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Bioactive sphingolipids – implications for liver cancer
Liver cancer is the fifth most common form of cancer, and is the third most common cause of cancer-related death worldwide. In the western countries liver cancer is not as common, but the number of affected persons is steadily increasing. The overall aim of this project is to develop new disease markers and treatment options that cause increased cell death of liver cancer cells without affecting normal tissue. The biologically active sphingolipids ceramide and sphingosine act as tumor suppressors by inhibiting cell growth and inducing apoptosis, while other sphingolipids can contribute to growth of cancer cells, resistance against chemotherapy, angiogenesis and metastasis. Modulation of the levels of different sphingolipids has been shown to alter the balance between cell growth and apoptosis in different types of cancer. We have earlier shown that modulation of enzymes that affect sphingolipid metabolism can sensitize lymphoma cells to receptor-mediated treatment.
• How high are the levels of the different isoforms of receptors to the cancer-promoting sphingolipid sphinogsine-1 phosphate in liver cancer cells compared to normal tissue?
• Does sphingosine-1 phosphate affect migration of liver cancer cells?
• Does inhibition of ceramide/ sphingosine-clearance lead to increased cell death / decreased growth, alone or following treatment of liver cancer cell lines with chemotherapeutics?
• How does treatment with chemotherapeutics affect the levels of the sphingolipid-metabolizing enzymes?
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