Tumoricidal effects of onconase on various tumors.
OBJECTIVE
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.
Lee
I
I
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6072, USA. ilee2@mail.med.upenn.edu
Lee
Y H
YH
Mikulski
S M
SM
Lee
J
J
Covone
K
K
Shogen
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001775:Blood Circulation; D004527:Egg Proteins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017078:Laser-Doppler Flowmetry; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D012260:Ribonucleases / Q000494:pharmacology*; D014343:Trypan Blue; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D004527:Egg Proteins; D012260:Ribonucleases; D014343:Trypan Blue; C058703:ranpirnase