Ishiko O, Hirai K, Nishimura S, Sumi T, Honda K, Deguchi M, Tatsuta I, Ogita S
Department of Obstetrics and Gynecology, Osaka City University Medical School, Osaka, Japan.
Clin Cancer Res. 1999 Sep;5(9):2660-5.
We carried out a fundamental study to search for a therapeutic modality that would remove the anemia-inducing substance (AIS) from the plasma of cancer patients because it is thought to be one of the substances responsible for anemia and immunodeficiency in advanced cancer patients. Using AIS isolated from the plasma of patients with advanced ovarian carcinoma, we confirmed that adsorption of AIS to noncoated charcoal was nonspecific and high. Moreover, it was verified that VX2 carcinoma-bearing rabbits are an optimal experimental model for plasma perfusion. The data obtained on day 40 after transplantation (hemoglobin, 9.1+/-2.1 g/dl; osmotic pressure inducing RBC lysis, 137+/-11 mosmol/kg; lymphocyte stimulation index, 8.8+/-8.6; and RBC fragility-inducing activity, 40+/-9 mosmol/kg) proved similar to the hematological findings in patients with cancer cachexia. A 1-h plasma perfusion (3 ml/min) through noncoated charcoal was performed in tumor-bearing rabbits, and it resulted in the restoration of RBC fragility-inducing activity and suppression of lymphocyte blast formation to pretransplantation values. When plasma perfusion was performed every 3 days, RBC fragility-inducing activity, which increased again 3 days after perfusion, was diminished, and RBC osmotic resistance was within the normal range from the fourth perfusion onward. These results showed that cyclic plasma perfusion is effective in sustained removal of RBC fragility-inducing factor from plasma, suggesting that it might have the potential for clinical application.
我们开展了一项基础研究,以寻找一种治疗方法,能够从癌症患者血浆中去除贫血诱导物质(AIS),因为该物质被认为是晚期癌症患者贫血和免疫缺陷的原因之一。利用从晚期卵巢癌患者血浆中分离出的AIS,我们证实AIS与未包被木炭的吸附是非特异性的且吸附率高。此外,还证实VX2荷瘤兔是血浆灌注的最佳实验模型。移植后第40天获得的数据(血红蛋白,9.1±2.1 g/dl;诱导红细胞裂解的渗透压,137±11 mosmol/kg;淋巴细胞刺激指数,8.8±8.6;以及诱导红细胞脆性的活性,40±9 mosmol/kg)与癌症恶病质患者的血液学检查结果相似。对荷瘤兔进行1小时(3 ml/分钟)的未包被木炭血浆灌注,结果红细胞脆性诱导活性恢复,淋巴细胞母细胞形成受到抑制,降至移植前水平。当每3天进行一次血浆灌注时,灌注后3天再次升高的红细胞脆性诱导活性降低,从第四次灌注起红细胞渗透压耐受性在正常范围内。这些结果表明,循环血浆灌注能有效持续去除血浆中的红细胞脆性诱导因子,提示其可能具有临床应用潜力。