Effect of Onconase ± Tamoxifen on ASPC-1 Human Pancreatic Tumors in Nude Mice

  • Intae Lee
  • Young H. Lee
  • Stanislaw M. Mikulski
  • Kuslima Shogen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 530)

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-inneedle 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.

Key words

ONCONASE tamoxifen tumor blood flow tumor interstitial fluid pressure intratumoral PO2 

Abbreviations

(ONC)

ONCONASE®

(TAMX)

tamoxifen

(TBF)

tumor blood flow

(TIFD)

tumor interstitial fluid pressure

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Intae Lee
    • 1
    • 2
  • Young H. Lee
    • 2
  • Stanislaw M. Mikulski
    • 3
  • Kuslima Shogen
    • 3
  1. 1.Department of Radiation OncologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Division of Radiation ResearchUMDNJ-Robert Wood Johnson Medical SchoolCamdenUSA
  3. 3.Alfacell CorporationBloomfieldAustralia

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