01194-A: Role of Hypoxia-Related Factors in Dog Glioblastoma Invasion
Grant Status: Closed
Project SummaryData from the principal investigator's laboratory demonstrated the isolation of glioblastoma in cell culture and the existence of cancer stem cells (CSCs) in dog glioblastoma for the first time. This finding implies that a minority of tumor cells in dog glioblastoma is responsible for resistance to conventional treatment modalities and maintaining and spreading the tumor cells into the brain. The underlying mechanism(s) of cancer stem cell migration needs to be fully understood to help us to design a novel therapeutic regimen for glioblastoma in dog and human. We have demonstrated that oxygen deprivation or "hypoxia" is a significant factor determining cancer stem cells migration and resistance to conventional therapy in dog glioblastoma, which is the most dreadful brain tumor in human and dog. The long term goal of our study is to understand the mechanism(s) underlying CSC differentiation into mature, non-migrating neural cells, which will help us to design novel therapeutic approaches to eliminate these invasive CSCs in dog glioblastoma. The cancer stem cells in glioblastoma are the ones which invade the brain, and we propose to target these cells by using conventional therapy and also growth factors that induce differentiation of CSCs to a mature form, which are more amenable to conventional therapy. The invasive nature of glioma cells is the obvious obstacle to effective therapy, making this issue of great significance in dog and humans.
Publication(s)"Identification of Cancer Stem Cells in Dog Glioblastoma". Veterinary Pathology, 46(3):391-406, 2009. "Dog astrocytic tumors". A review paper is submitted for publication in August, 2009.
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