STUDIES ON ANTITUMOR ACTIVITIES AND PULMONARY TOXICITY OF PEPLEOMYCIN SULFATE (NK631)

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  • EBIHARA KAZUO
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • EKIMOTO HISAO
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • ITCHODA YUKO
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • ABE FUMINORI
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • INOUE HIROSHI
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • AOYAGI SHOKO
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • YAMASHITA TAKUMI
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • KOYU AKIKO
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • TAKAHASHI KATSUTOSHI
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • YOSHIOKA OSAMU
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.
  • MATSUDA AKIRA
    Research Laboratories, Pharmaceutical Division, Nippon Kayaku Co., Ltd.

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Other Title
  • 硫酸ペプレオマイシン (NK631) の抗菌性, 抗腫瘍性, および肺線維化能に関する基礎的研究
  • リュウサン ペプレオマイシン NK631 ノ コウキンセイ コウ シュヨウセイ

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Abstract

The antimicrobial and antitumor activities, and the pulmonary toxicity of pepleomycin (NK631) were studied in comparison with bleomycin (BLM).<BR>NK631 showed a broad antimicrobial spectrum against gram positive and gram negative bacteria equally to BLM, and its activity was about twice higher than BLM.<BR>NK631 showed higher activity on cultured HeLa S3 cells and higher antitumor effect on the transplanted tumors of EHRLICH solid carcinoma in mice, AH66 and AH66F ascites hepatoma in rats, and lower antitumor effect on EHRLICH ascites carcinoma in mice than BLM. Similarly to BLM, NK631 did not show satisfactory activity on L1210 leukemia in mice. NK631 showed marked effect on chemically induced squamous cell carcinoma, spontaneous lymph sarcoma of a dog, human and dog gastric cancer heterotransplanted in nude mice equally to BLM. Furthermore NK631 exhibited remarkably higher antitumor activity on lymph node metastasis of AH66 ascites hepatoma of rats and chemically induced gastric carcinoma of rats than BLM.<BR>Pulmonary toxicity of NK631 was low as 1/3 in incidence and 1/4 in grade of the BLM in old mice system. This trend was confirmed by chemical analysis of hydroxyproline in lung.

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