""""""""We have been following two lines of research for developing strategies to utilize nitric oxide (NO) in cancer treatment. The first is by the use of NO donor compounds while the second is to control this diatomic radical's cellular production by modulating different cytokines. We have catalogued the effect of various NO donors on sensitizing hypoxic mammalian cells to radiation as well as evaluating the effects of these compounds on the cytotoxicity of different chemotherapeutic alkylating agents. We have been probing different methods which provide the correct NO chemistry from leukocytes and cells transfected with inducible nitric oxide synthase. Our goal is to create cells that produce the correct chemical stress in the local region of the tumors. We have developed a flourimetric assay which is able to screen various different cells for nitrosative stress. Our chemical donor experiments have suggested that nitrosative stress is the chemical profile most effective in enhancing the chemotherapeutic and radiation sensitization. A variety of murine macrophage cell lines have been examined with different cytokine and lipid polysaccharides. It appears that the optimal nitrosative stress was obtained in the presence of the lipid polysaccharides and not TNFa or IL-1b. Furthermore, we have examined different human tumor cells transfected with inducible nitric oxide synthase. It appears that maximal nitrosative stress is achieved from cytokine stimulated macrophages. Taking stimulated macrophages and co-culturing them with MCF7 human breast cancer cells have shown augmentation of the cytotoxicity of melphalan by over 100 times in preliminary experiments.""""""""
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