著者

Masaya IMOTO Kazuo UMEZAWA Keiko KOMURO Tsutomu SAWA Tomio TAKEUCHI Hamao UMEZAWA

出版者

The Japanese Cancer Association

雑誌

Japanese Journal of Cancer Research GANN (ISSN:09105050)

巻号頁・発行日

vol.78, no.4, pp.329-332, 1987 (Released:2008-03-17)

参考文献数

12

被引用文献数

3

---

A tyrosine protein kinase inhibitor, erbstatin, showed no antineoplastic effect on L-1210 mouse leukemia when it was injected alone. Erbstatin was found to be inactivated by incubation in serum, but not in dialyzed serum. It was also inactivated in reconstituted serum containing dialyzed serum components and ferric or ferrous ion. Because erbstatin was considered to be inactivated by the ferric or ferrous ion in serum, foroxymithine, which is a potent chelator for the ferric ion, was given to the mice together with erbstatin. Administration of both erbstatin and foroxymithine showed antineoplastic activity against L-1210 leukemia.

著者

HAMAO UMEZAWA MASAYA IMOTO TSUTOMU SAWA KUNIO ISSHIKI NAOKO MATSUDA TAKESHI UCHIDA HIRONOBU IINUMA MASA HAMADA TOMIO TAKEUCHI

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.39, no.1, pp.170-173, 1986 (Released:2006-04-19)

参考文献数

15

被引用文献数

123 159

著者

KATSUTOSHI TAKAHASHI HISAO EKIMOTO SHOKO AOYAGI AKIKO KOYU HIROSHI KURAMOCHI OSAMU YOSHIOKA AKIRA MATSUDA AKIO FUJII HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.32, no.1, pp.36-42, 1979 (Released:2006-04-12)

参考文献数

12

被引用文献数

30 31

---

Pepleomycin (PEP), 3-[(S)-1'-phenylethylamino]propylaminobleomycin has potent activity and is less pulmonary toxic than bleomycin (BLM). Biological activity and toxicity of the following degradation products of PEP have been studied in detail: the product of carbamoyl migration (ISO), the product of decarbamylation (DC), the product of ring closure of the side chain on the pyrimidine moiety (RC), the depyruvamide product (DP) and the product of an enzymatic inactivation (DA). These degradation products showed much lower activity than PEP in vitro: antimicrobial and anti-HeLa activities, inhibition of DNA synthesis in AH66 cells and the DNA strand cleavage. Acute toxicity and pulmonary toxicity were tested in mice. Results indicated much lower acute toxicity corresponding to the decreased in vitro activity when compared to PEP. DP and RC did not cause lung fibrosis in mice, while ISO and DC showed 1/2.6 and 1/5.7 degree of pulmonary toxicity, respectively, in comparison with PEP.

著者

Hisao EKIMOTO Kimihiko TAKADA Takao OHNUKI Katsutoshi TAKAHASHI Akira MATSUDA Tomohisa TAKITA Hamao UMEZAWA

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.2, no.1, pp.25-31, 1987 (Released:2010-02-25)

参考文献数

26

被引用文献数

7 11

---

Sensitivity to bleomycin-induced pulmonary fibrosis was tested in various strains of mice. Among the strains examined, ICR, C57BL/10(H-2b), and C3H/He(H-2k) mice were highly sensitive to the induced pulmonary fibrosis; C57BL/6(H-2b), DBA/2(H-2d), A/J(H-2a), B6C3F1 and BDF1 mice were moderately sensitive, and CBA/JN(H-2k), BALB/c(H-2d), CDF1 and CBF1 mice were less sensitive. In congenic mice, which differ from each other only in the H-2 locus, C57BL/10(H-2b) was highly sensitive; B10·D2(H-2d) was moderately sensitive; and B10·BR(H-2k) and B10·A(H-2a) were less sensitive. Thus, the sensitivity differed depending on the haplotype of the H-2 genes. Furthermore, non-H-2 genes also seemed to be involved in the sensitivity to the pulmonary fibrosis. There was no correlation between the sensitivity to pulmonary fibrosis and enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the lung tissues, but the levels of reducing agents such as ascorbic acid and tocopherol in the lungs were inversely correlated with the sensitivity to the pulmonary fibrosis, except in the case of BALB/c and its F1 mice.

