01698-A: Immunohistochemical quantification of the transcobalamin II protein and receptor in naturally occurring canine tumors.
Grant Status: Closed
AbstractAccording to the National Cancer Institute, a dog is diagnosed with cancer every 5 seconds in the United States each year. Despite advances in research, only one drug is currently FDA-approved for treatment of cancer in dogs. Unfortunately, use of this drug is limited to certain tumor types, and is complicated by adverse side effects. Cancer cells rely heavily on vitamin-B12 (cobalamin) for cell growth. Cancer cells produce transport proteins such as transcobalamin II (TCII) to scavenge vitamin-B12, and they express more vitamin-B12 receptors (TCIIR) on their surface than do healthy cells. Current research is focusing on the use of vitamin-B12 in tumor imaging as well as targeted anti-cancer therapy. Nitrosylcobalamin (NO-Cbl), a new anti-cancer compound, uses vitamin-B12 to target cancer cells. NO-Cbl is composed of vitamin-B12 bound to nitric oxide, which is toxic to cancer cells. Cancer cells cannot distinguish between circulating vitamin-B12 and NO-Cbl. NO-Cbl is bound to TCII proteins and shuttled to the TCII receptors on the cancer cells, thereby delivering a toxic nitric oxide payload. In a recent case study in dogs, NO-Cbl demonstrated significant anti-tumor response against different tumors without any systemic or local toxicity. The TCII protein and receptor have been quantified in approximately 20 different human tumors. Such work has never been performed in dogs. The purpose of this study is to quantify the TCII protein and receptor in canine tumors through immunohistochemical staining. Results from this study will be used to identify canine tumors susceptible to imaging and treatment with vitamin-B12 based analogs.
Publication(s)Bauer, J.A., et al., Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs. Invest New Drugs, 2010. 28(5): p. 694-702.
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