title: Effect of ONCONASE +/- tamoxifen on ASPC-1 human pancreatic tumors in nude mice.
abstract: To evaluate changes in tumor physiological parameters after treatment with ONCONASE (ONC), we used laser Doppler flowmetery for tumor blood flow (TBF) in legs of nude mice bearing AsPC-1 human pancreatic carcinoma. Tumor interstitial fluid pressure (TIFP) was measured using the wick-in-needle technique, while intratumoral pO2 utilized O2 sensitive needle electrodes. TBF was significantly increased by an i.p. injection of ONC, then returned to the untreated levels at 150 min post-treatment. Single and multiple intraperitoneal injections of ONC significantly reduced TIFP (post-treatment at 1-7 days). ONC significantly improved tumor oxygenation evidenced by an increase in median pO2 from 4.2 mm Hg to 8.2 mm Hg. Since ONC had a synergistic interaction with tamoxifen (TAMX) on the cytotoxic clonogenicity of AsPC-1 tumor cells in vitro, we evaluated the antitumoral effects in vivo by ONC +/- TAMX, using nude mice bearing AsPC-1 pancreatic tumor cells of ascite (intraperitoneally implanted) or solid (subcutaneously implanted to legs) tumors. ONC alone effectively retarded the tumor growth, but TAMX alone did not. ONC + TAMX was synergistically effective in inhibiting tumor growth.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Intae
authors.initials: I
authors.lastname: Lee
authors.forename: Young H
authors.initials: YH
authors.lastname: Lee
authors.forename: Stanislaw M
authors.initials: SM
authors.lastname: Mikulski
authors.forename: Kuslima
authors.initials: K
authors.lastname: Shogen
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D017078:Laser-Doppler Flowmetry; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D012260:Ribonucleases / Q000008:administration & dosage*; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D013629:Tamoxifen; D012260:Ribonucleases; C058703:ranpirnase