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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2001-12-3
pubmed:abstractText
Midkine (MK), a heparin-binding growth factor, is overexpressed in a wide range of human carcinomas and is believed to contribute to tumorigenesis and tumor progression. To develop an antitumor reagent, we designed a phosphorothioate antisense oligodeoxynucleotide molecule based on the secondary structure of MK mRNA. The antisense MK at the dosage of 5 microM suppressed MK production by CMT-93 mouse rectal carcinoma cells after cationic liposome-mediated transfection, to 13% of that in control cultures. The growth of CMT-93 cells and their colony formation in soft agar were inhibited by the addition of the antisense MK, whereas the control reagent, the sense MK, showed no effects. On s.c. injection into nude mice, CMT-93 cells transfected with the antisense MK formed tumors much smaller than those by control cells. Finally, untreated CMT-93 cells were inoculated to nude mice, and 7 days later the antisense MK (50 microM) with atelocollagen was directly injected into the preformed tumor region to evaluate the curative effect; the injection was repeated at the interval of 2 weeks. During the period of 10-41 days after initiation of therapy, the rate of increase of tumor volume treated with the antisense MK was found to be about 4.2-fold lower than that seen after treatment with the sense MK. On this occasion, proliferation of tumor cells as estimated by 5-bromodeoxyuridine incorporation was strongly inhibited, whereas angiogenesis was less affected. These findings strongly suggested the usefulness of MK antisense oligodeoxynucleotide as a new reagent for cancer therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8486-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Antisense oligodeoxynucleotide targeted to Midkine, a heparin-binding growth factor, suppresses tumorigenicity of mouse rectal carcinoma cells.
pubmed:affiliation
Department of Biochemistry, Nagoya University School of Medicine, Nagoya, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't