Dr Stephen W. Tuttle
Dr. Tuttle’s current NIH grant is to study the effects of curcumin, a natural plant phenolic, on radiation sensitivity in head and neck squamous cell carcinoma in vitro and in vivo. He is also examining chemically similar natural compounds to determine the properties that enhance the cancer cell response to ionizing radiation. Dr. Costas Koumenis is co-PI on these research efforts. Drs. Tuttle and Koumenis work closely with Dr. Harry Quon, a clinical radiation oncologist, interested in using these natural polyphenolics to protect against normal tissue damage in the oral mucosa of patients undergoing radiation therapy.
Dr. Tuttle has a longstanding expertise in tumor cell metabolism and redox regulation of the cellular radiation response. His lab was the first to demonstrate that glucose-6-phosphate dehydrogenase (G6PD) regulates radiation sensitivity in tumor cells by inhibiting apoptosis in a manner that is not dependent on P53 status.
Abstract: There are 40,000 cases of head and neck cancer diagnosed annually in the United States, and approximately 70% of these are at an advanced stage when initially diagnosed. Despite advances in surgery and radiation therapy, 5 year survival rates for patients with advanced stage head and neck squamous cell carcinoma remains below 30%. Moreover, even with successful treatment, as many as 20% of these patients develop second primary cancers within the nasopharyngeal cavity. We are studying the anticancer effects of polyphenolic antioxidants isolated from natural botanicals in HNSCC patients. Specifically we are looking at a class of polyphenols with Michael acceptor activity, including compounds such a curcumin, from the spice turmeric; oleocanthal, from extra virgin olive oil; and CAPE, a component of honey bee propolis. These compounds are preferentially cytotoxic in HNSCC cell lines, in vitro, and enhance the cellular response to ionizing radiation. At the same time they protect normal (nontransformed cells) against radiation-induced injury. Our specific aims are; 1) to investigate the molecular mechanisms involved in the anticancer properties of these compounds and 2) to examine the effectiveness of polyphenols in combination with ionizing radiation at inhibiting the growth of HNSCC tumors while limiting damage to the surrounding normal tissues. Since these are all natural compound, and therefore generally regarded as safe by the FDA, results from the proposed studies will translated into clinical trials for treating patients with head and neck cancer.
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