Gordon Miller Saul
Adjunct Professor, Bioengineering
Administrative Appointments
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Executive Director, Byers Center for Biodesign (2013 - Present)
Professional Education
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AB, Dartmouth College, Engineering Sciences (Chemistry) (1984)
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MBA, Stanford University (1991)
All Publications
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Dinitroazetidines Are a Novel Class of Anticancer Agents and Hypoxia-Activated Radiation Sensitizers Developed from Highly Energetic Materials
CANCER RESEARCH
2012; 72 (10): 2600-2608
Abstract
In an effort to develop cancer therapies that maximize cytotoxicity, while minimizing unwanted side effects, we studied a series of novel compounds based on the highly energetic heterocyclic scaffold, dinitroazetidine. In this study, we report the preclinical validation of 1-bromoacetyl-3,3-dinitroazetidine (ABDNAZ), a representative lead compound currently in a phase I clinical trial in patients with cancer. In tumor cell culture, ABDNAZ generated reactive free radicals in a concentration- and time-dependent manner, modulating intracellular redox status and triggering apoptosis. When administered to mice as a single agent, ABDNAZ exhibited greater cytotoxicity than cisplatin or tirapazamine under hypoxic conditions. However, compared with cisplatin, ABDNAZ was better tolerated at submaximal doses, yielding significant tumor growth inhibition in the absence of systemic toxicity. Similarly, when combined with radiation, ABDNAZ accentuated antitumor efficacy along with the therapeutic index. Toxicity studies indicated that ABDNAZ was not myelosuppressive and no dose-limiting toxicity was apparent following daily administration for 14 days. Taken together, our findings offer preclinical proof-of-concept for ABDNAZ as a promising new anticancer agent with a favorable toxicity profile, either as a chemotherapeutic agent or a radiosensitizer.
View details for DOI 10.1158/0008-5472.CAN-11-2303
View details for Web of Science ID 000307346800015
View details for PubMedID 22589277
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Dinitroazetidines are a novel class of anticancer agents and hypoxia-activated radiation sensitizers developed from highly energetic materials
AMER ASSOC CANCER RESEARCH. 2011
View details for DOI 10.1158/1538-7445.AM2011-676
View details for Web of Science ID 000209701401421