Influence of an anti-angiogenic treatment on 9L gliosarcoma: oxygenation and response to cytotoxic therapy

Int J Cancer. 1995 May 29;61(5):732-7. doi: 10.1002/ijc.2910610523.

Abstract

Tissue oxygen tensions were measured in subcutaneously growing rat 9L gliosarcoma under normal air and carbogen breathing conditions prior to and after i.v. administration of a perflubron emulsion. When these animals were treated with the anti-angiogenic agents TNP-470 and minocycline for 5 days prior to oxygen measurement, tumor hypoxia was decreased compared with untreated tumors. Hypoxia, defined as the percent of pO2 readings < or = 5 mm Hg, was decreased from 71% in untreated air-breathing controls to 34% in animals treated with the anti-angiogenic agents, the perflubron emulsion and carbogen breathing. These effects were manifest in the increased response of the tumor to single-dose (10, 20 and 30 Gy) radiation therapy. Twenty-four hours after treatment with BCNU oxygenation of the tumors was not altered; however, 24 hr after administration of adriamycin oxygenation of the tumors was increased such that hypoxia in adriamycin-treated tumors in animals receiving the perflubron emulsion and carbogen was reduced to 21%. Tumor growth delay in the s.c. tumors was increased by the addition of treatment with the anti-angiogenic agents from day 4 through day 18 post-tumor cell implantation along with BCNU or adriamycin on days 7-11. Administration of the perflubron emulsion and carbogen breathing resulted in increased tumor growth delay with the chemotherapeutic agents alone and in combination with the anti-angiogenic agents. Life span in animals bearing intracranially implanted 9L gliosarcoma progressively increased with administration of the anti-angiogenic agents and then the anti-angiogenic agents and perflubron emulsion/carbogen compared to treatment with BCNU or adriamycin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / therapeutic use*
  • Cyclohexanes
  • Drug Therapy, Combination
  • Female
  • Gliosarcoma / drug therapy*
  • Gliosarcoma / mortality
  • Minocycline / therapeutic use*
  • Neoplasm Transplantation
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Oxygen / metabolism
  • Rats
  • Rats, Inbred F344
  • Sarcoma, Experimental / drug therapy
  • Sarcoma, Experimental / mortality
  • Sesquiterpenes / therapeutic use*

Substances

  • Antibiotics, Antineoplastic
  • Cyclohexanes
  • Sesquiterpenes
  • Minocycline
  • Oxygen
  • O-(Chloroacetylcarbamoyl)fumagillol