Changes in tumor oxygenation/perfusion induced by the no donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI

Jordan, Bénédicte F.; Misson, Pierre‐Damien; Demeure, Roger; Baudelet, Christine; Beghein, Nelson; Gallez, Bernard

doi:10.1016/s0360-3016(00)00694-5

Cited by 105 publications

(96 citation statements)

References 17 publications

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“…Three strategies were considered for that purpose: (i) administration of a NO donor (isosorbide dinitrate), 5,6 (ii) slow infusion of insulin, 7 and (iii) electrical stimulation of the host tissue. 8 The first treatment acted by a direct release of exogenous NO whereas the others were actually shown to be mediated by the activation of endogenous NO synthase.…”

Section: Abstract: Tumor; Radiation Sensitivity; Enos ϫ/ϫ ; Nitric Omentioning

confidence: 99%

“…at a dose of 0.2 mg/kg. 5 Insulin (Actrapid HM, Novo Nordisk, Bagsvaerd, Denmark) was infused i.v. at a rate of 16 mU/kg/min for 25 min.…”

Section: Treatmentsmentioning

confidence: 99%

“…It was suggested that this increase in tumor oxygenation was achieved via alterations in blood flow and oxygen consumption through NO-mediated pathways. [5][6][7][8] Whether NO also had direct radiosensitizing effects was, however, not addressed in these studies. Besides the well-known 'oxygen effect' that is involved in tumor radiation response induced by these NO-mediated modulators, [5][6][7][8] NO produced in the tumor may also contribute to the radiosensitization of tumors.…”

mentioning

confidence: 99%

“…8 The first treatment acted by a direct release of exogenous NO whereas the others were actually shown to be mediated by the activation of endogenous NO synthase. [5][6][7][8] Accordingly, isosorbide dinitrate, insulin, and electrical stimulation of the host tissue are able to modulate the level of oxygenation in TLT and FSaII tumors. It was suggested that this increase in tumor oxygenation was achieved via alterations in blood flow and oxygen consumption through NO-mediated pathways.…”

mentioning

confidence: 99%

“…[5][6][7][8] Whether NO also had direct radiosensitizing effects was, however, not addressed in these studies. Besides the well-known 'oxygen effect' that is involved in tumor radiation response induced by these NO-mediated modulators, [5][6][7][8] NO produced in the tumor may also contribute to the radiosensitization of tumors. In that respect, previous reports suggested the potential role of NO as an intrinsic radiosensitizer using in vitro models, due to the likely fixation of radiation-induced damage in DNA.…”

mentioning

confidence: 99%

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Nitric oxide as a radiosensitizer: Evidence for an intrinsic role in addition to its effect on oxygen delivery and consumption

