- 著者
- 河野 彬 菅田 節朗 原 泰寛 田中 睦子 加留部 喜晴 松島 美一
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.31, no.5, pp.1666-1669, 1983-05-25 (Released:2008-03-31)
- 参考文献数
- 19
- 被引用文献数
- 2
A sensitive method for the assay of pyrimidine nucleoside phosphorylases in preparations of human and animal tissues by determination of pyrimidines is described. Pyrimidines formed enzymatically from thymidine, uridine, 5-fluorouridine, and 5'-deoxy-5-fluorouridine are determined by means of high-performance liquid chromatography with ultraviolet (UV) detection. The pyrimidines, after extraction with ethyl acetate, are separated by reversed-phase chromatography on μ-Bondapak C-18/Porasil. The limits of detection are 2.5, 1.0, and 2.0 pmol for thymine, uracil, and 5-fluorouracil, respectively.
- 著者
- 河野 彬 原 泰寛 菅田 節朗 松島 美一 上田 亨
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.32, no.5, pp.1919-1921, 1984-05-25 (Released:2008-03-31)
- 参考文献数
- 15
- 被引用文献数
- 12 16
A thymidine phosphorylase preparation was partially purified from human liver tumor tissues (poorly differentiated adenocarcinoma). The substrate specificity of the enzyme was investigated with eleven pyrimidine nucleosides. Thymidine and 2'-deoxyuridine were good substrates, while uridine, 3'-deoxyuridine, 5'-deoxyuridine, and 2', 3'-dideoxy-3'-hydroxy-methyluridine were not. Uridines substituted at the 5-position by a cyano, bromo, or chloro group were also phosphorolyzed by the enzyme, but the activity for 5-fluorouridine was much lower. 5'-Deoxy-5-fluorouridine was also cleaved. Either a 5-substituent or a 2'-deoxy structure seems to be essential for a good substrate.
- 著者
- 河野 彬 原 泰寛 菅田 節朗 加留部 善晴 松島 美一 石塚 秀夫
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.31, no.1, pp.175-178, 1983-01-25 (Released:2008-03-31)
- 参考文献数
- 20
- 被引用文献数
- 77 93
Activities of pyrimidine nucleoside phosphorylases were assayed in extracts of human tumors, normal tissues of the same organs and tumors of mice (Sarcoma-180) and guinea pigs (Line-10), with thymidine (dThd), uridine (Urd), and 5'-deoxy-5-fluorouridine (5'-DFUR) as substrates. The nucleoside cleaving activities were higher in extracts of human tumor tissues than in those of normal tissues of the same organs. In human tissues, phosphorolytic activitiy towards dThd was high, while that towards Urd was low. In animal tumors, Urd was the best substrate. 1-(2'-Deoxy-β-D-glucopyranosyl)-thymine (GPT), a specific inhibitor of uridine phosphorylase, inhibited the phosphorolysis of Urd and 5'-DFUR in extracts of animal tumors, but not that of dThd and 5'-DFUR in extracts of human tumors. A thymidine phosphorylase preparation was partialy purified from human lung cancer. Km values of the preparation were 2.43×10-4 M and 1.69×10-3 M for dThd and 5'-DFUR, respectively. We conclude that in human tumors a thymidine phosphorylase activity converts 5'-DFUR to 5-fluorouracil, an activated form.
- 著者
- 菅田 節郎 河野 彬 原 泰寛 加留部 善晴 松島 美一
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.34, no.3, pp.1219-1222, 1986-03-25 (Released:2008-03-31)
- 参考文献数
- 16
- 被引用文献数
- 5 11
A thymidine phosphorylase (TP) preparation was partially purified from human gastric cancer (poorly differentiated adenocarcinoma). The specific activity of the final preparation represented a 379-fold purification of the 7000g supernatant of tissue homogenate. The phosphorolytic activities toward thymidine (dThd), 5'-deoxy-5-fluorouridine (5'-DFUR), and 1-(tetrahydro-2-furanyl)-5-fluorouracil (Tegafur) remained closely in parallel during the whole purification procedure. The results provide evidence in support of the assumption that 5'-DFUR and Tegafur are converted into 5-fluorouracil, an activated form of the antitumor agents, in humn tumor tissues by a TP activity. The values of Km of the TP preparation were 1.68×10-4, 1.72×10-3, 1.33×10-2, and 4.76×10-2M for dThd, 5'-DFUR, Tegafur, and uridine, respectively.
- 著者
- 山下 正文 橋本 隆寿 平川 俊彦 福島 武雄 朝長 正道 原 泰寛 河野 彬 田中 睦子
- 出版者
- The Japan Neurosurgical Society
- 雑誌
- Neurologia medico-chirurgica (ISSN:04708105)
- 巻号頁・発行日
- vol.25, no.8, pp.613-619, 1985-08-15 (Released:2006-09-21)
- 参考文献数
- 17
- 被引用文献数
- 1 2
To evaluate the usefulness of 5'-deoxy-5-fluorouridine (5'-DFUR) therapy for brain tumor, the pharmacokinetics of 5'-DFUR and 5-fluorouracil (5-FU) in the tumor, in the white matter surrounding the tumor and in the serum were investigated, and the thymidine phosphorylase, the main activating enzyme of 5'-DFUR in human tissues, was also studied. Materials were obtained from 24 cases of primary brain tumors and from 4 cases of metastatic carcinoma. During the operation 500 or 1, 000 mg of 5'-DFUR was administrated intravenously, and blood, tumor tissue and white matter were taken mainly within 60 minutes and partly within 180 minutes after intravenous administration of 5'-DFUR. In some cases samplings were performed serially. Concentrations of 5'-DFUR and 5-FU were measured by high performance liquid chromatography, and thymidine phosphorylase activity in tissue extracts was obtained against d-thymidine and/or 5'-DFUR as substrates. The concentrations of 5'-DFUR and 5-FU in serum decreased immediately in an exponential mode after intravenous administration of 1, 000 or 500 mg of 5'-DFUR. High concentrations of 5'-DFUR and 5-FU in the tumor tissues were noticed in malignant tumors, such as glioblastoma, ependymoma and chondrosarcoma, and 5-FU concentrations in the tumor in two cases of glioblastoma and one of ependymoma were higher than that in their sera. An important characteristic of 5'-DFUR was that it was converted to 5-FU in various tissues predominantly in malignant neoplasms. Thymidine phosphorylase activity was more prominent in glioblastoma, metastatic carcinoma and chordoma. Although the 5'-DFUR concentration in white matter was considerable, the 5-FU concentration was negligible suggesting low enzyme activity. An effect of 5'-DFUR therapy on malignant brain tumor should be expected from the high concentration of 5' DFUR and 5-FU in the tumor tissue. However, these high concentrations rapidly decreased, therefore, the appropriate mode of prescription of 5'-DFUR should be considered in clinical practice.