", "last" : "Haar"}, {"first" : "Sylvia", "last" : "Musiol"}, {"first" : "Maria K.", "last" : "Storch"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Ricarda", "last" : "Diem"} ], "editor": [ "Ralf Andreas Linker" ], "editors": [ {"first" : "Ralf Andreas", "last" : "Linker"} ], "volume": "9","number": "2","pages": "e90117","abstract": "Tumour necrosis factor (TNF) is a proinflammatory cytokine that is known to regulate inflammation in a number of autoimmune diseases, including multiple sclerosis (MS). Although targeting of TNF in models of MS has been successful, the pathological role of TNF in MS remains unclear due to clinical trials where the non-selective inhibition of TNF resulted in exacerbated disease. Subsequent experiments have indicated that this may have resulted from the divergent effects of the two TNF receptors, TNFR1 and TNFR2. Here we show that the selective targeting of TNFR1 with an antagonistic antibody ameliorates symptoms of the most common animal model of MS, experimental autoimmune encephalomyelitis (EAE), when given following both a prophylactic and therapeutic treatment regime. Our results demonstrate that antagonistic TNFR1-specific antibodies may represent a therapeutic approach for the treatment of MS in the future.", "isbn" : "1932-6203 (Electronic)$\\backslash$r1932-6203 (Linking)", "pmid" : "24587232", "issn" : "19326203", "doi" : "10.1371/journal.pone.0090117", "bibtexKey": "Williams2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2e74706df08a436595f18c353d4b95097/pumaizi", "tags" : [ "izi","2014","pfizenmaier" ], "intraHash" : "e74706df08a436595f18c353d4b95097", "interHash" : "395b60c7150550000c385a8ac041ac5e", "label" : "Protein kinase D2 induces invasion of pancreatic cancer cells by regulating matrix metalloproteinases.", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Molecular biology of the cell", "year": "2014", "url": "https://doi.org/10.1091/mbc.E13-06-0334", "author": [ "Christoph Wille","Conny Köhler","Milena Armacki","Arsia Jamali","Ulrike Gössele","Klaus Pfizenmaier","Thomas Seufferlein","Tim Eiseler" ], "authors": [ {"first" : "Christoph", "last" : "Wille"}, {"first" : "Conny", "last" : "Köhler"}, {"first" : "Milena", "last" : "Armacki"}, {"first" : "Arsia", "last" : "Jamali"}, {"first" : "Ulrike", "last" : "Gössele"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Thomas", "last" : "Seufferlein"}, {"first" : "Tim", "last" : "Eiseler"} ], "volume": "25","number": "3","pages": "324--36","abstract": "Pancreatic cancer cell invasion, metastasis, and angiogenesis are major challenges for the development of novel therapeutic strategies. Protein kinase D (PKD) isoforms are involved in controlling tumor cell motility, angiogenesis, and metastasis. In particular PKD2 expression is up-regulated in pancreatic cancer, whereas PKD1 expression is lowered. We report that both kinases control pancreatic cancer cell invasive properties in an isoform-specific manner. PKD2 enhances invasion in three-dimensional extracellular matrix (3D-ECM) cultures by stimulating expression and secretion of matrix metalloproteinases 7 and 9 (MMP7/9), by which MMP7 is likely to act upstream of MMP9. Knockdown of MMP7/9 blocks PKD2-mediated invasion in 3D-ECM assays and in vivo using tumors growing on chorioallantois membranes. Furthermore, MMP9 enhances PKD2-mediated tumor angiogenesis by releasing extracellular matrix-bound vascular endothelial growth factor A, increasing its bioavailability and angiogenesis. Of interest, specific knockdown of PKD1 in PKD2-expressing pancreatic cancer cells further enhanced the invasive properties in 3D-ECM systems by generating a high-motility phenotype. Loss of PKD1 thus may be beneficial for tumor cells to enhance their matrix-invading abilities. In conclusion, we define for the first time PKD1 and 2 isoform-selective effects on pancreatic cancer cell invasion and angiogenesis, in vitro and in vivo, addressing PKD isoform specificity as a major factor for future therapeutic strategies.", "isbn" : "1939-4586 (Electronic)$\\backslash$r1059-1524 (Linking)", "pmid" : "24336522", "issn" : "1939-4586", "doi" : "10.1091/mbc.E13-06-0334", "bibtexKey": "Wille2014" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/267d23ecc1d3abdd0998a0e6af549cd3e/pumaizi", "tags" : [ "izi","2014","kulms" ], "intraHash" : "67d23ecc1d3abdd0998a0e6af549cd3e", "interHash" : "693560a357e86f38f670046e35fb669e", "label" : "Identification of New IκBα Complexes by an Iterative Experimental and Mathematical Modeling Approach", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 4, "pub-type": "article", "journal": "PLoS Computational Biology", "year": "2014", "url": "http://www.ncbi.nlm.nih.gov/pubmed/24675998", "author": [ "Fabian Konrath","Johannes Witt","Thomas Sauter","Dagmar Kulms" ], "authors": [ {"first" : "Fabian", "last" : "Konrath"}, {"first" : "Johannes", "last" : "Witt"}, {"first" : "Thomas", "last" : "Sauter"}, {"first" : "Dagmar", "last" : "Kulms"} ], "editor": [ "Feilim Mac Gabhann" ], "editors": [ {"first" : "Feilim Mac", "last" : "Gabhann"} ], "volume": "10","number": "3","pages": "e1003528","abstract": "The transcription factor nuclear factor kappa-B (NF$\\kappa$B) is a key regulator of pro-inflammatory and pro-proliferative processes. Accordingly, uncontrolled NF$\\kappa$B activity may contribute to the development of severe diseases when the regulatory system is impaired. Since NF$\\kappa$B can be triggered by a huge variety of inflammatory, pro-and anti-apoptotic stimuli, its activation underlies a complex and tightly regulated signaling network that also includes multi-layered negative feedback mechanisms. Detailed understanding of this complex signaling network is mandatory to identify sensitive parameters that may serve as targets for therapeutic interventions. While many details about canonical and non-canonical NF$\\kappa$B activation have been investigated, less is known about cellular I$\\kappa$B$\\alpha$ pools that may tune the cellular NF$\\kappa$B levels. I$\\kappa$B$\\alpha$ has so far exclusively been described to exist in two different forms within the cell: stably bound to NF$\\kappa$B or, very transiently, as unbound protein. We created a detailed mathematical model to quantitatively capture and analyze the time-resolved network behavior. By iterative refinement with numerous biological experiments, we yielded a highly identifiable model with superior predictive power which led to the hypothesis of an NF$\\kappa$B-lacking I$\\kappa$B$\\alpha$ complex that contains stabilizing IKK subunits. We provide evidence that other but canonical pathways exist that may affect the cellular I$\\kappa$B$\\alpha$ status. This additional I$\\kappa$B$\\alpha$:IKK$\\gamma$ complex revealed may serve as storage for the inhibitor to antagonize undesired NF$\\kappa$B activation under physiological and pathophysiological conditions.", "isbn" : "10.1371/journal.pcbi.1003528", "pmid" : "24675998", "issn" : "15537358", "doi" : "10.1371/journal.pcbi.1003528", "bibtexKey": "Konrath2014" } ] }