Butschak G, Schulze B, Küster A, Niederhausen T, Niemeryer U, Graffi A
Zentralinstitut für Molekularbiologie, Akademie der Wissenschaften DDR, Berlin-Buch.
Arch Geschwulstforsch. 1989;59(6):407-13.
Graffi et al. have proposed the use of exogenous enzymes for selective cleavage of inactive transport forms of cancerostatic substances in tumor tissue. Enzymes appropriate for this purpose should, if possible, show also a certain enrichment in the tumor tissue. In studies on the pH-labile alpha-L-arabinofuranosidase from G. myabena in tumor-bearing mice, under defined conditions in the tumors there could be demonstrated a higher concentration of the active form of the enzyme than in most of the normal tissues. However, the enzyme activity is eliminated from the organism in a relatively short time through excretion and inactivation. The application of glucose led to a strong increase of activity of the enzyme injected, both in the tumors and in the normal tissues. It has been shown in the present investigations that this increase in the enzyme activity can be curtailed more strongly in normal tissue by alkali application than in the tumors. In this way, a distribution of the enzyme activity favorable for therapy experiments is obtained. Only in the kidney and urine has a higher activity of the applied enzyme been measured than in the tumors. In the second part of this work it has been attempted to achieve accumulation of activity of the pH-stable alpha-L-arabinofuranosidase from A. niger through application of angiotensin, but no positive results have been reached under the various experimental conditions used.
格拉菲等人提出使用外源性酶对肿瘤组织中抗癌物质的无活性转运形式进行选择性裂解。适用于此目的的酶,如果可能的话,在肿瘤组织中也应表现出一定程度的富集。在对来自米曲霉的对pH敏感的α-L-阿拉伯呋喃糖苷酶在荷瘤小鼠中的研究中,在特定条件下,肿瘤中该酶活性形式的浓度高于大多数正常组织。然而,该酶活性会通过排泄和失活在相对较短的时间内从机体中消除。葡萄糖的应用导致所注射酶的活性在肿瘤和正常组织中均大幅增加。本研究表明,通过应用碱,正常组织中酶活性的增加比肿瘤中受到的抑制更强。通过这种方式,获得了有利于治疗实验的酶活性分布。仅在肾脏和尿液中测得的所应用酶的活性高于肿瘤中的活性。在这项工作的第二部分,尝试通过应用血管紧张素使黑曲霉的对pH稳定的α-L-阿拉伯呋喃糖苷酶的活性积累,但在所使用的各种实验条件下均未取得阳性结果。