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聚乙烯亚胺介导的基因转移至小鼠腹膜腔中的胰腺肿瘤播散处。

Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity.

作者信息

Aoki K, Furuhata S, Hatanaka K, Maeda M, Remy J S, Behr J P, Terada M, Yoshida T

机构信息

Section for Studies on Host-Immune Response, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan.

出版信息

Gene Ther. 2001 Apr;8(7):508-14. doi: 10.1038/sj.gt.3301435.

Abstract

Although peritoneal dissemination of cancer cells often occurs at the advanced stages of pancreatic, gastric or ovarian cancers, no effective therapy has been established. Cationic lipid-mediated gene transfer into peritoneal dissemination may offer a prospect of safe therapies, but vector improvements are needed with regard to the efficiency and specificity of the gene transfer. In this study, the intraperitoneal injection of plasmid DNA:polyethylenimine (PEI) complexes into mice was evaluated as a gene delivery system for the peritoneal disseminations. The luciferase and beta-galactosidase genes were used as marker genes. PEI was more efficient than the cationic lipids examined in this study in vivo, and the transgene was preferentially expressed in the tumors. Although PCR analysis showed that the injected DNA was delivered to various organs, the distributed DNA became undetectable by 6 months after the gene transfer. Blood chemistry and histological analysis showed no significant toxicity in the injected mice. This study demonstrated that the intraperitoneal injection of DNA:PEI is a promising delivery method to transduce a gene into disseminated cancer nodules in the peritoneal cavity.

摘要

尽管癌细胞的腹膜播散常发生于胰腺癌、胃癌或卵巢癌的晚期阶段,但尚未确立有效的治疗方法。阳离子脂质介导的基因转移至腹膜播散部位可能提供安全治疗的前景,但就基因转移的效率和特异性而言,载体仍需改进。在本研究中,评估了向小鼠腹腔内注射质粒DNA:聚乙烯亚胺(PEI)复合物作为腹膜播散的基因递送系统。荧光素酶和β-半乳糖苷酶基因用作标记基因。在体内,PEI比本研究中检测的阳离子脂质更有效,且转基因优先在肿瘤中表达。尽管PCR分析显示注射的DNA被递送至各个器官,但基因转移后6个月,分布的DNA就无法检测到了。血液生化和组织学分析表明,注射小鼠未出现明显毒性。本研究证明,腹腔内注射DNA:PEI是一种有前景的递送方法,可将基因转导至腹腔内播散的癌结节中。

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