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One of the goals of translational cancer research is to understand basic 'phenomena' so that tumour response to therapy can be improved. One such phenomenon is intermittent tumour blood flow. The impact of the transient hypoxia that results from decreased tumour blood flow is now beginning to be appreciated in preclinical systems, and also receiving some attention in clinical practise. Thus in this article we review the nature and frequency of microregional blood flow changes in preclinical and clinical tumours and examine the impact of those changes on response to both radiotherapy and chemotherapy. Additionally, the implications of non-constant blood flow for both the growth of the unperturbed tumour and the regrowth of surviving tumour clonogens during and after therapy are examined. [ABSTRACT FROM AUTHOR]

Tumour hypoxia is known to be associated with aggressiveness and poor response to treatment, which has stimulated the development of several methods able to detect hypoxic tumours. To date, only one method, the oxygen microelectrode, has been used to provide pretreatment measures of tumour oxygenation that correlate with local control and disease-free survival. In an effort to validate new methods, comparisons have been made between the Eppendorf oxygen microelectrode, the comet assay, and hypoxia marker binding in tumours of patients undergoing curative treatment or palliative radiotherapy. These comparisons suggest that tumours with median oxygen tensions below 10 mmHg have relatively high hypoxic fractions as measured by the comet assay (>0.20). The fraction of cells that binds pimonidazole, detected in cells obtained by fine-needle aspiration biopsy, correlates well with the hypoxic fraction measured using the comet assay. However, in general, hypoxic fractions measured by the comet assay and pimonidazole binding correlate only poorly with Eppendorf measurements performed for the same tumour. Factors that might be responsible for these differences, and problems associated with measuring the 'relevant' hypoxic population are discussed. [ABSTRACT FROM AUTHOR]

In the past few years, 'perfusion-limited' hypoxia caused by intermittent decreases in tumour blood flow has received increasing attention. Little effort, however, has gone into characterizing the nature, magnitude or duration of these changes, or their functional significance other than as modifiers of radiotherapy. We have therefore undertaken multiple, quantitative analyses of tumour blood flow in human tumour xenograft systems, and rigorously examined the ramifications of transient blood flow changes. Tumour blood flow in these experimental tumours is much less constant than has previously been assumed, and not only impacts on response to radiotherapy and chemotherapy, but also on the more fundamental processes of tumour growth and repopulation. Notably, responses entirely consistent with the laboratory results have been seen in our initial studies of human tumours sequentially biopsied during treatment. [ABSTRACT FROM AUTHOR]

The comet assay is a single-cell gel electrophoresis technique that measures DNA damage in individual cells. Since radiation produces 3-4 times more DNA damage in well-oxygenated cells compared with hypoxic cells, this assay can quantify the fraction of radiation-resistant hypoxic cells found in many solid tumours. This paper summarizes our results with 73 accessible metastatic tumours irradiated with palliative intent. Hypoxic fractions ranged from 0.0 to 0.67 with a mean of 0.15; 62% of these advanced tumours showed a hypoxic fraction >0.05. Comparisons between two sequential aspirates in 33 tumours gave a slope of 0.92 (r[sup 2]=0.88), suggesting that a single aspirate is generally representative of the tumour. A limitation, however, is that the hypoxic fraction could not be measured in clinical samples given a conventional dose of 2 Gy. [ABSTRACT FROM AUTHOR]