I Lee1, Y H Lee, S M Mikulski, J Lee, K Covone, K Shogen. 1. Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6072, USA. ilee2@mail.med.upenn.edu
Abstract
BACKGROUND AND OBJECTIVES: The effects of Onconase (Onc) on the tumor growth in vitro and in vivo were examined. Because elevated tumor interstitial fluid pressure (TIFP) is one of the major causes of inadequate drug delivery into solid tumors, we tested if Onc could lower TIFP in solid tumors. METHODS: We used several assays including a clonogenic assay and a growth delay assay for the determination of anti-tumoricidal effects of Onc. We also measured Onc-induced changes in several tumor physiological parameters. RESULTS: Onc demonstrated cytotoxic effects in all eight exponentially growing cell lines in vitro. It effectively inhibited the growth of all four transplanted tumors in vivo, and significantly reduced TIFP in all four tumors. Onc also induced increases in tumor blood flow (TBF) as well as increases in median tumor oxygen partial pressure (pO(2)) in solid tumors. CONCLUSIONS: Onc showed anti-tumoral effects on various tumor cells in vitro as well as in vivo. We also gained some insight regarding the potential physiological benefit of Onc as a new therapeutic agent in cancer treatment. Due to increases in both TBF and tumor pO(2), Onc could be a potential candidate as a novel radiation enhancer; therefore, the study of the radiation response in vivo is warranted.
BACKGROUND AND OBJECTIVES: The effects of Onconase (Onc) on the tumor growth in vitro and in vivo were examined. Because elevated tumor interstitial fluid pressure (TIFP) is one of the major causes of inadequate drug delivery into solid tumors, we tested if Onc could lower TIFP in solid tumors. METHODS: We used several assays including a clonogenic assay and a growth delay assay for the determination of anti-tumoricidal effects of Onc. We also measured Onc-induced changes in several tumor physiological parameters. RESULTS: Onc demonstrated cytotoxic effects in all eight exponentially growing cell lines in vitro. It effectively inhibited the growth of all four transplanted tumors in vivo, and significantly reduced TIFP in all four tumors. Onc also induced increases in tumor blood flow (TBF) as well as increases in median tumor oxygen partial pressure (pO(2)) in solid tumors. CONCLUSIONS: Onc showed anti-tumoral effects on various tumor cells in vitro as well as in vivo. We also gained some insight regarding the potential physiological benefit of Onc as a new therapeutic agent in cancer treatment. Due to increases in both TBF and tumor pO(2), Onc could be a potential candidate as a novel radiation enhancer; therefore, the study of the radiation response in vivo is warranted.
Authors: Nadezhda L Mironova; Irina Y Petrushanko; Olga A Patutina; Aexandra V Sen'kova; Olga V Simonenko; Vladimir A Mitkevich; Oleg V Markov; Marina A Zenkova; Alexander A Makarov Journal: Cell Cycle Date: 2013-06-10 Impact factor: 4.534
Authors: O A Patutina; N L Mironova; E I Ryabchikova; N A Popova; V P Nikolin; V I Kaledin; V V Vlassov; M A Zenkova Journal: Acta Naturae Date: 2010-04 Impact factor: 1.845
Authors: D Spalletti-Cernia; R Sorrentino; S Di Gaetano; R Piccoli; M Santoro; G D'Alessio; P Laccetti; G Vecchio Journal: Br J Cancer Date: 2004-01-12 Impact factor: 7.640