EXPERIMENTAL AND CLINICAL STUDIES ON THE ANTI-TUMOR AGENT PODOPHYLLIC ACID-ETHYL HYDRAZIDE
1970 Volume 18 Issue 2 Pages 189-205
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1970 Volume 18 Issue 2 Pages 189-205
In 1861 BENTLEY reported the effectiveness of podophyllin on skin cancer, and in 1942 KAPLAN used this substance on condyloma acuminata and also ascertained its effectiveness. The mechanism of its action was attributed by SULLIVAN et al. in 1947 to the impediment of the mitosis of the cells in its metaphase.
In the present studies, the antitumor agent ethyl hydrazide of podophillic acid (SP-I) was administered to the animals with such experimental tumors as YOSHIDA's sarcoma, EHRLICH's ascites carcinoma and sarcoma-180. and the antitumor effect of the substance in vitro and in vivo was explored together with a study on the clinical application of SP-I. The results obtained were as follows :
1. In the experiments in vitro, the antitumor effectof SP-1 on YOSHIDA's sarcoma was recognized at a concentration of 0.00125mcg/ml and above, and its inhibitory effect on the growth of the cells reached 50% at a concentration of 0.05 mcg/ml. Its anti-tumor effect on EHRLICH's ascites carcinoma was not remarkable so as to allow the survival of the animal until its concentration reached 12.5mcg/ml and above. The survival of the animal was most effected by keeping SP-I in contact with the tumor at 37°C for 12 hours.
2. In the experiments in vivo, SP-I had little life prolonging effect against a sarcoma-180 of the ascites type. As to the tumors of a solid type, it was noted that the increase of the tumor weight was inhibited up to 55.4% in the case of EIIRLICH's solid ascites carcinoma and 70.6%in the case of solid sarcoma-180 at a dose level of 50mg/kg body weight.
3. As to the morphological changes suffered by the cells, inhibition of karyokinesis was observed at SP-I concentrations between 50mg/ml and 0.8mcg/ml.
4. SP-I has been clinically applied to a total of 37 cases of cancers of the stomach, esophagus, liver etc. over five years and objective improvement was attained in 14 cases of postoperative cancer recurrence and 2 cases still under administration.
