著者

尾崎 庄一郎 秋山 隆彦 森田 剛夫 久米川 昌浩 長瀬 敏夫 上原 宣昭 星 昭夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.11, pp.3164-3166, 1990-11-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

12 12

---

Various kinds of 5'-O-unsaturated acyl 5-fluorouridines were synthesized to obtain 5-fluorouridine derivatives with low toxicity and high antitumor activity. Antitumor activity of the compounds against L-1210 leukemia in mice was examined, and the 5'-O-4-opentenoyl derivative showed the highest antitumor activity.

著者

吉田 光二 星 昭夫 榑谷 和男 金井 貞 市野 元信

出版者

The Japanese Cancer Association

雑誌

GANN Japanese Journal of Cancer Research (ISSN:0016450X)

巻号頁・発行日

vol.66, no.5, pp.561-564, 1975-10-31 (Released:2008-10-23)

参考文献数

12

---

Effect of substitution of 5-position of cyclocytidine with fluorine on its antitumor activity in cultured cells was examined. 5-Fluorocyclocytidine was active against cultured L-5178Y cells similar to cyclocytidine. IC50 of the compound was 0.054μg/ml. This compound inhibited thymidine incorporation into acid-insoluble fraction of the cells. Cell growth inhibition by 5-fluorocyclocytidine was reversed by deoxycytidine but not by thymidine and deoxyuridine. On the other hand, cell growth inhibition by 5-fluorouracil was reversed by thymidine and deoxyuridine. As a result, site of action of 5-fluorocyclocytidine was considered to be similar to that of cyclocytidine and not to 5-fluorouracil.

著者

星 昭夫 飯郷 正明 実吉 峯郎 榑谷 和男

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.21, no.7, pp.1535-1538, 1973-07-25 (Released:2008-03-31)

被引用文献数

4 4

---

Deamination of cytidine derivatives especially of cyclocytidine by mouse kidney cytidine deaminase was examined. Cyclocytidine was not deaminated at either pH6.5 or pH7.3 by the enzyme. Furthermore, cyclocytidine did not inhibit the deamination of aracytidine and ([I]/[S])0.5 value for cyclocytidine was over 100. As a result, cyclocytidine is found to be markedly active compound with resistance against cytidine deaminase.

著者

星 昭夫 官沢 文彦 飯郷 正明 榑谷 和男

出版者

The Japanese Cancer Association

雑誌

GANN Japanese Journal of Cancer Research (ISSN:0016450X)

巻号頁・発行日

vol.66, no.5, pp.539-546, 1975-10-31 (Released:2008-10-23)

参考文献数

12

被引用文献数

2

---

Combination effect of antitumor agents, including cyclocytidine and cytosine arabinoside, was evaluated on the conception of pharmacological synergism and not of therapeutic synergism. Ascites sarcoma-180 and L-1210 leukemia were used as tumor systems. In sarcoma-180 system, combinations of cyclophosphamide plus cyclocytidine or cytosine arabinoside by simultaneous administration and cyclocytidine plus Daunorubicin or Vinblastine by alternate administration provided synergism. In L-1210 system, many compounds in combination with cyclocytidine or cytosine arabinoside in both simultaneous and alternate administrations provided synergism. Combination effect of agents was affected by the schedule of drug administration. It was found that the combination effect of drugs in one tumor system cannot be generalized to that in other tumor systems, even though equally effective doses of agents were administered in both tumor systems. Toxicity of cytosine arabinoside in combination with other drugs was affected by the schedule of administration. Compounds which provided synergism in simultaneous administration provided antagonism in alternate one. As a result, it was found that alternate administration of drugs is advantageous for the activity and diminution of toxicity to the host animal.

著者

平山 八彦 杉原 太助 浜田 福三郎 金井 貞 疋田 重太郎 荒木 靖雄 博谷 和男 星 昭夫

出版者

The Japanese Cancer Association

雑誌

GANN Japanese Journal of Cancer Research (ISSN:0016450X)

巻号頁・発行日

vol.65, no.2, pp.153-161, 1974-04-30 (Released:2008-10-23)

