TY  - JOUR
A1  - Sturm, Julia B.
A1  - Hess, Michael
A1  - Weibel, Stephanie
A1  - Chen, Nanhei G.
A1  - Yu, Yong A.
A1  - Zhang, Quian
A1  - Donat, Ulrike
A1  - Reiss, Cora
A1  - Gambaryan, Stepan
A1  - Krohne, Georg
A1  - Stritzker, Jochen
A1  - Szalay, Aladar A.
T1  - Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy
N2  - Background: Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods: Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results: We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion: Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects.
KW  - Biologie
KW  - vaccinia virus
KW  - cancer
KW  - cytokine
KW  - hyper-IL-6
KW  - oncolysis
KW  - chemotherapy
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75224
ER  - 
TY  - JOUR
A1  - Hess, Michael
A1  - Stritzker, Jochen
A1  - Härtl, Barbara
A1  - Sturm, Julia
A1  - Gentschev, Ivaylo
A1  - Szalay, Aladar
T1  - Bacterial glucuronidase as general marker for oncolytic virotherapy or other biological therapies
N2  - Background: Oncolytic viral tumor therapy is an emerging field in the fight against cancer with rising numbers of clinical trials and the first clinically approved product (Adenovirus for the treatment of Head and Neck Cancer in China) in this field. Yet, until recently no general (bio)marker or reporter gene was described that could be used to evaluate successful tumor colonization and/or transgene expression in other biological therapies. Methods: Here, a bacterial glucuronidase (GusA) encoded by biological therapeutics (e.g. oncolytic viruses) was used as reporter system. Results: Using fluorogenic probes that were specifically activated by glucuronidase we could show 1) preferential activation in tumors, 2) rena l excretion of the activated fluorescent compounds and 3) reproducible detection of GusA in the serum of oncolytic vaccinia virus treated, tumor bearing mice in several tumor models. Time course studies revealed that reliable differentiation between tumor bearing and healthy mice can be done as early as 9 days post injection of the virus. Regarding the sensitivity of the newly developed assay system, we could show that a single infected tumor cell could be reliably detected in this assay. Conclusion: GusA therefore has the potential to be used as a general marker in the preclinical and clinical evaluation of (novel) biological therapies as well as being useful for the detection of rare cells such as circulating tumor cells
KW  - Virologie
KW  - beta-glucuronidase
KW  - oncolytic virus
KW  - cancer
KW  - reporter
KW  - fluorescent probe
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69163
ER  - 
TY  - JOUR
A1  - Donat, Ulrike
A1  - Rother, Juliane
A1  - Schäfer, Simon
A1  - Hess, Michael
A1  - Härtl, Barbara
A1  - Kober, Christina
A1  - Langbein-Laugwitz, Johanna
A1  - Stritzker, Jochen
A1  - Chen, Nanhai G.
A1  - Aguilar, Richard J.
A1  - Weibel, Stephanie
A1  - Szalay, Alandar A.
T1  - Characterization of Metastasis Formation and Virotherapy in the Human C33A Cervical Cancer Model
JF  - PLoS ONE
N2  - More than 90% of cancer mortalities are due to cancer that has metastasized. Therefore, it is crucial to intensify research on metastasis formation and therapy. Here, we describe for the first time the metastasizing ability of the human cervical cancer cell line C33A in athymic nude mice after subcutaneous implantation of tumor cells. In this model, we demonstrated a steady progression of lumbar and renal lymph node metastases during tumor development. Besides predominantly occurring lymphatic metastases, we visualized the formation of hematogenous metastases utilizing red fluorescent protein (RFP) expressing C33A-RFP cells. RFP positive cancer cells were found migrating in blood vessels and forming micrometastases in lungs of tumor-bearing mice. Next, we set out to analyze the influence of oncolytic virotherapy in the C33A-RFP model and demonstrated an efficient virus-mediated reduction of tumor size and metastatic burden. These results suggest the C33A-RFP cervical cancer model as a new platform to analyze cancer metastases as well as to test novel treatment options to combat metastases.
KW  - metastasis
KW  - renal cancer
KW  - oncolytic viruses
KW  - lymph nodes
KW  - kidneys
KW  - lung and intrathoracic tumors
KW  - secondary lung tumors
KW  - cancer treatment
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119674
SN  - 1932-6203
VL  - 9
IS  - 6
ER  -