Teicher B A, Holden S A, Ara G, Dupuis N P, Liu F, Yuan J, Ikebe M, Kakeji Y
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Int J Cancer. 1995 May 29;61(5):732-7. doi: 10.1002/ijc.2910610523.
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.
在静脉注射全氟溴烷乳剂之前和之后，于正常空气和碳合气呼吸条件下，测量皮下生长的大鼠9L胶质肉瘤组织的氧张力。当这些动物在进行氧测量前5天用抗血管生成剂TNP - 470和米诺环素治疗时，与未治疗的肿瘤相比，肿瘤缺氧情况有所减轻。缺氧定义为pO₂读数≤5 mmHg的百分比，在未治疗的空气呼吸对照组中为71%，在用抗血管生成剂、全氟溴烷乳剂和碳合气呼吸治疗的动物中降至34%。这些效应表现为肿瘤对单剂量（10、20和30 Gy）放射治疗的反应增强。用卡氮芥治疗24小时后，肿瘤的氧合情况未改变；然而，用阿霉素给药24小时后，肿瘤的氧合增加，使得接受全氟溴烷乳剂和碳合气的动物中阿霉素治疗的肿瘤缺氧情况降至21%。从肿瘤细胞植入后第4天到第18天，添加抗血管生成剂以及在第7 - 11天添加卡氮芥或阿霉素治疗，可增加皮下肿瘤的生长延迟。给予全氟溴烷乳剂和碳合气呼吸，单独使用化疗药物以及与抗血管生成剂联合使用时，均会导致肿瘤生长延迟增加。与用卡氮芥或阿霉素治疗相比，颅内植入9L胶质肉瘤的动物的寿命随着给予抗血管生成剂，然后给予抗血管生成剂和全氟溴烷乳剂/碳合气而逐渐延长。
