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Microenvironmental and cellular consequences of altered blood flow in tumours

Departments of ¹ Biochemistry and Molecular Biophysics, ² Applied Mathematics and Radiology, University of Arizona Health Sciences Center, Tucson, AZ 85724-5024, USA

View larger version (31K): [in a new window]   Figure 1. Axial T1 weighted MRI images of a SCID mouse bearing an MCF-7 human breast cancer xenograft in the flank (arrow): (a) pre-Magnevist®, (b) 10 min post-contrast, (c) 20 min post-contrast and (d) 30 min post-contrast. The heterogeneity of enhancement is indicative of non-uniform wash-in and wash-out kinetics of the contrast agent. Such heterogeneity is routinely observed in both animal and human tumours, and illustrates tumour perfusion heterogeneity.

View larger version (19K): [in a new window]   Figure 2. Wave-front profiles of the tumour-host interface generated from computer simulations and analytic solutions of coupled partial differential equations used to model the acid-mediated tumour invasion hypothesis. Details of this analysis are available in reference [158]. The wave-fronts are propagating left to right with a speed of about 0.03 mm day–1. Normal tissue is identified as 1 with the boundary of normal cells receding before the advancing wave-fronts of propagating tumour, identified as 2, and the accompanying acid gradient, identified as . Note the predicted acellular gap between the edges of the tumour and normal tissue. The mathematical models predict this gap will occur under some conditions as a result of rapid death of normal cells in the region of most severe extracellular acidosis.

View larger version (156K): [in a new window]   Figure 3. Heamotoxylin and eosin stained micrographs of the tumour-host interface of a formalin-fixed specimen from human squamous cell carcinoma of the head and neck. An acellular gap between the tumour and normal tissue edges is identified (arrows), consistent with the predictions of the mathematical model (cf. Figure 2). Note the dying normal cells just beyond this acellular gap (arrowheads) presumably due to acid-induced apoptosis.