For their characteristic of exhibiting no rejection of allogeneic tissue due to congenitally absent T-cell function, the nude mice reported by Issacson for the first time in 1962 have been calling for attention in the discipline of cancer research in recent years. It has been demonstrated by some investigators that the nude mice, when applied to experiments of cancer response to various treat ments, including carcinostatics, have proved an experimental system considerably close to an ideal one available at present, without the drawbacks of the other systems used for the same purpose. Since 1977, the author has been successfully subtransplanting various human urogenital malignant neoplasms in the nude mice, and recently performed experimental treatments of a human bladder cancer transplantable to the nude mice (B1-4).
1) B1-4 is a poorly differentiated transitional cell carcinoma, characterized by such a high successful transplantation rate as close to 100%, very stable growth, relatively small standard deviations (Fig. 3), and succession of the histologic characteristics of the primary tumor (Fig. 11, 12, 13, 14, 15), and has proved good enough for use as a system in experiments of carcinostatics in the treatment of human malignancies
2) B1-4 that had been subtransplanted for 5 or 6 generations was used for the experimental treatments. Observation was, as a rule, performed for 4 weeks after the transplantation (for 5 weeks after the transplantation in the treatments with adriamycin and 1-GHP). The therapeutic effects of the treatments were evaluated chiefly in terms of the gross regressive effect according to the tumor growth curve, together with histologic findings. The following treatments were performed (Table 1):
a) Extracorporeal
60Co radiation over the locality of tumor: Radiated only once every 2 weeks after the transplantation (500, 1000 and 2000 rads).
b) Subcutaneous application of adriamycin in the area adjacent to tumor: Applied once a day, for 10 consecutive days, from 24 hours after the transplantation (0.75 and 1.5mg/kg).
c) Platinum compounds:
i) CDDP (Cis platinum (II) diaminodichloride): Injected intaperitoneally 3 times in total, i.e., 24 hours, on day 5 and day 9 after the transplantation (2.5 and 5.0mg/kg).
ii) 1-GHP (Platinum glucuronate cyclohexane trans-1-dach): Injected intraperitoneally 3 times in total, i.e., 24 hours, on day 5 and day 9 after the transplantation (50 and 100mg/kg).
3) (a) It was adriamycin that proved most effective. The tested doses of 0.75 and 1.5mg/kg both inhibited the growth of the tumor significantly (P<0.001, respectively). Especially, in the group treated with 1.5mg/kg, the tumor almost disappeared in 3 weeks, and did not grow again thereafter (Table 3, Fig. 6). Histology disclosed a marked regression of the tumor, as well as atrophy degeneration and necrosis of tumor cells (Fig. 16, 17).
(b) It was the platinum compounds that proved second most effective. CDDP, in both doses of 2.5 and 5.0mg/kg, and 1-GHP, in a dose of 100mg/kg, inhibited the growth of the tumor significantly (0.02<P<0.05; 0.001<P<0.01; 0.05<P<0.1) (Fig. 7, 8). Although these compounds did not exert so marked a tumor growth-inhibitory effect as did adriamycin, they reduced the T/C ratio considerably (7.71%, 18.96% and 3.56%) (Table 3); hence, they may be expected to prove very effective in treating bladder cancer in the future.
(c) The
60Co radiation did not exert so marked an effect but a transient tumor regressing tendency with 2000 rads, which was suggestive of the limitations of a single therapy (Fig. 5).
4) In an attempt to establish a transplantation experimental system in other common experimental animals than the nude mice which can be reared in common experimental conditions, an experiment was made of heterotransplantation of the same tumor to hamsters.
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