Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1995-9-18
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
55
pubmed:geneSymbol
K-ras
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3810-6
pubmed:dateRevised
2006-11-15
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
pubmed:year
1995
pubmed:articleTitle
Liposome-mediated in vivo gene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity.
pubmed:affiliation
Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't