@article{OthmanNaseemAwadetal.2016,
  author    = {Othman, Eman M. and Naseem, Muhammed and Awad, Eman and Dandekar, Thomas and Stopper, Helga},
  title     = {The Plant Hormone Cytokinin Confers Protection against Oxidative Stress in Mammalian Cells},
  series = {PLoS One},
  volume    = {11},
  journal   = {PLoS One},
  number    = {12},
  doi       = {10.1371/journal.pone.0168386},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147983},
  pages     = {e0168386},
  year      = {2016},
  abstract  = {Modulating key dynamics of plant growth and development, the effects of the plant hormone cytokinin on animal cells gained much attention recently. Most previous studies on cytokinin effects on mammalian cells have been conducted with elevated cytokinin concentration (in the μM range). However, to examine physiologically relevant dose effects of cytokinins on animal cells, we systematically analyzed the impact of kinetin in cultured cells at low and high concentrations (1nM-10μM) and examined cytotoxic and genotoxic conditions. We furthermore measured the intrinsic antioxidant activity of kinetin in a cell-free system using the Ferric Reducing Antioxidant Power assay and in cells using the dihydroethidium staining method. Monitoring viability, we looked at kinetin effects in mammalian cells such as HL60 cells, HaCaT human keratinocyte cells, NRK rat epithelial kidney cells and human peripheral lymphocytes. Kinetin manifests no antioxidant activity in the cell free system and high doses of kinetin (500 nM and higher) reduce cell viability and mediate DNA damage in vitro. In contrast, low doses (concentrations up to 100 nM) of kinetin confer protection in cells against oxidative stress. Moreover, our results show that pretreatment of the cells with kinetin significantly reduces 4-nitroquinoline 1-oxide mediated reactive oxygen species production. Also, pretreatment with kinetin retains cellular GSH levels when they are also treated with the GSH-depleting agent patulin. Our results explicitly show that low kinetin doses reduce apoptosis and protect cells from oxidative stress mediated cell death. Future studies on the interaction between cytokinins and human cellular pathway targets will be intriguing.},
  language  = {en}
}
@article{VamanVSPoppeHoubenetal.2015,
  author    = {Vaman V. S., Anjana and Poppe, Heiko and Houben, Roland and Grunewald, Thomas G. P. and Goebeler, Matthias and Butt, Elke},
  title     = {LASP1, a Newly Identified Melanocytic Protein with a Possible Role in Melanin Release, but Not in Melanoma Progression},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {6},
  doi       = {10.1371/journal.pone.0129219},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125994},
  pages     = {e0129219},
  year      = {2015},
  abstract  = {The LIM and SH3 protein 1 (LASP1) is a focal adhesion protein. Its expression is increased in many malignant tumors. However, little is known about the physiological role of the protein. In the present study, we investigated the expression and function of LASP1 in normal skin, melanocytic nevi and malignant melanoma. In normal skin, a distinct LASP1 expression is visible only in the basal epidermal layer while in nevi LASP1 protein is detected in all melanocytes. Melanoma exhibit no increase in LASP1 mRNA compared to normal skin. In melanocytes, the protein is bound to dynamin and mainly localized at late melanosomes along the edges and at the tips of the cell. Knockdown of LASP1 results in increased melanin concentration in the cells. Collectively, we identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release.},
  language  = {en}
}
@article{PalettaFichtnerStaricketal.2015,
  author    = {Paletta, Daniel and Fichtner, Alina Suzann and Starick, Lisa and Porcelli, Steven A. and Savage, Paul B. and Herrmann, Thomas},
  title     = {Species Specific Differences of CD1d Oligomer Loading In Vitro},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {11},
  doi       = {10.1371/journal.pone.0143449},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124879},
  pages     = {e0143449},
  year      = {2015},
