The effects of Efaproxyn™ (Efaproxiral) on subcutaneous RIF-1 tumor oxygenation and enhancement of radiotherapy-mediated inhibition of tumor growth in mice
The effects of Efaproxyn™ (Efaproxiral) on subcutaneous RIF-1 tumor oxygenation and enhancement of radiotherapy-mediated inhibition of tumor growth in mice
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DOI：
10.1667/rr0962.1
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Swartz, Harold M.
中科院分区：
文献类型：
--
作者：
Hou, Huagang;Khan, Nadeem;Swartz, Harold M.
依法普罗沙星是一种血红蛋白的变构修饰剂，它降低了血红蛋白与氧的结合亲和力，促进了血红蛋白的氧气释放，这可能会增加组织Po(2)。本研究的目的是观察伊帕沙星对接受X线照射(4Gy)加吸氧的RIF-1肿瘤的肿瘤氧合和生长抑制的影响，并与每天照射加氧气加伊法洛沙的RIF-1肿瘤进行比较。将两种锂酞菁(LiPc)沉淀物植入C3H小鼠RIF-1肿瘤内，用EPR血氧仪测定肿瘤血氧含量。依法普罗在5天内显著增加肿瘤氧合8.4至43.4毫米汞柱，在治疗后22-31分钟达到最大值。单纯吸氧对肿瘤Po(2)无影响。在整个治疗过程中，放疗加氧气加依帕沙星对肿瘤的生长有抑制作用，从第3天到第5天，抑制作用与放疗加氧气相比有显著差异。这项研究结果提供了明确的定量信息，说明在5天的治疗过程中，依帕沙星持续且可重复地增加肿瘤的氧合能力，模拟了依帕沙星的临床应用。此外，基于对肿瘤生长的抑制，研究表明，伊法普罗增强的肿瘤氧合具有放射生物学意义。这是第一项研究表明，在5天的治疗过程中，伊法普罗能增加肿瘤的氧合，增强放疗对肿瘤生长的抑制作用。(C)2007年，由辐射研究学会提供。
Efaproxiral, an allosteric modifier of hemoglobin, reduces hemoglobin-oxygen binding affinity, facilitating oxygen release from hemoglobin, which is likely to increase tissue pO(2). The purpose of this study was to determine the effect of efaproxiral on tumor oxygenation and growth inhibition of RIF-1 tumors that received X radiation (4 Gy) plus oxygen breathing compared to radiation plus oxygen plus efaproxiral daily for 5 days. Two lithium phthalocyanine (LiPc) deposits were implanted in RIF-1 tumors in C3H mice for tumor pO(2) measurements using EPR oximetry. Efaproxiral significantly increased tumor oxygenation by 8.4 to 43.4 mmHg within 5 days, with maximum increases at 22-31 min after treatment. Oxygen breathing alone did not affect tumor pO(2). Radiation plus oxygen plus efaproxiral produced tumor growth inhibition throughout the treatment duration, and inhibition was significantly different from radiation plus oxygen from day 3 to day 5. The results of this study provide unambiguous quantitative information on the effectiveness of efaproxiral to consistently and reproducibly increase tumor oxygenation over the course of 5 days of treatment, modeling the clinical use of efaproxiral. Also, based on the tumor growth inhibition, the study shows the efaproxiral-enhanced tumor oxygenation was radiobiologically significant. This is the first study to demonstrate the ability of efaproxiral to increase tumor oxygenation and to increase the tumor growth inhibition of radiotherapy over 5 days of treatment. (c) 2007 by Radiation Research Society.