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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2010

Authors: Wolfesberger, B; Tonar, Z; Gerner, W; Skalicky, M; Heiduschka, G; Egerbacher, M; Thalhammer, JG; Walter, I

Title: The tyrosine kinase inhibitor sorafenib decreases cell number and induces apoptosis in a canine osteosarcoma cell line.

Source: Res Vet Sci. 2010; 88(1):94-100



Authors Vetmeduni Vienna:

Egerbacher Monika
Gerner Wilhelm
Skalicky Monika
Thalhammer Johann
Walter Ingrid
Wolfesberger Birgitt

Vetmed Research Units
University Clinic for Small Animals, Clinical Unit of Internal Medicine Small Animals
Institute of Immunology
Institute of Topographical Anatomy
Institute of Physiology, Pathohysiology and Biophysics, Unit of Physiology, Pathophysiology, and Experimental Endocrinology


Abstract:
Canine osteosarcoma, an aggressive cancer with early distant metastasis, shows still despite good chemotherapy protocols poor long term survival. The aim of our study was to determine whether sorafenib, a novel multikinase inhibitor, has any effect on D-17 canine osteosarcoma cells. A cell proliferation kit was used for detecting surviving cells after treatment for 72 h with sorafenib or carboplatin or their combination. A significant decrease of neoplastic cells was observed after incubation with 0.5-16 microM sorafenib or with 80-640 microM carboplatin. Using immunocytochemistry for activated caspase 3 to evaluate apoptosis, we found significantly more positive cells in the sorafenib treated groups. Paradoxically, expression of the nuclear proliferation marker Ki-67 was also significantly higher in sorafenib treated cells. The drug sorafenib showed potent antitumour activity against D-17 canine osteosarcoma cells in vitro, suggesting a potential as a therapeutic tool in the treatment of bone cancer in dogs.

Keywords Pubmed: Animals
Antineoplastic Agents/pharmacology
Antineoplastic Agents/therapeutic use*
Apoptosis/drug effects*
Benzenesulfonates/pharmacology
Benzenesulfonates/therapeutic use*
Bone Neoplasms/drug therapy
Bone Neoplasms/enzymology
Bone Neoplasms/veterinary*
Caspase 3/metabolism
Cell Count
Cell Line, Tumor
Dog Diseases/drug therapy*
Dog Diseases/enzymology
Dogs
Flow Cytometry
Ki-67 Antigen/metabolism
Microscopy, Electron, Transmission
Niacinamide/analogs & derivatives
Osteosarcoma/drug therapy
Osteosarcoma/enzymology
Osteosarcoma/veterinary*
Phenylurea Compounds
Protein-Tyrosine Kinases/antagonists & inhibitors*
Pyridines/pharmacology
Pyridines/therapeutic use*


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