  abstract  = {CD1d molecules are MHC class I-like molecules that present glycolipids to iNKT cells. The highly conserved interaction between CD1d:α-Galactosylceramide (αGC) complexes and the iNKT TCR not only defines this population of αβ T cells but can also be used for its direct identification. Therefore, CD1d oligomers are a widely used tool for iNKT cell related investigations. To this end, the lipid chains of the antigen have to be inserted into the hydrophobic pockets of the CD1d binding cleft, often with help of surfactants. In this study, we investigated the influence of different surfactants (Triton X-100, Tween 20, Tyloxapol) on in vitro loading of CD1d molecules derived from four different species (human, mouse, rat and cotton rat) with αGC and derivatives carrying modifications of the acyl-chain (DB01-1, PBS44) and a 6-acetamido-6-deoxy-addition at the galactosyl head group (PBS57). We also compared rat CD1d dimers with tetramers and staining of an iNKT TCR transductant was used as readout for loading efficacy. The results underlined the importance of CD1d loading efficacy for proper analysis of iNKT TCR binding and demonstrated the necessity to adjust loading conditions for each oligomer/glycolipid combination. The efficient usage of surfactants as a tool for CD1d loading was revealed to be species-specific and depending on the origin of the CD1d producing cells. Additional variation of surfactant-dependent loading efficacy between tested glycolipids was influenced by the acyl-chain length and the modification of the galactosyl head group with PBS57 showing the least dependence on surfactants and the lowest degree of species-dependent differences.},
  language  = {en}
}
@article{HaferkampHesbacherWeyandtetal.2014,
  author    = {Haferkamp, Sebastian and Hesbacher, Sonja and Weyandt, Gerhard and Vetter-Kauczok, Claudia S. and Becker, J{\"u}rgen C. and Motschenbacher, Stephanie and Wobser, Marion and Maier, Melissa and Schmid, Corinna P. and Houben, Roland},
  title     = {p53 regulation by TRP2 is not pervasive in melanoma},
  doi       = {10.1371/journal.pone.0087440},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111396},
  year      = {2014},
  abstract  = {p53 is a central tumor suppressor protein and its inhibition is believed to be a prerequisite for cancer development. In approximately 50\% of all malignancies this is achieved by inactivating mutations in the p53 gene. However, in several cancer entities, including melanoma, p53 mutations are rare. It has been recently proposed that tyrosinase related protein 2 (TRP2), a protein involved in melanin synthesis, may act as suppressor of the p53 pathway in melanoma. To scrutinize this notion we analyzed p53 and TRP2 expression by immunohistochemistry in 172 melanoma tissues and did not find any correlation. Furthermore, we applied three different TRP2 shRNAs to five melanoma cell lines and could not observe a target specific effect of the TRP2 knockdown on either p53 expression nor p53 reporter gene activity. Likewise, ectopic expression of TRP2 in a TRP2 negative melanoma cell line had no impact on p53 expression. In conclusion our data suggest that p53 repression critically controlled by TRP2 is not a general event in melanoma.},
  language  = {en}
}
@article{BuschWesthofenKochetal.2014,
  author    = {Busch, Martin and Westhofen, Thilo C. and Koch, Miriam and Lutz, Manfred B. and Zernecke, Alma},
  title     = {Dendritic Cell Subset Distributions in the Aorta in Healthy and Atherosclerotic Mice},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {2},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0088452},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119907},
  pages     = {e88452},
  year      = {2014},
  abstract  = {Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr-/-) mice, CD11c+ MHCII+ DCs could be discriminated into CD103- CD11b+F4/80+, CD11b+F4/80- and CD11b-F4/80- DCs and CD103+ CD11b-F4/80- DCs. Except for CD103- CD11b- F4/80- DCs, these subsets expanded in high fat diet-fed Ldlr-/- mice. Signal-regulatory protein (Sirp)-α was detected on aortic macrophages, CD11b+ DCs, and partially on CD103- CD11b- F4/80- but not on CD103+ DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l-/-) mice, a specific loss of CD103+ DCs but also CD103- CD11b+ F4/80- DCs was evidenced. Aortic CD103+ and CD11b+ F4/80- CD103- DCs may thus belong to conventional rather than monocyte-derived DCs, given their dependence on Flt3L-signalling. CD64, postulated to distinguish macrophages from DCs, could not be detected on DC subsets under physiological conditions, but appeared in a fraction of CD103- CD11b+ F4/80- and CD11b+ F4/80+ cells in atherosclerotic Ldlr-/- mice. The emergence of CD64 expression in atherosclerosis may indicate that CD11b+ F4/80- DCs similar to CD11b+ F4/80+ DCs are at least in part derived from immigrated monocytes during atherosclerotic lesion formation. Our data advance our knowledge about the presence of distinct DC subsets and their accumulation characteristics in atherosclerosis, and may help to assist in future studies aiming at specific DC-based therapeutic strategies for the treatment of chronic vascular inflammation.},
