Currently Funded Studies

Summaries of Completed Studies

Evaluation of Cyclopamine as a Therapy for Canine Bone Cancer

Dr. Heather M. Wilson, Texas A&M University, First Award Grant, D10CA-308

Cancer arises from a single mutated cell possessing the power to replicate, expand and eventually form a tumor. There are many theories as to what causes and prompts progression of this process. One theory states that a cell with stem cell capabilities divides to produce new tumor-initiating cells and daughter cells. Identifying pathways that can increase sensitivity of these cells to therapeutic intervention is paramount to finding a cure for bone cancer. Cyclopamine, a chemical found in the corn lily plant, inhibits the Sonic
Hedgehog pathway, which is responsible for normal embryo development and for maintaining adult stem cells and directing the regeneration of tissues. This study will research cyclopamine’s effectiveness at inhibiting tumor-initiating cells in canine osteosarcoma cell lines. The goal is to provide a new targeted therapy for pets with osteosarcoma. More Info from MAF.

Funded as a co-sponsorship - $5,000.00

Determining the Correct Dosing for a Novel Drug to Treat Canine Lymphoma

Dr. Alfred M. Legendre, University of Tennessee, D10CA-002

Lymphoma is a common tumor of the lymph nodes of dogs that is rarely cured because the tumor becomes resistant to chemotherapy. AD 198 is a new anthracycline drug that is similar to doxorubicin, which is used in chemotherapy. Though very effective, doxorubicin causes heart toxicity, which limits the total amount that can be safely given. AD 198 shows promise in treating lymphomas that are resistant to doxorubicin, and it does not produce heart toxicity. An injectable formulation of AD 198 has been developed and evaluated in healthy dogs. This study will determine the best dose for dogs with lymphoma, and researchers will study how well AD 198 affects cancer cells so that an alternative treatment option can be available to owners and veterinarians.

Funded as a co-sponsorship - $5,000.00

Examining How Bone Cancer Develops and Resists Chemotherapy

Dr. Luke B. Borst, North Carolina State University, Pilot Study, D10CA-816A

Canine osteosarcoma is the most common bone cancer in dogs, and large and giant breed dogs are commonly affected. This tumor is highly aggressive, and less than 25 percent of dogs survive for two years after initial diagnosis and treatment with conventional therapies. Death is often due to widespread metastasis to the lungs. Treatment options, which include amputation and chemotherapy, and prognosis
for this tumor type have not improved significantly in the past 20 years because little is known about how this cancer develops, metastasizes and resists treatment. Patients whose tumor cells produce greater amounts of rapamycin (mTOR ) protein, which regulates cell growth, have a poorer prognosis and decreased survival time, but it is not known how this increased level of mTOR affects tumor development. This study will explore the role that two complexes formed by this protein, mTOR C1 and mTOR C2, play in canine osteosarcoma metabolism and anticancer drug resistance. Data from this study could help improve current treatment models and help those breeds most affected by osteosarcoma. More Info from MAF.

Funded as a co-sponsorship - $3,000.00

Cutting Balloon Valvaplasty for Dogs with Subaortic Stenosis

chief investigator, Amara H Estrada DVM, DACVIM, University of Florida

This study will explore a balloon valvaplasty procedure for canines with SAS. They will use a balloon procedure that incorporates cutting blades to score/cut the fibrous ring inherit to SAS to prevent it from re-forming. This is a treatment option that would increase the life span of the dog. More Info from AKC CHF.

Funded as a co-sponsor - $10,000

Canine Non-Hodgkin Lymphoma: Characterization and Prognostic Value in Cancer Stem Cells

chief investigator, Timothy D. O’Brien, DVM, PhD, University of Minnesota

This study will concentrate on the function of stem cells in lymphoma. Does a population of stem cells become enriched and drive the cancer cells? The goal is to discover these cancer stem cells and target their disruption. More Info from AKC CHF.

Funded as a co-sponsor - $5,000

Measurement of Minimal Residual Disease Using real Time PCR in Canine Lymphoma

chief investigator, Susan E. Lana, DVM, DACVIM, Colorado State University

This study will use real time PCR to detect the residual that cannot be otherwise identified in biological samples. More Info from AKC CHF.

Funded as a co-cponsor - $5,000

Genetic Background and the Angiogenic Phenotype in Cancer

chief investigator, Dr. Jaime Modiano, VMD, PhD, at the University of Minnesota.

This study is multi-faceted with the potential for determining breed specific genetic profiles, improved treatments for all dogs, and comparative disease characterization for human medicine. More Info from AKC CHF.

