Funded Studies

Chase Away K9 Cancer Grant List

The grants listed below have already been funded with the help of the Chase campaign and demonstrates how each dollar you donate helps. We will provide an update on these studies once they are completed. We are so touched by the generosity of everyone who has supported this campaign.

In 2010 Chase Away K9 Cancer will fund the second year of Dr. Jennifer Ginn's Fellowship at the University of Wisconsin-Madison:

"Glutathione-S-transferase polymorphisms in dogs; association with risk for lymphoma and response to chemotherapy"

Dr. Jennifer Ginn, DACVIM (Small Animal Internal Medicine)
Mentors: Dr. Lauren Trepanier, DACVIM (Small Animal Internal Medicine) and Dr. Ruthanne Chun, DACVIM (Oncology)

Lymphoma is the most common cancer in dogs and closely resembles Non-Hodgkins lymphoma in people. Although lymphoma is often initially responsive to chemotherapy, long term survival in dogs is rare.

Dr. Ginn is studying a gene called glutathione transferase (GST) in dogs with lymphoma. The GST gene encodes an enzyme (also called GST), which helps to rid the body of certain environmental toxins. When there is a mutation in this gene, the enzyme’s function is decreased or lost, and the body is exposed to a higher level of these environmental toxins, some of which can cause cancer. Mutations in the GST gene have been associated with lymphoma and many other types of cancers in people, most likely because the body is exposed to more environmental toxins that cause cancer.

The GST enzyme is also responsible for metabolizing chemotherapy drugs, so mutation of the GST gene may lead to a longer time that the drug remains in the body, making the drug more effective, but also more toxic. The goal of Dr. Ginn's study is to identify the GST gene in dogs and to evaluate whether dogs with lymphoma have a higher frequency of mutations in this gene. They are also monitoring the progress of dogs with lymphoma that are treated with chemotherapy and looking to see whether mutations in the GST gene are associated with differences in survival time and toxicity to chemotherapy drugs.

When Dr. Ginn started her project about a year ago, her first goal was to find the GST gene in dogs. She has been able to isolate this gene and to prove that it exists and is active in the white blood cells that give rise to lymphoma (lymphocytes).

"Our hope is to discover a link between mutations in the GST gene and risk for lymphoma. This would support the idea that the body’s detoxification system plays a role in the risk of developing this cancer, and might help us to better understand any possible relationships between exposure of dogs to pesticides and other pollutants and the development of lymphoma. These results might also help us to design treatments to enhance this detoxification system, hopefully reducing the risk of cancer in dogs. An added benefit to this research is that lymphoma in dogs is similar to lymphoma in people, and the information we gain from this research may help people as well," states Dr. Ginn.

Grant#08-34D

"Efficacy of Vitamin D (Calcitriol) for Treatment of Canine Mast Cell Tumors." Dr. Kenneth Rassnick — $8,214.00 year one; $11,644.00 year two ($19,878.00 total for 2-year grant).

Mast cell tumors are common skin tumors in dogs. There is a tremendous need to develop effective therapies for this cancer in dogs. Calcitriol is the active form of vitamin D, and the potential for calcitriol as an anti-cancer agent has been demonstrated in laboratory studies. Clinical trials of calcitriol in people with cancer are underway.

Dr. Rassnick and his colleagues have established a safe oral dosing regimen for calcitriol in dogs and have already observed regression of an advanced mast cell tumor in a dog treated with calcitriol. The objectives of this proposal are to investigate the anti-tumor activity of calcitriol against a canine mast cell tumor cell line. Additionally, they will conduct a clinical trial using oral calcitriol to treat dogs with naturally occurring mast cell tumors. They expect that the results of this research will show that calcitriol is an effective treatment for mast cell tumors in dogs. These results will significantly impact the management of dogs with mast cell tumors as they will lead to future use of calcitriol as a palliative and/or standard therapy in dogs with this disease.

Grant#08-36D

"Preclinical Evaluation of Two-Photon-Targeted Photodynamic Therapy Triads." Dr. Antonella Borgatti-Jeffreys — $14,769.00 (1-year grant).

A significant effort has been made over the past decade to apply novel cancer treatments, but the vast majority of tumors are still managed via conventional therapy (surgery, chemotherapy, radiation therapy). Fine adjustment of conventional therapies is unlikely to improve outcomes much beyond what has been achieved over the past 30 years.

In contrast, photodynamic therapy (PDT), which leads to cancer cell death through a light-activated cancer drug (called a photosensitizer), is a cost-effective, noninvasive, contemporary treatment with considerable potential for development. Recent studies have successfully applied a newly developed PDT compound composed by 3 elements: (1) a photosensitizer, (2) a molecule that directs the photosensitizer to a specific tumor, and (3) an imaging agent that allows image-guided PDT even below the skin surface, at light doses that are harmless to surrounding tissues.

This technology can overcome the pitfalls of traditional PDT, which is unable to penetrate the skin more than a few millimeters, and which does not always discriminate between cancerous and normal tissue. This study will investigate if a new type of PDT compound can be used to target canine tumors. The investigators will use tumors known to express the receptors of interest to confirm PDT can target and kill these cancer cells. This will justify future safety and efficacy studies in tumor-bearing dogs that will set the stage for clinical use of this compound in tumor-bearing dogs. An additional benefit will be the extension of this information to the development of this drug for people with similar tumors.