参考文献数

23

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The distribution in tissues and excretion of cyclocytidine (2, 2'-anhydro-1-β-D-arabinofuranosylcytosine hydrochloride) and its metabolites in urine and feces of macaca monkeys (Macaca irus, Macaca fuscata, and Macaca mulata) and in beagle dogs were examined by the spectrophotometric assay. Distribution of cyclocytidine in plasma and tissues of rats was also examined.The administered cyclocytidine showed a half-life of 22min in plasma of dogs and monkeys, whereas the half-life of aracytidine (1-β-D-arabinofuranosylcytosine hydrochloride) was 47min in plasma of dogs and less than 5min in plasma of monkeys, because of rapid deamination of the comvound to arauridine (1-β-D-arabinofuranosyluracil) in the latter species. Cyclocytidine exhibited maximum concentration in tissues of rats and monkeys at 20 to 40min after the administration, but its metabolites, aracytidine and arauridine, were not detected in these tissues. Cyclocytidine levels in tissues diminished thereafter but were detected within the next 40 to 80min, Neither cyclocytidine nor its metabolites could be detected in the brain. When cyclocytidine was administered intravenously in dogs and monkeys, 65-85% of it was excreted in urine, almost all as intact cyclocytidine, and small amounts of aracytidine and arauridine were detected. On the other hand, the administered aracytidine was excreted only as arauridine in urine of monkeys, and aracytidine and arauridine in dogs. Cyclocytidine and its metabolites were not detected in feces of both species.It might be suggested that the distribution and elimination rate of cyclocytidine after its intravenous administration is not affected by the presence of cytidine deaminase in plasma and tissues.

著者

星 昭夫 官沢 文彦 榑谷 和男

出版者

The Japanese Cancer Association

雑誌

GANN Japanese Journal of Cancer Research (ISSN:0016450X)

巻号頁・発行日

vol.63, no.3, pp.353-360, 1972-06-30 (Released:2008-10-23)

参考文献数

12

被引用文献数

4

---

The antitumor activity of cyclocytidine was examined in a variety of tumors. Cyclocytidine was active against adenocarcinoma-755, Nakahara-Fukuoka sarcoma, ascites sarcoma-180, Ehrlich ascites carcinoma, L-1210 leukemia, and C-1498 leukemia. Cures (60-day survivors) were observed at 500mg/kg/day×5 or more of the compound in the L-1210 system and therapeutic ratio was as high as 50, though that of other known antitumor agents tested, including 1-β-D-arabinofuranosylcytosine (Ara-c), was less than 12. Therapeutic index of cyclocytidine in the solid and ascites tumors was always greater than that of Ara-c. Cumulative toxicity of cyclocytidine was surprisingly low and LD10 was 790mg/kg/day×5, whereas that of Ara-c was 82mg/kg/day×5. Cyclocytidine appears therefore to have advantages over Ara-c for clinical use.

著者

星 昭夫 官沢 文彦 榑谷 和男 実吉 峯郎 新井 祥子

出版者

The Japanese Cancer Association

雑誌

GANN Japanese Journal of Cancer Research (ISSN:0016450X)

巻号頁・発行日

vol.62, no.2, pp.145-146, 1971-04-30 (Released:2008-10-23)

参考文献数

8

被引用文献数

4

---

2, 2'-O-Cyclocytidine was active against L-1210 leukemia. Cures were observed at the optimal dose of the compound, though no cures were obtained at any dose of any of the known antitumor agents. The compound was less toxic than 1-β-D-arabinofuranosyl-cytosine and resistant to cytidine deaminase.

著者

濱田 福三郎 杉原 太助 津山 伸吾 平山 八彦 金井 貞 西村 昌数 榑谷 和男 星 昭夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.23, no.3, pp.586-591, 1975-03-25 (Released:2008-03-31)

被引用文献数

1 1

---

Newly synthesized 5-3H-cyclocytidine was injected intravenously in rhesus monkeys having a high level of cytidine deaminase which inactivates aracytidine, an antitumor substance analogous to cyclocytidine, in human plasma and tissues. After rapid distribution as intact molecule in the liver, kidney, spleen, and other organs, 46.5% of the administered radioactivity was excreted via the renal pathway within 160min. Metabolite analysis of 5-3H-cyclocytidine in plasma, tissues, and urine of the monkeys revealed that extensive or rapid degradation of cyclocytidine did not occur, and confirmed the resistance of cyclocytidine against the deaminase activity and its stability in biological condition in vivo. Phosphorylated derivatives of cyclocytidine were also detected in the monkey liver after injection.

