| Inhibition of spontaneous rat osteosarcoma lung metastasis by 3S-[4-(N-hydroxyamino)-2R-isobutylsuccinyl]amino-1-methoxy-3,4-dihydroc arbostyril, a novel matrix metalloproteinase inhibitor. | |
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MedLine Citation:
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PMID: 10359049 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the present experiment, we examined the effects of OPB-3206, 3S-[4-(N-hydroxyamino)-2R-isobutylsuccinyl]amino-1-methoxy-3,4- dihydrocarbostyril, a novel metalloproteinase inhibitor, on the growth and metastasis of transplantable osteosarcomas (spontaneous osteosarcoma, selected lung metastatic lesions; S-SLM), which were previously established in rats. OPB-3206 inhibited the activities of interstitial collagenase, gelatinases A and B, and stromelysin in vitro. After oral administration to rats, its serum concentration peaked at 40 min and the drug was no longer detectable at 8 h. When OPB-3206 was orally administered at 0%, 0.1% and 0.4% in the diet for 4 weeks, starting 7 days after subcutaneous transplantation of osteosarcomas to male Fischer 344 rats, numbers of lung metastatic nodules were significantly reduced by the highest dose, while the growth of subcutaneous tumors was not affected. Zymographic analysis showed the presence of pro matrix metalloproteinase (proMMP)-2, proMMP-9 and MMP-9 activities in S-SLM. In animals fed 0.4% OPB-3206, the activity of proMMP-9 was increased, but that for MMP-9 had become undetectable. The results thus suggest that OPB-3206 selectively inhibits lung metastasis of rat transplantable osteosarcomas by inhibiting MMP-9 activation. |
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Authors:
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A Kido; M Tsutsumi; K Iki; M Motoyama; M Takahama; T Tsujiuchi; T Morishita; K Tatsumi; S Tamai; Y Konishi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Japanese journal of cancer research : Gann Volume: 90 ISSN: 0910-5050 ISO Abbreviation: Jpn. J. Cancer Res. Publication Date: 1999 Mar |
Date Detail:
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Created Date: 1999-06-15 Completed Date: 1999-06-15 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8509412 Medline TA: Jpn J Cancer Res Country: JAPAN |
Other Details:
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Languages: eng Pagination: 333-41 Citation Subset: IM |
Affiliation:
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Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Animals Body Weight Collagenases / antagonists & inhibitors, metabolism Dose-Response Relationship, Drug Enzyme Inhibitors / administration & dosage, blood, pharmacology*, therapeutic use Enzyme Precursors / antagonists & inhibitors, genetics, metabolism Gelatinases / antagonists & inhibitors, metabolism Lung Neoplasms / drug therapy, enzymology, pathology, secondary* Male Matrix Metalloproteinase 3 / antagonists & inhibitors, metabolism Metalloendopeptidases / antagonists & inhibitors*, genetics, metabolism Molecular Weight Neoplasm Transplantation Organ Size Osteosarcoma / drug therapy, enzymology, pathology*, secondary Quinolones / administration & dosage, blood, pharmacology*, therapeutic use RNA, Messenger / metabolism Rats Rats, Inbred F344 Time Factors Tissue Inhibitor of Metalloproteinase-1 / genetics Tissue Inhibitor of Metalloproteinase-2 / genetics |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Enzyme Precursors; 0/OPB 3206; 0/Quinolones; 0/RNA, Messenger; 0/Tissue Inhibitor of Metalloproteinase-1; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC 3.4.24.-/Collagenases; EC 3.4.24.-/Gelatinases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.17/Matrix Metalloproteinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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