Funded as a co-sponsors - $10,000

D09CA-303: Prospective Objective Evaluation of the Surgical Treatment of
Fragmented Coronoid Processes in Dogs, Ursula Krotscheck, DVM

UPDATE: Fragmented coronoid process (FCP) is a frequent source of forelimb lameness in dogs. With this condition, two of the three bones that compose the elbow joint grow unequally, causing a fractured fragment. Removal of the fragment is the treatment of choice, yet decreasing the weight bearing in this area would be preferable to slow arthritis progression. Recent reports have suggested that arthritis progression could be decreased by cutting the ulna, allowing it to rotate out of the way, and reducing any remaining joint incongruity. The ulna is a non–weight-bearing bone, meaning that cutting it will not affect the dog's gait or comfort. Researchers from Cornell University are comparing the outcomes of two surgical techniques, the commonly used technique of arthroscopic fragment removal and a newer treatment option of making an additional cut in the ulna to help prevent arthritis progression. Researchers will be recruiting dogs for this study over the next 8 to 12 months. To date, five dogs are enrolled, two of which have reached the six-month recheck point. This study should help owners determine the best possible surgical intervention strategy for their dogs suffering from FCP. In addition, it will provide insight into the rate and degree of arthritis development after FCP.

UPDATE 3/5/11: Fragmented coronoid process (FCP) is a frequent source of forelimb lameness in dogs. With this condition, two of the three bones of the elbow joint grow unequally, causing a fractured fragment. Removal of the fragment is the treatment of choice, but decreasing the weight bearing in this area is preferable because it would slow arthritis progression. Recent reports have suggested that arthritis progression could be decreased by cutting the ulna, allowing it to rotate out of the way and reducing any remaining joint incongruity. The ulna is a non–weight-bearing bone, meaning that cutting it will not affect the dog's gait or comfort. Researchers from Cornell University are comparing the outcomes of two surgical techniques to determine which better prevents arthritis progression: the commonly used technique of arthroscopic fragment removal and a newer treatment option, ulnar osteotomy, that makes an additional cut in the ulna.

Researchers are still in the process of recruiting dogs for the study and have requested a one-year extension to reach their enrollment goal and add statistical power to their data analysis. To date, seven dogs have been recruited, three of which have completed the study. Although it is too early to determine whether the addition of ulnar osteotomy makes a significant difference in the long-term outcome of these dogs, preliminary observations at the six-month postoperative check show that the dogs receiving surgical correction of FCP, including both ulnar osteotomy and fragment removal, showed a noticeable improvement in their gaits. One of these dogs has recovered completely and now bears equal weight on both front legs. Another dog that received the commonly used arthroscopic fragment removal but not the ulnar osteotomy improved but had not completely regained normal gait as of the six-month follow-up. This study should help determine the best possible surgical intervention strategy for dogs suffering from FCP. In addition, it will provide insight into the rate and degree of arthritis development after FCP.

D09CA-083: Phase I Trial-Development of Bone-Seeking Nanoparticles Encapsulating Doxorubicin for Canine Appendicular Osteosarcoma, Timothy M. Fan, DVM, PhD

Osteosarcoma is a bone cancer that occurs most commonly in large dogs. As the cancer grows within the bone, it causes debilitating pain, which can usually be alleviated only through limb amputation. Following amputation, many dogs return to near-normal levels of physical activity and quality of life, but many pet owners are interested in alternative treatments that preserve the limb. To address this issue, researchers from the University of Illinois are designing and testing the safety and effectiveness of a novel chemotherapy delivery system —encapsulating doxorubicin in nanoparticles and delivering the anticancer drug directly to the tumor growth site.

UPDATE 9/14/10: This project remains in the early phases of execution. To date, researchers have treated only a few dogs with osteosarcoma, none of which showed overt adverse reactions. The researchers originally planned to track the long-term accumulation of the nanoparticles through computed tomography, a radiological imaging technique, using the contrast agent iohexol. However, in the first two dogs studied, iohexol did not provide appreciable contrast for detecting and studying the nanoparticles within the tumors, so the researchers abandoned the use of iohexol as a viable contrast agent. They are now exploring the possibility of fabricating bone-seeking nanoparticles containing gold, an inert mineral that has been used successfully in bone imaging studies in humans. The study of bone-seeking nanoparticles containing chemotherapeutics will lead to the development of more effective treatments for canine osteosarcoma.

