Systemic administration of hemoglobin vesicle elevates tumor tissue oxygen tension and modifies tumor response to irradiation.
Systemic administration of hemoglobin vesicle elevates tumor tissue oxygen tension and modifies tumor response to irradiation.
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DOI：
10.1016/j.jss.2007.12.770
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Manabu Yamamoto;Y. Izumi;H. Horinouchi;Y. Teramura;H. Sakai;M. Kohno;Masazumi Watanabe;M. Kawamura-M.-Kawa
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文献类型：
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作者：
Manabu Yamamoto;Y. Izumi;H. Horinouchi;Y. Teramura;H. Sakai;M. Kohno;Masazumi Watanabe;M. Kawamura-M.-Kawa
背景：我们研制了一种包裹浓缩人血红蛋白(血红蛋白囊泡，HBVe)的磷脂脂质体囊泡，作为人工氧载体，作为红细胞输注的替代。我们已经在各种临床前模型中验证了它的氧气运输能力。最近的证据表明，人工氧载体也可能适用于包括肿瘤在内的缺血或缺氧组织的更好的氧合。据我们所知，使用脂质体类型的人工氧载体进行肿瘤氧合还没有经过严格的测试。在本研究中，我们测试了全身注射乙肝病毒是否改变了肿瘤组织的氧分压，以及是否改变了肿瘤对照射的反应。材料和方法肺癌生长在C57BL/6小鼠的左后腿皮下。当肿瘤长到大约8毫米时，实验就开始了。所有实验都是在室内空气中进行的。全身给药后45min磷光猝灭测定肿瘤组织氧分压(生理盐水5例；乙肝病毒5例；高铁血红蛋白(MetHbV)4例；高氧亲和力低P50HbV(LowP50HbV)8例)。为了测试对照射反应的影响，在单次20-Gy射线照射前给予样本(生理盐水：n=7；乙肝病毒：n=7；metHbV：n=7；lowP50HbV：n=7)，并比较其对肿瘤生长的影响。结果：与其他样本相比，注射乙肝病毒后，肿瘤组织氧分压瞬时升高约2倍。与其他样本相比，先前给药的乙肝病毒照射后，肿瘤生长略有延迟。结论乙肝病毒照射后肿瘤生长延迟的增加至少部分是通过影响肿瘤组织氧分压来实现的。
BACKGROUNDWe have developed a phospholipid liposome vesicle encapsulating concentrated human hemoglobin (hemoglobin vesicle, HbV) as an artificial oxygen carrier, as an alternative to red cell transfusion. We have verified its oxygen transporting capability in a variety of preclinical models. Recent evidence suggests that artificial oxygen carriers may also be applicable for better oxygenation of ischemic or hypoxic tissues including tumors. To our knowledge, tumor oxygenation using a liposome-type artificial oxygen carrier has not been closely tested. In the present study, we tested whether systemic HbV administration changes tumor tissue oxygen tension, and if it modifies tumor response to irradiation.MATERIALS AND METHODSLewis lung carcinoma was grown subcutaneously in the left hindleg of C57BL/6 mice. Experiments were initiated when the tumors reached approximately 8 mm. All experiments were done under room air. Tumor tissue oxygen tension was measured by phosphorescence quenching up to 45 min after systemic sample administration (saline: n = 5; HbV: n = 5; HbV containing methemoglobin (metHbV): n = 4; HbV with high oxygen affinity (lowP50HbV): n = 8) and compared between samples. To test the effects on irradiation response, samples (saline: n = 7; HbV: n = 7; metHbV: n = 7; lowP50HbV: n = 7) were administered prior to single 20-Gy irradiation, and tumor growth was compared.RESULTSTumor tissue oxygen tension transiently increased approximately 2-fold after HbV administration in comparison to other samples. Tumor growth was marginally delayed after irradiation by prior administration of HbV in comparison to other samples. HbV administration without irradiation did not affect significant tumor growth delay.CONCLUSIONSThese results correlatively suggest that HbV augmented tumor growth delay following irradiation, at least in part, by affecting tumor tissue oxygen tension.