体内
胰腺癌
癌症研究
体外
胰腺
病理
化学
医学
生物
癌症
内科学
生物化学
生物技术
作者
Jürgen Tepel,Marie‐Luise Kruse,Christina March,Alexander Fiedler,Matthias Kapischke,Thomas Ketterer,Bence Sipos,Bernd Kremer,Holger Kalthoff
出处
期刊:Pancreas
[Ovid Technologies (Wolters Kluwer)]
日期:2004-01-01
卷期号:28 (1): 1-12
被引量:18
标识
DOI:10.1097/00006676-200401000-00001
摘要
Investigation of a terminally modified oligodeoxynucleotide (ODN) directed against p53 mRNA (p53-3' polyethylene glycol-5' tocopherol ODN as a novel drug for pancreatic ductal carcinoma therapy in vitro and in vivo.The impact of lipophilic modifications at the 5' end of p53-directed ODNs on cellular uptake was analyzed in vitro using proliferation assays, fluorescence-activated cell sorting analysis, and confocal laser scanning microscopy. The in vivo effects of p53-PT-ODN on the growth of orthotopically xenografted human pancreatic ductal carcinoma cells (PancTuI) were studied in SCID beige mice. Distribution was examined in vitro and in vivo using Cy3-labeled ODNs.Terminally modified p53-PT-ODN showed excellent cellular uptake without using transfection reagents. Microscopically detectable levels of p53-PT-ODN were reached in vivo within 3 hours after intraperitoneal injection, even in extraperitoneal organs. At this time, Cy3-labeled p53-PT-ODN was found in solid tumor formations. We observed a significant inhibition of tumor growth (50%) in vivo at low doses of p53-PT-ODN, whereas at high doses, 2 of 9 animals had no detectable tumors at necropsy. When p53-PT-ODN was injected on the day of tumor cell inoculation, the growth inhibition of solid tumors was significantly stronger compared with that with delayed treatment.p53-Directed modified ODNs might be of therapeutic value in pancreatic ductal carcinoma, particularly as adjuvant therapy after pancreatic tumor resection.
科研通智能强力驱动
Strongly Powered by AbleSci AI