TY - JOUR A1 - Dietl, Sebastian A1 - Schwinn, Stefanie A1 - Dietl, Susanne A1 - Riedl, Simone A1 - Deinlein, Frank A1 - Rutkowski, Stefan A1 - von Bueren, Andre O. A1 - Krauss, Jürgen A1 - Schweitzer, Tilmann A1 - Vince, Giles H. A1 - Picard, Daniel A1 - Eyrich, Matthias A1 - Rosenwald, Andreas A1 - Ramaswamy, Vijay A1 - Taylor, Michael D. A1 - Remke, Marc A1 - Monoranu, Camelia M. A1 - Beilhack, Andreas A1 - Schlegel, Paul G. A1 - Wölfl, Matthias T1 - MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties JF - BMC Cancer N2 - Background Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup. Methods We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma. Results Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture. Conclusions This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma. KW - cancer stem cells KW - anaplastic medulloblastoma KW - group 3 KW - orthotopic xenograft KW - animal model KW - brain tumor KW - children Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145877 VL - 16 IS - 115 ER - TY - JOUR A1 - Chopra, Martin A1 - Biehl, Marlene A1 - Steinfatt, Tim A1 - Brandl, Andreas A1 - Kums, Juliane A1 - Amich, Jorge A1 - Vaeth, Martin A1 - Kuen, Janina A1 - Holtappels, Rafaela A1 - Podlech, Jürgen A1 - Mottok, Anja A1 - Kraus, Sabrina A1 - Jordán-Garotte, Ana-Laura A1 - Bäuerlein, Carina A. A1 - Brede, Christian A1 - Ribechini, Eliana A1 - Fick, Andrea A1 - Seher, Axel A1 - Polz, Johannes A1 - Ottmueller, Katja J. A1 - Baker, Jeannette A1 - Nishikii, Hidekazu A1 - Ritz, Miriam A1 - Mattenheimer, Katharina A1 - Schwinn, Stefanie A1 - Winter, Thorsten A1 - Schäfer, Viktoria A1 - Krappmann, Sven A1 - Einsele, Hermann A1 - Müller, Thomas D. A1 - Reddehase, Matthias J. A1 - Lutz, Manfred B. A1 - Männel, Daniela N. A1 - Berberich-Siebelt, Friederike A1 - Wajant, Harald A1 - Beilhack, Andreas T1 - Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion JF - Journal of Experimental Medicine N2 - Donor CD4\(^+\)Foxp3\(^+\) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology. Expanding radiation-resistant host T reg cells in recipient mice using a mouse TNFR2-selective agonist before allo-HCT significantly prolonged survival and reduced GvHD severity in a TNFR2-and T reg cell-dependent manner. The beneficial effects of transplanted T cells against leukemia cells and infectious pathogens remained unaffected. A corresponding human TNFR2-specific agonist expanded human T reg cells in vitro. These observations indicate the potential of our strategy to protect allo-HCT patients from acute GvHD by expanding T reg cells via selective TNFR2 activation in vivo. KW - Tumor-necrosis-factor KW - Regulatory-cells KW - Bone marrow transplantantation KW - Graft-versus-leukemia KW - Rheumatoid arthritis KW - Autoimmune diseases KW - Factor receptor KW - Alpha therapy KW - Expression KW - Suppression Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187640 VL - 213 IS - 9 ER - TY - JOUR A1 - Beilhack, Andreas A1 - Chopra, Martin A1 - Kraus, Sabrina A1 - Schwinn, Stefanie A1 - Ritz, Miriam A1 - Mattenheimer, Katharina A1 - Mottok, Anja A1 - Rosenwald, Andreas A1 - Einsele, Hermann T1 - Non-Invasive Bioluminescence Imaging to Monitor the Immunological Control of a Plasmablastic Lymphoma-Like B Cell Neoplasia after Hematopoietic Cell Transplantation N2 - To promote cancer research and to develop innovative therapies, refined pre-clinical mouse tumor models that mimic the actual disease in humans are of dire need. A number of neoplasms along the B cell lineage are commonly initiated by a translocation recombining c-myc with the immunoglobulin heavy-chain gene locus. The translocation is modeled in the C.129S1-Ighatm1(Myc)Janz/J mouse which has been previously engineered to express