@article{EhrigKilincChenetal.2013,
  author    = {Ehrig, Klaas and Kilinc, Mehmet O. and Chen, Nanhai G. and Stritzker, Jochen and Buckel, Lisa and Zhang, Qian and Szalay, Aladar A.},
  title     = {Growth inhibition of different human colorectal cancer xenografts after a single intravenous injection of oncolytic vaccinia virus GLV-1h68},
  series = {Journal of Translational Medicine},
  volume    = {11},
  journal   = {Journal of Translational Medicine},
  number    = {79},
  doi       = {10.1186/1479-5876-11-79},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129619},
  year      = {2013},
  abstract  = {Background: Despite availability of efficient treatment regimens for early stage colorectal cancer, treatment regimens for late stage colorectal cancer are generally not effective and thus need improvement. Oncolytic virotherapy using replication-competent vaccinia virus (VACV) strains is a promising new strategy for therapy of a variety of human cancers. Methods: Oncolytic efficacy of replication-competent vaccinia virus GLV-1h68 was analyzed in both, cell cultures and subcutaneous xenograft tumor models. Results: In this study we demonstrated for the first time that the replication-competent recombinant VACV GLV-1h68 efficiently infected, replicated in, and subsequently lysed various human colorectal cancer lines (Colo 205, HCT-15, HCT-116, HT-29, and SW-620) derived from patients at all four stages of disease. Additionally, in tumor xenograft models in athymic nude mice, a single injection of intravenously administered GLV-1h68 significantly inhibited tumor growth of two different human colorectal cell line tumors (Duke's type A-stage HCT-116 and Duke's type C-stage SW-620), significantly improving survival compared to untreated mice. Expression of the viral marker gene ruc-gfp allowed for real-time analysis of the virus infection in cell cultures and in mice. GLV-1h68 treatment was well-tolerated in all animals and viral replication was confined to the tumor. GLV-1h68 treatment elicited a significant up-regulation of murine immune-related antigens like IFN-γ, IP-10, MCP-1, MCP-3, MCP-5, RANTES and TNF-γ and a greater infiltration of macrophages and NK cells in tumors as compared to untreated controls. Conclusion: The anti-tumor activity observed against colorectal cancer cells in these studies was a result of direct viral oncolysis by GLV-1h68 and inflammation-mediated innate immune responses. The therapeutic effects occurred in tumors regardless of the stage of disease from which the cells were derived. Thus, the recombinant vaccinia virus GLV-1h68 has the potential to treat colorectal cancers independently of the stage of progression.},
  language  = {en}
}
@article{WiegeringPfannUtheetal.2013,
  author    = {Wiegering, Armin and Pfann, Christina and Uthe, Friedrich Wilhelm and Otto, Christoph and Rycak, Lukas and M{\"a}der, Uwe and Gasser, Martin and Waaga-Gasser, Anna-Maria and Eilers, Martin and Germer, Christoph-Thomas},
  title     = {CIP2A Influences Survival in Colon Cancer and Is Critical for Maintaining Myc Expression},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0075292},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97252},
  year      = {2013},
  abstract  = {The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.},
  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}
}