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Nitric Oxide (NO) and Cancer pp 237–252Cite as

Sensitizing Effect of Nitric Oxide to Cytotoxic Stimuli

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

During irradiation of tumor tissue NO is released by myeloid cells, tumor cells, endothelial cells, and other stromal cells. By reacting with oxygen radicals NO will inflict tumor cell damage that will be added to the direct effect of DNA damage.

The relative role of the NO secreting cells during radiotherapy is not well studied and further knowledge in this field could help optimize dose and timing in order to achieve maximal tumor cell death. The use of NO donors during radiotherapy could possibly further potentiate these effects.

Release of nitric oxide and other cytotoxic molecules has been shown to mediate some of the secondary effects of chemotherapeutic agents. It is also obvious that release of nitric oxide can potentiate the cytotoxic effects of chemotherapeutic agents either by direct synergistic cytotoxic effects or by increase of blood supply and vascular permeability.

The induction of cytotoxicity by NO in vivo can boost T-cell responses by partially degrading tumor cells and thus facilitate antigen presentation of APC. Furthermore NO is essential in the early stages of T-cell activation. However prolonged secretion of NO can also induce tolerance and/or immunosuppression, which will dampen the anti-tumor immunity. Consequently, the combination of immunotherapy with NO-modulating approaches has to be specifically tailored, considering the tumor type, immunization timetable, and the suppressive network present in the tumor tissue.

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  1. The Rausing Laboratory, Section of Neurosurgery, Department of Clinical Sciences, University of Lund, 22185, Lund, Sweden

    Peter Siesjö

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  1. Peter Siesjö
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Correspondence to Peter Siesjö .

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  1. Dept. Microbiology, Immunology &, Molecular Genetics, University of California, Los Angeles, Charles E. Young Dr. E. 609, Los Angeles, 90095, California, USA

    Benjamin Bonavida

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Siesjö, P. (2010). Sensitizing Effect of Nitric Oxide to Cytotoxic Stimuli. In: Bonavida, B. (eds) Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1432-3_12

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