  language  = {en}
}
@article{AdamBaeurleBrodskyetal.2014,
  author    = {Adam, Christian and Baeurle, Anne and Brodsky, Jeffrey L. and Schrama, David and Wipf, Peter and Becker, J{\"u}rgen Christian and Houben, Roland},
  title     = {The HSP70 Modulator MAL3-101 Inhibits Merkel Cell Carcinoma},
  doi       = {10.1371/journal.pone.0092041},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112795},
  year      = {2014},
  abstract  = {Merkel Cell Carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer for which no effective treatment is available. MCC represents a human cancer with the best experimental evidence for a causal role of a polyoma virus. Large T antigens (LTA) encoded by polyoma viruses are oncoproteins, which are thought to require support of cellular heat shock protein 70 (HSP70) to exert their transforming activity. Here we evaluated the capability of MAL3-101, a synthetic HSP70 inhibitor, to limit proliferation and survival of various MCC cell lines. Remarkably, MAL3-101 treatment resulted in considerable apoptosis in 5 out of 7 MCC cell lines. While this effect was not associated with the viral status of the MCC cells, quantitative mRNA expression analysis of the known HSP70 isoforms revealed a significant correlation between MAL3-101 sensitivity and HSC70 expression, the most prominent isoform in all cell lines. Moreover, MAL3-101 also exhibited in vivo antitumor activity in an MCC xenograft model suggesting that this substance or related compounds are potential therapeutics for the treatment of MCC in the future.},
  language  = {en}
}
@article{SchubertUnkmeirSchneiderSchauliesGulbinsetal.2014,
  author    = {Schubert-Unkmeir, Alexandra and Schneider-Schaulies, Sibylle and Gulbins, Erich and Hebling, Sabrina and Simonis, Alexander},
  title     = {Differential Activation of Acid Sphingomyelinase and Ceramide Release Determines Invasiveness of Neisseria meningitidis into Brain Endothelial Cells},
  doi       = {10.1371/journal.ppat.1004160},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113031},
  year      = {2014},
  abstract  = {The interaction with brain endothelial cells is central to the pathogenicity of Neisseria meningitidis infections. Here, we show that N. meningitidis causes transient activation of acid sphingomyelinase (ASM) followed by ceramide release in brain endothelial cells. In response to N. meningitidis infection, ASM and ceramide are displayed at the outer leaflet of the cell membrane and condense into large membrane platforms which also concentrate the ErbB2 receptor. The outer membrane protein Opc and phosphatidylcholine-specific phospholipase C that is activated upon binding of the pathogen to heparan sulfate proteoglycans, are required for N. meningitidis-mediated ASM activation. Pharmacologic or genetic ablation of ASM abrogated meningococcal internalization without affecting bacterial adherence. In accordance, the restricted invasiveness of a defined set of pathogenic isolates of the ST-11/ST-8 clonal complex into brain endothelial cells directly correlated with their restricted ability to induce ASM and ceramide release. In conclusion, ASM activation and ceramide release are essential for internalization of Opc-expressing meningococci into brain endothelial cells, and this segregates with invasiveness of N. meningitidis strains. Author Summary Neisseria meningitidis, an obligate human pathogen, is a causative agent of septicemia and meningitis worldwide. Meningococcal infection manifests in a variety of forms, including meningitis, meningococcemia with meningitis or meningococcemia without obvious meningitis. The interaction of N. meningitidis with human cells lining the blood vessels of the blood-cerebrospinal fluid barrier is a prerequisite for the development of meningitis. As a major pathogenicity factor, the meningococcal outer membrane protein Opc enhances bacterial entry into brain endothelial cells, however, mechanisms underlying trapping of receptors and signaling molecules following this interaction remained elusive. We now show that Opc-expressing meningococci activate acid sphingomyelinase (ASM) in brain endothelial cells, which hydrolyses sphingomyelin to cause