PURPOSE: Oxygen deficiency in tumors reduces the efficacy of nonsurgical treatment modalities. We tested the hypothesis that electrical stimulation of the sciatic nerve could modify the oxygenation status and the blood flow of tumors implanted in the thigh of mice. MATERIALS AND METHODS: The sciatic nerve was electrically stimulated at 5 Hz. Local transplantable liver tumor (TLT) and fibrosarcoma (FSaII) tumor oxygen pressure (pO(2)) and perfusion measurements were carried out using electron paramagnetic resonance (EPR) oximetry and the OxyLite/OxyFlo technique. The radiosensitizing effect of the protocol was assessed by irradiating FSaII tumors with X-rays. RESULTS: Tumor pO(2) increased from approximately 3 mm Hg to approximately 8 mm Hg, and relative tumor blood flow was increased by 241% and 162% for TLT and FSaII tumor models, respectively. The effect on the tumor oxygenation was inhibited by a nitric oxide synthase (NOS) inhibitor, and an increase in the tumor nitric oxide (NO) content was observed using EPR spin-trapping. The tumor oxygen consumption rate was decreased after the stimulation protocol. In addition, the electrical stimulation of the host tissue increased regrowth delays by a factor of 1.65. CONCLUSIONS: This increase in tumor oxygenation is due to the temporary increase in tumor blood flow, but particularly to a decrease in the tumor oxygen consumption rate (inhibition of respiration) that is mediated by a local production of NO during the protocol. Those tumor hemodynamic changes resulted in a radiosensitizing effect.
PURPOSE:Oxygendeficiency in tumors reduces the efficacy of nonsurgical treatment modalities. We tested the hypothesis that electrical stimulation of the sciatic nerve could modify the oxygenation status and the blood flow of tumors implanted in the thigh of mice. MATERIALS AND METHODS: The sciatic nerve was electrically stimulated at 5 Hz. Local transplantable liver tumor (TLT) and fibrosarcoma (FSaII) tumoroxygen pressure (pO(2)) and perfusion measurements were carried out using electron paramagnetic resonance (EPR) oximetry and the OxyLite/OxyFlo technique. The radiosensitizing effect of the protocol was assessed by irradiating FSaII tumors with X-rays. RESULTS:TumorpO(2) increased from approximately 3 mm Hg to approximately 8 mm Hg, and relative tumor blood flow was increased by 241% and 162% for TLT and FSaII tumor models, respectively. The effect on the tumor oxygenation was inhibited by a nitric oxide synthase (NOS) inhibitor, and an increase in the tumornitric oxide (NO) content was observed using EPR spin-trapping. The tumoroxygen consumption rate was decreased after the stimulation protocol. In addition, the electrical stimulation of the host tissue increased regrowth delays by a factor of 1.65. CONCLUSIONS: This increase in tumor oxygenation is due to the temporary increase in tumor blood flow, but particularly to a decrease in the tumoroxygen consumption rate (inhibition of respiration) that is mediated by a local production of NO during the protocol. Those tumor hemodynamic changes resulted in a radiosensitizing effect.
Authors: Eui Jung Moon; Pierre Sonveaux; Paolo E Porporato; Pierre Danhier; Bernard Gallez; Ines Batinic-Haberle; Yu-Chih Nien; Thies Schroeder; Mark W Dewhirst Journal: Proc Natl Acad Sci U S A Date: 2010-11-08 Impact factor: 11.205
Authors: Fabienne Danhier; Pierre Danhier; Nicolas Magotteaux; Géraldine De Preter; Bernard Ucakar; Oussama Karroum; Bénédicte Jordan; Bernard Gallez; Véronique Préat Journal: PLoS One Date: 2012-07-12 Impact factor: 3.240
Authors: Sven De Bruycker; Christel Vangestel; Steven Staelens; Tim Van den Wyngaert; Sigrid Stroobants Journal: Contrast Media Mol Imaging Date: 2018-10-18 Impact factor: 3.161
Authors: G Sprugnoli; L Monti; L Lippa; F Neri; L Mencarelli; G Ruffini; R Salvador; G Oliveri; B Batani; D Momi; A Cerase; A Pascual-Leone; A Rossi; S Rossi; E Santarnecchi Journal: Sci Adv Date: 2019-08-14 Impact factor: 14.136