Grant#08-24D

"Matrix Metalloproteinase-2 and -9 and Cathepsin-B in Canine Meningiomas." Dr. Christopher Mariani — $7,652 year one; $3,872 year two ($11,524 total 2-year grant).

Meningiomas are common tumors of the membranes covering the brain. These tumors behave more aggressively in dogs than in other species, often invading adjacent normal brain tissue, and are difficult to effectively treat with conventional therapies, such as surgery. The investigators hypothesize that certain enzymes, matrix metalloproteinase-2 and -9, and cathepsin B, contribute to the invasive nature of these tumors, as has been demonstrated with other tumor types, and propose to evaluate this hypothesis through a number of techniques. Understanding the biological basis of this aggressive behavior is critical to designing newer and more effective therapies for these devastating tumors.

Grant #07-29R/Chase. Resident.

“Clinical Evaluation of Carboplatin plus Gemcitabine in Canine Osteosarcoma.” Dr. Cheryl London and Dr. Melanie McMahon (Resident) — $49,680.00 (1-year grant). The Ohio State University.

Osteosarcoma (OSA) is the most common bone tumor in dogs occurring primarily in the long bones resulting in bone destruction, pain, lameness and metastasis primarily to the lungs. Treatment involves limb amputation followed by chemotherapy. Despite the treatment, approximately 90% of dogs with OSA will die of metastasis within 2 years of amputation. Therefore, it is critical that more effective treatments be developed.

Gemcitabine is a chemotherapy drug that incorporates into the cell DNA, eventually leading to cell death. In a previous study funded by the ACVIM Foundation, the investigators have generated data demonstrating the efficacy of gemcitabine against canine OSA tumor cells in the laboratory. They have also demonstrated that when gemcitabine is combined with carboplatin, killing of tumor cells is greater than when either drug is used alone.

Objective: based on these encouraging preliminary findings, as well as evidence for superior clinical activity of combined gemcitabine and carboplatin for the treatment of human cancers, the investigators have initiated a clinical trial to determine whether gemcitabine administered in combination with carboplatin will improve outcome in dogs with OSA. In this study, 50 dogs with appendicular OSA will undergo limb amputation followed by four treatments with carboplatin and gemictabine administered on the same day. Dogs will then be followed to determine whether the combination of these two drugs is capable of significantly prolonging 1 year survival rates in affected dogs.

This clinical trial, funded by the ACVIM Foundation’s Chase Away K9 Cancer Campaign, represents a joint effort between the Ohio State University Veterinary Teaching Hospital and the New England Veterinary Medical Oncology Group in Waltham, MA.

Grant#07-33D/Chase. Diplomate.

“Developing novel single chain targeted agents for canine hemangiosarcoma.” Dr. Nicola Mason — $30,314.00 year one; $17,000.00 year two ($47,314.00 total for 2-year grant). University of Pennsylvania.

Canine hemangiosarcoma is an aggressive cancer of blood vessels that commonly affects large breed dogs. Currently, available chemotherapeutic regimens results in a median survival time of approximately 6 months. Recently, adjuvant immunotherapies (treatments to stimulate or restore the ability of the immune (defense) system to fight infection and disease) have extended the survival times but mortality rates remain high and novel targeting approaches for the treatment of this disease are needed. The use of target specific antibodies to directly target the tumors has shown promising results in human clinical trials. For the antibodies to be effective they first need to recognize the enemy that is the antigen. In dog models this immunotherapy approach has a great limitation because in dogs the tumor antigens have not been identified.

Objective: In this proposal, the investigators aim to use molecular techniques developed in their laboratory to generate a specific antibody from canine patients with hemangiosarcoma and screen them to identify an antibody that specifically targets cancerous blood vessel cells (antigens in this case). This work aims to break the self-tolerance (where the antibodies will not destroy the normal cells) and generate antibody responses against their own tumors in dogs.

Grant #06-11/Chase.Resident.

“Investigating the Biologic Activity of Gemcitabine in Canine Osteosarcoma.” Dr. Cheryl A. London and Dr. Melanie McMahon (Resident). Study sponsored in partnership with Chase Away K9 Cancer Campaign and the Sacramento Valley Dog Fanciers Association

Osteosarcoma (OSA) is the most common bone tumor in dogs, reportedly occurring in over 8,000 dogs each year in the United States and representing up to 85% of all bone malignancies. OSA occurs most often in the long bones and is locally aggressive causing local destruction of bone, leading to non weight bearing lameness on the affected limb. Treatment involves amputation of the affected limb followed by chemotherapy. However, approximately 90% of dogs with OSA will die of cancer spreading to other organs primarily lungs. To improve the survival advantage, new therapeutic approaches need to be explored. Gemcitabine is a synthetic analog of cytosine arabinoside that has anti-tumor activity in a variety of human cancers. Recent laboratory data and mouse models suggest that it can inhibit the viability and growth of human OSA cells.

Objective: the purpose of this study is to evaluate the anti-tumor activity of Gemcitabine against canine OSA cell lines to assess whether this chemotherapeutic agent has potential clinical utility. Additionally, the ability of Gemcitabine to work synergistically with other agents such as small molecule inhibitors and bisphosphonates, both of which have some activity against OSA, will be tested. This study may lead to a new treatment option for OSA.