著者

神野 峻至 西山 直志 長谷川 隆一

出版者

学習院大学史学会

雑誌

学習院史学 (ISSN:02861658)

巻号頁・発行日

no.54, pp.71-83, 2016-03

著者

西山 直志

出版者

日本アーカイブズ学会

雑誌

アーカイブズ学研究 (ISSN:1349578X)

巻号頁・発行日

vol.22, pp.164-170, 2015-06-30 (Released:2020-02-01)

著者

神野 峻至 西山 直志 長谷川 隆一 Takayuki Jinnno Tadashi Nishiwayama Ryuichi Hasegawa

出版者

学習院大学史学会

雑誌

学習院史学 = Gakushuin historical review (ISSN:02861658)

巻号頁・発行日

no.54, pp.71-83, 2016-03

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書評

著者

西山 直志 田中 潤 那須 香織

出版者

学習院大学史料館

雑誌

学習院大学史料館紀要 (ISSN:02890860)

巻号頁・発行日

no.27, pp.巻頭1枚,347-408, 2021-03

著者

松田 好史 長谷川 怜 西山 直志 芳澤 直之

出版者

学習院大学史料館

雑誌

学習院大学史料館紀要 (ISSN:02890860)

巻号頁・発行日

no.27, pp.51-81, 2021-03

著者

西山 直志

出版者

関西医科大学医学会

雑誌

関西医科大学雑誌 (ISSN:00228400)

巻号頁・発行日

vol.34, no.1, pp.193-216, 1982-03-20 (Released:2013-02-19)

参考文献数

72

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5-fluorocytosine (5-FC), which is currently used against fungal infections with low toxicity, lacks antineoplastic activity in man because of the absence of cytosine deaminase (CDase) in mammalian cells. If enough of 5-FC is delivered to the tumor tissue and CDase in the encapsulated form is implanted in the tumor bed, it is expected that 5-FC would be deaminated to 5-fluorouracil (5-FU) and antineoplastic activity will develop at the local site with minima l systemic toxicity. In the present study, basic experiment of antineoplastic effect induced by combined administration of 5-FC and CDase on the tissue cultured neoplastic cells was reported.CDase was extracted from cultivated Escherichia coli K-12 strain and purified. Based on the differential absorption of 5-FC at A280 and 5-FU at A280, CDase activity was measured by spectrophotometric analysis, which substantiated the conversion of 5-FC to 5-FU by CDase. For in vitro studies on its cytotoxicities,2 established cell lines including HeLa and EA-285 glioma cells, and 12 human brain tumor cells in one passage culture (3 glioblastomas,1medulloblastoma,2 astrocytomas,5 meningiomas, and 1 neurinoma) were used, and changes in cellular proliferations and morphological alterations of cultured cells, induced by this combined treatment, were examined.The results from these studies showed that the combined administration of 5-FC and CDase resulted in significant growth inhibition at higher than 5μg/ml of 5-FC on both HeLa and EA-285 glioma cells although 5-FC or CDase per se had no cytostatic effect. CDase was found to be little inactivated for at least a month in in vitro at 37°C. In cultured human tumor cells, significant growth inhibition was also noted at higher than 25μg/ml of 5-FC. Malignant tumor cells had slightly higher sensitivity to this treatment than benign ones.The light microscopy revealed cellular damage including loss of cyto p lasmic details, nuclear pyknosis and fragmentation. Changes in the fine structure of the cell surface such as flattening of the surface, decrease and shortening of the cell process, and loss of microvilli were noted by scanning electron microscopy.The effect of the drugs on the cell cycle traverse of established cells was also studied by a qualitative comparison of the DNA histogram using fluorocytograph. Fluorocytographic study confirmed that the converted 5-FU at higher than 25μg/m1 resulted in an irreversible block in the early S phase with a lethal effect on both established cells.To know the site of action of the converted 5-FU in the cell cycle, firstly the phase intervals of HeLa cell cycle were determined by evaluating the changes of DNA. histograms of the cells synchronized with the excess thymidine. G1, S, and G2M phase were estimated to be 12,5, and 5 hours respectively. Secondly, analysis of the cell growth and the patterns of the DNA histograms after the drug administration at various phases of the synchronized cells were performed. The site of action of the converted 5-FU was found to be mainly in S phase although the cells in G1 and G2M phases were also influenced.The author confirmed that 5-FC was converted to 5-FU b y adding CDase and significant antineoplastic activity developed in in vitro. And the author discussed the effects of converted 5-FU on the cell cycle progression as a mechanism of 5-FC and CDase treatment, and a design of capsule containing the enzyme for future clinical application.