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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1996-6-6
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pubmed:abstractText |
The potential role of transforming growth factor-beta in in vivo resistance was examined by administration of transforming growth factor-beta-neutralizing antibodies to animals bearing the EMT-6/Parent tumor or the antitumor alkylating resistance tumors, EMT-6/CTX or EMT-6/CDDP. Treatment of tumor bearing animals with anti-TGF-beta antibodies by intraperitoneal injection daily on days 0-8 post-tumor cell implantation increased the sensitivity of the EMT-6/Parent tumor to cyclophosphamide (CTX) and cisplatin (CDDP) and markedly increased the sensitivity of the EMT-6/CTX tumor to CTX and the EMT6/CDDP tumor to CDDP, as determined by tumor cell survival assay. Bone marrow granulocyte-macrophage colony-forming units (CFU-GM) survival was determined from these same animals. The increase in the sensitivity in the tumors upon treatment with the anti-TGF-beta antibodies was also observed in increased sensitivity of the bone marrow CFU-GM to CTX and CDDP. Treatment of non-tumor-bearing animals with the anti-TGF-beta regimen did not alter blood ATP or serum glucose level but did decrease serum lactate levels. This treatment also decreased hepatic glutathione, glutathione S-transferase, glutathione reductase, and glutathione peroxidase in non-tumor bearing animals by 40-60% but increased hepatic cytochrome P450 reductase in these normal animals. Animals bearing the EMT-6/CTX and EMT-6/CDDP tumors had higher serum lactate levels than normal or EMT-6/Parent tumor-bearing animals; these were decreased by the anti-TGF-beta regimen. Treatment of animals bearing any of the three tumors with the anti-TGF-beta regimen decreased by 30-50% the activity of hepatic glutathione S-transferase and glutathione peroxidase, and increased by 35-80% the activity of hepatic cytochrome P450 reductase. In conclusion, treatment with transforming growth factor-beta-neutralizing antibodies restored drug sensitivity in the alkylating agent-resistant tumors, altering both the tumor and host metabolic states.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0344-5704
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
601-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8612316-Animals,
pubmed-meshheading:8612316-Antineoplastic Agents, Alkylating,
pubmed-meshheading:8612316-Bone Marrow Cells,
pubmed-meshheading:8612316-Cell Survival,
pubmed-meshheading:8612316-Drug Resistance, Multiple,
pubmed-meshheading:8612316-Female,
pubmed-meshheading:8612316-Glutathione,
pubmed-meshheading:8612316-Hematopoiesis,
pubmed-meshheading:8612316-Liver,
pubmed-meshheading:8612316-Mammary Neoplasms, Experimental,
pubmed-meshheading:8612316-Mice,
pubmed-meshheading:8612316-Mice, Inbred BALB C,
pubmed-meshheading:8612316-Transforming Growth Factor beta
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pubmed:year |
1996
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pubmed:articleTitle |
Transforming growth factor-beta in in vivo resistance.
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pubmed:affiliation |
Dana-Farber Cancer Institute, Boston, 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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