title: Influence of an anti-angiogenic treatment on 9L gliosarcoma: oxygenation and response to cytotoxic therapy.
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.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Teicher
authors.forename: S A
authors.initials: SA
authors.lastname: Holden
authors.forename: G
authors.initials: G
authors.lastname: Ara
authors.forename: N P
authors.initials: NP
authors.lastname: Dupuis
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Yuan
authors.forename: M
authors.initials: M
authors.lastname: Ikebe
authors.forename: Y
authors.initials: Y
authors.lastname: Kakeji
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D003510:Cyclohexanes; D004359:Drug Therapy, Combination; D005260:Female; D018316:Gliosarcoma / Q000188:drug therapy* / Q000401:mortality; D008911:Minocycline / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000401:mortality; D012717:Sesquiterpenes / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D008911:Minocycline; D010100:Oxygen; D000077609:O-(Chloroacetylcarbamoyl)fumagillol