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Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in the United States and is increasing in incidence. Intravenous ascorbate (i.e., ascorbic acid, vitamin C), but not oral ascorbate, produces high plasma concentrations, which are in the range that are cytotoxic to tumor cells. Studies from our currently funded 2 year U01 grant CA166800 "Ascorbate-induced radiosensitization in pancreatic cancer" have demonstrated that ascorbate, in doses achievable in humans, synergizes with ionizing radiation in decreasing viability and proliferation in all pancreatic cancer cell lines examined, via a H2O2–mediated mechanism. Our recently completed phase I study demonstrated that pharmacological ascorbate combined with gemcitabine is safe and well-tolerated and may lead to overall clinical benefit in patients with stage IV pancreatic cancer. This proposal focuses on improvement of the therapeutic ratio of a standard anti-cancer therapy (ionizing radiation) using a complementary approach (high dose ascorbate), in the treatment of pancreatic cancer. If pancreatic cancer cells (relative to normal cells) are more susceptible to ascorbate-induced cytotoxicity due to increased ascorbate auto-oxidation leading to increased H2O2 production, then ascorbate would be expected to be efficacious and well-tolerated adjuvant to chemo-radiation in patients.
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论文共 268 篇作者统计合作学者相似作者
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Gloria Y. Chen, Brianne R. O'Leary,Juan Du,Rory S. Carroll, Garett J. Steers,Garry R. Buettner,Joseph J. Cullen
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Malvika Rawal, Samuel R. Schroeder,Brett A. Wagner,Cameron M. Cushing,Jessemae L. Welsh,Anna M. Button,Juan Du,Zita A. Sibenaller,Garry R. Buettner,Joseph J. Cullen
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Malvika Rawal, Samuel R. Schroeder,Brett A. Wagner,Cameron M. Cushing,Jessemae L. Welsh,Anna M. Button,Juan Du,Zita A. Sibenaller,Garry R. Buettner,Joseph J. Cullen
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