著者

福岡 文子 徳善 玲子 星 昭夫 江上 不二夫 長沢 金蔵 加藤 好雄

出版者

The Japanese Cancer Association

雑誌

GANN Japanese Journal of Cancer Research (ISSN:0016450X)

巻号頁・発行日

vol.60, no.2, pp.187-197, 1969-04-30 (Released:2008-10-23)

参考文献数

21

---

Derivatives of 2-acylamido-6-purinethiol and/or 2-acylamido-9-alkyl-6-purinethiol were synthesized and the 2-acylamide derivatives were compared with the parent compound as to their antitumor activity and toxicity. The antitumor activity was assayed mostly with NF-sarcoma, which is known to be highly sensitive to this class of nucleic acid base analogs, but also using other types of tumors.Among the 2-acylamide derivatives, formamide and especially isobutyroylamide derivatives were found to be the most active, but not markedly more active than the parent compound. A slight decrease in the toxicity was noted among the derivatives with high antitumor activity.

著者

官沢 文彦 星 昭夫 榑谷 和男

出版者

The Japanese Cancer Association

雑誌

GANN Japanese Journal of Cancer Research (ISSN:0016450X)

巻号頁・発行日

vol.65, no.1, pp.55-60, 1974-02-28 (Released:2008-10-23)

参考文献数

22

被引用文献数

3

---

Interaction of antitumor agents in activity and in toxicity was examined separately. Ascites sarcoma-180 and ddN mice were used as the tumor system.Interaction was evaluated on the concept of pharmacological synergism and not of therapeutic synergism. In activity, 18 out of 91 combinations provided synergism and most of them contained alkylating agents and antibiotics. Antitumor agents were therefore classified into two groups from the point of drug interaction. Synergism was observed in combinations of agents in Group I, alkylating agents, antibiotics, and alkaloids. In combination of agents in Group II (antimetabolites and others), additive action was observed. As a result, 18, 65, and 8 combinations provided synergism, additive action, and antagonism, respectively.On the other hand, in toxicity, 13, 27, and 38 out of 78 combinations provided synergism, additive action, and antagonism, respectively. The combination that provided synergism in activity and antagonism in toxicity were 8 out of 91 combinations tested. In general, fortunately, combinations of antitumor agents were more than additive in activity and less than additive in toxicity.

著者

吉田 光二 星 昭夫 / 実吉 峯郎 MINEO SANEYOSHI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.30, no.3, pp.1018-1023, 1982-03-25 (Released:2008-03-31)

参考文献数

23

被引用文献数

4 6

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The mode of antiproliferative action of two 5-fluorocytosine nucleosides, 5-fluoro-cytidine (FCR) and 5-fluoro-2'-deoxycytidine (FCdR), was examined using mouse leukemia L5178Y cells in vitro. FCR and FCdR were markedly active against L5178Y cells, though the cells were deficient in cytidine deaminase activity. Both compounds increased the incorporation of 14C-labeled thymidine into the acid-insoluble fraction of L5178Y cells and decreased labeled deoxycytidine incorporation. In reversal studies, the antiproliferative effects of both compounds were almost abolished by simultaneous addition of thymidine or deoxyuridine. Deoxycytidine completely reversed the growth inhibition caused by FCdR, but not that caused by FCR. These results demonstrate that the cytotoxicity of both compounds is due to inhibition of thymidylate synthetase, presumably through formation of 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) after deamination by deoxycytidylate deaminase in the pyrimidine de novo pathway.

著者

吉田 光二 榑谷 和男 星 昭夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.26, no.2, pp.429-434, 1978-02-25 (Released:2008-03-31)

被引用文献数

2 3

---

5-Fluorouridine and 1-β-D-arabinofuranosylcytosine are active against various tumors as antimetabolites. Antitumor activity and mode of action of their nucleotides, 5-fluorouridine 5'-phosphate and 1-β-D-arabinofuranosylcytosine 5'-phosphate, were examined. 5-Fluorouridine 5'-phosphate was active similar to the nucleoside against L1210 leukemia, but the nucleotide showed higher therapeutic ratio than 5-fluorouracil and 5-fluorouridine. The mode of action of these nucleotides was examined by the incorporation of labeled precursors into acid-insoluble fraction of the cells for 30 min. Inhibition patterns of these nucleotides were the same as those of the nucleosides, but the potency of the nucleotides was very weak, and increased with time. Analysis showed that these nucleotides were dephosphorylated on the cell surface and the dephosphorylation was greater than that of phenolphthalein monophosphate. 5-Fluorouridine 5'-phosphate was considered to be a good candidate for an antitumor agent.

