Thesis
Novel targeted therapies for the treatment of equine sarcoid tumors
Washington State University
Master of Science (MS), Washington State University
2013
Handle:
https://hdl.handle.net/2376/101143
Abstract
Sarcoids are the most common skin tumor in horses, affecting equine populations worldwide. Known for their unpredictability and invasiveness, sarcoids present a major therapeutic challenge, often requiring multiple treatments and resulting in significant economic loss for the equine industry. Unfortunately, there is no universally successful treatment. Our goal is to establish two novel targeted therapeutic approaches as new treatment paradigms for sarcoids in horses. The first approach is electrochemotherapy, a new and innovative modality that combines electric pulses and chemotherapeutic drugs. The application of electric pulses destabilizes the cell membrane increasing drug uptake and therefore enhancing their cytotoxic effects. The second approach is suicide gene therapy, which entails the delivery of a foreign gene to tumor cells combined with the administration of a prodrug. The gene encodes a suicide enzyme capable of converting a non-toxic prodrug into toxic metabolites, leading to targeted cell death. The use of electrochemotherapy to treat equine sarcoid tumors has already been reported in a retrospective study; however, the protocol utilized was based on human studies. In our study we tested the in vitro effects of electrochemotherapy in equine sarcoid cells. We chose to test the chemotherapeutic drug that is most commonly used to treat sarcoids (cisplatin) and two other drugs in combination with electric pulses. Our results indicate that when combined with electric pulses the drugs are capable of increased killing effects and a significant decrease in the IC50 is observed. To assess the effects of suicide gene therapy in equine sarcoid cells, we transfected cells with two improved mutants of the bacterial cytosine deaminase (bCD-1525) and of the Herpes Simplex Virus thymidine kinase (HSVTK-SR39) suicide genes. Such genes have already been tested and proven to work successfully in vitro and in vivo in different human tumor types. Our results show that the genes can be successfully delivered and expressed in the equine sarcoid cells and are capable of sensitizing the cells to the prodrugs ganciclovir and 5-fluorocytosine.
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Details
- Title
- Novel targeted therapies for the treatment of equine sarcoid tumors
- Creators
- Camila Rios Salomao de Souze
- Contributors
- Margaret E. Black (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900525395901842
- Language
- English
- Resource Type
- Thesis