著者

HISAO EKIMOTO HIROSHI KURAMOCHI KATSUTOSHI TAKAHASHI AKIRA MATSUDA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.33, no.4, pp.426-434, 1980 (Released:2006-04-12)

参考文献数

18

被引用文献数

21 22

---

The kinetics of the reaction of BLM-Fe(II)-O2 with DNA in the absence or presence of 2-mercaptoethanol (2-ME) were studied. The total number of bases released by BLM-Fe(II)-O2 in the presence of 2-ME increased about 6.5 times more than that in the absence of 2-ME in the reaction of 6 hours at 37°C. The molar ratios of the released bases ware little affected by the reaction time, temperature or 2-ME. Among the four bases, thymine was preferentially released. On the basis of a reaction scheme of BLM-Fe(II)-O2 with DNA, the equations were derived by the steady-state method. In the absence of 2-ME, the release of bases from DNA was dependent on the concentration of BLM-Fe(II)-O2, but independent of the concentration of DNA. In the presence of 2-ME, a biphasic reaction was observed; the first one is due to BLM-Fe (II) which originally existed and the second one is due to BLM-Fe(II) produced by the reduction of BLM-Fe(III) with 2-ME. In the second reaction, the rate of the release of bases from DNA was proportional to the concentration of BLM-Fe(II) and 2-ME, but inversely proportional to the concentration of DNA. The rate-determining step in the reaction of BLM-Fe(II)-O2 with DNA in the presence of 2-ME was found to be the reduction of BLM-Fe(III) to BLM-Fe(II). By these kinetic studies, the reaction of BLM-Fe(II)-O2 with DNA in the presence of 2-ME was elucidated to proceed in a catalytic fashion. Furthermore, the maximum number of bases released by BLM from DNA was one base per twelve to thirteen bases.

著者

HISAO EKIMOTO KATSUTOSHI TAKAHASHI AKIRA MATSUDA TOMOHISA TAKITA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.38, no.8, pp.1077-1082, 1985 (Released:2006-04-19)

参考文献数

12

被引用文献数

25 34

---

Lipid peroxidation catalyzed by bleomycin (BLM)-metal complexes was studied in vitro using arachidonic acid as the substrate. Iron complexes of BLM caused extensive lipid peroxidation, but other metal complexes did not. The lipid peroxidation caused by the iron complexes was inhibited by antioxidants such as dl-α-tocopherol, ascorbic acid etc., but not by other scavengers of hydroxyl and superoxide radicals, and of singlet oxygen. Cyanide ion suppressed the lipid peroxidation caused by BLM-Fe(II), but did not suppress the peroxidation activity of BLM-Fe(III). The peroxidation activity of BLM-Fe(II) was lost instantly by pre-incubation of the complex at 37°C before mixing with arachidonic acid, but that of BLM-Fe(III) was not. These results indicate that the active form for the lipid peroxidation derived from BLM-Fe(II) differs from that of BLM-Fe(III).

著者

HISAO EKIMOTO MINAKO AIKAWA TAKAO OHNUKI KATSUTOSHI TAKAHASHI AKIRA MATSUDA TOMOHISA TAKITA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.38, no.1, pp.94-98, 1985 (Released:2006-04-19)

参考文献数

16

被引用文献数

5 6

---

Pulmonary fibrosis in mice induced by peplomycin (PEP) was suppressed by administration of anti-inflammatory agents such as prednisolone and D-penicillamine during or after the administration of PEP. Pulmonary fibrosis was also suppressed by administration of cyclophosphamide, an immunosuppressive antitumor agent before, during or after the administration of PEP. The pulmonary fibrosis in athymic nude mice induced by PEP was less than that in normal mice. The low response in the nude mice was enhanced by transfer of thymocytes to the same level as that in the normal mice. This suggests that the immune system, especially thymus-dependent immunity, is involved in the pulmonary fibrosis induced by PEP.

著者

HISAO EKIMOTO KINIIHIKO TAKADA KATSUTOSHI TAKAHASHI AKIRA MATSUDA TOMOHISA TAKITA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.37, no.6, pp.659-663, 1984 (Released:2006-04-19)

参考文献数

30

被引用文献数

7 5

---

The pulmonary fibrosis caused by peplomycin (PEP) was studied in terms of oxygen toxicity using ICR mice. When 16μg of PEP was administered intratracheally in mice after exposure to the air containing 75% O2 for 10 days, the pulmonary fibrosis was completely suppressed, while when mice were exposed to 75% O2 after the administration of PEP, the fibrosis was much severe than that of mice raised in atmospheric air. In 50% O2 similar oxygen effect was also observed, but it was weaker than that in 75% O2. In 90% O2 the oxygen toxicity was observed in mice without administration of PEP. When mice were exposed to 75% O2 the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which are relevant to the detoxication of active oxygen species, were not increased in the lung, but the levels of reducing agents such as glutathione and ascorbic acid, and high molecular substances having 1O2-scavenging activity were enhanced. The results suggest that these materials have some roles to decrease the pulmonary fibrosis caused by PEP.