Modulation of tumor oxygenation

Vaupel, Peter; Kelleher, Debra K.; Thews, Oliver

doi:10.1016/s0360-3016(98)00324-1

Cited by 67 publications

(50 citation statements)

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“…24 The causal link between hypoxia and metastasis was later demonstrated in vivo. Hypoxia is able to promote tumor metastasis in two ways: (1) by inducing the expression of gene products involved in the metastatic cascade; and (2) by providing selection pressure for a more aggressive phenotype. The initiation of metastasis is a multiple pathway that involves three major processes: degradation of the basement membrane and extracellular matrix, modulation of cell adhesion molecules and cell migration.…”

Section: Tumor Hypoxia Promotes Metastasismentioning

confidence: 99%

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

2004

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This review paper attempts to provide an overview of the principles and techniques that are often termed electron paramagnetic resonance (EPR) oximetry. The paper discusses the potential of such methods and illustrates they have been successfully applied to measure oxygen tension, an essential parameter of the tumor microenvironment. To help the reader understand the motivation for carrying out these measurements, the importance of tumor hypoxia is first discussed: the basic issues of why a tumor is hypoxic, why these hypoxic microenvironments promote processes driving malignant progression and why hypoxia dramatically influences the response of tumors to cytotoxic treatments will be explained. The different methods that have been used to estimate the oxygenation in tumors will be reviewed. To introduce the basics of EPR oximetry, the specificity of in vivo EPR will be discussed by comparing this technique with NMR and MRI. The different types of paramagnetic oxygen sensors will be presented, as well as the methods for recording the information (EPR spectroscopy, EPR imaging, dynamic nuclear polarization). Several applications of EPR for characterizing tumor oxygenation will be illustrated, with a special emphasis on pharmacological interventions that modulate the tumor microenvironment. Finally, the challenges for transposing the method into the clinic will also be discussed.

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Section: Tumor Hypoxia Promotes Metastasismentioning

confidence: 99%

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

2004

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“…Although reactivity of the BCC supplying vessels (contained in healthy skin) was certain (healthy skin and BCC reacted identically during lidocaine injection, flap raising and temporary vascular occlusion), reactivity of the intra-tumoral vessels to temporary vascular occlusion remains an important question for future investigation using video-capillaroscopy, because intra-tumoral reactive vasoconstriction might have impaired the effect of PORH in tumor supplying vessels during tumor perfusion, as opposed to the vasodilatation or complete passivity of intra-tumoral vessels. However, the general immaturity of intra-tumoral vessels of malignant tumors with almost maximal vasodilatation and low vasodilatatory reserve (Suzuki et al 1981, Peterson 1991, Fukumura and Jain 1998, Vaupel et al 1998, Thews et al 2000, Isenberg et al 2008, Sonveaux et al 2009 should render those tumors vessels principally unreactive to temporary occlusion. Thus, PORH will be efficient through tumor upstream normal vessels dilatation.…”

Section: Discussionmentioning

confidence: 99%

“…While intratumoral microvascular density is high, tumoral vessels are abnormal and chaotic (Less et al 1991;Zama et al 1991;Sharma et al 2005;Dewhirst et al 2008;Fukumura and Jain 2008), leading to perfusion-mediated hypoxia (Hill et al 1996;Kimura et al 1996;Gillies et al 1999;Cardenas-Navia et al 2004;Dewhirst et al 2007), tumor progression, and radiotherapy resistance (Gray et al 1953;Roots and Smith 1974;Vaupel 2004;Moeller et al 2007;Overgaard 2007;Vaupel 2008). Pharmacological approaches for tumors have focused on vasodilatation of the supplying vessels (Suzuki et al 1981;Peterson 1991;Fukumura and Jain 1998;Vaupel et al 1998;Thews et al 2000;Isenberg et al 2008;Sonveaux et al 2009), mainly towards increasing tumor mean partial oxygen pressure and overcoming hypoxia-induced radio-resistance, but have been fundamentally limited by its non-selectivity, thus, greatly decreasing its efficacy and increasing side-effects.…”

mentioning

confidence: 99%

“…Since tumor supplying vessels (i.e., arterial vessels that enter a tumor) generally exhibit normal histology and are reactive (in contrast with intra-tumoral vessels which are abnormal and often un-reactive) (Suzuki et al 1981;Peterson 1991;Fukumura and Jain 1998;Vaupel et al 1998;Thews et al 2000;Isenberg et al 2008;Sonveaux et al 2009), and since PORH is an ubiquitous reaction, PORH could theoretically be used to treat all tumors, regardless of their location, and to the reactivity of the intra-tumoral vessels following vascular occlusion.…”

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confidence: 99%

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Post-Occlusive Reactive Hyperemia in Basal Cell Carcinoma and Its Potential Application to Improve the Efficacy of Solid Tumor Therapies

Reyal

Lebas

Fourme

et al. 2012

Tohoku J. Exp. Med.

