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    • 1. 发明申请
    • 5-FLUOROURACIL-RESISTANT BACTERIA AND METHOD FOR PRODUCTION THEREOF
    • 5-氟耐药细菌及其生产方法
    • US20090280091A1
    • 2009-11-12
    • US11910880
    • 2006-04-04
    • Yoshinori HamajiMinoru FujimoriJun AmanoShun 'Ichiro Taniguchi
    • Yoshinori HamajiMinoru FujimoriJun AmanoShun 'Ichiro Taniguchi
    • A61K35/74C12N1/20A61P35/00
    • C12N9/78C12N1/20
    • The present invention provides a method for producing a cytosine deaminase (CD)-expressing, 5-fluorouracil (5-FU)-resistant microorganism which can grow in anaerobic tumor tissues, can express CD, and has a resistance to 5-FU at a concentration that is at least effective for antitumor activity. More specifically, the method is a method (A) comprising performing subculture or acclimation culture of a CD-expressing microorganism which can grow in anaerobic tumor tissues, in the presence of 5-fluorocytosine (5-FC), or a method (B) comprising (1) performing subculture or acclimation culture of a microorganism which can grow in anaerobic tumor tissues and does not express CD, in the presence of 5-FU to produce a 5-FU-resistant microorganism and (2) transforming the 5-FU-resistant microorganism by introducing a CD gene. The present invention also provides the CD-expressing, 5-FU-resistant microorganism and a pharmaceutical composition comprising the microorganism.
    • 本发明提供了一种能够在厌氧性肿瘤组织中生长的胞嘧啶脱氨酶(CD)表达的5-氟尿嘧啶(5-FU)抗性微生物的制备方法,其可以表达CD,并且具有对5-FU的抗性 至少对抗肿瘤活性有效的浓度。 更具体地,该方法是包括在5-氟胞嘧啶(5-FC)或方法(B)的存在下进行可在厌氧性肿瘤组织中生长的表达CD的微生物的传代培养或适应培养的方法(A) 包括(1)在5-FU存在下进行在厌氧性肿瘤组织中生长并且不表达CD的微生物的传代培养或适应培养以产生5-FU抗性微生物,和(2)转化5-FU 引入CD基因的抗性微生物。 本发明还提供了表达CD的5-FU抗性微生物和包含微生物的药物组合物。