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 - GrĂ¼ndemann, Dirk
A1 - Gorboulev, Valentin
A1 - Gambaryan, Stepan
A1 - Veyhl, Maike
A1 - Koepsell, Hermann
T1 - Drug excretion mediated by a new prototype of polyspecific transporter
N2 - CATIO~IC drugs of different types and structures (antihistaminics, antiarrhythmics, sedatives, opiates, cytostatics and antibiotics, for example) are excreted in mammals by epithelial cells of the renal proximal tubules and by hepatocytes in the liver1-4. In the proximal tubules, two functionally disparate transport systems are involved which are localized in the basolateral and luminal plasma membrane and are different from the previously identified neuronal monoamine transporters and A TP-dependent multidrug exporting proteins1-3,5-12. Here we report the isolation of a complementary DNA from rat kidney that encodes a 556-amino-acid membrane protein, OCT1, which has the functional characteristics of organic cation uptake over the basolateral membrane of renal proximal tubules and of organic cation uptake into hepatocytes. OCTl is not homologous to any other known protein and is found in kidney, liver and intestine. As OCTl translocates hydrophobic and hydrophilic organic cations of different structures, it is considered to be a new prolotype of polyspecific transporters that are important for drug elimination.
KW - Biologie
Y1 - 1994
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59327
ER -