Dupuis N P, Kusumoto T, Robinson M F, Liu F, Menon K, Teicher B A
Dana-Farber Cancer Institute, Boston, MA, USA.
Artif Cells Blood Substit Immobil Biotechnol. 1995;23(3):423-9. doi: 10.3109/10731199509117958.
Female, Fisher 344 rats bearing 13762 mammary carcinoma implanted subcutaneously in a hind limb were treated with standard therapeutic single doses of antitumor treatments of several types including: 1) antitumor alkylating agents (cisplatin, cyclophosphamide); 2) natural products (adriamycin, taxol and etoposide); 3) antimetabolites (5-flourouracil); 4) hypoxic cell selective agents (mitomycin C, SR-4233) as well as 5) fractionated radiation therapy (3 Gray daily for 5 days). The oxygen levels in the tumors were measured in the absence of treatment and 24 hrs. after treatment using an Eppendorf p02 histograph. Fifty- to sixty-points were measured per tumor and 8-10 tumors comprised each group. The tumors were more hypoxic post treatment with every anticancer drug or radiation. The percent of p02 readings < or = 5 mmHg in the untreated tumors ranged from 85% (x-rays) to 59% (etoposide). Administration of the perflubron emulsion (8 ml/kg) and carbogen breathing (95% O2/5% CO2) increased the oxygenation of the tumors such that the percent of pO2 readings < or = 5 mmHg was 32% in the untreated controls and ranged from 27% (x-rays) to 56% (adria) in the treated tumors. These results indicate that administration of a perflubron emulsion/carbogen can increase the oxygen content of tumors when hypoxia is the result of cytotoxic therapy.
雌性Fisher 344大鼠,后肢皮下植入13762乳腺癌,接受几种类型的标准治疗单剂量抗肿瘤治疗,包括:1)抗肿瘤烷化剂(顺铂、环磷酰胺);2)天然产物(阿霉素、紫杉醇和依托泊苷);3)抗代谢物(5-氟尿嘧啶);4)乏氧细胞选择性药物(丝裂霉素C、SR-4233)以及5)分次放射治疗(每天3戈瑞,共5天)。在未治疗时以及治疗后24小时,使用Eppendorf p02组织氧张力仪测量肿瘤中的氧水平。每个肿瘤测量50至60个点,每组包括8至10个肿瘤。每种抗癌药物或放射治疗后肿瘤的乏氧程度更高。未治疗肿瘤中p02读数≤5 mmHg的百分比范围为85%(X射线)至59%(依托泊苷)。给予全氟溴烷乳剂(8 ml/kg)和卡波金呼吸(95% O2/5% CO2)可增加肿瘤的氧合,使得未治疗对照组中pO2读数≤5 mmHg的百分比为32%,治疗后肿瘤中该百分比范围为27%(X射线)至56%(阿霉素)。这些结果表明,当细胞毒性治疗导致缺氧时,给予全氟溴烷乳剂/卡波金可增加肿瘤的氧含量。