Australian Terrier International supports the Canine Health Foundation. ATI has donated $2500.00 to each of these ongoing research projects listed below:
Grant 1429: Mechanistic Relationship of IL-8 in Cell Proliferation and Survival of Canine Hemangiosarcoma
Grant Amount: $100,000
Dr. Jaime F Modiano, VMD PhD, University of Minnesota
Abstract (written by the investigator):
New insights into the mechanisms that control tumor progression have provoked considerable interest in the interaction of cancer cells with their microenvironment. Specifically, a molecule called IL-8 that can support tumor growth and survival, also recruits inflammatory cells and promotes blood vessel formation in the local tumor environment, enhances resistance to therapy, and facilitates metastasis in various aggressive cancers. Hemangiosarcoma (HSA) is an incurable, highly metastatic cancer that occurs commonly in dogs. There is virtually nothing known about how tumor cells and the microenvironment interact with each other in HSA, and more specifically, a role for IL-8 has not been investigated. In a recent study funded by CHF grant 422, we showed upregulation of IL-8 was a consistent feature that distinguished HSA cells from non-malignant endothelial cells, suggesting IL-8 might play a significant role in this disease. For this project, we will characterize the direct effects of IL-8 on HSA cells, an essential first step in the process to establish if and how this pleotropic molecule modulates disease progression. Our results will begin to clarify the importance of IL-8 production by HSA cells, and provide the foundation for subsequent studies to define its role regulating interactions between HSA cells and their microenvironment.
Grant 1139: Immune Targeting of Canine Hemangiosarcoma Using a Canine Derived Single Chain Antibody Approach
Grant Amount: $123,125.4
Dr. Nicola J Mason, BVetMed, PhD, University of Pennsylvania
Background: Canine hemangiosarcoma is a common and highly aggressive tumor of blood vessels that is often fatal. At diagnosis most dogs have evidence of metastatic disease and despite chemotherapy, survival times rarely exceed 6 months. New approaches to the treatment of this disease are needed. The use of monoclonal antibodies and antibody fragments to directly target different tumors has shown promise in clinical trials in man.
Objective: This project aims to use a new canine synthetic antibody system to target the tumor and deliver cytotoxic agents directly to both primary and metastatic lesions. Using advanced molecular techniques, the researchers intend to review antibody responses that dogs with hemangiosarcoma may make against their own tumors and use these as a template to generate canine antibody fragments that specifically recognize tumor particles. Tumor-specific antibody fragments will be linked to an exotoxin and evaluated for their ability to kill canine hemangiosarcoma cells in vitro. This allows for the direct delivery of cytotoxic agents to the tumor, which decreases side effects and increases therapeutic value. This work aims to develop the first canine-derived, tumor-specific targeting approach for the treatment of HSA and to provide proof-of-principal for this approach that can then be used to therapeutically target many other tumor types in this species in vivo.
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