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Title: Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy

Highlights: • Glycidyl nitrate (GLYN) is a NO generating small molecule and has ability to release NO on bioactivation in tumor cells. • GLYN-induced intracellular NO generation was attenuated by NO scavengers. • GLYN increases tumor blood flow in tumor-bearing animal model. • GLYN significantly increased the anti-tumor efficacy of cisplatin and radiation therapy in mice. • GLYN is well tolerated with no obvious systemic toxicities at its effective therapeutic doses in preclinical animal studies. - 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 effectivemore » 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.« less
Authors:
 [1] ;  [2] ; ;  [3] ;  [1]
  1. Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305 (United States)
  2. Department of Radiology, Stanford University Medical Center, Stanford, CA 94305 (United States)
  3. RadioRx, Inc., Mountain View, CA 94040 (United States)
Publication Date:
OSTI Identifier:
22416429
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 447; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; BLOOD FLOW; CHEMOTHERAPY; DOSES; DRUGS; IN VITRO; IN VIVO; INHIBITION; MICE; MOLECULES; NEOPLASMS; NITRATES; NITRIC OXIDE; RADIOTHERAPY; SACCHARIDES; TOXICITY; TUMOR CELLS