We have been developing strategies to utilize nitric oxide (NO) in cancer treatment. In addition to the use of synthetic NO donors, we are researching the mechanisms that control the endogenous cellular production. In collaboration with Martin Brechbiel, we are synthesizing and testing a new line of NO donating complexes of tamoxifen. We are evaluating their effectiveness to specifically target cells that have a high expression of the estrogen receptor. In addition, we are exploring ruthenium complexes that can release NO under different biological redox conditions. In our previous studies, we were able to show that nitrosative chemistry can dramatically increase the efficacy of some chemotherapeutic agents through the inhibition of DNA repair proteins such as PARP. Growth factor receptors IGFR and EGFR, but not VEGFR, are also negatively affected by nitrosation. The analytical methods for the study of NO and related reactive nitrogen oxide species in cells and tissue are complex. We have developed a series of sensitive techniques to monitor intracellular reactive nitrogen oxide chemistry. This will provide a valuable probe in designing new transfected cells as well as new drugs that can specifically target NO chemistry to the tumor.
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