ROOT EFFECT HEMOGLOBINS IN CANCER THERAPY

描述：这个项目的目的是调查潜在的 根效应血红蛋白在改善肿瘤氧合中的作用 癌症治疗。在一些鱼中发现了根效应血红蛋白。《根》 效应本质上是一种夸张的玻尔效应，其中氧亲和力是 在酸性pH条件下，酶活性大大降低。根效应血红蛋白作为压力 换能器。在适当的情况下，可以加载 在环境氧气压力下的血红蛋白，即人类或哺乳动物的呼吸 环境空气，并在极大地增加，甚至高压下输送氧气， 酸性组织中的压力。美国虹鲑鱼的血红蛋白病。 盖尔德内里将被用于这项工作。在pH为7.4时，它显示出 氧-血红蛋白解离曲线与大多数哺乳动物相似 血红蛋白。根据确切的实验条件， P(50)，在pH值时，血红蛋白达到一半饱和的分压。 大约6.8托可以高达1,000托。 两个成熟的啮齿动物肿瘤系统，EMT6小鼠乳腺癌 在BALB/C RW小鼠和WAG/RiJ大鼠的BA1112横纹肌肉瘤中， 已被证明含有耐缺氧细胞，可抵抗 电离辐射，将用于本研究。鲑鱼三号血红蛋白将 在荷瘤动物身上作为无基质血红蛋白或 作为重新包装在脂质体或完整的红细胞中的血红蛋白。它的影响 关于肿瘤缺氧和放射生物学反应的研究将使用 氧微电极测量及其经典的测定方法 “放射性生物低氧组分”包括体内-体外配对 放射克隆细胞存活法，肿瘤再生延迟，以及 长期的局部肿瘤控制。初步实验包括一个直接的 红血包埋根效应与非根效应的疗效比较 利用配对辐射细胞研究血红蛋白对肿瘤氧合的影响 BA1112横纹肌肉瘤的生存方法已经证明 这种方法的潜力。辐射响应将被确定为 单次放射治疗和分次放射疗程 心理治疗。平行研究将调查根效应的影响 血红蛋白对选定正常组织的辐射反应，包括 皮肤、骨骼再生和造血系统。

DESCRIPTION: The purpose of this project is to investigate the potential usefulness of Root effect hemoglobins to improve tumor oxygenation for cancer therapy. Root effect hemoglobins are found in some fish. The Root effect is essentially an exaggerated Bohr effect wherein oxygen affinity is greatly decreased at acid pH. Root effect hemoglobins serve as pressure transducers. Under appropriate circumstances it is possible to load hemoglobin at ambient oxygen pressure, i.e. a human or mammal breathing ambient air, and to deliver oxygen under vastly increased, even hyperbaric, pressure in acidic tissues. Hemoglobin Ill of the American rainbow trout S. gairdneri will be used for this work. At pH 7.4 it demonstrates an oxygen-hemoglobin dissociation curve similar to that of most mammalian hemoglobins. Depending upon the exact experimental conditions, the value of P(50), the partial pressure at which hemoglobin is one-half saturated, at pH circa 6.8 can be as high as 1,000 torr. Two well established rodent tumor systems, the EMT6 mouse mammary carcinoma in BALB/C Rw mice and the BA1112 rhabdomyosarcoma in WAG/Rij rats, which have been shown to contain hypoxic cells resistant to the effects of ionizing radiation, will be used for this study. Trout III hemoglobin will be administered to tumor bearing animals either as stroma-free hemoglobin or as hemoglobin repackaged in liposomes or intact red blood cells. Its effect on tumor hypoxia and radiobiological response will be investigated using oxygen microelectrode measurements and the classic methods for determining "radiobiological hypoxic fraction" including the in vivo-in vitro paired radiation clonogenic cell survival method, tumor regrowth delay, and long-term local tumor control. Preliminary experiments including a direct comparison of the effects of red blood encapsulated Root effect and non-Root effect hemoglobin on tumor oxygenation using the paired radiation cell survival method with the BA1112 rhabdomyosarcoma have demonstrated the potential of this approach. Radiation response will be determined for single radiation treatments and for fractionated courses of radiation therapy. Parallel studies will investigate the effects of the Root effect hemoglobin on the radiation reactions of selected normal tissues including skin, bone regrowth, and the hematopoietic system.