HYALURONIDASE REDUCES THE INTERSTITIAL FLUID PRESSURE IN SOLID TUMORSIN A NONLINEAR CONCENTRATION-DEPENDENT MANNER

Hyaluronidase has gained increasing interest as an adjuvant in local a nd systemic cancer therapy, despite the incomplete knowledge of its ph ysiological function. To this end, direct intratumoural injection of b ovine testicular hyaluronidase (500, 1600 or 7500 U in 50 mu 1 phospha te-buffered saline (PBS)) was performed in orthotopic (o.t.) osteosarc oma xenografts grown in the hind leg of nude mice. Control tumours rec eived 50 pi PBS alone or supplemented with 10% bovine serum albumin (B SA). Central tumour interstitial fluid pressure (IFP) and mean arteria l blood pressure (MABP) were measured using the wick-in-needle techniq ue and after cannulation of the carotid artery, respectively. IFP was 32 +/- 8 mmHg (n = 44, mean +/- SD) in untreated tumours and there was a significant correlation between tumour IFP and volume (P < 0.01). T he hyaluronidase injection reduced IFP to 63-84% after 1 h compared wi th controls (P < 0.05) and in a non-linear concentration-dependent man ner. MABP was not affected significantly. In conclusion, an intratumou ral hyaluronidase injection might reduce IFP temporally in solid osteo sarcoma xenografts. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.