UPDATE 4/15/11: To date, researchers have treated five dogs with bone-seeking nanoparticles containing either saline (control group) or doxorubicin. All dogs tolerated the treatment well, and none had overt clinical adverse reactions. The dogs receiving doxorubicin showed no signs of toxicity associated with the nanoparticle delivery system or the drug itself. Samples, including blood and urine, have been collected from all patients and will be assessed at the end of the study. Nuclear scintigraphy data indicate that bone-seeking nanoparticles accumulate within the bone tumor, and researchers are optimistic that the nanoparticles containing high concentrations of doxorubicin will be able to kill tumor cells. With these preliminary findings, researchers hope that the study of bone-seeking nanoparticles containing chemotherapeutics will lead to the development of more effective treatments, improving therapies for dogs suffering from osteosarcoma.

Pooled Association Mapping for Canine Hereditary Disorders

principal investigator: Dr. Gregory M. Acland, Cornell University

More than 450 canine genetic traits are listed on the Online Mendelian Inheritance in Animals list. These traits affect all body systems in dogs and can cause health problems ranging from mild disease susceptibility to severe illness and death. Researchers will use a genetic tool called the Affymetrix Canine SNP Chip to develop a mapping strategy using pooled DNA samples that will map genes for hereditary canine disorders. This method promises to be 10 times more efficient and cost effective than current methods for analyzing canine inherited traits. Once this method is validated, it will be used to map a series of hereditary retinal disorders affecting multiple breeds.

UPDATE 9/14/10: More than 450 canine diseases have an underlying genetic cause, so the task of researching and identifying genetic reasons for disease traits is daunting. Researchers from Cornell University are exploring a more efficient way to use canine SNP (pronounced "snip") chips to identify genetic mutations. Specifically, they have developed a pooled sample strategy that rapidly identifies genes for hereditary canine retinal disorders that cause blindness. With a pooled-sample strategy, scientists combine the DNA from several affected dogs into one sample and analyze them together. This allows more samples to be tested at a reduced cost. So far, the researchers have mapped the chromosomal location of genes for cone-rod dystrophy (a deterioration of the cones and rods in the retina) in American pit bull terriers and Irish Glen of Imaal terriers and have successfully developed a new DNA diagnostic tool for these breeds. This test is now available and will enable elimination of these diseases through informed breeding practices. These researchers are continuing to optimize the pooling strategy and are in the process of a genome-wide association mapping for cone-rod dystrophy in American Staffordshire terriers, adult-onset progressive retinal atrophy (degeneration of retina) in Italian greyhounds and coloboma (an absence or defect in the ocular tissue) in collies and other breeds. This project has established a more cost-efficient way of undertaking genome-wide association mapping studies using currently available SNP genotyping technology. This will, in turn, make the technology more widely accessible, applicable and affordable for the future development of DNA-based diagnostic tests.

UPDATE 3/5/11: Researchers have also completed a genome-wide association mapping for cone-rod dystrophy in American Staffordshire Terriers and for adult-onset progressive retinal atrophy (degeneration of retina) in Italian Greyhounds and have identified the location of candidate genes for further evaluation. The next step is to identify causative gene mutations and develop DNA diagnostic tests for these breeds. The researchers are also assessing a recently made available SNP chip platform for pooled-sample genotyping, which can yield twice as many genotypes as their original testing method at nearly half the cost. They are currently using this new method to perform genome-wide association mapping for colobomas (an absence or defect in the ocular tissue) in Collies, Border Collies, Australian Shepherds and Soft Coated Wheaten Terriers. This project continues to establish more cost-efficient ways of identifying the causative mutations for genetic diseases. This will make the tools for future development of DNA-based diagnostic tests more widely accessible and affordable and, thereby, allow for many of the genetic diseases affecting dogs to be eliminated.

Heritable and Sporadic Genetic Lesions in Canine Lymphoma

Dr. Breen, North Carolina State University and
Dr. Jaime Modiano, University of Colorado

It has been apparent for some time that certain dog breeds are prone to develop certain types of cancer. Specifically, studies completed between the late 1960's and the early 1980's defined relative risk of lymphoma for different dog breeds. Yet, there was little progress since then to define factors that account for this risk. As part of ongoing programs supported by the AKC CHF in our laboratories, we showed recently that the breed-specific risk of lymphoma extends beyond the simple disease condition to a predisposition for specific forms of lymphoma. More importantly, we showed there are recurrent chromosomal abnormalities that segregate with specific forms of lymphoma and that are more common in Golden Retrievers (with that form of the disease) than in other breeds, suggesting breed-specific profiles of genetic abnormalities will be found in canine lymphoma. To continue this work, we plan to use contemporary "array-based" technologies to identify genes that map to these regions and how they contribute to the disease. We anticipate that the results from this work will allow us to predict how heritable factors influence the occurrence of abnormalities in these genes, and will set the groundwork to identify specific genes associated with breed-dependent cancer risk. More Info from AKC CHF

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