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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
17
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pubmed:dateCreated |
1995-9-18
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pubmed:abstractText |
K-ras point mutation occurs at a characteristically high incidence in human pancreatic cancer. Plasmids expressing antisense (AS), AS-K-ras-LNSX or sense K-ras gene fragment, were first transduced into three human pancreatic cancer cell lines (AsPC-1, MIAPaCa-2, and BxPC-3) by liposome-mediated transfection. A stable expression of antisense or sense K-ras RNA was detected by Northern blot analysis, and Western blot analysis confirmed a reduction of up to 20% of K-ras-specific p21 protein in AsPC-1 cells transduced with AS-K-ras-LNSX. The growth of pancreatic cancer cells with K-ras point mutations (AsPC-1 and MIAPaCa-2) was significantly suppressed after transduction of AS-K-ras-LNSX, although the effect of antisense construct was not found in cells with a wild-type K-ras gene (BxPC-3). Next, to test the efficacy in vivo, AsPC-1 cells were inoculated into the intraperitoneal cavity of nude mice, and 3 days later, the AS-K-ras-LNSX:liposome complex was injected i.p. 3 times. Twenty-eight days after tumor cell inoculation, 9 of 10 control mice developed peritoneal dissemination and/or solid tumors on the pancreas, whereas only 2 of 12 mice treated with AS-K-ras-LNSX showed any evidence of tumors. Although PCR analysis indicated that the injected DNA was delivered to various organs except for the brain, treatment-related toxicity was not observed. This study shows that the liposome-mediated in vivo gene transfer of antisense K-ras construct may be a useful therapeutic strategy for pancreatic cancer.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Liposomes,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Antisense
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
55
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pubmed:geneSymbol |
K-ras
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3810-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7641198-Animals,
pubmed-meshheading:7641198-Base Sequence,
pubmed-meshheading:7641198-Blotting, Western,
pubmed-meshheading:7641198-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:7641198-Cyclins,
pubmed-meshheading:7641198-DNA,
pubmed-meshheading:7641198-Gene Transfer Techniques,
pubmed-meshheading:7641198-Genes, ras,
pubmed-meshheading:7641198-Genetic Vectors,
pubmed-meshheading:7641198-Humans,
pubmed-meshheading:7641198-Liposomes,
pubmed-meshheading:7641198-Mice,
pubmed-meshheading:7641198-Mice, Inbred BALB C,
pubmed-meshheading:7641198-Mice, Nude,
pubmed-meshheading:7641198-Molecular Sequence Data,
pubmed-meshheading:7641198-Pancreatic Neoplasms,
pubmed-meshheading:7641198-Peritoneal Neoplasms,
pubmed-meshheading:7641198-Polymerase Chain Reaction,
pubmed-meshheading:7641198-RNA, Antisense,
pubmed-meshheading:7641198-Tumor Cells, Cultured
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pubmed:year |
1995
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pubmed:articleTitle |
Liposome-mediated in vivo gene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity.
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pubmed:affiliation |
Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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