Abstract
In part 1, We demonstrated that fibrinolytic enzyme promoted penetration of an antitumor agent into tumors by changing the fibrin barrier of a tumor mass. Next meas ures are needed to faciliate the penetration of the anti-tumor drugs into individua l tumor cells. Reliable manifestation of their anti-tumor effect in cells should be arran ged. In this respect Kimura, Niitani and others at the National Cancer Center pr oposed a very reasonable method using lysosome labilizers. We also carried out FAMT therapy us i ng urokinase in cases of relapsed, metastasized or advanced tumor with excellent results in several cases, and recognized the effectiveness of chemotherapy combined with lysosome labilizers. Accordingly, in part 2, We examined the abilit y of fibrinolytic enzyme to potentiate penetration of anti-tumor drugs into tumor cells. The results are as follows:
1) The fibrinolytic enzyme p romoted the release of hydrolytic enzymes (Acid phosphatase and β-glucuronidase) into the surrounding medium from lysosomes in tumo r cells. The fibrinolytic enzyme also may produce changes in permeability of the cell membrane.
2) Under fluorescent microscopy using acridine orange in Yoshida sarcoma cells, lysosomes began to appear in cells about 30 minutes after urokinase administrati on, increased in size and number an hour later and began to decrease 3 hours later, when intracellular particles stained with orange were still found in cells. Then cha n ges in acid-phosphatase and β-glucuronidase activity were pursued in Yoshida s a rcoma cells by histochemical techniques after urokinase administration. In view of the above results urokinase is regarded as a lysosome labilizer and one of the promisin g agents potentiating the effect of anti-tumor drugs in tumor cells.
3) The incorporation of3H-5Fu into DNA and RNA of Yos hida sarcoma cells was potentiated by the fibrinolytic enzyme.
