Tumoricidal effects of onconase on various tumors

Background and Objectives: The effects of Onconase (Onc) on the tumor growt h in vitro and in vivo were examined. Because elevated tumor interstitial f luid pressure (TIFP) is one of the major causes of inadequate drug delivery into solid tumors, we tested if One could lower TIFP in solid tumors. Methods: We used several assays including a clonogenic assay and a growth d elay assay for the determination of anti-tumoricidal effects of One. We als o measured One-induced changes in several tumor physiological parameters. Results: One demonstrated cytotoxic effects in all eight exponentially grow ing cell lines in vitro. It effectively inhibited the growth of all four tr ansplanted tumors in vivo, and significantly reduced TIFP in all four tumor s. One also induced increases in tumor blood flow (TBF) as well as increase s in median tumor oxygen partial pressure (pO(2)) in solid tumors. Conclusions: One showed anti-tumoral effects on various tumor cells in vitr o as well as in vivo. We also gained some insight regarding the potential p hysiological benefit of One as a new therapeutic agent in cancer treatment. Due to increases in both TBF and tumor pO(2). One could be a potential can didate as a novel radiation enhancer; therefore, the study of the radiation response in vivo is warranted. (C) 2000 Wiley-Liss, Inc.