title: Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy.
abstract: Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds.
authors.affiliation: Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Shoucheng
authors.initials: S
authors.lastname: Ning
authors.affiliation: Department of Radiology, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Bednarski
authors.affiliation: RadioRx, Inc., Mountain View, CA 94040, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Oronsky
authors.affiliation: RadioRx, Inc., Mountain View, CA 94040, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Scicinski
authors.affiliation: Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305, USA. Electronic address: sknox@stanford.edu.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Knox
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004852:Epoxy Compounds / Q000627:therapeutic use*; D019073:HT29 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D009566:Nitrates / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects*
chemical_list: D001565:Benzoates; D004852:Epoxy Compounds; D007093:Imidazoles; D009566:Nitrates; D020030:Nitric Oxide Donors; D011838:Radiation-Sensitizing Agents; C000589983:glycidyl nitrate; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide
keywords: Blood flow; Cancer; Chemotherapy; Nitric oxide; Radiotherapy