Agroterrorism - University of Georgia College of Veterinary Medicine

Comparative biomedicine investigates how a particular disease affects one species versus another;that is, how a disease manifests itself for example in a mouse versus a human or cow. Researcherscan compare diseases between species because different species oftenshare substantial genetic information. Scientists studydata such as symptoms, disease progression, treatments,mortality, and so on. Thus, one species servesas a disease model for another. And interestingly, bothspecies may benefit. For example, researchers studycardiomyopathy in dogs and humans and both havebenefited in the short- and long-term.Evaluation of Chalcone Derivatives in a MurineModel of Canine NeoplasiaTherapeutic inhibition of angiogenesis as a treatmentfor cancer has gained much interest in thelast 30 years because of the potential for broad-spectrumefficacy, lack of acquired resistance, and lowincidence of associated adverse effects. Chalconeis a biologically active flavonoid compound that iswidely distributed in edible plants. Chalcone and itsderivatives have been identified as anti-proliferativeagents and their anti-angiogenic activity has beendemonstrated in vitro. The purpose of this studywas to evaluate chalcone derivities in vivo, using amouse model of canine cancer, the anti-angiogenic,anti-tumor, and anti-metastatic activity of syntheticchalcone derivatives designed and synthesized by theUniversity of Georgia, Department of Chemistry.One goal of this study was to standardize our productionof reliable, predictably behaving models of bothcanine prostatic carcinoma and osteosarcoma. UsingBALB/c-nu/nu (athymic) mice. In the first year ofthe study, we developed the ability to reliably producetransplanted canine prostatic carcinomas with aggressive,metastatic behavior. The canine osteosarcomacell line was not reliably tumorigenic in the athymicmice so this cell line was not included in the study.In preliminary studies, we encountered difficultyin solubilizing the test compounds into a formthat would be safe and reliable for administration.Although we were able to administer the compoundsorally, poor water solubility and the potential for ineffectivedrug delivery was a concern. The Departmentof Chemistry then developed several water-solublechalcone derivatives that could be safely administeredsubcutaneously. Based on in vitro testing ofanti-angiogenic activity at Emory University, themost effective water-soluble agent was selected forevaluation in our murine model of prostatic cancer.Unfortunately, this agent was uniformly hepatotoxic,resulting in the death of the mice, even when reformulatedand dosed at ½ and ¼ of the original dose.It is unclear why a compound that should be safewas so toxic. Consequently, further development ofchalcone derivatives has been put on hold pendingrecruitment of a pharmacologist to this collaborativeeffort.Using the expertise in creating mouse models ofcancer that was acquired in this study, we haverecently initiated a novel study to investigate molecularmechanisms controlling the biologic behavior ofinjection site sarcomas in cats. This is a particularlyaggressive type of cancer that is very invasive locallyand will metastasize in approximately 25% of cats.Understanding the mechanisms responsible forthe behavior of injection site sarcomas will help topredict the behavior of this tumor in individual catsand allow the development of more specific targetedtherapies to prevent or control this cancer.PI: Dr. Nicole Northrup (northrup@vet.uga.edu)Co-PI: Dr. Karen Cornell and Dr. Nancy StedmanComparative BiomedicineVeterinary Medical Experiment Station 17