Hypoxia in Tumours: Its Relevance, Identification, and Modification

Horsman, Michael R.

doi:10.1007/978-3-642-84918-3_9

Cited by 22 publications

(18 citation statements)

References 78 publications

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“…Definitive proof for the existence of hypoxia in human tumours has been more difficult to obtain, primarily because many of the direct procedures used in animal tumours are not applicable to the clinical situation ( 13). However, indirect estimates.…”

Section: The Hypoxia Problemmentioning

confidence: 99%

Nicotinamide and Other Benzamide Analogs as Agents for Overcoming Hypoxic Cell Radiation Resistance in Tumours

Horsman

1995

Acta Oncologica

118

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Section: The Hypoxia Problemmentioning

confidence: 99%

Nicotinamide and Other Benzamide Analogs as Agents for Overcoming Hypoxic Cell Radiation Resistance in Tumours

Horsman

1995

Acta Oncologica

118

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“…although in many cases the success has been only limited (for reviews see Hirst. 1986: Freitas et al 1991: Horsman. 1993 The possibility of modulating oxygen tensions in tumours through the use of hypothermia has been postulated previously.…”

mentioning

confidence: 99%

“…although in many cases the success has been only limited (for reviews see Hirst. 1986: Freitas et al 1991: Horsman. 1993).…”

mentioning

confidence: 99%

Localized hypothermia: impact on oxygenation, microregional perfusion, metabolic and bioenergetic status of subcutaneous rat tumours

Kelleher

Nauth²,

Thews³

et al. 1998

Br J Cancer

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al. : Vaupel. 1993). Hypoxic cells have been identified in both animal and human tumours and may limit tumour response to radiotherapy as hypoxia can protect cells from sparsely ionizing radiation (Bush et al. 1978: Dische et al. 1983: Bush. 1984). FurtherTnore. the success of various other treatment modalities [e.g. oxygen-dependent chemotherapeutic agents. cytokines such as tumour necrosis factor alpha (TNF-a) and interleukin 2 (IL-2). and photodynamic therapy] may also be influenced by tissue hypoxia (Freitas et al. 1991: Chaplin et al. 1997: Vaupel. 1997. Evidence is also accumulating that suggests hypoxia may also be responsible for the development of an aggressive phenotype of tumour cells (Graeber et al. 1996: Hoeckel et al. 1996a. 1996b). Indeed. tumour oxygenation has been identified as a significant and independent oncological parameter for prediction of patient survival and local recurrence (Hoeckel et al. 1993. 1996b: Nordsmark et al. 1996 and for the likelihood of distant metastases (Brizel et al. 1996). Thus. in order to address the problem of hypoxia. many studies undertaken have been aimed at improving tumour oxygenation using a wide range of measures. although in many cases the success has been only limited (for reviews see Hirst. 1986: Freitas et al. 1991: Horsman. 1993 The possibility of modulating oxygen tensions in tumours through the use of hypothermia has been postulated previously.Studies usinr whole-body hypothermia in mice showed an increase in radiation response upon whole-body hypothermia.which was purported to be due to an improvement in tumour oxygenation and a reduction in the hypoxic fraction resulting from a reduced oxygen consumption (Nias et al. 1986(Nias et al. . 1988

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“…Oxygen deficiency (hypoxia) can be found in many human malignancies (Vaupel et al, 1989;Höckel and Vaupel, 2001) and has been blamed for limiting the efficacy of several nonsurgical tumour treatments such as sparsely ionising radiation (Gray et al, 1953;Bush et al, 1978;Horsman, 1993), O 2 -dependent chemotherapeutic agents (Teicher et al, 1990;Thews et al, 2001) or photodynamic therapy (Henderson and Fingar, 1987). However, an increasing number of studies clearly demonstrate that tumour hypoxia also has an impact on gene expression, with changes in glycolytic enzymes, growth factors or angiogenic molecules (for a recent review, see Höckel and Vaupel, 2001).…”

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confidence: 99%

Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia

et al. 2004

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This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation, vascular endothelial growth factor (VEGF) expression and vascularisation) to chronic hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-sarcomas in rats. In order to induce more pronounced tumour hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O 2 ) for the whole period of tumour growth (chronic hypoxia). A second group was acutely exposed to inspiratory hypoxia for only 20 min prior to the measurements (acute hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute hypoxia reduced the median oxygen partial pressure (pO 2 ) dramatically (1 vs 10 mmHg in controls), whereas in chronically hypoxic tumours the pO 2 was significantly improved (median pO 2 ¼ 4 mmHg), however not reaching the control level. These findings reflect the changes in tumour perfusion where acutely hypoxic tumours show a dramatic reduction of perfused tumour vessels (maybe the result of a simultaneous reduction in arterial blood pressure). In animals under chronic inspiratory hypoxia, the number of perfused vessels increased (compared to acute hypoxia), although the perfusion pattern found in control tumours was not reached. In the chronically hypoxic animals, tumour cell proliferation and tumour growth were significantly reduced, whereas no differences in VEGF expression and vascular density between these groups were observed. These results suggest that long-term adaptation of tumours to chronic hypoxia in vivo, while not affecting vascularity, does influence the functional status of the microvessels in favour of a more homogeneous perfusion.

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Hypoxia in Tumours: Its Relevance, Identification, and Modification

Cited by 22 publications

References 78 publications

Nicotinamide and Other Benzamide Analogs as Agents for Overcoming Hypoxic Cell Radiation Resistance in Tumours

Nicotinamide and Other Benzamide Analogs as Agents for Overcoming Hypoxic Cell Radiation Resistance in Tumours

Localized hypothermia: impact on oxygenation, microregional perfusion, metabolic and bioenergetic status of subcutaneous rat tumours

Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia

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