Riley V
Nutr Cancer. 1981;2(3):165-80. doi: 10.1080/01635588109513678.
l-Asparaginase is used as a therapeutic enzyme to selectively destroy asparagine-dependent cancer cells. This study explores alternate means for depriving cancer tissues of l-asparagine and other specific amino acids or vital substrates required by normal and cancer cells. Hemodialysis, employing an artificial kidney, was used to remove free amino acids from the blood of a patient with lymphoblastic lymphosarcoma. Approximately 1200 mg, the equivalent of the patient's total amino acid pool, was removed every 100 minutes while the patient was on the artificial kidney. Despite this impressive clearance capacity, the dialyzer was not able to completely overcome the endogenous amino acid influx of the patient. The combined data indicate that hemodialysis is theoretically capable of removing specific amino acids to a therapeutic level, but that the clearance efficiency of the artificial kidney must be significantly increased or the endogeneous amino acid influx must be effectively blocked before hemodialysis can be successfully applied to cancer patients. An unexpected finding was strikingly increased during dialysis but returned to the original levels when dialysis was temporarily discontinued. The presence of a nonprotein inhibiting factor capable of suppressing an increase in the peripheral malignant lymphocyte population could be an explanation. This postulated factor behaved during dialysis as though its molecular weight was relatively low, possibly less than 500.
L-天冬酰胺酶被用作一种治疗性酶,以选择性地破坏依赖天冬酰胺的癌细胞。本研究探索了剥夺癌组织中天冬酰胺以及正常细胞和癌细胞所需的其他特定氨基酸或重要底物的替代方法。使用人工肾进行血液透析,以从一名淋巴细胞性淋巴肉瘤患者的血液中去除游离氨基酸。在患者使用人工肾期间,每100分钟大约能去除1200毫克,相当于患者的总氨基酸池量。尽管这种清除能力令人印象深刻,但透析器仍无法完全克服患者内源性氨基酸的流入。综合数据表明,血液透析理论上能够将特定氨基酸清除到治疗水平,但在血液透析能够成功应用于癌症患者之前,必须显著提高人工肾的清除效率,或者有效阻断内源性氨基酸的流入。一个意外发现是,在透析期间显著增加,但在暂时停止透析时恢复到原始水平。存在一种能够抑制外周恶性淋巴细胞群体增加的非蛋白质抑制因子可能是一种解释。这种假定的因子在透析期间的行为表明其分子量相对较低,可能小于500。