- 著者
- Masayoshi Furushiro Satoru Suzuki Yoshiyuki Shishido Masashi Sakai Hideyuki Yamatoya Satoshi Kudo Shusuke Hashimoto Teruo Yokokura
- 出版者
- The Japanese Pharmacological Society
- 雑誌
- The Japanese Journal of Pharmacology (ISSN:00215198)
- 巻号頁・発行日
- vol.75, no.4, pp.447-450, 1997 (Released:2006-03-27)
- 参考文献数
- 15
- 被引用文献数
- 20 21
Soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) was investigated for its effect on the impaired learning of a passive avoidance task by mice induced by scopolamine or cycloheximide. SB-tPS (240, 360, 480 mg/kg) administered orally significantly prolonged the step-through latency shortened by scopolamine. SB-tPS (240 mg/kg) administered orally also prolonged the step-through latency shortened by cycloheximide. These results suggest that the effect of SB-tPS on the impaired learning behavior may be related not only to the cholinergic system but also the serotonergic system.
- 著者
- Tatsuya TSUJI Norimasa KANEDA Kunio KADO Teruo YOKOKURA Tadashi YOSHIMOTO Daisuke TSURU
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Journal of Pharmacobio-Dynamics (ISSN:0386846X)
- 巻号頁・発行日
- vol.14, no.6, pp.341-349, 1991 (Released:2008-02-19)
- 参考文献数
- 25
- 被引用文献数
- 73 98
A rat serum enzyme that catalyzes the conversion of a pro-drug, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11), to an anticancer drug, 7-ethyl-10-hydroxycamptothecin (SN-38), was purified and its properties were characterized. The enzyme was purified by column chromatography on diethylaminoethyl Toyopearl 650M, QAE-Sephadex, Sephadex G-150, Con A-Sepharose and high performance liquid chromatography with an ion-exchanger column. It was most active at pH 7.5 and was stable at pH 4-9 for 1 h at 30°C. The molecular weight was estimated to be 60 and 57 kDa by gel filtration and sodium dodecylsulfate-polyacrylamide gel electrophoresis methods, respectively, and the isoelectric point was 4.6, as determined by isoelectric focusing. The Km value for CPT-11 was 0.28 μM. This enzyme was inhibited by diisopropyl phosphorofluoridate (DFP) and phenylmethanesulfonyl fluoride (PMSF) but insensitive to eserine, p-chloromercuribenzoate (PCMB) and ethylenediaminetetraacetate (EDTA). The enzyme also hydrolyzed p-nitrophenylacetate (p-NPA), a commonly used substrate for esterases, but was not active toward acetylcholine, suggesting that the enzyme is a carboxylesterase [EC 3.1.1.1]. During the hydrolyses of CPT-11 and p-NPA, an initial burst phenomenon similar to that found in the α-chymotrypsincatalyzed hydrolysis of p-NPA was observed. Kinetic analysis revealed that the deacylation of the enzyme is the rate-limiting step in substrate hydrolysis. This enzyme was found to also split other ester derivatives of SN-38 besides CPT-11.
1 0 0 0 OA ANTITUMOR ACTIVITY OF A NEW CAMPTOTHECIN DERIVATIVE, SN-22, AGAINST VARIOUS MURINE TUMORS
- 著者
- TAKEHIKO KUNIMOTO KAZUO NITTA TOMIKO TANAKA NOBUAKI UEHARA HIROYASU BABA MIEKO TAKEUCHI TERUO YOKOKURA SEIGO SAWADA TADASHI MIYASAKA MASAHIKO MUTAI
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Journal of Pharmacobio-Dynamics (ISSN:0386846X)
- 巻号頁・発行日
- vol.10, no.3, pp.148-151, 1987 (Released:2008-02-19)
- 参考文献数
- 7
- 被引用文献数
- 7 15
The antitumor activity of a new camptothecin derivative, SN-22, was evaluated by using various murine tumors. SN-22 showed strong activity against the ascites tumors Ehrlich carcinoma, MM46, CCM, L1210, L5178Y, P388, Meth A, and B16 melanoma. In particular, the maximum increase in life span values for Ehrlich, MM46 and CCM were as high as 253-606% and many mice were cured of these tumors. The effect of SN-22 against solid tumors was also determined. The inhibition ratios were higher than 70% for MM46 and L5178Y. The LD50 of SN-22 in ICR mice was about 1.5 times that of the parent camptothecin.
- 著者
- 常岡 和子 HIROSHI ISHIHARA ALEXANDER BORRISOV DIMCHEV KOJI NOMOTO TERUO YOKOKURA MIKIO SHIKITA
- 出版者
- Journal of Radiation Research 編集委員会
- 雑誌
- Journal of Radiation Research (ISSN:04493060)
- 巻号頁・発行日
- vol.35, no.3, pp.147-156, 1994-09-15 (Released:2006-05-19)
- 参考文献数
- 25
- 被引用文献数
- 9 14
A single subcutaneous injection of a preparation of heat-killed Lactobacillus casei (LC 9018), given before or after irradiation, significantly increased the survival rate of mice that had received 8.5-Gy 137Cs whole-body γ-irradiation. A similar radioprotective effect was observed when LC 9018 was administered within the period from 2 days before irradiation to 9 h after irradiation, the pre-irradiation treatment being slightly better than the post-irradiation treatment. Increases in the weight of the spleen and in the number of endogenous spleen colonies on days 8 and 12 after irradiation suggested that the radioprotective effect was based on enhanced recovery of hematopoietic tissues. The activity of macrophage colony-stimulating factor (M-CSF) in serum was rapidly increased by the treatment and was maintained at the elevated level for 13 days. At the same time, an increased level of M-CSF mRNA was detected in the livers of the treated mice. However, LC 9018 failed to save the lives of mice when administered 3 days after irradiation, although it increased serum M-CSF as effectively as noted above. The small advantage of the pre-irradiation over the post-irradiation treatment was not explained by the increases of metallothionein in the hematopoietic tissues of the treated mice.