ceramide release and formation of extended ceramide-enriched membrane platforms wherein ErbB2, an important receptor involved in bacterial uptake, clusters. Mechanistically, ASM activation relied on binding of N. meningitidis to its attachment receptor, HSPG, followed by activation of PC-PLC. Meningococcal isolates of the ST-11 clonal complex, which are reported to be more likely to cause severe sepsis, but rarely meningitis, barely invaded brain endothelial cells and revealed a highly restricted ability to induce ASM and ceramide release. Thus, our results unravel a differential activation of the ASM/ceramide system by the species N. meningitidis determining its invasiveness into brain endothelial cells.},
  language  = {en}
}
@article{RascheDuellMorgneretal.2013,
  author    = {Rasche, Leo and Duell, Johannes and Morgner, Charlotte and Chatterjee, Manik and Hensel, Frank and Rosenwald, Andreas and Einsele, Hermann and Topp, Max S. and Br{\"a}ndlein, Stephanie},
  title     = {The Natural Human IgM Antibody PAT-SM6 Induces Apoptosis in Primary Human Multiple Myeloma Cells by Targeting Heat Shock Protein GRP78},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0063414},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130125},
  pages     = {e63414},
  year      = {2013},
  abstract  = {In contrast to other haematological malignancies, targeted immunotherapy has not entered standard treatment regimens for de novo or relapsed multiple myeloma (MM) yet. While a number of IgG-formatted monoclonal antibodies are currently being evaluated in clinical trials in MM, our study aimed to investigate whether the fully human IgM monoclonal antibody PAT-SM6 that targets a tumour-specific variant of the heat shock protein GRP78 might be an attractive candidate for future immunotherapeutic approaches. We here show that GRP78 is stably and consistently expressed on the surface on tumour cells from patients with de novo, but also relapsed MM and that binding of PAT-SM6 to MM cells can specifically exert cytotoxic effects on malignant plasma cells, whereas non-malignant cells are not targeted. We demonstrate that the induction of apoptosis and, to a lesser extent, complement dependent cytotoxicity is the main mode of action of PAT-SM6, whereas antibody dependent cellular cytotoxicity does not appear to contribute to the cytotoxic properties of this antibody. Given the favourable safety profile of PAT-SM6 in monkeys, but also in a recent phase I trial in patients with malignant melanoma, our results form the basis for a planned phase I study in patients with relapsed MM.},
  language  = {en}
}
@article{HanKampikGrehnetal.2013,
  author    = {Han, Hong and Kampik, Daniel and Grehn, Franz and Schlunck, G{\"u}nther},
  title     = {TGF-beta 2-Induced Invadosomes in Human Trabecular Meshwork Cells},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0070595},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130074},
  pages     = {e70595},
  year      = {2013},
  abstract  = {Primary open-angle glaucoma (POAG) is a leading cause of blindness due to chronic degeneration of retinal ganglion cells and their optic nerve axons. It is associated with disturbed regulation of intraocular pressure, elevated intraocular levels of TGF-β2, aberrant extracellular matrix (ECM) deposition and increased outflow resistance in the trabecular meshwork (TM). The mechanisms underlying these changes are not fully understood. Cell-matrix interactions have a decisive role in TM maintenance and it has been suggested that TGF-β-induced inhibition of matrix metalloproteases may drive aberrant ECM deposition in POAG. Invadopodia and podosomes (invadosomes) are distinct sites of cell-matrix interaction and localized matrix-metalloprotease (MMP) activity. Here, we report on the effects of TGF-β2 on invadosomes in human trabecular meshwork cells. Human TM (HTM) cells were derived from donor tissue and pretreated with vehicle or TGF-β2 (2 ng/ml) for 3d. Invadosomes were studied in ECM degradation assays, protein expression and MMP-2 activity were assessed by western blot and zymography and ECM protein transcription was detected by RT-qPCR. HTM cells spontaneously formed podosomes and invadopodia as detected by colocalization of Grb2 or Nck1 to sites of gelatinolysis. Pretreatment with TGF-β2 enhanced invadosomal proteolysis and zymographic MMP-2 activity as well as MMP-2, TIMP-2 and PAI-1 levels in HTM cell culture supernatants. Rho-kinase inhibition by H1152 blocked the effects of TGF-β2. Concomitant transcription of fibronectin and collagens-1, -4 and -6 was increased by TGF-β2 and fibrillar fibronectin deposits were observed in areas of invadosomal ECM remodelling. In contrast to a current hypothesis, our data indicate that TGF-β2 induces an active ECM remodelling process in TM cells, characterized by concurrent increases in localized ECM digestion and ECM expression, rather than a mere buildup of material due to a lack of degradation. Invadosomal cell adhesion and signaling may thus have a role in POAG pathophysiology.},
