Cytosine deaminase suicide gene therapy for peritoneal carcinomatosis

被引：28

作者：

Bentires-Alj, M ^{[1
]}

Hellin, AC ^{[1
]}

Lechanteur, C ^{[1
]}

Princen, F ^{[1
]}

Lopez, M ^{[1
]}

Fillet, G ^{[1
]}

Gielen, J ^{[1
]}

Merville, MP ^{[1
]}

Bours, V ^{[1
]}

机构：

[1] Univ Liege, Lab Med Chem Med Oncol, B-4000 Liege, Belgium

来源：

CANCER GENE THERAPY | 2000年 / 7卷 / 01期

关键词：

cytosine deaminase; gene therapy; peritoneal carcinomatosis; colorectal carcinoma;

D O I：

10.1038/sj.cgt.7700093

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Gene therapy is a novel therapeutic approach that might soon improve the prognosis of some cancers. We investigated the feasibility of cytosine deaminase (CD) suicide gene therapy in a model of peritoneal carcinomatosis. DHD/K12 colorectal adenocarcinoma cells transfected in vitro with the CD gene were highly sensitive to 5-fluorocytosine (5-FC), and a bystander effect could also be observed. Treating CD+ cells with 5-FC resulted in apoptosis as detected by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling. In vitro, several human cell lines derived from ovarian or colorectal carcinomas, as well as the rat glioblastoma 9 L cell line, responded to CD/5-FC and showed a very strong bystander effect. 5-FC treatment of peritoneal carcinomatosis generated in syngeneic BDIX rats by CD-expressing DHD/K12 cells led to a complete and prolonged response and to prolonged survival. Our study thus demonstrated the efficacy of CD suicide gene therapy for the treatment of peritoneal carcinomatosis.

引用

页码：20 / 26

页数：7

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