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Efficacy of two-route chemotherapy using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, in combination with angiotensin II for rat liver tumor

✍ Scribed by Keitaro Hasuda; Hiroaki Kobayashi; Ken Aoki; Shun'ichiro Taniguchi; Tsuneo Baba


Publisher
John Wiley and Sons
Year
1989
Tongue
French
Weight
556 KB
Volume
44
Category
Article
ISSN
0020-7136

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✦ Synopsis


To improve the therapeutic effects of conventional TRC using i.a. CDDP plus simultaneous i.v. STS in a rat liver tumor, we made use of the AT-11-induced hypertension method, in combination with TRC. The decrease in tumor area (-IS%), measured 8 days after the TRC using CDDP I 2 mg/ kg i.a. plus i.v. post-administration (5 min later) of STS 1,264 mg/kg, was much greater than that (+ 13%) seen in the conventional TRC, but BUN level was elevated (44.9 mg/dl). AT-II (I5 pg/kg) administered i.a. simultaneously with CDDP normalized the BUN level (20.3 mg/dl) and further decreased (-15% to -31%) the tumor area (modified TRC). The modified TRC also exhibited a higher anti-tumor effect than did CDDP 3 mg/kg with A T 4 La. (5%) at a similar BUN level (22.2 mg/dl). Loss of body weight, decrease in WBC count and changes in serum transaminases of rats treated with the modified TRC were tolerable. The improved therapeutic effect of the modified TRC was explained as follows: during AT-Il-induced hypertension, ( I ) CDDP delivery to the tumor was increased by 150% and (2) CDDP delivery to the kidney was decreased by 35%. The latter effect of A T 4 made feasible the post-administration of STS to CDDP.


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## Abstract Systemic chemotherapy using high‐dose DDP and its antidote, STS, was combined with the AT‐II‐induced hypertension method and evaluated for efficacy against s.c. tumors in rats. After i.v. infusion of DDP plus AT‐II for 5 min, STS was administered i.v. over a further 5 min. The rats trea