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Tumor hypoxia is a hallmark of malignant tumors, and is a major factor in the resistance to anti-cancer therapies, particularly radiotherapy. Indeed, tumor blood flow often fluctuates, and thus the oxygen supply is often reduced, thereby inducing tumor hypoxia. We decided to explore whether post-occlusive reactive hyperemia, a physiological reaction known to occur in normal tissues, could be induced through a malignant tumor, basal cell carcinoma (BCC), in which angiogenesis occurs, as in all malignant tumors. Skin blood flow was measured in twelve patients with BCC, using Laser Speckle Contrast Imaging to determine BCC perfusion after three minutes of vascular occlusion, induced by limb tourniquet for limb tumors (4 BCC), and/or by clamping the pedicle of a skin flap with the BCC at its center, for other tumor locations (12 BCC). We demonstrated for the first time that post-occlusive reactive hyperemia occurs in malignant tumors in humans. BCC perfusion curves were similar to those of healthy skin, characterized by a peak of hyperemia after reperfusion followed by a progressive return to the pre-occlusion perfusion level. Induction of post-occlusive reactive hyperemia in malignant tumors is therefore a novel investigational approach that could lead to a new adjuvant tool to increase the efficacy of chemotherapy and radiotherapy, respectively through the synchronized temporary increase of tumor perfusion and oxygenation.

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“…Several possible mechanisms have been analysed for their capability of modulating tumour perfusion (Jain and Ward-Hartley, 1984;Vaupel et al, 1998;2000): (i) vasoactive agents, (ii) rheologically active drugs, (iii) haemodilution, (iv) lowering interstitial hypertension, (v) mild (low-dose) hyperthermia, and (vi) agents reducing intermittent occlusion of tumour vessels (Jirtle, 1988;Kelleher et al, 1998;Powell et al, 1997).…”

mentioning

confidence: 99%

Disparate responses of tumour vessels to angiotensin II: tumour volume-dependent effects on perfusion and oxygenation

2000

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Summary Perfusion and oxygenation of experimental tumours were studied during angiotensin II (AT II) administration whereby the rate of the continuous AT II infusion was chosen to increase the mean arterial blood pressure (MABP) by 50-70 mmHg. In subcutaneous DSsarcomas the red blood cell (RBC) flux was assessed using the laser Doppler technique and the mean tumour oxygen partial pressure (pO 2 ) was measured polarographically using O 2 -sensitive catheter and needle electrodes. Changes in RBC flux with increasing MABP depended mainly on tumour size. In small tumours, RBC flux decreased with rising MABP whereas in larger tumours RBC flux increased parallel to the MABP. As a result of these volume-dependent effects on tumour blood flow, the impact of AT II on tumour pO 2 was also mainly tumour volume-related. In small tumours oxygenation decreased with increasing MABP during AT II infusion, whereas in large tumours a positive relationship between blood pressure and O 2 status was found. This disparate behaviour might be the result of the co-existence of two functionally distinct populations of tumour vessels. In small tumours, perfusion decreases presumably due to vasoconstriction of pre-existing host vessels feeding the tumour. In larger malignancies, newly formed tumour vessels predominate and seem not to have this vasoresponsive capability (lack of smooth muscle cells and/or AT receptors), resulting in an improvement of perfusion which is not tumour-related per se, but is due to the increased perfusion pressure.

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Modulation of tumor oxygenation

Cited by 67 publications

References 36 publications

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

Post-Occlusive Reactive Hyperemia in Basal Cell Carcinoma and Its Potential Application to Improve the Efficacy of Solid Tumor Therapies

Disparate responses of tumour vessels to angiotensin II: tumour volume-dependent effects on perfusion and oxygenation

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