  language  = {en}
}
@article{LueckerathLapaSpahmannetal.2013,
  author    = {L{\"u}ckerath, Katharina and Lapa, Constantin and Spahmann, Annika and J{\"o}rg, Gerhard and Samnick, Samuel and Rosenwald, Andreas and Einsele, Herrmann and Knop, Stefan and Buck, Andreas},
  title     = {Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology},
  doi       = {10.1371/journal.pone.0084840},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111319},
  year      = {2013},
  abstract  = {Purpose Multiple myeloma is a hematologic malignancy originating from clonal plasma cells. Despite effective therapies, outcomes are highly variable suggesting marked disease heterogeneity. The role of functional imaging for therapeutic management of myeloma, such as positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG-PET), remains to be determined. Although some studies already suggested a prognostic value of 18F-FDG-PET, more specific tracers addressing hallmarks of myeloma biology, e.g. paraprotein biosynthesis, are needed. This study evaluated the amino acid tracers L-methyl-[11C]-methionine (11C-MET) and [18F]-fluoroethyl-L-tyrosine (18F-Fet) for their potential to image myeloma and to characterize tumor heterogeneity. Experimental Design To study the utility of 11C-MET, 18F-Fet and 18F-FDG for myeloma imaging, time activity curves were compared in various human myeloma cell lines (INA-6, MM1.S, OPM-2) and correlated to cell-biological characteristics, such as marker gene expression and immunoglobulin levels. Likewise, patient-derived CD138+ plasma cells were characterized regarding uptake and biomedical features. Results Using myeloma cell lines and patient-derived CD138+ plasma cells, we found that the relative uptake of 11C-MET exceeds that of 18F-FDG 1.5- to 5-fold and that of 18F-Fet 7- to 20-fold. Importantly, 11C-MET uptake significantly differed between cell types associated with worse prognosis (e.g. t(4;14) in OPM-2 cells) and indolent ones and correlated with intracellular immunoglobulin light chain and cell surface CD138 and CXCR4 levels. Direct comparison of radiotracer uptake in primary samples further validated the superiority of 11C-MET. Conclusion These data suggest that 11C-MET might be a versatile biomarker for myeloma superior to routine functional imaging with 18F-FDG regarding diagnosis, risk stratification, prognosis and discrimination of tumor subtypes.},
  language  = {en}
}
@article{BuchnerBlancoRedondoBunzetal.2013,
  author    = {Buchner, Erich and Blanco Redondo, Beatriz and Bunz, Melanie and Halder, Partho and Sadanandappa, Madhumala K. and M{\"u}hlbauer, Barbara and Erwin, Felix and Hofbauer, Alois and Rodrigues, Veronica and VijayRaghavan, K. and Ramaswami, Mani and Rieger, Dirk and Wegener, Christian and F{\"o}rster, Charlotte},
  title     = {Identification and Structural Characterization of Interneurons of the Drosophila Brain by Monoclonal Antibodies of the W{\"u}rzburg Hybridoma Library},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0075420},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97109},
  year      = {2013},
  abstract  = {Several novel synaptic proteins have been identified by monoclonal antibodies (mAbs) of the W{\"u}rzburg hybridoma library generated against homogenized Drosophila brains, e.g. cysteine string protein, synapse-associated protein of 47 kDa, and Bruchpilot. However, at present no routine technique exists to identify the antigens of mAbs of our library that label only a small number of cells in the brain. Yet these antibodies can be used to reproducibly label and thereby identify these cells by immunohistochemical staining. Here we describe the staining patterns in the Drosophila brain for ten mAbs of the W{\"u}rzburg hybridoma library. Besides revealing the neuroanatomical structure and distribution of ten different sets of cells we compare the staining patterns with those of antibodies against known antigens and GFP expression patterns