Russell James, Carlin Sean, Burke Sean A, Wen Bixiu, Yang Kwang Mo, Ling C Clifton
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Int J Radiat Oncol Biol Phys. 2009 Mar 15;73(4):1177-86. doi: 10.1016/j.ijrobp.2008.12.004.
Although hypoxia is a known prognostic factor, its effect will be modified by the rate of reoxygenation and the extent to which the cells are acutely hypoxic. We tested the ability of exogenous and endogenous markers to detect reoxygenation in a xenograft model. Our technique might be applicable to stored patient samples.
The human colorectal carcinoma line, HT29, was grown in nude mice. Changes in tumor hypoxia were examined by injection of pimonidazole, followed 24 hours later by EF5. Cryosections were stained for these markers and for carbonic anhydrase IX (CAIX) and hypoxia-inducible factor 1alpha (HIF1alpha). Tumor hypoxia was artificially manipulated by carbogen exposure.
In unstressed tumors, all four markers showed very similar spatial distributions. After carbogen treatment, pimonidazole and EF5 could detect decreased hypoxia. HIF1alpha staining was also decreased relative to CAIX, although the effect was less pronounced than for EF5. Control tumors displayed small regions that had undergone spontaneous changes in tumor hypoxia, as judged by pimonidazole relative to EF5; most of these changes were reflected by CAIX and HIF1alpha.
HIF1alpha can be compared with either CAIX or a previously administered nitroimidazole to provide an estimate of reoxygenation.
尽管缺氧是一个已知的预后因素，但其影响会因复氧速率和细胞急性缺氧程度而改变。我们在异种移植模型中测试了外源性和内源性标志物检测复氧的能力。我们的技术可能适用于储存的患者样本。
人结肠癌细胞系HT29在裸鼠体内生长。通过注射匹莫硝唑检测肿瘤缺氧的变化，24小时后注射EF5。对冰冻切片进行这些标志物以及碳酸酐酶IX（CAIX）和缺氧诱导因子1α（HIF1α）的染色。通过暴露于混合气体人工控制肿瘤缺氧。
在未受应激的肿瘤中，所有四种标志物显示出非常相似的空间分布。混合气体处理后，匹莫硝唑和EF5可检测到缺氧程度降低。相对于CAIX，HIF1α染色也减少，尽管其效果不如EF5明显。通过匹莫硝唑相对于EF5判断，对照肿瘤显示出肿瘤缺氧发生自发变化的小区域；其中大多数变化由CAIX和HIF1α反映。
HIF1α可与CAIX或先前给予的硝基咪唑进行比较，以估计复氧情况。
