Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1997-11-10
pubmed:abstractText
Treatment of mouse Lewis lung carcinoma with razoxane or dacarbazine was protracted for 10 transplant generations. While the capacity of the treated tumors to grow locally in immuno-competent or in immuno-depressed hosts was retained and not significantly modified, the metastatic phenotype was eliminated when the treated tumor cells were transplanted into immuno-competent hosts. The reduction in metastatic potential was slightly less pronounced, in terms of both number and volume of metastases, when the treated tumor cells were transplanted into immuno-depressed hosts. These properties were retained after 3 transplant generations without treatment. Northern blotting and zymography of primary-tumor crude extracts revealed that treatment with either razoxane or dacarbazine for one generation approximately doubled the expression of MMP-2 and MMP-9, while lacking any effect on that of 1.0 and of 3.5 kb TIMP-2. When the treatment was maintained for 10 generations, the expression of MMP-2 and MMP-9 for both drugs showed up-regulation of approximately 10- and 2-fold respectively. TIMP-2 mRNA of 1.0 kb doubled its expression, while that of 3.5 kb registered just above the control. Dacarbazine doubled the expression of uPA after 10 generations, while razoxane boosted it approximately 3-fold after either 1 or 10 generations. The permanent loss of metastatic phenotype induced in Lewis lung carcinoma by dacarbazine and razoxane is thus attributable to biological mechanisms independent of down-regulation of expression and/or activation of the 2 gelatinases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1056-61
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9378540-Animals, pubmed-meshheading:9378540-Collagenases, pubmed-meshheading:9378540-Dacarbazine, pubmed-meshheading:9378540-Gelatinases, pubmed-meshheading:9378540-Gene Expression Regulation, Enzymologic, pubmed-meshheading:9378540-Gene Expression Regulation, Neoplastic, pubmed-meshheading:9378540-Immunosuppression, pubmed-meshheading:9378540-Lung Neoplasms, pubmed-meshheading:9378540-Matrix Metalloproteinase 2, pubmed-meshheading:9378540-Matrix Metalloproteinase 9, pubmed-meshheading:9378540-Metalloendopeptidases, pubmed-meshheading:9378540-Mice, pubmed-meshheading:9378540-Mice, Inbred C57BL, pubmed-meshheading:9378540-Neoplasm Metastasis, pubmed-meshheading:9378540-RNA, Messenger, pubmed-meshheading:9378540-Razoxane, pubmed-meshheading:9378540-Transcription, Genetic, pubmed-meshheading:9378540-Urokinase-Type Plasminogen Activator
pubmed:year
1997
pubmed:articleTitle
Suppression of metastatic potential and up-regulation of gelatinases and uPA in LLC by protracted in vivo treatment with dacarbazine or razoxane.
pubmed:affiliation
Institute of Histology and Embryology, Medical School, University of Padua, Italy. garbisa@civ.bio.unipd.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't