Measurement of Tumor Oxygenation: A Comparison between Polarographic Needle Electrodes and a Time-Resolved Luminescence-Based Optical Sensor

Collingridge, David R.; Young, William K.; Vojnovic, B.; Wardman, Peter; Lynch, Eileen M.; Hill, Sally A.; Dj, Chaplin

doi:10.2307/3579340

Cited by 81 publications

(47 citation statements)

References 13 publications

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“…Hypoxia in human tumors has been estimated indirectly by measuring tumor vascularization (e.g., intercapillary distance, vascular density; West et al, 2001); the degree of DNA damage after radiation (Partridge et al, 2001); the expression of hypoxia-regulated genes (Airley et al, 2001(Airley et al, , 2003; and by hypoxia marker techniques (misonidazole; Chapman et al, 1983;pimonidazole: Arteel et al, 1995; the 2-nitroimidazole drug EF5; Evans et al, 2001). Direct measurements of tissue oxygen partial pressure (pO 2 ) have been obtained by utilizing oxygen sensitive polarographic electrodes (Eppendorf, Hamburg, Germany; e.g., Vaupel et al, 1991) and luminescence-based optical sensors (Collingridge et al, 1997). Using oxygen electrodes, it has been observed that the majority of solid tumors present median pO 2 levels lower than their normal tissue of origin.…”

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confidence: 99%

How to overcome (and exploit) tumor hypoxia for targeted gene therapy

Greco

Marples

Joiner

et al. 2003

Journal Cellular Physiology

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Tumor hypoxia has long been recognized as a critical issue in oncology. Resistance of hypoxic areas has been shown to affect treatment outcome after radiation, chemotherapy, and surgery in a number of tumor sites. Two main strategies to overcome tumor hypoxia are to increase the delivery of oxygen (or oxygen-mimetic drugs), or to exploit this unique environmental condition of solid tumors for targeted therapy. The first strategy includes hyperbaric oxygen breathing, the administration of carbogen and nicotinamide, and the delivery of chemical radiosensitizers. In contrast, bioreductive drugs and hypoxia-targeted suicide gene therapy aim at activating cytotoxic agents at the tumor site, while sparing normal tissue from damage. The cellular machinery responds to hypoxia by activating the expression of genes involved in angiogenesis, anaerobic metabolism, vascular permeability, and inflammation. In most cases, transcription is initiated by the binding of the transcription factor hypoxia-inducible factor (HIF) to hypoxia responsive elements (HREs). Hypoxia-targeting for gene therapy has been achieved by utilizing promoters containing HREs, to induce selective and efficient transgene activation at the tumor site. Hypoxia-targeted delivery and prodrug activation may add additional levels of selectivity to the treatment. In this article, the latest developments of cancer gene therapy of the hypoxic environment are discussed, with particular attention to combined protocols with ionizing radiation. Ultimately, it is proposed that by adopting specific transgene activation and molecular amplification systems, resistant hypoxic tumor tissues may be effectively targeted with gene therapy.

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confidence: 99%

How to overcome (and exploit) tumor hypoxia for targeted gene therapy

Greco

Marples

Joiner

et al. 2003

Journal Cellular Physiology

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“…2 The OxyLite allows pO 2 measurement that is based on the oxygen-quenched lifetime of a luminescent ruthenium dye. 18,19 This system was used for simultaneously and continuously monitoring local tissue oxygenation and temperature at the same location, before, during and after treatment. FSaII tumors were monitored with both techniques and for all treatments, whereas LLc tumors were studied with EPR oximetry alone for the treatments that induce endogenous production of NO (insulin and electrical stimulation) on control and eNOS Ϫ/Ϫ mice.…”

Section: Po 2 Measurementsmentioning

confidence: 99%

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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“…Oxygenation in the established tumour models was measured using the OxyLite pO 2 system (Oxford Optronix Ltd, Oxford, UK) (Young et al, 1996;Collingridge et al, 1997;Seddon et al, 2001). The OxyLite probes measure pO 2 by using a fluorescence quenching technique (Young et al, 1996).…”

Section: Direct Measurement Of Pomentioning

confidence: 99%