TY  - JOUR
A1  - Adelfinger, Marion
A1  - Bessler, Simon
A1  - Cecil, Alexander
A1  - Langbein-Laugwitz, Johanna
A1  - Frentzen, Alexa
A1  - Gentschev, Ivaylo
A1  - Szalay, Aladar A.
T1  - Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti-VEGF Single-Chain Antibody for Canine Cancer Therapy
JF  - Viruses
N2  - Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a novel approach for canine cancer therapy. Here we describe, for the first time, the characterization and the use of VACV strain GLV-5b451 expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as therapeutic agent against different canine cancers. Cell culture data demonstrated that GLV-5b451 efficiently infected and destroyed all four tested canine cancer cell lines including: mammary carcinoma (MTH52c), mammary adenoma (ZMTH3), prostate carcinoma (CT1258), and soft tissue sarcoma (STSA-1). The GLV-5b451 virus-mediated production of GLAF-2 antibody was observed in all four cancer cell lines. In addition, this antibody specifically recognized canine VEGF. Finally, in canine soft tissue sarcoma (CSTS) xenografted mice, a single systemic administration of GLV-5b451 was found to be safe and led to anti-tumor effects resulting in the significant reduction and substantial long-term inhibition of tumor growth. A CD31-based immuno-staining showed significantly decreased neo-angiogenesis in GLV-5b451-treated tumors compared to the controls. In summary, these findings indicate that GLV-5b451 has potential for use as a therapeutic agent in the treatment of CSTS.
KW  - canine cancer therapy
KW  - canine soft tissue sarcoma (CSTS)
KW  - oncolytic virus
KW  - cancer
KW  - canine cancer cell lines
KW  - antibody production
KW  - angiogenesis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125705
VL  - 7
ER  - 
TY  - JOUR
A1  - Cardani, Diego
A1  - Sardi, Claudia
A1  - La Ferla, Barbara
A1  - D'Orazio, Guiseppe
A1  - Sommariva, Michele
A1  - Marcucci, Fabrizio
A1  - Olivero, Daniela
A1  - Tagliabue, Elda
A1  - Koepsell, Hermann
A1  - Nicotra, Francesco
A1  - Balsari, Andrea
A1  - Rumio, Christiano
T1  - Sodium glucose cotransporter 1 ligand BLF501 as a novel tool for management of gastrointestinal mucositis
JF  - Molecular Cancer
N2  - Background: Recent studies demonstrated that engagement of sodium glucose transporter 1 (SGLT-1) by orally administered D-glucose protects the intestinal mucosa from lipopolysaccharide (LPS)-induced injury. We tested whether SGLT-1 engagement might protect the intestinal mucosa from doxorubicin (DXR)- and 5-fluorouracil (5-FU)-induced injury in animal models mimicking acute or chronic mucositis. 
Methods: Mice were treated intraperitoneally with DXR, alone or in combination with 5-FU, and orally with BLF501, a glucose-derived synthetic compound with high affinity for SGLT-1. Intestinal mucosal epithelium integrity was assessed by histological analysis, cellular proliferation assays, real-time PCR gene expression assays and Western blot assays. Student's t-test (paired two-tailed) and X-2 analyses were used for comparisons between groups. Differences were considered significant at p < 0.05. 
Results: BLF501 administration in mice treated with DXR and/or 5-FU decreased the injuries to the mucosa in terms of epithelial integrity and cellular proliferative ability. Co-treatment with BLF501 led to a normal expression and distribution of both zonula occludens-1 (ZO-1) and beta-catenin, which were underexpressed after treatment with either chemotherapeutic agent alone. BLF501 administration also restored normal expression of caspase-3 and ezrin/radixin/moesin (ERM), which were overexpressed after treatment with DXR and 5-FU. In SGLT1-/- mice, BLF501 had no detectable effects. BLF501 administration in wild-type mice with growing A431 tumors did not modify antitumor activity of DXR. 
Conclusions: BLF501-induced protection of the intestinal mucosa is a promising novel therapeutic approach to reducing the severity of chemotherapy-induced mucositis.
KW  - apoptosis
KW  - prevention
KW  - doxorubicin
KW  - cancer
KW  - gastrointestinal mucositis
KW  - SGLT-1
KW  - synthetic D-glucose analogy
KW  - chemotherapy
KW  - inflammation
KW  - clinical practice guidelines
KW  - intestinal mucositis
KW  - epithelial cells
KW  - oral mucositis
KW  - gene-expression
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117352
SN  - 1476-4598
VL  - 13
IS  - 23
ER  -