2009 Studies

“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.

“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.

“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.

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