c-myc under the control of the endogenous IgH promoter. This transgenic mouse exhibits B cell hyperplasia and develops diverse B cell tumors. We have isolated tumor cells from the spleen of a C.129S1-Ighatm1(Myc)Janz/J mouse that spontaneously developed a plasmablastic lymphoma-like disease. These cells were cultured, transduced to express eGFP and firefly luciferase, and gave rise to a highly aggressive, transplantable B cell lymphoma cell line, termed IM380. This model bears several advantages over other models as it is genetically induced and mimics the translocation that is detectable in a number of human B cell lymphomas. The growth of the tumor cells, their dissemination, and response to treatment within immunocompetent hosts can be imaged non-invasively in vivo due to their expression of firefly luciferase. IM380 cells are radioresistant in vivo and mice with established tumors can be allogeneically transplanted to analyze graft-versus-tumor effects of transplanted T cells. Allogeneic hematopoietic stem cell transplantation of tumor-bearing mice results in prolonged survival. These traits make the IM380 model very valuable for the study of B cell lymphoma pathophysiology and for the development of innovative cancer therapies. KW - B cells KW - T cells KW - Bioluminescence imaging KW - Bone marrow cells KW - Bone marrow transplantation KW - Cancer treatment KW - Spleen KW - Lymphomas Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111341 ER - TY - JOUR A1 - Siwka, Wieslaw A1 - Schwinn, Andreas A1 - Baczko, Knut A1 - Pardowitz, Iancu A1 - Mhalu, Fred A1 - Shao, John A1 - Rethwilm, Axel A1 - ter Meulen, Volker T1 - vpu and env sequence variability of HIV-1 isolates from Tanzania N2 - No abstract available KW - Virologie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61355 ER - TY - JOUR A1 - Chopra, Martin A1 - Lang, Isabell A1 - Salzmann, Steffen A1 - Pachel, Christina A1 - Kraus, Sabrina A1 - Bäuerlein, Carina A. A1 - Brede, Christian A1 - Jordán Garrote, Ana-Laura A1 - Mattenheimer, Katharina A1 - Ritz, Miriam A1 - Schwinn, Stefanie A1 - Graf, Carolin A1 - Schäfer, Viktoria A1 - Frantz, Stefan A1 - Einsele, Hermann A1 - Wajant, Harald A1 - Beilhack, Andreas T1 - Tumor Necrosis Factor Induces Tumor Promoting and Anti-Tumoral Effects on Pancreatic Cancer via TNFR1 JF - PLoS ONE N2 - 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. KW - Bioluminescence KW - cancer treatment KW - cell staining KW - cytokines KW - immune cells KW - metastasis KW - regulatory T cells KW - T cells Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97246 ER - TY - CHAP A1 - Mori, Kazuyasu A1 - Rethwilm, Axel A1 - Schwinn, Andreas A1 - Horak, Ivan T1 - Replication of human immunodeficiency virus type 1 in human t-cells expressing antisense RNA N2 - No abstract available. KW - HIV Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86426 ER - TY - CHAP A1 - Schwinn, Andreas A1 - Rethwilm, Axel A1 - Esers, Stefan A1 - Borisch, Bettina A1 - ter Meulen, Volker T1 - Interaction of HIV-1 and HHV-6 N2 - No abstract available. KW - HIV KW - Herpesviren Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86415 ER - TY - JOUR A1 - Schwinn, Stefanie A1 - Mokhtari, Zeinab A1 - Thusek, Sina A1 - Schneider, Theresa A1 - Sirén, Anna-Leena A1 - Tiemeyer, Nicola A1 - Caruana, Ignazio A1 - Miele, Evelina A1 - Schlegel, Paul G. A1 - Beilhack, Andreas A1 - Wölfl, Matthias T1 - Cytotoxic effects and tolerability of gemcitabine and axitinib in a xenograft model for c-myc amplified medulloblastoma JF - Scientific Reports N2 - Medulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma. KW - cancer KW - CNS cancer KW - paediatric cancer Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261476 VL - 11 IS - 1 ER -