| In vivo electroporetic transfer of bcl-2 antisense oligonucleotide inhibits the development of hepatocellular carcinoma in rats. | |
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MedLine Citation:
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PMID: 10629087 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To investigate the potential use of a bcl-2 antisense oligonucleotide for therapy against hepatocellular carcinoma, we examined the effects of the electroporetic transfer of a bcl-2 antisense oligonucleotide on rat hepatocarcinogenesis induced by N-nitrosomorpholine (NNM). Sprague-Dawley rats were given water containing 175 mg/l NNM for 8 weeks and received intraperitoneal injections of a bcl-2 antisense phosphorothioate oligonucleotide, a sense oligonucleotide or a scrambled sequence oligonucleotide encapsulated in empty liposomes, at a dose of 150 microg oligonucleotide/kg body weight, every 4 weeks. One hour after injection, in vivo electroporation was performed on the liver to achieve selective transfer of the oligonucleotides. By week 16, the rats that had received the bcl-2 antisense oligonucleotide had significantly fewer and smaller precancerous liver lesions positive for glutathione-S-transferase (placental type), and a significantly lower incidence of hepatocellular carcinoma in the electroporation zone than rats that had received the sense or the scrambled oligonucleotides. Moreover, the bcl-2 antisense oligonucleotide significantly increased the apoptotic indices in foci, neoplastic nodules and in hepatocellular carcinomas. The expression of bcl-2 mRNA also decreased, and 3'-fragments of bcl-2mRNA produced by cleavage at the antisense target site were detected in rat liver. Mean cellular fluorescence in the liver increased with higher doses of fluorescein-isothiocyanate-labeled antisense or sense oligonucleotides. Our results show that the electroporetic transfer of bcl-2 antisense oligonucleotide can inhibit rat hepatocarcinogenesis. |
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Authors:
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M Baba; H Iishi; M Tatsuta |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 85 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 2000 Jan |
Date Detail:
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Created Date: 2000-02-01 Completed Date: 2000-02-01 Revised Date: 2007-07-24 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 260-6 Citation Subset: IM |
Copyright Information:
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Copyright 2000 Wiley-Liss, Inc. |
Affiliation:
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Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / therapeutic use* Apoptosis / drug effects Blotting, Northern Carcinogens Carcinoma, Hepatocellular / chemically induced, pathology, prevention & control* Drug Carriers Drug Delivery Systems Liposomes Liver Neoplasms / chemically induced, pathology, prevention & control* Male Nitrosamines Oligonucleotides, Antisense / therapeutic use* Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*, genetics Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Carcinogens; 0/Drug Carriers; 0/Liposomes; 0/Nitrosamines; 0/Oligonucleotides, Antisense; 0/Proto-Oncogene Proteins c-bcl-2; 59-89-2/N-nitrosomorpholine |
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