Jordan

Sonveaux

Feron

et al. 2004

Intl Journal of Cancer

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Different nitric oxide (NO)-mediated treatments (e.g., isosorbide dinitrate, insulin and electrical stimulation of the host tissue) have been investigated for their effects on tumor oxygenation and radiation sensitivity. We further address the issue of the role played by modulation of the NO-pathway in tumor radiosensitivity. For this purpose, the local concentration of NO was monitored after treatment in FSaII tumors and a comparison between the sensitivity of LLC tumors implanted both on eNOS ؊/؊ and wild-type (WT) mice was carried out. First, we demonstrate the central role played by eNOS in the radiosensitizing effect after application of insulin treatment and electrical stimulation: a significant increase in tumor NO content is induced by these treatments and the increase in tumor oxygenation, as well as the radiosensitizing effect are abolished in eNOS knock-out mice, in contrast to WT mice. Second, by comparing the level of oxygen and NO achieved in tumors after NO-mediated treatments and carbogen, we provide evidence that these NO-mediated treatments are not simply acting by a single oxygen effect. These treatments induced significant regrowth delays compared to carbogen, despite a smaller increase in tumor oxygenation. For the NO-mediated treatments, there was a direct correlation between the NO content and the radiosensitizing effect. These data strongly suggest that NO is a complementary factor additive to oxygen in determining the sensitivity to irradiation and we therefore propose that NO acts as an intrinsic radiosensitizer in vivo. © 2004 Wiley-Liss, Inc. Key words: tumor; radiation sensitivity; eNOS Ϫ/Ϫ ; nitric oxide; oxygenTumor oxygenation and blood flow are of fundamental importance to many forms of cancer therapy. The partial pressure of oxygen (pO 2 ) plays an important role in the response of tumors to cytotoxic treatments such as chemotherapy, radiotherapy and photodynamic therapy. Both oxygen diffusion and oxygen consumption by tumor cell metabolism contribute to the occurrence of hypoxia. Oxygen deficiency is caused by an insufficient oxygen supply as a result of inadequate tumor perfusion (diffusion limited hypoxia) and fluctuations in red cell flux (acute hypoxia). 1 A promising approach in cancer therapy consists of the manipulation of tumor blood oxygen delivery and oxygen consumption to improve either radio-or chemotherapeutic response. Vasoactive agents, 2 modifiers of tumor cell oxygen consumption 3 or carbogen breathing 4 that is already being tested in Phase III clinical studies, are currently being evaluated for their potential therapeutic interest.We documented recently that nitric oxide (NO)-dependent modifiers of tumor hemodynamics were able to radiosensitize experimental tumors in vivo. Three strategies were considered for that purpose: (i) administration of a NO donor (isosorbide dinitrate), 5,6 (ii) slow infusion of insulin, 7 and (iii) electrical stimulation of the host tissue. 8 The first treatment acted by a direct release of exogenous NO whereas the others were actua...

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Section: Abstract: Tumor; Radiation Sensitivity; Enos ϫ/ϫ ; Nitric Omentioning

confidence: 99%

“…at a dose of 0.2 mg/kg. 5 Insulin (Actrapid HM, Novo Nordisk, Bagsvaerd, Denmark) was infused i.v. at a rate of 16 mU/kg/min for 25 min.…”

Section: Treatmentsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Nitric oxide as a radiosensitizer: Evidence for an intrinsic role in addition to its effect on oxygen delivery and consumption

Jordan

Sonveaux

Feron

et al. 2004

Intl Journal of Cancer

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Non‐Invasive Imaging of the Tumor Microenvironment

Jordan

Gallez

2010

Tumor Microenvironment

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Electron paramagnetic resonance: a powerful tool to support magnetic resonance imaging research

Danhier

Gallez

2014

Contrast Media & Molecular

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The purpose of this paper is to describe some of the areas where electron paramagnetic resonance (EPR) has provided unique information to MRI developments. The field of application mainly encompasses the EPR characterization of MRI paramagnetic contrast agents (gadolinium and manganese chelates, nitroxides) and superparamagnetic agents (iron oxide particles). The combined use of MRI and EPR has also been used to qualify or disqualify sources of contrast in MRI. Illustrative examples are presented with attempts to qualify oxygen sensitive contrast (i.e. T1 - and T2 *-based methods), redox status or melanin content in tissues. Other areas are likely to benefit from the combined EPR/MRI approach, namely cell tracking studies. Finally, the combination of EPR and MRI studies on the same models provides invaluable data regarding tissue oxygenation, hemodynamics and energetics. Our description will be illustrative rather than exhaustive to give to the readers a flavour of 'what EPR can do for MRI'.

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Changes in tumor oxygenation/perfusion induced by the no donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI

Cited by 105 publications

References 17 publications

Nitric oxide as a radiosensitizer: Evidence for an intrinsic role in addition to its effect on oxygen delivery and consumption

Nitric oxide as a radiosensitizer: Evidence for an intrinsic role in addition to its effect on oxygen delivery and consumption

Non‐Invasive Imaging of the Tumor Microenvironment

Electron paramagnetic resonance: a powerful tool to support magnetic resonance imaging research

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