driven by selected Gal4 lines employing regulatory sequences of neuronal genes. We present examples where our antibodies apparently stain the same cells in different Gal4 lines suggesting that the corresponding regulatory sequences can be exploited by the split-Gal4 technique for transgene expression exclusively in these cells. The detection of Gal4 expression in cells labeled by mAbs may also help in the identification of the antigens recognized by the antibodies which then in addition to their value for neuroanatomy will represent important tools for the characterization of the antigens. Implications and future strategies for the identification of the antigens are discussed.},
  language  = {en}
}
@article{ChopraLangSalzmannetal.2013,
  author    = {Chopra, Martin and Lang, Isabell and Salzmann, Steffen and Pachel, Christina and Kraus, Sabrina and B{\"a}uerlein, Carina A. and Brede, Christian and Jord{\´a}n Garrote, Ana-Laura and Mattenheimer, Katharina and Ritz, Miriam and Schwinn, Stefanie and Graf, Carolin and Sch{\"a}fer, Viktoria and Frantz, Stefan and Einsele, Hermann and Wajant, Harald and Beilhack, Andreas},
  title     = {Tumor Necrosis Factor Induces Tumor Promoting and Anti-Tumoral Effects on Pancreatic Cancer via TNFR1},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0075737},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97246},
  year      = {2013},
  abstract  = {Multiple activities are ascribed to the cytokine tumor necrosis factor (TNF) in health and disease. In particular, TNF was shown to affect carcinogenesis in multiple ways. This cytokine acts via the activation of two cell surface receptors, TNFR1, which is associated with inflammation, and TNFR2, which was shown to cause anti-inflammatory signaling. We assessed the effects of TNF and its two receptors on the progression of pancreatic cancer by in vivo bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02 cells. Mice deficient for TNFR1 were unable to spontaneously reject Panc02 tumors and furthermore displayed enhanced tumor progression. In contrast, a fraction of wild type (37.5\%), TNF deficient (12.5\%), and TNFR2 deficient mice (22.2\%) were able to fully reject the tumor within two weeks. Pancreatic tumors in TNFR1 deficient mice displayed increased vascular density, enhanced infiltration of CD4+ T cells and CD4+ forkhead box P3 (FoxP3)+ regulatory T cells (Treg) but reduced numbers of CD8+ T cells. These alterations were further accompanied by transcriptional upregulation of IL4. Thus, TNF and TNFR1 are required in pancreatic ductal carcinoma to ensure optimal CD8+ T cell-mediated immunosurveillance and tumor rejection. Exogenous systemic administration of human TNF, however, which only interacts with murine TNFR1, accelerated tumor progression. This suggests that TNFR1 has basically the capability in the Panc02 model to trigger pro-and anti-tumoral effects but the spatiotemporal availability of TNF seems to determine finally the overall outcome.},
  language  = {en}
}
@article{BeyersdorfWernerWolfetal.2011,
  author    = {Beyersdorf, Niklas and Werner, Sandra and Wolf, Nelli and Herrmann, Thomas and Kerkau, Thomas},
  title     = {Characterization of a New Mouse Model for Peripheral T Cell Lymphoma in Humans},
  series = {PLoS One},
  volume    = {6},
  journal   = {PLoS One},
  number    = {12},
  doi       = {10.1371/journal.pone.0028546},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137946},
  pages     = {e28546},
  year      = {2011},
  abstract  = {Peripheral T cell lymphomas (PTCLs) are associated with a poor prognosis due to often advanced disease at the time of diagnosis and due to a lack of efficient therapeutic options. Therefore, appropriate animal models of PTCL are vital to improve clinical management of this disease. Here, we describe a monoclonal CD8\(^+\) CD4\(^-\) αβ T cell receptor Vβ2\(^+\) CD28\(^+\) T cell lymphoma line, termed T8-28. T8-28 cells were isolated from an un-manipulated adult BALB/c mouse housed under standard pathogen-free conditions. T8-28 cells induced terminal malignancy upon adoptive transfer into syngeneic BALB/c mice. Despite intracellular expression of the cytotoxic T cell differentiation marker granzyme B, T8-28 cells appeared to be defective with respect to cytotoxic activity as read-out in vitro. Among the protocols tested, only addition of interleukin 2 in vitro could partially compensate for the in vivo micro-milieu in promoting growth of the T8-28 lymphoma cells.},
  language  = {en}
}