Evaluation of Microregional Variations in Tumor Hypoxia Following the Administration of Endostatin

Abstract

Endostatin, a fragment of collagen XVIII, has been shown to potently inhibit both angiogenesis and the growth of experimental tumors, primarily through inhibition of endothelial cell migration and proliferation with minimal direct effects on tumor cells. Recent studies have also demonstrated that endostatin can enhance the antitumor effects of ionizing radiation, when administered before and during radiotherapy’. In order to optimize such combination therapies, an understanding of the accompanying changes in tumor pathophysiology, i.e., oxygenation and blood flow, is clearly of prime importance. The primary aim of the current work was to implement an improved method for determination of the effects of endostatin on the microregional relationship between tumor perfusion and hypoxic marker uptake. By combining information from multiple images taken from the same frozen sections, additional pathophysiological information could be deduced that was unobtainable from the individual images.