%0 Journal Article
%T Hypoxia and oxidative stress in breast cancer: Hypoxia and tumourigenesis
%A Helen J Knowles
%A Adrian L Harris
%J Breast Cancer Research
%D 2001
%I BioMed Central
%R 10.1186/bcr314
%X Hypoxia is a feature of solid tumours which generally occurs over 100 ¦Ìm away from functional blood vessels [1], this O2 diffusion distance being determined by metabolism. As human tumours have an inadequate vasculature, hypoxia is widespread in both primary tumours and their metastases [2]. During tumour growth an increasingly compromised blood supply generally results in a tumour oxygen tension of 0¨C20 mmHg, compared with 24¨C66 mmHg in normal human tissues [3]. The majority of these measurements in human tumours in vivo have been performed using polarographic needle electrodes [2,3] although other less invasive methods, which do not always show good concordance, are at various stages of development. These include magnetic resonance spectroscopy, phosphorescence quenching microscopy and chemical hypoxia probes such as pimonidazole. In addition to chronic diffusion-limited hypoxia tumours can exhibit regions of acute hypoxia, a transient state caused by perfusion fluctuations such as vessel closure, which is also evident in both primary and metastatic human tumour tissue [4]. Factors that have an impact on the rate of O2 utilisation, including the effects of oncogenic transformation on the metabolic rate of tumour tissue, also significantly affect O2 levels [5].In addition to being a consequence of the growth of a malignant tumour and so a potential marker, hypoxia also acts to promote tumour development. Hypoxic conditions are known to affect the response of solid malignancies to radiation, limiting its efficacy in both primary tumours and metastatic tissue [6,7]. As well as conferring resistance to current therapies, hypoxia can act as a negative clinical prognostic indicator. An association between hypoxia and metastatic potential has been demonstrated in human tumours [6,8] with tumour oxygenation being a strong predictor of both overall and disease-free survival, regardless of the mode of primary treatment [8]. The clinical impact of hypoxia is supported by the
%K angiogenesis
%K apoptosis
%K glycolysis
%K macrophage
%U http://breast-cancer-research.com/content/3/5/318