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1. 发明授权

US06703375B2 Molecular chemotherapy enhancement of radiotherapy 失效
标题翻译：分子化疗放疗增强
公开(公告)号：US06703375B2
公开(公告)日：2004-03-09
申请号：US10304436
申请日：2002-11-26
申请人： Donald J. Buchsbaum , C. Ryan Miller , G. Yancey Gillespie , Robert J. Garyer, Jr.
发明人： Donald J. Buchsbaum , C. Ryan Miller , G. Yancey Gillespie , Robert J. Garyer, Jr.
IPC分类号： A61K4800
CPC分类号： C12N15/86 , A61K38/45 , A61K38/50 , A61K41/00 , A61K48/00 , C12N2710/10343 , C12N2810/859 , Y02A50/473
摘要： The present invention provides a new approach for cancer treatment by utilizing gene therapy combined with radiation therapy to enhance cytotoxicity in malignant cells. Specifically, the present invention demonstrates that molecular chemotherapy with the cytosine deaminase gene and 5-fluorocytosine is an effective radiosensitizing strategy which may lead to substantial improvement in tumor control, with less normal tissue toxicity than conventional systemic administration of 5-fluorouracil, that would translate into improved cure rates and better survival. A noninvasive method is described for continuous in vivo monitoring of 5-fluorouracil production via magnetic resonance spectroscopy An adenovirus encoding cytosine deaminase gene which selectively replicates in tumor cells with a defective p53 pathway was constructed. Also provided is an adenovirus which encodes a fusion protein of cytosine deaminase and uracil phosphoribosyltransferase.
摘要翻译：本发明通过利用与放射治疗相结合的基因治疗来增强恶性细胞中的细胞毒性提供了一种新的癌症治疗方法。具体来说，本发明表明，具有胞嘧啶脱氨酶基因和5-氟胞嘧啶的分子化学疗法是一种有效的放射增敏策略，其可以导致肿瘤控制的显着改善，具有比常规全身施用5-氟尿嘧啶更少的正常组织毒性，这将翻译改善治愈率和更好的生存。描述了用于通过磁共振光谱法连续体内监测5-氟尿嘧啶的非侵入性方法。构建了在肿瘤细胞中选择性复制缺陷型p53途径的编码胞嘧啶脱氨酶基因的腺病毒。还提供了编码胞嘧啶脱氨酶和尿嘧啶磷酸核糖转移酶的融合蛋白的腺病毒。

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