著者

尾崎 庄一郎 秋山 隆彦 池 祥雅 森 春樹 星 昭夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.37, no.12, pp.3405-3408, 1989-12-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

14 15

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With the aim of diminishing the toxicity of 5-fluorouridine (1) and obtaining biologically active derivatives of 1, various kinds of 5'-O-acyl-8-fluorouridines 2 were synthesized. The antitumor activity of the compounds against L-1210 leukemia in mice was examined. The 5'-O-heptanoyl derivative 2h showed the highest antitumor activity.

著者

星 昭夫 池川 哲郎 池田 善明 白川 貞雄 飯郷 正明 榑谷 和男 福岡 文子

出版者

The Japanese Cancer Association

雑誌

GANN Japanese Journal of Cancer Research (ISSN:0016450X)

巻号頁・発行日

vol.67, no.2, pp.321-326, 1976-04-30 (Released:2008-10-23)

参考文献数

13

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The antitumor activity of berberine, berberrubine, and their derivatives against sarcoma-180 ascites was determined by the total packed cell volume method. Berberine and tetrahydroberberine derivatives had no antitumor activity, but berberrubine (9-demethylberberine) and the ester derivatives of berberrubine had a strong antitumor activity. ED90 of berberrubine, its acetate and benzoate, were 15, 23, and 44mg/kg, respectively. The therapeutic indices (LD10/ED90 by the present method) of these compounds were as follows: Berberrubine hydrochloride, 6.7∼9.4; 9-acetyl-9-demethylberberine (9-acetylberberrubine) chloride, 7.6∼8.7; 9-benzoyl-9-demethylberberine (9-benzoylberberrubine) chloride, 3.4∼4.9.

著者

星 昭夫 新田 正広 本郷 祥子 花井 一也 西川 全海 小林 泰之 島 正則 花井 禎 兵地 信彦 臼井 幸男 宮北 英司 寺地 敏郎

出版者

泌尿器科紀要刊行会

雑誌

泌尿器科紀要 (ISSN:00181994)

巻号頁・発行日

vol.52, no.8, pp.645-649, 2006-08

被引用文献数

2

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症例1(63歳男).levofloxacin(LVFX)を予防投与し経直腸的生検を施行したが,急性前立腺炎の診断で入院した.敗血症に伴う播種性血管内凝固症候群(DIC)と診断し膀胱瘻造設をし治療を開始した.敗血症性ショックと診断しdopamineを投与し,徐々に安定4日目に中止したが全身の炎症所見に改善は見られず,5日目に多剤耐性大腸菌が原因と判明した.抗生剤をmeropenem(MEPN),teicoplanin(TEIC)に変更したが7日目も改善は認められず,エンドトキシン検査結果の陽性からエンドトキシン吸着療法を施行後,全身状態,炎症所見は改善傾向となった.12日目に抗DIG療法を中止し,14日目に抗生剤をcefdinir(CFDN)に変更し投与継続のまま27日目に退院となった.症例2(64歳男).cefazolin(CE2)の予防抗生剤を投与後,経直腸的前立腺生検を実施した.翌日退院したが2日目に生検後前立腺炎の診断で入院となった.敗血症に伴うDICと判断し,膀胱瘻造設し抗DIC療法を開始し,5日目に全身状態改善で抗DIC療法を中止した.原因菌は多剤耐性大腸菌で6日目から抗生剤をLVFXに変更した.17日目にLVFXを中止したが19日目に再然した.MEPNの治療開始後,主症状改善が見られ27日目にLVEXへ変更し投与継続で退院したWe report two cases of sepsis and disseminated intravascular coagulation (DIC), potentially fatal complications, following transrectal prostate biopsy. We also review similar cases reported in Japan. Case 1: A 63-year-old man received a cathartic and levofloxacin (LVFX) for prophylaxis. After transrectal prostate biopsy, he presented with fever and chills. Blood cultures grew Escherichia coli resistant to LVFX. Under a diagnosis of sepsis, he received intensive management that included endotoxin removal therapy. The patient was hospitalized for 27 days. Case 2: A 64-year-old man received a cathartic and cefazolin (CEZ) for prophylaxis. He presented with fever and chills after biopsy, and was admitted to hospital. Blood cultures grew E. coli resistant to CEZ. Under a diagnosis of sepsis, he received intravenous antibiotics, transfusion, and anti-DIC drugs. The patient was hospitalized for 11 days.