Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors

Rampling, Roy; Cruickshank, Garth; Lewis, Alexander D.; Fitzsimmons, Sara A.; Workman, Paul

doi:10.1016/0360-3016(94)90432-4

Cited by 275 publications

(128 citation statements)

References 13 publications

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“…In contrast, pO2 histography in human gliomas in situ during anaesthesia has suggested extensive hypoxia in the lesions themselves and in peritumoral oedema (Cruickshank and Rampling, 1994a, b;Rampling et al, 1994). These data appear to support the clinical trials currently underway testing the therapeutic role of hypoxic cytotoxins in malignant gliomas.…”

mentioning

confidence: 88%

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

Parliament¹,

Franko²,

Allalunis-Turner³

et al. 1997

Br J Cancer

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Summary In contrast to reports of extensive hypoxia in human gliomas in situ measured by P02 histography, non-invasive methods of assessing glioma oxygenation, including nitroimidazole binding, have yielded surprisingly contradictory results. In order to investigate the relationship of necrosis, hypoxia, nitroreductase activity and cellular respiration in human gliomas, subcutaneous models using the human glioma cell lines M059K, M006 and M01 Ob were developed in the murine SCID host. Intracranial growth of the M006 line was achieved in nude rats. The nitroreductive capacity of glioma cell lines was assessed and found to be similar to transplanted tumours previously reported in the literature. This suggests that if substantial numbers of viable hypoxic cells were present in situ in gliomas, then nitroimidazole-binding techniques should be capable of identifying them. Inter-tumour variability in the amount of necrosis was seen. M006 xenografts growing in subcutaneous and intracranial sites revealed extensive necrotic regions histologically, some of which were surrounded by cells labelled heavily for [3H]misonidazole, while other areas were lightly labelled. Similar binding patterns were seen for subcutaneous M059K tumours, while subcutaneous M01 Ob tumours display necroses of which almost all were surrounded by heavily labelled cells. The oxygen consumption rates of tumour cell lines grown in vivo, in which venous P02 concentrations are of the order of 2-5%, were two to sevenfold less than those of the same lines grown as monolayers in vitro under oxygen concentrations of 18%. We postulate that glioma cell lines behave as 'oxygen conformers', in that their rate of oxygen consumption appears to vary with the availability of oxygen. Together with the misonidazole-binding data, the results in this glioma tumour model are consistent with coordinate inhibition or down-regulation of respiration under moderate hypoxia.

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mentioning

confidence: 88%

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

Parliament¹,

Franko²,

Allalunis-Turner³

et al. 1997

Br J Cancer

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“…Vascular morphology is a critical parameter in assessing malignant potential and survival, since tumour growth beyond 1 to 2 mm largely depends on the development of adequate vascular supply [1]. Brain tumours disrupt the integrity of the blood brain barrier (BBB) and exhibit other pathological features, including marked angiogenesis with endothelial proliferation, severe hypoxia and tumour necrosis [2][3][4]. The degree of tumour angiogenesis and capillary permeability can be assessed by bolus-tracking perfusion MRI measurements, for example, dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI).…”

Section: Introductionmentioning

confidence: 99%

Correlation between arterial blood volume obtained by arterial spin labelling and cerebral blood volume in intracranial tumours

Westen

Petersen

Wirestam

et al. 2011

Magn Reson Mater Phy

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Objective: To compare measurements of the arterial blood volume (aBV), a perfusion parameter calculated from arterial spin labelling (ASL), and cerebral blood volume (CBV), calculated from dynamic susceptibility contrast (DSC) MRI. In the clinic, CBV is used for grading of intracranial tumours Conclusion:These results suggest that measurement of aBV is a potential tool for non-invasive assessment of blood volume in intracranial tumours.

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“…4 The vast majority of human solid cancers, including glioblastoma, have lower median pO 2 levels than their normal tissue of origin. 5,6 The presence of this hypoxic subpopulation of cancer cells is clinically significant for several reasons. In terms of radiation therapy, it is believed that the DNA radicals generated by radiation must react with oxygen in order to form the organic peroxides that ''fix'' the radiation damage and prevent it from being repaired.…”

mentioning

confidence: 99%

Functionality of hypoxia-induced BAX expression in a human glioblastoma xenograft model

Ozawa

et al. 2005

Cancer Gene Ther

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The effectiveness of radiation therapy for human brain tumors is limited by the presence of radiation-resistant hypoxic cells. In order to improve patient outcomes, therapeutic methods that increase hypoxic cell killing must be developed. To investigate the possibility of using the hypoxic tumor microenvironment itself as a target for gene therapy, we stably transfected U-251 MG human glioblastoma cells with constructs containing the suicide gene Bax under the regulation of a nine-copy concatemer of hypoxia responsive elements (HREs). Previously, we demonstrated that the expression of BAX protein under anoxic conditions in transfected U-251 MG clones leads to increased cell killing in vitro. Our recent studies revealed that HIF-1a induction under anoxic conditions occurs prior to the increase in BAX expression, thereby implicating HIF-1 induction as the basis of BAX upregulation. To test the effect of BAX-mediated cell killing in vivo, we implanted five stably transfected clones subcutaneously into the flanks of athymic mice. Compared to nontransfected controls, tumor growth in four of five clones was significantly retarded. Histopathological analysis demonstrated decreased hypoxic fractions and increased amounts of apoptosis in clone-derived tumors. These results suggest that the tumor microenvironment is sufficiently hypoxic to trigger HRE-mediated cell killing via the BAX apoptotic pathway.

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Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors

Cited by 275 publications

References 13 publications

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

Anomalous patterns of nitroimidazole binding adjacent to necrosis in human glioma xenografts: possible role of decreased oxygen consumption

Correlation between arterial blood volume obtained by arterial spin labelling and cerebral blood volume in intracranial tumours

Functionality of hypoxia-induced BAX expression in a human glioblastoma xenograft model

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